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Biomedical subjects

D Wheatley

Publications and source records attributed to D Wheatley.

At least 19 recordsLinked to original sources

Minaprine in depression. A controlled trial with amitriptyline.

Minaprine (200 mg daily, either once or divided b.d.) was compared with amitriptyline (25-50 mg t.d.s.) over six weeks in 144 patients with major depression. Significant reductions in HRSD scores at the end of six weeks' treatment were recorded with both dose regimes of minaprine and with amitriptyline, with no significant differences between them. There was a significantly greater incidence of drowsiness and dry mouth with amitriptyline than with minaprine.

Adult

Macronuclear differentiation in conjugating pairs of Tetrahymena treated with the antitubulin drug nocodazole.

During Tetrahymena conjugation gamic nuclei (pronuclei) are produced, reciprocally exchanged, and fused in each mate. The synkaryon divides twice; the two anterior nuclei develop into new macronuclei while the two posterior nuclei become micronuclei. The postzygotic divisions were blocked with the antitubulin drug nocodazole (ND). Then pronuclei (gamic nuclei) developed directly into macronuclear anlagen (primordial macronuclei), inducing amicronucleate cells with two anlagen, or, rarely, cells with one anlagen and one micronucleus. ND had a similar effect on cells that passed the first postzygotic division inducing amicronucleate cells with two anlagen, while cells treated with ND at the synkarya stage produced only one large anlage. Different intracytoplasmic positioning of the nuclei treated with ND (pronuclei, synkarya and two products of the first division) shows that most of cell cytoplasm is competent for inducing macronuclear development. Only posteriorly positioned nuclei--products of the second postzygotic division--remain micronuclei. The total cell DNA content, measured cytophotometrically in control and in ND-induced amicronucleate conjugant cells with one and two anlagen, was similar in all three samples at 12 h of conjugation. Eventually, at 24 h this content was about 2 pg (8 C) per anlagen both in nonrefed control and in amicronucleate exconjugants. Therefore "large" nuclei developing in the presence of ND were true macronuclear anlagen.

Animals

Zopiclone.

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Azabicyclo Compounds

The stress profile.

The Stress Profile consists of a number of questionnaires which have been developed to assess the severity of stress in nine areas of life: social habits, social relationships, life events, sexual problems, sleep, psychiatric symptoms, old age, menstrual stresses, and 'stress and the heart'. The questionnaires have been validated for inter-rater reliability and against the Hamilton anxiety and depression rating scales. Using the Profile, the inter-relationships between different stress areas can be assessed, appropriate treatments advised, and the response to treatment in relation to different components evaluated.

Anxiety Disorders

Stress and the heart.

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Adrenergic beta-Antagonists

Minaprine: an anticholinergic-free antidepressant? Results of a controlled trial of mianserin.

Minaprine is an amino-phenylpyridazine antidepressant reported to be relatively free of anticholinergic effects, cardiotoxicity, drowsiness, and weight gain. Minaprine (100 mg t.d.s. and 100 mg b.d.) was compared with mianserin (20 mg t.d.s.) in 117 depressed patients, and all three regimes produced significant reductions in scores on the HRSD at the end of six weeks' treatment. There were no anticholinergic effects, but there was a significantly greater incidence of drowsiness with mianserin than with minaprine.

Antidepressive Agents

Changes in iron, zinc, and copper concentrations in serum and in their binding to transport proteins after cholecystectomy and cardiac surgery.

Concentrations of iron, zinc, and copper and of their respective transport proteins transferrin, albumin, and ceruloplasmin were measured in serum after elective cholecystectomy and cardiac surgery. The pattern of changes in the concentrations of iron, zinc, and copper was reproducible, with an early increase in serum iron and zinc, then a decrease in the concentrations as these metals are dissociated from their serum transport proteins. Zinc and iron concentrations change before the increase in C-reactive protein, which begins 8 h after incision, whereas the copper concentration in the serum remains constant in the early postoperative period. Quantitative and kinetic differences were observed in both the trace metal and protein changes after cardiac surgery and cholecystectomy. These studies indicate the complexity of interpreting changes in trace elements in serum after surgery.

Adult

Arnold-Chiari malformation: a diagnostic challenge.

Arnold-Chiari malformation is a disorder of embryologic development. In Type I, there is cerebellar displacement into the spinal canal, but hydrocephalus and syringomyelia are variable. Type II usually is manifested by severe hydrocephalus and myelomeningocele in infancy. Type I malformations may pose diagnostic challenges because they often produce bizarre and vague symptoms. A careful history and physical examination, coupled with neurologic testing, especially magnetic resonance imaging, will lead to the correct diagnosis.

