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Biomedical subjects

D M Flynn

Publications and source records attributed to D M Flynn.

At least 37 records · Page 2Linked to original sources
PubMed1990

High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation.

Cardiac scintigraphy has been performed in 60 beta-thalassaemia major patients aged 8-35 years who received regular blood transfusions and subcutaneous desferrioxamine (DFX) chelation. Fifty-seven showed no clinical, radiological or electrocardiographic evidence of heart disease and 3 had clinically apparent cardiac failure. Twenty-two patients (37%) showed severe cardiac functional impairment defined by a resting left ventricular ejection fraction (LVEF) less than 45% and/or a drop of greater than 12% on stress, while 19 were normal and 19 had a mild abnormality. There was no significant correlation between abnormality of LVEF and age, serum ferritin, number of units transfused, dose and duration of subcutaneous DFX therapy, liver disease or sexual maturation. Non-compliant patients (defined as the use of subcutaneous DFX less than 4 times weekly) generally showed worse cardiac function. Repeat study on 17 patients after 6-28 months of better compliance with subcutaneous or intravenous DFX (using an indwelling catheter) showed a significant overall improvement in LVEF associated with a significant drop in serum ferritin. We conclude that cardiac scintigraphy uncovers a high incidence of cardiac functional abnormality in asymptomatic, well-transfused thalassaemia patients, particularly those poorly compliant with chelation. Those with poor LVEF results should be offered intensive chelation therapy to improve cardiac function.

Adolescent↗
PubMed1989

Glycine enhances NMDA-receptor mediated synaptic potentials in neocortical slices.

One class of excitatory amino-acid receptors, the N-methyl-D-aspartate (NMDA) receptors, mediates transmission at a small, but important, group of synapses in the neocortex. These receptors are implicated in neuronal plasticity during development in young mammals and in memory acquisition in adults. Recently, responses of isolated membrane patches to NMDA were shown to be greatly enhanced by glycine. This, together with the demonstration that the strychnine-insensitive glycine-binding site is distinct from, but linked to, the NMDA receptor has excited intense interest in glycine as a synaptic modulator. Before proposing a physiological function, however, it is important to determine whether glycine could enhance synaptic responses to NMDA receptor activation in intact, adult tissue. An earlier study failed to demonstrate enhancement of NMDA responses when glycine was applied and it was proposed that in intact tissue the high-affinity glycine site was already saturated by endogenous glycine. It remained possible that glycine concentrations can be maintained at low levels close to synaptic receptors. We have examined responses of neurons in slices of adult neocortex to focal applications of excitatory amino acids and glycine and report enhancement by glycine of NMDA receptor-mediated excitatory postsynaptic potentials.

Action Potentials↗
PubMed1988

Infections with gram-negative bacilli in a cardiac surgery intensive care unit: the relative role of enterobacter.

A 7-month prospective survey for cefazolin-resistant Gram-negative bacilli in cardiac surgery patients, receiving cefazolin prophylaxis, showed that 58 (67%) of 87 were colonized with enterobacter, 37 (64%) with citrobacter, 33 (57%) with Pseudomonas aeruginosa, and seven (2%) with Serratia marcescens. About 50% of colonization occurred before cefazolin prophylaxis and was present on admission to the intensive care unit. Typing of strains showed that horizontal transmission accounted for at most 14% of carriage. Cefazolin prophylaxis (and high gastric pH) were associated with increased levels of postoperative colonization, most notably for enterobacter. About 25% of colonization with enterobacter, pseudomonas, and serratia was followed by clinical infection. Enterobacter cloacae was the most common pathogen and pneumonia the most common infection. Infections contributed to eight of 11 deaths; four of the eight involved enterobacter. Potential control measures include eliminating endogenous Gram-negative flora by gut decontamination or at least stemming the increase in level of colonization that occurred after surgery.

Adult↗
PubMed1987

Patients' endogenous flora as the source of "nosocomial" Enterobacter in cardiac surgery.

