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Biomedical subjects

J Kelleher

Publications and source records attributed to J Kelleher.

At least 19 recordsLinked to original sources

Familial thrombocytopenia with micromegakaryocytes.

Chronic thrombocytopenia was noted in two siblings and a first cousin. The initial impression was of immune thrombocytopenic purpura (ITP) with decreased megakaryocytes. One patient had splenectomy for presumed chronic ITP but showed no improvement. Bone marrow buffy coat slides were examined in the three children with thrombocytopenia, four normal controls, and five children with "classic" acute ITP. Megakaryocyte size, maturation, and ploidy were determined with Wright-Giemsa and Feulgen-stained material. Mean megakaryocyte diameters were 23.1 microns in the three related patients, 30.8 microns in normal controls, and 63.1 microns in children with "classic" acute ITP. Many "micromegakaryocytes" were noted in the three related children with chronic thrombocytopenia. An exhaustive family history was obtained, which showed multiple points of consanguinity. These patients represent an apparently new autosomal recessive disorder of megakaryocytopoiesis, characterized by disturbed megakaryocyte ploidization and maturation. More sensitive recognition of micromegakaryocytes should be attempted in children with atypical chronic thrombocytopenia, familial history of thrombocytopenia, or patients who have ITP and who have not responded to initial therapy.

Bone Marrow Examination

Symptomatic zinc deficiency in experimental zinc deprivation.

An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkaline phosphatase activity. Alcohol induced hepatitis, which was suspected in this subject, may have caused a predisposition to altered zinc metabolism and possible zinc deficiency which was exacerbated by subsequent zinc deprivation. The report supports the value of neutrophil zinc concentration as an indicator of poor zinc status.

Adult

Monocyte zinc and in vitro prostaglandin E2 and interleukin-1 beta production by cultured peripheral blood monocytes in patients with Crohn's disease.

This study investigated the relationship between zinc status and prostaglandin E2 and interleukin-1 beta production by cultured monocytes in patients with Crohn's disease. Monocyte zinc was significantly decreased in both 12 inpatients and 22 outpatients compared with controls (P less than 0.001) but lymphocyte and polymorphonuclear cell zinc were normal. When cultured monocytes from 10 outpatients with Crohn's disease were stimulated with lipopolysaccharide, prostaglandin E2 production increased markedly, coupled with a fall in monocyte zinc. In matched controls, prostaglandin E2 production was significantly less and monocyte zinc remained stable. No difference in interleukin-1 release was noted between patients and controls. The addition of prednisolone to cell cultures suppressed prostaglandin E2, interleukin-1 synthesis, and monocyte zinc did not change. Zinc chloride augmented prostaglandin E2 production in patients, but not controls, and interleukin-1 remained stable. These results demonstrate a link between low monocyte zinc concentration and excessive prostaglandin production in patients with Crohn's disease.

Cells, Cultured

Ageing and duodenal mucosal immunity.

The production of immunoglobulins by duodenal mucosa in young and old subjects was studied. For 20 elderly people (mean age 85.3 years) and 18 young subjects (mean age 34.5 years) the amounts of the immunoglobulins IgA, IgG and IgM synthesized and secreted by a duodenal biopsy over a 2-day period were compared. There was no significant difference in the immunoglobulin production between the two groups. This suggests that age itself may have no effect on duodenal mucosal immunity.

Adult

The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized controlled trial.

Thirty elderly long-stay patients were randomly allocated to receive either placebo or dietary supplementation with vitamins A, C and E for 28 days. Nutritional status and cell-mediated immune function were assessed before and after the period of supplementation. Following vitamin supplementation, cell-mediated immune function improved as indicated by a significant increase in the absolute number of T cells (p less than 0.05), T4 subsets (p less than 0.05), T4 to T8 ratio (p less than 0.01) and the proliferation of lymphocytes in response to phytohaemagglutinin (p less than 0.01). In contrast, no significant changes were noted in the immune function of the placebo group. We conclude that supplementation with the dietary antioxidants vitamins A, C and E can improve aspects of cell-mediated immune function in elderly long-stay patients.

