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J Neuberger

Publications and source records attributed to J Neuberger.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effect of CCK on food intake in man: physiological or pharmacological effect?

The present study was designed to determine in humans the dose of CCK which suppresses food intake. 18 male subjects received in randomized order either i.v. saline or Thr28 Nle31 CCK 25-33 (CCK-9) at 100 or 500 pmol/kgh, respectively. In addition, 7 subjects received CCK together with the opiate receptor antagonist naloxone to examine if activation of endogenous opioids might interfere with the potential satiating effect of CCK. Food intake during saline was 32 +/- 2 sandwiches (mean +/- SEM), during CCK-9 100 pmol/kgh 28 +/- 2 (n.s.) and only 12 +/- 3 during CCK-9 500 pmol/kgh (p less than 0.01). The respective water intake was 730 +/- 70 ml, 590 +/- 60 ml (n.s.) and 320 +/- 50 ml (p less than 0.01). Naloxone further reduced food and water intake during high but not low dose CCK or saline. During saline postprandial insulin levels rose by 49 +/- 6 microU/ml within 45 min which was attenuated during low dose (23 +/- 6 microU/ml; p less than 0.01) and high dose CCK-9 (1 +/- 1 microU/ml; p less than 0.001). Plasma glucagon did not change in control or CCK experiments. The postprandial rise of pancreatic polypeptide was attenuated during high dose CCK. Naloxone had no effect on the hormonal response except for a prolonged reduction of insulin and glucose levels following high dose CCK + naloxone. Plasma CCK levels rose by 5.4 pmol/l in controls but by 55 and 255 pmol/l during the low and high dose CCK infusion, respectively. These data demonstrate that suppression of food intake in man by i.v. CCK is a pharmacological rather than a physiological effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Circulating osteocalcin in primary biliary cirrhosis following liver transplantation and during treatment with ciclosporin.

Circulating osteocalcin, a non-collagen bone protein is considered a useful indirect index of turnover. Osteocalcin levels were measured by radioimmunoassay in 57 female patients with primary biliary cirrhosis (PBC) from two centres, 52 normal female controls, 11 female patients following liver transplantation for PBC and seven female patients with PBC treated with Ciclosporin. Serum levels were significantly less in the PBC group (median 10 ng/ml) compared to normals (median 15 ng/ml: p less than 0.001). Patients with PBC treated with Ciclosporin had significantly higher levels than untreated patients (median 23 ng/ml: p less than 0.001). Levels also increased significantly following transplantation when all patients were receiving Ciclosporin (median 40 ng/ml: p less than 0.001). The results suggest that the abnormal bone metabolism of PBC is significantly altered by Ciclosporin and liver transplantation.

Adrenal Cortex Hormones↗
PubMed1990

Churg-Strauss vasculitis and ascaris infection.

A patient with Churg-Strauss vasculitis presenting with mononeuritis multiplex, who developed obstructive jaundice, is described. On investigation the jaundice proved to be due to ascaris infestation. As the immune abnormalities associated with ascaris infection are also typical of those seen in the Churg-Strauss syndrome it is speculated that the vasculitis occurred because of a failure to regulate the anti-ascaris immune response.

Antigen-Antibody Complex↗
PubMed1989

Evidence for disease recurrence after liver transplantation for primary biliary cirrhosis. Clinical and histologic follow-up studies.

Twenty three patients with primary biliary cirrhosis surviving for greater than 1 yr after liver transplantation were studied. All reported marked symptomatic improvement, and had significant falls in serum bilirubin, alkaline phosphatase (p less than 0.0001), immunoglobulin M, and antimitochondrial antibody levels (p less than 0.005). Beyond 1 yr, liver biopsies showed features compatible with disease recurrence in 9 of 10 patients, and a further 4 patients developed pruritus or associated abnormalities. Immunoglobulin M levels were raised in 80%, with elevated antimitochondrial antibody titers in all those tested. Cyclosporine treatment in some patients initially given prednisone and azathioprine was followed by regression of histologic abnormalities. Of 102 patients with nonprimary biliary cirrhosis followed similarly, 50 underwent biopsy, and although 12 showed features of bile duct damage, all had additional histologic and clinical changes supporting an alternative diagnosis. These findings are consistent with previous reports that primary biliary cirrhosis can recur after transplantation, possibly modified by the use of cyclosporine.

Autoantibodies↗
PubMed1989

Drug-induced jaundice.

