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pubmed23n0125_13777

Xenobiotic metabolism in suspensions and primary cultures of isolated hepatocytes prepared from the caudate process of bovine liver.

Isolated hepatocytes were prepared from 100- to 125-kg Holstein male calves (n = 10) by perfusion of the caudate process of the caudate lobe of the liver. The 11th or 12th rib on the right side was resected to provide exposure of the caudate process. Complete postsurgical recovery of the donor from partial lobectomy was confirmed by growth data and serum chemical and hematologic criteria. Hepatocytes were isolated under aseptic conditions, using a 2-step collagenase vascular perfusion procedure. Hepatocyte preparations averaged 85% viability, and the yield averaged 1.2 X 10(7) viable hepatocytes/g of (wet weight) liver. Morphologic characteristics of hepatocytes examined under light and scanning electron microscopy were considered normal, except for occasional surface blebs. Freshly isolated hepatocytes in suspension rapidly decreased in viability and xenobiotic metabolizing capacity (aldrin epoxidation and ethoxycoumarin 0-deethylation and 7-hydroxycoumarin glucuronidation and sulfation), and hepatocytes surviving the initial 2 to 3 hours appeared to undergo repair. As an alternative, primary monolayer cultures on collagen-coated plates were evaluated. Hepatocytes attached to the collagen surface within 4 hours and appeared flattened by 12 hours. Although metabolic activity decreased about 30% over 8 hours in culture, the pattern of ethoxycoumarin metabolites was relatively constant. It was not determined to what extent the apparent loss of metabolic capacity was caused by hepatocyte detachment from the collagen surface. Although complicated by the requirement for asepsis, primary cultures were superior to suspensions for xenobiotic metabolism studies in cattle.

Xenobiotic metabolism in suspensions and primary cultures of isolated hepatocytes prepared from the caudate process of bovine liver. Isolated hepatocytes were prepared from 100- to 125-kg Holstein male calves (n = 10) by perfusion of the caudate process of the caudate lobe of the liver. The 11th or 12th rib on the right side was resected to provide exposure of the caudate process. Complete postsurgical recovery of the donor from partial lobectomy was confirmed by growth data and serum chemical and hematologic criteria. Hepatocytes were isolated under aseptic conditions, using a 2-step collagenase vascular perfusion procedure. Hepatocyte preparations averaged 85% viability, and the yield averaged 1.2 X 10(7) viable hepatocytes/g of (wet weight) liver. Morphologic characteristics of hepatocytes examined under light and scanning electron microscopy were considered normal, except for occasional surface blebs. Freshly isolated hepatocytes in suspension rapidly decreased in viability and xenobiotic metabolizing capacity (aldrin epoxidation and ethoxycoumarin 0-deethylation and 7-hydroxycoumarin glucuronidation and sulfation), and hepatocytes surviving the initial 2 to 3 hours appeared to undergo repair. As an alternative, primary monolayer cultures on collagen-coated plates were evaluated. Hepatocytes attached to the collagen surface within 4 hours and appeared flattened by 12 hours. Although metabolic activity decreased about 30% over 8 hours in culture, the pattern of ethoxycoumarin metabolites was relatively constant. It was not determined to what extent the apparent loss of metabolic capacity was caused by hepatocyte detachment from the collagen surface. Although complicated by the requirement for asepsis, primary cultures were superior to suspensions for xenobiotic metabolism studies in cattle.

pubmed23n0125_13778

Pharmacokinetic evaluation of a slow-release cefotaxime suspension in the dog and in sheep.

Three Merino ewes were given cefotaxime IM, and 3 were given cefotaxime subcutaneously (50 mg/kg of body weight each); each dose was suspended in 6 ml of oil. Five dogs were also given an oily suspension of cefotaxime subcutaneously (SC) (50 mg/kg of body weight). The plasma concentrations (Cp) and pharmacokinetic data obtained after cefotaxime in the oily suspension was injected IM and SC were compared with data from the same animals after they were given an aqueous solution of cefotaxime by the same routes. Key pharmacokinetic values obtained after cefotaxime was administered IV to sheep and to dogs are discussed. Mean peak Cp (Cpeak) in sheep when given the oily suspension IM was approximately 53 micrograms/ml at 0.18 to 0.40 hour, and that value in sheep given the aqueous preparation was 62 micrograms/ml 0.08 to 0.18 hour. Mean Cpeak values after the oily suspension and the aqueous preparation were injected SC were 11.0 micrograms/ml (between 0.8 and 1 hour) and 51 micrograms/ml (between 0.25 and 1 hour), respectively. Bioavailabilities were approximately 70% after IM injection was done and 90% after SC injection was done. The beta-plasma half-lives were 0.7 hour after IM injection was done and 2.9 hours after SC injection was done. Mean Cpeak in dogs when given the oily suspension SC was 30 micrograms/ml at 1.0 hour, and when dogs were given the aqueous preparation SC, Cpeak was 27 micrograms/ml at 0.6 hour. Absorption was virtually complete after the oily suspension and aqueous preparations were given.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic evaluation of a slow-release cefotaxime suspension in the dog and in sheep. Three Merino ewes were given cefotaxime IM, and 3 were given cefotaxime subcutaneously (50 mg/kg of body weight each); each dose was suspended in 6 ml of oil. Five dogs were also given an oily suspension of cefotaxime subcutaneously (SC) (50 mg/kg of body weight). The plasma concentrations (Cp) and pharmacokinetic data obtained after cefotaxime in the oily suspension was injected IM and SC were compared with data from the same animals after they were given an aqueous solution of cefotaxime by the same routes. Key pharmacokinetic values obtained after cefotaxime was administered IV to sheep and to dogs are discussed. Mean peak Cp (Cpeak) in sheep when given the oily suspension IM was approximately 53 micrograms/ml at 0.18 to 0.40 hour, and that value in sheep given the aqueous preparation was 62 micrograms/ml 0.08 to 0.18 hour. Mean Cpeak values after the oily suspension and the aqueous preparation were injected SC were 11.0 micrograms/ml (between 0.8 and 1 hour) and 51 micrograms/ml (between 0.25 and 1 hour), respectively. Bioavailabilities were approximately 70% after IM injection was done and 90% after SC injection was done. The beta-plasma half-lives were 0.7 hour after IM injection was done and 2.9 hours after SC injection was done. Mean Cpeak in dogs when given the oily suspension SC was 30 micrograms/ml at 1.0 hour, and when dogs were given the aqueous preparation SC, Cpeak was 27 micrograms/ml at 0.6 hour. Absorption was virtually complete after the oily suspension and aqueous preparations were given.(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13779

Effects of aflatoxin on the growth performance and immune responses of weanling swine.

Aflatoxin (AF)-contaminated ground corn was mixed with a commercial swine ration to yield 2 concentrations (500 mg of AFB1/kg of feed [A] and 300 mg of AFB1/kg [B]) and was fed to 2 groups of pigs. Groups A and B were fed the AF-containing ration, whereas control group C was fed the same commercial ration mixed with ground corn devoid of AF. A comparative analysis of the average weight gain per pig in each of the treatment groups, compared with that in the control group, indicated a significantly (P less than 0.01) greater weight gain in the control group. The average feed conversion rate was also significantly (P less than 0.01) lower in group A pigs, compared with that in the control group. The humoral immune response to Erysipelothrix rhusiopathiae, measured by enzyme-linked immunosorbent assay, did not reveal a significant difference among groups; there were no consistent differences observed in the proliferative responses of lymphocytes to mitogens. In contrast, a significant (P less than 0.05) reduction in complement titers was observed, whereas an increase in serum immunoglobulin G and M values occurred in the AF-treated group A, compared with that in group C. Gross enlargement of the liver, substantiated by histologic evidence of toxic damage to the hepatic parenchyma, revealed that AF at concentrations of 500 mg/kg of feed was toxigenic and produced an adverse effect on the growth rate, feed efficiency, and general well-being of young pigs.

Effects of aflatoxin on the growth performance and immune responses of weanling swine. Aflatoxin (AF)-contaminated ground corn was mixed with a commercial swine ration to yield 2 concentrations (500 mg of AFB1/kg of feed [A] and 300 mg of AFB1/kg [B]) and was fed to 2 groups of pigs. Groups A and B were fed the AF-containing ration, whereas control group C was fed the same commercial ration mixed with ground corn devoid of AF. A comparative analysis of the average weight gain per pig in each of the treatment groups, compared with that in the control group, indicated a significantly (P less than 0.01) greater weight gain in the control group. The average feed conversion rate was also significantly (P less than 0.01) lower in group A pigs, compared with that in the control group. The humoral immune response to Erysipelothrix rhusiopathiae, measured by enzyme-linked immunosorbent assay, did not reveal a significant difference among groups; there were no consistent differences observed in the proliferative responses of lymphocytes to mitogens. In contrast, a significant (P less than 0.05) reduction in complement titers was observed, whereas an increase in serum immunoglobulin G and M values occurred in the AF-treated group A, compared with that in group C. Gross enlargement of the liver, substantiated by histologic evidence of toxic damage to the hepatic parenchyma, revealed that AF at concentrations of 500 mg/kg of feed was toxigenic and produced an adverse effect on the growth rate, feed efficiency, and general well-being of young pigs.

pubmed23n0125_13780

Delta-aminolevulinic acid dehydratase (EC4.3.1.24) activity in erythrocytes from cattle administered low concentrations of lead acetate.

Four different age groups of cattle, which had never been exposed to Pb, were used to determine normal age-related values for erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity. Acute or chronic Pb intoxication was experimentally induced in young calves, and their ALAD values were compared with the normal values. Results indicated that ALAD of normal bovine erythrocytes increased 2- to 3-fold from 1 week to 9 weeks of age and then slowly returned to the initial (1 week old) value by 9 months of age. Erythrocyte ALAD from cattle greater than or equal to 9 months old was uniform. Because of the age-related changes in normal ALAD of cattle less than 9 months old, the age of an animal should be carefully established and age-matched controls evaluated simultaneously when ALAD is used to assess calves suspected of having Pb poisoning. A significant negative correlation was found between blood Pb concentration and ALAD during the first 24 hours after the initial administration of Pb, indicating a high sensitivity of erythrocyte ALAD to Pb. However, when blood Pb concentrations reached 50 micrograms/dl, ALAD did not change further. Because single ingestions of Pb can raise blood Pb concentrations greater than 50 micrograms/dl, ALAD appears to have little value in differentiating acute from chronic Pb intoxication. Within 7 days after Pb administration ceased, ALAD did not increase significantly, even when calves were given calcium ethylenediaminetetraacetic acid (CaNa2EDTA); however, blood Pb concentration decreased by 50%. The rapid change in blood Pb concentration gave a false indication of a positive treatment effect when no real effect was detected by ALAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Delta-aminolevulinic acid dehydratase (EC4.3.1.24) activity in erythrocytes from cattle administered low concentrations of lead acetate. Four different age groups of cattle, which had never been exposed to Pb, were used to determine normal age-related values for erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity. Acute or chronic Pb intoxication was experimentally induced in young calves, and their ALAD values were compared with the normal values. Results indicated that ALAD of normal bovine erythrocytes increased 2- to 3-fold from 1 week to 9 weeks of age and then slowly returned to the initial (1 week old) value by 9 months of age. Erythrocyte ALAD from cattle greater than or equal to 9 months old was uniform. Because of the age-related changes in normal ALAD of cattle less than 9 months old, the age of an animal should be carefully established and age-matched controls evaluated simultaneously when ALAD is used to assess calves suspected of having Pb poisoning. A significant negative correlation was found between blood Pb concentration and ALAD during the first 24 hours after the initial administration of Pb, indicating a high sensitivity of erythrocyte ALAD to Pb. However, when blood Pb concentrations reached 50 micrograms/dl, ALAD did not change further. Because single ingestions of Pb can raise blood Pb concentrations greater than 50 micrograms/dl, ALAD appears to have little value in differentiating acute from chronic Pb intoxication. Within 7 days after Pb administration ceased, ALAD did not increase significantly, even when calves were given calcium ethylenediaminetetraacetic acid (CaNa2EDTA); however, blood Pb concentration decreased by 50%. The rapid change in blood Pb concentration gave a false indication of a positive treatment effect when no real effect was detected by ALAD.(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13781

Chloramphenicol concentrations in calf muscle tissue.

Twenty-five 9- to 11-week-old calves were administered 2 doses of chloramphenicol prepared in propylene glycol (13.6 mg/kg of body weight IV; 6.8 mg/kg IM; or 13.6 mg/kg IM) at 24-hour intervals. Calves were euthanatized at designated times from 2 to 72 hours after the last dose was administered. Muscle tissues were collected immediately after euthanasia, and chloramphenicol concentrations in the tissues were determined.

Chloramphenicol concentrations in calf muscle tissue. Twenty-five 9- to 11-week-old calves were administered 2 doses of chloramphenicol prepared in propylene glycol (13.6 mg/kg of body weight IV; 6.8 mg/kg IM; or 13.6 mg/kg IM) at 24-hour intervals. Calves were euthanatized at designated times from 2 to 72 hours after the last dose was administered. Muscle tissues were collected immediately after euthanasia, and chloramphenicol concentrations in the tissues were determined.

pubmed23n0125_13782

Histochemical changes in skeletal muscles of four male horses with neuromuscular disease.

Skeletal muscle biopsy specimens were taken from 4 male horses with neuromuscular disease such as myotonia congenita, chronic myositis, exertional rhabdomyolysis, and shivers. Histologic and histochemical techniques were used to evaluate skeletal muscle morphologic features and fiber-type population, size, and area, as well as muscle enzyme activities (acid phosphatase, alkaline phosphatase, and esterase). A histochemical and histologic profile were described for each muscle biopsy specimen.

Histochemical changes in skeletal muscles of four male horses with neuromuscular disease. Skeletal muscle biopsy specimens were taken from 4 male horses with neuromuscular disease such as myotonia congenita, chronic myositis, exertional rhabdomyolysis, and shivers. Histologic and histochemical techniques were used to evaluate skeletal muscle morphologic features and fiber-type population, size, and area, as well as muscle enzyme activities (acid phosphatase, alkaline phosphatase, and esterase). A histochemical and histologic profile were described for each muscle biopsy specimen.

pubmed23n0125_13783

Relationships between stride length, stride frequency, velocity, and morphometrics of foals.

Velocity-dependent changes in stride length and frequency were studied in 19 male foals, 6 to 8 months of age, and were related to body morphometrics. Eighteen distance and 8 angle measurements were digitized from 16-mm films of standing foals. The total mass and the percentage of total mass acting through the forelimbs were also recorded. Stride length and frequency data were extracted from 16-mm films of 239 strides of the walk, trot, and canter-gallop. Polynomial-regression analysis was used to determine the equation that best described the relationship between data of stride length or frequency vs velocity and stride length vs stride frequency for each foal, for the total population, and for the walk, trot, and canter-gallop data from the total population. Stepwise-regression analysis was done of stride length, or slope of the stride length-velocity line (frequency-1) vs distance, angle, and mass measurements. The stride length for each foal was calculated for a stride frequency of 2 strides/s. The maximum recorded velocity was 11.45 m/s. There was overlap in the velocity ranges at which gaits were used: the walk or trot were used at velocities between 1.7 to 2.0 m/s and a trot or canter were used over a wider velocity range of 3.2 to 5.8 m/s. Stride length did not exceed 4.72 m. The mean stride length at a frequency of 2 strides/s was 2.57 m and was significantly (P less than 0.05) correlated to total mass (r = 0.6335) and length of the metacarpus (r = -0.5115), but not to wither height.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships between stride length, stride frequency, velocity, and morphometrics of foals. Velocity-dependent changes in stride length and frequency were studied in 19 male foals, 6 to 8 months of age, and were related to body morphometrics. Eighteen distance and 8 angle measurements were digitized from 16-mm films of standing foals. The total mass and the percentage of total mass acting through the forelimbs were also recorded. Stride length and frequency data were extracted from 16-mm films of 239 strides of the walk, trot, and canter-gallop. Polynomial-regression analysis was used to determine the equation that best described the relationship between data of stride length or frequency vs velocity and stride length vs stride frequency for each foal, for the total population, and for the walk, trot, and canter-gallop data from the total population. Stepwise-regression analysis was done of stride length, or slope of the stride length-velocity line (frequency-1) vs distance, angle, and mass measurements. The stride length for each foal was calculated for a stride frequency of 2 strides/s. The maximum recorded velocity was 11.45 m/s. There was overlap in the velocity ranges at which gaits were used: the walk or trot were used at velocities between 1.7 to 2.0 m/s and a trot or canter were used over a wider velocity range of 3.2 to 5.8 m/s. Stride length did not exceed 4.72 m. The mean stride length at a frequency of 2 strides/s was 2.57 m and was significantly (P less than 0.05) correlated to total mass (r = 0.6335) and length of the metacarpus (r = -0.5115), but not to wither height.(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13784

The effects of occupation and smoking on respiratory disease mortality.

The effects of occupation and smoking on respiratory symptoms and ventilatory lung function were examined in 1957 among random samples of men 25 to 34 and 55 to 64 yr of age from 4 occupational categories (miners, foundry workers, mixed dust and chemical workers, and non-dust-exposed workers) living in an industrial English town. Mortality has been established 20 yr after the initial survey. This report focuses on the effects of smoking, lung function, and respiratory symptoms among the older men. All-cause mortality was very similar in the nondusty, foundry, and mixed dust groups, but slightly lower in the miners and ex-miners. In contrast, smokers had 2 times the death rates of nonsmokers. There was consistency in the smoking effect within each occupational group. Poor lung function and to some extent bronchitic symptoms in 1957 were predictive of mortality by 1977, regardless of smoking habits. However, the effect of symptoms in the absence of concomitant poor lung function, though consistent, was small.

The effects of occupation and smoking on respiratory disease mortality. The effects of occupation and smoking on respiratory symptoms and ventilatory lung function were examined in 1957 among random samples of men 25 to 34 and 55 to 64 yr of age from 4 occupational categories (miners, foundry workers, mixed dust and chemical workers, and non-dust-exposed workers) living in an industrial English town. Mortality has been established 20 yr after the initial survey. This report focuses on the effects of smoking, lung function, and respiratory symptoms among the older men. All-cause mortality was very similar in the nondusty, foundry, and mixed dust groups, but slightly lower in the miners and ex-miners. In contrast, smokers had 2 times the death rates of nonsmokers. There was consistency in the smoking effect within each occupational group. Poor lung function and to some extent bronchitic symptoms in 1957 were predictive of mortality by 1977, regardless of smoking habits. However, the effect of symptoms in the absence of concomitant poor lung function, though consistent, was small.

pubmed23n0125_13785

Isoniazid prophylaxis in hepatitis B carriers.

Both tuberculosis and hepatitis B are endemic in southeast Asia and are common among refugees to the United States from that region. Isoniazid, used for the prophylactic treatment of tuberculosis, is a potentially hepatotoxic drug. Carriers of the hepatitis B virus are likely to have some degree of liver damage due to their chronic infection. We hypothesized that prophylactic treatment of carriers with isoniazid would cause greater liver damage, as measured by serum alanine aminotransferase (ALT) levels, than would such therapy of noncarriers. Cross-sectional and longitudinal studies of the southeast Asian refugee population in Philadelphia failed to support this hypothesis. Isoniazid did not cause greater hepatotoxicity in hepatitis B carriers than in noncarriers. Although carriers had higher ALT levels than noncarriers, both groups experienced transient ALT elevations during the first 2 months of isoniazid prophylactic therapy. Therefore, we concluded that chronic infection with hepatitis B virus is not a contraindication to the prophylactic use of isoniazid.

Isoniazid prophylaxis in hepatitis B carriers. Both tuberculosis and hepatitis B are endemic in southeast Asia and are common among refugees to the United States from that region. Isoniazid, used for the prophylactic treatment of tuberculosis, is a potentially hepatotoxic drug. Carriers of the hepatitis B virus are likely to have some degree of liver damage due to their chronic infection. We hypothesized that prophylactic treatment of carriers with isoniazid would cause greater liver damage, as measured by serum alanine aminotransferase (ALT) levels, than would such therapy of noncarriers. Cross-sectional and longitudinal studies of the southeast Asian refugee population in Philadelphia failed to support this hypothesis. Isoniazid did not cause greater hepatotoxicity in hepatitis B carriers than in noncarriers. Although carriers had higher ALT levels than noncarriers, both groups experienced transient ALT elevations during the first 2 months of isoniazid prophylactic therapy. Therefore, we concluded that chronic infection with hepatitis B virus is not a contraindication to the prophylactic use of isoniazid.

pubmed23n0125_13786

Pseudomonas cepacia: decrease in colonization in patients with cystic fibrosis.

The incidence and prevalence of Pseudomonas cepacia pulmonary colonization were noted to be increasing in patients with cystic fibrosis (CF). Previous work had indicated a greater prevalence of P. cepacia among siblings (with CF) of patients colonized by P. cepacia as well as an association of initial positive P. cepacia cultures with a hospitalization. Because of uncertainty regarding the source and mode of transmission, limited precautionary measures were instituted in 1983, including physical separation of hospitalized patients colonized with P. cepacia from non-colonized patients, reeducation of staff concerning basic infection control procedures, explanation to families regarding these precautionary efforts, and institution of separate summer camp sessions. Repeated environmental cultures throughout the hospital were negative for P. cepacia. Coincident with the institution of control measures, a sharp decline in incidence occurred (8.2% in 1983 versus 1.7% in 1984). These results are suggestive of patient-to-patient transmission. Because P. cepacia infections have been associated with shorter survival in some patients with CF, we will continue our current segregation measures.

Pseudomonas cepacia: decrease in colonization in patients with cystic fibrosis. The incidence and prevalence of Pseudomonas cepacia pulmonary colonization were noted to be increasing in patients with cystic fibrosis (CF). Previous work had indicated a greater prevalence of P. cepacia among siblings (with CF) of patients colonized by P. cepacia as well as an association of initial positive P. cepacia cultures with a hospitalization. Because of uncertainty regarding the source and mode of transmission, limited precautionary measures were instituted in 1983, including physical separation of hospitalized patients colonized with P. cepacia from non-colonized patients, reeducation of staff concerning basic infection control procedures, explanation to families regarding these precautionary efforts, and institution of separate summer camp sessions. Repeated environmental cultures throughout the hospital were negative for P. cepacia. Coincident with the institution of control measures, a sharp decline in incidence occurred (8.2% in 1983 versus 1.7% in 1984). These results are suggestive of patient-to-patient transmission. Because P. cepacia infections have been associated with shorter survival in some patients with CF, we will continue our current segregation measures.

pubmed23n0125_13787

Nutritional intervention in malnourished patients with emphysema.

