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Biomedical subjects

R F Smith

Publications and source records attributed to R F Smith.

At least 163 records · Page 9Linked to original sources
PubMed1981

Circadian clock phenotypes of chromosome aberrations with a breakpoint at the per locus.

The circadian rhythm phenotypes of eight chromosome aberrations with a breakpoint in the region of the per locus (3B1-2) were analyzed. Two duplications and five deficiencies with a 3B1-2 breakpoint produce either a wild-type or an arrhythmic clock phenotype while one translocation with a 3B1-2 breakpoint. T(1;4)JC43, produces locomotor-activity rhythms with either very-long period (31--39 h), rhythms that grade into arrhythmicity, or completely arrhythmic phenotypes. This is a unique phenotype that had not previously been observed for mutants at the per locus. An extensive complementation analysis of 3B1-2 chromosome aberrations and per mutant alleles provided no compelling evidence for genetic complexity at the per locus. This is in contrast to the report of Young and Judd (1978). Analysis of both the locomotor-activity and eclosion phenotypes of 3B1-2 chromosome aberrations did not uncover differences in the genetic control of these two rhythms. The clock phenotypes of 3B1-2 chromosome aberrations, the three per mutant alleles, and per+ duplications suggest that mutations at the per locus shorten, lengthen, or eliminate periodicity by respectively increasing, decreasing, or eliminating per activity.

Animals↗
PubMed1981

Recurrent ventricular tachycardia in the absence of overt heart disease: clinical characteristics and response to drug therapy.

Eight patients, seven of them women, have been followed up for a mean of 8.1 years (range, three to 18) with the uncommon syndrome of recurrent frequent episodes of ventricular tachycardia in the absence of overt cardiac abnormality. The mean age at diagnosis was 25 years (range, 12 to 44). Serious symptoms were common: five patients had syncope, cardiac arrest, and/or cerebrovascular accidents. Multiple measures to characterize this population, including study of symptoms, response to exercise, degree of prematurity of ventricular ectopic depolarizations, and response to antiarrhythmic drugs, showed little uniformity. An individualized approach to therapy, taking into account age and symptoms as well as frequency of arrhythmia, was used. Excellent control of arrhythmia was eventually achieved in four patients, but only after multiple drug trials (mean 5.3, range two to eight trials per patient) had been ineffective. Prognosis in this syndrome is generally good, but serious complications occur frequently enough that vigorous therapy is justified in selected patients.

Adolescent↗
PubMed1981

Sex and surgical stress.

The endocrine and metabolic response to anaesthesia and surgery was studied in 12 men and eight women undergoing elective total hip replacement using buprenorphine as the intra- and postoperative analgesic. Plasma glucose, cortisol and prolactin were measured, and the results obtained for men and women compared. Statistically significant difference between men and women were found for prolactin during and after operation, and also for cortisol postoperatively. Men, but not women, demonstrated a significant fall in plasma cortisol following a dose of buprenorphine after operation. These results are discussed in relation to known procedures for ablating the stress response and to the neuroendocrine effects of opiate agonists and partial agonists.

Aged↗
PubMed1980

Detection of unrecognised nocturnal hypoglycaemia in insulin-treated diabetics.

Cortisol to creatinine ratios in overnight urine samples, urinary glucose excretion, and plasma glucose concentrations were determined in 43 diabetic inpatients. All initially had normal cortisol to creatinine ratios (less than 55 x 10(-6)) and were initially treated by increasing their long-acting insulin component. Nine patients in whom this ratio became raised then had their long-acting insulin component reduced until their fasting plasma glucose concentration was 4-7 mol/l (72-126 mg/100 ml). The 34 patients who had never had a raised ratio were treated by increasing their long-acting insulin component until their fasting plasma glucose concentration was in the range 4-7 mmol/l. All the raised cortisol to creatinine ratios were clearly separate from the other values. A mean reduction in total insulin dose of 23% and in long-acting insulin dose of 53% was achieved, abolishing presumptive nocturnal hypoglycaemia by reducing the ratio to normal and dramatically improving diabetic control. Although there was no definite evidence that the patients who had raised cortisol to creatinine ratios had suffered from nocturnal hypoglycemia, these results strongly support the view that a raised ratio indicates an otherwise unrecognised episode of this condition.

