Fatal marrow aplasia associated with non-A, non-B hepatitis.
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Biomedical subjects
Publications and source records attributed to M S Losowsky.
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Serum vitamin A, retinol binding protein, prealbumin and transferrin have been studied in chronic renal failure patients receiving maintenance haemodialysis and after renal transplantation. Vitamin A and retinol binding protein were uniformly raised in haemodialysis patients and this was unrelated to the period on dialysis. There was a molar excess of retinol binding protein to both vitamin A and prealbumin as compared with normal individuals. Renal transplantation significantly reduces serum vitamin A and retinol binding protein concentrations but has no effect on prealbumin concentrations. The reduction in vitamin A and retinol binding protein is variable in individual patients and cannot be predicted either by the allograft function or time since transplantation. Several years after transplantation, with normal serum creatinine, both serum vitamin A and retinol binding protein levels may still be greatly increased. Despite the very high vitamin A and retinol binding protein concentrations, the close correlation between the two seen in normal individuals is well maintained. The continuing high vitamin A and retinol binding protein levels in patients with satisfactorily functioning transplants is unexplained.
Results of the direct leucocyte migration inhibition (LMI) test using gluten fraction III as antigen were unaffected by incorporation of puromycin into the culture medium at concentrations shown to prevent lymphokine mediated inhibition. Results of the LMI test performed with purified polymorphs were similar to and correlated with results of the standard LMI test using mixed leucocytes in both coeliacs and controls. The addition of purified T lymphocytes did not increase migration inhibition. Normal leucocytes incubated with serum from coeliac patients and washed showed marked migration inhibition when incubated with gluten fraction III. This sensitisation of normal leucocytes was prevented by preincubation with aggregated human IgG. These results suggest that leucocyte migration inhibition by gluten in coeliac disease is not due to lymphokine production by sensitised lymphocytes but is caused by cytophilic antibody.
Seven cases of ulceration of the small intestine are described and the relationship to coeliac disease is discussed. Evidence for coeliac disease is found in all cases but is less strong in some than in others, and coeliac disease was proved in only two cases. The ulcers were examined histologically in each case and in three cases were associated with malignant histiocytosis but the others showed only non-specific chronic inflammation. This suggests a spectrum of disorders with an inconsistent relationship to gluten sensitivity and small intestinal lymphoma.
A 48-year-old man presented with haematemesis and was found to have Menetrier's disease. Three and a half years later early gastric cancer was detected at routine follow-up endoscopy. This is the first report of the development of early gastric cancer during follow-up in a case of Menetrier's disease. It is probable that patients with Menetrier's disease are at increased risk of gastric cancer, and should have regular endoscopic follow-up with gastric biopsy.
We have measured plasma fibronectin in 28 patients with well-compensated chronic liver disease, 4 patients with non-cirrhotic portal hypertension and 6 patients who have undergone shunt surgery for the relief of portal hypertension and splenectomy. 17 patients with portal hypertension had significantly lower levels of fibronectin (207 +/- 54; mean +/- SD) compared with 15 patients without portal hypertension (315 +/- 75, p less than 0.001) and the 6 patients who had undergone shunting and splenectomy (330 +/- 66, p less than 0.001). We suggest that in patients with portal hypertension and splenomegaly, low levels of fibronectin might result from increased consumption by the enlarged spleen.
Jejunal biopsies from 13 patients with treated coeliac disease were maintained in organ culture for 24 h with and without the addition of gluten fraction III, in each case with and without autologous peripheral blood mononuclear cells. Biopsies cultured with gluten alone or with lymphocytes alone showed no significant reduction in mean enterocyte height compared with those cultured in control medium, but those cultured with both gluten and lymphocytes had significantly lower enterocyte height than control biopsies, than those cultured with gluten alone, and than those cultured with lymphocytes alone. These results demonstrate that the combination of gluten and lymphocytes is more toxic to treated coeliac mucosa in vitro than either one alone and support the suggestion that immune reactions to gluten may be important in the pathogenesis of the mucosal lesion of coeliac disease.
