Biomedical subjects
Publications and source records attributed to R Manchanda.
The issue of using substitute consent to obtain treatment for patients who are not competent to consent to treatment is complex. The authors present a case which illustrates that patients may delay treatment for extended periods of time by repeatedly challenging their incompetency status. The authors present proposals to change the present system.
The time-courses of junction potentials and junction currents at the sympathetic neuroeffector junction of guinea-pig vas deferens were investigated using simultaneous intracellular and focal extracellular recording. Excitatory junction potentials produced in the smooth muscle cells following electrical stimulation of the sympathetic nerves had duration of 600-1000 ms and were prolonged in time-course compared with the underlying excitatory junction currents which had durations of 40-150 ms. The time-course of the excitatory junction potential could be predicted accurately from the time-course of the underlying excitatory junction current by assuming that the smooth muscle cells were isopotential during the excitatory junction potential. In contrast, the time-course of the spontaneous excitatory junction potential, produced by the action of a single quantum of transmitter, was identical to the time-course of the underlying spontaneous excitatory junction current, both events having durations of 40-150 ms. Local application of 10(-4) M adenosine 5'-triphosphate in the vicinity of an intracellular microelectrode produced depolarizations ("adenosine 5'-triphosphate potentials") of durations ranging between 400 and 2500 ms. When adenosine 5'-triphosphate was applied close to the rim of an extracellular electrode, negative-going signals ("adenosine 5'-triphosphate currents") were produced which reflected the time-course of postjunctional membrane currents evoked by adenosine 5'-triphosphate. Adenosine 5'-triphosphate currents were abolished by alpha, beta-methylene adenosine 5'-triphosphate (10(-6) M) but were unaffected by tetrodotoxin (3 x 10(-7) M or 10(-6) M) and the alpha-adrenoceptor blockers prazosin (10(-6) M) and phentolamine (10(-6) M). The time-courses of adenosine 5'-triphosphate currents were similar to the time-courses of excitatory junction currents recorded in the same preparation. Adenosine 5'-triphosphate currents were generally brief compared with simultaneously recorded adenosine 5'-triphosphate potentials which had durations or greater than or equal to 1000 ms. The time-courses of relatively brief adenosine 5'-triphosphate potentials (duration less than or equal to 800 ms) followed the time-courses of the underlying adenosine 5'-triphosphate currents. These results indicate that the time-course of decay of the excitatory junction potential in the guinea-pig vas deferens is determined mainly by the passive membrane properties of the smooth muscle cells, the duration of underlying transmitter action being brief. However, the factors determining the time-course of adenosine 5'-triphosphate potentials are less clear, and may include passive membrane properties and diffusion of locally applied adenosine 5'-triphosphate.(ABSTRACT TRUNCATED AT 400 WORDS)
The efficacy and side-effect profile for three dose ranges of remoxipride were compared with haloperidol in 242 schizophrenic inpatients in 13 centres. All patients were in a productive phase of schizophrenia according to DSM-III criteria. Relative efficacy of low dose (30-90 mg daily) vs middle dose (120-240 mg daily) vs high dose (300-600 mg daily) was compared with the standard dose of haloperidol (15-45 mg daily), as were the side effects. It was concluded that the therapeutic efficacy of remoxipride was comparable to that of haloperidol for acute episodes of schizophrenia; that the low dose range was significantly less effective than the higher ranges; that there was a clear advantage of remoxipride over haloperidol with respect to incidence and severity of extrapyramidal symptoms. The general safety profile of remoxipride as assessed from clinical chemistry, haematology, and cardiovascular variables suggests that remoxipride in the dose ranges studied can be used safely for the treatment of schizophrenic patients.
A study was conducted to investigate a novel approach to the prophylaxis of schizophrenic relapse. The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared. Fifty four stable, remitted outpatients meeting the American Psychiatric Association's DSM-III criteria for schizophrenia were randomised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections. Only three patients given placebo injections and two controls were admitted to hospital during one year of follow up. Eight (30%) of the patients given placebo injections and only 2 (7%) of the controls, however, had a recurrence of schizophrenic symptoms. Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia. Dysphoric and neurotic symptoms were identified before eight out of 11 relapses, and these symptoms were more frequent in patients given placebo depot injections. These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill, chronic, stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse.
Simultaneous recordings were made of spontaneous excitatory junction potentials and the underlying spontaneous excitatory junction currents in guinea-pig and mouse vas deferens using adjacent intracellular and focal extracellular electrodes. Concurrent spontaneous excitatory junction potentials and spontaneous excitatory junction currents were observed in a small proportion of smooth muscle cells penetrated intracellularly within 50-200 microns of the extracellular electrode. These simultaneous events had identical variations in time course, indicating that they were caused by the same transmitter release event. Their amplitudes were not related. Concurrent spontaneous excitatory junction potentials and currents had identical durations, rise times and time constants of decay, showing that the spontaneous excitatory junction potential reflects the time course of quantal transmitter action. In contrast, spontaneous "discrete events" obtained by differentiating the rising phases of spontaneous excitatory junction potentials with respect to time were brief compared with the underlying currents. Excitatory junction potentials evoked by electrical stimulation of the hypogastric nerve were prolonged compared to the underlying excitatory junction currents. The peaks in the first time differential of individual excitatory junction potentials (evoked discrete events) were brief compared to corresponding excitatory junction currents. It is concluded that at the neuroeffector junction of the rodent vas deferens the membrane potential response to a quantum of spontaneously released transmitter is a good estimate of the duration of transmitter action, in accordance with some of the predictions for three-dimensional syncytial tissues. The first time differential of the membrane potential, the "discrete event", does not reflect the time course of spontaneous or evoked quantal transmitter action in these syncytial tissues.
