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Biomedical subjects

M S Losowsky

Publications and source records attributed to M S Losowsky.

At least 91 records · Page 5Linked to original sources

The immunology of coeliac disease.

Coeliac disease is defined as that disorder in which there is an abnormality of the small intestinal mucosa manifested by contact with the gluten of wheat and certain other cereal grains. In the immunological theory of the pathogenesis of coeliac disease, gluten, or a component, is viewed as the antigen responsible for the immune response. The search for the gluten component responsible for 'toxicity' and, by implication, antigenicity, is described. The antigen may be presented differently to the immune system by an abnormal cell membrane, either of the enterocyte, lymphocyte or macrophage. Alternatively, increased amounts of antigen may be absorbed due to increased membrane binding or permeability, either of which could be genetically determined. As a further possibility, coeliac disease may occur because the patients are immunologically hyperresponsive and this too appears to be genetically determined. The perturbations which occur in the mucosal immune system and the systemic immune system are described. It is conceivable that the major complications described (intestinal ulceration, malignancy and splenic atrophy) result from immunological disturbances. The incidence of childhood coeliac disease is declining, which may be due to altered exposure to, or increased protection from, the antigen in infancy, or to changes in environmental factors. The immunological mystery of coeliac disease continues to excite interest and fascination, and has certainly been a stimulus to our deeper understanding of gastrointestinal immunology.

Celiac Disease↗

The use of the visual evoked potential (VEP) in delineating a state of subclinical encephalopathy. A comparison with the number connection test (NCT).

Visual evoked potential determinations and the number connection test were performed for 49 patients with stable chronic liver disease and portal hypertension but without clinical evidence of hepatic encephalopathy. The latencies of the evoked potential components N2, P2 and N3 were significantly prolonged compared to the controls. Seven patients had a prolonged N2, 10 had a prolonged P2, and 14 patients had a prolonged N3 latency. Only five of these patients had increased theta activity of the electroencephalogram. When age norms were applied, the number connection test was significantly prolonged only in the 16-36-years age group. It is concluded that the visual evoked potential identifies a group of patients with neurophysiological abnormalities and may be useful in identifying those at risk of developing overt encephalopathy.

Adult↗

Evidence for gamma-aminobutyric acid as the inhibitor of gamma-aminobutyric acid binding in the plasma of humans with liver disease and hepatic encephalopathy.

1. Gas-liquid chromatography and a radioreceptor assay were used to measure plasma gamma-aminobutyric acid (GABA) in patients with liver disease and hepatic encephalopathy. 2. There was a significant correlation between the results obtained by the two methods, and compared with controls plasma GABA was elevated. 3. These findings suggest that the increased GABA binding inhibitory activity of plasma of these patients is probably due to GABA itself.

Chromatography, Gas↗

Pituitary function tests in the elderly: are hypothalamic releasing factors the investigation of choice?

The use of the new hypothalamic releasing factors corticotrophin releasing factor (CRF) and growth hormone releasing factor (GHRH) has been proposed as a potential replacement for the insulin stress test in the investigation of pituitary function. The response to the injection of 100 micrograms of each compound was studied in nine elderly in-patient subjects. In response to GHRH, only four subjects demonstrated a rise in growth hormone; in response to CRF, only one subject showed a rise in cortisol. In the patients studied the combined GHRH and CRF test did not cause any cortisol or GH response in the majority.

Aged↗

Chronic hepatitis B carriers found at blood donation: do they need regular follow-up?

It is recommended by the Department of Health and Social Security that hepatitis B virus (HBV) carriers found at blood donation should be followed up by specialist liver units. We attempted to do this in 74 such patients found by the Yorkshire Regional Blood Transfusion Service during a 4.5-year period. Only 32 of the patients eventually attended for further investigation and follow-up. However, 43 chronic HBV carriers found at blood donation have been followed for varying periods from 2 to 14 years, and the prognosis has been good. Although this raises the question as to whether such carriers need to be seen routinely in a specialist unit, we suggest that there are good reasons to continue to advocate this policy.

Biopsy↗

Sex hormone changes in chronic liver disease: a matched study of alcoholic versus non-alcoholic liver disease.

Men with liver disease are hypogonadal and feminized. European workers consider the liver disease itself to be the major factor but American workers blame alcohol consumption. We studied sexual dysfunction and sex hormones in three matched groups of men; controls (n = 22), those with alcoholic liver disease (n = 21), and those with non-alcoholic liver disease (n = 21). Men with alcoholic liver disease had more sexual dysfunction. Testosterone and androstenedione concentrations were lower and oestradiol and dehydroepiandrosterone sulphate levels were raised in the liver disease groups. The changes were greatest in the alcoholic liver disease group. In this, the first controlled study, liver disease per se appears to cause sexual dysfunction and sex hormone changes but these changes are amplified by ethanol.

