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Biomedical subjects

S T McCarthy

Publications and source records attributed to S T McCarthy.

At least 19 recordsLinked to original sources
PubMed1997

Linear transduction of natural stimuli by dark-adapted and light-adapted rods of the salamander, Ambystoma tigrinum.

1. We examined signal, noise and response properties of salamander rod photoreceptors by measuring: (a) the circulating current of rods which were adapted to darkness and to a wide range of backgrounds; (b) contrasts of natural environments; (c) the effect of adaptation on the linear response range of rods; and (d) the behaviour of rods responding to dynamically modulated stimuli having a range of contrasts found in nature. 2. In the dark, the circulating current contained two noise components analogous to those described in toad. A discrete noise component consisted of events occurring at a rate of 1 event per 32 s (21 degrees C) and had a variance of 0.036 pA2. A continuous noise component contributed 0.022 pA2 to the dark current, roughly equal to the discrete noise variance. 3. Exposure to a wide range of steady backgrounds (suppressing up to 80% of the circulating current), elicited a sustained fluctuating photocurrent having a power spectrum which resembled those of single photon responses and was consistent with the linear summation of single photon events; this indicates that the primary source of noise in the current is caused by the light. 4. Eighty-nine per cent of the contrasts (C) measured in natural environments had magnitude of C < 50%, where C = magnitude of I - Imean/magnitude of Imean. The linear response range elicited by brief flashes expanded with brighter backgrounds, well-encompassing flash contrasts of 100%. 5. Dynamically modulated stimuli and incremental flashes having contrasts similar to those in natural scenes elicited small currents which deviated by a few picoamps about the mean and the transfer functions computed from each type of stimulus-response pair closely corresponded to one another. These results indicate that in natural environments, rods behave as linear small-signal transducers of light.

Adaptation, Ocular↗
PubMed1996

Light-dependent control of calcium in intact rods of the bullfrog Rana catesbeiana.

1. Using Fura-2, we measured cytosolic free calcium concentrations in rod outer segments of the bullfrog (Rana catesbeiana) under a wide range of steady-state, adapting light intensities. We also measured rod circulating currents under the same adapting conditions. 2. Both the steady-state cytosolic free calcium concentration and the steady-state circulating current were halved by background lights that isomerized approximately 100 rhodopsin molecules per rod per second. A just-measurable reduction in calcium was evoked by a background 1/10 as bright. The steady-state calcium concentration and the steady-state circulating current were proportional to each other over the full range of intensities tested, the brightest of which suppresses the circulating current by 75% and reduces flash sensitivity by about two orders of magnitude relative to the rods' sensitivity in darkness. 3. Additional experiments, in which the Na+:Ca2+,K+ exchanger in the rod outer segment was inactivated while maintaining intracellular calcium at physiological levels, demonstrated that steady-state calcium concentrations in the outer segment are set only by the influx of calcium through the light-sensitive channels and its efflux via the Na+:Ca2+,K+ exchanger. We found no measurable light-induced release of calcium from internal stores and no evidence of any other calcium flux between the cytosol and intracellular compartments. 4. Taken together, these findings lead us to conclude that over the normal operating range of the rod, the selectivity of the cGMP-gated channels for calcium does not change as a result of background illumination. 5. Our data also suggest that a major role of calcium-dependent cGMP synthesis by guanylyl cyclase is to stabilize both the circulating current and the cytosolic free calcium concentration in darkness. This would minimize the dark noise of the rod and thereby increase the reliability with which dim stimuli can be detected in the dark-adapted state.

Animals↗
PubMed1996

Dynamic, spatially nonuniform calcium regulation in frog rods exposed to light.

