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Biomedical subjects

M J Elliott

Publications and source records attributed to M J Elliott.

At least 145 records · Page 8Linked to original sources

Regulation of human monocyte adherence by granulocyte-macrophage colony-stimulating factor.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to increase the adherence of purified peripheral blood monocytes to plastic surfaces and to monolayers of human umbilical vein endothelial cells. With plastic surfaces as a model 9-hr culture with GM-CSF was necessary for enhancement, and maximum levels were obtained after 24-hr stimulation. GM-CSF-stimulated adherence must require new RNA and protein synthesis because actinomycin D and cycloheximide abolished existing adherence and prevented further monocyte attachment. Interestingly, shorter incubations (1-2 hr) with cycloheximide increased adherence, suggesting a labile inhibitor. Formaldehyde fixation of monocytes but not of human vein endothelial cells abolished adherence, indicating the need for actively metabolizing monocytes. Thus, a hemopoietic growth factor, responsible for the proliferation and differentiation of monocytes, can also alter their adhesive characteristics. These observations may have important implications in pathological situations and in the in vivo use of GM-CSF.

Biological Factors↗

Congenital left ventricular inflow obstruction: is the outcome related to the site of the obstruction?

Between 1978 and 1987, 39 patients aged 1 day to 15 years underwent surgery for symptomatic left ventricular inflow obstruction. Four diagnostic groups were identified: cor triatriatum (6 patients), supravalvar mitral membrane (SVMM) with a normal mitral valve (7 patients), SVMM with an abnormal mitral valve (9 patients) and mitral stenosis (17 patients). Associated cardiac anomalies occurred in 26 patients (67%). There were 8 deaths (21%), 3 in patients with SVMM and an abnormal mitral valve and 5 in patients with mitral stenosis. Survival for patients with normal mitral valves was significantly better than that for patients with abnormal mitral valves (13/13 vs 18/26, P less than 0.05). There was also high morbidity in patients requiring prosthetic mitral valve replacement. These data suggest that the outcome of surgical treatment for left ventricular inflow obstruction may be predicted according to the site of the obstruction. This is best determined preoperatively by cross-sectional echocardiography which allows optimal planning of surgical strategy.

Adolescent↗

The role of the priming fluid in the metabolic response to cardiopulmonary bypass in children of less than 15 kg body weight undergoing open-heart surgery.

The major metabolic response to open-heart surgery using cardiopulmonary bypass has been shown in adults to be modified by the components of the pump priming fluid. This effect is likely to be more significant in children. Data on 29 children less than 15 kg body weight are presented. Patients were randomised to receive a prime containing one of three crystalloid priming fluids: 100% Hartmann's (H), 50% Hartmann's + 50% 5%-Dextrose (HD), or 100% Plasmalyte 148 (P). The remainder of the prime was CPD stored blood and the prime was buffered with sodium bicarbonate. Severe hyperglycaemia 22.4 +/- 1.3 mmol/l occurred during bypass in the HD group but moderate hyperglycaemia occurred in the other prime groups. Hyperlactataemia occurred in all prime groups during bypass and was highest in the H prime group at 3.9 +/- 0.4 mmol/l. These changes in intermediary metabolites were only partly explained by the crystalloid components of the priming fluid. A subsiduary study revealed the important contribution of CPD stored blood to those intermediary metabolite concentrations. Therefore, the well recognised changes in intermediary metabolites as components of the metabolic response to surgery, namely hyperglycaemia and hyperlactataemia were augmented by the composition of the priming fluids. In addition, CPD stored blood and the sodium bicarbonate buffer increased the sodium concentration of the prime to hypernatraemic levels in both the H and P groups which caused an increase in sodium concentration during bypass. Therefore important changes during bypass occur as a direct result of the individual components of the priming fluid. These changes may result in osmolal flux, hyperglycaemia and hyperlactataemia, all of which have been reported to be potentially harmful.

Blood Glucose↗

Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series.

Recombinant human (rh) interleukin-3 (IL-3) stimulated the proliferation and differentiation of erythroid, granulocyte, macrophage, eosinophil (Eo), and mixed colonies as well as megakaryocytes from human bone marrow cells. rh IL-3 was a weaker stimulus than rh granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 14 myeloid cell colonies. At day 7 of incubation, rh IL-3 stimulated a few G, M, and Eo clusters but no colonies. This loss of responsiveness of myeloid cells to rh IL-3 was accentuated with further differentiation of the cells. rh IL-3 stimulated very few or no clones after five-day incubation with enriched promyelocytes and myelocytes, whereas rh GM-CSF was an efficient stimulus. Responsiveness to rh IL-3 was completely lost in postmitotic mature neutrophils. Incubation of these cells with rh IL-3 did not result in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells or superoxide anion production after stimulation with formyl-methyl-leucyl-phenylalanine (FMLP), although they could be stimulated by rh GM-CSF. In addition, preincubation of neutrophils with different concentrations of rh IL-3 failed to increase or decrease their response to rh GM-CSF. In contrast to neutrophils, mature Eos could be stimulated by rh IL-3 to kill antibody-coated tumor cells. These results show that cells of the neutrophilic myeloid series lose their responsiveness to h IL-3 as they differentiate and suggest that although h IL-3 may be an important therapeutic agent to use for hematopoietic regeneration in vivo, the lack of stimulation of mature neutrophil function makes it an unlikely sole candidate as adjunct therapy for treatment of infectious diseases.

