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Biomedical subjects

M S Losowsky

Publications and source records attributed to M S Losowsky.

At least 55 records · Page 3Linked to original sources
PubMed1989

Chronic liver disease. A case control study of the effect of previous blood transfusion.

A means of assessing hepatitis NANB virus infection, via blood transfusion, as a cause of chronic liver disease was investigated in a hospital in each of two cities in England. Patients with chronic liver disease were matched for age and sex with other patients in the same hospital and histories taken included details of previous operations and blood transfusions; if these were within ten years of the study enquiries were made of hospital records officers. All positive histories were found correct, but about one third of previous transfusions had been omitted by both case and control patients. Sixty-seven male and 35 female patients with chronic liver disease and their controls were included in analyses. The only clear difference which emerged related to residence for more than a year in the Middle or Far East by male case- (40%) or control- (21%) patients (P less than 0.05). The exclusion of patients with this history left only 34 pairs in which five (15%) of the case patients and one (3%) of the control patients had a transfusion history: this difference was not statistically significant. Although the study results have shown no clear evidence of blood transfusion as a major cause of chronic liver disease in Britain, the study method, with sufficient numbers to allow analyses of newly diagnosed patients with confirmed transfusion histories, could be used to provide an ongoing assessment of the risk.

Adolescent↗
PubMed1989

Rebound surges of intracranial pressure as a consequence of forced ultrafiltration used to control intracranial pressure in patients with severe hepatorenal failure.

Cerebral edema remains the most common immediate cause of death in patients with fulminant hepatic failure. We have used ultrafiltration as a method of controlling intracranial pressure (ICP) when other measures have failed. Two cases in which an initial decrease in ICP was followed by a marked rebound increase resulting in death are reported.

Acetaminophen↗
PubMed1989

Ascorbic acid: a factor concentrated in human gastric juice.

1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A + D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology. 2. A significant reduction in gastric juice ascorbic acid (A + D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis. 3. Concentrations of ascorbic acid (A + D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach. 4. These data demonstrate that considerable quantities of ascorbic acid (A + D) are normally 'secreted' into the stomach. 5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form.

Adult↗
PubMed1989

The prognosis of elderly subjects with oesophageal varices.

Discharge survival following variceal bleeding was similar in 27 elderly subjects, aged 65-93 years, and 125 younger subjects, aged under 65 (63% versus 70%, p greater than 0.05). Of 39 elderly subjects with varices which were not bleeding on admission, 82% were discharged alive but subsequent mortality was higher and long-term survival was similar (median 1 year) on life-table analysis. The overall long-term survival in the 66 elderly subjects was far worse than in the comparable group of 269 subjects under 65 (p less than 0.001). However, the excess deaths were from causes unrelated to hepatic failure or bleeding (e.g. stroke). Considering only deaths from hepatic failure or bleeding, long-term survival in the elderly and young was similar (p greater than 0.5). We conclude that elderly subjects with varices should be managed as actively as younger subjects since the majority are discharged alive and prolonged survival is common (25% at 3 years).

Actuarial Analysis↗
PubMed1989

Glycoprotein synthesis and secretion by cultured small intestinal mucosa in coeliac disease.

Glycoprotein biosynthesis by jejunal mucosa was examined during culture in vitro in 26 patients with coeliac disease and 19 controls. The incorporation rates of tritiated glucosamine into tissue and secreted glycoproteins were determined using established techniques. The total glucosamine incorporation in untreated coeliac patients was significantly greater than that of histologically normal mucosa (p less than 0.001) and jejunal tissue from patients with treated coeliac disease (p less than 0.01). Enhanced secretion of in vitro labelled glycoproteins was observed in untreated coeliac patients. The total incorporation of tritiated glucosamine in intestinal tissues was correlated with goblet cell numbers. These results indicate that quantitative changes in glycoprotein synthesis and secretion occur in coeliac disease.

Adolescent↗
PubMed1989

Plasma leucine enkephalin is increased in liver disease.

