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Biomedical subjects

M Sarner

Publications and source records attributed to M Sarner.

At least 19 recordsLinked to original sources

The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element.

Lactase activity is present at high levels in the small intestine of some human adults and not others. This is due to a genetically determined polymorphism which affects the developmental regulation of the expression of the lactase gene. This polymorphism is of considerable interest in relation to cultural differences in nutrition but despite exhaustive studies, the molecular basis has not yet been found. It has not even been shown whether the sequence differences reside within or adjacent to the lactase gene itself or in a trans-acting factor. We have therefore exploited known DNA 'marker' polymorphisms within the exons of the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in order to determine whether the regulation is in cis or trans. Our results show that in certain lactase persistent individuals one allele of the lactase gene is expressed at much lower levels than the other and these individuals tend to have intermediate lactase activities. It is proposed that these people are heterozygous for the lactase persistence and non-persistence alleles and that this means that the nucleotide substitutions responsible for the lactase persistence/non-persistence polymorphism are cis-acting. This narrows down considerably the area of the genome that needs to be searched for the relevant sequence differences.

Adult

Studies on the expression of intestinal lactase in different individuals.

Sixty one duodenal biopsy specimens were examined for the expression of lactase at the level of enzyme activity, protein, and messenger RNA. Of the 51 samples with normal villous architecture, 39 were lactase persistent, 11 were nonpersistent (adult type hypolactasia), and one was of indeterminate status. All the lactase persistent individuals showed high mRNA and a high level of the lactase protein as detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis. All the 11 non-persistent individuals tested showed a low level of lactase protein. Nine of the 10 samples tested showed low mRNA and one high mRNA. These results suggest that the lactase persistence polymorphism is controlled at the level of the expression of the lactase gene, though there may be some heterogeneity of the lactase non-persistence phenotype.

Adult

Classification of pancreatitis.

An international group of doctors interested in pancreatic disease met in Cambridge in March 1983, under the auspices of the Pancreatic Society of Great Britain and Ireland, to discuss the classification of pancreatitis in the light of developments that have taken place in the 20 years since the crucial conference in Marseille.

Acute Disease

Analgesic ingestion and other factors preceding relapse in ulcerative colitis.

To investigate factors which predispose to relapse in patients with ulcerative colitis, we conducted a survey to compare the events occurring in the four weeks preceding the clinic attendance of 62 outpatients in remission with those taking place in the same period before the onset of relapse in 21 patients attending with active disease. The only event which occurred significantly more often in patients who subsequently relapsed was ingestion of paracetamol and other inhibitors of prostaglandin synthesis (76% (16/21) relapse vs 39% (24/62) remission, p less than 0 . 01). Recent upper respiratory tract infection (38% vs 26%) was not significantly more common in patients in relapse than in remission, and emotional stress, atopic events, antibiotic treatment, dietary indiscretions, foreign travel, and gastroenteritis were relatively rare in both groups. The surprisingly high prevalence of analgesic ingestion before relapse itself requires confirmation but does lend indirect support to the theory that colonic mucosal prostaglandin deficiency induces relapse in some patients with ulcerative colitis.

Acetaminophen

Indium-111 tagged leucocytes in the diagnosis of inflammatory bowel disease.

The distribution of autologous leucocytes labelled with the gamma-ray emitting radioisotope indium-111 was studied in 25 patients with inflammatory bowel disease, 15 with Crohn's disease, and 10 with ulcerative colitis. In all instances the bowel lesion was identified. Radioactivity rapidly accumulated in the lesions over the first 2 h and then passed into the lumen of the bowel within the next 48 h, being redistributed from the liver and spleen. Normally, about 1% of the radioactivity passes into the stools in the 48 h after injection whereas approximately 20% of the administered radioactivity was found in the stools of the patients with inflammatory bowel disease. This noninvasive technique can show the extent of disease in patients too ill for conventional procedures. It can display abscesses and other lesions, and can be performed in outpatients.

Blood Platelets

The diagnosis of Ménétrier's disease.

Two cases of Ménétrier's disease are reported to illustrate the clinical presentation and diagnosis of this unusual condition. The literature has been reviewed of all the reported cases to establish the relative importance of the individual symptomatology, the value of the diagnostic methods, and to highlight the diagnostic pitfalls. Recognition of the barium meal appearances and snare biopsy at gastroscopy may avoid the necessity of diagnostic laparotomy.

Adolescent

Controlled trial of cimetidine in upper gastrointestinal haemorrhage.

One hundred and one patients were studied in a double-blind controlled trial to assess the role of oral cimetidine in preventing the continuation or recurrence of acute upper gastrointestinal haemorrhage from various sources, chiefly peptic ulcer. The dose of cimetidine was 800 mg on entering the study followed by 400 mg six hourly. The source of bleeding was identified endoscopically in 96% of patients, peptic ulcer comprising 70%. Bleeding continued or recurred in 11 of 51 (21.5%) of patients on cimetidine and in 12 of 50 (24%) of patients on placebo. Analysis of the effect of cimetidine according to age or severity of bleeding showed no significant advantage for the drug.

Adult

Oxalate loading test: a screening test for steatorrhoea.

To investigate the possibility of measuring urinary oxalate output instead of faecal fat excretion as an outpatient screening test for steatorrhoea, we determined 24 hour urinary oxalate and five day faecal fat excretion before and during an oral load of sodium oxalate 600 mg daily (oxalate 4.44 mmol), in 32 patients with suspected malabsorption on a diet containing oxalate 30 mg (0.33 mmol), fat 50 g (180 mmol), and calcium 1 g (25 mmol). Nineteen patients proved to have steatorrhoea (mean faecal fat 62 mmol/24 h, range 19--186 mmol) of varying aetiologies. On the diet alone, urinary oxalate was raised in only nine of these patients (mean 0.25 mmol/24 h, range 0.08--0.59 mmol) (normal less than 0.20). By contrast, when the diet was supplemented with oral sodium oxalate, all 19 patients with steatorrhoea had hyperoxaluria (mean 0.91 mmol/24 h, range 0.46--1.44 mmol) (normal less than 0.44). There was a significant positive linear relationship between urinary oxalate and faecal fat when the 32 patients were on the high oxalate intake (r = 0.73, P less than 0.001), but not when they were on the low oxalate intake. Mean percentage absorption of orally administered oxalate was 5.8 +/- 0.99% (+/- 1 SD) in normal subjects and 14.7 +/- 6.0% (P less than 0.002) in patients with steatorrhoea. Measurement of urinary oxalate output during oral sodium oxalate loading appears to be a reliable and convenient screening test for steatorrhoea.

Adult