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Biomedical subjects

M S Losowsky

Publications and source records attributed to M S Losowsky.

At least 127 records · Page 7Linked to original sources
PubMed1985

Defective activation of neutrophils after splenectomy.

Neutrophil chemotaxis and phagocytosis in the presence of serum from 20 patients who had undergone splenectomy and from 15 healthy volunteers was studied. The mean distance migrated by normal neutrophils in the presence of serum from the patients after splenectomy was significantly less than that when normal serum was used (p less than 0.005). The percentage of neutrophils phagocytosing a yeast was also significantly reduced in the presence of serum from patients after splenectomy (p less than 0.02). In addition, when neutrophils from these patients were studied both chemotaxis and phagocytosis were enhanced in normal compared with autologous serum (p less than 0.05).

Adolescent↗
PubMed1985

Expression of the common acute lymphoblastic leukaemia antigen (CALLA gp100) in the brush border of normal jejunum and jejunum of patients with coeliac disease.

Expression of the gp100 common acute lymphoblastic leukaemia antigen (CALLA) was studied in the mucosa of the gut by means of indirect immunofluorescence on cryostat tissue sections with a panel of eight monoclonal antibodies to common acute lymphoblastic leukaemia antigen (anti-CALLA antibodies) and two antibodies to non-CALLA leukaemic antigens. Expression of CALLA was absent from normal stomach epithelium, adult and fetal colonic epithelium of normal histology, and colonic epithelium from patients with Crohn's disease or ulcerative colitis. By contrast, all eight anti-CALLA antibodies gave a characteristic reaction in normal adult and fetal small bowel mucosa, with specific localisation to the entire brush border of jejunal epithelium. Whereas seven of these antibodies reacted both with normal jejunal epithelium and with the damaged epithelium of patients with coeliac disease, antibody RFAL-2 reacted strongly only with histologically normal small bowel but more weakly in patients with coeliac disease to a degree related to the amount of histological abnormality. Expression of the moeity like CALLA identified with RFAL-2 was strongest in crypt epithelium and proportionally diminished along the villi according to the amount of histological damage in coeliac disease, being essentially absent in patients with "subtotal villous atrophy."

Adult↗
PubMed1985

Primary biliary cirrhosis and chronic active hepatitis: an examination of clinical, biochemical, and histopathological features in differential diagnosis.

Seventy four liver biopsies from 59 patients were reviewed by two observers and histologically graded in the absence of clinical information, firstly, to assess the level of agreement with previous diagnoses; secondly, to identify differences between primary biliary cirrhosis and chronic active hepatitis; and, thirdly, to assess the specificity of Shikata orcein staining and antimitochondrial antibody positivity and titre for primary biliary cirrhosis. Thirty six patients with adequate histology were initially selected as typical of primary biliary cirrhosis or chronic active hepatitis; agreement both between observers and with original diagnoses was reached in 26 (72%) (15 with primary biliary cirrhosis (group 1), 11 with chronic active hepatitis (group 2)). In 19 diagnostically difficult patients in whom clinical and original histological findings had been at variance, histological agreement between observers was reached in 17 (group 3) and original underdiagnosis of primary biliary cirrhosis was suggested. The main clinical and histological differences between groups 1 and 2 are discussed in this paper. Although a high grade of positivity for copper associated protein in the Shikata orcein stain was seen only in primary biliary cirrhosis, a high titre of antimitochondrial antibody positivity was not unique to this condition.

Alkaline Phosphatase↗
PubMed1985

The microenvironment of coeliac disease: T cell phenotypes and expression of the T2 'T blast' antigen by small bowel lymphocytes.

