Computerized Angiographic Occlusion Rating for Ruptured Clipped Aneurysms is Superior to Subjective Occlusion Rating.

BACKGROUND AND PURPOSE: The computerized occlusion rating to estimate angiographic occlusion of embolized aneurysms is superior to the subjective occlusion rating. In this study, we compared the 2 methods in the analysis of aneurysms clipped after subarachnoid hemorrhage. MATERIALS AND METHODS: The pre- and postoperative angiographic images (DSA) of 95 selected patients were analyzed and stratified in 4 grades (grade 0 for 100%, grade I for <99%-90%, grade II for <89%-70%, grade III for <70% occlusion) by using the subjective (angiographic) occlusion rating and the computerized (angiographic) occlusion rating. For the subjective occlusion rating, the occlusion rate was estimated; for the computerized occlusion rating, the "occluded" and "nonoccluded" aneurysm areas were automatically calculated in square millimeters after outlining the ideal occlusion line. RESULTS: With the subjective occlusion rating, 75 (78.9%), 12 (12.6%), 7 (7.4%), and 1 (1.1%) and with the computerized occlusion rating 45 (47.4%), 24 (25.3%), 20 (21.0%), and 6 (6.3%) patients had aneurysms stratified to grades 0, I, II and III, respectively. The interobserver variation was significant with the subjective occlusion rating but not with the computerized occlusion rating. The subjective occlusion rating overestimated aneurysm occlusion in 30 (31.6%) patients. Mean values were the following: subjective occlusion rating of 97.5 ± 6.3% and computerized occlusion rating of 93.5 ± 9.7%; P = < .001. No patient rebled, and 4 patients underwent retreatment during 36 ± 38.9 months; the predictive value (log-rank, Kaplan-Meier) of the subjective and computerized occlusion ratings with respect to retreatment was highly significant for both methods (subjective occlusion rating: χ(2), 29.65; P < .001; computerized occlusion rating: χ(2), 35.57, P < .001). CONCLUSIONS: The 2 methods showed remarkable differences in the estimation of the angiographic occlusion rates of clipped aneurysms. The clearly lower interobserver variation of the computerized versus subjective occlusion rating may indicate a superiority of the computerized occlusion rating.

The Minnesota Regional Peripheral Arterial Disease Screening Program: toward a definition of community standards of care.

The Minnesota Regional Peripheral Arterial Disease Screening Program was designed to define the efficacy of community PAD detection efforts, to assess the disease-specific and health-related morbidity, to assess PAD awareness rates, and to determine the magnitude of atherosclerosis disease risk factors and the intensity of their management. The target population was recruited via mass media efforts directed at individuals over 50 years of age and those with leg pain with ambulation. Screening sessions included assessments of the ankle-brachial index, blood pressure, fasting lipid profile, and use of validated tools to detect symptomatic claudication (by the Modified WHO-Edinburgh Claudication Questionnaire), walking impairment (Walking Impairment Questionnaire - WIQ), quality of life (MOS SF-36), PAD awareness, and the intensity of PAD medical therapeutic interventions. PAD was defined as any ankle-brachial index < or =0.85 or a history of lower extremity revascularization. The program evaluated 347 individuals and identified 92 subjects with PAD and 255 subjects without PAD, yielding a detection rate of 26.5%. Individuals with PAD were older, tended to have higher blood pressures, and had a significant walking impairment and an impaired health-related quality of life compared with the non-PAD subjects. Current rates of tobacco use were low. Lipid-lowering, estrogen replacement, anti-platelet, and antihypertensive medications and exercise therapies were underutilized in the PAD cohort. Peripheral arterial disease awareness was low in these community-identified patients. This Program demonstrated that individuals with PAD can be efficiently identified within the community, but that current standards of medical care are low. These data can assist in the future development of PAD awareness, education, and treatment programs.

Active renin and angiotensinogen in cardiac interstitial fluid after myocardial infarction.