Antibody-Dependent Cell Cytotoxicity↗

Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis.

In a double blind noncrossover study, dietary supplementation with fish oil (18 g/day), was compared with an olive oil supplement over a 12-week period in patients with rheumatoid arthritis receiving established conventional therapies. An improvement in tender joint score and grip strength was seen at 12 weeks in the fish oil treated group but not in the olive oil treated group. The more subjective measures of mean duration of morning stiffness and analogue pain score improved to a similar extent in both groups, although statistical significance was only achieved in paired analyses in the olive oil treated group. Production of leukotriene B4 by isolated neutrophils stimulated in vitro was reduced by 30% in the fish oil treated group and unchanged in the olive oil treated group.

Adult↗

Coarctation of the aorta with arch hypoplasia: improvements on a new technique.

The association between coarctation and arch hypoplasia can be difficult to manage surgically. Several complex techniques have been designed for its management (e.g., resection of coarctation with either retrograde subclavian flap or carotid subclavian angioplasty). However, residual gradients are frequent. Recently, a new technique of extensive end-to-end anastomosis was described that has the advantages of leaving the left subclavian artery intact and resulting in a wide anastomosis. The present report details a modification of this technique, which more extensively dissects the arch branches and clamps the aortic arch almost 50% of the way across the innominate branch. The descending aorta is mobilized to the diaphragm. Anastomosis is completed with 7-0 PDS or polypropylene sutures. This type of repair has been performed in 7 patients, with a maximum residual gradient at the end of the procedure of 5 mm Hg. These modifications represent an excellent option to the surgeon in the management of this difficult clinical entity.

Aorta, Thoracic↗

Ocular changes in the mouse embryo following acute maternal ethanol intoxication.

The development of the eye was investigated in the mouse embryo following a single administration of ethanol plus [3H]thymidine to the dam on day 13 of gestation. After 1 hr there was no difference in the number of labelled cells/100 micron 2 in the neural layer of the retina compared to controls, but there was an alcohol-related reduction in labelling density. After 24 hr there was an increase in the numbers of both pyknotic cells and mitotic figures, breaks occurred in the inner surface of the retina and cell debris was being extruded into the posterior chamber. At 48 hr the increase in pyknotic cells persisted, but there was less evidence of cell debris and the borders had been repaired. The estimated cell cycle time in the neural progenitor cells following maternal alcohol administration was increased 7-fold compared to controls. Morphometric analysis revealed that after 48 hr there were significant alcohol-related reductions in the width and depth of the eye, in the thickness of the neural layer and in the interocular distance. It appears that many of the ophthalmic abnormalities reported in human fetal alcohol syndrome can be produced in the mouse embryo following a single episode of acute maternal intoxication during a critical period of ocular ontogeny, and that they evolve primarily from disturbances in the normal patterns of recruitment and loss of neural progenitor cells in the developing retina.

Animals↗

Diabetes mellitus and open heart surgery. A simple, practical closed-loop insulin infusion system for blood glucose control.

A method, based on bedside determinations of blood glucose by nursing staff, was designed to control the administration of insulin to diabetic patients during and following open heart surgery. A computer-controlled intravenous infusion pump was used to deliver the insulin. Excellent control of the hyperglycaemia normally associated with open heart surgery was achieved, with 84 percent of measured blood glucose values falling within 2 mmol/litre of the target value of 6 mmol/litre. The method proved to be simple, effective, and safe.

Adult↗

The metabolic load of stored blood. Implications for major transfusions in infants.

Plasma electrolyte, intermediary metabolite, and hormone concentrations were measured in samples of 110 units of citrate phosphate dextrose blood being used for clinical transfusions. The most important changes from the physiological range were in sodium, potassium, glucose, and lactate concentrations. Mean sodium concentrations fell from 170 mmol/l at the beginning of storage to 156 mmol/l at the end and mean potassium concentrations rose from 7 mmol/l to 25 mmol/l. Glucose had a mean concentration of 20 mmol/l at the beginning of storage and had only fallen to 15 mmol/l at the end. Mean lactate concentrations increased from 7 mmol/l at the beginning of storage to 25 mmol/l at the end. Many samples had cortisol, insulin, and growth hormone concentrations within the physiological range. Citrate phosphate dextrose blood contains a large substrate load that changes during storage and that should be taken into account when infants are transfused large volumes of blood. The strong correlation coefficients with duration of storage for sodium, potassium, and lactate (-0.71, 0.91, and 0.90, respectively) indicate that concentrations of these substrates can be predicted within a narrow range if the duration of blood storage is known.

