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Biomedical subjects

M S Losowsky

Publications and source records attributed to M S Losowsky.

At least 163 records · Page 9Linked to original sources
PubMed1982

Cell-mediated immunity to dietary antigens in coeliac disease.

By means of the leukocyte migration inhibition test a significant depression of migration index (indicating increased immunity) was found in 10 untreated coeliac patients compared with 24 control subjects with the dietary antigens bovine serum albumin (BSA) and egg white but not with milk. The degree of immunity was similar to that obtained with gluten fraction III as antigen. Treatment with a gluten-free diet led to a decrease in immunity to egg white and BSA, but immunity to gluten fraction III was increased in the early months of treatment.

Adolescent↗
PubMed1982

Suppressor cell activity, splenic function and HLA B8 status in man.

The enhanced proliferative response of peripheral blood lymphocytes (P.B.L.) to Concanavalin A (Con A) occurring after a 24 hr period of incubation was used as the basis of a suppressor cell assay and the results expressed as a suppressor index (S.I.) which if low implies impaired suppressor cell activity. S.I. was measured on P.B.L. from 26 patients with coeliac disease and defined splenic function, 8 patients with splenic atrophy not associated with coeliac disease, 30 patients after surgical splenectomy, and 52 controls. S.I. was lower than control in the splenectomy group (P less than 0.01) and in the coeliac group, but coeliacs with splenic atrophy were no different from coeliacs with apparently normal splenic function, nor were the non-coeliac splenic atrophy group different from control. Coeliacs with the HLA B8 gene had lower S.I. than those without, as did controls. Suspensions of cells from spleens removed at laparotomy demonstrated suppressor activity but this was no more marked than in P.B.L. It is concluded that the intact spleen is required for normal activation of suppressor cells in man, but this function is retained in splenic atrophy, and that the HLA B8 gene is associated with low suppressor cell activity in coeliac disease and in health.

Celiac Disease↗
PubMed1982

Osteomalacia, vitamin D deficiency and cholestasis in chronic liver disease.

Twenty-nine patients with chronic liver disease, nine of whom had symptoms suggesting bone disease, were studied by bone histology. Nine had osteomalacia; six associated with cholestatic liver disease and three with primarily hepatocellular disease. Two of these had clinical and biochemical features of cholestasis for at least a year and the other had alcoholic cirrhosis associated with severe malnutrition. Excluding the latter patient, histological osteomalacia was significantly associated with presence and duration of cholestasis. Plasma 25-hydroxyvitamin D was low and fasting urine hydroxyproline/creatinine ratio was high in all patients with osteomalacia but were abnormal also in some patients who did not have histological osteomalacia. Serum calcium, phosphate, alkaline phosphatase, vitamin D-binding protein and radiology were unhelpful in many patients with osteomalacia. Vitamin D-deficiency correlated significantly with deficiency of other fat-soluble vitamins and those patients with rachitic levels of plasma 25-hydroxyvitamin D showed no seasonal variation, suggesting a combination of malabsorption of vitamin D and reduced sunlight exposure. We suggest that patients with chronic liver disease with cholestasis for at least a year are at risk from osteomalacia and that those likely to have this complication may be identified by plasma 25-hydroxyvitamin D and/or fasting urine hydroxyproline/creatinine ratio measurements. The diagnosis can only be made with certainty by bone biopsy.

25-Hydroxyvitamin D 2↗
PubMed1981

Blood viscosity after splenectomy.

Blood viscosity and its contributory factors--namely, plasma viscosity, fibrinogen concentration, packed cell volume, red-cell deformability, and platelet count--were measured in 20 asymptomatic patients after splenectomy and compared with those in controls. Whole-blood viscosity was significantly increased after splenectomy and was associated with increased platelet count and, more importantly, decreased red-cell deformability. Blood viscosity was measured in six patients before and after splenectomy and in each an increase in viscosity occurred that did not occur in patients who underwent laparotomy without splenectomy. these findings suggest that the inclusions and protein complexes within the red cell that are normally removed by the spleen decrease red-cell deformability and lead to an increase in blood viscosity. This may account for the observed increase in deaths from ischaemic heart disease many years after splenectomy.

Adolescent↗
PubMed1981

Preliminary evaluation of a single-day tubeless test of pancreatic function.

The test for pancreatic exocrine function using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BTP test) does not require duodenal intubation, but misleadingly abnormal results often occur in patients with liver or bowel disease because the p-aminobenzoic acid (PABA) released by chymotrypsin hydrolysis of the peptide either is not conjugated or is malabsorbed. This study evaluated a modified BTP test, using a tracer dose of 14C-PABA to eliminate misleading results, to assess exocrine function from a single six-hour collection of urine. The test clearly distinguished all patients with pancreatic steatorrhoea from normal subjects and identified patients with less severe pancreatitis as often as did the Lundh test. Furthermore, in patients with bowel or liver disease the misleadingly abnormal results of the unmodified BTP test were eliminated by the modified test in all but one case. These findings suggest that the modified BTP test provides a practical alternative to conventional tests of pancreatic function that entail duodenal intubation.