The renin-angiotensin system promotes cardiac hypertrophy after myocardial infarction. The purpose of this study was to measure renin and angiotensinogen in plasma and myocardium 10 days after myocardial infarction. Infarction involving 45 +/- 4% of left ventricular circumference with accompanying hypertrophy was induced in rats (n = 14). Plasma and myocardial renin were increased after infarction compared with sham controls (n = 8) (27.4 +/- 3.2 vs. 7.5 +/- 1.8 ng ANG I. ml plasma. h-1, P < 0.0002; and 8.8 +/- 1.6 vs. 2. 5 +/- 0.1 ng ANG I. g myocardium-1. h-1, P < 0.008, respectively). After infarction, myocardial renin was correlated with infarct size (r = 0.62, P < 0.02) and plasma renin (r = 0.55, P < 0.04). Plasma angiotensinogen decreased in infarct animals, but myocardial angiotensinogen was not different from shams (1.1 +/- 0.08 vs. 2.03 +/- 0.06 nM/ml plasma, P < 0.002; and 0.081 +/- 0.008 vs. 0.070 +/- 0.004 nM/g myocardium, respectively). In conclusion, myocardial renin increased after infarction in proportion to plasma renin and infarct size, and myocardial angiotensinogen was maintained after infarction despite decreased plasma angiotensinogen and increased levels of myocardial renin.

Temporal induction of clusterin in the peri-infarct zone after experimental myocardial infarction in the rat.

Clusterin, a glycoprotein with potent cellular cohesive properties, is induced in many organs at times of tissue injury or remodeling. After renal infarction, for example, clusterin is localized to tubular epithelial cells in the peri-infarct zone. The purpose of this study was to examine the spatial and temporal expression of cardiac clusterin after myocardial infarction. Sprague-Dawley rats underwent permanent coronary ligation or sham operation. Hearts were harvested at 6 hours and at 2, 14, and 28 days after infarction. Cardiac clusterin expression was examined by immunohistochemistry and in situ hybridization. Left ventricular clusterin staining was evident at 6 hours and 2 days after myocardial infarction, although not at later time periods. Clusterin was localized to peri-infarct zone myocytes and endothelial cells of this region, and local synthesis of clusterin by myocytes was confirmed by in situ hybridization. Clusterin was not present in inflammatory cells or in left ventricular tissue distant from the infarct. The distribution of clusterin was different from the membrane attack complex of complement (C5b-9), with the latter being present diffusely throughout the infarct zone. Although the role of cardiac clusterin is not known, we speculate that clusterin's cohesive properties serve to promote myocyte interactions that are perturbed in the peri-infarct zone after myocardial infarction.

Effect of bilateral nephrectomy on active renin, angiotensinogen, and renin glycoforms in plasma and myocardium.

In an attempt to clarify the relationship of the circulating and myocardial renin-angiotensin systems, active renin concentration, its constituent major glycoforms (active renin glycoforms I through V), and angiotensinogen were measured in plasma and left ventricular homogenates from sodium-depleted rats under control conditions or 2 minutes, 3 hours, 6 hours, and 48 hours after bilateral nephrectomy (BNX). Control myocardial renin concentration was 1.4+/-0.1 ng angiotensin I (Ang I) per gram myocardium per hour and plasma renin concentration was 6.7+/-1.1 ng Ang I per milliliter plasma per hour. Control myocardial angiotensinogen was 0.042+/-0.004 micromol/kg myocardium and plasma angiotensinogen was 1.5 micromol/L plasma. Two minutes after BNX and corresponding stimulation of renin secretion by anesthesia and surgery, plasma renin concentration was increased disproportionately compared with myocardial renin. Three, 6, and 48 hours after BNX, renin decay occurred significantly faster from the plasma than from the myocardium. Forty-eight hours after BNX, myocardial renin concentrations had fallen to 15% of control values, while myocardial angiotensinogen concentrations had increased 12-fold and plasma angiotensinogen concentrations had increased by only 3.5-fold. Myocardial renin glycoform proportions were identical in myocardial homogenates and plasma in control animals. At 6 hours BNX, the proportions of plasma active renin glycoforms I+II fell, while those in the myocardium significantly increased. We conclude that in control rats, active renin and active renin glycoforms are distributed as if in diffusion equilibrium between plasma and the myocardial interstitial space. After BNX, myocardial renin concentration falls dramatically, suggesting that most cardiac renin is derived from plasma renin of renal origin. After BNX, renin glycoforms I+II are preferentially cleared from the plasma but preferentially retained by the myocardium. Control myocardial angiotensinogen concentrations are too low to result from simple diffusion equilibrium between plasma and the myocardial interstitium.

Minocycline-induced liver injury.

Tetracycline may cause fatty infiltration of the liver; more recently, it has been reported to cause intrahepatic cholestasis with bile duct depletion. However, minocycline, a derivative of tetracycline, is not generally recognized to be hepatotoxic. We report a series of six cases of presumed minocycline-induced liver injury; five of these patients had acute hepatitic illness, whereas one had a more prolonged course with histological evidence of chronic hepatitis. In addition, three patients demonstrated abnormal anti-nuclear antibody levels, and one had positive double-stranded DNA.

