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Biomedical subjects

R D Soloway

Publications and source records attributed to R D Soloway.

At least 55 records · Page 3Linked to original sources
PubMed1987

Hepatocanalicular injury associated with vitamin A derivative etretinate. An idiosyncratic hypersensitivity reaction.

A patient with pustular psoriasis developed jaundice, peripheral blood eosinophilia, and biochemical evidence of hepatocanalicular dysfunction four weeks after the initiation of etretinate therapy. A liver biopsy specimen showed bile duct damage, a periportal inflammatory infiltrate composed of neutrophils, eosinophils and lymphocytes, canalicular cholestasis, and focal hepatocyte necrosis. Clinical exclusion of other possible etiologic factors coupled with near resolution of the biochemical abnormalities within six weeks after complete discontinuation of the drug indicates that etretinate may induce an idiosyncratic hypersensitivity reaction. This is the first report to document etretinate associated bile duct injury.

Aged↗
PubMed1987

An animal model of pigment cholelithiasis.

Pigment stones of high calcium content were induced in male hamsters of the Harlan Sprague-Dawley strain fed a nutritionally adequate semipurified diet for a period of 14 weeks. The diet contained moderate amounts of cholesterol (0.30 percent) and ethinyl estradiol (15 micrograms/day per animal). At sacrifice, the incidence of pigment stones was 50 percent. When stones were present, they were in the form of numerous black amorphous rods about 0.1 to 0.4 mm in length. Infrared analysis of the dried stones indicated the following composition: calcium phosphate 26.7 percent, calcium bilirubinate 12.8 percent, cholesterol 15.1 percent, and protein 45.4 percent. Pigment stones were associated with an elevated biliary total calcium level (probably induced by the dietary cholesterol) and a paradoxic decrease in the biliary total bilirubin level. The lithogenic diet produced marked elevations in liver and plasma cholesterol levels and cholesterol saturation of bile, but no cholesterol crystals or stones were observed. The accumulation of elevated levels of cholesterol in the livers of the experimental animals produced mild to moderate hepatotoxicity. The precise mechanism of the dietary induction of pigment stones in this hamster model remains to be elucidated.

Animals↗
PubMed1987

Primary sclerosing cholangitis and pregnancy.

Primary sclerosing cholangitis is a chronic, fibrosing, inflammatory disorder of unknown etiology affecting the biliary tree. We describe a case of a pregnancy complicated by this condition. Remarkably, maternal cholestasis improved with advancing gestation. Despite a marked elevation of bile acid levels in cord blood, the patient was delivered of a healthy term infant. The principles of management and potential effects of primary sclerosing cholangitis on pregnancy care are discussed.

Adult↗
PubMed1986

Evaluation of postprandial serum bile acid response as a test of hepatic function.

Commercial assays for serum bile acids (SBA) have made this measurement practical. The purpose of this study was to examine the utility of SBA measured every 30 min after a standardized meal in controls and in patients with acute viral hepatitis, cholestasis, and anicteric cirrhosis. In five controls, repeated examination of the area under the bile acid curve (AUC) was not statistically different, whereas the fasting and 2-hr postprandial levels were significantly different. In the group of patients with anicteric cirrhosis, AUC identified disease in 18/20 using total serum bile acids (TSBAs) and in 15/20 using cholylglycine (CG). AUC can be calculated from three samples obtained at 0, 60, and 120 min without losing the sensitivity achieved with seven serial samples. SGOT, alkaline phosphatase, and serum albumin were compared for sensitivity to the total SBA response curve in 20 patients with anicteric cirrhosis. SGOT and alkaline phosphatase identified only 50% and 55% as abnormal and serum albumin was less sensitive. Using total SBA, combining the fasting level and AUC identified 100% as abnormal; using CG, 85% of these patients were detected. As a stepwise cost-effective approach, the fasting level of SBAs can identify most patients with anicteric liver disease. In cases with normal fasting levels where liver disease is suspected, the three-point AUC determination may identify additional patients.

Acute Disease↗
PubMed1986

Pigment gallstone composition in patients with hemolysis or infection/stasis.