Aged

Evidence of cellular zinc depletion in hospitalized but not in healthy elderly subjects.

Cellular immune function declines with age and is implicated in the increased incidence of cancer, and morbidity and mortality associated with infections in elderly people. Elderly people are at risk of nutritional depletion, including of zinc, and zinc is known to influence immunity. The present study assessed zinc status in both healthy elderly subjects and elderly inpatients. Polymorphonuclear-cell zinc was decreased in the hospitalized subjects and 27% had values below the reference range for healthy elderly and young subjects. Since PMNC zinc is decreased in experimental zinc depletion and correlates with muscle zinc, we suggest that 27% of the patients studied may be zinc depleted and may benefit from zinc supplementation.

Aged

Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption.

Adult

Alcohol consumption in patients with colorectal adenomatous polyps.

The risk of developing colorectal adenomatous polyps is probably increased by a variety of dietary and environmental factors. We found an association with current alcohol and cigarette consumption. The risk of polyps was increased three times in drinkers who did not smoke and two times in smokers who did not drink, with those who both drank and smoked having 12 times the risk of total abstainers. Since colonic adenomatous polyps are generally regarded as premalignant lesions, these results lend support to the view that alcohol consumption may be an important factor in the pathogenesis of colorectal neoplasia, thus reinforcing the proposed polyp/carcinoma sequence in colorectal carcinogenesis. The role of smoking, however, is less clear particularly since the lack of association of colorectal carcinoma and smoking has been reported in many other studies.

Aged

Effect of fasting, self-selected and isocaloric glucose and fat meals and intravenous feeding on plasma zinc concentrations.

This study investigated the effect of fasting, self-selected meals and isocaloric oral glucose and fat meals and intravenous (i.v.) feeding on plasma zinc concentrations in men. Plasma zinc remained stable when volunteers fasted all day, but self-selected meals and 600 kCal of dextrose or fat emulsion caused significantly reduced plasma zinc concentrations [mean (SD) 12.1 (1.4), 12.3 (0.6) and 12.2 (0.7) mumol/L at 1400 h, respectively, compared with a fasting level of 13.9 (1.6) mumol/L at 0800 h, P less than 0.05]. In patients undergoing intravenous hyperalimentation, plasma zinc decreased from 12.0 (1.4) mumol/L at 0800 h to 10.0 (1.1) mumol/L at 1400 h [mean (SD), P less than 0.01]. These data show that both enteral and i.v. feeding cause a decline in plasma zinc and that glucose alone is not responsible for this post-prandial fall since ingestion of isocaloric amounts of glucose or fat have a similar effect.

Circadian Rhythm

HIV testing.

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Communication

Pancreatic exocrine function after a sutureless pancreatico-jejunostomy following pancreaticoduodenectomy.

Exocrine pancreatic function was measured in 14 patients after pancreaticoduodenectomy for periampullary neoplasms in order to assess the patency of a sutureless pancreatico-enteric anastomosis. Pancreatic function was examined by the p-aminobenzoic acid/p-aminosalicylic acid (PABA/PAS) test 3-160 months after operation and compared with age- and sex-matched controls. There were no significant differences between mean (s.e.m.) serum PABA concentrations 3 h after ingestion of N-benzoyl-L-tyrosyl-PABA (25.5 (3.6)) mumol/l for patients, 26.1 (2.0) mumol/l for controls). However, the mean (s.e.m.) PABA excretion index was significantly lower in the patients (0.58 (0.08)) than in the controls (0.76 (0.04)). Four patients required pancreatic enzyme supplements for control of diarrhoea. Self-limiting pancreatic leaks occurred in two patients. The results suggests that the sutureless pancreatico-enteric anastomosis has an acceptably low leakage rate but that pancreatic exocrine function is diminished following pancreaticoduodenectomy with this technique. However, the majority of patients require no enzyme supplements and no significant tendency to late stenosis of the anastomosis was demonstrated.

