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Biomedical subjects

A Wakeling

Publications and source records attributed to A Wakeling.

At least 19 recordsLinked to original sources

Anorexia nervosa of late onset.

Forty-two female anorexia nervosa patients, with onset of first illness at 25 or more years of age, are described and compared with 143 patients with onset of first illness between the ages of 15 and 20 years. The data support the view that the older group forms part of the total population of anorexia nervosa patients, but that age exerts a pathoplastic influence on psychopathology and psychosocial stressors. Older patients lost more weight, but did not have significantly higher rates of concurrent mood disorder.

Adolescent

Differential changes in alpha- and beta-adrenoceptor linked [45Ca2+] uptake in platelets from patients with anorexia nervosa.

[45Ca2+] Uptake was studied in response to adrenaline, isoprenaline, noradrenaline, and (Bu)2cAMP in platelets from patients with anorexia nervosa. In both controls and anorectics, adrenaline, isoprenaline, noradrenaline, and (Bu)2cAMP stimulated [45Ca2+] uptake. In receptor subtype characterisation studies on control platelets, adrenaline-stimulated [45Ca2+] uptake was blocked by yohimbine (an alpha 2-adrenoceptor antagonist) and the specific beta 2-adrenoceptor antagonist ICI 118,551, but not by atenolol (a beta 1-antagonist). Isoprenaline action was blocked by ICI 118,551, but not by yohimbine. Noradrenaline-stimulated [45Ca2+] uptake was blocked by yohimbine but not by ICI 118,551. In platelets from anorectic patients, there was a significant increase in noradrenaline-stimulated [45Ca2+] uptake, a significant diminution in adrenaline and isoprenaline-stimulated [45Ca2+] uptake, but no significant difference in (Bu)2cAMP-stimulated [45Ca2+] uptake, when compared with controls. Basal uptake was also significantly enhanced in anorectics and was found to be inhibited with verapamil but not adrenoceptor antagonist. These data firstly indicate that both alpha 2- and beta 2-adrenoceptor activation elicits [45Ca2+] uptake by platelets. It is proposed that this stimulated [45Ca2+] uptake does not reflect changes in cytosolic Ca2+ but to localized changes of Ca2+ at the plasma membrane, possibly associated with receptor activation, per se. The respective increase and decrease of alpha- and beta-adrenoceptor activity in platelets from anorectic patients is in accord with other reports of changes of adrenoceptor number and type in platelets and other cells from anorectic patients. There may also be an increase in calcium channel activity in platelets from anorectics.

Adolescent

Circumvention of doxorubicin resistance in multi-drug resistant human leukaemia and lung cancer cells by the pure antioestrogen ICI 164384.

ICI 164384, a new steroidal antioestrogen, entirely devoid of oestrogenic activity, modulates doxorubicin resistance in vitro. At non-cytotoxic concentrations, ICI 164384 potentiated the cytotoxicity of doxorubicin in a dose-dependent manner in both the classical multi-drug resistant (MDR) human leukaemia cell lines CEM/VLB 100 and CEM/VLB 1000 and the human small cell lung cancer cell line H69 LX4. ICI 164384 had no effect on the two respective parental cell lines, CEM/CCRF and H69 P. None of these cell lines expressed the oestrogen receptor. In comparative studies at concentrations ranging from 1.25 to 10 mumols/l, ICI 164384 was significantly more effective (1.2-6-fold) than tamoxifen in reducing the IC50 of doxorubicin in the CEM/VLB 100 line. In resistant cells, ICI 164384 increased 3H-daunomycin accumulation in a dose-dependent manner and was significantly more effective than tamoxifen at concentrations ranging from 2.5 to 10 mumol/l. ICI 164384 reduced the efflux of daunomycin from resistant cells more effectively than tamoxifen. These studies suggest that ICI 164384 is an effective modulator of MDR.

Carcinoma, Small Cell

Abnormal eating attitudes in London schoolgirls--a prospective epidemiological study: outcome at twelve month follow-up.

The occurrence and course of eating disorder in a large representative population of 15-year-old London schoolgirls has been assessed using a two-stage survey methodology. Attempts to control weight were common and often transient. Dieting was in the great majority of girls found to be a benign practice without progression to more extreme concerns about food and weight. However, a small proportion of dieters did become cases and formed the majority of new cases found at follow-up. The relative risk of dieters becoming cases was eight times that of non-dieters. Many factors conventionally associated with eating disorder were associated more with attempting weight control than caseness. These included pre-morbid personality, pre-morbid obesity and family weight pathology. Other factors, including social class, career choice and psychosexual development, had no association either with attempting weight control or caseness.