Peroral jejunal biopsies were studied by double-label immunofluorescence on cryostat tissue sections from control patients of normal histology and patients with coeliac disease. A panel of monoclonal antibodies was used to identify T cells and T cell subsets, together with antibody markers of cell stimulation (the T2 40 kdalton T blast specificity), proliferation (T9 and Ki67) and activation (HLA-DR and Ig receptors). In normal mucosa, expression of T2 was predominantly found in the T8+ intraepithelial cytotoxic/suppressor population. In coeliac disease there was little alteration of T4:T8 ratios per se, but a much higher percentage of T8-T4+ helper/inducer cells expressed the T2 antigen (approx. 30% compared to approx. 10%), manifest as an accretion of T2+T8- cells in the epithelium and subjacent stroma. Additionally, T cell lymphoid aggregates were observed in the lamina propria, consisting of greater than 90% T4+ cells, of which the majority (60-80%) were also T2+. The increase of stimulated helper cells correlated well with the pathology of coeliac disease, being most marked in untreated cases of maximal tissue damage, and least in well treated cases with restoration of normal morphology. By contrast, an increased tendency for the T8+ cells to co-express T1 in untreated coeliac disease was not observed in treated disease, even in cases where failure to adhere to a strict gluten free diet had resulted in little histological improvement. There was little evidence of T cell activation or proliferation. The observation that T helper cells undergo migration and stimulation suggests an imbalance in immunoregulation which causes a breakdown of normal immune tolerance to dietary gluten, and therefore may be a crucial mechanism of tissue damage in coeliac disease.

Adolescent↗
PubMed1985

Hyposplenism and T lymphocyte subpopulations in coeliac disease and after splenectomy.

An imbalance in immunoregulatory cells might explain the increase in autoimmune phenomena associated with hyposplenism. Using the monoclonal antibodies OKT3, OKT4 and OKT8 to identify T-lymphocyte subsets, we have studied 19 patients with treated coeliac disease, 9 of whom had hyposplenism, 10 splenectomized subjects, 10 gastrointestinal control patients and 10 normal subjects. There was no significant difference in the proportion of lymphocytes, OKT3+, OKT4+ or OKT8+ cells, nor in the OKT4+/OKT8+ ratio, between any of the patient groups and normal or control subjects. Splenectomized subjects had higher total lymphocyte counts than normals (p less than 0.01). Hyposplenic coeliac patients had higher total lymphocyte counts than other coeliacs (p less than 0.05). Hyposplenic coeliac patients and splenectomized subjects tended to have an increase in the absolute number of OKT8+ cells, which in the latter group was statistically significant (p less than 0.05). We conclude that the increased frequency of autoimmune phenomena associated with hyposplenism due to coeliac disease or after splenectomy is not the result of an altered ratio of OKT4+/OKT8+ cells or a deficiency of OKT8+ cells.

Antibodies, Monoclonal↗
PubMed1985

Natural killer cells in coeliac disease.

Lymphoma is a well recognized but unexplained complication of coeliac disease. Natural killer (NK) cells are a distinct population of lymphocytes with the capacity to lyse some tumour cell-lines in vitro and there is evidence that they may play a role in immune surveillance and protection against the development of malignancy. Using a monoclonal antibody (Leu 11b) and a functional assay, we have measured NK cell numbers and activity in 32 patients with treated coeliac disease (9 of whom had evidence of hyposplenism), 10 splenectomized subjects, 14 biopsied, control patients and 26 normal subjects. The proportions (mean +/- SD) of Leu 11b + cells in normals (17 +/- 5%) and coeliac patients (19 +/- 7%) were similar. NK activity in all the coeliac patients (34 +/- 15%) was not significantly different from normal (31 +/- 15%) and control (26 +/- 15%) subjects. NK activity was correlated with % Leu 11b + cells (r = 0.64; p less than 0.01). The NK activity in patients with hyposplenism associated with coeliac disease (32 +/- 18%) and after splenectomy (29 +/- 15%) was similar to that in normals. We conclude that the increased risk of malignancy in patients with coeliac disease is not due to deficient NK cell numbers or activity.

Adolescent↗
PubMed1984

Oxalate-loading tests to screen for steatorrhoea: an appraisal.

