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Biomedical subjects

R Hadley

Publications and source records attributed to R Hadley.

15 recordsLinked to original sources
PubMed2001

Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity.

Considerable evidence supports a Ca(2+) dysregulation hypothesis of brain aging and Alzheimer's disease. However, it is still not known whether (1) intracellular [Ca(2+)](i) is altered in aged brain neurons during synaptically activated neuronal activity; (2) altered [Ca(2+)](i) is directly correlated with impaired neuronal plasticity; or (3) the previously observed age-related increase in L-type voltage-sensitive Ca(2+) channel (L-VSCC) density in hippocampal neurons is sufficient to impair synaptic plasticity. Here, we used confocal microscopy to image [Ca(2+)](i) in single CA1 neurons in hippocampal slices of young-adult and aged rats during repetitive synaptic activation. Simultaneously, we recorded intracellular EPSP frequency facilitation (FF), a form of short-term synaptic plasticity that is impaired with aging and inversely correlated with cognitive function. Resting [Ca(2+)](i) did not differ clearly with age. Greater elevation of somatic [Ca(2+)](i) and greater depression of FF developed in aged neurons during 20 sec trains of 7 Hz synaptic activation, but only if the activation triggered repetitive action potentials for several seconds. Elevated [Ca(2+)](i) and FF also were negatively correlated in individual aged neurons. In addition, the selective L-VSCC agonist Bay K8644 increased the afterhyperpolarization and mimicked the depressive effects of aging on FF in young-adult neurons. Thus, during physiologically relevant firing patterns in aging neurons, postsynaptic Ca(2+) elevation is closely associated with altered neuronal plasticity. Moreover, selectively increasing postsynaptic L-VSCC activity, as occurs in aging, negatively regulated a form of short-term plasticity that enhances synaptic throughput. Together, the results elucidate novel processes that may contribute to impaired cognitive function in aging.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes.

Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients. However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity. A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model. All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug. These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration.

Animals↗
PubMed1998

Knotted ureteral stent: a minimally invasive technique for removal.

PURPOSE: We describe a useful technique for untying a knotted ureteral catheter. MATERIALS AND METHODS: An Amplatz super stiff guide wire was advanced through the lumen of the stent and with uniform force the knot was untied. RESULTS: The knot was untied and the stent was removed. A nephrostomy tube or other more invasive techniques for removal were avoided. CONCLUSIONS: An Amplatz super stiff guide wire passed retrograde via the ureteral stent lumen should be considered as a valid alternative to percutaneous removal of a knotted ureteral stent.

Aged↗
PubMed1995

Electrovaporization of the prostate: new technique for treatment of symptomatic benign hyperplasia.

This pilot study evaluated the efficacy of a newly configured roller electrode (Circon/ACMI Vaportrode) in the treatment of symptomatic benign prostatic hyperplasia. The electrode is used with a cutting current and an otherwise-standard (ACMI) resectoscope. Thirty-four patients with significant symptoms of bladder outlet obstruction were treated and evaluated. Among them, 20 were in urinary retention, and 14 had moderate to severely symptomatic bladder outlet obstruction. Thirty-three patients are voiding and available for follow-up. The other patient has not returned. All available patients have shown both subjective and objective voiding improvement. In the evaluable patients, the AUA Symptom Index decreased from a mean of 26 to 12. The mean postoperative peak urinary flow rate was 13 mL/sec. Complications occurred in three patients (post-operative bleeding in one, urinary retention in two). Electrovaporization allowed definitive treatment of bladder outlet obstruction with subjectively better visibility than transurethral resection (TURP). The potential for fluid and electrolyte shifts and resulting complications appears to be less than with TURP. Further study of this technique appears warranted.

Aged↗
PubMed1995

Where the reforms did not reach: doctors as front line managers.

The importance of the behavioral dimension of the management of front line teams in the health service has been neglected both in the training of doctors and in the recent reforms of the health service. Drawing on three case studies carried out by doctors, explores the influence of the level of understanding of behavioral factors in determining the effectiveness or ineffectiveness of management at this level. Concludes by considering some implications of the discussion for giving a more central place to these factors in the selection, training and promotion of doctors.