We have previously reported the association of significant malnutrition with pulmonary emphysema and noted that the degree of malnutrition correlated with some measures of pulmonary function. The purpose of this study was to examine the energy requirements of malnourished patients with emphysema and acute effects of nutritional repletion on indices of pulmonary function and nutrition. We studied 6 malnourished patients with emphysema during a 3-wk admission to a clinical research unit. Initially, patients were allowed access to standard food sources ad libitum. Subsequently, if caloric goals were not met, nutritional supplementation was given orally. All patients receiving the ad libitum diet ingested calories in excess of their maintenance energy requirements. All patients increased their body weight (p less than 0.001) and percent ideal body weight (p less than 0.001). Anthropometric nutritional parameters showed a small but significant improvement (p less than 0.05). Although there was no significant change in spirometric results, lung volumes or DLCO after 3 wk maximal inspiratory mouth and transdiaphragmatic pressures increased (p less than 0.005). Peripheral skeletal muscle strength as measured by handgrip also improved (p less than 0.001). We conclude that inability to ingest an adequate number of calories was not the cause of weight loss in these patients. We also found that when given sufficient calories in excess of their needs, patients gain weight. Weight gain and improvement in anthropometric measurements are accompanied by significant improvement in ventilatory and peripheral muscle strength.

Nutritional intervention in malnourished patients with emphysema. We have previously reported the association of significant malnutrition with pulmonary emphysema and noted that the degree of malnutrition correlated with some measures of pulmonary function. The purpose of this study was to examine the energy requirements of malnourished patients with emphysema and acute effects of nutritional repletion on indices of pulmonary function and nutrition. We studied 6 malnourished patients with emphysema during a 3-wk admission to a clinical research unit. Initially, patients were allowed access to standard food sources ad libitum. Subsequently, if caloric goals were not met, nutritional supplementation was given orally. All patients receiving the ad libitum diet ingested calories in excess of their maintenance energy requirements. All patients increased their body weight (p less than 0.001) and percent ideal body weight (p less than 0.001). Anthropometric nutritional parameters showed a small but significant improvement (p less than 0.05). Although there was no significant change in spirometric results, lung volumes or DLCO after 3 wk maximal inspiratory mouth and transdiaphragmatic pressures increased (p less than 0.005). Peripheral skeletal muscle strength as measured by handgrip also improved (p less than 0.001). We conclude that inability to ingest an adequate number of calories was not the cause of weight loss in these patients. We also found that when given sufficient calories in excess of their needs, patients gain weight. Weight gain and improvement in anthropometric measurements are accompanied by significant improvement in ventilatory and peripheral muscle strength.

pubmed23n0125_13788

Oxygen consumption and transport in stable patients with chronic obstructive pulmonary disease.

We studied the relationship between oxygen consumption and systemic oxygen transport in 30 clinically stable patients with chronic obstructive pulmonary disease (COPD) before and after increasing oxygen transport by passive leg elevation to raise the cardiac output. Results were compared with those observed in 10 patients with silicosis. The effect of leg elevation on oxygen consumption was also studied in 12 normal subjects. Oxygen consumption was measured by a closed circuit system, cardiac output by the direct Fick method, and arterial oxygen content by a cooximeter. Supine oxygen consumption was correlated with oxygen transport in patients with COPD (r = 0.50, p less than 0.01), and with leg elevation transport increased from a mean of 516 +/- 23 (SEM) to 567 +/- 26 ml X min-1 X m-2 and consumption increased from a mean of 136 +/- 3 to 148 +/- 4 ml X min-1 X m-2 (both p less than 0.01). In patients with silicosis, leg elevation raised mean oxygen transport from 620 +/- 40.0 to 745 +/- 54.0 ml X min-1 X m-2 and mean consumption from 161 +/- 6 to 192 +/- 6 ml X min-1 X m-2 (both p less than 0.01). In normal subjects, no change in oxygen consumption was observed with leg elevation (154 +/- 8 to 152 +/- 6 ml X min-1 X m-2).(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen consumption and transport in stable patients with chronic obstructive pulmonary disease. We studied the relationship between oxygen consumption and systemic oxygen transport in 30 clinically stable patients with chronic obstructive pulmonary disease (COPD) before and after increasing oxygen transport by passive leg elevation to raise the cardiac output. Results were compared with those observed in 10 patients with silicosis. The effect of leg elevation on oxygen consumption was also studied in 12 normal subjects. Oxygen consumption was measured by a closed circuit system, cardiac output by the direct Fick method, and arterial oxygen content by a cooximeter. Supine oxygen consumption was correlated with oxygen transport in patients with COPD (r = 0.50, p less than 0.01), and with leg elevation transport increased from a mean of 516 +/- 23 (SEM) to 567 +/- 26 ml X min-1 X m-2 and consumption increased from a mean of 136 +/- 3 to 148 +/- 4 ml X min-1 X m-2 (both p less than 0.01). In patients with silicosis, leg elevation raised mean oxygen transport from 620 +/- 40.0 to 745 +/- 54.0 ml X min-1 X m-2 and mean consumption from 161 +/- 6 to 192 +/- 6 ml X min-1 X m-2 (both p less than 0.01). In normal subjects, no change in oxygen consumption was observed with leg elevation (154 +/- 8 to 152 +/- 6 ml X min-1 X m-2).(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13789

Is respiratory mucus hypersecretion really an innocent disorder? A 22-year mortality survey of 1,061 working men.

The relation of chronic air-flow limitation and respiratory mucus hypersecretion to all causes of mortality was studied in a population of 1,061 men working in the Paris area, surveyed initially in 1960/1961, and followed for 22 yr. During this period, 369 deaths occurred; VC, FEV1, FEV1/H3, and FEV1/VC were significantly associated with mortality, even when age, smoking, occupational dust exposure, and chronic phlegm were taken into account. Besides the obstructive disorder, the hypersecretory disorder (chronic phlegm) was significantly associated with mortality. Controlling, using Cox's model, for age, FEV1/H3, smoking habits, and dust exposure, all factors associated with chronic mucus hypersecretion and mortality, showed that phlegm production remained significantly related to death (relative risk, = 1.35; p less than 0.01). Although relatively weak, this relationship is not negligible in terms of public health because of the high prevalence of chronic phlegm.

Is respiratory mucus hypersecretion really an innocent disorder? A 22-year mortality survey of 1,061 working men. The relation of chronic air-flow limitation and respiratory mucus hypersecretion to all causes of mortality was studied in a population of 1,061 men working in the Paris area, surveyed initially in 1960/1961, and followed for 22 yr. During this period, 369 deaths occurred; VC, FEV1, FEV1/H3, and FEV1/VC were significantly associated with mortality, even when age, smoking, occupational dust exposure, and chronic phlegm were taken into account. Besides the obstructive disorder, the hypersecretory disorder (chronic phlegm) was significantly associated with mortality. Controlling, using Cox's model, for age, FEV1/H3, smoking habits, and dust exposure, all factors associated with chronic mucus hypersecretion and mortality, showed that phlegm production remained significantly related to death (relative risk, = 1.35; p less than 0.01). Although relatively weak, this relationship is not negligible in terms of public health because of the high prevalence of chronic phlegm.

pubmed23n0125_13790

Involuntary breath-stacking. An alternative method for vital capacity estimation in poorly cooperative subjects.

Performed correctly, the vital capacity (VC) is a useful indicator of the mechanical properties of the thorax and of neuromuscular performance. Unfortunately, its use is often limited by impaired comprehension, altered mental status, or inability to sustain forceful effort. Our purpose was to develop a measure of VC independent of subject cooperation. We estimated the subcomponents of VC (inspiratory capacity (IC) and expiratory reserve volume (ERV], using one-way valving of an external circuit to enforce cumulation or elimination of the tidal breaths stimulated by endogenous ventilatory drive. When configured to measure IC, gas entered the chest incrementally, until tidal effort became insufficient to overcome thoracic recoil. Valve rearrangement permitted analogous estimation of ERV. We tested the validity of this method in cooperative but naive subjects by comparing the VC measured in standard fashion (VCC) to the breath-stacked estimate (VCS). Thirty normal subjects and 20 ambulatory patients with diverse causes for respiratory impairment were studied. Peak and mean values of VCS correlated strongly with the corresponding values of VCC (r greater than or equal to 0.91). The coefficient of variation for sequential V VCS determinations (approximately equal to 5.5%) was comparable to that observed for VCC (approximately equal to 3.5%) in both subject groups, indicating acceptable reproducibility of the involuntary VCS measurement. VCS maneuvers were quickly completed and well tolerated. Involuntary breath-stacking may provide a useful estimate of VC in clinical settings where conventional methodology cannot be confidently applied.

Involuntary breath-stacking. An alternative method for vital capacity estimation in poorly cooperative subjects. Performed correctly, the vital capacity (VC) is a useful indicator of the mechanical properties of the thorax and of neuromuscular performance. Unfortunately, its use is often limited by impaired comprehension, altered mental status, or inability to sustain forceful effort. Our purpose was to develop a measure of VC independent of subject cooperation. We estimated the subcomponents of VC (inspiratory capacity (IC) and expiratory reserve volume (ERV], using one-way valving of an external circuit to enforce cumulation or elimination of the tidal breaths stimulated by endogenous ventilatory drive. When configured to measure IC, gas entered the chest incrementally, until tidal effort became insufficient to overcome thoracic recoil. Valve rearrangement permitted analogous estimation of ERV. We tested the validity of this method in cooperative but naive subjects by comparing the VC measured in standard fashion (VCC) to the breath-stacked estimate (VCS). Thirty normal subjects and 20 ambulatory patients with diverse causes for respiratory impairment were studied. Peak and mean values of VCS correlated strongly with the corresponding values of VCC (r greater than or equal to 0.91). The coefficient of variation for sequential V VCS determinations (approximately equal to 5.5%) was comparable to that observed for VCC (approximately equal to 3.5%) in both subject groups, indicating acceptable reproducibility of the involuntary VCS measurement. VCS maneuvers were quickly completed and well tolerated. Involuntary breath-stacking may provide a useful estimate of VC in clinical settings where conventional methodology cannot be confidently applied.

pubmed23n0125_13791

Comparison of tremor responses to orally administered albuterol and terbutaline.

This study was designed to compare the initial tremor response to 4.0 mg albuterol and 5.0 mg terbutaline orally administered and to study the question of tachyphylaxis by rechallenge after 3 wk of maintenance dosing. Twenty fasting patients with severe COPD in whom orally administered sympathomimetics were withheld for 2 wk were challenged with single doses of each drug in a crossover, randomized fashion 1 wk apart. Then after a further 3 wk of dosing 3 times a day of the second medication (10 patients received each medication), they were challenged once more 16 h after the last dose. Rest and postural tremor were measured at zero and 2 h using an accelerometer affixed to the finger, and measurements of subjective tremor, tremor power spectrum, plasma cyclic AMP and lactate, and forced vital capacity were also made. Postural tremor increased from 25.05 to 36.20 relative units for albuterol, an increase of 11.15 units, and from 24.90 to 57.70 units for terbutaline, an increase of 32.80 units (difference significant at p = 0.01). Plasma cyclic AMP (p less than 0.01) and lactate (p = 0.05) increases were also less for albuterol, and the FEV1 and FVC responses, though about one third less, did not differ significantly. After 3 wk, mean baseline tremor for both drugs was elevated even 16 h after the last 3 times a day dosing (38.00 and 33.10) for albuterol and terbutaline (difference, NS), and responses were much less to the single tablet (3.40 and 9.10, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of tremor responses to orally administered albuterol and terbutaline. This study was designed to compare the initial tremor response to 4.0 mg albuterol and 5.0 mg terbutaline orally administered and to study the question of tachyphylaxis by rechallenge after 3 wk of maintenance dosing. Twenty fasting patients with severe COPD in whom orally administered sympathomimetics were withheld for 2 wk were challenged with single doses of each drug in a crossover, randomized fashion 1 wk apart. Then after a further 3 wk of dosing 3 times a day of the second medication (10 patients received each medication), they were challenged once more 16 h after the last dose. Rest and postural tremor were measured at zero and 2 h using an accelerometer affixed to the finger, and measurements of subjective tremor, tremor power spectrum, plasma cyclic AMP and lactate, and forced vital capacity were also made. Postural tremor increased from 25.05 to 36.20 relative units for albuterol, an increase of 11.15 units, and from 24.90 to 57.70 units for terbutaline, an increase of 32.80 units (difference significant at p = 0.01). Plasma cyclic AMP (p less than 0.01) and lactate (p = 0.05) increases were also less for albuterol, and the FEV1 and FVC responses, though about one third less, did not differ significantly. After 3 wk, mean baseline tremor for both drugs was elevated even 16 h after the last 3 times a day dosing (38.00 and 33.10) for albuterol and terbutaline (difference, NS), and responses were much less to the single tablet (3.40 and 9.10, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13792

Ozone enhancement of platinum asthma in a primate model.

Three groups of adult male cynomolgus monkeys (Macaca fascicularis) were exposed to either 200 micrograms/m3 ammonium hexachloroplatinate [(NH4)2PtCl6], 200 micrograms (NH4)2PtCl6 concurrently with 1 ppm ozone (O3), or to 1 ppm O3 only. The animals were exposed by inhalation for 6 h per day, 5 days per week for 12 wk. The experimental design included methacholine preexposure and Na2PtCl6 bronchoprovocation challenge evaluations, Na2PtCl6 threshold skin tests, and sera for analyses of antibodies. Two weeks after the 12-wk exposures, these same indices were reevaluated. Baseline pulmonary function was not significantly affected by the exposure regimens; however, the combination of exposure to O3 and (NH4)2PtCl6 significantly reduced the concentration of platinum (Pt) salt and methacholine necessary to increase average pulmonary flow resistance (RL) 200% (EC200 RL). Ozone or Pt exposure alone had no significant effect on these parameters. Platinum and methacholine EC200 RL values were highly correlated for both Pt-exposed groups after exposure. These data indicated that combined O3 and Pt exposure significantly increased specific (Pt) and nonspecific (methacholine) bronchial hyperreactivity more often than did exposure to either O3 or the Pt salt alone. Combined O3 plus Pt exposure also significantly increases the incidence of positive Pt skin tests when compared with the other exposure groups. Similar to the human experience, radioallergosorbent testing (RAST) for Pt-specific antibodies was not as sensitive as direct skin testing in identifying allergic persons.

Ozone enhancement of platinum asthma in a primate model. Three groups of adult male cynomolgus monkeys (Macaca fascicularis) were exposed to either 200 micrograms/m3 ammonium hexachloroplatinate [(NH4)2PtCl6], 200 micrograms (NH4)2PtCl6 concurrently with 1 ppm ozone (O3), or to 1 ppm O3 only. The animals were exposed by inhalation for 6 h per day, 5 days per week for 12 wk. The experimental design included methacholine preexposure and Na2PtCl6 bronchoprovocation challenge evaluations, Na2PtCl6 threshold skin tests, and sera for analyses of antibodies. Two weeks after the 12-wk exposures, these same indices were reevaluated. Baseline pulmonary function was not significantly affected by the exposure regimens; however, the combination of exposure to O3 and (NH4)2PtCl6 significantly reduced the concentration of platinum (Pt) salt and methacholine necessary to increase average pulmonary flow resistance (RL) 200% (EC200 RL). Ozone or Pt exposure alone had no significant effect on these parameters. Platinum and methacholine EC200 RL values were highly correlated for both Pt-exposed groups after exposure. These data indicated that combined O3 and Pt exposure significantly increased specific (Pt) and nonspecific (methacholine) bronchial hyperreactivity more often than did exposure to either O3 or the Pt salt alone. Combined O3 plus Pt exposure also significantly increases the incidence of positive Pt skin tests when compared with the other exposure groups. Similar to the human experience, radioallergosorbent testing (RAST) for Pt-specific antibodies was not as sensitive as direct skin testing in identifying allergic persons.

pubmed23n0125_13793

Impaired exercise performance and pulmonary function in elite cyclists during low-level ozone exposure in a hot environment.

We evaluated the effects of low concentrations of ozone on the exercise performance and pulmonary function of 17 top-caliber endurance cyclists under conditions simulating competition and realistic temperature (31 degrees C). Each subject was randomly exposed to filtered air (FA), 0.12 and 0.20 ppm O3 on separate days in an environmental chamber. Each subject attempted to maintain submaximal exercise on a cycle ergometer equivalent to approximately 70% of maximal oxygen consumption (VO2max) for 60 min, followed by incremented (maximal) exercise until exhaustion. During submaximal exercise, average minute ventilation (VE) (89 L/min), VO2 (51 ml/min/kg or 72% VO2max), work load (260 W), and work time (57 min) were similar across all exposures. During maximal exercise, average peak VE (150 L/min), VO2 (68 ml/min/kg), work load (382 W), and ride time (263 s) were similar between 0.12 ppm O3 and FA. However, significant reductions in peak VE (18%), VO2 (16%), tidal volume (22%), work load (8%), and ride time (30%) occurred in 0.20 ppm O3 compared with those in FA. Postexercise decrements in forced expired volume in one second (FEV1) averaged 5.6% and 21.6% in 0.12 and 0.20 ppm O3, respectively. Ozone-related symptoms were mild in 0.12 ppm O3 but intensified and probably limited maximal performance in 13 subjects in 0.20 ppm O3. Changes in carbon monoxide diffusing capacity (adjusted for alveolar volume) were not significant across exposures. Nine subjects showed histamine hyperresponsiveness (i.e., greater than 20% decrease from the control postdiluent FEV1) after exposure to 0.20 ppm O3 as compared with 1 subject in 0.12 ppm O3.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired exercise performance and pulmonary function in elite cyclists during low-level ozone exposure in a hot environment. We evaluated the effects of low concentrations of ozone on the exercise performance and pulmonary function of 17 top-caliber endurance cyclists under conditions simulating competition and realistic temperature (31 degrees C). Each subject was randomly exposed to filtered air (FA), 0.12 and 0.20 ppm O3 on separate days in an environmental chamber. Each subject attempted to maintain submaximal exercise on a cycle ergometer equivalent to approximately 70% of maximal oxygen consumption (VO2max) for 60 min, followed by incremented (maximal) exercise until exhaustion. During submaximal exercise, average minute ventilation (VE) (89 L/min), VO2 (51 ml/min/kg or 72% VO2max), work load (260 W), and work time (57 min) were similar across all exposures. During maximal exercise, average peak VE (150 L/min), VO2 (68 ml/min/kg), work load (382 W), and ride time (263 s) were similar between 0.12 ppm O3 and FA. However, significant reductions in peak VE (18%), VO2 (16%), tidal volume (22%), work load (8%), and ride time (30%) occurred in 0.20 ppm O3 compared with those in FA. Postexercise decrements in forced expired volume in one second (FEV1) averaged 5.6% and 21.6% in 0.12 and 0.20 ppm O3, respectively. Ozone-related symptoms were mild in 0.12 ppm O3 but intensified and probably limited maximal performance in 13 subjects in 0.20 ppm O3. Changes in carbon monoxide diffusing capacity (adjusted for alveolar volume) were not significant across exposures. Nine subjects showed histamine hyperresponsiveness (i.e., greater than 20% decrease from the control postdiluent FEV1) after exposure to 0.20 ppm O3 as compared with 1 subject in 0.12 ppm O3.(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13794

Reperfusion of ischemic dog lung results in fever, leukopenia, and lung edema.

Pulmonary artery obstruction results in minimal parenchymal abnormalities in normal lung and diminishes edema formation in dog lungs injured by oleic acid. We tested the hypothesis that reperfusion of ischemic regions would result in significant injury in normal lung and would ablate the protective effect of ischemia in oleic acid injury. The pulmonary artery of the left diaphragmatic lobe was occluded for 48 h in 12 oleic-acid-injured and 10 normal animals. Observations made immediately before reperfusion and for 4 h after reperfusion in the awake dogs indicated that reperfusion resulted in systemic abnormalities in both groups of animals, including a rise in temperature, a fall in cardiac output, and a marked drop in circulating leukocytes. In uninjured animals, the reperfused lobe demonstrated an elevated wet-to-dry weight ratio of 5.70 +/- 0.13 compared with 4.42 +/- 0.06 for the right diaphragmatic lobe (p less than 0.05). Histologic examination revealed edema and white cell infiltrates in the alveoli of the reperfused lobe in uninjured animals. In injured animals, there was no difference in either wet-to-dry ratios or morphologic aspects between the lobes. The results demonstrate both a local and systemic toxic effect of reperfusion in normal animals and ablation of the partial protective effect of pulmonary artery occlusion in oleic-acid-injured animals.

Reperfusion of ischemic dog lung results in fever, leukopenia, and lung edema. Pulmonary artery obstruction results in minimal parenchymal abnormalities in normal lung and diminishes edema formation in dog lungs injured by oleic acid. We tested the hypothesis that reperfusion of ischemic regions would result in significant injury in normal lung and would ablate the protective effect of ischemia in oleic acid injury. The pulmonary artery of the left diaphragmatic lobe was occluded for 48 h in 12 oleic-acid-injured and 10 normal animals. Observations made immediately before reperfusion and for 4 h after reperfusion in the awake dogs indicated that reperfusion resulted in systemic abnormalities in both groups of animals, including a rise in temperature, a fall in cardiac output, and a marked drop in circulating leukocytes. In uninjured animals, the reperfused lobe demonstrated an elevated wet-to-dry weight ratio of 5.70 +/- 0.13 compared with 4.42 +/- 0.06 for the right diaphragmatic lobe (p less than 0.05). Histologic examination revealed edema and white cell infiltrates in the alveoli of the reperfused lobe in uninjured animals. In injured animals, there was no difference in either wet-to-dry ratios or morphologic aspects between the lobes. The results demonstrate both a local and systemic toxic effect of reperfusion in normal animals and ablation of the partial protective effect of pulmonary artery occlusion in oleic-acid-injured animals.

pubmed23n0125_13795

The pathogenesis of experimental pulmonary histoplasmosis. Correlative studies of histopathology, bronchoalveolar lavage, and respiratory function.

A murine model of acute pulmonary histoplasmosis was employed to study the pathogenesis of the disease process by means of histopathology, bronchoalveolar lavage, and respiratory function tests. These studies were performed on C57BL/6 mice from 8 h to 8 wk after intranasal inoculation of 10(5) yeast forms of Histoplasma capsulatum and on age-matched control animals that received saline only. At Week 1, the histopathology was characterized by subacute inflammation consisting of polymorphonuclear leukocytes (PMN), lymphocytes, and macrophages that infiltrated the interstitium around small bronchioles and adjacent alveoli. At Weeks 2 and 4, the infiltrates were comprised predominantly of lymphocytes and macrophages; noncaseating granulomas were present at Week 2. Aggregates of lymphoid cells were prominent along the bronchial tree and in perivascular distribution. Those in close contact with bronchiolar epithelium resembled hyperplastic bronchus associated lymphoid tissue. Quantitative studies of cells in the BAL fluid revealed a large influx of PMN at Week 1 with return to normal range by Week 2. At this time there was a significant (p less than 0.02) increase in lymphocytes that persisted through Week 8, although histopathologic changes were minimal in lung at this time. A significant decrease in the DLCO/TLC at Week 2 in association with a normal vital capacity indicated impairment of respiratory function secondary to the alveolitis induced by H. capsulatum infection rather than a reduction of lung volume. This model offers promise for additional correlative studies of lymphocyte subsets in lung tissue and alveolar spaces as well as of the functions subserved by these respective populations.