1. In intact rods of the bullfrog, Rana Catesbeiana, that were loaded with Fura-2 by incubation, we made high-resolution measurements of Na:Ca,K exchange currents and measured cytosolic free calcium concentrations during exposure to steps of illumination. The calcium dynamics we observed are indicative of unmanipulated rods because Fura-2 had little effect on calcium buffering within the outer segment. 2. In the dark, the total concentration of calcium within the outer segment, determined by integrating the exchange current, was near 50 microM. The free calcium concentration in darkness was 200-400 nM, indicating that > of = 99% of the internal calcium was bound to buffer molecules or equivalently sequestered. 3. During saturating illumination, the concentration of free calcium near the membrane (assayed by the exchange current) fell more rapidly than the space-averaged free calcium concentration (measured with Fura-2), but both had time courses that were best described by a sum of three exponential terms. The time constants were the same for each assay, but the weighting factors were different. 4. The relationship between the exchange current and space-averaged calcium concentration is consistent with significant concentration gradients within the outer segment resulting from high buffering power, diffusional restrictions, and the fact that all net gain and loss of calcium occurs at the membrane. The data further indicate that effective buffering, and hence calcium mobility, is not uniform within the outer segment. 5. Calcium kinetics were independent of the calcium concentration, indicating that the dominant buffers effectively have a low affinity for calcium (KD >> [Ca2+]dark free). 6. The dynamics of calcium changes and of exchange currents evoked by saturating and nonsaturating illumination are completely predictable from changes in the circulating current. Calcium and current are related by a linear transformation, indicating that calcium fluxes within the outer segment are passive and that buffers equilibrate rapidly. 7. Although calcium concentrations change slowly with respect to changes in the circulating current, both measured and calculated calcium dynamics are well correlated with changes in light adaptation. Responses to test flashes depended weakly on the detailed time course of the adapting stimulus but strongly on the free cytosolic calcium concentration at the time the test flash was delivered.

Adaptation, Ocular↗
PubMed1994

Free calcium concentrations in bullfrog rods determined in the presence of multiple forms of Fura-2.

We employed the fluorescent calcium indicator Fura-2, loaded into intact retinas of the bullfrog Rana catesbeiana, to measure free calcium concentrations in the rod outer-segment cytosol. We determined that traditional methods of calculation yielded erroneous values of calcium. This error results from the presence of at least two distinct pools of Fura-2 in rod outer segments. Application of manganese quenches each pool, but quenching occurs at different rates. Using this fact, we show that the pools can be isolated by brief exposure to manganese and examined separately. One of these pools has the same fluorescent properties as the free salt of Fura-2 we use in our in vitro calibrations. The other source of fluorescence has more unusual properties. Although insensitive to calcium concentrations in the physiological range, it contributes significant anomalous fluorescence when cytosolic free calcium concentrations are elevated by application of IBMX. Nevertheless, the experimentally isolated, classic pool of Fura-2 is well behaved and allows us to calculate calcium concentrations relative to the Kd of Fura-2 by the usual ratio method. We show that when rods are exposed to saturating light, the free calcium concentration in their outer segments falls to a level not significantly different from zero within 20-30 s.

Animals↗
PubMed1990

A placebo-controlled crossover study of ketanserin in elderly hypertensive patients.

The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly, and it is in this group of patients that the maximum benefit of treatment might be expected. The present study was designed to study in detail the efficacy and tolerability of ketanserin in an elderly population. Seventeen elderly (greater than 70 years) patients with a lying systolic blood pressure of 160 mmHg and/or a diastolic blood pressure of greater than or equal to 90 mmHg were included in the study. For the 12 patients who completed the study, the mean blood pressure was significantly reduced on ketanserin compared with placebo (p less than 0.001) in the supine and erect positions. The mean net changes in blood pressure after 8 weeks were 21/17 mmHg and 23/16 mmHg erect. Heart rate was also significantly reduced (p less than 0.001) by a mean of 8 beats/min lying and 9 beats/min erect. Analysis of ambulatory 24-hour ECG tapes showed no significant effect of ketanserin on heart rhythms. Ketanserin therapy had no significant effect on routine hematology, plasma electrolytes, biochemistry, or urinalysis. Total exchangeable sodium and potassium and body weight were also unchanged. On ketanserin treatment, the overall quality of life score was significantly improved (p = 0.002; analysis of variance on log transformed data) compared with the placebo phase.

Aged↗
PubMed1989

Geriatric day hospitals: consultant and community units compared.

A consultant-led day hospital in a district general hospital (DGH) was compared with general practitioner-controlled day hospitals in community hospitals (CHs). CHs were more generously provided for their populations, 3.87 compared with 1.38 places per 1000, but less well staffed at 70% of the DGH levels. Patients were similar demographically and in dependence, but differed in some diagnoses; 33% of CH patients were referred for social reasons alone, compared with 2% in the DGH. CH patients received fewer treatment sessions each day, 2.11 compared with 2.55 in the DGH and the difference was mainly in medical input. Median duration of attendance was 332 days in the CH and 92 days in the DGH; the 6-month discharge rate was 67% in the CH and 35% in the DGH, with 48% of patients attending for more than a year in the CH compared with 24% in the DGH. This study suggests that while the DGH unit provides an active service the CH units offer supportive care which largely duplicates that which could be provided more cheaply in day centres.

