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Biomedical subjects

J Kelleher

Publications and source records attributed to J Kelleher.

At least 73 records · Page 4Linked to original sources

Plasma and leucocyte zinc concentrations and their response to zinc supplementation in an elderly population.

Plasma, mononuclear cell and granulocyte zinc were assessed in a group of 15 institutionalised elderly female patients, and the effect of different levels of zinc supplements (50, 100, 150 mg elemental zinc/day) on these parameters was measured. Plasma but not cellular zinc was lower in the elderly compared with a young control group, but a diminished serum albumin may explain the plasma results. Plasma zinc increased with supplementation, but only when the daily intake was 100 or 150 mg/day; the greatest response was with the higher dose. Mononuclear cell zinc did not respond to zinc supplements. There was a decrease in granulocyte zinc at all levels of zinc supplements, the greatest decrease being found with the highest dose (150 mg/day). The decrease in granulocyte zinc at high intakes may have implications in phagocytosis and chemotaxis.

Aged↗

Does super efficient starch absorption promote diverticular disease?

The amount of starch escaping absorption in the small intestine was measured in eight patients with symptomatic diverticular disease and eight controls. Unabsorbed starch was calculated from breath hydrogen measurements after a potato meal compared with the hydrogen response to lactulose. The proportion of unabsorbed starch was low in all the patients (mean 3.3%) and was only about a quarter of that in the controls (12.4%; p less than 0.01). These findings confirm that unabsorbed starch provides an important quantity of carbohydrate reaching the colon and suggest that super efficient starch absorption, by reducing this provision, may promote the development of diverticular disease.

Aged↗

Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial.

Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin V potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients vs. 2 of 105; P = 0.0025), with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia.

Administration, Oral↗

Fatty acid composition of plasma and erythrocyte phospholipids in preterm infants.

Erythrocyte and plasma phospholipid fatty acids were determined in preterm babies at 0, 6 and 10 weeks. There were highly significant changes in fatty acid composition between birth and 6 weeks in both plasma and erythrocyte phospholipids, the changes being more numerous and quantitatively greater in phosphatidyl choline. There was little further change by 10 weeks. Linoleic acid increased by approximately 100% at 6 weeks in plasma phosphatidyl ethanolamine and 200% in phosphatidyl choline. In erythrocyte phosphatidyl ethanolamine, linoleic acid increased by approximately 150% at 6 weeks and in phosphatidyl choline increased 170%. Arachidonic acid decreased by 54%. The essential fatty acid status of the preterm babies studied using contemporary feeding regimes was satisfactory and by 6 weeks phospholipid fatty acid profiles were comparable with published data for normal healthy breast-fed infants.

Erythrocytes↗

T-lymphocyte subsets and interleukin-2 production in zinc-deficient rats.

1. It has been suggested that zinc-deficiency impairs cellular (T-lymphocyte-mediated) immune responses via a selective effect on helper T-lymphocytes. We have addressed this question in the rat by employing recently developed reagents in the form of monoclonal antibodies which specifically identify rat T-lymphocyte subsets (identifying total T-cells, helper T-cells and suppressor T-cells) and also by quantifying helper T-cell function by measurement of the helper T-cell-derived molecule interleukin-2 (IL-2). 2. Zn-deficiency induced T-cell atrophy (assessed morphologically and phenotypically with anti-rat T-cell monoclonal antibodies) in both peripheral blood and spleen. The use of these specific monoclonal antibodies failed to demonstrate a selective effect of Zn deficiency on the helper T-cell fraction of the total T-lymphocyte population. 3. In contrast, the results of functional assays of the T-lymphocyte response were dependent on the conditions of culture but suggested that the generation of IL-2 and its corresponding receptor were determined by the intracellular Zn status. Thus, in vivo, helper T-lymphocyte numbers are non-specifically reduced since other T-cell subsets are also reduced in response to appropriate stimulation. The functional consequences of this are dependent on the intracellular concentration of Zn but appear to influence both IL-2 production and its receptors on activated T-cells.

Animals↗

Nutrition and cellular immunity in hospital patients.