The effect of hemolysis and infection/stasis on pigment gallstones was assessed by comparing the composition of stones from (1) U.S. patients without hemolysis or cirrhosis, (2) U.S. patients with sickle cell disease, and (3) Japanese patients with biliary infections. Gallstone composition was quantitated by infrared spectroscopy and chemical analyses. Gallstones from patients with sickle cell anemia contained more pigment, carbonate, calcium, and measured components than stones from U.S. patients without hemolysis (P less than 0.05). However, the similar types of calcium salts in black stones from patients with and without sickle cell anemia suggested that intermittent hemolysis may be a potential mechanism in the formation of black stones found in the general population. In Japanese patients with brown pigment stones, there was an absence of calcium carbonate, low levels of calcium phosphate, and the presence of calcium salts of fatty acids (P less than 0.05). Thus, the accompanying stasis and/or infection in this latter group was associated with the formation of a distinctive stone type and was not involved in the formation of the black stones. The similarly small proportion of cholesterol in each of these groups suggested that it was present due to coprecipitation rather than to cholesterol supersaturation.

Anemia, Sickle Cell↗
PubMed1986

Hepatolithiasis in East Asia. Retrospective study.

Hepatolithiasis is a major disease in Asia but differences in operative incidence between countries have not been examined. A retrospective study was conducted in Taiwan, Hong Kong, and Singapore, and the results were compared with those in Japan with the aim of defining factors involved in the etiology of the condition. In order to ensure uniformity of the data collected, the same form was used throughout the study and was completed by the same personnel after reviewing the patient's record and radiographs in each case. The years 1976-1980 were chosen for the study, since the newer methods of diagnosis such as ultrasound, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography became available during that period. The most significant finding was the difference in the relative prevalence of hepatolithiasis as a proportion of all gallstone cases in Taiwan, Hong Kong, and Singapore, where the majority of the population consisted of patients of Chinese descent. The highest prevalence, 53.5%, was found in Taiwan, while in Hong Kong it was 3.1% and in Singapore 1.7%. Environmental rather than ethnic factors are implicated in the cause of hepatolithiasis.

Adult↗
PubMed1986

Chemical and morphologic characteristics of cholesterol gallstones that failed to dissolve on chenodiol. The National Cooperative Gallstone Study.

During the National Cooperative Gallstone Study, chenodiol (chenodeoxycholate), 750 or 375 mg/day, resulted in complete gallstone dissolution in only 13.5% and 5.2% of patients, respectively. The purpose of this study was to analyze the composition and morphology of gallstones from patients who underwent cholecystectomy during the National Cooperative Gallstone Study to determine if calcium salts on the gallstone surface could have been responsible for failure of dissolution. Total gallstone calcium content was not different between the treated and placebo groups; however, surface calcium levels were different, being greater than 1.0% in 47.6% of stones from chenodiol-treated patients (n = 63) but in only 16.7% of those from placebo-treated patients (n = 18), p less than 0.02. Pigmented outer rims were found in 52.4% of the stones from the chenodiol-treated group compared with only 16.7% of stones from the placebo group, p less than 0.01. The rim calcium content of 36 stones with pigmented outer rims was 3.7% +/- 1.0%, whereas that of 45 stones with nonpigmented outer rims was only 1.0% +/- 0.3%, p less than 0.01. We conclude that the presence of rings of increased concentrations of calcium salts on the gallstone surface may impair dissolution by chenodiol.

Bilirubin↗
PubMed1986

Azathioprine and hepatic venocclusive disease in renal transplant patients.