4-Aminobenzoic Acid

Interactions of retinoic acid and androgens in human prostatic tissue.

The effect of retinoic acid (RA) on testosterone metabolic pathway was investigated in hyperplastic and neoplastic human prostatic tissues, and also the effects of steroids on RA binding to its receptor. Steroids only had a minimal effect on the binding of RA by its receptor. The conversion of testosterone to DHT by 5 alpha-reductase was reduced in the presence of retinoic acid. The inhibition was probably due to competition with NADPH for enzyme binding sites. The degree of inhibition found with retinoic acid at a concentration of 10(-4)M was greater for hyperplastic (41%) than that for neoplastic tissue (24%). The inhibition of 5 alpha-reductase by retinoic acid was dose-dependent. The activity of 5 alpha-reductase is significantly less in neoplastic compared with hyperplastic tissue.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Cellular and muscle zinc in surgical patients with and without gastrointestinal cancer.

1. The zinc status of surgical patients with and without gastrointestinal cancer was studied. 2. Plasma zinc was lowest in patients with cancer concurrent with depressed plasma albumin concentrations. 3. Polymorphonuclear cell zinc was decreased in both patient groups and correlated strongly with abdominal muscle zinc (r = 0.89, P less than 0.001). 4. Mononuclear cell and total leucocyte zinc were similar to control values in both groups of patients. Total leucocyte, but not mononuclear cell, zinc correlated weakly with muscle zinc (r = 0.48, P less than 0.05). 5. The results suggest that polymorphonuclear cell zinc may be better than leucocyte zinc in assessing zinc status and that some surgical patients may be zinc-depleted. The presence of gastrointestinal cancer did not influence the zinc status.

Adult

Clinical monitoring of steatorrhoea in cystic fibrosis.

In 100 patients with cystic fibrosis the severity of steatorrhoea was assessed by three separate methods. Using chemical faecal fat assay as the gold standard, two other rapid and inexpensive methods were compared with it. The steatocrit method proved unreliable in our hands and gave little indication of the presence or severity of steatorrhoea. The more simple microscopy method was highly sensitive (97%) and only three of 80 patients with steatorrhoea were missed. All patients with severe steatorrhoea (greater than 60 mmol fat/day) were clearly demonstrated. The method is applicable to spot faecal samples and can readily be carried out on an outpatient basis. In centres where faecal fat assays are not available, the simple and cheap microscopic examination will give some indication of the response to enzyme treatment and may also help to identify non-compliant individuals.

Adolescent

Relation between zinc status and hepatic functional reserve in patients with liver disease.

Patients with liver disease may be at risk of zinc depletion. We measured polymorphonuclear cell, mononuclear cell, plasma, and erythrocyte zinc values, and erythrocyte carbonic anhydrase activity to assess zinc status in 17 patients with non-alcoholic liver disease (primary biliary cirrhosis and chronic active hepatitis) and 13 patients with alcoholic liver disease. The plasma zinc concentration was reduced in both patient groups and correlated strongly with the plasma albumin concentration. The mean polymorphonuclear cell zinc value in both groups was similar to that of controls but when results were combined and grouped according to hepatic functional reserve, patients with more severe liver damage (grade C) had a lower polymorphonuclear cell zinc value (mean (SD) 0.86 (0.24) nmol/mg protein) than patients with grade A (1.44 (0.43) nmol/mg protein, p less than 0.01) or grade B liver damage (1.08 (0.30) nmol/mg protein, p less than 0.05), or control subjects (1.26 (0.28) nmol/mg protein, p less than 0.001). The polymorphonuclear cell zinc value did not correlate with other indices of zinc status. The mononuclear cell zinc value was normal in all patients and was unrelated to hepatic damage. The erythrocyte zinc value and carbonic anhydrase activity were raised in alcoholic patients only. Since the polymorphonuclear cell zinc concentration is low in human experimental zinc deficiency and also correlates with tissue zinc, we suggest that our results provide evidence of progressive leucocyte zinc depletion in patients with liver disease.

Adult