The pathogenesis of experimental pulmonary histoplasmosis. Correlative studies of histopathology, bronchoalveolar lavage, and respiratory function. A murine model of acute pulmonary histoplasmosis was employed to study the pathogenesis of the disease process by means of histopathology, bronchoalveolar lavage, and respiratory function tests. These studies were performed on C57BL/6 mice from 8 h to 8 wk after intranasal inoculation of 10(5) yeast forms of Histoplasma capsulatum and on age-matched control animals that received saline only. At Week 1, the histopathology was characterized by subacute inflammation consisting of polymorphonuclear leukocytes (PMN), lymphocytes, and macrophages that infiltrated the interstitium around small bronchioles and adjacent alveoli. At Weeks 2 and 4, the infiltrates were comprised predominantly of lymphocytes and macrophages; noncaseating granulomas were present at Week 2. Aggregates of lymphoid cells were prominent along the bronchial tree and in perivascular distribution. Those in close contact with bronchiolar epithelium resembled hyperplastic bronchus associated lymphoid tissue. Quantitative studies of cells in the BAL fluid revealed a large influx of PMN at Week 1 with return to normal range by Week 2. At this time there was a significant (p less than 0.02) increase in lymphocytes that persisted through Week 8, although histopathologic changes were minimal in lung at this time. A significant decrease in the DLCO/TLC at Week 2 in association with a normal vital capacity indicated impairment of respiratory function secondary to the alveolitis induced by H. capsulatum infection rather than a reduction of lung volume. This model offers promise for additional correlative studies of lymphocyte subsets in lung tissue and alveolar spaces as well as of the functions subserved by these respective populations.

pubmed23n0125_13796

Airways hyperreactivity and inflammation produced by aerosolization of human C5A des arg.

The premise of this study was that complement fragments would lead to granulocyte infiltration and to associated changes in airways reactivity. Inflammation was induced in large airways (greater than 1.0 mm) by aerosolization of the complement chemotactic factor, C5a des arg, which was isolated from activated human serum. Pulmonary function (resistance, compliance, and lung volume) and histamine reactivity were assessed at 4 and at 48 h after C5a des arg or a saline sham aerosol. Four hours after exposure to C5a des arg, the animals exhibited evidence of significant bronchoconstriction and hyperinflation. In addition, an increased responsiveness to histamine was demonstrated, which was not correlated with the degree of bronchospasm. By 48 h, these alterations were partially or completely resolved. Histologic examination and quantitation demonstrated significant accumulation of neutrophils, which was limited to airways 0.5 mm in or larger. Saline-treated animals also demonstrated a neutrophil infiltration, but significantly less than those treated with C5a des arg. However, these animals did not demonstrate hyperreactivity to histamine, and there was little change in baseline mechanical function. The mild inflammation associated in the saline control animals was demonstrated to be a result of intubation of the airways. Granulocyte dependence of the effects of C5a des arg was partially established by abrogation of these effects when the animals were rendered granulocytopenic with nitrogen mustard. We conclude that the physiologic responses of the airways to C5a des arg were largely granulocyte dependent. However, since granulocyte accumulation could occur without airways dysfunction, it is suggested that cell activation is an important step in producing neutrophil-associated airways hyperresponsiveness.

Airways hyperreactivity and inflammation produced by aerosolization of human C5A des arg. The premise of this study was that complement fragments would lead to granulocyte infiltration and to associated changes in airways reactivity. Inflammation was induced in large airways (greater than 1.0 mm) by aerosolization of the complement chemotactic factor, C5a des arg, which was isolated from activated human serum. Pulmonary function (resistance, compliance, and lung volume) and histamine reactivity were assessed at 4 and at 48 h after C5a des arg or a saline sham aerosol. Four hours after exposure to C5a des arg, the animals exhibited evidence of significant bronchoconstriction and hyperinflation. In addition, an increased responsiveness to histamine was demonstrated, which was not correlated with the degree of bronchospasm. By 48 h, these alterations were partially or completely resolved. Histologic examination and quantitation demonstrated significant accumulation of neutrophils, which was limited to airways 0.5 mm in or larger. Saline-treated animals also demonstrated a neutrophil infiltration, but significantly less than those treated with C5a des arg. However, these animals did not demonstrate hyperreactivity to histamine, and there was little change in baseline mechanical function. The mild inflammation associated in the saline control animals was demonstrated to be a result of intubation of the airways. Granulocyte dependence of the effects of C5a des arg was partially established by abrogation of these effects when the animals were rendered granulocytopenic with nitrogen mustard. We conclude that the physiologic responses of the airways to C5a des arg were largely granulocyte dependent. However, since granulocyte accumulation could occur without airways dysfunction, it is suggested that cell activation is an important step in producing neutrophil-associated airways hyperresponsiveness.

pubmed23n0125_13797

Nontraumatic fat embolization. A rare cause of new pulmonary infiltrates in an immunocompromised patient.

Diffuse pulmonary infiltrates and hypoxemia are common in immunocompromised patients. We describe a patient with lymphoma who developed hypoxemia and diffuse pulmonary infiltrates during treatment with corticosteroids. Open lung biopsy and postmortem examination indicated that the cause of the infiltrates was nontraumatic fat embolization (NTFE). Most previous cases of NTFE have implicated a fatty liver as the source of emboli; however, this patient had no fatty changes of the liver. The diagnosis of NTFE in an immunocompromised patient is difficult to make because its distinguishing features, such as hypoxemia, petechiae, and altered mental status, are nonspecific in this setting.

Nontraumatic fat embolization. A rare cause of new pulmonary infiltrates in an immunocompromised patient. Diffuse pulmonary infiltrates and hypoxemia are common in immunocompromised patients. We describe a patient with lymphoma who developed hypoxemia and diffuse pulmonary infiltrates during treatment with corticosteroids. Open lung biopsy and postmortem examination indicated that the cause of the infiltrates was nontraumatic fat embolization (NTFE). Most previous cases of NTFE have implicated a fatty liver as the source of emboli; however, this patient had no fatty changes of the liver. The diagnosis of NTFE in an immunocompromised patient is difficult to make because its distinguishing features, such as hypoxemia, petechiae, and altered mental status, are nonspecific in this setting.

pubmed23n0125_13798

Sarcoidosis simulating pulmonary veno-occlusive disease.

We describe a young woman who presented with a 6-month history of progressive pulmonary hypertension. At autopsy she was found to have noncaseating granulomas obliterating pulmonary veins, without granulomatous involvement of pulmonary arteries. Noncaseating granulomas were also present in the liver and hilar lymph nodes, confirming the diagnosis of sarcoidosis. To our knowledge this is the first reported case of pulmonary hypertension caused by sarcoidosis simulating pulmonary veno-occlusive disease.

Sarcoidosis simulating pulmonary veno-occlusive disease. We describe a young woman who presented with a 6-month history of progressive pulmonary hypertension. At autopsy she was found to have noncaseating granulomas obliterating pulmonary veins, without granulomatous involvement of pulmonary arteries. Noncaseating granulomas were also present in the liver and hilar lymph nodes, confirming the diagnosis of sarcoidosis. To our knowledge this is the first reported case of pulmonary hypertension caused by sarcoidosis simulating pulmonary veno-occlusive disease.

pubmed23n0125_13799

Delayed skin oxygenation following distal tibial revascularization (DTR). Implications for wound healing in late amputations.

This article summarizes the authors' experience with prospective transcutaneous oxygen mapping (PtcO2 mm Hg) in patients requiring distal tibial revascularization. Simultaneous measurements were performed measuring preoperatively and early (1-3 days) and late (5-8 days) postoperatively in eight patients undergoing DTR (Group 1) at the chest (CT), below-knee (BK), and midfoot (FT) levels. In an additional 12 patients (Group 2), PtcO2 was measured late postoperatively adjacent to forefoot amputations. PtcO2 measurements were made at room air (RA) and after inhalation of oxygen (O2) in order to evaluate restriction of oxygen delivery. Late postoperative PtcO2 at both BK and FT sites increased (P less than .05) compared to either preop or early postop values. Inhaled O2 increased PtcO2 greatest at the FT late postop time (P less than .001). Group 1 amputations and ischemic ulcers all healed within 4 weeks postoperatively, when PtcO2 values were greater than 25 mm Hg. More extensive amputations required in Group 2 also healed when PtcO2 values exceeded 25 mm Hg, but required a hospitalization period almost three times as long as that of Group 1.

Delayed skin oxygenation following distal tibial revascularization (DTR). Implications for wound healing in late amputations. This article summarizes the authors' experience with prospective transcutaneous oxygen mapping (PtcO2 mm Hg) in patients requiring distal tibial revascularization. Simultaneous measurements were performed measuring preoperatively and early (1-3 days) and late (5-8 days) postoperatively in eight patients undergoing DTR (Group 1) at the chest (CT), below-knee (BK), and midfoot (FT) levels. In an additional 12 patients (Group 2), PtcO2 was measured late postoperatively adjacent to forefoot amputations. PtcO2 measurements were made at room air (RA) and after inhalation of oxygen (O2) in order to evaluate restriction of oxygen delivery. Late postoperative PtcO2 at both BK and FT sites increased (P less than .05) compared to either preop or early postop values. Inhaled O2 increased PtcO2 greatest at the FT late postop time (P less than .001). Group 1 amputations and ischemic ulcers all healed within 4 weeks postoperatively, when PtcO2 values were greater than 25 mm Hg. More extensive amputations required in Group 2 also healed when PtcO2 values exceeded 25 mm Hg, but required a hospitalization period almost three times as long as that of Group 1.

pubmed23n0125_13800

Role of preoperative hemodynamic monitoring in intraoperative fluid management.

In this study the hemodynamic factors which contribute to postoperative mortality and morbidity were evaluated in 41 patients. Preoperative data were prospectively collected over a 5-year period. The patients underwent vascular and general surgical operative procedures. Among them, 23 patients had minor or no postoperative complications (group 1) and 18 patients suffered serious complications or died (group 2). Preoperative cardiac function was better in group 1, but both groups achieved their best cardiac index (CI) with fluids or pharmacologic manipulation preoperatively. Group 2 patients had longer operations, more blood loss, and were significantly hypovolemic postoperatively as indicated by lower pulmonary arterial wedge pressure (PAWP) and CI in comparison to the best preoperative values. When postoperative PAWP was higher than or within 3 mm Hg of the best preoperative level, complication rate was 14 per cent (3 of 21). In 15 of the 19 or 79 per cent of the patients, postoperative complications developed when PAWP decreased by 4 mm Hg or more. The difference in complications was significant (P less than 0.01). However, commonly measured parameters such as the amount of fluid infused, urine output, immediate postoperative heart rate, blood pressure, central venous pressure, and hemoglobin failed to reveal hemodynamically significant hypovolemia or lacticacidemia in group 2. The authors were unable to demonstrate a reduction in mortality or morbidity in group 2 patients in whom serious technical operative difficulties were also encountered.

Role of preoperative hemodynamic monitoring in intraoperative fluid management. In this study the hemodynamic factors which contribute to postoperative mortality and morbidity were evaluated in 41 patients. Preoperative data were prospectively collected over a 5-year period. The patients underwent vascular and general surgical operative procedures. Among them, 23 patients had minor or no postoperative complications (group 1) and 18 patients suffered serious complications or died (group 2). Preoperative cardiac function was better in group 1, but both groups achieved their best cardiac index (CI) with fluids or pharmacologic manipulation preoperatively. Group 2 patients had longer operations, more blood loss, and were significantly hypovolemic postoperatively as indicated by lower pulmonary arterial wedge pressure (PAWP) and CI in comparison to the best preoperative values. When postoperative PAWP was higher than or within 3 mm Hg of the best preoperative level, complication rate was 14 per cent (3 of 21). In 15 of the 19 or 79 per cent of the patients, postoperative complications developed when PAWP decreased by 4 mm Hg or more. The difference in complications was significant (P less than 0.01). However, commonly measured parameters such as the amount of fluid infused, urine output, immediate postoperative heart rate, blood pressure, central venous pressure, and hemoglobin failed to reveal hemodynamically significant hypovolemia or lacticacidemia in group 2. The authors were unable to demonstrate a reduction in mortality or morbidity in group 2 patients in whom serious technical operative difficulties were also encountered.

pubmed23n0125_13801

Electrocardiographic changes in cardiac patients with acute gallbladder disease.

Acute cholecystitis or biliary colic may be associated with angina pectoris, arrhythmias, or nonspecific ST-T wave changes on the electrocardiogram. A vagally mediated cardio-biliary reflex is the presumed cause of these changes. Three cases of acute exacerbation of biliary tract disease in patients with known coronary artery disease associated with transient electrocardiographic changes and no concurrent cardiac complaints or abnormalities are reported. The signs and symptoms of gallbladder and heart disease may overlap, making diagnosis difficult. These patients underwent extensive workups of both their cardiac and biliary disease, which did not document any acute cardiac problem. In patients with known coronary artery disease and acute cholecystitis, the surgeon should not be discouraged from cholecystectomy merely because of a "questionable" electrocardiogram. Undue delay in treatment while awaiting the results of the cardiac screen may result in both cardiac and septic complications.

Electrocardiographic changes in cardiac patients with acute gallbladder disease. Acute cholecystitis or biliary colic may be associated with angina pectoris, arrhythmias, or nonspecific ST-T wave changes on the electrocardiogram. A vagally mediated cardio-biliary reflex is the presumed cause of these changes. Three cases of acute exacerbation of biliary tract disease in patients with known coronary artery disease associated with transient electrocardiographic changes and no concurrent cardiac complaints or abnormalities are reported. The signs and symptoms of gallbladder and heart disease may overlap, making diagnosis difficult. These patients underwent extensive workups of both their cardiac and biliary disease, which did not document any acute cardiac problem. In patients with known coronary artery disease and acute cholecystitis, the surgeon should not be discouraged from cholecystectomy merely because of a "questionable" electrocardiogram. Undue delay in treatment while awaiting the results of the cardiac screen may result in both cardiac and septic complications.

pubmed23n0125_13802

Quality assessment of tetanus prophylaxis in the wounded patient.

New guidelines on tetanus prophylaxis in wound management have been prepared by the American College of Surgeons and are available in a poster format or in bulletins. The purpose of this study was to determine the impact of these educational brochures on tetanus prophylaxis in a hospital setting. The results of this study indicate that these informational brochures and posters had insignificant impact on the quality of prophylaxis against tetanus in our hospital. Innovative programs of information exchange and quality assurance are urgently needed to improve the delivery of health care.

Quality assessment of tetanus prophylaxis in the wounded patient. New guidelines on tetanus prophylaxis in wound management have been prepared by the American College of Surgeons and are available in a poster format or in bulletins. The purpose of this study was to determine the impact of these educational brochures on tetanus prophylaxis in a hospital setting. The results of this study indicate that these informational brochures and posters had insignificant impact on the quality of prophylaxis against tetanus in our hospital. Innovative programs of information exchange and quality assurance are urgently needed to improve the delivery of health care.

pubmed23n0125_13803

Pelvic fractures at a community hospital.

One hundred twenty-eight pelvic fractures were reviewed. Of the 128 patients with pelvic fractures, there were seven deaths. Pelvic fractures associated with the greatest blood loss and complications were those which occurred in crush-type injuries secondary to automobile accidents or other heavy impact injuries. Unless fractures were of a crush-type with massive fractures, the amount of blood loss correlated more closely with the history of injury than it did with the x-ray appearance of pelvic fracture. A single patient in this series had greater than 45 units blood loss and exhibited many of the basic problems encountered when dealing with patients with major pelvic fractures. The case of this patient is reviewed in detail, including component therapy for massive blood loss. The prophylactic use of caval filtration or an umbrella device might be warranted in patients with massive pelvic fractures.

Pelvic fractures at a community hospital. One hundred twenty-eight pelvic fractures were reviewed. Of the 128 patients with pelvic fractures, there were seven deaths. Pelvic fractures associated with the greatest blood loss and complications were those which occurred in crush-type injuries secondary to automobile accidents or other heavy impact injuries. Unless fractures were of a crush-type with massive fractures, the amount of blood loss correlated more closely with the history of injury than it did with the x-ray appearance of pelvic fracture. A single patient in this series had greater than 45 units blood loss and exhibited many of the basic problems encountered when dealing with patients with major pelvic fractures. The case of this patient is reviewed in detail, including component therapy for massive blood loss. The prophylactic use of caval filtration or an umbrella device might be warranted in patients with massive pelvic fractures.

pubmed23n0125_13804

Perforated gastric ulcers. A retrospective study of 32 patients.

During the last 6 years the authors have treated 99 patients with perforated peptic ulcers. Sixty-six patients had perforated pyloro-duodenal ulcers, while 32 patients were treated for perforated gastric ulcers, a ratio of 2:1. This article deals with the gastric ulcers treated by a surgical unit in an urban, 600-bed multidisciplinary hospital. The mean age of the patients was 58.7 years. In 71.8 per cent of the patients, the perforation was the first major manifestation of the ulcer disease. Seven patients (21.8%), all in the high-risk group according to the criteria of Boey et al. died. There was no death among the low-risk patient group. Eleven patients, all high-risk, had excision and/or biopsy of the ulcer followed by simple closure; three of these patients died (27.2%). Twenty patients, of whom seven were in the high-risk group, underwent gastrectomy; three deaths occurred (15%). The authors conclude that the underlying general health of the patient is a major determinant of the outcome following gastric ulcer perforation.

Perforated gastric ulcers. A retrospective study of 32 patients. During the last 6 years the authors have treated 99 patients with perforated peptic ulcers. Sixty-six patients had perforated pyloro-duodenal ulcers, while 32 patients were treated for perforated gastric ulcers, a ratio of 2:1. This article deals with the gastric ulcers treated by a surgical unit in an urban, 600-bed multidisciplinary hospital. The mean age of the patients was 58.7 years. In 71.8 per cent of the patients, the perforation was the first major manifestation of the ulcer disease. Seven patients (21.8%), all in the high-risk group according to the criteria of Boey et al. died. There was no death among the low-risk patient group. Eleven patients, all high-risk, had excision and/or biopsy of the ulcer followed by simple closure; three of these patients died (27.2%). Twenty patients, of whom seven were in the high-risk group, underwent gastrectomy; three deaths occurred (15%). The authors conclude that the underlying general health of the patient is a major determinant of the outcome following gastric ulcer perforation.

pubmed23n0125_13805

The competence and bacteriologic effect of the telescoped intestinal valve after small bowel resection.

In 20 dogs the distal one-third of the small intestine and the proximal 10 cm of the ascending colon were resected. Bowel continuity was established by the telescoping technique to create an intestinal valve in ten dogs (group A) and by conventional end-to-end anastomosis in ten dogs (group B). Diarrhea and weight loss were similar in both groups. The ileal bacterial growth was significantly higher than the jejunum in group A (P less than 0.001) but not in group B. The jejunal bacterial growth in group B was significantly higher than that in group A (P less than 0.01). Intestinal transit times were 212 +/- 16.0, 219 +/- 152.4, and 163 +/- 85.8 minutes for normal dogs, groups A and B respectively. The competence of the normal ileocecal valve, the telescoped valve, and conventional anastomosis were 56 +/- 1.7, 49.9 +/- 17.4 and 13.2 +/- 7.8 cm of barium, respectively. Artificial intestinal valve formed by the telescoping technique is safe, simple, and effective in reducing bacterial overgrowth in the jejunum and appears to prolong intestinal transit time.

The competence and bacteriologic effect of the telescoped intestinal valve after small bowel resection. In 20 dogs the distal one-third of the small intestine and the proximal 10 cm of the ascending colon were resected. Bowel continuity was established by the telescoping technique to create an intestinal valve in ten dogs (group A) and by conventional end-to-end anastomosis in ten dogs (group B). Diarrhea and weight loss were similar in both groups. The ileal bacterial growth was significantly higher than the jejunum in group A (P less than 0.001) but not in group B. The jejunal bacterial growth in group B was significantly higher than that in group A (P less than 0.01). Intestinal transit times were 212 +/- 16.0, 219 +/- 152.4, and 163 +/- 85.8 minutes for normal dogs, groups A and B respectively. The competence of the normal ileocecal valve, the telescoped valve, and conventional anastomosis were 56 +/- 1.7, 49.9 +/- 17.4 and 13.2 +/- 7.8 cm of barium, respectively. Artificial intestinal valve formed by the telescoping technique is safe, simple, and effective in reducing bacterial overgrowth in the jejunum and appears to prolong intestinal transit time.

pubmed23n0125_13806

Splanchnic hemodynamic changes after the distal spleno renal shunt.

Marked changes in preoperative to postoperative corrected sinusoidal pressures (CSP) occurred in 51 per cent of a series of 51 patients undergoing the distal splenorenal shunt. Twenty patients who had the highest incidence of partial portal vein thrombosis, (48%--Group I), showed minimal pre- to postoperative changes in CSP. Twelve patients (Group II) who increased their CSP to 4 mm Hg or greater had marked postoperative hyperbilirubinemia and decreased portal blood flow. Fourteen patients who decreased their CSP 4 mm Hg or more postoperatively also showed moderate portal blood flow decrease without significant changes in liver enzymes. Morbidity and mortality were not significantly different among the three groups. The significance of these hemodynamic changes is not known.

Splanchnic hemodynamic changes after the distal spleno renal shunt. Marked changes in preoperative to postoperative corrected sinusoidal pressures (CSP) occurred in 51 per cent of a series of 51 patients undergoing the distal splenorenal shunt. Twenty patients who had the highest incidence of partial portal vein thrombosis, (48%--Group I), showed minimal pre- to postoperative changes in CSP. Twelve patients (Group II) who increased their CSP to 4 mm Hg or greater had marked postoperative hyperbilirubinemia and decreased portal blood flow. Fourteen patients who decreased their CSP 4 mm Hg or more postoperatively also showed moderate portal blood flow decrease without significant changes in liver enzymes. Morbidity and mortality were not significantly different among the three groups. The significance of these hemodynamic changes is not known.

pubmed23n0125_13807

Isolation and partial characterization of a protein fraction from the opossum (Didelphis marsupialis) serum, with protecting property against the Bothrops jararaca snake venom.

Two separated methods were used to purify a fraction from the opossum (Didelphis marsupialis) serum able to protect mice against Bothrops jararaca venom. The first of them included an initial batch DEAE-Cellulose ion-exchange of the serum, followed by another ion-exchange chromatography on a Carboxymethyl Sepharose column. The second method was a column ion-exchange chromatography on DEAE-Sephacel. These techniques allowed to obtain a protein fraction which resulted homogeneous in cellulose acetate and conventional polyacrylamide gel electrophoresis. The obtained protein fraction proved to be a glycoprotein according to the positive staining with periodic acid Schiff. Sodium dodecylsulfate polyacrylamide gel electrophoresis of the B-mercaptoethanol-reduced fraction showed heterogeneity and allowed to estimate molecular weights in the range of 42,000 to 58,000 daltons. The obtained serum fraction could effectively block the lethal effect of B. jararaca venom when jointly injected to laboratory mice by peritoneal route.