Adult↗

Jejunal plasma cells and in vitro immunoglobulin production in adult coeliac disease.

IgA, IgE, IgG and IgM plasma cells in small bowel mucosal biopsies from 15 controls, 16 untreated and 14 treated coeliac patients and five patients with selective serum IgA deficiency (four of whom also had coeliac disease) were quantified using an indirect immunoperoxidase technique. The IgA, IgG and IgM plasma cell counts were significantly increased in the untreated coeliac patients. The cell counts were intermediate in the treated coeliac group. These changes were in parallel to production in vitro of IgA and sIgA, IgG, and IgM by cultured mucosal biopsies from the same patients. The IgA deficient patients had very few mucosal IgA cells but elevated IgG and IgM plasma cell numbers; again these changes were reflected in the production in vitro of immunoglobulins. IgE plasma cell counts were very low in all patients and there were no differences between patient groups. The changes in cell counts and mucosal immunoglobulin production were not reflected in serum IgA, IgM and IgG concentrations but serum secretory IgA was significantly elevated in the untreated coeliac patients compared with controls, with the treated coeliac patients being intermediate. The raised mucosal plasma cell counts reflect the local mucosal production of immunoglobulin but not the immunoglobulin concentrations of serum, emphasising the importance of studying the immune function of the gut itself in coeliac disease rather than immunological abnormalities in serum.

Adolescent↗

The clinical effect of correction of vitamin E depletion in cystic fibrosis.

Thirty patients with cystic fibrosis, 24 of whom had longstanding low serum vitamin E, were treated with 50 mg alpha-tocopherol acetate per day for periods of 18-24 months. None of the patients received haematinics during the study period. Throughout the period of study the overall clinical state of the patients did not alter significantly. The serum vitamin E level increased in all patients, but to a variable degree which was not related to the severity of steatorrhoea. A range of nutritional parameters, including anthropometry, vitamin levels, essential elements, haemoglobin and albumin, as well as dietary intake and faecal fat excretion, were assessed at the beginning and end of the study. Haemoglobin was the only parameter to change significantly from 13.14 to 13.47 g/100 ml. Twenty one of the 30 patients showed some increase in haemoglobin values and this increase could not be related to clinical state, fat absorption or dietary intake but was related to the improved vitamin E status.

Adolescent↗

Organ culture of fetal rat small intestine for testing gluten toxicity: a reappraisal.

Jejunal segments from fetal rats of 18 days gestation were maintained in an organ culture system for up to 72 h. During this period, villi developed within the intestinal lumen and the epithelium changed from stratified to simple columnar. Peristaltic activity was observed during in-vitro culture. Alkaline phosphatase specific activity of the bowel segments fell after 48 hours culture, compared with pre-culture values (P less than 0.05), but that of alpha-glucosidase increased. The addition of Frazer's gluten fraction III to the culture medium caused slowing in the rate of morphological maturation of the jejunal explants, but there was no additional effect on enzyme specific activities compared with segments cultured in gluten-free medium. The place of organ culture of fetal rat intestine as an animal model for testing cereal toxicity in the study of coeliac disease remains unclear.

Animals↗

Hypogonadism in chronic liver disease: impaired release of luteinising hormone.

Alcohol abuse leads to impotence, infertility, and feminisation. Patients with chronic alcoholism may have impaired hypothalamic-pituitary function. The release of luteinising hormone was investigated in men with alcoholic cirrhosis with and without hypogonadism and controls. Blood was sampled every 15 minutes for six or eight hours and luteinising hormone concentrations measured by radioimmunoassay. Data were analysed by iterative computerised analysis and spectral analysis to assess pulsatile release and the length of the cycle, respectively. Pulsatile release of luteinising hormone was shown in all the control subjects; in the men with alcoholic liver disease it was normal in those with subclinical primary testicular failure but absent or grossly attenuated in those with overt combined central and primary gonadal failure. The impaired release of luteinising hormone in the men with overt gonadal failure might be due to a hypothalamic defect.

Adult↗

Does super efficient starch absorption promote diverticular disease?

The amount of starch escaping absorption in the small intestine was measured in eight patients with symptomatic diverticular disease and eight controls. Unabsorbed starch was calculated from breath hydrogen measurements after a potato meal compared with the hydrogen response to lactulose. The proportion of unabsorbed starch was low in all the patients (mean 3.3%) and was only about a quarter of that in the controls (12.4%; p less than 0.01). These findings confirm that unabsorbed starch provides an important quantity of carbohydrate reaching the colon and suggest that super efficient starch absorption, by reducing this provision, may promote the development of diverticular disease.

Aged↗