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Biomedical subjects

S Redmond

Publications and source records attributed to S Redmond.

At least 19 recordsLinked to original sources

Myocardial enlargement in defective heart development.

BACKGROUND: The cardiac neural crest (neural crest extending from the mid-otic placode to the caudal region of somite 3) provides ectomesenchymal cells that contribute to aortic arch development and are essential for aortico-pulmonary septation of the outflow tract. Bilateral ablation of the cardiac neural crest in the chick embryo, prior to migration, leads to aortic arch anomalies and failure of septation of the cardiac outflow tract, which produces a severe defect known as persistent truncus arteriosus (PTA). Altered hemodynamics resulting from abnormal aortic arch artery development and PTA and other unknown factors related to the absence of neural crest, are likely to alter the developmental history of the myocardium. METHODS: In this study the wet and dry weights of ventricles and whole embryos, the total number of myocytes per ventricle and the myocyte density (number of myocytes per unit volume of ventricular myocardium) were compared in control (unwindowed eggs), sham-operated and cardiac neural crest ablated chick embryos at day 11 of incubation. RESULTS: We found that the wet and dry weights of ventricles from hearts with PTA were not different from normal hearts in control and sham-operated embryos. However, the embryos with PTA weighed less than embryos with normal hearts. Thus, the ventricle to embryo weight ratios were greater in embryos with PTA compared to control and sham-operated embryos for both wet (14 and 20%, respectively) and dry (30 and 59%) weights. The data further implied that more water was present with respect to body weight in comparison with sham-operated and control embryos which indicated that the embryos with PTA were edematous. The total number of myocytes and the number of myocytes per unit volume were not different when comparing sham-operated with PTA. Further, there was no indication that the myocardium from hearts with PTA was abnormal despite the small size and edema of the embryos. CONCLUSIONS: It appears that hemodynamic stresses, resulting from the structural defects produced by neural crest ablation, are insufficient to increase heart growth, although cardiac function is depressed as evidenced by edema and failure of the embryo to thrive.

Animals

Diabetes and alternative medicine: cause for concern.

'Alternative' medicines are becoming increasingly popular, and in this paper we describe our experience with alternative approaches to orthodox diabetes management. Four patients with insulin-dependent diabetes reduced or stopped their insulin in favour of therapeutic approaches including prayer, faith healing, unusual diets, and supplements of vitamins and trace elements. This resulted in ketoacidosis in three, in one case life-threatening; and weight loss and hyperglycaemia in the other. One patient developed serious retinopathy. Additionally, eight other types of alternative diabetic treatment are described, not as far as we know associated with such serious complications. These include homeopathy, reflexology, meditation, herbal treatment, 'cellular nutrition', 'subconscious healing', 'pearl therapy' (drinking milk in which pearls have been boiled) and 'astrotherapy' (typing pieces of coral around the arm). Diabetes is a chronic incurable disease, for which modern treatments remain somewhat unsatisfactory. It is therefore perhaps not surprising that some patients seek alternative treatments with more attractive claims. Diabetes health professionals need to be aware of the potential dangers associated with some of these treatments.

Adult

Insulin treatment, time-zones and air travel: a survey of current advice from British diabetic clinics.

To investigate current advice given to insulin-treated diabetic patients undertaking international flights crossing time-zones, we have conducted a survey of UK physicians running diabetic clinics. Consultants were asked to give the general advice they would give to travellers on twice-daily short- and intermediate-acting insulins in four different flight situations: westward London to New York (morning and evening departures) and eastward Manchester to Singapore (morning and evening departures). Response rate was poor (37%). Six percent of replies were unhelpful (e.g. 'ring the BDA', 'carry on as usual'), and 14% liable to cause hypoglycaemia. Thirteen percent advocated change to a 'basal-bolus' system of insulin administration. The rest used variants of additional insulin for westward flights and reduced flights eastward. There was great variation in advice, and many regimens were excessively complicated. We recommend simple individualized advice, without attempts at over-zealous glycaemic control during travel. Local arrival and departure times may fit in easily with insulin and meals at standard times before and after flying, and little or no dosage alteration may be needed.

Aviation

A survey of UK diabetic pregnancy management.