Behavior↗
PubMed1993

Sodium/calcium exchanger in heart muscle: molecular biology, cellular function, and its special role in excitation-contraction coupling.

The Na/Ca exchanger has been examined with respect to its molecular biology, its cellular function, and its role in excitation-contraction coupling. The Na/Ca exchanger plays a central part in excitation-contraction coupling, setting the level of sarcoplasmic reticular calcium and contributing to the triggering of sarcoplasmic reticular calcium release. Functional biophysical studies with isolated single cells and caged calcium provide evidence that the Na/Ca exchanger works as a two step sequential transporter. In the heart there are about 250 exchangers.mu-2, operating at a turnover rate of up to about 2500.s-1, with the exchanger carrying -2.56 charges under normal conditions. The Na/Ca exchanger has been recently cloned from diverse mammalian species and several tissues and is largely conserved. It is clear, however, that the function of the Na/Ca exchanger is different in the different tissues. Thus work is in progress in several laboratories, including ours, to determine how the Na/Ca exchanger achieves its tissue specific function. Several modulatory motifs have been seen in studies of the exchanger that may explain some of the tissue specific differences. Interestingly the modulation of the Na/Ca exchanger (for example, by protons, sodium, calcium, ATP, calmodulin) seems to arise from interactions with the intracellular loop.

Animals↗
PubMed1989

The NHS reforms. Conditions for successful change.

The NHS Review has proposed the most radical organisational change in health care since the inception of the service itself in 1948. Yet, the problems entailed in gaining acceptance for reforms of such magnitude are scarcely touched on in the white paper. The scale and strength of opposition which the proposals have subsequently met within the NHS have shown clearly that the issue of the management of change is likely to be central in the acceptance or otherwise of the proposals and subsequently their success or failure. Donald Forster and Roger Hadley outline the framework within which the issues posed by change can be analysed and assessed. In keeping with the government's preference for a management perspective, they emphasise insights from the literature on the management of change rather than the detail of the white paper.

Organizational Innovation↗
PubMed1986

High affinity and low affinity ouabain binding sites in the rat heart.

Ventricular muscle of rat heart has two classes of receptors which are responsible for the positive inotropic effect of ouabain. Low affinity receptors are apparently related to Na+, K+-ATPase. To determine if high affinity receptors are also sarcolemmal Na+, K+-ATPase of muscle cells, their characteristics were examined. Binding of [3H]ouabain to the high affinity binding site required ATP in the presence of Mg2+ and Na+, was stimulated by Na+ in the presence of Mg2+ and ATP, and was inhibited by K+. Digoxin, digitoxin and cassaine all inhibited [3H]ouabain binding to the high affinity site. Cassaine was about an order of magnitude less potent than the glycosides. These results indicate similarities in high affinity ouabain binding sites in ventricular muscle of rat heart and Na+, K+-ATPase obtained from other sources. Destruction of sympathetic nerve terminals with 6-hydroxydopamine failed to affect the high affinity ouabain binding sites indicating that high affinity sites do not represent the Na+, K+-ATPase in sympathetic nerve terminals. Labeling of Na+, K+-ATPase from [gamma-32P]ATP indicates that high affinity ouabain binding sites account for 25% of the total enzyme molecules present in ventricular muscle of rat heart.

Animals↗
PubMed1985

Effects of calcium and verapamil on normal and tumor murine leukocytes.

Although no differences in membrane stabilization by calcium were noted between leukemic (P-388) and normal murine leukocytes, tumor cells were shown to be more resistant to damage by ethanol but not by desmethylchlorpromazine. Furthermore, verapamil protected tumor cells but not normal cells against the disruptive effect of desmethylchlorpromazine but not that of ethanol. The protective action of verapamil was evident even in the absence of calcium. Thus leukemic cells appear to be altered so that the effects of certain membrane active agents are changed but the membrane stabilizing function of calcium is normal.

Animals↗