Efficacy of cisapride therapy in functional dyspepsia.

AIM: To assess the efficacy of cisapride therapy in relieving symptoms of functional dyspepsia. METHODS: After a 2-week placebo run-in period, 61 out of 74 patients were eligible to enter a 4-week double-blind treatment phase, consisting of treatment with cisapride (10 mg) or placebo tablets t.d.s. Gastric emptying was assessed scintigraphically at entry to the study. Patients were stratified before treatment into those with or without active chronic (Helicobacter pylori) gastritis. Patients were also classified retrospectively into those with 'reflux-like' dyspepsia (n = 29) and those with 'motility-like' dyspepsia (n = 32). RESULTS: At the end of the active treatment phase, there was a similar significant (P < 0.001) reduction in total symptom score from baseline in both cisapride (8.9 +/- 0.5 to 5.8 +/- 0.6) and placebo (9.7 +/- 0.6 to 5.5 +/- 0.6) groups. Scores for heartburn and continual bloating were significantly reduced in the cisapride but not the placebo group; improvement was attributable to patients with normal, rather than delayed, rates of gastric emptying. For continual bloating, significant improvement also occurred in the cisapride subgroup without gastritis, but not in the subgroup with gastritis (mean symptom score reduction 0.48 +/- 0.18, P = 0.03). For global evaluation by the investigator and by the patient, the overall improvement rates were not statistically different between cisapride and placebo groups. In those with normal gastric emptying, however, there was a significant (P = 0.01) improvement in general well-being in the cisapride but not in the placebo group. CONCLUSIONS: We were unable to show major differences in the short-term efficacy of cisapride and placebo in functional dyspepsia. There were indications, however, of beneficial effects of cisapride over placebo in those with 'reflux-like' dyspepsia, and in those without gastroparesis.

Intragastric distribution and gastric emptying of solids and liquids in functional dyspepsia. Lack of influence of symptom subgroups and H. pylori-associated gastritis.

The relative contributions of altered gastric motor function and Helicobacter pylori-associated active chronic gastritis to the pathogenesis of functional dyspepsia are controversial. We therefore evaluated scintigraphically the intragastric distribution and gastric emptying of a mixed solid-liquid meal in 75 patients with functional dyspepsia; patients were subdivided on the basis of both specific symptom clusters and the presence or absence of H. pylori gastritis. Twenty-one (28%) patients displayed abnormal solid and/or liquid gastric emptying, with prolonged solid lag time the most prominent alteration detected. The number of patients with abnormal scintigraphic patterns increased to 36 (48%) when intragastric distribution parameters (fundal half-emptying time and antral maximal fraction) were examined. Although patients with reflux-like dyspepsia (N = 36) demonstrated significantly slower rates of liquid emptying at 45 and 70 min and a higher prevalence of abnormal liquid intragastric distribution when compared to patients with motility-like dyspepsia (N = 39) or to controls (N = 34), the absolute differences were small and unlikely to be of clinical significance. Patients without H. pylori gastritis (N = 50) demonstrated a significantly more prolonged solid lag time when compared to those with H. pylori gastritis (N = 25), but the difference was small and there were no other differences between these two subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Flucloxacillin induced liver disease: histopathological findings at biopsy and autopsy.

The histological appearances of liver biopsies of 13 patients who developed cholestasis following courses of flucloxacillin are presented. In most of the cases jaundice and pruritus were protracted and in nearly all cases liver function tests are yet to return to normal after mean follow-up of 18 mths. One patient died after 7 mths of jaundice and another shows clinical evidence of secondary biliary cirrhosis. Biopsies typically showed hepatocellular and canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts were reduced in number and in 6 cases reduced in size. Bile duct epithelium showed degenerative changes but only occasional infiltration by inflammatory cells. Ductular proliferation was quite variable and in some cases--most noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The appearances suggested damage not only of hepatocytes but also of bile ducts and proliferating ductules. This may explain the prolonged and occasionally irreversible hepatic disease associated with the use of flucloxacillin. Flucloxacillin should be included amongst the causes of vanishing bile duct syndrome.

Osteoporosis and skeletal fractures in chronic liver disease.

