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Biomedical subjects

J Crowe

Publications and source records attributed to J Crowe.

At least 91 records · Page 5Linked to original sources

Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial.

The effect of azathioprine on survival of patients with primary biliary cirrhosis was studied prospectively in a multinational, double-blind, randomized clinical trial including 248 patients of whom 127 received azathioprine and 121 placebo. There were 57 deaths in the azathioprine group and 62 in the placebo group. The actual survival was slightly longer during azathioprine than during placebo treatment. Using Cox multiple regression analysis and adjusting for slight imbalance between the two treatment groups, the therapeutic effect of azathioprine was statistically significant (p = 0.01), with azathioprine reducing the risk of dying to 59% of that observed during placebo treatment (95% confidence interval 40%-90%) or improving survival time by 20 mo in the average patient. Furthermore, azathioprine slowed down progressing incapacitation. Side effects of azathioprine were relatively few. The analysis revealed that the following five variables independently implied poor prognosis: high serum bilirubin, old age, cirrhosis, low serum albumin, and central cholestasis. These factors were combined to a "prognostic index" for prediction of outcome in new patients. The index was validated on independent patient data. On the basis of these results we recommend azathioprine as a routine treatment of primary biliary cirrhosis.

Actuarial Analysis↗

Small bowel capillary dilatation in portal hypertension.

A patient with small bowel capillary dilatation and cirrhosis is reported. This patient had persistent, unexplained gastrointestinal bleeding. Small bowel capillary dilatation appears to be unique to patients with portal hypertension. The possible role of small bowel capillary dilatation in causing gastrointestinal bleeding is discussed.

Adult↗

Early features of primary biliary cirrhosis: an analysis of 85 patients.

A standardized clinical, laboratory, and histological assessment was carried out on 85 patients with primary biliary cirrhosis within 1 year of developing symptoms. Presenting symptoms included pruritus (n = 30), jaundice (n = 9), variceal bleeding (n = 6), ascites (n = 5), fatigue (n = 4), and abdominal pain (n = 4). Ten patients had symptoms not immediately suggestive of hepatic etiology and a further 17 were asymptomatic, the diagnosis being made fortuitously. Eighty four percent were not incapacitated and 52 were anicteric. Less than half were pigmented, 22% had xanthoma, and only 12% were deeply jaundiced. In contrast, all had significant laboratory abnormalities with alkaline phosphatase activity greater than 400 IU/L in 60% and IgM greater than 2.5 g/L in 75%. Mitochondrial antibody was detectable in 83% with a titer greater than 1:160 in 70%. Cirrhosis was present in 24 patients, nine of whom were anicteric and a further 11 had fibrosis or scarring.

Adult↗

Evidence for a water-soluble intermediate in exchange of cholesterol between membranes.

The mechanism of inter-membrane cholesterol exchange has been a matter of some debate. Evidence from kinetic studies indicates that cholesterol must transfer to and from membranes in a water-soluble form. In this study attempts have been made to demonstrate that this occurs using either dialysis membranes or a barrierless multiphase polymer system to physically separate the membranes. In both systems small amounts of cholesterol were seen to transfer from one membrane pool to another using both liposomes and erythrocyte membranes as donors or acceptors. The cholesterol transfer was shown to be independent of the movement of other membrane components. The amount of transfer observed was limited by the physical properties of the systems employed. The barrier to cholesterol transfer in the dialysis membrane system is primarily the pore size of the membrane, while in the multiphase polymer system the transfer was limited by the viscosity of the medium and the distance between the lower and upper phases containing the membranes. Nevertheless, the results provide evidence that cholesterol transfer is by a dissociation of molecules from membranes into the aqueous medium and does not require the formation of a collision complex between the membranes.

Cholesterol↗

Cholesterol ester storage disease in an adult presenting with sea-blue histiocytosis.

An adult patient is described with hepatomegaly and sea-blue histiocytes in the bone marrow. A diagnosis of cholesterol ester storage disease was established following enzyme and lipid analyses on liver biopsy and cultured skin fibroblasts. Acid esterase activity was deficient (approx. 5% of controls) in liver and fibroblasts using [14C]-triolein or 4-methylumbelliferyl palmitate as substrates. Cholesterol ester levels were raised about 70-fold in liver, whereas triglyceride levels were only marginally raised. Marked accumulation of cholesterol esters was also demonstrated in cultured fibroblasts. Clinically, the patient responded favourably to phenobarbitone treatment. However, this was not reflected in liver acid esterase or lipid levels.

Adult↗

Effects of hypophysectomy and metyrapone on the catecholamine content and volumes of adrenaline- and noradrenaline-storing cells in the rat adrenal medulla.