We prospectively studied Enterobacter colonization in cardiac surgery patients receiving cefazolin prophylaxis. Fifty-eight (67%) of 87 patients became colonized, 28 by the time of admission to a Cardiac Surgery Intensive Care Unit. Enterobacter cloacae was four times more prevalent than Enterobacter aerogenes. We found increased Enterobacter colonization, after prophylaxis, in 45% of surgery patients. None of 25 control patients, who underwent coronary angioplasty and received no antibiotic prophylaxis, showed increased colonization (P = .001). Both groups had similar baseline rates of Enterobacter carriage. Typing showed 50 distinct strains of E. cloacae and 11 of E. aerogenes; 25% of patients carried greater than or equal to 2 strains simultaneously. In the nine cases of horizontal transmission, source patients were intubated for greater than or equal to 5 days and had heavy throat carriage of Enterobacter. No environmental sources of transmission were found. Clinical Enterobacter infection developed in 12 patients; at least nine of these were infected with a strain that had been isolated by surveillance culture. We conclude that Enterobacter, part of the patients' endogenous flora, becomes an important pathogen when amplified by prophylactic antibiotics and is less often transmitted horizontally.

Aged↗
PubMed1987

Serum 1,25 dihydroxyvitamin D and osteocalcin concentrations in thalassaemia major.

In view of the claim that low 25-hydroxyvitamin D (25-OHD) concentrations may contribute to the pathogenesis of bone disease in patients with beta thalassaemia major and iron overload, we have assessed the concentrations of 25-OHD, 1 alpha,25 dihydroxyvitamin D (1 alpha,25(OH)2D), parathyroid hormone, and osteocalcin in such patients. 25-OHD concentrations were significantly lower in patients with thalassaemia major and iron overload than in controls and in some patients were subnormal or undetectable. 1 alpha,25(OH)2D concentrations were, however, normal in all patients and were similar to those in controls. Serum parathyroid hormone and plasma calcium concentrations were also normal and not significantly different from those in controls. Although 25-OHD concentrations increased significantly between January and June, there was no change in 1 alpha,25(OH)2D concentrations. 25-OHD concentrations remained lower than control values, even in June. Parathyroid hormone concentrations fell, but not significantly, between January and June, but calcium concentrations did not alter. Osteocalcin concentrations were normal in all patients except one, who had extremely low concentrations of this protein. The concentration of osteocalcin was not related to 25-OHD or 1 alpha,25(OH)2D concentrations. Thus normal calcium homeostasis is maintained in patients with thalassaemia major despite low or low-normal 25-OHD concentrations; this is probably achieved through the maintenance of normal 1 alpha,25(OH)2D concentrations, which were indistinguishable from those in controls. Normal 1 alpha,25(OH)2D, parathyroid hormone, and osteocalcin concentrations argue against an important role for vitamin D deficiency in the pathogenesis of thalassemia bone disease.

Adolescent↗
PubMed1987

Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine.

Liver biopsies were performed on 51 regularly transfused patients with beta thalassaemia, age range 5-36 (mean 18.6) years, who had received regular subcutaneous desferrioxamine (DFX) treatment for periods between one and eight years (40 for eight years). The biopsy specimens were examined by light microscopy and immunofluorescence for hepatitis B virus surface and core antigens (HBsAg and HBcAg), and the iron content was determined chemically. The results were compared with serum ferritin concentration and aspartate transaminase (AST) activity and with hepatitis B virus serology. Biopsy specimens, in which chemical liver iron had been determined in 12, were also available from 17 patients. Mean serum ferritin (+/- SD) had fallen from 5885 (3245) micrograms/l to 1638 (976) micrograms/l in 36 patients after eight years' chelation, while mean (+/- SD) liver iron concentration had fallen from 2945 (900) micrograms/100 mg dry weight to 857 (435) micrograms/100 mg dry weight in 12 of them. All biopsy specimens examined were negative for HBs and HBc antigens. The presence of histological features of hepatitis was associated with increased liver iron content, increased fibrosis, and with progression of fibrosis between the two biopsies. Procollagen III peptide was assayed in 28 patients but did not correlate with the degree of hepatitis, fibrosis, or with chemical liver iron content. We conclude that with regular subcutaneous DFX, mean concentrations of serum ferritin and liver iron are maintained in these patients at about five and 10 times the normal value, respectively, and that progression of liver damage is more likely to be due to viral hepatitis, presumably related to the parenterally transmitted non-A, non-B agents than to iron overload.