We have evaluated two procedures as screening tests for steatorrhoea: firstly, a simplified, two-day, oxalate-loading test and secondly the rate of urinary oxalate excretion following a single oral dose of oxalate. Following two-day oxalate loading there was almost complete overlap of the values for 24-h urinary oxalate between 15 apparently healthy volunteers and 10 patients with steatorrhoea. The rate of oxalate excretion following a single dose of oxalate was increased in one patient with Crohn's disease and ileal resection who had normal faecal fat excretion, but three patients with steatorrhoea due to other causes had normal rates of excretion. We conclude that these oxalate-loading tests are not a useful alternative to faecal fat estimation in patients with suspected malabsorption.

Adult↗
PubMed1984

Prospective comparison of three non-invasive tests for pancreatic disease.

Ultrasonography, computed tomography (CT), and an oral pancreatic function test were evaluated prospectively in 107 consecutive patients suspected of having pancreatic disease, the final diagnosis being made independently of these tests. Seventeen patients proved to have either chronic pancreatitis or a pancreatic neoplasm. Five had an unfused ventral pancreas and 10 had "minimal change" pancreatograms. Seventy five patients did not have pancreatic disease. Among the 17 patients with pancreatic disease the sensitivities of ultrasound, CT, and the pancreatic function test were 70%, 71%, and 76% respectively; among those without disease values of specificity of the three tests were 75%, 87%, and 72%. All three tests failed to detect most of the patients with unfused ventral pancreases or minimal change pancreatograms. The predictive values of a positive result for the three tests were 43%, 67%, and 34%. The predictive value of a negative result was greater than 90% for all the tests. Results improved when CT was combined with either of the two other tests. These findings show that CT is the most accurate of the three tests in diagnosing pancreatic disease but that a combination of ultrasound and the oral pancreatic function test offers a more widely applicable and almost as accurate alternative.

4-Aminobenzoic Acid↗
PubMed1984

Asymptomatic neonatal colonisation by Clostridium difficile.

In a prospective survey of infants born in a single maternity unit, asymptomatic faecal colonisation by Clostridium difficile occurred in 31 (47%) of 66 babies who provided a faecal sample during week one of life and at age 14 and 28 days, and in 46 (30.7%) of the total of 150 babies for whom at least one faecal sample was obtained during the month of study. There was no evidence for acquisition of the organism from the mother during delivery and colonisation was unrelated to the means of delivery, infant sex, means of feeding, duration of hospital stay, or antibiotic treatment. New colonisation occurred throughout the month of the study and further evidence for environmental acquisition was obtained by the finding of a similar strain of C difficile in 7 babies from one ward together with positive environmental cultures. Colonisation was frequently transient and occasionally intermittent; most infants kept the same strain during their period of carriage. Twenty two (47.8%) babies colonised by C difficile had low titres of cytopathic faecal toxin but none had symptomatic diarrhoea or features of necrotizing enterocolitis. The in vitro toxigenic potential of 57 toxigenic isolates from 36 babies was low and 12 babies carried non-toxigenic strains. Transient colonisation by C difficile in early life is almost certainly more common than is generally recognized and the neonate provides an important reservoir of potential infection.

Bacterial Toxins↗
PubMed1984

Routine colonoscopy service.

We report our experience of 50 paediatric colonoscopies in a relatively unselected group of patients. Collaboration between an experienced colonoscopist and a paediatrician has provided a smooth, routine service and the examination has proved extremely useful for the diagnosis and management of children with colonic symptoms.

Child↗
PubMed1984

Degradation of cellulose within the gastrointestinal tract in man.

14C-labelled cellulose was administered orally to 10 subjects without gastrointestinal disease and its absorption measured by faecal 14C excretion and 14CO2 in expired air. A mean of 57.2% of oral cellulose was excreted in the faeces and up to 14% (mean 7.5 +/- 4.4 1SD) of faecal radioactivity was water soluble. Whole gut transit time did not correlate with the quantity of 14C-cellulose excreted in the faeces. A significant quantity of 14CO2 appeared in the expired air as early as 30 minutes after administration of the labelled cellulose. The cumulative excretion of 14CO2 varied from 7.6-32.2% of the administered radioactivity but did not correlate with faecal 14C excretion. The present data show that a significant quantity of oral cellulose is metabolised within the human gastrointestinal tract and appears in the expired air as 14CO2.