4-Aminobenzoic Acid↗
PubMed1981

Simple method of assessing splenic function in coeliac disease.

1. Erythrocytes with membrane abnormalities seen on interference contrast microscopy ('pitted erythrocytes') were counted in venous blood samples from patients with treated coeliac disease and dermatitis herpetiformis, and from control subjects and patients who had had an elective splenectomy. 2. The percentage of 'pitted erythrocytes' was compared with the 99mTc-labelled heat-damaged erythrocyte clearance, and with the splenic size computed from scintiscans. 3. There was a significant correlation between percentage 'pitted erythrocytes' and the above methods of measuring splenic function and size. Increase in the percentage of 'pitted erythrocytes' above the control range indicated splenic hypofunction. 4. The number of coeliac patients with percentage 'pitted erythrocytes' above the control range increased with increasing age at which they started a gluten-free diet. 5. Counting of 'pitted erythrocytes' is a simple and sensitive method of assessing splenic hypofunction in treated coeliac disease. It avoids radiation exposure, and is applicable to all ages and repeatable without risk. 6. The incidence of splenic hypofunction in coeliac patients may be related to the duration of untreated disease.

Adolescent↗
PubMed1981

Evidence for secondary hyperparathyroidism in the osteomalacia associated with chronic liver disease.

Previous reports have suggested that secondary hyperparathyroidism is extremely uncommon in hepatic osteomalacia. This, together with other findings, has led to suggestions that in chronic liver disease there may be selective resistance of bone to vitamin D or a specific bone mineralization defect unrelated to Vitamin D. To examine these possibilities, twenty-five patients with chronic liver disease have been studied by bone biopsy, serum calcium and inorganic phosphate, plasma 25-hydroxyvitamin D, plasma immunoreactive parathormone (iPTH), fasting urine cAMP, fasting renal tubular maximal reabsorptive capacity for phosphate (TmP/GFR) and fine grain hand x-rays. Nine of the patients had osteomalacia on bone biopsy, eight of these had subnormal levels of plasma 25-hydroxyvitamin D and the other had a borderline result. Based on the consensus of all the tests, five of these had evidence of secondary hyperparathyroidism. Plasma iPTH was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.01) or controls (P less than 0.01). Urine cAMP was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.001) or controls (P less than 0.01). TmP/GFR was significantly lower in patients with osteomalacia than in controls (P less than 0.05) but not significantly different from patients without osteomalacia. The findings of this study indicate that hyperparathyroidism occurs in a substantial proportion of patients with the osteomalacia of chronic liver disease. Moreover, osteomalacia in chronic liver disease is clearly related to reduced levels of plasma 25-hydroxyvitamin D. We conclude that hepatic osteomalacia is a vitamin D deficiency state and there is no need to suggest an unusual aetiology.

25-Hydroxyvitamin D 2↗
PubMed1981

Vitamin status in treated patients with cystic fibrosis.

The water-soluble (B1, B2, B6, C, folic acid) and fat-soluble vitamin (A, carotene, E, and D) status of 36 patients with cystic fibrosis was assessed and compared with a control group of 21 age-matched normal children. Twenty-seven of the patients were receiving vitamin supplements (except folic acid and vitamin E) at the time of investigation. Vitamin B1, B2, and B6 status was adequate in all patients, and there was little evidence of folic acid deficiency. Vitamin C stores might not have been adequate in some of these patients, despite daily supplements with 50 mg of the vitamin. Steatorrhoea, often severe, was present in most of them. Serum carotene and vitamin E concentrations were low in over 90% of patients and were related to the severity of steatorrhoea. Vitamin A was low in over 40% of the patients despite daily vitamin supplements of 4000 IU and correlated with the serum retinol-binding protein level. Serum 25-OH cholecalciferol was low in some patients whether or not they were receiving a daily supplement of 400 IU vitamin D. In a short-term supplementation trial with water-miscible preparations of vitamin A and E in 14 patients, the serum levels of both vitamins responded well to 2 weeks of treatment with 50 mg vitamin E and 4000 IU vitamin A. Except for serum vitamin A, which was lowest in patients with the poorest clinical grading, the other vitamins were not influenced by the clinical grade of the patients.

Adolescent↗
PubMed1981

Hyposplenism, adult coeliac disease, and autoimmunity.

Functional hyposplenism is associated with a variety of disorders including coeliac disease. The aims of this study were to estimate the need for a small intestinal biopsy in the investigation of hyposplenism, and to assess the relationship of autoimmunity to hyposplenism and coeliac disease. During one year, the features of hyposplenism were found in blood films of 27 patients who had not had a splenectomy. Ten patients were already known to have coeliac disease. Intestinal biopsy was performed in another 13 patients; coeliac disease was diagnosed in six. Of the 23 patients biopsied, coeliac disease was present in 16 (70%). Autoantibodies were detected in significantly more patients with hyposplenism than in healthy controls (P less than 0.05), and in significantly more coeliacs with hyposplenism than coeliacs with normal blood films (P less than 0.01). The increased incidence of autoantibodies in coeliacs with hyposplenism compared with other coeliacs was not associated with a difference in the incidence of HLA-B8. Small bowel biopsy should be carried out in the investigation of unexplained hyposplenism. There may be a link between hyposplenism and the autoimmune manifestations of coeliac disease.

