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Biomedical subjects

J Neuberger

Publications and source records attributed to J Neuberger.

At least 19 recordsLinked to original sources
PubMed1992

Community health services.

The Tomlinson report, with its emphasis on primary and community care, offers great scope to community health services, for long the poor relation of the NHS, and particularly poorly resourced in London. The aim is to create services that break down the barriers between primary, secondary, and tertiary health care and concentrate on providing high quality care tailored to individual patients' needs. Thus a range of flexible options needs to be developed between acute hospital based care and the standard home care arrangements currently provided by district nurses. Examples, include hospital at home schemes, nursing beds, and rehabilitation beds. Together community and primary care services need to consider weekend coverage, to conduct research, and to become a setting for education. The infrastructure for primary and community care must, however, be put in place before acute facilities are shut.

Community Health Services↗
PubMed1992

Membrane dihydrolipoamide acetyltransferase (E2) on human biliary epithelial cells in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is associated with serum antibodies that react with the dihydrolipoamide acetyltransferase component (E2) of the mitochondrial pyruvate dehydrogenase complex. We have sought the presence of E2 on the surface of human intrahepatic biliary epithelial cells (BEC). Cultured BECs from PBC but not normal liver were found to have E2 on the membrane after three days' culture. Isolated, viable cells examined by laser-scanning confocal microscopy revealed the pattern of E2 staining on the membrane to be similar to that seen with the membrane glycoprotein marker, HEA-125. By contrast, BECs from normal liver showed membrane staining only with HEA-125. When BECs were fixed before incubation with antibody to E2, cytoplasmic staining was observed. Our results suggest that E2 is present on the surface of biliary epithelial cells in PBC, and support the idea of a pathogenetic association between antimitochondrial antibodies and bileduct damage.

Acetyltransferases↗
PubMed1992

Psychiatric and social consequences of liver transplantation.

We assessed the prevalence of psychiatric morbidity and level of social adjustment in 32 of 34 adults who received liver transplants between 1 August 1987 and 31 July 1988 and who survived more than 6 months postoperatively. The prevalence of psychiatric morbidity was comparable with that found in the general population. Subjective complaints of cognitive impairment were common (40.6%). Liver transplant recipients were not significantly more handicapped in overall social functioning, but did show significant impairment in several role areas when compared with a community sample. Psychiatric morbidity was associated with greater social impairment, whereas liver function and other medical problems were not. We suggest that identification and treatment of psychiatric illness following transplantation needs to be better established as part of the treatment program.

Adult↗
PubMed1992

Computerised protocols for laboratory investigation and their effect on use of medical time and resources.

AIMS: To devise a computerised management system protocol which not only proposes the laboratory investigations to be performed on each patient but also performs related clinical functions. METHODS: The system was designed by senior members of staff. The protocols defined all laboratory investigations including haematology, biochemistry, immunology and cross-matching, and included static and dynamic rules. Patients can be changed to different or additional protocols, as required; likewise proposed tests can be deleted or added. The software is written in MUMPS and runs on a 386 PC running MSM MUMPS under MSDOS. RESULTS: The number of clinical chemistry tests requested per patient per day fell by 9.5% (p less than 0.01) for transplant recipients and by 28.8% (p less than 0.01) for non-transplant recipients. The average time spent by junior medical staff requesting laboratory investigations and enquiring about results fell from 10 minutes per patient per day to 4.1 minutes (p less than 0.001). CONCLUSIONS: The introduction of this system in no way abrogates clinicians' responsibility for the management of patients, because all proposed investigations must be confirmed or modified by the authorising doctor. The system allows for the audit of requesting patterns and subsequent improvement in protocols by recording any alterations made to the proposed investigations. Significant benefits in terms of better use of house officer time and medical resources were also achieved.

Clinical Laboratory Information Systems↗
PubMed1992

Endothelium myeloperoxidase-antimyeloperoxidase interaction in vasculitis.