Isolation and partial characterization of a protein fraction from the opossum (Didelphis marsupialis) serum, with protecting property against the Bothrops jararaca snake venom. Two separated methods were used to purify a fraction from the opossum (Didelphis marsupialis) serum able to protect mice against Bothrops jararaca venom. The first of them included an initial batch DEAE-Cellulose ion-exchange of the serum, followed by another ion-exchange chromatography on a Carboxymethyl Sepharose column. The second method was a column ion-exchange chromatography on DEAE-Sephacel. These techniques allowed to obtain a protein fraction which resulted homogeneous in cellulose acetate and conventional polyacrylamide gel electrophoresis. The obtained protein fraction proved to be a glycoprotein according to the positive staining with periodic acid Schiff. Sodium dodecylsulfate polyacrylamide gel electrophoresis of the B-mercaptoethanol-reduced fraction showed heterogeneity and allowed to estimate molecular weights in the range of 42,000 to 58,000 daltons. The obtained serum fraction could effectively block the lethal effect of B. jararaca venom when jointly injected to laboratory mice by peritoneal route.

pubmed23n0125_13808

Intravenous propafenone for termination of reentrant supraventricular tachycardia. A placebo-controlled, randomized, double-blind, crossover study.

To assess the antiarrhythmic efficacy of intravenous propafenone, 20 patients with inducible sustained supraventricular tachycardia received propafenone, 2 mg/kg body weight, or placebo in a double-blind, randomized, crossover study. Three patients had intra-atrial reentrant tachycardia, 3 had atrioventricular nodal reentrant tachycardia, and 14 had atrioventricular reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Termination of supraventricular tachycardia occurred in 15 of the 20 patients receiving propafenone but 0 of the 11 patients receiving placebo (p less than 0.01). Propafenone prolonged refractoriness and slowed conduction of the atrium, the atrioventricular node, and accessory atrioventricular bypass tracts, and these effects provided antiarrhythmic action to halt tachycardia. No adverse effects were observed in any patient. We conclude that intravenous propafenone is safe and effective in the acute treatment of various forms of reentrant supraventricular tachycardia.

Intravenous propafenone for termination of reentrant supraventricular tachycardia. A placebo-controlled, randomized, double-blind, crossover study. To assess the antiarrhythmic efficacy of intravenous propafenone, 20 patients with inducible sustained supraventricular tachycardia received propafenone, 2 mg/kg body weight, or placebo in a double-blind, randomized, crossover study. Three patients had intra-atrial reentrant tachycardia, 3 had atrioventricular nodal reentrant tachycardia, and 14 had atrioventricular reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Termination of supraventricular tachycardia occurred in 15 of the 20 patients receiving propafenone but 0 of the 11 patients receiving placebo (p less than 0.01). Propafenone prolonged refractoriness and slowed conduction of the atrium, the atrioventricular node, and accessory atrioventricular bypass tracts, and these effects provided antiarrhythmic action to halt tachycardia. No adverse effects were observed in any patient. We conclude that intravenous propafenone is safe and effective in the acute treatment of various forms of reentrant supraventricular tachycardia.

pubmed23n0125_13809

Reversible cold-induced abnormalities in myocardial perfusion and function in systemic sclerosis.

The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis.

Reversible cold-induced abnormalities in myocardial perfusion and function in systemic sclerosis. The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis.

pubmed23n0125_13810

Aeromonas intestinal infections in the United States.

To evaluate the clinical and epidemiologic aspects of aeromonas enteritis, we studied the cases of 34 persons nationwide from whom Aeromonas hydrophila had been isolated in large numbers from stool in 1984. Compared with 68 control subjects, these patients were more likely to have drunk untreated water, usually from private wells (odds ratio = 20.9; p less than 0.01). Eighteen of the isolates belonged to a single DNA-relatedness group of the eight described for Aeromonas species, but no clear correlation between illnesses in patients and any tested genotypic or phenotypic characteristic of recovered organisms was found. Gastrointestinal complaints tended to be chronic in infected adults and acute and severe in children. Nine patients had become ill after taking antimicrobial agents to which recovered Aeromonas species were resistant; 5 persons took antimicrobials to which their Aeromonas strains were susceptible and had alleviation or resolution of their gastrointestinal symptoms. These findings indicate that at least some Aeromonas strains are enteropathogenic for the normal host and that these organisms are acquired by drinking untreated water.

Aeromonas intestinal infections in the United States. To evaluate the clinical and epidemiologic aspects of aeromonas enteritis, we studied the cases of 34 persons nationwide from whom Aeromonas hydrophila had been isolated in large numbers from stool in 1984. Compared with 68 control subjects, these patients were more likely to have drunk untreated water, usually from private wells (odds ratio = 20.9; p less than 0.01). Eighteen of the isolates belonged to a single DNA-relatedness group of the eight described for Aeromonas species, but no clear correlation between illnesses in patients and any tested genotypic or phenotypic characteristic of recovered organisms was found. Gastrointestinal complaints tended to be chronic in infected adults and acute and severe in children. Nine patients had become ill after taking antimicrobial agents to which recovered Aeromonas species were resistant; 5 persons took antimicrobials to which their Aeromonas strains were susceptible and had alleviation or resolution of their gastrointestinal symptoms. These findings indicate that at least some Aeromonas strains are enteropathogenic for the normal host and that these organisms are acquired by drinking untreated water.

pubmed23n0125_13811

Plesiomonas enteric infections in the United States.

Thirty-one persons nationwide from whom Plesiomonas shigelloides was isolated in large numbers from stool in 1984 were compared with 62 matched control subjects. Infection with P. shigelloides was strongly associated with eating uncooked shellfish, usually raw oysters, in the 48 hours before the onset of illness (p less than 0.00001) and with foreign travel (p less than 0.00006), usually to Mexico. Most ill persons had self-limited diarrhea with blood and mucus in stool and other clinical findings that suggested enteroinvasiveness of infecting organisms. Two patients developed their illnesses after taking ampicillin for reasons unrelated to diarrhea; plesiomonads recovered from their stools were resistant to ampicillin. Seven persons with gastrointestinal complaints had alleviation or resolution of their symptoms after taking antimicrobial agents to which recovered plesiomonads were susceptible. These findings suggest that P. shigelloides may cause enteric disease in the normal host, that it may be acquired from eating uncooked shellfish, and that it may be a cause of travelers' diarrhea.

Plesiomonas enteric infections in the United States. Thirty-one persons nationwide from whom Plesiomonas shigelloides was isolated in large numbers from stool in 1984 were compared with 62 matched control subjects. Infection with P. shigelloides was strongly associated with eating uncooked shellfish, usually raw oysters, in the 48 hours before the onset of illness (p less than 0.00001) and with foreign travel (p less than 0.00006), usually to Mexico. Most ill persons had self-limited diarrhea with blood and mucus in stool and other clinical findings that suggested enteroinvasiveness of infecting organisms. Two patients developed their illnesses after taking ampicillin for reasons unrelated to diarrhea; plesiomonads recovered from their stools were resistant to ampicillin. Seven persons with gastrointestinal complaints had alleviation or resolution of their symptoms after taking antimicrobial agents to which recovered plesiomonads were susceptible. These findings suggest that P. shigelloides may cause enteric disease in the normal host, that it may be acquired from eating uncooked shellfish, and that it may be a cause of travelers' diarrhea.

pubmed23n0125_13812

Clinically silent atrial septal defects with evidence for cerebral embolization.

The cause of stroke in young patients frequently cannot be established. Eleven consecutive patients, age 50 and younger, had clinical evidence of cerebral embolization. Results of physical, radiographic, electrocardiographic, and two-dimensional echocardiographic examinations were normal in all patients. During normal respiration, eight of the patients had right-to-left shunts at the atrial level shown by microcavitation contrast two-dimensional echocardiography. Six of the eight patients with positive contrast studies had cardiac catheterization. Five of six patients had an atrial septal defect, normal right and left heart pressures, and small right-to-left shunts during a Valsalva strain. Four patients had surgical closure of the defect, which ranged in size from 5 to 10 mm. The remaining patients received anticoagulants. Interatrial communications appear to be common in young patients with stroke, suggesting paradoxical embolization as a possible mechanism. Contrast two-dimensional echocardiography should be done in such patients because it is the only noninvasive technique that reliably finds these defects.

Clinically silent atrial septal defects with evidence for cerebral embolization. The cause of stroke in young patients frequently cannot be established. Eleven consecutive patients, age 50 and younger, had clinical evidence of cerebral embolization. Results of physical, radiographic, electrocardiographic, and two-dimensional echocardiographic examinations were normal in all patients. During normal respiration, eight of the patients had right-to-left shunts at the atrial level shown by microcavitation contrast two-dimensional echocardiography. Six of the eight patients with positive contrast studies had cardiac catheterization. Five of six patients had an atrial septal defect, normal right and left heart pressures, and small right-to-left shunts during a Valsalva strain. Four patients had surgical closure of the defect, which ranged in size from 5 to 10 mm. The remaining patients received anticoagulants. Interatrial communications appear to be common in young patients with stroke, suggesting paradoxical embolization as a possible mechanism. Contrast two-dimensional echocardiography should be done in such patients because it is the only noninvasive technique that reliably finds these defects.

pubmed23n0125_13813

Assessing clinical skills of residents with standardized patients.

Current techniques do not provide a reproducible, reliable, or valid basis for assessing clinical skills. The need for large-scale direct observation and standardized assessment procedures has precluded development of better techniques. A project using standardized patients presenting with common clinical problems evaluated the skills of 336 internal medicine residents at 14 New England residency programs in 1289 standardized patient and resident encounters. Results indicated that reproducible assessment of the clinical skills could be achieved in approximately 1 day of testing time using standardized patients. Resident performance improved with years of training, and senior residents and those from programs with stronger reputations performed better and were more homogeneous in ability. Low correlations between standardized-patient-based measures of clinical skills and other evaluation techniques suggested that standardized patients provided unique information. Reactions of residents and faculty to standardized-patient-based evaluations were favorable.

Assessing clinical skills of residents with standardized patients. Current techniques do not provide a reproducible, reliable, or valid basis for assessing clinical skills. The need for large-scale direct observation and standardized assessment procedures has precluded development of better techniques. A project using standardized patients presenting with common clinical problems evaluated the skills of 336 internal medicine residents at 14 New England residency programs in 1289 standardized patient and resident encounters. Results indicated that reproducible assessment of the clinical skills could be achieved in approximately 1 day of testing time using standardized patients. Resident performance improved with years of training, and senior residents and those from programs with stronger reputations performed better and were more homogeneous in ability. Low correlations between standardized-patient-based measures of clinical skills and other evaluation techniques suggested that standardized patients provided unique information. Reactions of residents and faculty to standardized-patient-based evaluations were favorable.

pubmed23n0125_13814

Digitalis and diuretics: still the standard therapy?

Although digitalis preparations are effective in controlling the ventricular rate in atrial fibrillation and certain other supraventricular tachyarrhythmias, with consequent haemodynamic benefit, there is increasing controversy about significant sustained inotropic efficacy in patients in sinus rhythm. Digoxin toxicity is a serious hazard and subtherapeutic dosing a deception and waste of resources; blood levels are the key to optimum dosing. A considered withdrawal of the drug and reintroduction if haemodynamic deterioration ensues is probably the only way of proving in an individual patient if the drug is really worth using long-term. Diuretics have had a major place in management of cardiac failure, correcting the fluid overload. However there are a number of troublesome metabolic and other consequences, and excessive diuresis can be dangerous. Vasodilator therapy has recently had a major impact on management of more severe forms of cardiac failure, usually with coadministration of diuretics, but the predominant pattern of drug use in milder heart failure is to rely primarily or even exclusively on diuretics. Rational use of drugs in cardiac failure would be greatly facilitated by availability of simple non-invasive techniques to measure cardiac function and filling pressures. Until this becomes possible it will be difficult to alter the traditional pattern of long-term use of digoxin and diuretics whenever there have been symptoms attributable to heart failure.

Digitalis and diuretics: still the standard therapy? Although digitalis preparations are effective in controlling the ventricular rate in atrial fibrillation and certain other supraventricular tachyarrhythmias, with consequent haemodynamic benefit, there is increasing controversy about significant sustained inotropic efficacy in patients in sinus rhythm. Digoxin toxicity is a serious hazard and subtherapeutic dosing a deception and waste of resources; blood levels are the key to optimum dosing. A considered withdrawal of the drug and reintroduction if haemodynamic deterioration ensues is probably the only way of proving in an individual patient if the drug is really worth using long-term. Diuretics have had a major place in management of cardiac failure, correcting the fluid overload. However there are a number of troublesome metabolic and other consequences, and excessive diuresis can be dangerous. Vasodilator therapy has recently had a major impact on management of more severe forms of cardiac failure, usually with coadministration of diuretics, but the predominant pattern of drug use in milder heart failure is to rely primarily or even exclusively on diuretics. Rational use of drugs in cardiac failure would be greatly facilitated by availability of simple non-invasive techniques to measure cardiac function and filling pressures. Until this becomes possible it will be difficult to alter the traditional pattern of long-term use of digoxin and diuretics whenever there have been symptoms attributable to heart failure.

pubmed23n0125_13815

Idiopathic calcium urolithiasis: genetic aspects.

Seventy-nine stone-formers underwent a metabolic investigation and ABO blood group determination. Incidence of blood groups in patients was similar to ABO phenotypes distribution in general population. The 37.7 p. 100 showed family history for stones. Idiopathic hypercalciuria was present in 40.3 p. 100 of cases; stone-formers with positive family history had a higher incidence of hypercalciuria (46.8 p. 100) than subjects without affected relatives (31.5 p. 100). Patients with blood group A displayed hypercalciuria in the 54.5 p. 100 of cases while subjects with blood group O only in the 30.7 p. 100 (p less than 0.05). Glycosaminoglycans (GAGs) were reduced in the 36.9 p. 100 of the whole group and particularly in patients of blood group A. Patients with blood group A, with positive family history, showed higher mean values of calcium excretion and lower ones of GAGs. Our results seem to suggest that not only familiar factors play a significant role in stone disease pathogenesis but also some metabolic alteration may be linked to ABO phenotypes.

Idiopathic calcium urolithiasis: genetic aspects. Seventy-nine stone-formers underwent a metabolic investigation and ABO blood group determination. Incidence of blood groups in patients was similar to ABO phenotypes distribution in general population. The 37.7 p. 100 showed family history for stones. Idiopathic hypercalciuria was present in 40.3 p. 100 of cases; stone-formers with positive family history had a higher incidence of hypercalciuria (46.8 p. 100) than subjects without affected relatives (31.5 p. 100). Patients with blood group A displayed hypercalciuria in the 54.5 p. 100 of cases while subjects with blood group O only in the 30.7 p. 100 (p less than 0.05). Glycosaminoglycans (GAGs) were reduced in the 36.9 p. 100 of the whole group and particularly in patients of blood group A. Patients with blood group A, with positive family history, showed higher mean values of calcium excretion and lower ones of GAGs. Our results seem to suggest that not only familiar factors play a significant role in stone disease pathogenesis but also some metabolic alteration may be linked to ABO phenotypes.

pubmed23n0125_13816

[Clinical value of assays of parathyroid hormone and 25-hydroxyvitamin D in internal medicine].

Over a 3 years period, PTH, 25 OHD, calcium and phosphate levels were measured in all patients admitted to a department of Internal Medicine with abnormal phospho-calcic metabolism or bone disease. The diagnostic value of iPTH was analysed, especially in cases of hyper- and hypocalcaemia. In hypercalcaemia, the iPTH did not differentiate between the two main differential diagnoses: hyperparathyroidism and cancer. In patients with a negative calcium balance, the iPTH level is often raised and many help towards diagnosis. However, it should first of all orientate the clinician towards the detection of renal failure which is a common cause of this condition.

[Clinical value of assays of parathyroid hormone and 25-hydroxyvitamin D in internal medicine]. Over a 3 years period, PTH, 25 OHD, calcium and phosphate levels were measured in all patients admitted to a department of Internal Medicine with abnormal phospho-calcic metabolism or bone disease. The diagnostic value of iPTH was analysed, especially in cases of hyper- and hypocalcaemia. In hypercalcaemia, the iPTH did not differentiate between the two main differential diagnoses: hyperparathyroidism and cancer. In patients with a negative calcium balance, the iPTH level is often raised and many help towards diagnosis. However, it should first of all orientate the clinician towards the detection of renal failure which is a common cause of this condition.

pubmed23n0125_13817

Studies on the hydroxylation of vitamin D in man.

The authors have studied some of the factors influencing vitamin D hydroxylases in man, using two indirect experimental approaches. In the first study they have considered the effect of a long-term treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the serum levels of 25-hydroxyvitamin D (25-OHD) in postmenopausal osteoporosis, a condition in which high serum levels of 25-OHD and low mean levels of 1,25(OH)2D have been observed. In the second study the effects of the infusion of physiological doses of human parathyroid hormone (PTH) on the serum levels of 1,25(OH)2D and 24,25(OH)2D have been investigated. In the first study a decrease in the circulating levels of 25-OHD was observed during 1,25(OH)2D3 treatment. This could be considered as an indirect evidence of an inhibitory action of 1,25(OH)2D3 on 25-hydroxylase: in this view 1,25(OH)2D3 treatment decreases 25-hydroxylase activity, which is higher than normal in postmenopausal osteoporosis due to the low levels of 1,25(OH)2D. In the second study PTH infusion was followed by a remarkable increase in 1,25(OH)2D serum levels as a result of 1 alpha-hydroxylase stimulation, which was much higher in patients with hypoparathyroidism. The determination of 24,25(OH)2D levels during PTH infusion indicated an inhibitory effect on 24-hydroxylase.

Studies on the hydroxylation of vitamin D in man. The authors have studied some of the factors influencing vitamin D hydroxylases in man, using two indirect experimental approaches. In the first study they have considered the effect of a long-term treatment with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the serum levels of 25-hydroxyvitamin D (25-OHD) in postmenopausal osteoporosis, a condition in which high serum levels of 25-OHD and low mean levels of 1,25(OH)2D have been observed. In the second study the effects of the infusion of physiological doses of human parathyroid hormone (PTH) on the serum levels of 1,25(OH)2D and 24,25(OH)2D have been investigated. In the first study a decrease in the circulating levels of 25-OHD was observed during 1,25(OH)2D3 treatment. This could be considered as an indirect evidence of an inhibitory action of 1,25(OH)2D3 on 25-hydroxylase: in this view 1,25(OH)2D3 treatment decreases 25-hydroxylase activity, which is higher than normal in postmenopausal osteoporosis due to the low levels of 1,25(OH)2D. In the second study PTH infusion was followed by a remarkable increase in 1,25(OH)2D serum levels as a result of 1 alpha-hydroxylase stimulation, which was much higher in patients with hypoparathyroidism. The determination of 24,25(OH)2D levels during PTH infusion indicated an inhibitory effect on 24-hydroxylase.

pubmed23n0125_13818

Vitamin D status in the extreme age of life.

The aim of the present study was to investigate vitamin D status in the extreme age of life and to assess the ability of elderly people to synthesize vitamin D in skin, in response to artificial ultraviolet irradiation, and to hydroxylate the newly synthesized vitamin in the liver. The authors have determined the serum 25-hydroxyvitamin D concentrations in 43 healthy subjects (17 males and 26 females) aged 84 years or more. The changes induced in 25-OHD serum levels by whole-body artificial ultraviolet irradiation have also been studied in 10 healthy volunteers aged 41-90 years and, as a control, in 8 normal subjects aged 24-40 years. Serum 25-OHD has been determined, after lipid extraction of samples and column chromatography, by competitive protein binding assay using rat serum as the source of binding protein. The mean 25-OHD serum level in the group studied was 5.7 +/- 4.3 ng/ml, much lower than the mean observed in normal subjects aged 20-40 years (21.3 +/- 8.2 ng/ml). Men had higher levels than women. In the age group 84-89 years 25-OHD levels were higher than in subjects aged 90-96. Serum 25-OHD increased remarkably in all our normal subjects in response to artificial ultraviolet irradiation. Age-related differences in 25-OHD response to irradiation were not significant. The results of the present study indicate that vitamin D deficiency is common in the extreme age of life. It is probably a consequence of poor diet and lack of exposure to sunshine rather than of an impairment of cutaneous synthesis or liver hydroxylation of vitamin D.

Vitamin D status in the extreme age of life. The aim of the present study was to investigate vitamin D status in the extreme age of life and to assess the ability of elderly people to synthesize vitamin D in skin, in response to artificial ultraviolet irradiation, and to hydroxylate the newly synthesized vitamin in the liver. The authors have determined the serum 25-hydroxyvitamin D concentrations in 43 healthy subjects (17 males and 26 females) aged 84 years or more. The changes induced in 25-OHD serum levels by whole-body artificial ultraviolet irradiation have also been studied in 10 healthy volunteers aged 41-90 years and, as a control, in 8 normal subjects aged 24-40 years. Serum 25-OHD has been determined, after lipid extraction of samples and column chromatography, by competitive protein binding assay using rat serum as the source of binding protein. The mean 25-OHD serum level in the group studied was 5.7 +/- 4.3 ng/ml, much lower than the mean observed in normal subjects aged 20-40 years (21.3 +/- 8.2 ng/ml). Men had higher levels than women. In the age group 84-89 years 25-OHD levels were higher than in subjects aged 90-96. Serum 25-OHD increased remarkably in all our normal subjects in response to artificial ultraviolet irradiation. Age-related differences in 25-OHD response to irradiation were not significant. The results of the present study indicate that vitamin D deficiency is common in the extreme age of life. It is probably a consequence of poor diet and lack of exposure to sunshine rather than of an impairment of cutaneous synthesis or liver hydroxylation of vitamin D.

pubmed23n0125_13819

[Bone involvement in hypothyroidism in adults. Apropos of 20 patients].

Although bone changes in hyperthyroidism are well known, they have been much less studied in hypothyroidism and we set out to establish whether they did occur in the latter condition. We present the results of a prospective study of 20 adult patients, with acquired primary hypothyroidism. No changes in urinary or blood calcium or phosphorus metabolism were observed and serum parathormone, 25-hydro, 125-dihydro and 24-25-dihydroxycholecalciferol concentrations were normal. Histological examination of iliac crest bone biopsy after double labelling with tetracycline showed normal bone trabeculation volume, surface of resorption and rates of calcification. However, the relative osteoid volume was increased and there was a much higher osteoid thickness index. These observations may be explained by a global decrease in the activation and activity of the multicellular units of bone remodeling due to the general slowing of cellular metabolism encountered in that condition.

