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Biomedical subjects

A Fletcher

Publications and source records attributed to A Fletcher.

At least 181 records · Page 10Linked to original sources
PubMed1991

Risks and benefits in the trial of the European Working Party on High Blood Pressure in the Elderly.

Hypertensive patients over the age of 60 years were admitted to a double-blind placebo-controlled trial. Patients in the actively treated group received a combined potassium-losing and -sparing diuretic (triamterene 50 mg plus hydrochlorothiazide 25 mg; n = 416); this dose could be doubled and methyldopa (up to 2 g, daily) was added in 35% of patients when blood pressure remained high. The placebo group (n = 424) received matching capsules and tablets. Adverse effects were assessed in the double-blind period of the trial by calculating the incidence of abnormal biochemical results, investigator reports of diseases and prescriptions of concomitant therapy and a self-administered symptom questionnaire completed by patients. In 1000 hypertensive subjects over 60 years of age, 1 year of active treatment would prevent 11 fatal cardiac events, 6 fatal and 11 non-fatal strokes and 8 cases of severe congestive heart failure. No unexpected adverse treatment effects were observed. A significant excess incidence rate (per 1000 person years) was found in the active group compared with placebo for: (1) impaired renal function, a serum creatinine greater than 180 mumol/l (2.0 mg/dl); (2) mild hypokalaemia, a serum potassium less than 3.5 mmol/l; (3) reports of gout; and (4) an elevated serum uric acid greater than 0.52 mmol/l in men or greater than 0.46 in women. Elevated blood sugar and prescriptions for hypoglycaemic drugs tended to be more frequent in the actively treated group, but this difference was not statistically significant. In both groups, there was a low incidence (less than 7 per 1000 person years) of anaemia and depression and diseases of the liver, gall bladder or pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Trichothiodystrophy.

We describe a case of classic trichothiodystrophy occurring as an isolated disorder. This is the second reported case of trichothiodystrophy unassociated with systemic disorders, in contradistinction to other cases where there have been profound associated neuro-ectodermal abnormalities. The hair has shown the pathognomonic polarizing light-microscopic findings and the sulphur content has been confirmed to be reduced to approximately 50% by energy dispersive X-ray micro-analysis. Formal light-microscopic studies of hair cross-sectional shape using a Hardy microtome have confirmed the previous finding of a very thin or absent cuticle. An additional previously unreported finding was a 'scalloped' contour in a majority of hairs. The previously described ribbon shape could not be confirmed. Follow-up observation of the patient has shown clinical improvement with time.

Alopecia↗
PubMed1991

Counts of S-100 positive epidermal dendritic cells in Kveim test skin biopsies.

S-100 positive epidermal dendritic cells were counted in skin biopsies from 48 Kveim tests and four known foreign-body reactions. Counts in histologically positive Kveim biopsies (mean 11.3 per 200 basal cells) were significantly higher than in either negative biopsies (5.1; P less than 0.001) or foreign-body reactions (4.7; P less than 0.05). A similar difference was found, irrespective of the histological appearances, between biopsies from patients diagnosed clinically as having sarcoidosis (10.5) and those in which another diagnosis had been made (4.1; P less than 0.001). In biopsies from patients with sarcoidosis 70% had a positive Kveim test, 70% had a raised epidermal dendritic cell count and one or the other was positive in 90%. All cases in which both the Kveim test was positive and the dendritic cell count was raised had a final clinical diagnosis of sarcoidosis. Counts of S-100 positive epidermal dendritic cells are useful in differentiating positive reactions to Kveim suspension from non-specific reactions to foreign material and increase the diagnostic confidence of the Kveim test.

Cell Count↗
PubMed1991

Direct evidence for an important species difference in the mechanism of 8-OH-DPAT-induced hypothermia.

