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Biomedical subjects

P Bell

Publications and source records attributed to P Bell.

At least 19 recordsLinked to original sources
PubMed1992

A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.

The cardiac sodium channel alpha subunit (RHI) is less sensitive to tetrodotoxin (TTX) and saxitoxin (STX) and more sensitive to cadmium than brain and skeletal muscle (microliter) isoforms. An RHI mutant, with Tyr substituted for Cys at position 374 (as in microliter) confers three properties of TTX-sensitive channels: (i) greater sensitivity to TTX (730-fold); (ii) lower sensitivity to cadmium (28-fold); and (iii) altered additional block by toxin upon repetitive stimulation. Thus, the primary determinant of high-affinity TTX-STX binding is a critical aromatic residue at position 374, and the interaction may take place possibly through an ionized hydrogen bond. This finding requires revision of the sodium channel pore structure that has been previously suggested by homology with the potassium channel.

Amino Acid Sequence↗
PubMed1992

The McCollough effect as a measure of central cholinergic activity in man.

The McCollough Effect (ME) is an orientation contingent colour after-effect which has been proposed as an indicator of central neurotransmitter activity. Shute (1979) suggested that the ME could reflect a hippocampal "forgetting" mechanism which should be inhibited by GABAergic neurones and stimulated by cholinergic neurones. The purpose of the present study was to demonstrate that the ME is in fact sensitive to cholinergic and anticholinergic drugs and to compare its sensitivity to more conventional tests of psychomotor and cognitive function. Ten healthy subjects received single doses of physostigmine (0.75 mg SC), hyoscine (1.2 mg), temazepam (20 mg), flecainide (200 mg) or placebo in a double-blind double-dummy presentation. Subjects were tested on a battery of psychomotor and cognitive function tests at baseline and 1 h, and adapted to the ME at 1.5 h. Visual analogue rating scales and conventional tests of psychomotor function and saccadic eye movements indicated that both subjective and objective measures of arousal were impaired by temazepam. The subjective, but not the objective, measures of arousal were also impaired by both hyoscine and physostigmine, but not by flecainide. Initial strength and duration of the ME were decreased by physostigmine and increased by hyoscine and temazepam, relative to placebo (P less than 0.01). Thus, the ME is capable of detecting cholinergic, anticholinergic and GABA mimetic drug effects in man, in therapeutic doses.

Adaptation, Ocular↗
PubMed1992

In vitro assembly of prenucleolar bodies in Xenopus egg extract.

Nuclei assembled in Xenopus egg extract from purified DNA or chromatin resemble their natural counterparts in a number of structural and functional features. However, the most obvious structural element of normal interphase nuclei, the nucleolus, is absent from the in vitro reconstituted nuclei. By EM, cytological silver staining, and immunofluorescence microscopy employing antibodies directed against various nucleolar components we show that nuclei assembled in vitro contain numerous distinct aggregates that resemble prenucleolar bodies (PNBs) by several criteria. Formation of these PNB-like structures requires pore complex-mediated nuclear transport of proteins but is independent of the genetic content of the in vitro nuclei as well as transcriptional and translational events. Our data indicate that nuclei assembled in vitro are capable of initiating early steps of nucleologenesis but that the resulting PNBs are unable to fuse with each other, probably due to the absence of a functional nucleolus organizer. With appropriate modifications, this experimental system should be useful to define and analyze conditions promoting the site-specific assembly of PNBs into a coherent nucleolar body.

Animals↗
PubMed1992

Familial Conn's syndrome.

We describe the occurrence of primary hyperaldosteronism in two sisters. Although this is only the second published report of familial Conn's syndrome, it does have implications for the relatives of patients with Conn's syndrome and these are discussed.

Adenoma↗
PubMed1991

Donor-recipient age difference--an independent risk factor in cyclosporin-treated renal transplant recipients.

Whilst HLA matching is routine in renal transplantation the possible benefits of matching donor to recipient age have not been previously explored. The simultaneous effect on graft survival of donor and recipient age was therefore investigated for 274 consecutive first cadaver transplant recipients treated by cyclosporin immunosuppression in two centres. The overall graft survival was 77%, and was not significantly different between the two centres. Individually there was no significant effect of donor or recipient age but taken together, the difference in age significantly affected graft survival (P less than 0.01) regardless of the mode of failure. The 1-year graft survival for all failures was 66.2% when the donor was 5 or more years older. 84.5% when the donor was 5 or more years younger and 71.7% when the donor was within 5 years of the recipient's age. Multivariate analysis, taking into account other variables (HLA matching, dialysis time and type, donor/recipient sex, local/imported kidneys, sensitivity, operation time, total ischaemic time, pre-operative transfusions) indicated that age difference was the single most important variable (P less than 0.01). The only other important covariate risk factor in improving graft survival was HLA-DR matching (P less than 0.05). Donor-recipient age difference is a potentially important recipient selection criterion in cyclosporin-treated renal transplant patients.

