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Biomedical subjects

J G Edwards

Publications and source records attributed to J G Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1984

Does viloxazine have epileptogenic properties?

Six cases of convulsive seizures occurring during treatment with viloxazine notified to the Committee on Safety of Medicines (CSM) and two other cases from Japan were reviewed. A critical study of the patient's histories suggests a possible causal connection between drug and seizures in only two of these cases. The occurrence of convulsions is not in keeping with the results of animal experiments and of clinical trials in which epileptic patients were included, both of which suggest that viloxazine does not have epileptogenic properties and may have anticonvulsant actions. A worldwide review of clinical trials in which unwanted effects have been recorded suggests that viloxazine, even if possessing convulsive properties like other anti-depressants, is probably less epileptogenic than conventional tricyclics and is not contraindicated in epileptic patients requiring antidepressant medication.

Adult↗
PubMed1984

Responses of SHR to combinations of chemical sympathectomy, adrenal demedullation, and training.

The single and combined influences of exercise training, chemical sympathectomy (SYMX), and surgical adrenal demedullation (D) were examined in four separate spontaneously hypertensive rat (SHR) groups. SYMX was accomplished by subcutaneous injections of antinerve growth factor (ANGF) over a 5-day period after birth followed by 20 separate injections of guanethidine sulfate during a 27-day period. Measurements of urine, plasma, or tissue levels of catecholamines indicated that these experimental procedures were effective. The animals were exercise trained (T) for 10 wk or longer at 40-60% of their VO2max capacity, and all T groups exhibited longer run times or higher muscle cytochrome oxidase activity; however, only the SHR + T subgroup had a significantly higher VO2max value than its control (NT). Training lowered resting systolic blood pressure (SBP) in the SHR subgroup but normalization of SBP occurred only with SYMX. Interestingly, only the SYMX + T subgroup with intact adrenal glands also had lower SBP values than the NT. The SHR + T and SYMX + T subgroups but not the SYMX + D + T had less cardiac acceleration after ip injections of atropine than their controls. Heavier heart weights were observed only in the SHR + T subgroup; SYMX was associated with lighter heart weights regardless of whether the rats had been T or D. These collective findings demonstrated again the importance of the sympathetic nervous system to an exercise response, suggesting that an intact adrenal medulla was essential for SHR groups to achieve many of the adaptations associated with training.

Adrenal Medulla↗
PubMed1984

Chick embryonic pigmented retina is one of the group of epithelioid tissues that lack cytokeratins and desmosomes and have intermediate filaments composed of vimentin.

Using sodium dodecyl sulphate/polyacrylamide gels to analyse detergent-insoluble residues, and indirect immunofluorescence, we have found that the major protein of intermediate filaments in cultures and freshly explanted fragments of chick embryonic retinal pigment epithelium (RPE) is vimentin. Moreover, these cells also fail to stain with antibodies against cytokeratins and most components of true desmosomes (maculae adhaerentes). Staining with anti-vinculin antibody suggests that the principal intercellular junction is the zonula adherens. Thus although RPE is an epithelium according to all other criteria, it belongs to a group of tissues (including vascular endothelium, iris and lens-forming epithelium) that have intermediate filaments composed of vimentin and possess neither cytokeratins nor desmosomes. That a tissue can be fully epithelial by other criteria, whilst lacking these components, is in agreement with other work, which has shown a lack of effect of micro-injection of antibodies to cytokeratin, and of the suppression of desmosome formation, on epithelial organization in culture. Although our observations were made solely on chick embryonic tissue, we suggest that published ultrastructural studies are consistent with the possibility that RPE of other species, including human, may lack true desmosomes.

Animals↗
PubMed1984

Renal function during lithium treatment.

Renal function tests were performed in 101 unselected patients who had been on lithium for two weeks to 12 years. None had a recorded episode of lithium intoxication. The glomerular filtration rate (GFR), was not correlated with the cumulative dose of lithium or the duration of use of other psychotropic drugs. Nine patients had creatinine clearances lower than predicted; in six of these, no cause was identified and the small reductions in GFR may have been related to lithium use. Urinary concentrating ability (Umax) declined with age, and total dose of lithium received. Although the concurrent use of neuroleptics did not significantly reduce the Umax, the total duration of treatment with these drugs showed a negative correlation. The results suggest that prolonged use of neuroleptics, particularly in patients treated with lithium, may be responsible for an irreversible reduction in urine concentrating ability. Microalbuminuria was present in 40 per cent of the patients, although the rate of albumin excretion was not correlated with duration of use of psychotropic drugs. beta 2 microglobulin excretion was only raised in nine of these patients, suggesting that increased glomerular permeability rather than impaired proximal tubular protein reabsorption was responsible for the proteinuria. The urinary excretion of beta 2 microglobulin and N-acetyl-beta-glucosaminidase were slightly increased in small numbers of patients, indicating little evidence for proximal tubular damage. Increased NAG excretion did not correlate with reduced distal tubular function. However, there was a tendency to higher urinary beta 2 microglobulin excretion in patients with a reduced Umax.