In order to determine the prevalence and severity of hepatic osteodystrophy by non-invasive means we compared 115 consecutive ambulant patients with histologically proven chronic liver disease to 113 age and sex matched control subjects. Methods used included the assessment of fracture prevalence rates, spinal radiography, and measurements of bone mineral density in the spine and the forearm. Spinal and peripheral fractures were more prevalent in the patients than in the control subjects (p less than 0.03 and p less than 0.01 respectively). The type of the underlying liver disease did not significantly affect the fracture prevalence rates, but alcoholic patients sustained more peripheral fractures than patients with other hepatic disorders (p less than 0.05). The bone mineral densities of the spines and the forearms were significantly reduced in male patients of all age groups and in female patients aged 60 years or more (p less than 0.001 for men and p less than 0.01 for women for both measurements). The prevalence rates of spinal and forearm osteoporosis were twice as high among patients with liver disease than in control subjects regardless of the definitions used. The presence of cirrhosis and hypogonadism were major risk factors for development of both spinal (Beta coef = 0.190 and 0.176; SE = 0.079 and 0.086 respectively) and forearm osteoporosis (Beta coef = 0.20 and 0.29; SE = 0.073 and 0.80 respectively). Spinal bone density was the predominant determinant of spinal fractures (Beta coef = -0.007; SE = 0.001), while hypogonadism (Beta coef = 0.363; SE = 0.075) and cirrhosis (Beta coef = 0.185; SE = 0.068) were the major predictors of peripheral fractures. The concentrations of serum calcium and serum vitamin D metabolites and the use of corticosteroids were apparently without effect on the prevalence of skeletal fractures or bone density.

Prolonged hepatic cholestasis after flucloxacillin therapy.

A severe prolonged illness that was characterized by deep jaundice and debilitating pruritus occurred in five patients after the use of flucloxacillin. The symptoms and signs of liver disease took at least two months to resolve; after four- to nine-months' follow-up, liver enzyme activities have remained abnormal in all patients. Examination of liver biopsy specimens showed severe cholestasis in all cases, with evidence of significant bile-duct injury in three cases. In one patient, in whom symptoms have persisted for nine months, examination of a liver biopsy specimen showed marked bile-duct depletion. All patients were seen during a four-month period and it is felt that flucloxacillin-induced liver disease probably has been under-diagnosed and underreported. The use of flucloxacillin has been increasing rapidly and it is anticipated that more cases of flucloxacillin hepatotoxicity will occur in the future.

The prevalence of serological markers for hepatitis B virus infection in Australian Naval personnel.

In order to determine the prevalence of hepatitis B virus infection in Royal Australian Navy personnel and to formulate policies for their education, screening and vaccination, a voluntary survey was undertaken. Seven hundred and forty-eight subjects completed a questionnaire that provided details of age, sex, rank, ethnic origin, service abroad, length of service, history of tattooing, liver disease and blood transfusions. Serum was assayed by radioimmunoassay for the presence of hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (antiHBs) and antibody to hepatitis B core antigen (antiHBc). The presence of markers of hepatitis B virus infection was correlated with "risk factors" by means of the chi 2 test of independence. Fourteen (74%) of 19 personnel from the Pacific Islands, Asia and Africa who were excluded from analysis showed one-or-more such markers. The prevalence of any marker of hepatitis B virus infection was 4.4% (95% confidence interval [CI], 2.9%-5.9%). The individual markers HBsAg, antiHBs and antiHBc were found in 0.4% (95% CI, 0.1%-1.2%), 3.6% (95% CI, 2.2%-4.9%) and 3.9% (95% CI, 2.5%-5.3%) of subjects, respectively. The annual attack rate was estimated to be less than 1%. Factors which had a significant correlation with an increased prevalence of markers of hepatitis B virus infection included tattooing (especially if this had been performed in Asia), age, the duration of service and service abroad. Based on these data, and given the reduced cost of hepatitis B vaccines, vaccination now is considered worth while. A policy of vaccinating all personnel who may be required for service at sea, and others at risk, now is in effect. Educational programmes that are aimed at minimizing the risk of exposure to hepatitis B and other viral infections have been instituted.

Jaundice in pregnancy.