Adolescent↗
PubMed1991

A preliminary study of the effects of flosequinan on psychomotor function in healthy volunteers.

The central nervous system effects of flosequinan (100 mg), a chemically novel quinolone vasodilator, were assessed by a double-blind crossover comparison with placebo and diazepam (10 mg) in 12 healthy volunteers. After five practice sessions on a battery of automated psychomotor tests, assessments of psychomotor function and mood ratings were made on each volunteer at baseline and 1, 3, 6 and 24 h after dosing. Compared with placebo, diazepam (10 mg), the verum control, significantly (p less than 0.05) reduced subjective alertness, impaired critical flicker fusion threshold at 1 and 3 h, digit symbol substitution at 6 h, overall total choice reaction time and overall rate on two of five finger tapping tests. Flosequinan (100 mg), however, was indistinguishable from placebo in all tests with two contrasting exceptions: improved alternate right and left finger tapping (mean 5.1/s) compared to either diazepam (4.7/s) or placebo (4.8/s) (p less than 0.05), and impaired digit symbol substitution at 6 h (45.7/min) in comparison with placebo (50.7/min) (p less than 0.01). Ten volunteers reported 12 adverse effects after flosequinan treatment (10 of which were headaches), two reported drowsiness after diazepam and one reported headache after placebo. It was concluded that flosequinan has no central nervous system depressant effects despite the occurrence of headache in 10 volunteers.

Administration, Oral↗
PubMed1991

AIDS: knowledge and attitudes of student nurses in Australia and Canada.

In summary it would appear that Australian and Canadian nursing students, at least in these limited samples, generally have similar knowledge and attitudes regarding AIDS. This study, with its acknowledged limitations, could be regarded as a pilot study for future collaborative comparative research, targeting a wider population of nursing students in two very similar countries.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Intraoperative management of patients with heparin-induced thrombocytopenia.

For 11 patients with confirmed heparin-induced thrombocytopenia, we used reversible platelet inhibition with iloprost, a stable prostacyclin analogue, to permit safe heparin administration for cardiac (n = 9) or vascular (n = 2) operations. In vitro, iloprost (0.01 mumol/L) prevented both heparin-induced platelet aggregation and 14C-serotonin release in all patients. Therefore, intraoperatively, a continuous infusion of iloprost was started before administration of heparin and was continued until 15 minutes after administration of protamine. For cardiac patients, after heparin administration, the whole blood platelet count did not change (171,000 +/- 29,000/microL versus 174,000 +/- 29,000/microL, mean +/- standard error of the mean); no spontaneous platelet aggregation was observed, and plasma levels of the alpha-granule constituents platelet factor 4 and beta-thromboglobulin increased from 38 +/- 14 and 140 +/- 18 ng/mL to 591 +/- 135 and 235 +/- 48 ng/mL, respectively. Fibrinopeptide A levels actually decreased from 287 +/- 150 to 27 +/- 6 ng/mL. Furthermore, adenosine diphosphate-induced platelet activation was preserved, postoperative bleeding times were unchanged, and no heparin-related deaths occurred. Similar results were obtained in both vascular patients. We conclude that temporary platelet inhibition with iloprost now permits safe heparin administration in all patients with heparin-induced thrombocytopenia who require a cardiac or vascular operation.

Adult↗
PubMed1990

Psychological consequences of the Enniskillen bombing.

Eleven people were killed and 60 injured in the Enniskillen bombing of November 1987. Survivors were psychologically appraised six months and one year later. At six months 50% had developed post-traumatic stress disorder (PTSD). This group comprised more females than males. However, all victims had high scores on the GHQ. We found no correlation between psychological injury (as measured by the GHQ) and physical injury (as measured by the ISS), calling into question previous assertions.

Adolescent↗
PubMed1990

Choice and use of tracers.

The isotope dilution method has been widely employed to measure glucose turnover in man. The validity of this technique depends upon several assumptions. First, it is assumed that the selected model of glucose kinetics is valid. Under nonsteady state conditions this has recently been challenged for the most commonly used single compartment model. Secondly, it is assumed that the isotope is metabolized in the same manner as unlabeled glucose. If the isotope loses its label when subject to a substrate cycle (for example, [2-3H]glucose in glucose to glucose 6-phosphate cycling), an overestimate of glucose disposal will result. In contrast, if isotope that has been cleared (for example [6-3H]glucose in hepatic glucogen) is recycled into the systemic circulation, an underestimation of glucose turnover will result. Thirdly, it is assumed that measurement of specific activity is accurate. It has recently been shown that many commercially available tritiated (but not 14C) isotopes contain radioactive nonglucose contaminants which have a slower clearance rate than glucose under conditions of high glucose turnover. This can result in overestimates of specific activity and underestimates of glucose appearance, leading to calculated negative hepatic glucose release. While this problem may be avoided with purified tritiated glucose tracers, a similar problem with stable isotopes of glucose remains to be determined. In summary, the choice of glucose isotope should reflect the probability of substrate cycling and isotope cycling in the experiment in question. Care should be taken to ensure purified isotopes are selected and that the model of glucose kinetics used is valid during the conditions to be studied.