Using morphometric analysis and high-pressure liquid chromatography with electrochemical detection of catecholamines the volumes of adrenaline-storing (A) and noradrenaline-storing (NA) cells and the adrenaline and noradrenaline contents of adrenal glands of normal and age-matched hypophysectomized rats were determined and compared. Some hypophysectomized rats were also administered 150 mg metyrapone/kg daily for a 4-week period. Hypophysectomy resulted in an increase in noradrenaline storage in adrenal glands. This was more marked in hypophysectomized animals not treated with metyrapone even though the combination of metyrapone and hypophysectomy resulted in a reduction of blood corticosterone concentration to only approximately 6% normal. There was no evidence of a change in proportion of A and NA cells in the adrenal medulla of hypophysectomized rats or hypophysectomized animals treated with metyrapone and it is concluded that the changes in amine concentrations and proportions observed reflect an increase in the storage of noradrenaline in A cells as a consequence of less efficient methylation of noradrenaline after hypophysectomy. The findings also showed that the left adrenal gland and medulla was usually slightly larger and had a greater catecholamine content and slightly higher proportion of NA cells than the right adrenal gland. During the period of the experiment (animals aged 6-15 weeks) there was an increase in the concentration of both adrenaline and noradrenaline in the normal adrenal glands. In normal Sprague-Dawley rats weighing 140 and 400 g the adrenal medulla accounted for some 5% of adrenal volume; this increased to 13% after hypophysectomy; A and NA cells together accounted for 50-60% of the volume of adrenal medulla.

Adrenal Medulla↗

Azathioprine in primary biliary cirrhosis: a preliminary report of an international trial.

The effects of azathioprine on the course of primary biliary cirrhosis were studied prospectively in a multinational, double-blind randomized clinical trial involving 236 patients, of which 124 received azathioprine and 112 placebo. No significant effects were seen on survival, clinical course, hepatic histologic features, hepatic tests, or immunologic abnormalities after a median follow-up period of 18 mo, but most of the trends observed were in favor of azathioprine. The results obtained so far indicate that the effect of azathioprine as a single treatment is limited and probably of little clinical importance, but more years of follow-up will be needed to provide a definite conclusion.

Actuarial Analysis↗

Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients.

A prospective study of the clinical pattern and course of primary biliary cirrhosis based on the data of 236 patients (211 females, 25 males) in an international randomized trial has been performed mainly using life-table technique. The median follow-up period has been 18 mo. After the entry into the study, at which time the median duration of symptoms was 2.1 yr, the estimated 5-yr increase in the cumulative percentage of patients was for pruritus from 75% to 95%, jaundice 59% to 82%, hepatomegaly 54% to 86%, pigmentation 54% to 85%, xanthomas 27% to 50%, GI bleeding 17% to 46%, ascites 7% to 49%, and vertebral collapse 3% to 20%. The frequency of cirrhosis increased from 30% to 82% in 4 yr. The mitochondrial antibody titer showed a high rate of progression with time. In analysis of subgroups, age, histologic stage, and particularly the serum bilirubin level were important prognostic factors. Sex, duration of symptoms, and character of first symptom or sign had no independent prognostic influence. The most important indication of seriously progressive course was rapid development of severe cholestasis independent of the histologic stage.

Adult↗

Preoperative diagnosis of unilateral multicystic kidney with hydropelvis.

We present 2 patients with congenital unialteral multicystic kidney disease with hydropelvis. In the first patient the diagnosis was made by precutaneous puncture of a renal cyst followed by injection of contrast medium; in the second the diagnosis was confirmed by percutaneous puncture of the renal pelvis and injection of contrast medium, although an earlier ultrasonic examination had been strongly suggestive. Since in this condition the cysts and the renal pelvis communicate, either can be punctured to make the diagnosis. The procedures herein described are definitive for the diagnosis and should be followed whenever the urologist desires such a diagnosis.

Biopsy, Needle↗

Death following fiberoptic gastroscopy caused by pheochromocytoma.

A 45-year-old woman was admitted to hospital for investigation of weight loss, sciatica and excess sweating. On examination, whe was found to have a tachycardia and the stigmata of von Recklinghausen's disease. Her investigations included a barium meal and gastroscopy. Following the gastroscopy, she developed ventricular tachycardia and died. An autopsy revealed a pheochromocytoma of the left adrenal gland.

Adrenal Gland Neoplasms↗

On the fixation of catecholamines including adrenaline in tissue sections.

Following intravenous or intraperitoneal injections of 3H-l-dopa radioactivity in adrenal medullary chromaffin cells of the mouse has been followed by autoradiographic and radioisotopic assay methods. For autoradiographic purposes tissues were fixed in either phosphate buffered glutaraldehyde or in 1-5% potassium dichromate in glutaraldehyde pH 7-2. A high initial radioactivity is demonstrated by both autoradiography and radioisotopic assay. During the first hour dopamine is the predominant labelled amine. Between 1 and 4 hours after the injection noradrenaline is in highest concentration and from 1 to 24 hours labelled adrenaline appears and becomes the predominant labelled amine (about 70%) after 24 hours. Autoradiographs of tissues fixed in glutaraldehyde alone confirm that adrenaline is lost from sections by this technique. When 1-5% potassium dichromate is added to glutaraldehyde then adrenline is fixed in A cells and these show only a slightly decreased grain count as compared to NA cells at 5 days; this slight decrease is probably due to more rapid turnover of amines by A cells.

Adrenal Glands↗