Adult↗
PubMed1983

Orthopedic effects with "conventional" fixed orthodontic appliances: a preliminary report.

This retrospective study involved sixty previously treated patients between the ages of 9 and 14 years, all of whom initially had Class II dental malocclusions. The primary purpose of the investigation was to determine whether orthodontic treatment with a specific round-wire edgewise technique (no extraoral forces) was simply producing dentoalveolar manipulations or was actually affecting measurable skeletal or orthopedic alterations in the craniofacial system. The mean linear changes before and after orthodontic treatment in the maxilla (Ar-ANS), mandible (Ar-PGN), and lower facial height (ANS-MN) were statistically compared with an untreated control group (the Burlington Growth Study). The study sample was analyzed selectively according to sex and also according to the angulation of the mandibular base to the anterior cranial base (the SNMP angle). Apparently, from the observations in this study, the particular edgewise technique employed for the orthodontic treatment of the sixty sample patients did statistically affect more than merely dentoalveolar alterations. The normal forward growth of the maxilla appeared to be hindered, the lower facial height was significantly increased (usually without an appreciable increase in the SNMP angle), and the mean increased growth of the mandible was also statistically significant. Admittedly not its primary purpose, this preliminary report appeared to at least indirectly compare, if not the actual treatment modalities, at least the treatment results between a specific fixed orthodontic appliance and certain removable "functional" appliances.

Adolescent↗
PubMed1983

Placebo-controlled trial of mianserin and maprotiline in primary depressive illness: a preliminary report.

1 Preliminary results of a double-blind placebo-controlled trial of mianserin and maprotiline carried out in 58 outpatients with primary depressive illness are reported. 2 Patients received six weeks' treatment with 30 to 90 mg mianserin, 75 to 225 mg maprotiline or one to three capsules of placebo, all medication being taken at night. 3 There were statistically significant improvements in each treatment group and a better response to mianserin than to placebo or maprotiline on the Hamilton Rating Scale for Depression, after one week's treatment. 4 Neither mianserin nor maprotiline was superior to placebo after two or four weeks' treatment and relatively few patients completed six weeks' treatment because of a generally unsatisfactory response. 5 Unwanted effects were not particularly troublesome, though mianserin and maprotiline caused more drowsiness and blurred vision than did placebo, while maptrotiline produced more constipation than either of the other two treatments. 6 The importance of placebo-controlled trials of antidepressants is emphasized and the precautions that should be taken when they are carried out in outpatients are described.

Adolescent↗
PubMed1983

Mianserin, maprotiline and intracardiac conduction.

1 High speed surface electrocardiograms were recorded in 35 patients during the baseline and after four weeks' treatment in a placebo-controlled trial of mianserin and maprotiline in primary depressive illness. 2 Measurements of the RR, PR and QT intervals, QRS width and T wave height were made blind to patient, drug and treatment interval and compared with plasma drug concentrations. The presence or absence of cardiac arrhythmias was recorded. 3 The only significant findings were an increased heart rate and PR interval and decreased QTc interval in the maprotiline group. Only one patient receiving maprotiline had a cardiac arrhythmia. There was no significant correlation between measurements of ECG parameters and plasma drug levels. 4 The results confirm the lack of cardiac effects of mianserin and show both anticholinergic activity and effects of an intracardiac conduction in the case of maprotiline. The mechanisms of these effects are discussed.

Adolescent↗
PubMed1983

Mianserin, maprotiline and the electroencephalogram.

1 EEGs were recorded from patients with depressive illness before and after four weeks of treatment with mianserin, maprotiline or placebo. 2 Visual analysis of the records showed a small but statistically significant increase in frequency of beta activity in the mianserin group. 3 One subject taking maprotiline developed spike and wave discharges but had no convulsive seizures. 4 The findings do not support those of previous studies. It seems that changes seen in the EEG early after treatment are not sustained for four weeks.

Adult↗
PubMed1983

Mianserin and convulsive seizures.

1 Forty patients have been reported to the Committee on Safety of Medicines (CSM) because of convulsions occurring during treatment with mianserin, suggesting that this drug is more epileptogenic than tricyclic antidepressants. 2 Details concerning 83% of these cases were obtained in a questionnaire study carried out in collaboration with the CSM and compared with those of a control group. 3 Ratings of the relationship between drug and effect carried out by neurologists and J.G.E. showed considerable variations and confidence of a causal connection in only a minority of patients. 4 As the CSM data do not allow for a reliable assessment of the relative epileptogenic effects of antidepressants, a comparison has been made between unpublished work on seizures occurring during treatment with imipramine and amitriptyline and published research on mianserin. This suggests that mianserin is no more epileptogenic than tricyclic antidepressants. 5 Factors that might predispose to seizures include relevant family and past medical history, starting treatment, a change in dose, benzodiazepine withdrawal and concomitant treatment with other drugs that have epileptogenic properties.

Adolescent↗
PubMed1982

Metabolic and cardiovascular adaptations in trained hypophysectomized rats.