Adolescent↗
PubMed1980

Tocainide therapy for refractory ventricular arrhythmias.

Tocainide, a congener of lidocaine, was used to treat symptomatic ventricular arrhythmias in 19 patients resistant to or unable to tolerate conventional agents. In this highly selected group, 15 showed good initial responses to oral therapy. Ventricular tachycardia was suppressed to a greater extent than isolated ventricular ectopic depolarizations at any plasma concentration, and upward dose-ranging showed progressive suppression of both. Arrhythmia responsiveness to lidocaine was found to be an excellent predictor of tocainide response. Of the 15 responders, one died 24 hours after stopping therapy, three died while receiving tocainide, nine stopped because of adverse reactions (five allergic), and two continue on therapy at 1 and 4 years. We conclude that tocainide is an effective agent for the short-term suppression of ventricular arrhythmias, particularly ventricular tachycardia sensitive to lidocaine, but a high incidence of adverse effects limits its application to chronic therapy in many patients.

Adult↗
PubMed1980

Antiarrhythmic efficacy, pharmacokinetics and safety of N-acetylprocainamide in human subjects: comparison with procainamide.

The antiarrhythmic efficacy and pharmacokinetics of N-acetylprocainamide (NAPA), the major metabolite of procainamide, were investigated in 23 patients with chronic, high frequency ventricular ectopic depolarizations. An extensive trial design incorporated the approaches of (1) generation of dose-response relations, (2) randomized crossover, and (3) prolonged electrocardiographic monitoring. Seven patients with reproducible suppression of arrhythmias (70 percent or greater reduction in frequency) were thus identified. The mean plasma concentration of acecainide associated with efficacy was 14.3 micrograms/ml (range 9.4 to 19.5) and with side effects (primarily gastrointestinal) was 22.5 micrograms/ml (10.6 to 37.9). The antiarrhythmic response to procainamide did not predict response to acecainide; this finding implies that estimates of the antiarrhythmic contribution of acecainide concentrations achieved during long-term procainamide therapy are unlikely to be meaningful in a given person. The mean half-life of elimination after a single 500 mg dose of acecainide was 7.5 hours; this had prolonged significantly (p < 0.05) to 10.3 hours after higher dosages. No variable examined (including acetylator phenotype) was found to be a predictor of responsiveness to acecainide. Outpatient therapy (2 to 20 months) was not associated with the development of antinculear antibodies or the lupus syndrome; one patient's procainamide-induced arthritis resolved during therapy. Acecainide, unlike procainamide, is an agent whose pharmacokinetics allow long-term therapy on a practical schedule. It is effective in a subset of patients with ventricular arrhythmias yet appears much less likely to induce the lupus syndrome seen with the parent compound.

Acecainide↗
PubMed1980

Arterial embolization: problems of source, multiplicity, recurrence, and delayed treatment.

The clinical course of 225 patients who had experienced 309 arterial embolic episodes was reviewed with special reference to the problems of the identification of the source of embolization, multiplicity of involvement, significance of recurrence, and the effects of some therapeutic means, including anticoagulation, on the early and late results. The most common source of embolization was cardiac (in 85% of the cases). Persistent search, at times by complex diagnostic methods, uncovered the origin in all but 11% of the cases. Within a range of 8 hours to 7 days the effect of delayed treatment had a linear relationship to the severity of ischemic changes and the deterioration of favorable results. Angiography was helpful and often essential in the diagnosis of visceral embolism and in differentiating local thrombosis from embolism in the periphery. Recurrent embolization was common (in 28% of the cases), was often multiple, and had a grave prognosis. Permanent anticoagulant therapy, preferably with but even without the removal of the source of embolization, reduced the rate of recurrence and, in general, reduced early and late morbidity and mortality rates.

Adult↗