Plasma methionine enkephalin is increased in liver disease and may contribute to some of the clinical manifestations of hepatic failure. To determine if another 'small' opioid peptide is increased in the plasma of patients with liver disease, leucine enkephalin was measured by radioimmunoassay. Its plasma concentration was raised approximately five-fold in patients with acute liver disease (median 1490 pmol/l, range 830-2420) and three-fold in patients with cirrhosis with ascites (960 pmol/l, 470-2900), compared with disease controls (325 pmol/l, 180-740) and healthy controls (305 pmol/l, 180-560). The increase in plasma leucine enkephalin was proportional to the degree of liver damage, as judged in the patients with acute liver disease by its correlation with the prothrombin time (r = 0.691, p less than 0.01) and alanine aminotransferase (r = 0.502, p less than 0.05), and in the patients with cirrhosis by its negative correlation with the plasma albumin (r = -0.743, p less than 0.001). It is unclear whether the raised plasma leucine enkephalin in liver disease is a consequence of diminished hepatic inactivation, increased secretion from sympathetic nerves and adrenal glands, or both.

Acute Disease↗
PubMed1989

Fatal variceal haemorrhage after paracetamol overdose.

A patient is described where oesophageal varices developed and bled 13 days after a paracetamol overdose. The bleeding was unresponsive to medical management and proved fatal. There was no evidence that the patient had pre-existing liver disease. At necropsy the liver showed severe acute parenchymal necrosis but chronic lesions were absent. The portal vein and hepatic veins were patent.

Acetaminophen↗
PubMed1989

Gastric mucosa in patients with portal hypertension: prevalence of capillary dilatation and Campylobacter pylori.

To determine whether the "congestive" gastropathy associated with portal hypertension showed distinctive histological features independent of inflammatory gastritis, endoscopic biopsy specimens of gastric mucosa from 23 patients with portal hypertension and 25 patients with non-ulcer dyspepsia were examined. Active chronic gastritis associated with Campylobacter pylori was found in three patients with portal hypertension compared with 13 patients with non-ulcer dyspepsia. The changes of reflux gastritis were seen in nine patients with portal hypertension compared with three patients with non-ulcer dyspepsia. Mucosal capillary dilatation, assessed on sections stained for factor VIII related antigen, a specific marker for endothelial cells, was significantly greater in biopsy specimens from patients with portal hypertension but this difference was not apparent on sections stained conventionally. The degree of capillary dilatation was unrelated to the presence of histological gastritis. These observations support the view that portal hypertension is associated with a distinctive gastropathy characterised by prominence and dilatation of mucosal capillaries.

Adolescent↗
PubMed1989

Pneumococcal Waterhouse-Friderichsen syndrome despite a normal spleen.

A previously fit 56 year old female presented with a rapidly progressive and fatal pneumococcal septicaemia with disseminated intravascular coagulation. Post-mortem studies confirmed a Waterhouse-Friderichsen syndrome and revealed an anatomically normal spleen; intracellular diplococci were seen within splenic macrophages providing evidence of normal splenic function. This appears to be only the second case of Waterhouse-Friderichsen syndrome due to pneumococcal septicaemia in a patient with a normal spleen.

Female↗
PubMed1989

Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy.

Seven consecutive patients with grade IV hepatic encephalopathy, due to fulminant hepatic failure complicated by oliguric renal failure were allocated at random to treatment with daily machine haemofiltration (MHF) or continuous arteriovenous haemofiltration (CAVHF). Intracranial pressure (ICP) was continuously monitored using a subdural catheter. Four patients received 17 treatments by MHF, and ICP increased from 8.4 +/- 1.5 mm Hg (mean + SEM) prior to treatment to 12.6 +/- 1.8 mm Hg on completion (p less than 0.05). Active intervention was required on twenty occasions to treat sustained increases in ICP (greater than 25 mm Hg maintained for 5 min or longer). A total of 12 haemofilters were used in the treatment of 3 patients by CAVHF. The ICP showed greater stability during CAVHF therapy, the mean pressure prior to treatment was 15.6 +/- 5.2 mm Hg and fell to 11.7 +/- 2.3 mm Hg at 4 h. Sustained increases in ICP occurred in only 1 patient as a preterminal event. These findings suggest that CAVHF is the preferred method of treatment in patients with fulminant hepatic failure complicated by oliguric renal failure who are at risk of developing cerebral oedema.

Acute Kidney Injury↗
PubMed1989

Variceal bleeding is associated with reduced risk of severe cholestasis in primary biliary cirrhosis.