The provision of care and current management strategies for diabetic pregnancy in the United Kingdom were assessed by canvassing British diabetologists. Questionnaires were sent to 376 Consultant Physicians known to have an interest in diabetes, in 239 Health Districts. The response rate was 52% providing information from 182 (76%) Districts. In 66 (36%) Districts, there was an existing combined diabetes/obstetric clinic, with median annual caseloads of 13 (range 1-200) patients. Preconception counselling was offered in 22 clinics. In 153 (84%) of the clinics, the standard WHO diagnostic criteria for diabetes were applied to pregnant patients and 149 (97%) of the clinics using WHO criteria treated patients with 'Impaired Glucose Tolerance' as if they were overtly diabetic. Reflectance meters for home monitoring were employed in 119 (65%) clinics. Target pre-meal blood glucose values were less than or equal to 6.0 (range 3.0-12.0) mmol l-1 (n = 172) and post-meal less than or equal to 8.0 (5.0-10.5) mmol l-1 (n = 139). Insulin was introduced when blood glucose values exceeded 7.0 (5.0-12.0) mmol l-1 (n = 162) pre-meal or 9.0 (5.5-15.0) mmol l-1 (n = 129) post-meal. No unit used oral hypoglycaemic agents during pregnancy. Sixty percent of respondents were unable to provide accurate fetal loss/perinatal mortality rates, usually due to lack of recorded data. Where data were available, fetal loss was almost always intra-uterine. Only 78 (43%) centres allowed pregnancy to progress to term.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Selective inhibition of primitive hemopoietic colony-forming cells by an extract from normal marrow: comparison with transforming growth factor-beta.

An extract from normal bone marrow (NBME) which inhibits proliferation of spleen colony-forming units CFU-S selectively inhibits interleukin 3 (IL-3)-driven colony formation by primitive hemopoietic progenitors. This activity is distinct from transforming growth factor-beta (TGF beta), which also inhibits development of primitive progenitors. There is evidence that the two activities inhibit proliferation of target cells by different mechanisms and that the bone marrow extract has a direct effect on cell cycling, whereas the effect of TGF beta to suppress proliferation is probably indirect.

Animals

The effect of orthostatic hypotension on cerebral blood flow and middle cerebral artery velocity in autonomic failure, with observations on the action of ephedrine.

Cerebral blood flow (CBF) and middle cerebral artery velocity (MCAv) have been measured using 133xenon washout and transcranial Doppler in ten patients with autonomic failure. Four pure autonomic failure and four multiple system atrophy patients behaved similarly: tilting them sufficiently to induce significant orthostatic hypotension without causing syncopal symptoms led to a significant fall in their mean MCAv, but no change in their mean CBF. These findings suggest that cerebral autoregulation is preserved in autonomic failure, orthostatic hypotension resulting in a reactive vasodilatation which lowers MCAv, reduces vascular resistance, and maintains CBF. Ephedrine helped to correct the orthostatic hypotension, but had no direct effect on CBF. Two siblings with orthostatic hypotension secondary to dopamine-beta-hydroxylase deficiency also had preserved cerebral autoregulation, but ephedrine led to paradoxical hypotension in these patients.

Adult

The effects of TGF beta on haemopoietic cells.

Transforming growth factor beta (TGF beta) suppresses the growth of differentiation inducible, murine IL-3-dependent multipotential cell lines but has no growth inhibitory effect upon an IL-3-independent (leukaemic) cell line arising from one of them, nor on IL-3-dependent cell lines that are unable to undergo differentiation. TGF beta inhibits in vitro colony formation by normal multipotential haemopoietic progenitor cells. Bipotential progenitors recruited by GM-CSF are, however, more resistant to the inhibitory effects of TGF beta, whereas progenitors recruited by the lineage restricted factor, M-CSF, are sensitive to the inhibitory effects. These data indicate that responsiveness to TGF beta is differentiation linked and studies with the cell lines suggest that response (or lack of response is not determined solely by levels of expression of TGF beta receptors. Furthermore, the effects of TGF beta 2 on haemopoietic progenitors are very similar to those induced by TGF beta.

Animals

Induction of transforming growth factor alpha expression in mouse mammary epithelial cells after transformation with a point-mutated c-Ha-ras protooncogene.

NOG-8 ras cells are a normal mouse mammary epithelial cell line transfected with a plasmid containing a glucocorticoid-inducible mouse mammary tumor virus long terminal repeat linked to the activated c-Ha-ras protooncogene. After addition of dexamethasone, there is a rapid induction (within 1-3 h) of p21ras protein that is concomitant with a parallel induction of the c-Ha-ras specific mRNA. After 4-6 days of dexamethasone treatment, NOG-8 ras cells are able to grow as colonies in semisolid medium. Between 9 and 12 days of dexamethasone treatment, there is a 5- to 6-fold increase of transforming growth factor alpha (TGF alpha) activity in the conditioned medium from NOG-8 ras cells. A 60-65% reduction in epidermal growth factor cell surface receptors on NOG-8 ras cells also occurs during this time interval. A 3- to 4-fold increase of the expression of a specific TGF alpha mRNA can be detected within 2 days of dexamethasone treatment, preceding the increase in TGF alpha protein found in the conditioned medium. Exogenous TGF alpha is able to stimulate in a dose-dependent fashion the anchorage-dependent and anchorage-independent growth of NOG-8 ras cells to a level comparable to that observed in dexamethasone treated ras-transformed NOG-8 ras cells. These results suggest that the enhanced expression of TGF alpha after induction of an activated ras protooncogene may be necessary for the anchorage-independent growth and subsequent morphological changes and the enhanced growth rate observed in ras-transformed mammary epithelial cells.

Animals

Cerebral blood velocity in subarachnoid haemorrhage: a transcranial Doppler study.