1. The interrelations between nutritional and cellular immune function measurements were studied in seventy patients suffering from various degrees of malnutrition. They included patients with liver disease, inflammatory bowel disease, neoplastic disease, neurological patients, post-operative surgical patients and patients with respiratory problems. 2. Nutritional measurements included: anthropometry, serum proteins, various vitamins and trace elements, and a prognostic nutritional index (PNI) was calculated. 3. Immunological measurements included: (1) natural killer (NK) cell activity, (2) antibody-dependent cellular cytotoxicity (ADCC), (3) lymphocyte proliferation in response to the mitogens concanavalin A (Con A), phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) in both AB and autologous serum. 4. There was no association between anthropometric measurements and tests of immune function. 5. The lymphocyte proliferation in response to mitogenic stimulation in the malnourished patients was depressed in autologous serum compared with the response of the same lymphocytes in pooled AB serum. The lymphocyte proliferation in response to Con A correlated with transferrin in autologous serum (r 0.46, n 49, P less than 0.01) and to a lesser extent in AB serum (r 0.33, n 51, P less than 0.05). There was a difference in the Con A-stimulated tritiated-thymidine uptake between patients with low and normal serum zinc levels (P less than 0.05) for cultures performed in autologous serum, but not AB serum. 6. There was a significant correlation between NK cell activity and vitamin C (r 0.43, n 60, P less than 0.01). There was no relation between nutritional measurements and ADCC or the lymphocyte response to stimulation with PHA or PWM. 7. The results suggest that the severity of overall malnutrition does not influence several different aspects of the cellular immune response. However, the results do suggest that certain individual nutrients, particularly vitamin C and Zn, do influence the immunoreactivity of different lymphocyte subpopulations.

Hospitalization↗

The early anaemia of the premature infant: is there a place for vitamin E supplementation?

1. The efficacy of oral vitamin E supplementation in preventing the early anaemia of the premature infant was assessed in a 10-week double-blind trial. Forty-two babies received either a placebo or 5 or 15 mg supplementary vitamin E/d with oral feeding. No infant received less than the recommended vitamin E:polyunsaturated fatty acid (E:PUFA) value of 0.6. No iron supplement was given. 2. Weekly full blood counts were taken, and plasma vitamin E assay and in vitro haemolysis tests performed on blood sampled on day 1, and also at 6 and 10 weeks of age. All blood withdrawn and transfused and all feeds were documented. 3. Thirty-six (86%) of the babies had a plasma vitamin E level at birth below the accepted adult norm, i.e. less than 5200 micrograms/l. At 6 weeks of age thirty-three (79%) and at 10 weeks thirty-five (83%) of the babies had levels within the normal adult range. No baby showed either clinical or haematological evidence of a vitamin E deficiency state during the trial. 4. It is concluded that in the absence of Fe supplementation and observing the minimum recommended E:PUFA value, contemporary feeding practices allow for the absorption of sufficient vitamin E by the premature baby to prevent the development of an early haemolytic anaemia. 5. No significant relation was found between plasma vitamin E levels and the degree of peroxide haemolysis.

Anemia↗

Essential element nutritional status in cystic fibrosis.

Serum calcium, magnesium, iron, copper and zinc were measured in 117 patients with cystic fibrosis. Apart from serum iron levels, all the other essential element levels were well maintained and there was no evidence of a need for supplementation. Serum iron was frequently low and the need for iron supplements must be considered after further investigation. The subjects studied covered a wide age range, had widely varying fat malabsorption and clinical grading, and also varying degrees of pulmonary involvement. We found no evidence that any of these parameters directly influenced essential element status as assessed by serum levels.

Adolescent↗

The influence of long-term cimetidine as an adjuvant to pancreatic enzyme therapy in cystic fibrosis.

Seventeen patients on constant doses of pancreatic enzymes were randomised to receive either cimetidine or placebo for either of two successive six month periods. Nutritional state and maldigestion were assessed at the beginning and end of each period. Reductions in mean values of faecal fat, nitrogen, wet weight, and bile salts of approximately 30% were found on cimetidine therapy. Results showed considerable variation and only the fall in faecal fat was statistically significant. No benefit was demonstrated for height, weight, skinfold thickness, albumin, vitamin A, bone age or Crispin-Norman score.

Adolescent↗

Protein carboxyl methylation-demethylation in rat thymocytes.