1. Parallel series of experiments were carried out in the rat and mouse in order to investigate the mechanism(s) underlying the hypothermia induced in rodents by the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2. In the mouse, lesioning of central 5-hydroxytryptaminergic neurones (by use of the neurotoxin, 5,7-dihydroxytryptamine; 5,7-DHT) abolished the hypothermic response to 8-OH-DPAT, and depletion of brain 5-hydroxytryptamine (5-HT) levels (with the 5-HT synthesis inhibitor, p-chlorophenylalanine) markedly attenuated the response in this species. These pretreatments did not significantly attenuate 8-OH-DPAT-induced hypothermia in the rat, except for a significant attenuation of the response in 5,7-DHT-lesioned rats at the top dose of 8-OH-DPAT (1.0 mg kg-1, s.c.). 3. Pharmacological pretreatments which facilitate 5-HT release (selective 5-HT uptake inhibitors, precursor (5-hydroxytryptophan) loading, or fenfluramine), markedly attenuated or abolished 8-OH-DPAT-induced hypothermia in the mouse. These pretreatments generally had no significant effect on 8-OH-DPAT-induced hypothermia in the rat. 4. The selective noradrenaline uptake inhibitor, desipramine, had no effect on the hypothermic response to 8-OH-DPAT in either species. The selective dopamine uptake inhibitor, nomifensin, significantly increased the hypothermic response to 8-OH-DPAT in the mouse, but did not affect the response in the rat except at high, motor stimulant doses, when the response was attenuated. 5. These data are consistent with the hypothesis that 8-OH-DPAT-induced hypothermia is mediated by presynaptic autoreceptors in the mouse and by postsynaptic 5-HT1A receptors in the rat. Preliminary data also indicate an involvement of dopamine release in the mouse but not in the rat.

5,7-Dihydroxytryptamine↗
PubMed1991

Treatment of basal cell carcinoma with intralesional interferon alpha-2b.

We report a series of 11 basal cell carcinomas of various types treated with nine intra-lesional injections of 1.5 million units of interferon alpha-2b. The diagnosis was confirmed histologically in each case. After 3 months' follow-up six tumours had resolved both clinically and histologically. In three cases the tumour size was reduced. One tumour grew larger. Side effects were well tolerated except by one subject who was withdrawn. Those cases which responded have now been followed-up for between 12 and 26 months with no clinical or histological evidence of tumour recurrence. This is the longest period of follow-up so far reported for this novel treatment. The results are encouraging and, if maintained in future series, may indicate a useful role for interferon alpha in the management of this common cutaneous malignancy.

Aged↗
PubMed1991

[A comparison of the effects of verapamil and nifedipine on the quality of life].

Aspects of quality of life (symptoms, psychological well-being and activity) were evaluated by self-administered questionnaires in a 4 months randomized double-blind trial of titrated doses of verapamil slow release (n = 41) compared with nifedipine retard (n = 40). An untreated diastolic blood pressure of 95 to 115 mm Hg was required for inclusion in the trial. The mean age in both groups was 55 years. A significant difference between the two drugs was found in the average reporting of symptoms with an increase on nifedipine (p less than 0.01). The reporting of swollen ankles and flushing (p less than 0.05) increased on nifedipine, and nocturia (p less than 0.05) increased on verapamil. Measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine (p = 0.05). There was no difference between the two groups in the fall in diastolic blood pressure (average 18 mm Hg on nifedipine and 17 mm Hg on verapamil). There was a significantly greater fall in systolic blood pressure on nifedipine (23 mm Hg) compared with verapamil (13 mm Hg) (p less than 0.01). The two drugs differed in their effects on measures of quality of life. The improvements in symptomatic complaints and psychological well-being on verapamil may have been due to inclusion in a trial, although we cannot exclude the possibility of a drug effect. Conversely the increase in symptoms and self-assessed cognitive impairment on nifedipine were considered to be side-effects of the drug.

Adult↗
PubMed1991

Histochemical demonstration of 5'-nucleotidase activity in inflammatory muscle disease.