Aged↗
PubMed1987

Cerebral blood flow increases during insulin-induced hypoglycaemia in type 1 (insulin-dependent) diabetic patients and control subjects.

The effect of insulin-induced hypoglycaemia on cerebral blood flow was examined using the intravenous xenon-clearance technique in 9 patients with Type 1 (insulin-dependent) diabetes (aged 20 to 43 years) and 9 age-matched control subjects before, during and after hypoglycaemia. Cerebral blood flow rose in both groups. The mean basal cerebral flood flow values were not significantly different and during hypoglycaemia mean cerebral blood flow increased by 17% (p = 0.008) in the diabetic patients and by 21% (p = 0.0003) in the control subjects. The results suggest that in young diabetic patients without autonomic neuropathy or microangiopathy cerebral vessels dilate normally in response to hypoglycaemia. The physiological importance of an increase in cerebral blood flow during hypoglycaemia is uncertain; but glucose availability is increased.

Adult↗
PubMed1986

Low-dose subcutaneous heparin in the prevention of deep-vein thrombosis and pulmonary emboli following acute stroke.

Venous thrombo-embolism is a major and often unrecognized cause of morbidity and mortality in patients after acute strokes. Three hundred and five elderly patients were randomly allocated to either control (161) or treatment (144) with 5000 units calcium heparin subcutaneously 8-hourly for two weeks. A reduction in deep-vein thrombosis rate from 72.7% in the control group to 22.2% in treatment patients was achieved. In patients who died (84), post-mortem examination to look for pulmonary emboli was performed in 71. Comparison between treated and untreated patients showed significantly fewer deaths and pulmonary emboli in the treated group. Most of the beneficial effect on mortality was seen in patients with lighter strokes. When patients with pulmonary emboli at post-mortem were excluded, there was no significant difference in the death rate in treatment (17) and control (14) groups. At post-mortem, 9.9% of the strokes were haemorrhagic (4 in the treatment and 3 in the control group). Low-dose calcium heparin given subcutaneously following acute stroke reduced the number of deep-vein thromboses, pulmonary emboli and deaths without increasing the number of haemorrhagic strokes in this study.

Aged↗
PubMed1986

The influence of chlormethiazole in comparison to thioridazine on body temperature and postural hypotension in healthy adults and healthy elderly volunteers.

Certain drugs used to treat the elderly are known to precipitate hypothermia. In this study, the effects of chlormethiazole and thioridazine in producing postural hypotension were compared. In a study of hypothermia in the elderly the effects of chlormethiazole, thioridazine and lormetazepam were examined. Only three patients showed a postural drop following chlormethiazole, while 11 showed a postural drop following thioridazine. Chlormethiazole showed little variation from the control group in the hypothermia study, while thioridazine and lormetazepam caused a fall in temperature. For behaviour control in the elderly and for a short course as a hypnotic, chlormethiazole seems to be safer than thioridazine or lormetazepam.

Adult↗
PubMed1982

Body fluid, electrolytes and diuretics.

The results of a series of studies on body fluid, electrolytes and diuretics are discussed. The findings to date indicate that the sex difference between mean potassium plasma levels in men and women is preserved into old age. Contrary to previous suggestions, there would appear to be no transient self-correcting hypokalaemia associated with illness uncomplicated by potassium-losing therapy, and treatment with potent loop diuretics, provided it is accompanied by potassium supplementation, does not commonly give rise to hypokalaemia even in elderly patients. It has not been possible so far to confirm the relationship between total exchangeable sodium and blood pressure, as previously suggested in elderly patient with essential hypertension. It has been shown that hypokalaemia of a mild degree is associated with an increase in the number of ventricular ectopic beats. It is suggested, therefore, that the conclusion that mild hypokalaemia (between 3.0 and 3.5 mmol/l) is of no significance, at least as far as elderly patients are concerned, may well be untrue.

Aged↗
PubMed1979

Failure of cerebral autoregulation as a cause of brain dysfunction in the elderly.

Cerebral blood flow in relation to change in arterial pressure was measured in 11 elderly patients with postural hypotension. Seven patients with symptoms showed bilateral or unilateral failure of cerebral autoregulation, while the four asymptomatic patients did not. Variations in cerebral autoregulation would explain why some elderly people with minor falls of systemic arterial pressure develop clinical signs of cerebral ischaemia whereas others with greater falls in blood pressure remain asymptomatic. Elderly patients with impaired autoregulation may be at risk of brain damage from minor falls in blood pressure.

Adult↗