[Bone involvement in hypothyroidism in adults. Apropos of 20 patients]. Although bone changes in hyperthyroidism are well known, they have been much less studied in hypothyroidism and we set out to establish whether they did occur in the latter condition. We present the results of a prospective study of 20 adult patients, with acquired primary hypothyroidism. No changes in urinary or blood calcium or phosphorus metabolism were observed and serum parathormone, 25-hydro, 125-dihydro and 24-25-dihydroxycholecalciferol concentrations were normal. Histological examination of iliac crest bone biopsy after double labelling with tetracycline showed normal bone trabeculation volume, surface of resorption and rates of calcification. However, the relative osteoid volume was increased and there was a much higher osteoid thickness index. These observations may be explained by a global decrease in the activation and activity of the multicellular units of bone remodeling due to the general slowing of cellular metabolism encountered in that condition.

pubmed23n0125_13820

[Renal lithiasis in idiopathic hypercalciuria and primary hyperparathyroidism].

The high incidence of renal lithiasis in hyperparathyroidism (55 p. 100) suggests that PTH plays a causal role in stone production. It also motivates a systematic search for primary hyperparathyroidism in all patients with renal stones although it is only found in about 7 p. 100 of cases. PTH acts through the stimulation of 1.25(OH)2 vitamin D production and therefore, the absorption of calcium from the intestine, which in turn increases the filtrable calcium, hence the calciuria. In renal stones, in general, hypercalciuria represents one of the major metabolic disturbances, besides the hyperoxaluria, hyperuricosuria and the reduction of the inhibitors of crystallization. However, hypercalciuria is rarely the indirect result of excess PTH. It is usually caused by increased dietary ingestion of NaCl, meat, calcium and possibly carbohydrates.

[Renal lithiasis in idiopathic hypercalciuria and primary hyperparathyroidism]. The high incidence of renal lithiasis in hyperparathyroidism (55 p. 100) suggests that PTH plays a causal role in stone production. It also motivates a systematic search for primary hyperparathyroidism in all patients with renal stones although it is only found in about 7 p. 100 of cases. PTH acts through the stimulation of 1.25(OH)2 vitamin D production and therefore, the absorption of calcium from the intestine, which in turn increases the filtrable calcium, hence the calciuria. In renal stones, in general, hypercalciuria represents one of the major metabolic disturbances, besides the hyperoxaluria, hyperuricosuria and the reduction of the inhibitors of crystallization. However, hypercalciuria is rarely the indirect result of excess PTH. It is usually caused by increased dietary ingestion of NaCl, meat, calcium and possibly carbohydrates.

pubmed23n0125_13821

[Sensitivity of bone to parathyroid hormone in type I pseudohypoparathyroidism. 6 cases].

The sensitivity of bone to parathormone in pseudoparathyroidism is not well known. Six patients with Type I pseudohypoparathyroidism (4 with Albright's osteodystrophy) had increased alkaline phosphatase levels (5 patients) and radiological signs of periosteal resorption in the hand in one case. All patients had histological signs of increased surfaces of resorption and periosteocytic lacunae, increased osteoid surfaces and relative osteoid volume with no change of the index of osteoid thickness. These changes are identical to those observed in hyperparathyroidism which leads on to the discussion of the role of the increased parathormone secretion induced by the lack of calcium on the remodeling of bone. Our six cases show that there is no bone resistance to parathormone. The diversity of bone changes in hyperparathyroidism, similar to that of primary hyperparathyroidism, is without doubt dependent on the degree of renal insensitivity to PTH through the inactivation of vitamin D.

[Sensitivity of bone to parathyroid hormone in type I pseudohypoparathyroidism. 6 cases]. The sensitivity of bone to parathormone in pseudoparathyroidism is not well known. Six patients with Type I pseudohypoparathyroidism (4 with Albright's osteodystrophy) had increased alkaline phosphatase levels (5 patients) and radiological signs of periosteal resorption in the hand in one case. All patients had histological signs of increased surfaces of resorption and periosteocytic lacunae, increased osteoid surfaces and relative osteoid volume with no change of the index of osteoid thickness. These changes are identical to those observed in hyperparathyroidism which leads on to the discussion of the role of the increased parathormone secretion induced by the lack of calcium on the remodeling of bone. Our six cases show that there is no bone resistance to parathormone. The diversity of bone changes in hyperparathyroidism, similar to that of primary hyperparathyroidism, is without doubt dependent on the degree of renal insensitivity to PTH through the inactivation of vitamin D.

pubmed23n0125_13822

Diagnosis and treatment of heart failure in different European countries: a young AEMIE questionnaire.

To compare diagnosis and treatment of heart failure among different European countries, an anonymous questionnaire was developed and sent to young AEMIE members all over Europe. 159 filled-in questionnaires were received: 30 p. 100 from France (F), 25 p. 100 from Great Britain (GB), 21 p. 100 from the Benelux countries (NL), 13 p. 100 from Italy (I) and 11 p. 100 from West-Germany (D). Baseline characteristics of the participating physicians (age, years of hospital training, available equipment, etc.) were comparable among the different countries. There was good agreement in the value of history, clinical examination, ECG and chest X-ray for the diagnosis of heart failure. In all countries breathlessness, basal crepitations and gallop rhythm were counted among the most important signs of left heart failure. Whereas the value of gated-blood-pool scanning and Holter monitoring as a first diagnostic approach was unanimously denied, the value of 2D-echocardiography in heart failure was discussed controversially: in I, F and D 50-80 p. 100 of the physicians thought echocardiography a first-hand diagnostic tool, whereas only 20-30 p. 100 of the physicians in GB and NL recommended echocardiography in the first place. Diuretics, sodium reduced diet and afterload reduction (in GB only) are the first therapeutic measures in GB, NL and F. However, in I and D digitalis is still the cornerstone of therapy (greater than or equal to 50 p. 100!). Physicians of all European countries with the exception of the physicians in D prefer pure digoxin as the first digitalis preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis and treatment of heart failure in different European countries: a young AEMIE questionnaire. To compare diagnosis and treatment of heart failure among different European countries, an anonymous questionnaire was developed and sent to young AEMIE members all over Europe. 159 filled-in questionnaires were received: 30 p. 100 from France (F), 25 p. 100 from Great Britain (GB), 21 p. 100 from the Benelux countries (NL), 13 p. 100 from Italy (I) and 11 p. 100 from West-Germany (D). Baseline characteristics of the participating physicians (age, years of hospital training, available equipment, etc.) were comparable among the different countries. There was good agreement in the value of history, clinical examination, ECG and chest X-ray for the diagnosis of heart failure. In all countries breathlessness, basal crepitations and gallop rhythm were counted among the most important signs of left heart failure. Whereas the value of gated-blood-pool scanning and Holter monitoring as a first diagnostic approach was unanimously denied, the value of 2D-echocardiography in heart failure was discussed controversially: in I, F and D 50-80 p. 100 of the physicians thought echocardiography a first-hand diagnostic tool, whereas only 20-30 p. 100 of the physicians in GB and NL recommended echocardiography in the first place. Diuretics, sodium reduced diet and afterload reduction (in GB only) are the first therapeutic measures in GB, NL and F. However, in I and D digitalis is still the cornerstone of therapy (greater than or equal to 50 p. 100!). Physicians of all European countries with the exception of the physicians in D prefer pure digoxin as the first digitalis preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13823

New inotropic-vasodilating drugs in acute and chronic heart failure.

Clinical trials with new inotropic, non-adrenergic agents with vasodilating properties have open new perspectives for the treatment of acute and chronic heart failure. If their mechanism of action is not exactly known, they are likely to increase C.AMP by phosphodiesterase inhibition. A clear distinction has to be made concerning short- and long-term administration of these drugs. Amrinone (A) has been administered to 10 patients with low postoperative cardiac output as unique inotropic therapy and to 34 patients in severe cardiogenic shock, despite optimal treatment. In the latter group, A was added to the preliminary drugs. In both groups of patients, hemodynamics improved significantly, except in 4 patients in group II, who died. Except in one case with thrombocytopenia and one with supraventricular dysrhythmias, no serious side-effects were noted. No long-term treatment has been carried out in our institution. The literature has widely reported that the new inotropic drugs used in class III and IV patients, are likely to increase patient's well-being and exercise capacity, but not life expectancy.

New inotropic-vasodilating drugs in acute and chronic heart failure. Clinical trials with new inotropic, non-adrenergic agents with vasodilating properties have open new perspectives for the treatment of acute and chronic heart failure. If their mechanism of action is not exactly known, they are likely to increase C.AMP by phosphodiesterase inhibition. A clear distinction has to be made concerning short- and long-term administration of these drugs. Amrinone (A) has been administered to 10 patients with low postoperative cardiac output as unique inotropic therapy and to 34 patients in severe cardiogenic shock, despite optimal treatment. In the latter group, A was added to the preliminary drugs. In both groups of patients, hemodynamics improved significantly, except in 4 patients in group II, who died. Except in one case with thrombocytopenia and one with supraventricular dysrhythmias, no serious side-effects were noted. No long-term treatment has been carried out in our institution. The literature has widely reported that the new inotropic drugs used in class III and IV patients, are likely to increase patient's well-being and exercise capacity, but not life expectancy.

pubmed23n0125_13824

[Usefulness of ambulatory blood pressure monitoring in hypertensive patients].

Treated or untreated hypertensive patients may have very different blood pressure levels when measured by the doctor in his surgery and when measured by ambulatory monitoring during their usual everyday activities. It is now possible to record blood pressure non-invasively with a portable blood pressure measuring device, the Remler M2000. Using this device, we observed that less than half of the patients referred by their medical practitioner for hypertension had abnormally high blood pressures during their everyday activities. We also noted that the ambulatory blood pressure profile of a given hypertensive patient cannot be predicted from the blood pressure recorded by his or her doctor. Consequently, we concluded that ambulatory blood pressure recordings would appear to be essential for the detection of patients with high blood pressure readings at the doctor's surgery and during everyday activities. These patients probably include the only group which really needs appropriate antihypertensive therapy.

[Usefulness of ambulatory blood pressure monitoring in hypertensive patients]. Treated or untreated hypertensive patients may have very different blood pressure levels when measured by the doctor in his surgery and when measured by ambulatory monitoring during their usual everyday activities. It is now possible to record blood pressure non-invasively with a portable blood pressure measuring device, the Remler M2000. Using this device, we observed that less than half of the patients referred by their medical practitioner for hypertension had abnormally high blood pressures during their everyday activities. We also noted that the ambulatory blood pressure profile of a given hypertensive patient cannot be predicted from the blood pressure recorded by his or her doctor. Consequently, we concluded that ambulatory blood pressure recordings would appear to be essential for the detection of patients with high blood pressure readings at the doctor's surgery and during everyday activities. These patients probably include the only group which really needs appropriate antihypertensive therapy.

pubmed23n0125_13825

[Respiratory encephalopathy].

Encephalopathy is a common and sometimes a presenting feature of decompensated chronic respiratory failure. There is a wide number of clinical and paraclinical signs of this condition and four grades of severity without a close correlation with blood gas changes. This condition is the consequence of complex metabolic and circulatory disturbances resulting from the blood gas abnormalities. The prognosis is good when the respiratory failure is quickly and correctly treated.

[Respiratory encephalopathy]. Encephalopathy is a common and sometimes a presenting feature of decompensated chronic respiratory failure. There is a wide number of clinical and paraclinical signs of this condition and four grades of severity without a close correlation with blood gas changes. This condition is the consequence of complex metabolic and circulatory disturbances resulting from the blood gas abnormalities. The prognosis is good when the respiratory failure is quickly and correctly treated.

pubmed23n0125_13826

[Endocrine encephalopathies].

Endocrine encephalopathy, excepting hypoglycaemia and diabetes mellitus, is usually the clinical expression of non specific neuronal suffering secondary to a severe endocrine disturbance. The presentation is sometimes atypical and the prognosis poor but reversible with appropriate treatment; the condition should be recognised as the diagnosis can be made by simple investigations.

[Endocrine encephalopathies]. Endocrine encephalopathy, excepting hypoglycaemia and diabetes mellitus, is usually the clinical expression of non specific neuronal suffering secondary to a severe endocrine disturbance. The presentation is sometimes atypical and the prognosis poor but reversible with appropriate treatment; the condition should be recognised as the diagnosis can be made by simple investigations.

pubmed23n0125_13827

Cryoglobulinaemia: clinical features and response to treatment.

We report the clinical features and outcome of 16 patients with cryoglobulinaemia. Two patients with Type I cryoglobulinaemia both had IgG kappa monoclonal paraproteins. Nine of 10 with Type II disease had monoclonal IgM kappa and polyclonal IgG; one had monoclonal IgG kappa and polyclonal IgG in the cryoglobulin. Underlying disorders identified in 3 of the 4 Type III patients were Sjogren's syndrome, infective endocarditis, and non-A non-B hepatitis and HTLV III infection. The commonest presenting features were rash in 94 p. 100 (ulceration 25 p. 100), arthralgia in 63 p. 100 (erosive arthritis 32 p. 100), renal disease in 63 p. 100, neurological involvement in 56 p. 100, hepatomegaly in 32 p. 100 and splenomegaly in 32 p. 100. Major associated conditions were progressive bronchiectasis in one case, and severe peripheral vascular disease in another; underlying malignancy was found in 2 cases (lymphoma and malignant melanoma). Treatment was with plasma exchange (PE) and immunosuppressive drugs (ID) in 10, PE alone in 3, ID alone in 2 and antibiotics [corrected] in 1. Fourteen of 16 patients showed an initial clinical response and fall in cryoglobulin levels. Four patients have died, one each from gastro-intestinal haemorrhage, sepsis, pulmonary embolism and lymphoma. Of the remaining 12 patients, all are symptomatically controlled and 10 have persisting cryoglobulinaemia (3 on PE and ID, 2 on PE, 2 on ID and 3 on no treatment). Of the two cases in whom cryoglobulinaemia resolved, one (Type II) had received PE and ID and the other (Type III) had been treated with antibiotics and surgery for infective endocarditis.

Cryoglobulinaemia: clinical features and response to treatment. We report the clinical features and outcome of 16 patients with cryoglobulinaemia. Two patients with Type I cryoglobulinaemia both had IgG kappa monoclonal paraproteins. Nine of 10 with Type II disease had monoclonal IgM kappa and polyclonal IgG; one had monoclonal IgG kappa and polyclonal IgG in the cryoglobulin. Underlying disorders identified in 3 of the 4 Type III patients were Sjogren's syndrome, infective endocarditis, and non-A non-B hepatitis and HTLV III infection. The commonest presenting features were rash in 94 p. 100 (ulceration 25 p. 100), arthralgia in 63 p. 100 (erosive arthritis 32 p. 100), renal disease in 63 p. 100, neurological involvement in 56 p. 100, hepatomegaly in 32 p. 100 and splenomegaly in 32 p. 100. Major associated conditions were progressive bronchiectasis in one case, and severe peripheral vascular disease in another; underlying malignancy was found in 2 cases (lymphoma and malignant melanoma). Treatment was with plasma exchange (PE) and immunosuppressive drugs (ID) in 10, PE alone in 3, ID alone in 2 and antibiotics [corrected] in 1. Fourteen of 16 patients showed an initial clinical response and fall in cryoglobulin levels. Four patients have died, one each from gastro-intestinal haemorrhage, sepsis, pulmonary embolism and lymphoma. Of the remaining 12 patients, all are symptomatically controlled and 10 have persisting cryoglobulinaemia (3 on PE and ID, 2 on PE, 2 on ID and 3 on no treatment). Of the two cases in whom cryoglobulinaemia resolved, one (Type II) had received PE and ID and the other (Type III) had been treated with antibiotics and surgery for infective endocarditis.

pubmed23n0125_13828

Cryoproteins.

Proteins producing phenomena after exposure to the cold are reviewed but concentrating mainly on those that can produce aggregates within the laboratory. From three large series the frequencies were I. Mixed Cryoglobulins (polyclonal 50 p. 100, monoclonal 18 p. 100); II. Monoclonal Cryoglobulin (25 p. 100); III. Cryofibrinogen (3 p. 100) and IV. Cold Agglutinins (polyclonal 2 p. 100, monoclonal 2 p. 100). Mixed cryoglobulins present with any of the features of immune complex disease, but with the onset of renal involvement, over 50 p. 100 of the patients are dead within 5 years. Monoclonal cryoglobulins present with flat lesions in dependent areas, most reflecting an underlying or impending malignant B-cell neoplasm. Cryofibrinogen, missed in heparinised samples, is associated with thrombophlebitis migrans and sometimes underlying cancer, especially of the pancreas. Cold agglutinins cause Raynaud's phenomenon and haemolytic anaemia and the blood must be centrifuged at 37 degrees C. Treatments are discussed and are certainly encouraging in about one-third of the patients.

Cryoproteins. Proteins producing phenomena after exposure to the cold are reviewed but concentrating mainly on those that can produce aggregates within the laboratory. From three large series the frequencies were I. Mixed Cryoglobulins (polyclonal 50 p. 100, monoclonal 18 p. 100); II. Monoclonal Cryoglobulin (25 p. 100); III. Cryofibrinogen (3 p. 100) and IV. Cold Agglutinins (polyclonal 2 p. 100, monoclonal 2 p. 100). Mixed cryoglobulins present with any of the features of immune complex disease, but with the onset of renal involvement, over 50 p. 100 of the patients are dead within 5 years. Monoclonal cryoglobulins present with flat lesions in dependent areas, most reflecting an underlying or impending malignant B-cell neoplasm. Cryofibrinogen, missed in heparinised samples, is associated with thrombophlebitis migrans and sometimes underlying cancer, especially of the pancreas. Cold agglutinins cause Raynaud's phenomenon and haemolytic anaemia and the blood must be centrifuged at 37 degrees C. Treatments are discussed and are certainly encouraging in about one-third of the patients.

pubmed23n0125_13829

Lack of correlation of glycosylated haemoglobin level with the duration of diabetes or diabetic angiopathy.

Patients with severe diabetic angiopathy show an increased physiologic haemolysis. The aim of the present study was to evaluate the practical influence of the resulting reduced red cells half-life on the glycosylated haemoglobin (GHb) level as determined by a routine method. 168 diabetics, aged 55.7 +/- 1.3 years, were studied. The duration of disease ranged from 3 months to 34 years; 66 patients were insulin-treated and 87 had clinical features of arteritis and/or patent microangiopathy. A highly significant correlation was found between the mean plasma glucose level determined on the first day after admission and the GHb value. The slopes of regression curves of diabetics with and without angiopathies were similar. For a given mean glucose level there was no correlation between the GHb value and the duration of diabetes. So, in clinical practice, it is not necessary to take into account the duration of diabetes or the presence of angiopathies for explaining the GHb results.

Lack of correlation of glycosylated haemoglobin level with the duration of diabetes or diabetic angiopathy. Patients with severe diabetic angiopathy show an increased physiologic haemolysis. The aim of the present study was to evaluate the practical influence of the resulting reduced red cells half-life on the glycosylated haemoglobin (GHb) level as determined by a routine method. 168 diabetics, aged 55.7 +/- 1.3 years, were studied. The duration of disease ranged from 3 months to 34 years; 66 patients were insulin-treated and 87 had clinical features of arteritis and/or patent microangiopathy. A highly significant correlation was found between the mean plasma glucose level determined on the first day after admission and the GHb value. The slopes of regression curves of diabetics with and without angiopathies were similar. For a given mean glucose level there was no correlation between the GHb value and the duration of diabetes. So, in clinical practice, it is not necessary to take into account the duration of diabetes or the presence of angiopathies for explaining the GHb results.

pubmed23n0125_13830

An algorithm for differential diagnosis in jaundice and its applications.

During the recent years a broad spectrum of diagnostic methods have appeared for the differentiation of obstructive and nonobstructive jaundice: ultrasound examination, CT-scan, direct cholangiography, etc. These investigations are costly and not without risks. It is therefore essential to devise an optimal diagnostic strategy for each patient. Extensive clinical and clinical chemical information was collected from 1,002 jaundiced patients. By application of Bayes' theorem and logistic discriminant analysis a diagnostic algorithm was developed based upon 21 variables of the 107 variables collected. This algorithm permitted a probabilistic classification of jaundiced patients into four diagnostic categories: acute non-obstructive, chronic non-obstructive, benign obstructive and malignant obstructive jaundice. Adopting a probability limit of 0.80, 683 patients (69 p. 100) were correctly classified, 34 patients (3.5 p. 100) were wrongly so, and 268 patients (27 p. 100) could not be classified with a probability above 0.80 (doubtful cases). The algorithm was also tested in a further series of 110 jaundiced patients and found to perform equally well: 88 patients classified, 22 patients remaining doubtful. Patients with doubtful diagnoses should be referred to a non-invasive test such as ultrasound examination, whereas patients with definite diagnoses can be referred to invasive tests (liver biopsy, direct cholangiography) as appropriate. The diagnostic algorithm seems to be a reliable tool for the primary differential diagnosis of the jaundiced patient and can be used in the planning of further diagnostic tests for the individual patient.

An algorithm for differential diagnosis in jaundice and its applications. During the recent years a broad spectrum of diagnostic methods have appeared for the differentiation of obstructive and nonobstructive jaundice: ultrasound examination, CT-scan, direct cholangiography, etc. These investigations are costly and not without risks. It is therefore essential to devise an optimal diagnostic strategy for each patient. Extensive clinical and clinical chemical information was collected from 1,002 jaundiced patients. By application of Bayes' theorem and logistic discriminant analysis a diagnostic algorithm was developed based upon 21 variables of the 107 variables collected. This algorithm permitted a probabilistic classification of jaundiced patients into four diagnostic categories: acute non-obstructive, chronic non-obstructive, benign obstructive and malignant obstructive jaundice. Adopting a probability limit of 0.80, 683 patients (69 p. 100) were correctly classified, 34 patients (3.5 p. 100) were wrongly so, and 268 patients (27 p. 100) could not be classified with a probability above 0.80 (doubtful cases). The algorithm was also tested in a further series of 110 jaundiced patients and found to perform equally well: 88 patients classified, 22 patients remaining doubtful. Patients with doubtful diagnoses should be referred to a non-invasive test such as ultrasound examination, whereas patients with definite diagnoses can be referred to invasive tests (liver biopsy, direct cholangiography) as appropriate. The diagnostic algorithm seems to be a reliable tool for the primary differential diagnosis of the jaundiced patient and can be used in the planning of further diagnostic tests for the individual patient.

pubmed23n0125_13831

[Simulation of mental disorders. 1. Psychopathologic and psychosociodynamic aspects in a military environment].

In this paper, the author studies the malingering as a problem in the relationship between the doctor, patients and environment. Our field is the military community. After descriptive approach in the psychopathological disorders, the psychopathological and psychodynamic points of view give us the possibility to reach the most important level. This author's ideas are as follow--malingering is not a diagnostic but will be amount the general conditions of the relationship between doctor and his patient. The malingering is in some community, more one behavior of suspicion about some people than an attribution supported by facts. Finally, the suspicion of malingering as to be considered as an expression of the psychic phenomena in real groups funermore in the psychanalytical approach of the groups.