Adult↗
PubMed1984

Localisation of factor XIII in human tissues using an immunoperoxidase technique.

An immunoperoxidase technique has been used to localise clotting factor XIII subunits A and S in human tissues. The presence of factor XIII in placenta and megakaryocytes was confirmed. Factor XIII was also found in fibroblasts, a hitherto unreported finding. Factor XIII subunits were not detected in hepatocytes, although factor XIII was found in fibroblasts in portal tracts. These findings suggest that factor XIII is not synthesised in the liver as previously thought.

Animals↗
PubMed1984

An acquired inhibitor of factor XIII with a qualitative abnormality of fibrin cross-linking.

A patient with an acquired inhibitor to factor XIII is reported. The patient's plasma produced a profound inhibition of factor XIII activity in normal plasma measured by a dansylcadaverine casein assay and stimulated a very abnormal pattern of fibrin cross-linking, not normally seen with factor XIII. Partial characterisation of the inhibitor suggests that it is heat stable and not an immunoglobulin.

Acetates↗
PubMed1984

A survey of vitamin D deficiency in gastrointestinal and liver disorders.

A survey of vitamin D status in 152 patients with chronic gastrointestinal conditions and 104 patients with chronic liver diseases is presented. Mild deficiency was common and severe deficiency, as judged by plasma 25-OHD levels less than 8 nmol/l, was encountered in every disease category tested. In the gastrointestinal disease patients, deficiency was significantly more common in patients following gastroenterostomy than other gastric surgery, in patients with active Crohn's disease than in those with inactive disease and in patients with chronic pancreatitis or pancreatic carcinoma with cholestatic features than in those without cholestatic features. Deficiency was as common in patients with Crohn's disease who had not been treated surgically as in those who had. There was no significant correlation between plasma 25-OHD levels and any laboratory index of malabsorption or malnutrition except for serum albumin in the gastric surgery patients, haemoglobin and ESR in the Crohn's disease patients and albumin and vitamin E in the group of patients with gastrointestinal disorders taken as a whole. In the chronic liver disease patients, those with late primary biliary cirrhosis had lower plasma 25-OHD levels than those with histological Stage I and II disease who all had normal levels, and those with pruritus and jaundice were more commonly severely deficient. Whatever the underlying disease process, patients with other coincidental medical conditions were much more likely to be deficient as were patients with cholestasis. Evidence of secondary hyperparathyroidism and osteomalacia on bone histology indicated the clinical relevance of the vitamin D deficiency. This study showed no relationship between abnormal plasma vitamin D binding protein levels and vitamin deficiency.

Aged↗
PubMed1983

Factor XIII levels in five families of patients with inherited factor XIII deficiency: support for an autosomal recessive inheritance.

Using quantitative methods, f.XIII activity and levels of subunits a and b have been measured in 5 families of 6 patients with inherited XIII deficiency, including 2 children of a XIII deficient male. The parents, as a group, and the children, individually, have low XIII activity and low levels of subunit A when compared to controls. These findings provide further support for an autosomal inheritance of f.XIII deficiency. The measurements, however, did not allow confident selection of individual heterozygotes as has been previously suggested and an explanation of this finding is offered.

Adult↗
PubMed1983

The half life of factor XIII in the management of inherited deficiency.

Following the injection of a large dose of factor XIII concentrate the in vivo half life of factor XIII was estimated in a patient with inherited deficiency. Factor XIII activity and enzyme concentration were measured quantitatively, and a qualitative assessment of the crosslinking of fibrin was also made for upto 6 weeks after the injection. The half life was found to be about 9--10 days. This is longer than most previous reports suggest. An explantation for this finding is offered. The relevance of the long half life of factor XIII to the prophylactic treatment of patients with inherited deficiency is demonstrated.

Factor XIII↗