Metabolic and cardiovascular changes resulting from acute and chronic exercise were examined in male Sprague-Dawley rats assigned to sham-control or hypophysectomized groups. Two weeks after surgery, the hypophysectomized rats had decreased their maximum oxygen consumption (VO2 max) and heart rate values by 4 ml X min-1 X kg-1 and 142 beats X min-1, respectively. Twenty weeks later, hypophysectomy was associated with a 22 ml X min-1 X kg-1 decrease in VO2 max and a 215 beat X min-1 decline in their maximal heart rates when compared with sham-control means. Endurance training was responsible for the significantly higher O2 consumption values. Additionally, trained animals exhibited longer run times, higher muscle cytochrome oxidase activity, and reduced food consumption. Measurements of right atrial choline acetyltransferase (CAT) activity and [3H]quinuclidinyl benzilate (QNB) binding revealed significantly higher CAT values and fewer muscarinic receptors. However, training had no significant effect on resting blood pressure, blood pressure changes with conditions of lower body negative pressure, muscle glycogen concentrations, CAT levels and QNB binding of the left atrium and ventricular regions, or receptor density. These results indicated that many of the adaptations that are characteristic of normal populations can occur in the absence of the hormones from the pituitary gland.

Adaptation, Physiological↗
PubMed1981

Influence of streptozotocin-induced diabetes and insulin on the functional capacity of rats.

Male Sprague-Dawley rats were assigned to three groups designated as diabetic, diabetic-plus-insulin, and control and tested for maximum oxygen consumption (VO2max) and maximum heart rate on three different occasions during the 6- to 8-wk experimental period. Compared with the prediabetic values and the means of the other two groups, diabetic animals had significantly higher submaximum and lower maximum VO2 values. These relationships prevailed when the groups were evaluated in terms of ml.kg-1.min-1 or ml.(kg0.79-1).min-1. In addition, the diabetic animals had significantly lower submaximum and maximum heart rates and shorter run times. Daily injections of insulin (2 U.day-1.rat-1) restored VO2max to within the limits of the control animals but did not normalize heart rates or run-time values. The linear relationship between heart rates and VO2 was repeatedly demonstrated with normal animals. However, this relationship progressively declined with the time course of diabetes. These results indicate that, in untreated diabetes, functional capacity is markedly reduced with the progression of the disease and suggest that alterations in the autonomic nervous system, tissue metabolic capacity, and decreases in lean body mass are responsible for the changes noted.

Animals↗
PubMed1981

Diazepam, propranolol and their combination in the management of chronic anxiety.

The therapeutic benefit of combining propranolol with diazepam over either of these drugs given alone was tested in a placebo-controlled crossover study with twenty-four chronically anxious out-patients. The combination was generally more effective than diazepam. Diazepam was more effective than placebo or propranolol. A reduction in the resting pulse rate by propranolol of more than 7.5 beats per minute resulted in a greater therapeutic response to this drug, alone and in combination. Lesser degrees of pathology responded better to treatment. Psychological factors in treatment showed themselves to be important in moderating pharmacological response. Chronically anxious patients generally derived little benefit from continued anti-anxiety treatment.

Adult↗
PubMed1981

Adverse effects of antianxiety drugs.

Antianxiety drugs, like other drugs used in psychiatry, can cause a wide range of adverse effects. Many physiological systems may be affected, but, as the main action of antianxiety drugs is on the central nervous system, this system is particularly vulnerable. All antianxiety drugs have the potential to produce untoward effects on higher cerebral functions, although the effect seen is also influenced by psychological and social factors. The most common effects is oversedation, which is a particular problem for the very young and the very old. It is also a serious problem for those who drive motor vehicles and may be a hazard when working in dangerous situations. Subjects are especially vulnerable when (a) antianxiety drugs are first introduced; (b) the dose is increased; and (c) these agents are taken in combination with alcohol and other drugs. Dependence on antianxiety drugs is well known, but only recently has it been recognised that dependence on benzodiazepines is a larger problem than previously realised. Other adverse effects are reviewed and summarised according to the system they predominantly affect. A review of this kind can easily give a biased impression of the dangers of antianxiety drugs; it should be made clear at the outset that many effects are rare, and in some instances a causal connection with the drug has not been established with certainty. Overall, benzodiazepines are the most widely used of all drugs and are remarkably safe-even when taken in massive overdoses. Some unwanted effects are readily preventable if antianxiety drugs are used with caution or avoided altogether in conditions where pathological disturbances of tissue sensitivity or drug disposition lead to exaggerated reactions. Particular care should be taken when prescribing these drugs for children and the elderly, and drugs that are not clearly essential for the well-being of the mother should be avoided during pregnancy and breast feeding. Antianxiety agents are grossly overprescribed. The frequency of occurrence of some adverse effects is therefore not so much a manifestation of the intrinsic toxicity of antianxiety drugs, but a reflection of their widespread use. Overprescribing and irrational prescribing also contribute to self-poisoning with these and other agents and to the cost of health services. The reasons for overprescribing are complex, but one contributing factor is the ready availability of effective antianxiety drugs.

Anti-Anxiety Agents↗