A large number of drugs may be associated with impaired bile flow. Drug-associated cholestasis presents like other forms of cholestasis with pale stools, dark urine, pruritus and jaundice. Abdominal pain may be present in some instances and can be so severe as to lead to a false diagnosis of acute cholecystitis. Biochemically, drug-associated cholestasis resembles other forms of cholestasis although the presence of eosinophilia may suggest drug involvement. Many types of drug-induced cholestasis run a benign course with resolution of signs and symptoms within 3 months but occasionally the jaundice can take a year or more to resolve. Progression to cirrhosis is uncommon. Some patients may develop a syndrome resembling primary biliary cirrhosis. The mechanisms of drug-associated cholestasis are uncertain but may arise from alteration of bile formation within the hepatocyte or bile excretion at the level of the canaliculus or the extrahepatic ducts. Histological examination of the liver may be helpful in classifying the types of jaundice but the diagnosis of drug-induced cholestasis is usually one of temporal association and exclusion of other causes.

Cholestasis↗
PubMed1989

Prognosis after liver transplantation for primary biliary cirrhosis.

Timing of transplantation for patients with primary biliary cirrhosis (PBC) requires identification not only of individual risk factors for the operation but estimation of survival with and without transplantation. To identify those risk factors and develop a prognostic model, 82 patients grafted for PBC since 1980 in the Birmingham and Cambridge/King's College Hospital series have been analyzed. Using logrank tests it was found that treatment with diuretics, hemoglobin above 10 g/dl, prothrombin time less than 5 sec prolonged, serum sodium above 130 mmol/L and serum bilirubin less than 350 mumol/L were all individually associated with a better prognosis. Using Cox regression analysis to identify independent variables, it was found that year of transplant, serum bilirubin, serum urea, and diuretic responsive ascites had a significant association with survival. Using these four variables, it was possible to develop a model to identify those patients with a good and a poor probability of survival after transplantation.

Bilirubin↗
PubMed1989

Immune mechanisms in tienilic acid associated hepatotoxicity.

In order to investigate the mechanisms underlying the hepatotoxicity associated with tienilic acid (Ticrynafen) ingestion we have looked for evidence of sensitisation to drug altered liver cell determinants using an indirect antibody dependent, cell mediated cytotoxicity assay (ADCC). As targets, hepatocytes were isolated from rabbits pretreated with either tienilic acid or its isomer with or without previous enzyme induction with either phenobarbitone or B-naphthoflavone (BNF). Sera from 16 of 36 patients with presumed tienilic acid hepatotoxicity induced significant cytotoxicity to hepatocytes isolated from rabbits pretreated with BNF and subsequently tienilic acid. Three of 10 sera from patients receiving tienilic acid but without overt liver damage also induced significant cytotoxicity to these hepatocytes, however, although none of 20 normal controls or of 16 patients with other liver diseases did so. Non-organ specific autoantibodies, classified as anti-LKM2, were also detectable. These were present in association with tienilic acid associated antibodies: of the 36 patients with presumed tienilic acid hepatotoxicity, 38% had both antibodies, 18% had only anti-LKM2 antibodies and 9% only tienilic acid associated antibodies. These results suggest that this drug reaction is associated with sensitisation to drug altered liver cell antigens and autoantigens. If ticrynafen associated hepatotoxicity is immune mediated, then one possible mechanism is that the drug induced antigens break tolerance, leading to an immune attack on normal liver cell components.

Adult↗
PubMed1989

Massive haemorrhagic necrosis of the liver after liver transplantation.

Six of the first 85 patients who received the first 100 liver transplantations carried out in Birmingham developed a syndrome of fulminant liver failure with distinctive clinical and pathological features. The typical clinical presentation was of an uneventual initial postoperative period, followed by a sudden deterioration in graft function, progressing rapidly to graft failure. All six patients died. The characteristic pathological changes were those of massive haemorrhage and hepatocyte necrosis with only mild inflammation and without occlusive lesions in large arteries or veins. These distinctive features differed from other recognised patterns of graft damage and seemed to comprise a specific post-transplant syndrome. The pathogenesis was not clear and in the absence of any definite aetiology it is suggested that the term "massive haemorrhagic necrosis" be used to describe these cases. Additional findings seen in five of the six cases were venoocclusive lesions (n = 4) and a combination of ductopenia and foam cell arteriopathy (n = 2). The presence of these associated lesions suggests that there may be an overlap with other types of graft damage.

Adult↗