The occurrence of hepatobiliary disease with or without jaundice during pregnancy provides both the hepatologist and obstetrician with an interesting and urgent diagnostic challenge. Advances in our understanding and management of liver disorders unique to pregnancy and hepatobiliary disease in general have resulted in a significant improvement in the outcome for both mother and fetus. Certain disorders such as acute fatty liver of pregnancy and hepatic haemorrhage associated with toxaemia should be considered medical emergencies and delay in diagnosis of these conditions will probably adversely affect maternal and fetal outcome. A careful clinical history, physical examination, appropriate laboratory tests and radiological investigations should allow a diagnosis within 24-48 hours of presentation. Liver biopsy is rarely required. A careful history may provide important information. Does the patient have pre-existent liver disease? Has there been contact with hepatitis, intravenous drug abuse or any other factor predisposing to acute viral hepatitis? Does the patient have a family history of pruritus and/or jaundice to suggest intrahepatic cholestasis of pregnancy? Is the patient's alcohol consumption excessive? Has the patient received any hepatotoxic medications? Has there been abdominal pain and/or fever to suggest gallstones, hepatic bleeding or acute fatty liver of pregnancy? Laboratory investigations may give valuable diagnostic clues. Marked aminotransferase elevation would suggest acute viral or 'ischaemic' hepatitis. Haematological features of microangiopathic haemolysis would point towards toxaemia or AFLP. Hepatitis A and B serological tests may be helpful in viral liver disease. Radiological investigations may be indicated depending on the clinical context. Abdominal ultrasonography may be useful in the diagnosis of gallstones, biliary obstruction, liver tumours or intrahepatic bleeding. Fatty infiltration of the liver may be diagnosed by ultrasonography but computed tomography (CT) of the abdomen is probably more reliable for a diagnosis of acute fatty liver of pregnancy as it allows measurement of liver density which is typically reduced by fatty infiltration. CT scanning is also probably more valuable than ultrasound in assessing the extent of capsular rupture and haemorrhage into the liver and peritoneal cavity.

Ethanol reduces bone formation and may cause osteoporosis.

INTRODUCTION: The etiology of ethanol-associated osteopenia is not fully understood. In order to define the role of ethanol in the pathogenesis of hepatic osteodystrophy, we compared two groups of alcoholic patients with histologically established alcoholic liver disease. PATIENTS AND METHODS: Twenty-eight patients currently drinking ethanol ("drinkers") and 12 claiming not to have consumed any ethanol for at least six months ("abstainers") were enrolled in the study. In addition, 35 non-alcoholic control subjects without clinical or biochemical evidence of liver disease were also studied. Bone mineral density and various biochemical and hormonal values were measured in each subject; iliac crest biopsies were taken under local anesthesia in the patients and under general anesthesia in the control subjects. RESULTS: Forearm bone mineral densities, spinal bone mineral densities, and iliac crest cancellous bone areas were significantly lower in the alcoholic patients compared with control subjects (p less than 0.01 for all measurements), but these values did not differ between the drinkers and the abstainers. The drinkers, however, had significantly less osteoblastic activity than the abstainers, as assessed by dynamic bone histomorphometry (p less than 0.001). Serum bone Gla-protein concentrations were higher in the abstainers than in the drinkers (p less than 0.001). No differences were seen relating to histologic parameters of bone resorption, although the alcoholic patients who had lower serum free testosterone concentrations than the control subjects also had higher urinary hydroxyproline excretion rates. CONCLUSION: These data suggest that ethanol may be responsible for osteoblastic dysfunction resulting in diminished bone formation and reduced bone mineralization.

Hepatic osteodystrophy. Static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver disease.

To study the pathogenesis of osteoporosis in patients with chronic liver disease, we performed dynamic bone histomorphometry and measured serum bone Gla-protein in 80 patients with various types of chronic liver disease. These results were compared with results obtained in 40 healthy controls. Mean trabecular bone volume and mean trabecular thickness were significantly reduced in both men and women with chronic liver disease (p less than 0.001 for both measurements in men and p less than 0.01 for both measurements in women). Osteoporosis as defined by histologic parameters was present in 17 (21%) patients with no significant differences in prevalence rates among the various hepatic disorders. No patient had histologic evidence of osteomalacia, although mineralization lag times were prolonged (p less than 0.01 for men and women). Bone formation rates were significantly reduced in 46 (57%) patients, and unlike the static measurements, were related to the type and severity of the underlying liver disease. Patients with alcoholic liver disease, hemochromatosis, and cholestatic liver disease had lower bone turnover rates and osteoblastic surfaces (p less than 0.001 and p less than 0.05, respectively) than patients with chronic active hepatitis. Furthermore, the presence of hepatic cirrhosis was associated with diminished bone formation and lower osteoblast surfaces. Serum bone Gla-protein levels were significantly correlated with bone formation rates and osteoblast surfaces (r = 0.585 and r = 0.434, respectively). A reduction in osteoblast surfaces has not previously been demonstrated in liver disease. This reduction and the associated impairment of osteoblastic activity may contribute to the pathogenesis of osteoporosis and can be assessed by the measurement of serum bone Gla-protein.