We report 3 cases of hepatic venocclusive disease occurring in renal transplant patients receiving azathioprine and combine our experience with 4 other previously reported cases. The data suggest a clinical syndrome characterized by (a) delayed clinical onset, (b) striking male predominance, (c) presentation with jaundice followed by evidence of portal hypertension, and (d) poor prognosis. One of our patients, who is still alive 40 mo after the first onset of symptoms of liver disease, showed striking clinical improvement with discontinuation of azathioprine and subsequent deterioration on reinstitution. We suggest that azathioprine may be closely linked with the development of venocclusive disease in renal transplant patients and that the frequency of this disorder may be more common than previously reported. To attempt to prevent a fatal outcome, this group of patients should be closely monitored for the earliest signs of hepatic venocclusive disease through periodic serum bilirubin and alkaline phosphatase determinations. Patients with abnormal tests should undergo liver biopsy. If hepatic venocclusive disease is found, prompt withdrawal of azathioprine is indicated.

Adult↗
PubMed1985

Cancer of the gallbladder in Bolivia: suggestions concerning etiology.

In order to investigate the very high incidence of gallbladder cancer in Bolivia, a series of patients with gallbladder cancer and/or cholelithiasis from a hospital in La Paz was compared to a series of patients with cholelithiasis from Philadelphia. Each group demonstrated a similar female predilection. Bolivian patients with gallbladder cancer were older than patients with cholelithiasis who, in turn, were older than the general population (p less than 0.001). Racial differences demonstrated previously were confirmed. Bolivian gallstones were uniformly cholesterol in type, in contrast to the US series, in which 27% of patients had black pigment stones. Bile specimens obtained from Bolivian patients with cholelithiasis had a lower concentration of bile salts, phospholipids, and cholesterol than bile specimens from US cholelithiasis patients (p less than 0.01, less than 0.001, and less than 0.001, respectively). These biochemical differences may help to explain the differing incidence of cholelithiasis and gallbladder cancer in the US and Bolivia.

Bile↗
PubMed1985

Cyclic deposition of calcium salts during growth of cholesterol gallstones.

Some cholesterol gallstones contain darkly pigmented centers or peripheral concentric pigmented bands. We examined the cross-sectional surface of three cholesterol gallstones which contained both central and peripheral pigmented areas with electron-probe microanalysis (EPM) and energy dispersive x-ray microanalysis (EDXA) to determine the elemental composition of the pigmented regions. Linear EPM across the cross-sectional surface of the stones demonstrated that most of the pigmented regions of all three stones had high Ca and P signals; the non-pigmented intervening areas had markedly lower or no detectable Ca and P signals. In two of the three stones, high O signals coincided with the high Ca and P signals suggesting that both calcium bilirubinate and calcium phosphate were present in these pigmented areas. EDXA of the central and peripheral pigmented areas of each stone confirmed the presence of a high Ca signal. Our results demonstrate that in some cholesterol gallstones there is cyclic deposition of calcium bilirubinate and other calcium salts.

Bile Acids and Salts↗
PubMed1984

Additional chenodiol therapy after partial dissolution of gallstones with two years of treatment.

During the National Cooperative Gallstone Study, therapy with chenodiol, 750 or 375 mg/d, for 2 years resulted in confirmed, complete gallstone dissolution in 14% and 5% of patients, respectively, and partial dissolution (greater than 50%) in 27% and 18%. The present study was done to determine the frequency with which complete dissolution occurs in patients having partial dissolution of gallstones who receive additional therapy. Eighty-six of one hundred thirty-eight eligible patients continued to receive 750 mg/d (61 patients) or 375 mg/d (25 patients) of chenodiol for 1 year. Patients whose oral cholecystogram at the end of the year showed further (greater than 50%) dissolution continued to receive chenodiol, (28 patients at 750 mg/d and 11 patients at 375 mg/d) for a second year (total duration of therapy, 4 years). A final oral cholecystogram was taken at the end of the fourth year. Complete dissolution occurred in 23% and 16% of patients receiving chenodiol, 750 or 375 mg/d, respectively, for an additional 1 or 2 years.

Chenodeoxycholic Acid↗
PubMed1983

The epidemiology of cancer of the extra-hepatic biliary tract in Bolivia.