[Simulation of mental disorders. 1. Psychopathologic and psychosociodynamic aspects in a military environment]. In this paper, the author studies the malingering as a problem in the relationship between the doctor, patients and environment. Our field is the military community. After descriptive approach in the psychopathological disorders, the psychopathological and psychodynamic points of view give us the possibility to reach the most important level. This author's ideas are as follow--malingering is not a diagnostic but will be amount the general conditions of the relationship between doctor and his patient. The malingering is in some community, more one behavior of suspicion about some people than an attribution supported by facts. Finally, the suspicion of malingering as to be considered as an expression of the psychic phenomena in real groups funermore in the psychanalytical approach of the groups.

pubmed23n0125_13832

[Application of D.S.M. III to prison psychiatry: apropos of 100 diagnostic evaluations].

From hundred diagnostic evaluations according to D.S.M.-III classification, the authors bring to light the frequency of psychiatric disorders among the prisoners. "Substance use disorder" (axis 1) and "antisocial personality" (axis 2) are the more frequent diagnosis and they are often associated. "Schizophrenic disorders" are not unusual. On the other hand, there are not isolated "anxious disorders" on axis 1. Presence of anti-LAV antibodies (axis 3) among 51% of imprisoned drug addicts is pointed out.

[Application of D.S.M. III to prison psychiatry: apropos of 100 diagnostic evaluations]. From hundred diagnostic evaluations according to D.S.M.-III classification, the authors bring to light the frequency of psychiatric disorders among the prisoners. "Substance use disorder" (axis 1) and "antisocial personality" (axis 2) are the more frequent diagnosis and they are often associated. "Schizophrenic disorders" are not unusual. On the other hand, there are not isolated "anxious disorders" on axis 1. Presence of anti-LAV antibodies (axis 3) among 51% of imprisoned drug addicts is pointed out.

pubmed23n0125_13833

Neodymium: YAG laser surgery: the treatment of pediatric cataract disease.

Cataract extraction in children has undergone dramatic changes during the past 20 years, largely as a result of technologic advances. The neodymium: yttrium aluminum garnet (Nd:YAG) laser has indirectly brought the surgical technique full circle. The posterior capsule may be preserved at surgery and treated successfully with the Nd:YAG when necessary. In 16 such cases reported here, 11 patients with congenital and five with acquired cataracts all had improved vision after treatment with the Nd:YAG laser. The youngest patient was aged four years. The safety of Nd:YAG laser therapy is supported by this study.

Neodymium: YAG laser surgery: the treatment of pediatric cataract disease. Cataract extraction in children has undergone dramatic changes during the past 20 years, largely as a result of technologic advances. The neodymium: yttrium aluminum garnet (Nd:YAG) laser has indirectly brought the surgical technique full circle. The posterior capsule may be preserved at surgery and treated successfully with the Nd:YAG when necessary. In 16 such cases reported here, 11 patients with congenital and five with acquired cataracts all had improved vision after treatment with the Nd:YAG laser. The youngest patient was aged four years. The safety of Nd:YAG laser therapy is supported by this study.

pubmed23n0125_13834

Optic disc edema and Lyme disease.

A seven-year-old child developed a febrile rash, migratory arthritis, and neurologic signs. Three days earlier, the child had been bitten by a tick. An eye examination two months later revealed bilateral papilledema, although the cerebrospinal fluid pressure was 170 mm. The IgM antibody titer for the Ixodes dammini spirochete was 1:256. I dammini is the tick vector for the Borrelia spirochete that causes Lyme disease. The papilledema receded with treatment over a month's time, and bilateral pigment epithelial mottling at the fovea was present after one year.

Optic disc edema and Lyme disease. A seven-year-old child developed a febrile rash, migratory arthritis, and neurologic signs. Three days earlier, the child had been bitten by a tick. An eye examination two months later revealed bilateral papilledema, although the cerebrospinal fluid pressure was 170 mm. The IgM antibody titer for the Ixodes dammini spirochete was 1:256. I dammini is the tick vector for the Borrelia spirochete that causes Lyme disease. The papilledema receded with treatment over a month's time, and bilateral pigment epithelial mottling at the fovea was present after one year.

pubmed23n0125_13835

Neurosyphilis and retrobulbar neuritis in a patient with AIDS.

A 33-year-old homosexual patient with acquired immune deficiency syndrome (AIDS) developed sudden unilateral loss of vision. Slit-lamp and funduscopic examination of the affected eye was completely within normal limits. The patient, however, had a Marcus Gunn pupil, decreased color vision, and a large central scotoma on visual field examination. This was consistent with retrobulbar optic neuritis. Laboratory investigation revealed a highly positive serum and cerebrospinal fluid venereal disease reaction level (VDRL). A diagnosis of neurosyphilis was made, and the patient was treated with ten days of intravenous penicillin therapy. Ophthalmologists should be aware that many patients with AIDS have also been exposed to syphilis. Regardless of their clinical presentation, all AIDS patients should be examined and tested for syphilis and treated as is necessary.

Neurosyphilis and retrobulbar neuritis in a patient with AIDS. A 33-year-old homosexual patient with acquired immune deficiency syndrome (AIDS) developed sudden unilateral loss of vision. Slit-lamp and funduscopic examination of the affected eye was completely within normal limits. The patient, however, had a Marcus Gunn pupil, decreased color vision, and a large central scotoma on visual field examination. This was consistent with retrobulbar optic neuritis. Laboratory investigation revealed a highly positive serum and cerebrospinal fluid venereal disease reaction level (VDRL). A diagnosis of neurosyphilis was made, and the patient was treated with ten days of intravenous penicillin therapy. Ophthalmologists should be aware that many patients with AIDS have also been exposed to syphilis. Regardless of their clinical presentation, all AIDS patients should be examined and tested for syphilis and treated as is necessary.

pubmed23n0125_13836

Opportunistic infections of the retina and posterior segment.

Opportunistic infections of the retina are becoming a more frequent diagnostic and therapeutic challenge as immunosuppressed patients become more common. Viral, fungal, protozoan, and bacterial agents may be encountered. Diagnostic and therapeutic considerations, illustrated by case histories, are presented in this article. Viral infections are characterized by progressive exudation and hemorrhagic necrosis in a segmental distribution corresponding to the retinal vasculature. Protozoan, fungal, and bacterial infections may demonstrate more focal lesions with greater vitreous involvement. Diagnosis is established by clinical examination of body fluids. Antimicrobial drugs alone or combined with vitrectomy are effective therapy for fungal, bacterial, and protozoan infections. Antiviral drugs have yielded more disappointing results in the management of viral retinitis.

Opportunistic infections of the retina and posterior segment. Opportunistic infections of the retina are becoming a more frequent diagnostic and therapeutic challenge as immunosuppressed patients become more common. Viral, fungal, protozoan, and bacterial agents may be encountered. Diagnostic and therapeutic considerations, illustrated by case histories, are presented in this article. Viral infections are characterized by progressive exudation and hemorrhagic necrosis in a segmental distribution corresponding to the retinal vasculature. Protozoan, fungal, and bacterial infections may demonstrate more focal lesions with greater vitreous involvement. Diagnosis is established by clinical examination of body fluids. Antimicrobial drugs alone or combined with vitrectomy are effective therapy for fungal, bacterial, and protozoan infections. Antiviral drugs have yielded more disappointing results in the management of viral retinitis.

pubmed23n0125_13837

Posterior decompensation syndrome: macular failure versus senile macular degeneration.

Macular cone death in adults is caused by failure of the system that carries away the retinal biologic wastes. This failure may be termed the posterior decompensation syndrome, a name intended to convey the dynamic concept of imbalance between formation and elimination of waste. Because of centripetal fluid flow in the subretinal space, a disproportionate amount of drusen-like debris accumulates upon the surface of the lamina vitrea at the posterior pole. Recognition of this concept is the key to prevention of macular failure by reducing the amount of waste generated from the peripheral retina or its transport to the macula.

Posterior decompensation syndrome: macular failure versus senile macular degeneration. Macular cone death in adults is caused by failure of the system that carries away the retinal biologic wastes. This failure may be termed the posterior decompensation syndrome, a name intended to convey the dynamic concept of imbalance between formation and elimination of waste. Because of centripetal fluid flow in the subretinal space, a disproportionate amount of drusen-like debris accumulates upon the surface of the lamina vitrea at the posterior pole. Recognition of this concept is the key to prevention of macular failure by reducing the amount of waste generated from the peripheral retina or its transport to the macula.

pubmed23n0125_13838

Anatomy of the round window niche.

The contributing elements to boundaries of the round window niche are superiorly the tegmen fossula fenestra rotunda (roof support), inferiorly the fustis (depth) and area concamerata, anteriorly the sustentaculum (support) and postis anterior (anterior pillar), and posteriorly the postis posterior (posterior pillar) and the subiculum (underlying supporting structure). Variations in their size and orientation can give rise to significant variability in the overall size and shape of the round window niche.

Anatomy of the round window niche. The contributing elements to boundaries of the round window niche are superiorly the tegmen fossula fenestra rotunda (roof support), inferiorly the fustis (depth) and area concamerata, anteriorly the sustentaculum (support) and postis anterior (anterior pillar), and posteriorly the postis posterior (posterior pillar) and the subiculum (underlying supporting structure). Variations in their size and orientation can give rise to significant variability in the overall size and shape of the round window niche.

pubmed23n0125_13839

Middle cranial fossa acoustic neuroma excision: results and complications.

The middle cranial fossa surgical approach has been used for the removal of acoustic neuromas in 43 patients at the University of Iowa since 1974. Hearing was maintained in 50% of patients with tumors 1.5 cm or less outside the porus acusticus. Postoperative hearing, facial nerve function, and complications were similar to reports using the suboccipital or retrosigmoid approach to preserve hearing for this size tumor. The character of the tumor appears to dictate the postoperative outcome rather than the surgical approach.

Middle cranial fossa acoustic neuroma excision: results and complications. The middle cranial fossa surgical approach has been used for the removal of acoustic neuromas in 43 patients at the University of Iowa since 1974. Hearing was maintained in 50% of patients with tumors 1.5 cm or less outside the porus acusticus. Postoperative hearing, facial nerve function, and complications were similar to reports using the suboccipital or retrosigmoid approach to preserve hearing for this size tumor. The character of the tumor appears to dictate the postoperative outcome rather than the surgical approach.

pubmed23n0125_13840

Verrucous carcinoma of the temporal bone.

Verrucous carcinoma, a familiar lesion of the oral cavity and larynx, is distinctly rare in the ear. We report five cases of verrucous carcinoma of the temporal bone, each of which fulfills Ackerman's histologic and biologic criteria. Only three cases of verrucous carcinoma of the ear have been previously reported. Most cases of verrucous cancers of the head and neck demonstrate a lack of nodal involvement, relatively slow growth potential, local invasiveness, and responsiveness to surgical treatment. In our five cases of verrucous carcinoma of the temporal bone, three had a biologic behavior similar to other verrucous tumors, while two cases were unusually aggressive. Three patients were treated surgically and had favorable outcomes, while the remaining two were treated with combination therapy. These cases highlight the difficulty in diagnosis and treatment as well as the lack of understanding of the biologic behavior of this rare otologic entity.

Verrucous carcinoma of the temporal bone. Verrucous carcinoma, a familiar lesion of the oral cavity and larynx, is distinctly rare in the ear. We report five cases of verrucous carcinoma of the temporal bone, each of which fulfills Ackerman's histologic and biologic criteria. Only three cases of verrucous carcinoma of the ear have been previously reported. Most cases of verrucous cancers of the head and neck demonstrate a lack of nodal involvement, relatively slow growth potential, local invasiveness, and responsiveness to surgical treatment. In our five cases of verrucous carcinoma of the temporal bone, three had a biologic behavior similar to other verrucous tumors, while two cases were unusually aggressive. Three patients were treated surgically and had favorable outcomes, while the remaining two were treated with combination therapy. These cases highlight the difficulty in diagnosis and treatment as well as the lack of understanding of the biologic behavior of this rare otologic entity.

pubmed23n0125_13841

Histologic findings in two very small intracanalicular solitary schwannomas of the eighth nerve.

Two very small intracanalicular tumors, resected en bloc with the complete eighth nerve, were serially sectioned in order to study the relationship between the tumors and the nerves of origin. Both cases met the size criteria for hearing conservation surgery; however, the patient with the smaller tumor and the better hearing had no recognizable cochlear nerve fibers passing the tumor. The cochlear nerve in the patient with poorer hearing was completely free of tumor. The tumor with the infiltrated cochlear nerve seemed to originate from the inferior vestibular nerve. The other tumor seemed to arise from the superior vestibular nerve. Proximally, the tumors occupied a more central location in the involved nerves, but they abruptly became eccentric and exophytic as they proceeded laterally. Nerve fibers remaining about the tumors were displaced to the periphery. These nerve fiber aggregates became quite thin and attenuated, frequently separating into smaller aggregates which, ultimately, were incorporated into the tumors. As fibers came closer to the tumors, they tended to change from their longitudinal direction toward a more circumferential orientation about the surface of the tumors. The tumor-nerve fiber interfaces were quite variable throughout the course of the tumor, ranging from large aggregates of nerve fibers distinctly separate from the tumors to aggregates separate but tightly applied to the tumors without a tissue plane between, to aggregates partially incorporated within the periphery of the tumors, to aggregates completely incorporated into the periphery of the tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Histologic findings in two very small intracanalicular solitary schwannomas of the eighth nerve. Two very small intracanalicular tumors, resected en bloc with the complete eighth nerve, were serially sectioned in order to study the relationship between the tumors and the nerves of origin. Both cases met the size criteria for hearing conservation surgery; however, the patient with the smaller tumor and the better hearing had no recognizable cochlear nerve fibers passing the tumor. The cochlear nerve in the patient with poorer hearing was completely free of tumor. The tumor with the infiltrated cochlear nerve seemed to originate from the inferior vestibular nerve. The other tumor seemed to arise from the superior vestibular nerve. Proximally, the tumors occupied a more central location in the involved nerves, but they abruptly became eccentric and exophytic as they proceeded laterally. Nerve fibers remaining about the tumors were displaced to the periphery. These nerve fiber aggregates became quite thin and attenuated, frequently separating into smaller aggregates which, ultimately, were incorporated into the tumors. As fibers came closer to the tumors, they tended to change from their longitudinal direction toward a more circumferential orientation about the surface of the tumors. The tumor-nerve fiber interfaces were quite variable throughout the course of the tumor, ranging from large aggregates of nerve fibers distinctly separate from the tumors to aggregates separate but tightly applied to the tumors without a tissue plane between, to aggregates partially incorporated within the periphery of the tumors, to aggregates completely incorporated into the periphery of the tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13842

Stapedectomy results in a residency training program.

As the total number of stapedectomy procedures has declined, the adequacy of residency training for this procedure must be evaluated. Results of 5 years of stapedectomies performed by the resident otology service at the Massachusetts Eye and Ear Infirmary from Oct 1, 1979, through Sept 30, 1984, are reviewed and compared with other published results. A suggestion is made for improving the residency teaching program.

Stapedectomy results in a residency training program. As the total number of stapedectomy procedures has declined, the adequacy of residency training for this procedure must be evaluated. Results of 5 years of stapedectomies performed by the resident otology service at the Massachusetts Eye and Ear Infirmary from Oct 1, 1979, through Sept 30, 1984, are reviewed and compared with other published results. A suggestion is made for improving the residency teaching program.

pubmed23n0125_13843

Perilymphatic fistula: a histopathologic study.

Over the last two decades, clinical criteria for perilymphatic fistulae have been defined to the extent that differentiation can be made between such fistulae and other balance-affecting disorders such as Meniere's syndrome. On the assumption that the specimens in the temporal bone bank of the University of Chicago Medical School that had been obtained from patients having vertigo, hearing loss, or both, before those clinical criteria were so defined might have been classified incorrectly, we proposed a retrospective histopathologic study, with prediction of two independent variables: a clinical history and physical findings consistent with the diagnosis of perilymphatic fistula and communication between the vestibule and the middle ear adjacent to or via the fissula ante fenestram. Eleven pairs of temporal bones with the histologic diagnosis of idiopathic labyrinthine hydrops were evaluated before the clinical histories relevant to those specimens were reviewed. In one specimen, a communication between the vestibule and the middle ear space was identified. In none of the other specimens was there a similar communication. As this study continued, significance was given to the histologic details of the communication between the middle ear and posterior canal ampulla. The temporal bones without these communications did not have clinical histories consistent with the diagnosis of perilymphatic fistula.

Perilymphatic fistula: a histopathologic study. Over the last two decades, clinical criteria for perilymphatic fistulae have been defined to the extent that differentiation can be made between such fistulae and other balance-affecting disorders such as Meniere's syndrome. On the assumption that the specimens in the temporal bone bank of the University of Chicago Medical School that had been obtained from patients having vertigo, hearing loss, or both, before those clinical criteria were so defined might have been classified incorrectly, we proposed a retrospective histopathologic study, with prediction of two independent variables: a clinical history and physical findings consistent with the diagnosis of perilymphatic fistula and communication between the vestibule and the middle ear adjacent to or via the fissula ante fenestram. Eleven pairs of temporal bones with the histologic diagnosis of idiopathic labyrinthine hydrops were evaluated before the clinical histories relevant to those specimens were reviewed. In one specimen, a communication between the vestibule and the middle ear space was identified. In none of the other specimens was there a similar communication. As this study continued, significance was given to the histologic details of the communication between the middle ear and posterior canal ampulla. The temporal bones without these communications did not have clinical histories consistent with the diagnosis of perilymphatic fistula.

pubmed23n0125_13844

Diagnosis and management of anomalies of the craniovertebral junction.

The term craniovertebral junction refers to an area comprising the inferior portion of the occipital bone surrounding the foramen magnum and the first two cervical vertebrae. A variety of anomalies of bony, meningeal, and neural elements are known to occur in this region, producing a wide spectrum of clinical symptoms. These can range from dizziness, ataxia, and nuchal headaches to obvious quadriparesis and cranial nerve palsies. Often the symptoms are vague with an evolution marked by temporary exacerbations and remissions. The diagnosis can be difficult, and in our experience is best achieved by combining a neurotologic and neurologic evaluation. We discuss here the symptoms and diagnosis in ten patients with lesions at the craniovertebral junction. The surgical management of two cases of basilar invagination is described, and the controversies regarding the technique are discussed.

Diagnosis and management of anomalies of the craniovertebral junction. The term craniovertebral junction refers to an area comprising the inferior portion of the occipital bone surrounding the foramen magnum and the first two cervical vertebrae. A variety of anomalies of bony, meningeal, and neural elements are known to occur in this region, producing a wide spectrum of clinical symptoms. These can range from dizziness, ataxia, and nuchal headaches to obvious quadriparesis and cranial nerve palsies. Often the symptoms are vague with an evolution marked by temporary exacerbations and remissions. The diagnosis can be difficult, and in our experience is best achieved by combining a neurotologic and neurologic evaluation. We discuss here the symptoms and diagnosis in ten patients with lesions at the craniovertebral junction. The surgical management of two cases of basilar invagination is described, and the controversies regarding the technique are discussed.

pubmed23n0125_13845

[Incontinentia pigmenti. Study of 3 families].

Ten cases of incontinentia pigmenti are reported. All patients, corresponding to three families, were female. In one case a Turner's syndrome phenotype (XO) with mosaicism 46 XX/46 X; i (Xq) was observed. This finding seems to confirm that the disease is transmitted through a dominant gene carried on the X chromosome. Dental alterations were the most frequent of associated abnormalities, being present in all 10 patients. We regard these abnormalities as important as they permit a retrospective diagnosis in adult patients after the skin lesions have disappeared. EEG alterations (essentially an increase in the slow component) were also observed in the majority of cases.

[Incontinentia pigmenti. Study of 3 families]. Ten cases of incontinentia pigmenti are reported. All patients, corresponding to three families, were female. In one case a Turner's syndrome phenotype (XO) with mosaicism 46 XX/46 X; i (Xq) was observed. This finding seems to confirm that the disease is transmitted through a dominant gene carried on the X chromosome. Dental alterations were the most frequent of associated abnormalities, being present in all 10 patients. We regard these abnormalities as important as they permit a retrospective diagnosis in adult patients after the skin lesions have disappeared. EEG alterations (essentially an increase in the slow component) were also observed in the majority of cases.

pubmed23n0125_13846

Clinical use of an insert earphone.

There are several applications of and advantages to using an insert earphone. An insert earphone has three parts: a transducer to convert electrical energy to sound, a conduit to deliver the sound into the ear canal, and a coupler connecting the device to the canal. The data from this study indicate that there is a distinct advantage in using insert earphones over TDH-49 phones (standard headphones) in the attenuation of low frequency ambient noise. The use of insert earphones will permit one to test hearing in areas of higher ambient noise than was previously possible. Insert earphones are used to shorten the hearing aid selection process. A technique is described in which only one real ear measurement is required for an accurate hearing aid fitting. Most, but not all, of the masking dilemmas that are encountered with standard headphones are circumvented or eliminated by using insert earphones. In brain stem auditory evoked response testing, the insert earphone reduces the stimulus artifact without influencing the acoustic signal. Finally, the insert earphone solves the collapsing ear canal problem.

Clinical use of an insert earphone. There are several applications of and advantages to using an insert earphone. An insert earphone has three parts: a transducer to convert electrical energy to sound, a conduit to deliver the sound into the ear canal, and a coupler connecting the device to the canal. The data from this study indicate that there is a distinct advantage in using insert earphones over TDH-49 phones (standard headphones) in the attenuation of low frequency ambient noise. The use of insert earphones will permit one to test hearing in areas of higher ambient noise than was previously possible. Insert earphones are used to shorten the hearing aid selection process. A technique is described in which only one real ear measurement is required for an accurate hearing aid fitting. Most, but not all, of the masking dilemmas that are encountered with standard headphones are circumvented or eliminated by using insert earphones. In brain stem auditory evoked response testing, the insert earphone reduces the stimulus artifact without influencing the acoustic signal. Finally, the insert earphone solves the collapsing ear canal problem.

pubmed23n0125_13847

Comparative study of age-related cochlear hair cell loss.

Age-related hair cell loss has been studied in squirrel monkeys using surface preparation of the organ of Corti. Increasing hair cell loss starting at the apex is seen as a function of age. This finding is discussed in the light of our studies in guinea pigs, chinchillas, and rabbits. Reviewed with other human and experimental data, it would appear that many species of animals have age-related histological damage similar to that seen in the human organ of Corti.

Comparative study of age-related cochlear hair cell loss. Age-related hair cell loss has been studied in squirrel monkeys using surface preparation of the organ of Corti. Increasing hair cell loss starting at the apex is seen as a function of age. This finding is discussed in the light of our studies in guinea pigs, chinchillas, and rabbits. Reviewed with other human and experimental data, it would appear that many species of animals have age-related histological damage similar to that seen in the human organ of Corti.

pubmed23n0125_13848

[Association of a pediatric bullous eruption, cutaneous and muscular atrophy, hyperpigmentation and dysmorphism. A new entity?].