Comparative sensitivity of serum cholylglycine concentration and bromsulphalein retention in patients with early and late alcoholic liver disease.

Measurement of serum bile acids has been claimed to be a sensitive and specific biochemical test of hepatic function. We have prospectively measured post-prandial serum glycocholate (cholylglycine) concentrations in 31 patients with alcoholic liver disease and compared these measurements with those of bromsulphalein (BSP) retention, prothrombin time, and serum albumin. In the patients with early (non-cirrhotic) alcoholic liver disease (N = 14) BSP retention was abnormal significantly more frequently than was serum cholylglycine concentration (100% vs 29%, p less than 0.001). In contrast, amongst patients with late (cirrhotic) alcoholic liver disease, BSP retention and serum cholylglycine were abnormal with equal frequency (94%). In both groups of patients BSP retention and serum cholylglycine were abnormal significantly more often than were prothrombin time and serum albumin concentrations. We conclude that moderately severe hepatocellular dysfunction is required before serum cholylglycine can become a reliable biochemical indicator of liver disease.

Serum bile acid concentrations during pregnancy and their relationship to obstetric cholestasis.

We have prospectively studied changes in serum postprandial cholylglycine (CG) concentration during 297 pregnancies. We found an increase in CG concentration from 0.3 mumol/L at 15 weeks' pregnancy to 0.6 mumol/L at 40 weeks' pregnancy. Although this increase was statistically significant (p less than 0.005), median concentrations of CG remained well within the normal range (0-1.5 mumol/L). However, 10% of the group showed markedly elevated serum CG concentrations at 30 weeks' pregnancy, and the CG level in this group continued to rise during the third trimester. Pruritus was significantly more common in the group with elevated CG concentrations (48%) than in the group with normal CG levels (20%) (p less than 0.005). Serum CG was a much more sensitive predictor of pruritus during pregnancy than other biochemical liver tests. Elevated CG levels were found more commonly in Mediterranean and Asian patients than patients of other ethnic origins (p less than 0.025). No statistically significant associations were found between elevated CG concentrations and maternal age, number of previous pregnancies, pruritus during previous pregnancies, contraceptive-induced cholestasis, and fetal maturity. We conclude that obstetric cholestasis is probably much more common than previously suspected and that consideration should be given to the measurement of serum bile acids in all pregnant individuals with unexplained pruritus.

Fulminant hepatic failure due to allopurinol.

A 58-year-old Chinese woman was admitted to hospital with a presumed hypersensitivity reaction to allopurinol. Her illness was characterised by high fever, eosinophilia, exfoliative dermatitis and jaundice. She developed fulminant hepatic failure and septicemia with a fatal outcome. Clinical details are presented and the possible relationship of allopurinol hypersensitivity to renal impairment is discussed.

Urinary coproporphyrin excretion in Rotor's syndrome: a family study.

A family of seven is described in which a teenage boy and two siblings were found to have Rotor's syndrome. Total urinary coproporphyrin excretion was found to be significantly elevated in the patients with Rotor's syndrome (mean 59 . 0 mumol/mol creatinine), when compared with control subjects (mean 16 . 3 mumol/mol creatinine) (p less than 0 . 005). Similarly, urinary excretion of both coproporphyrin isomer I and coproporphyrin isomer III was greater in the subjects with Rotor's syndrome than in controls (p less than 0 . 005). Coproporphyrin I comprised 60 . 2% of total urinary coproporphyrin excretion in the subjects with Rotor's syndrome, compared with 38 . 6% in the controls, but the difference was not significant. In the parents and clinically unaffected siblings neither total urinary coproporphyrin excretion (13 . 3 and 19 . 3 mumol/mol creatinine respectively) nor percentage coproporphyrin I excretion (36 . 8 and 30 . 4%) differed from controls. Thus, although we have confirmed the previous finding of increased urinary coproporphyrin excretion in subjects with Rotor's syndrome, we have not found the previously noted intermediate increase in coproporphyrin I excretion amongst phenotypically normal relatives of subjects with this autosomal recessive disorder.