Data on patients with cancer of the gall bladder and cancer of the extra-hepatic bile ducts were obtained from the tumour registry in La Paz, Bolivia. Incidence rates were calculated using the Bolivian census data and compared to US incidence data from the Third National Cancer Survey. The age and population standardized incidence rates for cancer of the gall bladder in Bolivia were 5.3/100,000 males/year and 10.3/100,000 females/year. Comparable US rates were 1.0/100,000 males/year and 2.1/100,000 females/year. The age and population standardized incidence rates for cancer of the extra-hepatic bile ducts in Bolivia were 1.1/100,000 males/year and 4.1/100,000 females/year. Comparable US rates were 1.6/100,000 males/year and 1.0/100,000 females/year respectively. Both diseases occurred at younger ages in Bolivia than in the US and both showed marked racial variation. Differences in disease incidence between Bolivia and the US could not be fully explained by differences in age, sex, or racial distributions. Studies designed to investigate the causes of this remarkable variation in disease incidence could provide important clues to disease aetiology.

Adolescent↗
PubMed1982

Mechanism of deoxycholic acid stimulation of the rabbit colon.

Previous studies showed that deoxycholic acid (DCA) stimulated migrating action potential complexes (MAPC) in the colon. The aim of this study was to clarify the mechanism of DCA-stimulated colonic motility. Myoelectrical and contractile activity were measured in New Zealand White rabbits from a loop constructed in the proximal colon. During the control period, slow waves were present at a frequency of 10.8 +/- 0.5 cycle/min and there were 1.5 +/- 0.5 MAPC/ h. After adding DCA (16 mM) to the loop the slow wave activity was unchanged. However, MAPC increased to 15.1 +/- 2.4 MAPC/h (P less than 0.001). MAPC activity was not stimulated in the colonic smooth muscle outside the loop. The intraluminal addition of procaine or tetrodotoxin to the colonic loop inhibited the DCA-stimulated increase in MAPC activity (0.2 +/- 0.2 MAPC/h) (P less than 0.005). Intravenous administration of atropine or phentolamine also inhibited MAPC activity that had been stimulated by DCA (P less than 0.005). Pretreatment with 6-hydroxydopamine also inhibited an increase in MAPC activity. Propranolol, trimethaphan camsylate, or hexamethonium had no effect on DCA stimulation of MAPC activity. Although the concentration of bile salt increased in the mesenteric venous outflow from the colonic loop, the intravenous administration of bile salt did not stimulate colonic MAPC activity. These studies suggest: (a) the action of DCA on smooth muscle activity is a local phenomenon, (b) the increase in MAPC activity is dependent on intact cholinergic and alpha adrenergic neurons, and (c) an increase in the concentration of bile salts in the serum is not associated with an increase in colonic MAPC activity.

Action Potentials↗
PubMed1982

Response of total and individual serum bile acids to endogenous and exogenous bile acid input to the enterohepatic circulation.

The response of total nonsulfated serum bile acids, cholylglycine, and chenodeoxycholyl species was examined every 20 min for 3 h in 6 subjects. Noncaloric feeding led to a progressive decline or no change in bile acids, while there was a progressive rise in response to a standard liquid meal. After reaching a peak at 60 min, total bile acids declined progressively but cholylglycine and chenodeoxycholyl species remained elevated. Continuous infusion of cholecystokinin led to significantly greater levels most probably due to more rapid enterohepatic recirculation. Oral administration of 250 mg of chenodeoxycholic acid with water resulted in a rise in total bile acids and chenodeoxycholyl species, but not cholylglycine, indicating the rise was due to the administered bile acid and not gallbladder contraction. Administration of a meal and chenodeoxycholic acid simultaneously caused no greater rise of total serum bile acids or cholylglycine than either stimulus alone. Peak response and area under the curve were compared for each patient. The increase for chenodeoxycholyl species was additive for the two stimuli, suggesting that free chenodeoxycholic acid, when administered with a meal, decreased the absorption of endogenous conjugated bile acids. This study is compatible with the thesis that serum bile acids accurately reflect enterohepatic cycling and that administration of chenodeoxycholic acid with a meal may decrease its efficacy because exogenous chenodeoxycholic acid may compete with endogenous bile acids for absorption.

Adult↗
PubMed1982

Biliary lipid composition in healthy and diseased infants, children, and young adults.