Antibodies to myeloperoxidase (MPO) are found in the sera of patients with microscopic polyarteritis and idiopathic crescentic glomerulonephritis. Their pathogenicity is unknown. Studies were carried out on the binding of MPO to cultured human umbilical vein endothelial cells and the recognition of endothelium-bound MPO by antibody to MPO. Endothelial cells were cultured from human umbilical veins. The binding of MPO to endothelial cells and its inhibition by poly-D-lysine was detected using a monoclonal antibody to MPO and direct staining with APAAP and also by an enzyme-linked immunoassay (ELISA). The binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was detected by ELISA. MPO bound to endothelial cells both on direct staining and ELISA and this binding was inhibited by the polycation poly-D-lysine, suggesting that it was charge mediated. Binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was significantly higher than the binding of sera from normal subjects (P = 0.04), patients with idiopathic glomerulonephritis (P = 0.0005), and patients with lupus nephritis (P = 0.009). MPO binds to cultured human umbilical vein endothelium probably by a charge mechanism, and can react with anti-MPO antibodies in the sera of patients with microscopic polyarteritis as well as with a mouse monoclonal anti-MPO antibody. This binding of anti-MPO antibody to MPO fixed to the endothelial cell surface provides a mechanism by which endothelial injury and inflammation might occur in microscopic polyarteritis.

Endothelium, Vascular↗
PubMed1991

Primary sclerosing cholangitis: surgical options, prognostic variables and outcome.

The natural history of primary sclerosing cholangitis (PSC) is poorly defined and its management remains controversial. Forty-eight symptomatic patients (median age 39 years, range 8-67 years; 30 male) with PSC were reviewed retrospectively. Thirty patients had inflammatory bowel disease. Four patients (8 per cent) developed or had an associated malignancy. Twenty-one (44 per cent) died; overall 5 year actuarial survival was 30 per cent. Twenty-three patients had 27 non-transplant related biliary operations (16 patients specifically for PSC) of whom 12 died. Serum bilirubin was the only parameter to improve after biliary surgery. Seventeen patients (35 per cent) underwent orthotopic liver transplantation (OLT) of whom nine are currently alive (1 year projected survival of 55 per cent). Previous biliary surgery correlated with a poor outcome (P less than 0.0001) after OLT. Being male, presence of cirrhosis, duration of symptomatic disease (greater than 3 years) and a serum bilirubin level greater than 100 mumol/l at presentation, were independently associated with a poor outcome (P less than 0.05). These data provide evidence that PSC is a progressive disease and conventional surgical options have little influence on the outcome. Previous biliary surgery adversely affects outcome following OLT. For progressive liver disease, liver transplantation should be considered the treatment of choice.

Adolescent↗
PubMed1991

Vanishing bile-duct syndrome following liver transplantation--is it reversible?

Loss of bile ducts is a characteristic feature of chronic rejection in the liver allograft (also known as irreversible rejection and vanishing bile-duct syndrome). Typically, this occurs as a progressive lesion resulting in irreversible damage and graft failure requiring retransplantation. In this study, we describe 6 patients who developed a transient loss of bile ducts following liver transplantation. This occurred in a series of 138 patients who underwent the first 160 liver transplant operations in the Birmingham Liver Transplant Programme (incidence = 4.4% of patients, 3.7% of grafts). Forty needle biopsies were obtained from the 6 patients between 6 and 1303 days after transplantation. Thirteen specimens, taken between 8 and 1253 days posttransplant (median 98 days) showed an absence of bile ducts in more than 50% of portal tracts. Other histologic features of chronic rejection, inflammatory bile-duct lesions, perivenular cholestasis, and hepatocyte dropout were also seen in these biopsies, and severe cholestasis was present biochemically (median serum bilirubin level 240 mumol/L). The histologic and biochemical changes were thought to be compatible with a diagnosis of chronic/irreversible rejection, but the decision to carry out retransplantation was deferred on the basis of stable and, subsequently, improving biochemistry. Follow-up biopsies showed recovery of duct loss and other histologic abnormalities. All 6 patients are currently alive and well with good graft function. It is concluded that a transient, reversible bile-duct loss can occur after liver transplantation and that cases with this condition are indistinguishable from those who subsequently develop irreversible graft damage. In view of the risks associated with additional immunosuppression and/or retransplantation, caution is advocated in the interpretation of ductopenia in posttransplant liver biopsies. We suggest that the term "early chronic rejection" might be appropriate to describe cases in which a definite diagnosis of irreversible graft damage cannot be made.

Adolescent↗
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↗