We report the case of a young patient who presented with dysmorphism, bullous eruption of childhood, cutaneous and muscular atrophy and hyperpigmentation. Attempts were made to find out where this case fits in the nosological framework. This young boy without any particular family history was born with facial dysmorphism consisting of micrognathia, right microphtalmos, gothic palate and left facial palsy of the peripheral type. At the age of 2 years and 9 months, generalized fragility of the skin appeared in the form of a recurrent bullous eruption. The bullae left numerous atrophic and depigmented scars; they spared the mucosae, and there was no photosensitivity. At the same time, generalized skin atrophy developed: the subcutaneous venous network was abnormally visible and there was diffuse hyperpigmentation. The hair was fine, curly and thin. The teeth dystrophic and abnormally positioned. The cornea of the right eye was invaded by conjunctiva. The bullous eruption subsided when the child was about 6 years' old, but the skin atrophy became worse and was accompanied with amyotrophy of the limbs and retraction in flexion of the joints at the extremities. Chronic ulcerations were present on the lower limbs. Statural and ponderal growth, as well as mental development were normal. The biochemical examinations performed revealed no abnormality. Light and electron microscopy of the skin showed a normal dermis-epidermis junction, but the anchorage fibres were rarefied. The dermal connective tissue was abnormal, with thin collagen fibres and disorganized fibrillae. Fibroblasts were hypoplastic and numerous. The elastic network was meagre and elastic fibres had a slashed appearance. Biopsy of a palmar nodule showed cheloid-like lesions. The nosological discussion involved some congenital bullous diseases and certain forms of connective tissue dystrophia. Among the bullous diseases, congenital poikiloderma, as described by Weary and Kindler, is unaccompanied with amyotrophy, articular retraction or dysmorphism. According to Verret et al., the bulla is located at the dermis-epidermis junction. Recessive dystrophic epidermolysis bullosa seems to differ from our case in that skin atrophy is localized and amyotrophy, dysmorphism and disorders of pigmentation are absent. In addition, we found no histological evidence of collagenolysis. Mendes Da Costa's bullous dystrophy can be excluded, as there was no nanism, microcephaly or diffuse alopecia in our patient. Among connective tissue dystrophias, acrogeria Ehlers-Danlos type IV syndrome does not include bullous eruption, amyotrophy or articular retraction.(ABSTRACT TRUNCATED AT 400 WORDS)

[Association of a pediatric bullous eruption, cutaneous and muscular atrophy, hyperpigmentation and dysmorphism. A new entity?]. We report the case of a young patient who presented with dysmorphism, bullous eruption of childhood, cutaneous and muscular atrophy and hyperpigmentation. Attempts were made to find out where this case fits in the nosological framework. This young boy without any particular family history was born with facial dysmorphism consisting of micrognathia, right microphtalmos, gothic palate and left facial palsy of the peripheral type. At the age of 2 years and 9 months, generalized fragility of the skin appeared in the form of a recurrent bullous eruption. The bullae left numerous atrophic and depigmented scars; they spared the mucosae, and there was no photosensitivity. At the same time, generalized skin atrophy developed: the subcutaneous venous network was abnormally visible and there was diffuse hyperpigmentation. The hair was fine, curly and thin. The teeth dystrophic and abnormally positioned. The cornea of the right eye was invaded by conjunctiva. The bullous eruption subsided when the child was about 6 years' old, but the skin atrophy became worse and was accompanied with amyotrophy of the limbs and retraction in flexion of the joints at the extremities. Chronic ulcerations were present on the lower limbs. Statural and ponderal growth, as well as mental development were normal. The biochemical examinations performed revealed no abnormality. Light and electron microscopy of the skin showed a normal dermis-epidermis junction, but the anchorage fibres were rarefied. The dermal connective tissue was abnormal, with thin collagen fibres and disorganized fibrillae. Fibroblasts were hypoplastic and numerous. The elastic network was meagre and elastic fibres had a slashed appearance. Biopsy of a palmar nodule showed cheloid-like lesions. The nosological discussion involved some congenital bullous diseases and certain forms of connective tissue dystrophia. Among the bullous diseases, congenital poikiloderma, as described by Weary and Kindler, is unaccompanied with amyotrophy, articular retraction or dysmorphism. According to Verret et al., the bulla is located at the dermis-epidermis junction. Recessive dystrophic epidermolysis bullosa seems to differ from our case in that skin atrophy is localized and amyotrophy, dysmorphism and disorders of pigmentation are absent. In addition, we found no histological evidence of collagenolysis. Mendes Da Costa's bullous dystrophy can be excluded, as there was no nanism, microcephaly or diffuse alopecia in our patient. Among connective tissue dystrophias, acrogeria Ehlers-Danlos type IV syndrome does not include bullous eruption, amyotrophy or articular retraction.(ABSTRACT TRUNCATED AT 400 WORDS)

pubmed23n0125_13849

[Cutaneous expansion by inflatable implant].

The capacity of the skin to stretch and expand, as shown in pregnancy, has been used by Radovan who, in 1976, introduced skin expanders made of silicone. These are empty balloons of different sizes and shapes which are surgically placed under the skin and gradually filled with saline. The saline solution is introduced through a valve with a syringe and a 21 G needle. Skin expansion usually requires 6 to 8 weeks to be completed. Transient redness of the skin is frequently observed. A thin capsule can be found around the expander but does not need to be removed. The excess skin can be utilized as advancement flap, rotation flap or even two-stage distant flap. Our experience is based on 33 expansions performed in 26 patients (table I). Giant naevi were the most frequent lesions treated (20 cases), and face, scalp and neck were the most frequent localizations (27/33 cases) (table II). Complications occurred in 21 p. 100 of the cases, and 5 expanders had to be removed. Nevertheless, expansion could be completed in most cases, sometimes after replacement of the prosthesis. The results of repair surgery using expanded skin have always been satisfactory: in colour and texture the expanded skin was similar to that of adjacent areas, and sensation was preserved. Skin expansion in fact made it possible to perform local flaps--which usually represent the best solution for skin replacement--by creating hyperlaxity in areas adjacent to the pathological areas. There has been no retraction of the expanded skin, and the scars have shown no tendency to hypertrophic reaction or distension.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cutaneous expansion by inflatable implant]. The capacity of the skin to stretch and expand, as shown in pregnancy, has been used by Radovan who, in 1976, introduced skin expanders made of silicone. These are empty balloons of different sizes and shapes which are surgically placed under the skin and gradually filled with saline. The saline solution is introduced through a valve with a syringe and a 21 G needle. Skin expansion usually requires 6 to 8 weeks to be completed. Transient redness of the skin is frequently observed. A thin capsule can be found around the expander but does not need to be removed. The excess skin can be utilized as advancement flap, rotation flap or even two-stage distant flap. Our experience is based on 33 expansions performed in 26 patients (table I). Giant naevi were the most frequent lesions treated (20 cases), and face, scalp and neck were the most frequent localizations (27/33 cases) (table II). Complications occurred in 21 p. 100 of the cases, and 5 expanders had to be removed. Nevertheless, expansion could be completed in most cases, sometimes after replacement of the prosthesis. The results of repair surgery using expanded skin have always been satisfactory: in colour and texture the expanded skin was similar to that of adjacent areas, and sensation was preserved. Skin expansion in fact made it possible to perform local flaps--which usually represent the best solution for skin replacement--by creating hyperlaxity in areas adjacent to the pathological areas. There has been no retraction of the expanded skin, and the scars have shown no tendency to hypertrophic reaction or distension.(ABSTRACT TRUNCATED AT 250 WORDS)

pubmed23n0125_13850

Effect of conductive hearing loss and middle ear surgery on binaural hearing.

This study investigated whether conductive hearing loss reduces normal binaural hearing advantages and whether binaural hearing advantages are normal in patients who have had hearing thresholds improved by middle ear surgery. Binaural hearing was assessed at a test frequency of 500 Hz using the masking level difference and interaural time discrimination thresholds. Results indicated that binaural hearing is often poor in conductive lesion patients and that the reduction in binaural hearing is not always consistent with a simple attenuation of the acoustic signal. Poor binaural hearing sometimes occurs even when middle ear surgery has resulted in bilaterally normal hearing thresholds. Our preliminary results are consistent with the interpretation that auditory deprivation due to conductive hearing loss may result in poor binaural auditory processing.

Effect of conductive hearing loss and middle ear surgery on binaural hearing. This study investigated whether conductive hearing loss reduces normal binaural hearing advantages and whether binaural hearing advantages are normal in patients who have had hearing thresholds improved by middle ear surgery. Binaural hearing was assessed at a test frequency of 500 Hz using the masking level difference and interaural time discrimination thresholds. Results indicated that binaural hearing is often poor in conductive lesion patients and that the reduction in binaural hearing is not always consistent with a simple attenuation of the acoustic signal. Poor binaural hearing sometimes occurs even when middle ear surgery has resulted in bilaterally normal hearing thresholds. Our preliminary results are consistent with the interpretation that auditory deprivation due to conductive hearing loss may result in poor binaural auditory processing.

pubmed23n0125_13851

Recurrent mixed tumor.

Recurrence of benign neoplasms can usually be attributed to incomplete excision. Such is the case with benign mixed tumors of salivary glands. Certain histopathologic features of mixed tumors, however, appear to facilitate recurrences. These are: a predominantly myxoid composition, and transcapsular extension by the tumor. Multicentric origin is possible, but it must be regarded as a much lower order of probability.

Recurrent mixed tumor. Recurrence of benign neoplasms can usually be attributed to incomplete excision. Such is the case with benign mixed tumors of salivary glands. Certain histopathologic features of mixed tumors, however, appear to facilitate recurrences. These are: a predominantly myxoid composition, and transcapsular extension by the tumor. Multicentric origin is possible, but it must be regarded as a much lower order of probability.

pubmed23n0125_13852

Malleus grip prosthesis.

The malleus grip prosthesis is designed for ears with conductive hearing loss caused by pathologic conditions of the stapes in association with pathologic conditions of the malleus or incus. The malleus grip procedure was performed on 220 ears, and follow-up studies are available on 203. Mild to profound sensorineural hearing losses occurred in 16 (8.37%). The remaining 187, on the first postoperative test, had an average air-bone gap of 14 dB, and subsequent examinations on 100 of them showed no significant change with the passage of time. The procedure is technically more difficult than stapes surgery for otosclerosis, and success is highly dependent upon selection of appropriate cases and meticulous implantation of the prosthesis.

Malleus grip prosthesis. The malleus grip prosthesis is designed for ears with conductive hearing loss caused by pathologic conditions of the stapes in association with pathologic conditions of the malleus or incus. The malleus grip procedure was performed on 220 ears, and follow-up studies are available on 203. Mild to profound sensorineural hearing losses occurred in 16 (8.37%). The remaining 187, on the first postoperative test, had an average air-bone gap of 14 dB, and subsequent examinations on 100 of them showed no significant change with the passage of time. The procedure is technically more difficult than stapes surgery for otosclerosis, and success is highly dependent upon selection of appropriate cases and meticulous implantation of the prosthesis.

pubmed23n0125_13853

Effect on biochemical values of heat treatment of plasma for the safe handling of samples from AIDS patients.

There is widespread concern amongst laboratory workers over the risks of exposure to human T cell lymphotrophic virus III [HTLV III] and the possibility of the subsequent development of the acquired immune deficiency syndrome [AIDS]. HTLV III is thermolabile and is completely inactivated by heating at 56 degrees C for 30 min. We have studied the effect that such heating would have on analyses performed routinely in our laboratory.

Effect on biochemical values of heat treatment of plasma for the safe handling of samples from AIDS patients. There is widespread concern amongst laboratory workers over the risks of exposure to human T cell lymphotrophic virus III [HTLV III] and the possibility of the subsequent development of the acquired immune deficiency syndrome [AIDS]. HTLV III is thermolabile and is completely inactivated by heating at 56 degrees C for 30 min. We have studied the effect that such heating would have on analyses performed routinely in our laboratory.

pubmed23n0125_13854

Whole blood osmolality.

The osmolality of plasma and heparinised whole blood samples collected from hospital patients was estimated using measurement of the depression of freezing point. There was no clinically significant difference between osmolality measurement made on either whole blood, or plasma taken from the same patient. Neither cell volume nor haemolysis was found to affect the measurement. The reproducibility of whole blood measurements was similar to that for determinations carried out on plasma. Measurement of osmolality on whole blood is quicker and cheaper and needs a smaller specimen than if serum or plasma is used.

Whole blood osmolality. The osmolality of plasma and heparinised whole blood samples collected from hospital patients was estimated using measurement of the depression of freezing point. There was no clinically significant difference between osmolality measurement made on either whole blood, or plasma taken from the same patient. Neither cell volume nor haemolysis was found to affect the measurement. The reproducibility of whole blood measurements was similar to that for determinations carried out on plasma. Measurement of osmolality on whole blood is quicker and cheaper and needs a smaller specimen than if serum or plasma is used.

pubmed23n0125_13855

Regional quality assessment of pH and blood gas analysers.

The performance of 41 pH and blood gas analysers in 20 hospitals was assessed using commercially available blood gas ampoules provided by seven manufacturers. The stability of the material and the effect of ambient temperature on Po2 was assessed. The overall mean values were outside the manufacturers' assigned values on eight out of 64 values. Using IL413 analysers as a basis for comparison, significant differences were found for Pco2 on ABL1, Corning 168 and 178 analysers and for Po2 on ABL1 and 2 and Corning 178. No significant differences were found for pH. Poor performers were identified in terms of imprecision. Analysers within or associated with clinical biochemistry departments gave better performance than those outside the laboratory. The five analysers that provided insufficient data for inclusion in the study were all situated outside the laboratory. Analysers from different manufacturers performed equally well provided they were used regularly and in accordance with manufacturers' instructions.

Regional quality assessment of pH and blood gas analysers. The performance of 41 pH and blood gas analysers in 20 hospitals was assessed using commercially available blood gas ampoules provided by seven manufacturers. The stability of the material and the effect of ambient temperature on Po2 was assessed. The overall mean values were outside the manufacturers' assigned values on eight out of 64 values. Using IL413 analysers as a basis for comparison, significant differences were found for Pco2 on ABL1, Corning 168 and 178 analysers and for Po2 on ABL1 and 2 and Corning 178. No significant differences were found for pH. Poor performers were identified in terms of imprecision. Analysers within or associated with clinical biochemistry departments gave better performance than those outside the laboratory. The five analysers that provided insufficient data for inclusion in the study were all situated outside the laboratory. Analysers from different manufacturers performed equally well provided they were used regularly and in accordance with manufacturers' instructions.

pubmed23n0125_13856

Radioimmunoassay of buprenorphine with iodine label: analysis of buprenorphine and metabolites in human plasma.

Quantitative analysis of potent opiate drugs in plasma by radioimmunoassay is potentially inaccurate because of the occurrence of cross-reacting metabolites. This paper describes the chemical synthesis of buprenorphine-3-O-glucuronide, a metabolite of buprenorphine, and an extraction procedure coupled with radioimmunoassay which allows the sensitive and specific measurement of buprenorphine using an iodinated buprenorphine derivative. The measurement of extracted and unextracted samples using two different antisera allowed investigation of the metabolism of buprenorphine. In four patients who had taken sublingual buprenorphine for at least one month, N-dealkyl buprenorphine was present in similar concentrations to those of buprenorphine, while buprenorphine-3-O-glucuronide was present in two to three times those concentrations.

Radioimmunoassay of buprenorphine with iodine label: analysis of buprenorphine and metabolites in human plasma. Quantitative analysis of potent opiate drugs in plasma by radioimmunoassay is potentially inaccurate because of the occurrence of cross-reacting metabolites. This paper describes the chemical synthesis of buprenorphine-3-O-glucuronide, a metabolite of buprenorphine, and an extraction procedure coupled with radioimmunoassay which allows the sensitive and specific measurement of buprenorphine using an iodinated buprenorphine derivative. The measurement of extracted and unextracted samples using two different antisera allowed investigation of the metabolism of buprenorphine. In four patients who had taken sublingual buprenorphine for at least one month, N-dealkyl buprenorphine was present in similar concentrations to those of buprenorphine, while buprenorphine-3-O-glucuronide was present in two to three times those concentrations.

pubmed23n0125_13857

Thyroid function tests in patients with familial dysalbuminaemic hyperthyroxinaemia (FDH).

Two patients with familial dysalbuminaemic hyperthyroxinaemia (FDH) are described in whom the albumin variant resulted in raised total T4 levels, and artefactually raised free T4 using a 'single-step' technique employing an analogue of T4 as tracer. The first patient was clinically euthyroid and presented with relapse of schizophrenia and abnormal thyroid function tests (total T4 336 nmol/L, total T3 4.2 nmol/L, TSH 1.8 mU/L, free T4 73 pmol/L). These results led to diagnostic confusion and the patient was treated with a short course of anti-thyroid drugs. The second patient had signs and symptoms of thyrotoxicosis at her first visit but was clinically euthyroid 5 months later when she was 10 weeks pregnant. Thyroid function tests were total T4 259 nmol/L, total T3 3.6 nmol/L, TSH 3.8 mU/L, free T4 46 pmol/L. Further studies showed both patients to be biochemically euthyroid. A variant albumin was confirmed in both patients by a screening test for FDH and by reverse-flow electrophoresis. Family studies on 10 relatives of the first patient identified eight with FDH. A simple screening procedure for the indentification of FDH is described and the use of laboratory tests in suspected cases is discussed.

Thyroid function tests in patients with familial dysalbuminaemic hyperthyroxinaemia (FDH). Two patients with familial dysalbuminaemic hyperthyroxinaemia (FDH) are described in whom the albumin variant resulted in raised total T4 levels, and artefactually raised free T4 using a 'single-step' technique employing an analogue of T4 as tracer. The first patient was clinically euthyroid and presented with relapse of schizophrenia and abnormal thyroid function tests (total T4 336 nmol/L, total T3 4.2 nmol/L, TSH 1.8 mU/L, free T4 73 pmol/L). These results led to diagnostic confusion and the patient was treated with a short course of anti-thyroid drugs. The second patient had signs and symptoms of thyrotoxicosis at her first visit but was clinically euthyroid 5 months later when she was 10 weeks pregnant. Thyroid function tests were total T4 259 nmol/L, total T3 3.6 nmol/L, TSH 3.8 mU/L, free T4 46 pmol/L. Further studies showed both patients to be biochemically euthyroid. A variant albumin was confirmed in both patients by a screening test for FDH and by reverse-flow electrophoresis. Family studies on 10 relatives of the first patient identified eight with FDH. A simple screening procedure for the indentification of FDH is described and the use of laboratory tests in suspected cases is discussed.

pubmed23n0125_13858

Drug screening: evaluation of the Toxi-Lab TLC system.

An evaluation of a commercial TLC Kit System (Toxi-Lab) is described. The performance of the system is assessed in the detection of drugs in overdose and in therapy, and is compared with a GC drug screening system. Toxi-Lab performed well in investigating drug overdoses. We found data on metabolite patterns essential for the identification of drugs in urine and for this reason the system performed much better than GC screening in which information on metabolites is limited. In our experience Toxi-Lab screening was not sufficiently sensitive for the detection of commonly prescribed psychiatric drugs taken in therapeutic doses. This system is rapid, versatile and suitable for small laboratories, but is comparatively expensive and some expertise is necessary to interpret results. A major deficiency of the kit is that the identification procedures are designed for the detection of drugs available in the USA and many drugs prescribed in the UK have been omitted.

Drug screening: evaluation of the Toxi-Lab TLC system. An evaluation of a commercial TLC Kit System (Toxi-Lab) is described. The performance of the system is assessed in the detection of drugs in overdose and in therapy, and is compared with a GC drug screening system. Toxi-Lab performed well in investigating drug overdoses. We found data on metabolite patterns essential for the identification of drugs in urine and for this reason the system performed much better than GC screening in which information on metabolites is limited. In our experience Toxi-Lab screening was not sufficiently sensitive for the detection of commonly prescribed psychiatric drugs taken in therapeutic doses. This system is rapid, versatile and suitable for small laboratories, but is comparatively expensive and some expertise is necessary to interpret results. A major deficiency of the kit is that the identification procedures are designed for the detection of drugs available in the USA and many drugs prescribed in the UK have been omitted.

pubmed23n0125_13859

Glycosylated haemoglobin: comparison of five different methods, including measurement on capillary blood samples.

Glycosylated haemoglobin was measured in venous blood samples and in blood collected in 'Unistep' bottles by isoelectric focusing (IEF), as the reference method, and by electroendosmosis (EEO), the thiobarbituric acid method (TBA), ion-exchange chromatography (IEC) and affinity chromatography (AC). Isoelectric focusing, electroendosmosis and thiobarbituric acid gave similar results. Affinity chromatography gave lower results than isoelectric focusing for normal values but similar results for diabetics. Ion-exchange chromatography gave 24% lower results than isoelectric focusing across the range. Using Unistep collected blood samples and comparing multiple samples from the same patient, electroendosmosis gave the best results (coefficient of variation 4%) and thiobarbituric acid gave slightly less good precision that other methods. Re-use of affinity chromatography columns gave less good precision. Collection of blood samples into a Unistep bottle gave similar results to venous sample results. Storage of venous capillary blood samples in Unistep bottles over 1 week at 21 degrees C gave similar results to immediate assay. Electroendosmosis of blood samples in Unistep bottles gave stable results over 2 weeks. Home collection by a patient of a capillary blood sample into a Unistep bottle allows glycosylated haemoglobin results to be available when seen in the clinic.

Glycosylated haemoglobin: comparison of five different methods, including measurement on capillary blood samples. Glycosylated haemoglobin was measured in venous blood samples and in blood collected in 'Unistep' bottles by isoelectric focusing (IEF), as the reference method, and by electroendosmosis (EEO), the thiobarbituric acid method (TBA), ion-exchange chromatography (IEC) and affinity chromatography (AC). Isoelectric focusing, electroendosmosis and thiobarbituric acid gave similar results. Affinity chromatography gave lower results than isoelectric focusing for normal values but similar results for diabetics. Ion-exchange chromatography gave 24% lower results than isoelectric focusing across the range. Using Unistep collected blood samples and comparing multiple samples from the same patient, electroendosmosis gave the best results (coefficient of variation 4%) and thiobarbituric acid gave slightly less good precision that other methods. Re-use of affinity chromatography columns gave less good precision. Collection of blood samples into a Unistep bottle gave similar results to venous sample results. Storage of venous capillary blood samples in Unistep bottles over 1 week at 21 degrees C gave similar results to immediate assay. Electroendosmosis of blood samples in Unistep bottles gave stable results over 2 weeks. Home collection by a patient of a capillary blood sample into a Unistep bottle allows glycosylated haemoglobin results to be available when seen in the clinic.

pubmed23n0125_13860

An examination of the hexokinase method for serum glucose assay using external quality assessment data.