Biliary lipid composition and cholesterol saturation were measured in 17 infants and children (age, 4 mo to 9 yr) who had recovered from chronic diarrhea (control subjects), 9 infants and children (age, 4 mo to 9 yr) with interruption of the enterohepatic circulation of bile salts from birth, and in 20 healthy young adults (age, 21-35 yr). The cholesterol molar fraction in pediatric controls was 3.7 +/- 0.2% (mean +/- SE), and in patients with ileal dysfunction or resection was 3.4 +/- 0.4%. Both values were significantly lower than that found in adults (5.7 +/- 0.5%, p less than 0.01). Cholesterol saturation, calculated using the method of Thomas and Hofmann, was significantly reduced in patients with ileal dysfunction or resection (0.60 +/- 0.10; p less than 0.01) and juvenile controls (0.72 +/- 0.04; p less than 0.05) compared with adults (1.08 +/- 0.09). It appears that proportionately larger bile salt pools (adjusted to body size) in both pediatric groups compared with their normal and diseased adult counterparts contribute to the observed reduction in the biliary molar fraction of cholesterol and reduced cholesterol saturation. However, both normal and diseased infants and children primarily have reduced biliary cholesterol/bile salt excretion ratios such that, even at low rates of secretion, bile is not saturated with cholesterol. Therefore, age-related differences in biliary lipid secretory rates seem to produce unsaturated bile in both normal and diseased prepubertal humans.

Adult↗
PubMed1982

Pretreatment biliary lipid composition in white patients with radiolucent gallstones in the National Cooperative Gallstone Study.

Biliary lipid classes (bile acids, phospholipids, cholesterol) as well as individual biliary bile acids were measured in duodenal bile samples obtained before treatment from 284 white men and 264 white women participating in the National Cooperative Gallstone Study. The patients had radiolucent gallstones present in visualizing gallbladders. Calculated biliary cholesterol saturation was significantly higher in women (143 +/- 43, mean +/- SD, vs. 132 +/- 39 for men). Chenodeoxycholic acid was the major biliary bile acid in both sexes (40.0 +/- 9.9 in men; 38.8 +/- 9.3 in women, NS). Cholic acid was the second most common bile acid, constituting 32.9 +/- 8.8 in men and 31.8 +/- 8.9 in women (NS). When other demographic and clinical characteristics, including serum lipids, were related with biliary lipid composition, only percent ideal body weight correlated significantly. The partial correlation coefficient adjusted for percent ideal body weight indicated that the proportion of chenodeoxycholic acid correlated negatively with the mole fraction of cholesterol in bile in men, but not in women. Multiple regression analyses showed that bile saturation could not be predicted reliably from any clinical, chemical, or radiologic measurement in either sex. Published data for biliary lipid composition in individuals with biliary disease showed considerable overlap with the National Cooperative Gallstone Study data reported here, suggesting that cholesterol gallstone disease is not caused solely by increased biliary cholesterol saturation.

Adult↗
PubMed1981

Identification of patients with cholesterol or pigment gallstones by discriminant analysis of radiographic features.

In a search for a way to distinguish cholesterol gallstones from pigment gallstones by oral cholecystography, we evaluated 56 patients with surgically confirmed cholelithiasis. Only buoyancy was highly predictive of gallstone composition: all 14 patients with floating stones had cholesterol stones (P less than 0.01), but only one third of the patients with cholesterol stones had stone buoyancy. Using a function derived by stepwise discriminant analysis, we separated patients with cholesterol stones from those with pigment stones. The predictive accuracy was significantly improved: sensitivity was 95 per cent (37 of 39 patients with cholesterol stones), specificity was 82 per cent (14 of 17 patients with pigment stones), and efficiency was 91 per cent (51 of 56 total patients). The resultant function, applied prospectively to 17 additional cases, classified all of them correctly. In patients with cholelithiasis and gallbladders visualized on oral cholecystography, discriminant analysis can improve the prediction of gallstone composition and the subsequent selection of medial or surgical therapy.

Adult↗