A study examining the utility of transcranial Doppler ultrasound for the determination of cerebral vasospasm following subarachnoid haemorrhage is reported. A control group of 21 patients and a second group of 20 patients suffering from subarachnoid haemorrhage or aneurysm and a group of 26 with other intracranial pathologies were studied. The Doppler flow velocity (DFV) was significantly higher when vasospasm was present. If it was higher than 100 cm/s, the patients were found to have vasospasm in 80% of cases. If Doppler flow velocity was below 100, less than 10% had spasm. Doppler flow velocity was not found to increase following craniotomy in patients not suffering from subarachnoid haemorrhage. In subarachnoid haemorrhage patients there was a trend to increased Doppler flow velocity especially in patients who developed neurological deficit. Doppler flow velocity and Initial Slope Index by xenon clearance (ISI) were not found to correlate with clinical grade. The ISI/DFV quotient (which can be shown mathematically to be related to vessel diameter) was found to correlate well with clinical grade. In this largely post-operative group, absolute levels, or rate of change of Doppler flow velocity could not be shown to be related to the onset or existence of neurological deficit.

Adult

Comparison of fast flow and initial slope index values for cerebral blood flow following subarachnoid haemorrhage.

Forty five patients with subarachnoid haemorrhage proved by lumbar puncture underwent serial measurements of cerebral blood flow and central conduction time. When the initial slope index (ISI) value for cerebral blood flow is considered there is a clear relationship between reduction of cerebral blood flow and deteriorating clinical grade. This relationship is not so clearly demonstrated using the fast flow (f1) value for cerebral blood flow. When cerebral blood flow is compared to central conduction time those patients with a central conduction time longer than 6 X 4 ms have a significantly lower CBFisi but not a significant lower CBFf1. Furthermore, using the ISI value, there is a linear relationship between the fall in cerebral blood flow and the lengthening of CCT below a threshold blood flow of about 35 ml/100 g/min. This relationship is not demonstrated with the CBFf1 value. It therefore appears that the ISI value for cerebral blood flow shows a greater correlation between clinical and electrophysiological events than the f1 value.

Adolescent

Monoclonal antibodies for purification and assay of IL-2.

Mouse monoclonal antibodies (Mac 002 and Mac 003) raised against recombinant human Interleukin-2 (rec IL-2), were developed for use as assay and purification reagents. In the Immunoradiometric assay, (IRMA), 125I-Mac 002 is used as tracer, with sheep polyclonal anti-rec IL-2 on the solid phase. This reliably measures rec IL-2 in the range 3-1000 ng/ml. The assay measures natural IL-2 with a lower sensitivity. For some samples of IL-2, the amount detected by IRMA is greater than expected from the biological assays, presumably because there are IL-2 molecules with antigenic, but not biological activity. This is a possible source of variation in the specific activities observed in different preparations of of IL-2. In the purification reagent, Mac 003 is immobilised on sepharose CL-4B to purify recombinant IL-2 from less than 1% in an E. Coli extract, to greater than 90% purity, in a single step with greater than 80% yield.

Animals

The glomerular hyperfiltration of diabetes is not associated with elevated plasma levels of glucagon and growth hormone.

Plasma concentrations of glucagon, growth hormone and glucose were measured hourly during an ordinary treatment day in 11 Type 1 (insulin-dependent) diabetic patients with high glomerular filtration rate, 11 Type 1 diabetic patients with normal glomerular filtration rate matched for age, diabetes duration and sex, and five healthy control subjects, simultaneously with the measurement of the glomerular filtration rate using 51Cr EDTA clearance. Plasma glucagon profiles were not statistically distinguishable (p = 0.49) from control values in either group, although they were somewhat lower in the hyperfiltering group. Plasma growth hormone values were higher than control (p = 0.07) in both diabetic groups, but were not different between these two groups (p = 0.94). All indices of glycaemic control (glycosylated haemoglobin, urinary glucose excretion, and plasma glucose concentration) were higher in the hyperfiltering group, although no single index reached statistical significance. No correlations between concentrations of these substances and glomerular filtration rate were found. Elevated plasma concentrations of glucagon and growth hormone do not characterise those diabetic patients with high glomerular filtration rate.

Adolescent

A comparative study of the portable regional CBF monitor and the portable mean hemispheral CBF monitor: advantages and disadvantages in clinical practice.

CBF determination can provide additional valuable information which can be used in clinical practice to enhance our capabilities in patient evaluation. The initial techniques requiring intraarterial injections have been largely replaced by the noninvasive inhalation and intravenous methods. The recent refinement of microcomputers and the development of portable CBF monitors have made CBF determination a nontraumatic, dependable and easily repeatable examination at the patient's bedside. In this communication we compare a portable region CBF monitor and a portable mean hemispheral CBF monitor; we study their advantages and disadvantages in clinical practice. Emphasis is placed on the practical characteristics and the information provided by each monitor and its contribution to patient evaluation. Illustrative cases are presented.

Brain