Adolescent

A cognitive behavioural group approach for the treatment of bulimia nervosa--a preliminary study.

A group treatment for bulimia nervosa based on a cognitive behavioural approach is described. Eight women with a self reported average of 14 binging episodes per week attended a weekly group for 15 weeks. The techniques used in the group are described. Outcome measures included self reported frequency of binging episodes, eating attitudes, depression and anxiety. These were assessed both pre and post treatment. In addition binge frequency was assessed at 3 and 6 month follow up. Binging frequency decreased over the treatment period to an average of 1.1 per week and of 1.9 per week at 6 month follow up. Significant changes in eating attitudes, and a reduction in depression and anxiety were obtained over the treatment period. Although this study was not controlled it may represent a promising step towards the development of a cost-effective treatment for this common condition.

Adolescent

Diminished [3H] ouabain binding and 86Rb influx by leukocytes in anorexia nervosa.

Leukocyte Na-K ATPase was assessed in ten patients with anorexia nervosa. The indices of Na-K ATPase measured were 86Rb influx and [3H]-ouabain binding. Both 86Rb influx and [3H]-ouabain binding were significantly lower in patients with anorexia nervosa than in controls. Following weight gain (4.1 to 11.9 kg) in seven patients both 86Rb influx and [3H]-ouabain binding increased in each patient to levels similar to those in controls, although the patients still remained underweight. Acute oral glucose challenge (75 g) also resulted in an increase in 86Rb influx and [3H]-ouabain binding in each of the eight patients tested. There was a significant correlation between 86Rb influx and [3H]-ouabain binding. We conclude that the leukocytes of patients with anorexia nervosa have a significantly diminished number of Na-K ATPase units with a parallel decrease in 86Rb influx. Weight gain and acute glucose challenge result in an increase in both indices of Na-K ATPase. Nutrition appears to play an important role in the modulation of this enzyme.

Adolescent

Structural brain changes in patients with anorexia nervosa.

Twenty-five patients with anorexia nervosa were compared with 17 normal healthy control subjects in terms of their cerebral computed tomographic (CT) scan appearances. The patients displayed significantly greater ventricular and sulcal enlargement when compared to control subjects. There were no relationships between the CT scan appearance and clinical indices of illness severity or weight loss in the patient group. In 14 patients who had repeat scans after attaining normal body weight, no significant change was observed in the ventricular appearance, but there was a significant lessening in the degree of sulcal widening.

Adult

Abnormal eating attitudes in London schoolgirls--a prospective epidemiological study: factors associated with abnormal response on screening questionnaires.

One thousand and ten unselected London state schoolgirls were screened by questionnaire to identify an 'at risk' cohort displaying abnormal eating attitudes and two control cohorts, one with probable general psychiatric morbidity, one without. Members of all cohorts were assessed at interview for the presence of eating disorder and for putative risk factors implicated in the development of anorexia nervosa. A prevalence rate of 0.99% was detected for clinical eating disorder and 1.78% for the partial syndrome of eating disorder. Factors specifically associated with abnormal eating attitudes were identified, in particular, current or past overweight, history of amenorrhoea and perceived stress in school and social life. Some commonly accepted risk factors for eating disorders were discovered to be associations with general psychiatric morbidity. These were perceived parental pressure to eat more, taking exercise to lose weight, perceived stress at home and reporting a family history of anxiety or depression. Other well reported putative risk factors for eating disorder, including social class, birth order, age at menarche, obsessional personality and weight related career choice were not associated specifically with abnormal eating attitudes in schoolgirls. These findings represent cross-sectional data at entry into a prospective epidemiological study.

Adolescent

Vitamin D deficiency and low osteocalcin concentrations in anorexia nervosa.

The calcium, vitamin D, and osteocalcin concentrations were investigated in 17 patients with anorexia nervosa. Serum 25-hydroxyvitamin D (25 OHD) concentrations below normal were observed in 15 (88%); only two patients has serum 1,25 dihydroxycholecalciferol (1,25(OH)2D) concentrations below normal. Serum parathyroid hormone (PTH) concentration was also normal in all except these two patients. Serum osteocalcin concentration was below normal in seven of 14 patients. Although a low concentration of serum 25 OHD is common in patients with anorexia nervosa in the United Kingdom, 1,25(OH)2D concentrations are usually normal. Hypovitaminosis D with secondary hyperparathyroidism is relatively uncommon. The subnormal osteocalcin concentrations observed in these patients probably reflect diminished osteoblastic activity, which may contribute to their osteopenia.

1-Carboxyglutamic Acid

Cognitive impairment, emotional disorder and length of stay of elderly patients in a district general hospital.