1. The effects of reserpine pretreatment on neurotransmission in the guinea-pig vas deferens have been re-examined with a view to study the role of noradrenaline (NA) in mediating postjunctional electrical responses and, in particular, excitatory junction potentials (EJP). 2. Reserpine (5 mg/kg, i.p.) caused almost total depletion (below detection levels) of the NA content of the vas deferens. However, spontaneous and evoked excitatory junction potentials (SEJP, EJP) and currents (SEJC, EJC) could still be recorded in NA-depleted tissues. The amplitude distribution of SEJC in control and reserpinized tissues was similar. 3. Facilitation of EJP and EJC was markedly slowed in reserpinized tissues, EJP taking 50-60 pulses to facilitate fully. However the amplitudes of fully facilitated EJP were comparable to EJP recorded in control tissues. 4. EJPs in reserpinized vasa deferentia were unaffected by the NA synthesis inhibitor, alpha-methyl tyrosine, but were abolished in the presence of the stable ATP analogue alpha,beta-methylene ATP which desensitizes postjunctional P2-purinoceptors. 5. Local application of ATP, but not NA, mimicked the EJP. These results indicate that EJP are mediated by a non-noradrenergic neurotransmitter possibly ATP.
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Procedural requirements under the provisions of the Mental Health Act can delay the implementation of treatment for an involuntary psychiatric patient refusing treatment. The authors present such a case where treatment could not be given for nearly two months during which the patient's condition sharply deteriorated. With treatment, the patient improved within two weeks and was allowed to go home. Considerable time and money was spent in the Regional Review Board hearings. The implications of the case are discussed and it is recommended that steps be taken to prevent the interference of a bureaucratic legal system in the day to day practice of psychiatry.
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1. The properties of junction potentials evoked by nerve stimulation and by local application of drugs, and currents evoked by nerve stimulation, in the smooth muscle cells of the guinea-pig vas deferens have been investigated. The effects of temperature on these responses have been studied using intracellular and extracellular recording. 2. Local, brief (5-15 ms) application of 10(-4) M-adenosine-5'-triphosphate (ATP) from glass micropipettes onto the surface of the vas deferens, using pressure pulses (103-206 kPa), elicited a depolarization of the smooth muscle cell membranes which closely resembled the nerve stimulation-evoked excitatory junction potential (EJP). 3. Local application of 10(-4) M-noradrenaline (NA) failed to produce any detectable membrane potential response. Junction potentials elicited by a mixture of 10(-4) M-ATP and 10(-4) M-NA (ratio by volume 1:50) in the drug ejection micropipette were similar in shape to those evoked by ATP alone. 4. Cooling the tissue from 35 to 25 degrees C did not significantly alter resting membrane potentials but resulted in a significant prolongation of the rising and decaying phases of the EJPs. Fifty per cent decay times for EJPs at 35 and 25 degrees C were (mean +/- S.D.) 236 +/- 20 and 434 +/- 30 ms respectively (P less than 0.01). 5. Extracellularly recorded excitatory junction currents (EJCs) elicited by nerve stimulation, believed to reflect the transmembrane current underlying the EJPs, were prolonged in parallel at low temperatures (50% decay times of EJCs at 35 and 25 degrees C: 11.73 +/- 3.94 and 26.15 +/- 8.4 ms, respectively, P less than 0.01). 6. Junction potentials evoked by locally applied, exogenous ATP were also significantly prolonged by cooling (50% decay times: 663 +/- 88 ms at 35 degrees C and 1955 +/- 79 ms at 25 degrees C, P less than 0.01). 7. Bath application of 10(-6) M-alpha,beta-methylene ATP, the enzymatically stable, desensitizing analogue of ATP, reversibly abolished nerve-evoked EJPs. Local application of 10(-6) M-alpha,beta-methylene ATP led to a prolonged depolarization of the smooth muscle cells lasting between 20 and 60 s. 8. Junction potentials elicited by locally applied alpha,beta-methylene ATP were not prolonged or otherwise significantly altered on cooling. The durations of the depolarizations were 46.0 +/- 12.1 s at 35 degrees C and 43.4 +/- 10.6 s at 25 degrees C (P greater than 0.1).(ABSTRACT TRUNCATED AT 400 WORDS)
A review of treatment trials with DT gamma E revealed widely discrepant results. Relevant variables were the variety of measures employed for monitoring psychotic symptoms, and the different criteria used to judge the degree of improvement. The authors suggest a uniform outcome criterion for early trials of new treatments, which would generate more consistent and comparable results between studies, and give a stronger indication of the value of the treatment under test. When the data from the various treatment trials of DT gamma E were reanalysed, applying a uniform outcome criterion of improvement of a change of 80% or more on rating-scale score, the results were more consistent than would have been suspected from the original reports.
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1. 36 acute schizophrenic patients were randomly assigned to dextro-propranolol or placebo in a double blind trial lasting four weeks. 2. Detailed assessments were made using the Present State Examination, the Brief Psychiatric Rating Scale and the Manchester Scale before, during and at the end of the trial. 3. The authors report on the change in depressive symptomatology during the period of the trial. 4. One patient in each group became suicidal and was withdrawn at week 2 1/2. 5. With regard to ratings of depression, there was an overall reduction in mean depression scores at the end of the trial in both groups. 6. Emergence of depressive symptoms and increase in the severity of existing symptoms was seen in a small number of patients in both groups, but more so in the placebo group. 7. A depressogenic effect for d-propranolol was not observed in the population studied.
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