The in vitro carboxyl methylation-demethylation of exogenous and endogenous proteins was investigated in rapidly proliferating thymocytes. Of all the cell fractions tested protein carboxyl methyltransferase activity was highest in the nucleoplasmic fraction (3.2 pmol/mg per minute with ACTH and 0.8 pmol/mg per minute with endogenous substrates). The only other fraction with significant activity was the cytosol (1.2 pmol/mg per minute with ACTH). The nuclei from thymocytes are extremely large; consequently some 70-80% of protein carboxyl methyltransferase in these cells is of nuclear origin. The cellular concentration of protein carboxyl methyltransferase and methyl acceptor proteins paralleled the development of the thymus. Mature lymphocytes contained about 25% of the activity of immature thymocytes. Failure to accumulate protein methyl esters, either in vitro in in vivo, was most likely due to the presence of a very active protein methylesterase. This rapid turnover of protein methyl esters was manifest by the continuous production of [3H]methanol when soluble fractions were incubated with S-adenosyl-L-[methyl-3H]methionine ([methyl-3H]AdoMet). [3H]Methanol production was enhanced upon the further addition of the particulate fractions, particularly chromatin. The turnover of protein methyl esters was primarily enzymatic, since no [3H]methanol was formed when ACTH was incubated with AdoMet and purified protein carboxyl methyltransferase. Utilizing [3H]methanol formation as an index of the rate of protein methylation-demethylation would yield minimal values, since this compound was oxidized via alcohol dehydrogenase or oxidase in these cells. The majority of the methyl acceptor proteins were located in the nuclei. The rapid methylation-demethylation of these proteins may play some role in development and (or) differentiation.

Animals↗

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↗

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↗

Intussusception: influence of age on reducibility.

Our experience of hydrostatic reduction of intussusception by barium enema over the last 7 years is reviewed. There were 115 attempted hydrostatic reductions out of a total of 129 patients diagnosed as having intussusception on barium enema or at surgery. Age at presentation varied from one month to nine years, 81% of patients presenting before one year of age. Of 115 attempted reductions, 63 were successful giving an overall success rate of 55%. Looking at the different age groups, it was found that hydrostatic reduction was much less successful in infants aged 3 months and younger; success rate 20% compared to a 60% success rate in the remainder. Conscious of recent reports in the literature of bowel perforation during attempted hydrostatic reduction in young infants, we suggest that there should be a reappraisal of the role of hydrostatic reduction in the three months and younger age group.

Age Factors↗

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↗

Benign hepatocellular tumors in the young. A clinicopathologic spectrum.

Hepatic tumors unassociated with cirrhosis were encountered in seven patients aged 10 to 19 years. Four patients had received androgens for aplastic anemia. Two patients had transfusional hemosiderosis. One patient had had a renal transplant 2 1/2 years ago. Two patients are alive at 2 3/4 and 2 1/2 years after surgical resections. Nodules were found at autopsy in the others. The tumors were well differentiated and, in the androgen-related cases, differed from the others in the following features: canalicular bile retention, mild nuclear atypia, and acinar formation. No mitoses, vascular invasion, or metastatic tumor were evident. The clinical setting was variable; different factors, including iron overload and androgen therapy, played a role in the development of tumor. Although the androgen-related cases showed mild cellular atypia, biologic evidence of malignancy was lacking as in most previous reports.

Adolescent↗

Physical fitness in children with hemophilia.

Eleven boys, 8.3 to 15.5 (mean 11.6) years old, with hemophilia, were studied by bicycle ergometry to determine their physical fitness. Parameters analyzed and compared to data for normal children included total work, mean power minutes of exercise, heart rate (HR), and blood pressure (BP), as well as catecholamine levels. The hemophilic child performs significantly less total work (67%), mean power (49%), minutes of exercise, (30%), and HR (8%). There were no differences in BP. Norepinephrine rose from a resting level of 204.5 to 652pg /ml after exercise, and epinephrine rose from 20.5 to 76.6pg/ml, levels comparable to those achieved by normal children during exercise. Children with hemophilia demonstrate poor exercise performance, which we believe is due to a lack of physical conditioning. Recommendations are made for individual exercise prescriptions to improve the fitness of these children.

Adolescent↗

Nutritional and immunological assessment of patients with anorexia nervosa.

The nutritional and immunological status of patients with anorexia nervosa was assessed. Anthropometric measurements were found to be lowered as were the serum levels of zinc (p<0.01), copper (p<0.01) and ceruloplasmin (p<0.05) in comparison with the control group. However the serum levels of albumin, pre-albumin, transferrin and retinol binding protein, vitamins A and D and leucocyte vitamin C were generally found to be within normal limits. Lymphocyte transformation was measured in response to stimulation with the mitogens Con A, PHA and PWM. Responses were normal in all patients with the exception of one who showed a depressed response to Con A. Natural killer cell activity was measured against the target cell line K562 and was not found to differ significantly from controls. It is suggested that the relatively normal protein and vitamin status is responsible for maintaining the apparently normal cellular immune function in patients with anorexia nervosa.

Journal Article↗