To test the hypothesis that, in primary biliary cirrhosis, bleeding from oesophageal varices implies a reduced risk that a patient will subsequently develop severe cholestasis, the case records of 76 patients with this condition who had died were examined. Fifty-nine patients (78 per cent) had died solely or largely as a consequence of liver disease. Their median survival from the onset of symptoms was 72 months. Most died from either hepatic failure with marked jaundice, infected ascites or variceal bleeding. Fifteen patients had a plasma bilirubin less than 100 mumol/l at the time of death. Twenty-eight patients had had variceal bleeding. Compared with the remaining 31 who had also died from cirrhosis, the patients who had bled from varices survived longer, were much less likely to die of hepatic failure and to become severely jaundiced but were more likely to develop fatal infected ascites.

Adult↗
PubMed1989

Plasma gamma aminobutyric acid concentrations provide evidence of different mechanisms in the pathogenesis of hepatic encephalopathy in acute and chronic liver disease.

Plasma gamma aminobutyric acid (GABA) concentrations were measured using a radioreceptor assay in 24 patients with acute liver disease with and without clinical encephalopathy; 15 patients with chronic liver disease with and without clinical encephalopathy, and 16 control subjects with no evidence of liver disease or hepatic dysfunction. Plasma GABA concentrations were significantly elevated in the patients with acute liver disease and clinical encephalopathy as compared with the controls. There was a positive relationship between the clinical grade of encephalopathy, the changes in the EEG and the plasma GABA concentrations. Plasma GABA concentrations in patients with chronic liver disease did not relate to the clinical grade of encephalopathy or the changes in the EEG. It is concluded that elevated plasma GABA concentrations are in keeping with the pathogenesis of encephalopathy in acute liver disease, but not in chronic liver disease.

Acute Disease↗
PubMed1989

Changes in intracranial pressure during machine and continuous haemofiltration.

Nine consecutive patients with both fulminant hepatic failure and acute oliguric renal failure were treated either by daily machine haemofiltration (MHF), or by continuous arterio-venous haemofiltration (CAVHF). Six patients received a total of twenty treatments by MHF and four CAVHF, mean duration of treatment 56 hours, range 24-160. Intracranial pressure (ICP) was measured using a subdural catheter. During treatment with MHF, the mean ICP increased from 8.9 +/- 1.4 mmHg at the start of filtration to 14.8 +/- 2.1 mmHg at the end of treatment (p less than 0.05), whereas there was no corresponding increase during the same period of time with CAVHF treatment, the mean ICP fell, but not significantly from 19.4 +/- 4.8 mmHg to 11.2 +/- 2.3 mmHg. The mean ICP increased to greater than 25 mmHg on eleven occasions during treatment with MHF, requiring treatment with bolus mannitol or propofol, during the same period of treatment with CAVHF no such surges in ICP were recorded. This suggests that continuous haemofiltration is to be preferred to intermittent machine haemofiltration in the management of patients with acute hepatorenal failure.

Adult↗
PubMed1989

Serum interleukin-2-receptor in coeliac disease: response to treatment and gluten challenge.

Concentrations of the soluble interleukin-2 receptor (sIL-2R) in the serum of 33 patients with coeliac disease were measured by ELISA. The levels of sIL-2R were significantly raised in 15 patients with untreated coeliac disease compared with treated patients and age- and sex-matched symptomatic and non-symptomatic control groups. Longitudinal studies in individual coeliac patients showed that serum sIL-2R fell following commencement of a gluten-free diet. Gluten challenge of 16 treated coeliac patients for 1 week resulted in a significant increase in serum sIL-2R, which returned to prechallenge levels within 4 weeks of recommencement of a gluten-free diet. We suggest that serum sIL-2R levels in patients with coeliac disease reflect specific immunological activation in response to gluten ingestion. Measurement of serum sIL-2R may therefore be useful in the assessment of response to treatment in patients with coeliac disease.

Adolescent↗
PubMed1988

Opioid peptides and primary biliary cirrhosis.

Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal reaction on starting the drug. In the nine patients with primary biliary cirrhosis pruritus was greatly alleviated, fatigue seemed to improve, and plasma bilirubin concentration, which had been rising, showed a modest fall in all except one patient. These results indicate that blocking opioid receptors has an effect on some of the metabolic abnormalities of liver disease.

Adult↗