Adult↗
PubMed1981

In vitro diagnosis of coeliac disease: an assessment.

Jejunal biopsies from controls and coeliac patients were maintained in organ culture for up to 48 hours. The in vitro effect of gluten fraction III during the period of culture was assessed by measurement of the activity of the brush border enzymes alkaline phosphatase and alpha-glucosidase. Mucosa from controls and treated and untreated coeliacs behaved similarly and no reproducible in vitro effect of gluten was demonstrated. These results cast doubt on the in vitro diagnosis of coeliac disease by monitoring brush border enzyme activity.

Alkaline Phosphatase↗
PubMed1981

HLA-B8 and cell-mediated immunity to gluten.

The leucocyte migration inhibition (LMI) test was used as an indicator of cell mediated immunity to gluten fraction III in 30 healthy controls and 58 patients with adult coeliac disease and the results related to HLA status and duration of treatment with a gluten-free diet. HLA-B8 controls showed significantly lower leucocyte migration indices, indicating greater immune response, than non-HLA B8 controls. Untreated coeliacs showed no difference from HLA-B8 controls. There was no difference between results from HLA-B8 and non-HLA-B8 coeliacs. Leucocyte migration was even lower in coeliacs early in treatment but rose after treatment for over one year. These results may reflect an immune response gene for gluten in linkage disequilibrium with HLA-B8. The increased immune response to gluten as measured in this test cannot be the sole factor in aetiology of coeliac disease. Furthermore, it is necessary to re-evaluate earlier results of cell-mediated immunity in coeliac disease with reference to HLA status of the controls.

Celiac Disease↗
PubMed1981

Gastritis and cirrhosis--no association.

Endoscopically sited gastric mucosal biopsies were taken from 98 patients with hepatic cirrhosis, and from 48 control patients. Nineteen patients with cirrhosis were found to have gastric ulcers, including eight with multiple erosions. In four of these eight, erosions were shown to arise in histologically normal mucosa. Among the remaining 79 patients with cirrhosis, the prevalence of chronic gastritis was not increased compared with controls of the same age-group. There was no increase in chronic gastritis in patients with alcoholic cirrhosis compared with either controls or patients with chronic active hepatitis and cirrhosis. The increased proneness of patients with cirrhosis to acute and chronic gastric mucosal lesions cannot be explained on the basis of an underlying chronic gastritis.

Adult↗
PubMed1981

Gluten sensitivity of small intestinal mucosa in vitro: quantitative assessment of histologic change.

In view of the importance to the patient of demonstrating mucosal sensitivity to gluten we have quantitated morphologic change during organ culture of small bowel mucosa by measuring enterocyte height. In 27 normal controls the mean preculture enterocyte height was 28.3 micrometer +/- 1.8 (+/- 1 SD), decreasing to 25.6 micrometer +/- 1.9 and 26.1 micrometer +/- 2.0 after 24 h culture in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but there was no difference between culture with or without gluten. In 9 abnormal controls, the mean preculture enterocyte height was 27.0 micrometer +/- 2.7, decreasing significantly (p < 0.05) to 24.5 micrometer +/- 1.1 after 24 h culture without gluten, and to 25.4 micrometer +/- 2.3 with gluten (NS). In 17 untreated celiac patients, the mean preculture enterocyte height was 19.6 micrometer +/- 1.9 increasing significantly to 23.8 micrometer +/- 2.0 (p < 0.001) after 24 h culture without gluten but decreasing to 18.7 micrometer +/- 3.1 after 24 h culture with gluten (NS). There was a significant difference between culture with or without gluten (p < 0.001). In 21 treated celiac patients, the mean preculture enterocyte height was 28.1 micrometer +/- 1.9 decreasing to 25.4 micrometer +/- 2.0 and 24.2 +/- 1.9 in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but more importantly there was a significant decrease (p < 0.001) after culture with gluten compared with culture without gluten. These data indicate that it is possible to quantify morphologic change during organ culture and to demonstrate gluten-sensitivity not only in untreated, but also in treated celiac mucosa. These studies have important implications as regards the diagnosis and further investigation of the etiology of celiac disease.

Caseins↗
PubMed1980

Prospective study of thrombophlebitis and "pseudothrombophlebitis".

43 non-surgical patients presenting with calf pain and a clinical diagnosis of deep venous thrombosis (DVT) were studied by arthrography, venography, and ultrasound. Only 14 had venographic evidence of DVT; 5 of these had popliteal cysts, which in 4 cases probably contributed to symptoms. 11 patients had popliteal cysts and normal venograms, and 9 of these cysts were thought likely to be the cause of the symptoms. In 18 patients all investigations were normal. Physical signs were not helpful in distinguishing between the three groups of patients. Ultrasonography detected only 2 of the 16 popliteal cysts. Popliteal cysts should be considered in the differential diagnosis and as a possible coexisting condition in patients suspected clinically of having DVT. Also, the finding of a Baker's cyst should not deter one from doing a venogram.

Adolescent↗