Blood Glucose↗

The ontogeny of placental Na+-K+ ATPase in the mouse and its impairment by ethanol.

We have investigated the normal ontogeny of Na+-K+ ATPase in the mouse placenta and the possibility that impairment in placental transport capacity, as reflected in reductions in NA+-K+ ATPase activity, is associated with alcohol-related embryonic growth restriction. We have demonstrated that over the normal course of pregnancy there is a dramatic increase in placental NA+-K+ ATPase activity which occurs in concert with the embryofetal body growth spurt. Maternal ethanol administration during the early period of placental enzymogenesis (days 7-9) resulted in a significant reduction (up to 40%) of placental Na+-K+ ATPase activity on day 15. Both the severity and the frequency of the reduction were dose dependent. The effect was associated with significant reductions in embryonic body and brain weight but no change in body length or prenatal mortality. Incubation of term placental fragments for 2 h in increasing concentrations of ethanol resulted in a comparable reduction in enzyme activity. Our studies demonstrate that direct ethanol exposure produces a reduction of placental Na+-K+ ATPase activity, that exposure during the early stages of enzymogenesis results in persistent reductions in Na+-K+ ATPase activity in the mature placenta, and that this effect is associated with deficits of embryonic body and brain growth. A direct causal relationship has not been proven; however, it is conceivable that the correlation between reduced placental Na+-K+ ATPase activity and impaired embryofetal growth reflects a common causal pathway.

Animals↗

Practical closed-loop insulin infusion.

A method was designed to control the insulin infusion given to diabetic patients at the time of open-heart surgery. Excellent control of the blood glucose concentration was achieved, with eighty-four percent of blood glucose values falling between 4 and 8 mmol/l.

Adult↗

The effects of four different crystalloid bypass pump-priming fluids upon the metabolic response to cardiac operation.

The crystalloid solutions used to prime cardiopulmonary bypass pumps frequently contain metabolically active substrates. However, there is a lack of controlled studies to investigate the metabolic response to cardiac operations using different pump primes. We have carried out a prospective, randomized study of 24 patients divided into four groups, each group receiving a different crystalloid prime. The primes contained glucose, lactate, glucose and lactate, or neither glucose nor lactate. Using identical anesthetic, surgical, and perfusion techniques, we estimated the metabolic response to cardiac operation in all patients by frequent blood sampling for measurement of hormone (insulin, glucagon, cortisol, and growth hormone) and metabolite concentrations (glucose, lactate, pyruvate, glycerol, alanine, and 3-hydroxybutyrate) from the day before operation to the seventh postoperative day. The results demonstrated that, after 4 hours postoperatively, the endocrine and metabolic response to cardiac operation was unaffected by the nature of the priming fluid. However, major endocrine and metabolic changes occurred before that time, which were related directly to the glucose and lactate contents of the prime. Very high concentrations of both glucose and lactate were observed at the end of bypass if they were induced in the prime. Given the known dangers of hyperglycemia in cerebral ischemia and the potential gluconeogenic effects of infused lactate, we suggest that glucose-free and lactate-free primes be employed in the extracorporeal circuit.

3-Hydroxybutyric Acid↗

Primary adenocarcinoma of the gastro-oesophageal junction in childhood. A case report.

Primary adenocarcinoma of the gastro-oesophageal junction, oesophagus or stomach is very rare in childhood (3, 5). Within that small patient population, dysphagia is an unusual presenting feature. We wish to report such a condition, occurring in a 14-year-old boy, to emphasise that dysphagia in childhood should always be taken seriously.

Adenocarcinoma, Mucinous↗

Heart transplantation in an infant with rhabdomyoma.

Rhabdomyoma is the most common primary cardiac tumor in infants and children and is often associated with tuberous sclerosis. Surgical resection may be indicated and, if so, is usually curative. We describe a rhabdomyoma in an infant who presented with severe myocardial ischemia necessitating orthotopic heart transplantation.

Diagnosis, Differential↗

Heart transplantation for Barth syndrome.

Barth syndrome is an X-linked recessive disorder comprising dilated cardiomyopathy, muscular hypotonia, and cyclical neutropenia. Affected children usually die during infancy as a consequence of septicemia, cardiac failure, or both. We report a patient with Barth syndrome who underwent successful heart transplantation.

Cardiomyopathies↗