Using a histochemical method, 5'-nucleotidase activity was investigated in 80 muscle biopsy specimens, including specimens from eight patients with muscular dystrophy, 18 with nonspecific type II fiber atrophy, 15 with polymyositis, and 29 histologically normal controls. An interstitial reaction for 5'-nucleotidase was associated with an inflammatory infiltrate in 19 of 21 positive cases. Of the 15 cases of polymyositis, 14 showed an extensive interstitial reaction surrounding most of the myofibers and extending well away from the areas infiltrated by inflammatory cells. The extensive nature of this reaction makes 5'-nucleotidase activity a useful adjuvant in the diagnosis of inflammatory muscle disease.

5'-Nucleotidase↗
PubMed1990

Four and a half year follow up of women with dyskaryotic cervical smears.

OBJECTIVE: To determine the proportion of women with mild or moderate dyskaryosis in cervical smears who (a) progress to cervical intraepithelial neoplasia grade III or worse or (b) regress. DESIGN: Four and a half year cytological follow up study of women with mild or moderate dyskaryosis in cervical smears. SETTING: 666 Women (mean age 28 (SD 8) years; range 14-74) found to have borderline, mild, or moderate dyskaryosis on routine screening. RESULTS: 45 Women (6.8%) had a cone biopsy recommended on the basis of an abnormal follow up smear (severe dyskaryosis suggestive of cervical intraepithelial neoplasia grade III or invasive cancer), and in one patient cervical intraepithelial neoplasia grade III was reported in a biopsy specimen after dilatation and curettage. Life table analysis gave a 14% probability of a patient being recommended for a biopsy after four and a half years of follow up (95% confidence interval 12% to 15%). There was a significant excess incidence of invasive cancer of the cervix in the series compared with the general population (five cases observed compared with less than 0.1 expected). 157 Patients (24%) showed reversion to a normal cell pattern sustained in several smears over more than 18 months but a single negative smear was an unreliable indicator of apparent regression. Having two successive smears showing mild dyskaryosis or a smear at any time showing moderate dyskaryosis was a significant predictor of a subsequent severely dyskaryotic smear. CONCLUSIONS: Women found to have mild or moderate dyskaryosis in cervical smears should be kept under regular surveillance. The optimum management of these patients--by cytology or colposcopy--needs to be determined by randomised controlled trials.

Adolescent↗
PubMed1990

Screening for cancer of the cervix in elderly women.

A substantial proportion of women aged over 65 years has not been screened for cancer of the cervix and women in this age group are not included in current screening programmes. This policy is not supported by evidence from the natural history of preinvasive lesions. Since older women present with late disease (and therefore have a poor survival) 5-year survival rates adjusted for stage were used to estimate the reduction in number of deaths in women aged 20 years or older (during a 5-year period) if opportunistic screening were to identify more cases of cervical cancer at an earlier stage. 353 lives would be saved and women older than 65 would benefit most, with a 63% improvement in 5-year mortality. Thus, there is no reason to exclude women aged over 65 years from screening for cancer of the cervix.

Adult↗
PubMed1990

A comparison of verapamil and nifedipine on quality of life.

1. Aspects of quality of life (symptoms, psychological well-being and activity) were evaluated by self-administered questionnaires in a 4 month randomised double-blind trial of titrated doses of verapamil slow release (n = 41) compared with nifedipine retard (n = 40). An untreated diastolic blood pressure of 95-115 mm Hg was required for inclusion in the trial. 2. The mean age in both groups was 55 years. A significant difference between the two drugs was found in the average reporting of symptoms with an increase on nifedipine (P less than 0.01). The reporting of swollen ankles and flushing (P less than 0.05) increased on nifedipine, and nocturia (P less than 0.05) increased on verapamil. Measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine (P = 0.05). 3. There was no difference between the two groups in the fall in diastolic blood pressure (average 18 mm Hg on nifedipine and 17 mm Hg on verapamil). There was a significantly greater fall in systolic blood pressure on nifedipine (23 mm Hg) compared with verapamil (13 mm Hg) (P less than 0.01). 4. The two drugs differed in their effects on measures of quality of life. The improvements in symptomatic complaints and psychological well-being on verapamil may have been due to inclusion in a trial, although we cannot exclude the possibility of a drug effect. Conversely the increase in symptoms and self-assessed cognitive impairment on nifedipine were considered to be side-effects of the drug.