A new, rapid assay for pancreatic isoamylase (PIA) has been evaluated in normal subjects and patients with either proven chronic pancreatic disease or diseases in which chronic pancreatitis commonly enters the differential diagnosis. A wide normal range limited the diagnostic usefulness of the test. In non-pancreatic disease the serum levels of PIA were normal in 107 of 109 patients with non-pancreatic disease, but only 3 of 16 patients with chronic pancreatitis and proven exocrine insufficiency had a low PIA level, and variable levels occurred in pancreatic carcinoma. These results suggest that measurement of serum PIA is of limited value as a screening test for chronic pancreatic disease.
Serum from 45 splenectomised patients was screened for 8 auto antibodies and compared with controls, either age and sex matched (35) or the same patients measured before splenectomy (10). Sixteen splenectomised patients had demonstrable auto-antibodies compared with 7 controls (p less than 0.05). Three patients who did not have auto-antibodies before splenectomy developed them after an interval of a few months. It is suggested that splenectomy-leads to loss of suppressor cell activity and this permits the development of auto-antibodies.
The vitamin status (vitamins A, E, C, Carotene, B1, B2 and B6) of 18 patients receiving maintenance haemodialysis was assessed. All patients were receiving vitamin B1, B2 and B6 supplements and the effect of stopping these supplements on subsequent vitamin status was further studied. Apart from vitamin A, which was significantly increased in all patients, the mean level of all other vitamins was similar to the control group. Despite these normal group means, individual patients could be identified with low or marginally low vitamin C and B2 levels. When the vitamin B complex supplements were stopped, vitamin B2 and B6 remained normal over the subsequent six months maintenance haemodialysis but there was deterioration in vitamin B2 status. Leucocyte vitamin C levels responded well to oral supplements of 400 mg vitamin C per day. This study suggests that vitamin C and B2 supplements are necessary in patients receiving maintenance haemodialysis, other vitamin supplements being unnecessary.
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Jejunal biopsies from controls and coeliac patients were maintained in organ culture in the presence of gluten fraction III. The culture media were assayed for evidence of lymphokine activity in a migration inhibition test using normal peripheral blood leucocytes. Significant inhibition of migration was produced by media from untreated coeliac patients compared with controls (P less than 0.005) or treated coeliac patients (P less than 0.001), indicating the production of a leucocyte migration inhibition factor (LIF) by untreated coeliac mucosa in response to gluten fraction III. The degree of inhibition correlated with the preculture interepithelial lymphocyte count in the coeliac biopsies (P less than 0.02). In six coeliac patients studied when on a normal diet and on a gluten-free diet, LIF was produced while on a normal diet, but not while on a gluten-free diet. These results suggest that a local cell-mediated immune reaction to gluten is present in the mucosa of patients with untreated coeliac disease but that this is reversed by treatment with a gluten-free diet.
Blood films from 41 cases of coeliac disease complicated by malignancy were examined and evidence of hyposplenism found in 12 cases (29%). This is similar to the proportion of adult coeliacs without malignancy who have hypoplenism and it is concluded that impaired splenic function is not associated with the development of malignancy in coeliac disease.
We have measured serum immunoreactive trypsin (IRT) and serum pancreatic isoamylase (PIA) activities using commercially available kits in 37 cystic fibrosis (CF) patients and 46 hospital controls of similar age range. Immunoreactive trypsin was more often abnormal than PIA (26/37 v 18/37 abnormal respectively); IRT will be particularly useful as an additional diagnostic test in older children, in whom interpretation of the sweat test may be difficult, as 14/15 CF patients aged over 10 years had abnormal IRT results. Less than half of our patients who were aged between one and nine years had abnormal IRT activity, limiting the value of the test, though a low activity would still support the diagnosis of CF. Comparison with faecal fat estimations in 31 patients suggests that neither IRT nor PIA can be used as a non-invasive test of pancreatic function in order to identify those few CF patients who do not require pancreatic enzyme supplements.
A case of acquired von Willebrand's disease is reported in which the patient developed a swelling on the dorsum of the tongue. Histology of this lesion closely resembled that described in angiodysplasia of the colon.
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