All patients over 65 in a district general teaching hospital (n = 204) were screened for cognitive impairment and emotional disorder using the Clifton Assessment Procedures for the Elderly, the Mini-Mental State and the General Health Questionnaire. Patients scoring in the disordered range were psychiatrically assessed. These procedures gave an estimated prevalence of cognitive impairment of 22 per cent in the 164 patients satisfactorily assessed. Forty-three per cent of patients scored beyond the GHQ cut-off, but there was a high false positive rate. Cognitively impaired patients had a significantly longer hospital stay than the unimpaired. The majority (60 per cent) of these patients could not be discharged because of lack of an appropriate place elsewhere. Amongst all elderly patients whose discharge was prevented in this way, the cognitively impaired were markedly over-represented. The data have implications for the efficient use of hospital beds and for the welfare of elderly patients in acute hospitals.

Affective Symptoms

Adrenaline-induced hyperaggregability of platelets and enhanced thromboxane release in anorexia nervosa.

Platelet aggregation and thromboxane A2 release in response to adrenaline and the relationship of this response to body weight was investigated in female patients with anorexia nervosa. Platelets obtained from patients with body weights below 75% of the expected average weight (Group I) showed significantly greater aggregation and TXA2 release in response to adrenaline when compared with controls matched for sex and age. Patients with body weights 75-95% of the expected average weight (Group II) did not show enhancement of platelet aggregation or TXA2 release. In Group I patients, platelet hyperaggregability and enhanced TXA2 release induced by adrenaline tended to normalise following inpatient treatment and weight gain: with 0.5 mumol/l adrenaline, the pre-weight gain median aggregation was 65%, whereas the post-weight gain value was 37% - P less than 0.01. Markedly underweight patients also had hyperaggregability following stimulation with ADP and collagen. This hyperaggregability also tended to normalise after weight gain but these changes were not statistically significant. Platelet hyperaggregability (especially in response to adrenaline) in anorexia nervosa is therefore secondary to weight loss and reverts to normal with normalisation of weight. These changes may reflect the previously documented increase in platelet alpha-adrenoceptors in thin patients with anorexia nervosa and their normalisation following weight gain. However, the hyperaggregability in response to agonists other than adrenaline suggests that an additional post-receptor mechanism may be involved.

Adenosine Diphosphate

A second open letter to the General Medical Council.

In an open letter to the General Medical Council this independent group, drawn from several branches of the profession, expressed the belief that undergraduate medical education was failing in two respects; first, in the extent to which it equips doctors with the capacity to think critically for themselves; and secondly, in the degree to which it inculcates a broad and sensitive outlook towards the health of both individuals and communities. A remedy for both lies, in our opinion, in the better co-ordination of the different stages of medical education. Particularly important in this context is the period immediately after graduation. We therefore welcome the attention which the General Medical Council's Education Committee is now paying to this second stage. We welcome also the view which it has expressed that it is necessary to continue a broad education into the period when the qualified doctor is assuming responsibility for patient care. In this second letter we propose and discuss six aims for this period; and changes in educational organization needed if these aims are to be fulfilled.

Clinical Clerkship

Heparin-induced platelet aggregation in anorexia nervosa and in severe peripheral vascular disease.

We have previously demonstrated that platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease are hyperaggregable. Since conventional heparins are known to activate platelets in vitro and occasionally induce thrombosis and consumptive thrombocytopenia in vivo, we have investigated the direct effect of a conventional heparin on platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease. Heparin at therapeutic concentrations was found to induce platelet aggregation of such platelets in vitro. In contrast, a recently developed low molecular weight heparinoid (Org 10172), at therapeutic concentrations, had no effect on these hyperaggregable platelets. We conclude that: heparin may be potentially harmful to patients with hyperaggregable platelets; thrombocytopenia and thrombosis associated with heparin therapy may be mediated through a direct effect of heparin on platelets; it is unlikely that heparin induced thrombocytopenia is always mediated by classical immunological mechanisms, especially in patients with hyperaggregable platelets; and low molecular weight heparinoids may be safer anticoagulants in patients with platelet hyperaggregability.

Adolescent

Life events, depression and hypothalamic-pituitary-adrenal axis function.

The relationship between antecedent life events, clinical profile, and hypothalamic-pituitary-adrenal function was examined in 72 depressed patients. Antecedent life events were associated with first episodes of depression and with greater severity of illness, but their presence did not distinguish between patients diagnosed as endogenous or neurotic, and status on the dexamethasone suppression test was not associated with a greater or lesser likelihood of antecedent events. However, urinary free cortisol levels were higher in those patients with life events and difficulties.

Adult