Hexokinase methods for serum glucose assay appeared to give slightly but consistently higher inter-laboratory coefficients of variation than all methods combined in the UK External Quality Assessment Scheme; their performance over a two-year period was therefore compared with that for three groups of glucose oxidase methods. This assessment showed no intrinsic inferiority in the hexokinase method. The greater variation may be due to the more heterogeneous group of instruments, particularly discrete analysers, on which the method is used. The Beckman Glucose Analyzer and Astra group (using a glucose oxidase method) showed the least inter-laboratory variability but also the lowest mean value. No comment is offered on the absolute accuracy of any of the methods.

An examination of the hexokinase method for serum glucose assay using external quality assessment data. Hexokinase methods for serum glucose assay appeared to give slightly but consistently higher inter-laboratory coefficients of variation than all methods combined in the UK External Quality Assessment Scheme; their performance over a two-year period was therefore compared with that for three groups of glucose oxidase methods. This assessment showed no intrinsic inferiority in the hexokinase method. The greater variation may be due to the more heterogeneous group of instruments, particularly discrete analysers, on which the method is used. The Beckman Glucose Analyzer and Astra group (using a glucose oxidase method) showed the least inter-laboratory variability but also the lowest mean value. No comment is offered on the absolute accuracy of any of the methods.

pubmed23n0125_13861

Determination of aluminium in human tissues by flameless atomic absorption spectroscopy and comparison of reference values.

Aluminium in human tissues has been determined by flameless atomic absorption spectroscopy (AAS). Tissues were dried at 110 degrees C and digested with concentrated nitric acid at 50 degrees C overnight. After dilution with distilled water the samples were measured. The aluminium levels of the controls (healthy individuals who died as a result of an accident) appeared to be: grey matter 2.1 +/- 1.0 (mean +/- SD), white matter 1.7 +/- 0.5, spinal cord, 3.3 +/- 1.5, kidney 1.9 +/- 0.7, heart 2.1 +/- 1.1, vertebral cortex 1.9 +/- 1.8, and vertebral trabeculae 3.1 +/- 1.8 micrograms/g dry weight. For a patient with dialysis motor neuropathy significantly higher values were found. Comparison with values in the literature shows that our reference values are in agreement with published results obtained by flameless atomic absorption spectroscopy.

Determination of aluminium in human tissues by flameless atomic absorption spectroscopy and comparison of reference values. Aluminium in human tissues has been determined by flameless atomic absorption spectroscopy (AAS). Tissues were dried at 110 degrees C and digested with concentrated nitric acid at 50 degrees C overnight. After dilution with distilled water the samples were measured. The aluminium levels of the controls (healthy individuals who died as a result of an accident) appeared to be: grey matter 2.1 +/- 1.0 (mean +/- SD), white matter 1.7 +/- 0.5, spinal cord, 3.3 +/- 1.5, kidney 1.9 +/- 0.7, heart 2.1 +/- 1.1, vertebral cortex 1.9 +/- 1.8, and vertebral trabeculae 3.1 +/- 1.8 micrograms/g dry weight. For a patient with dialysis motor neuropathy significantly higher values were found. Comparison with values in the literature shows that our reference values are in agreement with published results obtained by flameless atomic absorption spectroscopy.

pubmed23n0125_13862

Testosterone assays: guidelines for the provision of a clinical biochemistry service.

Approximately one year after the devolution of testosterone assays from the SAS, the Analytical Methods Working Party of the Association of Clinical Biochemists set up a working party to investigate the performance of the assays, to survey the available methodology and to give guidance on the factors that influence the assay. This document represents a summary of the deliberations of the group and forms one of a series of similar reports.

Testosterone assays: guidelines for the provision of a clinical biochemistry service. Approximately one year after the devolution of testosterone assays from the SAS, the Analytical Methods Working Party of the Association of Clinical Biochemists set up a working party to investigate the performance of the assays, to survey the available methodology and to give guidance on the factors that influence the assay. This document represents a summary of the deliberations of the group and forms one of a series of similar reports.

pubmed23n0125_13863

Acceptance of values assigned to serum-based calibration materials.

A questionnaire sent to laboratories in the UK and Ireland elicited information on acceptance or otherwise of values assigned to serum-based calibration materials for 14 analytes. Overall, 33% of assigned values were changed by users. The reasons for change, together with the degree of magnitude and direction of change, were studied for each analyte. Unidirectional changes made to assigned values were related to particular batches and manufacturers. Detailed information is presented for protein (Beckman RIIC Ltd.) on Astras, and sodium, bicarbonate and bilirubin on SMACs and SMAs (Technicon Instrument Co. Ltd.).

Acceptance of values assigned to serum-based calibration materials. A questionnaire sent to laboratories in the UK and Ireland elicited information on acceptance or otherwise of values assigned to serum-based calibration materials for 14 analytes. Overall, 33% of assigned values were changed by users. The reasons for change, together with the degree of magnitude and direction of change, were studied for each analyte. Unidirectional changes made to assigned values were related to particular batches and manufacturers. Detailed information is presented for protein (Beckman RIIC Ltd.) on Astras, and sodium, bicarbonate and bilirubin on SMACs and SMAs (Technicon Instrument Co. Ltd.).

pubmed23n0125_13864

Changes in sample isoferritin composition as a possible cause of dilutional discrepancies in ferritin 2-site immunoradiometric assay results.

The effect of changes in sample isoferritin composition on the behaviour of ferritin 2-site immunoradiometric assays was investigated using a computer model and experimental studies. Modelling studies predicted that under conditions where a sample has a different isoferritin composition from the assay standards, progressively higher values will be generated for the apparent ferritin content of the sample when it is analysed at increasing dilutions. In addition, the assay results will underestimate the actual ferritin content of such samples at all dilutions. Dilutional discrepancies in assay results and underestimation of sample ferritin concentrations were found in practical assays when synthetic samples with demonstrably different isoferritin profiles were analysed. Differences in isoferritin composition between assay standards and assayed samples may therefore be a cause of dilutional discrepancies in some results from ferritin 2-site immunoradiometric assays.

Changes in sample isoferritin composition as a possible cause of dilutional discrepancies in ferritin 2-site immunoradiometric assay results. The effect of changes in sample isoferritin composition on the behaviour of ferritin 2-site immunoradiometric assays was investigated using a computer model and experimental studies. Modelling studies predicted that under conditions where a sample has a different isoferritin composition from the assay standards, progressively higher values will be generated for the apparent ferritin content of the sample when it is analysed at increasing dilutions. In addition, the assay results will underestimate the actual ferritin content of such samples at all dilutions. Dilutional discrepancies in assay results and underestimation of sample ferritin concentrations were found in practical assays when synthetic samples with demonstrably different isoferritin profiles were analysed. Differences in isoferritin composition between assay standards and assayed samples may therefore be a cause of dilutional discrepancies in some results from ferritin 2-site immunoradiometric assays.

pubmed23n0125_13865

A fluorimetric method for measurement of erythrocyte transketolase activity.

A method for measuring erythrocyte transketolase activity (ETKA) is described that is precise, economical of reagents and capable of high throughput with partial or full automation. The transketolase-dependent transformation of ribose-5-phosphate, yielding glyceraldehyde-3-phosphate, is linked via 'indicator enzymes' to glycerol production and NADH consumption, the latter being followed fluorimetrically. Conditions under which ETKA and 'TPP Effect' are derived have been examined and optimised. Values are comparable with those obtained by other methods but a relatively narrow adult reference range for ETKA is observed. Data are presented for optimal preparation and storage of samples.

A fluorimetric method for measurement of erythrocyte transketolase activity. A method for measuring erythrocyte transketolase activity (ETKA) is described that is precise, economical of reagents and capable of high throughput with partial or full automation. The transketolase-dependent transformation of ribose-5-phosphate, yielding glyceraldehyde-3-phosphate, is linked via 'indicator enzymes' to glycerol production and NADH consumption, the latter being followed fluorimetrically. Conditions under which ETKA and 'TPP Effect' are derived have been examined and optimised. Values are comparable with those obtained by other methods but a relatively narrow adult reference range for ETKA is observed. Data are presented for optimal preparation and storage of samples.

pubmed23n0125_13866

Reduced serum carnosinase activity in hypothyroidism.

Carnosinase hydrolyses carnosine in muscle, and its deficiency is associated with extensive neuromuscular abnormalities. We measured serum carnosinase activity in patients with thyroid dysfunction which often involves neuromuscular systems. In hyperthyroidism, the carnosinase activity was not significantly different from that in normal subjects. In hypothyroidism, however, it was significantly lower than that in normal subjects. The activity examined in five patients with hypothyroidism returned to normal after replacement therapy. In hypothyroidism, the carnosinase activity showed significant correlation with concentration of serum thyroxine and negative correlation with serum creatine kinase activity. This finding may be of practical importance in the differential diagnosis of disorders causing carnosinase deficiency.

Reduced serum carnosinase activity in hypothyroidism. Carnosinase hydrolyses carnosine in muscle, and its deficiency is associated with extensive neuromuscular abnormalities. We measured serum carnosinase activity in patients with thyroid dysfunction which often involves neuromuscular systems. In hyperthyroidism, the carnosinase activity was not significantly different from that in normal subjects. In hypothyroidism, however, it was significantly lower than that in normal subjects. The activity examined in five patients with hypothyroidism returned to normal after replacement therapy. In hypothyroidism, the carnosinase activity showed significant correlation with concentration of serum thyroxine and negative correlation with serum creatine kinase activity. This finding may be of practical importance in the differential diagnosis of disorders causing carnosinase deficiency.

pubmed23n0125_13867

Screening for early diabetic nephropathy.

An albumin excretion rate of 30-150 micrograms/min is a strong predictor of future clinical diabetic nephropathy. The collection of urine samples commonly used is cumbersome and tedious for both patients and laboratory staff. We have therefore examined the usefulness of albumin:creatinine ratio measurement as a predictor of albumin excretion rates greater than 30 micrograms/min. Values above 3.5 for the albumin:creatinine ratio gave high sensitivity (98%) but low specificity (63%) while a value greater than 4.5 had a sensitivity of 96% and specificity of 72%. We conclude that the albumin:creatinine ratio in a first morning urine sample is useful as an initial screening test for microalbuminuria but that further analysis is required to select those with definite microalbuminuria.

Screening for early diabetic nephropathy. An albumin excretion rate of 30-150 micrograms/min is a strong predictor of future clinical diabetic nephropathy. The collection of urine samples commonly used is cumbersome and tedious for both patients and laboratory staff. We have therefore examined the usefulness of albumin:creatinine ratio measurement as a predictor of albumin excretion rates greater than 30 micrograms/min. Values above 3.5 for the albumin:creatinine ratio gave high sensitivity (98%) but low specificity (63%) while a value greater than 4.5 had a sensitivity of 96% and specificity of 72%. We conclude that the albumin:creatinine ratio in a first morning urine sample is useful as an initial screening test for microalbuminuria but that further analysis is required to select those with definite microalbuminuria.

pubmed23n0125_13868

Glycosylated plasma protein measurement by a semi-automated method.

A semi-automated method for determination of glycosylation of plasma proteins using the thiobarbituric acid method is described. Plasma samples (100 microL) and a plasma pool used as a secondary standard were incubated in 0.3 M oxalic acid at 100 degrees C for exactly 2 h. The hydroxymethyl furfural released and the total protein were measured concurrently on a Technicon AAII Autoanalyzer. Addition of 10 or 20 mmol glucose to plasma samples caused a minimal increase in the measured glycosylated protein. Within-batch and between-batch coefficients of variation were 3.1% and 4.9% respectively. The mean glycosylated protein levels for 52 normals and 48 maturity-onset diabetics were (+/- 1SD) 0.96 +/- 0.13 and 1.75 +/- 0.32 nmol HMF/mg protein/2 h incubation.

Glycosylated plasma protein measurement by a semi-automated method. A semi-automated method for determination of glycosylation of plasma proteins using the thiobarbituric acid method is described. Plasma samples (100 microL) and a plasma pool used as a secondary standard were incubated in 0.3 M oxalic acid at 100 degrees C for exactly 2 h. The hydroxymethyl furfural released and the total protein were measured concurrently on a Technicon AAII Autoanalyzer. Addition of 10 or 20 mmol glucose to plasma samples caused a minimal increase in the measured glycosylated protein. Within-batch and between-batch coefficients of variation were 3.1% and 4.9% respectively. The mean glycosylated protein levels for 52 normals and 48 maturity-onset diabetics were (+/- 1SD) 0.96 +/- 0.13 and 1.75 +/- 0.32 nmol HMF/mg protein/2 h incubation.

pubmed23n0125_13869

Glycosylated haemoglobin by affinity chromatography in diabetic and non-diabetic children.

We have made an evaluation of glycosylated haemoglobin measurements by affinity chromatography in a paediatric population. Age-related reference values for non-diabetic infants and children are reported. A poor correlation (r = 0.24) was found between glycosylated haemoglobin values in 26 insulin-dependent diabetic children and the paediatrician's independent assessment of clinical control.

Glycosylated haemoglobin by affinity chromatography in diabetic and non-diabetic children. We have made an evaluation of glycosylated haemoglobin measurements by affinity chromatography in a paediatric population. Age-related reference values for non-diabetic infants and children are reported. A poor correlation (r = 0.24) was found between glycosylated haemoglobin values in 26 insulin-dependent diabetic children and the paediatrician's independent assessment of clinical control.

pubmed23n0125_13870

Comparison of three parathyroid hormone assays.

The efficiency of three parathyroid hormone (PTH) assays in the diagnosis of primary hyperparathyroidism has been investigated. Two assays used commercial reagents and measured the intact hormone and middle region of parathyroid hormone and the third assay employed the antiserum AS 211/32. Although the intact and mid-molecule assays showed a greater increase in PTH above normal than the laboratory PTH assay, patients with proven primary hyperparathyroidism were not distinguished from healthy subjects in every case. The intact and in house assays gave elevated values in seven out of nine patients with proven hyperparathyroidism and the mid-molecule assay in eight out of nine assays. The intact PTH and in-house assays were more successful than the mid-molecule method in separating patients with primary hyperparathyroidism from those with hypercalcaemia due to malignancy.

Comparison of three parathyroid hormone assays. The efficiency of three parathyroid hormone (PTH) assays in the diagnosis of primary hyperparathyroidism has been investigated. Two assays used commercial reagents and measured the intact hormone and middle region of parathyroid hormone and the third assay employed the antiserum AS 211/32. Although the intact and mid-molecule assays showed a greater increase in PTH above normal than the laboratory PTH assay, patients with proven primary hyperparathyroidism were not distinguished from healthy subjects in every case. The intact and in house assays gave elevated values in seven out of nine patients with proven hyperparathyroidism and the mid-molecule assay in eight out of nine assays. The intact PTH and in-house assays were more successful than the mid-molecule method in separating patients with primary hyperparathyroidism from those with hypercalcaemia due to malignancy.

pubmed23n0125_13871

Performance and clinical utility of a commercially available 'C-terminal' PTH assay.

The performance and clinical utility of a 'C-terminal' parathyroid hormone (PTH) radioimmunoassay (Dac-Cel, Wellcome Diagnostics) is described. Parathyroid hormone, as measured by the Dac-Cel method, is stable in whole blood samples for at least 24 h. 84% of patients with hypercalcaemia due to primary hyperparathyroidism have values above the upper limit seen in normocalcaemic subjects (0.5 micrograms/L), with detectable serum PTH demonstrable in the remaining 16%. In patients with hypocalcaemia due to hypoparathyroidism serum PTH was undetectable in 73% and 'inappropriately' low in the remainder. In 50% of patients with malignancy-associated hypercalcaemia serum PTH was undetectable, but was above 0.5 micrograms/L in 13%. Increased PTH concentrations were invariably found in patients with renal failure. The Dac-Cel method is a reliable and robust technique for measurement of PTH and in conjunction with determination of calcium facilitates the diagnosis of primary parathyroid disorders. Caution is required in the interpretation of PTH measurements in patients with renal failure; the significance of detectable PTH in some patients with malignancy-associated hypercalcaemia is not clear.

Performance and clinical utility of a commercially available 'C-terminal' PTH assay. The performance and clinical utility of a 'C-terminal' parathyroid hormone (PTH) radioimmunoassay (Dac-Cel, Wellcome Diagnostics) is described. Parathyroid hormone, as measured by the Dac-Cel method, is stable in whole blood samples for at least 24 h. 84% of patients with hypercalcaemia due to primary hyperparathyroidism have values above the upper limit seen in normocalcaemic subjects (0.5 micrograms/L), with detectable serum PTH demonstrable in the remaining 16%. In patients with hypocalcaemia due to hypoparathyroidism serum PTH was undetectable in 73% and 'inappropriately' low in the remainder. In 50% of patients with malignancy-associated hypercalcaemia serum PTH was undetectable, but was above 0.5 micrograms/L in 13%. Increased PTH concentrations were invariably found in patients with renal failure. The Dac-Cel method is a reliable and robust technique for measurement of PTH and in conjunction with determination of calcium facilitates the diagnosis of primary parathyroid disorders. Caution is required in the interpretation of PTH measurements in patients with renal failure; the significance of detectable PTH in some patients with malignancy-associated hypercalcaemia is not clear.

pubmed23n0125_13872

The effect of hydropenia and oral water loading on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase excretion in man.

To substantiate the effects of urine flow rate on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase (NAG) excretion, experiments were performed in normal human subjects. Urine flow rate was varied by overnight fluid deprivation and progressive diuresis induced by oral water loading. Lysozyme measurements were made using an improved turbidimetric method and NAG determinations using a modified fluorometric assay utilising individual recovery techniques. Fractional lysozyme clearance and lysozyme excretion demonstrated a nearly linear relationship with urine flow rate (r = 0.78, r = 0.80, P less than 0.0005), and both were elevated significantly in samples obtained during diuresis. NAG excretion, however, demonstrated a significant but weak correlation (r = 0.47, P less than 0.005) with fractional urine flow rate. A significant (P less than 0.05) difference in NAG activity occurred only during the period of hydropenia, when a decrease in excretion was observed. These findings suggest that the effect of diuresis on lysozyme excretion should be considered in studies utilising this enzyme as a marker of renal injury.

The effect of hydropenia and oral water loading on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase excretion in man. To substantiate the effects of urine flow rate on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase (NAG) excretion, experiments were performed in normal human subjects. Urine flow rate was varied by overnight fluid deprivation and progressive diuresis induced by oral water loading. Lysozyme measurements were made using an improved turbidimetric method and NAG determinations using a modified fluorometric assay utilising individual recovery techniques. Fractional lysozyme clearance and lysozyme excretion demonstrated a nearly linear relationship with urine flow rate (r = 0.78, r = 0.80, P less than 0.0005), and both were elevated significantly in samples obtained during diuresis. NAG excretion, however, demonstrated a significant but weak correlation (r = 0.47, P less than 0.005) with fractional urine flow rate. A significant (P less than 0.05) difference in NAG activity occurred only during the period of hydropenia, when a decrease in excretion was observed. These findings suggest that the effect of diuresis on lysozyme excretion should be considered in studies utilising this enzyme as a marker of renal injury.

pubmed23n0125_13873

Effect of ethanol on erythrocyte acetylcholinesterase activity.

Erythrocyte acetylcholinesterase (AchE) activity was measured in the blood of 36 alcoholic subjects and 41 healthy volunteers. The mean activity in the alcoholics was significantly lower than that in the control subjects. In vitro experiments showed that ethanol inhibited the AchE activity immediately and in proportion to the concentration of ethanol used. Incubation times up to 6 h did not increase the inhibition significantly. Incubation of normal red cells with ethanol for 15 h, followed by washing, showed also that AchE activity was inhibited by the previous exposure to ethanol and that washing did not reduce the inhibitory effect. The possibility is considered that depressed erythrocyte AchE activity may be an early indication of potential disturbances of the autonomic nervous system. The importance of reporting ethanol intake in patients with organophosphorus poisoning is stressed.

Effect of ethanol on erythrocyte acetylcholinesterase activity. Erythrocyte acetylcholinesterase (AchE) activity was measured in the blood of 36 alcoholic subjects and 41 healthy volunteers. The mean activity in the alcoholics was significantly lower than that in the control subjects. In vitro experiments showed that ethanol inhibited the AchE activity immediately and in proportion to the concentration of ethanol used. Incubation times up to 6 h did not increase the inhibition significantly. Incubation of normal red cells with ethanol for 15 h, followed by washing, showed also that AchE activity was inhibited by the previous exposure to ethanol and that washing did not reduce the inhibitory effect. The possibility is considered that depressed erythrocyte AchE activity may be an early indication of potential disturbances of the autonomic nervous system. The importance of reporting ethanol intake in patients with organophosphorus poisoning is stressed.

pubmed23n0125_13874

The blunder-rate in a clinical biochemistry service.

We describe a study undertaken to investigate the frequency and type of mistake detected in a large biochemistry laboratory. Blunders were recorded over three non-consecutive 3-week periods. The returns to the external quality assessment schemes during a 12-month period were also monitored. Despite changes in laboratory practice, the nature of the errors found has not altered substantially from those described by earlier investigators. The detected blunder rate was 0.3%.

The blunder-rate in a clinical biochemistry service. We describe a study undertaken to investigate the frequency and type of mistake detected in a large biochemistry laboratory. Blunders were recorded over three non-consecutive 3-week periods. The returns to the external quality assessment schemes during a 12-month period were also monitored. Despite changes in laboratory practice, the nature of the errors found has not altered substantially from those described by earlier investigators. The detected blunder rate was 0.3%.

pubmed23n0125_13875

Long-term trends in biochemical data obtained from two population surveys.

A study has been made of the variations in monthly mean values of 10 serum constituents in subjects participating in two partly-concurrent long-term epidemiological surveys. Closely similar patterns of variation were found in men in both surveys and in men and women in one survey. During the 6 years of the study, four types of variation of the monthly mean concentrations were identified in varying combinations: abrupt changes of less than 2% not detected by quality control procedures; a gradual drift in mean value; haphazard variations in mean values; and seasonal variations in bilirubin and urea, identical in men and women. The implications of these findings for the design of long-term epidemiological surveys, and the criteria for designating variations as seasonal, are discussed.

Long-term trends in biochemical data obtained from two population surveys. A study has been made of the variations in monthly mean values of 10 serum constituents in subjects participating in two partly-concurrent long-term epidemiological surveys. Closely similar patterns of variation were found in men in both surveys and in men and women in one survey. During the 6 years of the study, four types of variation of the monthly mean concentrations were identified in varying combinations: abrupt changes of less than 2% not detected by quality control procedures; a gradual drift in mean value; haphazard variations in mean values; and seasonal variations in bilirubin and urea, identical in men and women. The implications of these findings for the design of long-term epidemiological surveys, and the criteria for designating variations as seasonal, are discussed.

pubmed23n0125_13876

A simple method for the measurement of glycerol in serum.

An automated enzymic assay for the measurement of glycerol in serum is described. As it uses a centrifugal analyser, this method does not require prior extraction. It is precise, sensitive, and can be performed rapidly at low cost.

A simple method for the measurement of glycerol in serum. An automated enzymic assay for the measurement of glycerol in serum is described. As it uses a centrifugal analyser, this method does not require prior extraction. It is precise, sensitive, and can be performed rapidly at low cost.