Adult↗
PubMed1990

Epidermal dendritic S100 positive cells in necrobiosis lipoidica and granuloma annulare.

Using an antibody to S100 protein, the number of dendritic cells above the basal layer in the epidermis was assessed in necrobiosis lipoidica and granuloma annulare. A statistically significantly higher number of these cells was found within the epidermis in necrobiosis lipoidica compared with granuloma annulare and normal skin. The numbers were similar to those seen in sarcoidosis and tuberculous reactions in the skin, which raises the possibility of an immune pathogenesis for necrobiosis lipoidica.

Cell Count↗
PubMed1990

The initial effects on workload and outcome of a public education campaign on early diagnosis and treatment of malignant melanoma in Leicestershire.

We report our experience of the initial effects of a publicity campaign directed at early presentation of malignant melanoma in Leicestershire. The campaign resulted in a dramatic increase in workload and, at the pigmented lesion clinic, the numbers of new patients rose from 12.3 to 54.5 per clinic. There was a large rise in the number of new melanomas presenting in Leicestershire: from 1.02 per week before the campaign to 1.88 per week in the immediate post-publicity period. This was statistically significant (P less than 0.001). Although there was also an apparently encouraging rise in the percentage of thinner 'good prognosis' tumours, it was not possible to isolate this statistically from a pre-existing trend.

Dermatology↗
PubMed1990

Cutaneous malignant fibrous histiocytoma. A rare but serious malignancy.

We report 3 cases of malignant fibrous histiocytoma occurring as primary neoplasms of the skin. The first case developed in a leg ulcer of traumatic origin. The second developed on the lower lip at the site of a squamous cell carcinoma which had been treated by radiotherapy. The third arose on a calf at a site of previous surgery. The literature on this malignancy is reviewed, with emphasis on cutaneous involvement.

Aged↗
PubMed1990

Exposure to high pressure may produce the 5-HT behavioral syndrome in rats.

In addition to the motor events associated with high pressure neurologic syndrome (HPNS), we have observed behavioral changes that resemble the 5-hydroxytryptamine (5-HT) syndrome in free-moving rats exposed to pressures up to 70 ATA. These include a flat body posture, head weaving, reciprocal forepaw treading, and hyperlocomotion. Such changes occur when brain 5-HT levels are raised or when 5-HT receptors are activated. We have therefore studied the behavior of rats at pressure treated either with saline or with one of the following drugs: p-chlorophenylalanine (pCPA) which depletes brain 5-HT by 85-90%, Wy 27587 which inhibits 5-HT reuptake, 5-hydroxytryptophan (5-HTP) and carbidopa which increase brain 5-HT synthesis, and quipazine which is a 5-HT receptor-agonist. After treatment, rats were individually exposed to pressure, and behavioral scores were made for 5 min every 10 ATA up to 70 ATA by an unbiased observer who was not aware of the treatment given. Analysis of all control rats indicated that only a flat body posture, forepaw treading, and hyperlocomotion were positively correlated with pressure, and these events were used in all subsequent analysis. Rats treated with pCPA with whole brain 5-HT levels reduced by 90% had scores significantly less than controls. Rats treated with Wy 27587 showed significantly increased scores. Rats treated with 5-HTP and quipazine failed to show a significant increase in scores. These results suggest that a modified form of the 5-HT syndrome occurs when rats are exposed to increased pressure, and the behavioral events seen are consistent with some activation of the 5-HT1A receptor subtype.

5-Hydroxytryptophan↗
PubMed1990

A deficit of bladder cancer in an Asian community in the UK.

Over a 10-year period, the incidence of bladder cancer in the local Asian community living within the Ealing hospital catchment area was compared with that in the indigenous population and that in England and Wales. A significantly reduced incidence was seen in the Asian community, using both comparisons.

Asian People↗