Adolescent↗
PubMed1985

A biomechanical model of the posterior knee capsule of the cat.

A biomechanical model is presented which represents the upper edge of the posterior knee capsule in the cat as a two-segment, vertically loaded catenary suspension cable from which the capsule sheet is suspended. Data are presented which show that the upper edge of the capsule is organized as a cable, which spans the notch between the femoral condyles. When a point load is applied to the cable, measurement of the cable shape allows for calculation of the cable tension and the downward distributed loads acting on the cable. This method was used to measure the in-vivo cable tension and the distributed downward loading acting on the capsule cable. The results show that the lateral side of the posterior joint capsule sustains a higher loading than the medial side.

Animals↗
PubMed1985

Oxidative effects of iron on erythrocytes.

In this work we have investigated the effects of iron-induced free radical formation in normal human erythrocytes in vitro, as a model system for studying iron damage, and in erythrocytes from patients with beta-thalassaemia major. The resulting oxidative effects were measured in terms of methaemoglobin formation and reduced glutathione loss. The effects of desferrioxamine, an iron-chelating agent, were also investigated. The results show that the increased methaemoglobin formation after iron-induced oxidative stress is consistent with a decline in the intracellular glutathione levels and that this process is inhibited by desferrioxamine. Similar treatment of red cell haemolysates produces less methaemoglobin. This suggests that, on exposure of intact erythrocytes to iron-induced free radical effects, the red cell membrane exacerbates the breakdown of the antioxidant defences of the cell and the oxidation of haemoglobin.

Ascorbic Acid↗
PubMed1983

Insulin resistance and iron overload.

Glucose tolerance tests performed in 15 patients (10 males and 5 females, age range 6-34 years, mean 16 years) with transfusional iron overload revealed fasting and subsequent blood glucose concentrations within the normal range in all except one patients who was overtly diabetic. However, in all patients except one, blood glucose concentration at 2 hours was higher than the respective fasting glucose concentration. All but two of the patients (one of whom was diabetic) showed fasting and post glucose hyperinsulinism. All the patients had hepatic dysfunction of varying severity. It is hence suggested that the initial disturbance of carbohydrate metabolism in transfusional siderosis is insulin resistance, similar to that found in chronic liver disease. Overt diabetes is probably a later event, occurring when sufficient damage to pancreatic cells has occurred and appropriate hyperinsulinaemia cannot be sustained.

Adolescent↗
PubMed1982

Survival and desferrioxamine in thalassaemia major.

A small randomised trial and observation of all patients homozygous for beta-thalassaemia in Britain born in or before 1963 indicated that those patients who had received average weekly doses of more than 4 g of desferrioxamine over the previous few years were less likely to die in the near future than were patients of similar ages who had received less, or no, desferrioxamine.

Adolescent↗
PubMed1982

Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta-thalassaemia major and iron overload.

The incidence of ascorbic acid (AA) deficiency and its effect on serum ferritin concentration relative to body iron stores was studied in 61 unchelated patients with beta-thalassaemia major. Thirty-nine (64%) of patients had subnormal leucocyte ascorbate concentrations without clinical evidence of scurvy. The lowest leucocyte ascorbate concentrations tended to occur in the most transfused patients. No correlation was found between the units transfused and serum ferritin concentration in the AA-deficient patients but a close correlation (r = +0.82; p less than 0.005) existed for the AA-replete group. Similarly a close correlation (r = +0.77; p less than 0.005) was obtained between liver iron concentration and serum ferritin in AA-replete patients but only a weak correlation (r = +0.385; p less than 0.025) existed for the AA-deficient group. When AA-deficient patients were treated with ascorbic acid, serum iron and percentage saturation of iron binding capacity rose significantly; serum ferritin rose in 13 of 21 patients despite the simultaneous commencement of desferrioxamine therapy. In contrast all three measurements tended to fall in AA-replete patients with ascorbic acid and desferrioxamine therapy. Thus, AA deficiency is commonly present in beta-thalassaemia patients with iron overload and may give rise to inappropriate serum ferritin concentrations in relation to body iron stores.

Adolescent↗