Animals↗
PubMed1990

Hostel placement of mentally handicapped patients in Northern Ireland.

All patients discharged to hostels from an 800 bed hospital for the mentally handicapped were studied over a 12 year period. Those whose placement was successful were compared with those who returned to the hospital. Youth and early institutional upbringing were associated with failure of placement. Twelve specific problems were identified by hostel staff and of these aggression, psychosis, absconding and interpersonal difficulties were associated with failure. A worrying trend was that the more modern hostels had a lower success rate and a higher proportion of problems than those which were older and more established.

Adult↗
PubMed1989

Femoro-popliteal versus femoro-distal bypass grafting for limb salvage in patients with an "isolated" popliteal segment.

In a prospective, multicentre trial, 59 patients with an ischaemic limb and an "isolated" popliteal segment on angiography were randomised to undergo infrainguinal bypass grafting to either the popliteal segment or to a reconstituted distal vessel lower in the calf. Limb salvage was attained with 88% of the femoro-popliteal grafts and 80% of the femoro-distal grafts. There was no difference in the one year graft patency rate between the femoro-popliteal group (79%) and the femoro-distal group (70%). Mean postoperative increase in ankle/brachial pressure index was similar in the two groups despite the presence of occluded or significantly diseased vessels distal to the popliteal anastomoses. Technical difficulties were encountered in 8% of the popliteal group and 24% of the distal group. Femoro-distal bypass grafting confers no apparent benefit over femoral bypass grafting into a patent popliteal segment, even though the popliteal run-off is impaired or occluded.

Aged↗
PubMed1989

Electrophysiologic effects of Org 7797, a new steroidal antiarrhythmic agent: comparison with class 1a, 1b, and 1c drugs.

The in vitro electrophysiologic effects of a new class I steroidal antiarrhythmic agent, Org 7797 (2-10 microM) were evaluated in porcine ventricular and Purkinje tissue using conventional microelectrode techniques. Org 7797-induced decreases in Vmax were both frequency- and voltage-dependent. Both the rate of onset and the time course of decay of sodium channel block were slow and similar to those obtained with the 1c drug propafenone. The kinetics of block by lignocaine (1b) were fast whereas those of disopyramide (1a) were intermediate. Rate constants (determined at 1.0 Hz) were 0.187, 0.078, and 0.074 for disopyramide, propafenone, and Org 7797, respectively, in concentrations giving approximately equivalent decreases in Vmax. Onset block with lignocaine was too fast to measure. The effective refractory period (ERP) was prolonged to a greater extent by lignocaine and disopyramide than by propafenone or Org 7797, but the increase in ERP in response to disopyramide resulted largely from prolongation of action potential duration (APD). The effects of Org 7797 on ERP relative to APD were more similar to those of propafenone. We conclude that Org 7797 is a class 1c agent.

Action Potentials↗
PubMed1989

Psychomotor performance and counterregulatory responses during mild hypoglycemia in healthy volunteers.

The effect of mild hypoglycemia on psychomotor performance and counterregulatory responses was studied among 12 healthy volunteers. Each volunteer received two modified hyperinsulinemic glucose clamps. One morning, plasma glucose was held constant at euglycemic levels (4.9 mM) for 95 min, and another morning, it was lowered over 35 min and then held constant at hypoglycemic levels (3.4 mM) for 60 min. A battery of psychomotor tests and a questionnaire assessing hypoglycemic symptoms were administered before and repeated during the last 30 min of each clamp. The questionnaire and three selected psychomotor tests were also administered repetitively during the 1st h of each clamp. During the hypoglycemic studies, a rise was seen in plasma epinephrine and pancreatic polypeptide at 45 min. An increase in symptom scores was first recorded at 50 min during the hypoglycemic studies [median 4 (range 0-13) vs. 2 (5-6), P less than .05]. Performance was impaired on two psychomotor tests included in the battery. One was the trail making test on fine motor performance (-19.3 +/- 4.2 targets/min, mean +/- SE vs. 1.2 +/- 4.8 targets/min, P less than .05), and the other was the digit-symbol substitution (DSS) test on information processing and memory (18 +/- 3 vs. 29 +/- 4 symbols/min, P less than .03). Of the tests administered during the 1st h, performance was impaired on the DSS. This impairment became significant at 45 min (14 +/- 4 vs. 22 +/- 4 symbols/min, P less than .005). In conclusion, mild hypoglycemia selectively impairs psychomotor performance in healthy volunteers but not before the onset of glucose counterregulation and warning symptoms.

Adult↗