Adult

New hypnotic agents: clinical studies in general practice.

The type of sleep problem should be determined so that the most appropriate hypnotic can be used, and in this respect duration of action is an important property. The benzodiazepine hypnotics are adequate for this purpose, but problems may arise due to daytime after-effects and the possibility of dependence developing. Non-benzodiazepine hypnotics may be useful alternatives and our group has undertaken double-blind comparative trials with two such compounds, namely zopiclone and zolpidem. Zopiclone was compared to temazepam in a cross-over trial on 36 patients and similar hypnotic effects were recorded. In a parallel group study, zolpidem 10 mg was compared to zolpidem 20 mg and placebo in 88 patients. Both doses of zolpidem were significantly better than placebo on a number of the parameters recorded, side-effects were negligible and there was no evidence of any rebound insomnia during the final control week.

Clinical Trials as Topic

Use of anti-anxiety drugs in the medically ill.

The Stress Clinic at the Maudsley Hospital investigates anxiety due to stress and its pharmacological treatment. Nine stress areas are investigated and their relative severities estimated: social habits, social relationships, life events, psychiatric morbidity, sexual stresses, sleep, stress in old age, menstrual stresses and stress and the heart. From the results a Stress Profile can be constructed for each patient to compare the importance of these different stresses and this can also be used as a measure of change in response to treatment. The benzodiazepine (BZD) anxiolytics can be divided into two groups according to duration of action, medium (8-12 h) and long (30-100 h). Short-acting BZD drugs are particularly useful for situational anxiety, when treatment can be interrupted over night and at weekends. To overcome problems of dependence, withdrawal effects, and daytime side-effects, new non-BZD anxiolytics have been developed: buspirone, alpidem and suriclone. These may be particularly useful for long-term treatment of anxiety. Another alternative is the use of adrenergic beta-blocking drugs of which propranolol and betaxolol have been used in the Clinic, because of their relatively high concentration in the brain when taken orally. Anxiety accompanying coronary heart disease and hypertension can be controlled with anxiolytic drugs and other illnesses with an anxiety component are: sexual disorders, menstrual disorders, asthma, gastro-intestinal conditions, dermatological conditions and chronic illnesses such as malignancy and AIDS. Lack of sleep is a subtle form of stress exerting an adverse effect in almost every illness known to man. BZD hypnotics can be divided into four groups: ultra-short-acting (3-4 h), short-acting (5-6 h), medium-acting (7-8 h) and long-acting (9-12 h). Depending on the nature of the insomnia, ultra-short-acting and short-acting BZD are particularly convenient with minimal disadvantages. Nevertheless, new non-BZD hypnotics are also being developed, i.e. zolpidem and zopiclone. These drugs are relatively short-acting and of equivalent potency to the BZD without problems of dependence etc. Anxiety, as either cause or effect, accompanies many medical illnesses and the use of anti-anxiety drugs as concomitant therapy can both reduce morbidity and improve prognosis.

Anti-Anxiety Agents

Experiences of a stress clinic.

The Stress Clinic has been established for the systematic investigation and quantification of various stress factors that may produce adverse effects on health. Nine areas are investigated: social habits, social relationships, life events, psychiatric, sexual, sleep, geriatric, menstrual, and stress and the heart. The degree of stress in each area is quantified and a Stress Profile constructed for each patient. The Stress Profile can then be used to determine in which areas stress is most important and appropriate treatment can then be prescribed. In a preliminary analysis, the commonest principal diagnosis was depression (47%), followed by anxiety (27%), whilst in 18% the main stress was insomnia and in three patients an organic illness (7%). The Stress Profile is also used to assess improvement and significant reduction in many of the main stress areas has been demonstrated, coincident with response to treatment. In particular, we have been using centrally acting beta-blocking drugs in the treatment of anxiety and panic attacks with similar results.

Adrenergic beta-Antagonists

Interpreting significance in an antidepressant drug trial.

In a clinical trial to compare two antidepressants, mianserin and dothiepin, the Last Visit Carried Forward (LVCF) analysis was used for the statistical tests. By this method, no significant differences were demonstrated between the antidepressant response of each drug, as measured by the Hamilton Depression Scale. Statistical significance (or lack of it) does not necessarily correlate with clinical significance and, since antidepressant drugs usually take 10-14 days to exert any effect, a further analysis was undertaken excluding patients who completed less than 2 weeks of the trial. This further analysis then demonstrated a statistically significant difference in favour of mianserin (p less than 0.05). In designing statistical analysis for clinical drug trials, it is important to take into account the therapeutic characteristics of the drugs under trial.

Adult