EXPERIENCE WITH TRILOSTANE IN THE TREATMENT OF CUSHING'S SYNDROME

Five patients with pituitary dependent Cushing's syndrome and two with adrenal carcinoma were treated with increasing doses of trilostane (up to 1440 mg daily). There was no consistent fall in serum cortisol levels. In addition there was no rise in the levels of precursors immediately preceding the proposed site of action of trilostane. These results suggest that trilostane does not effectively block the enzyme 3β-hydroxysteroid dehydrogenase Δ4,Δ5 isomerase in patients with Cushing's syndrome and that it should no longer be recommended for their treatment.     

DEMYELINATION INDUCED IN MICE BY AVIRULENT SEMLIKI FOREST VIRUS. II. AN ULTRASTRUCTURAL STUDY OF FOCAL DEMYELINATION IN THE BRAIN

Four-week-old mice were infected intraperitoneally with an avirulent strain A7(74) of Semliki Forest virus (SFV) and killed at 4, 10, 15, 21 and 29 days after inoculation. Focal demyelinating lesions were present by 10 days. These were usually accompanied by a mononuclear infiltrate which included lymphocytes possessing characteristic cytoplasmic projections. These latter extended deep into the cytoplasm of adjacent cells, which were usually astrocytes and macrophages. Other features of the focal lesions were expansion of the extracellular space and demyelination which appeared to be fragmentation or lysis rather than stripping of myelin by macrophages. Although healing occurred in some mice after 4 weeks, acute lesions were still found in others of the same age. It was concluded that the demyelination probably had an immunological basis, and interaction between elements of the immune system and glial cells was a factor which inhibited orderly remyelination of the relatively mild lesions resulting from this infection.     

Predictive value of, and observer variability in, several ways of reporting antepartum cardiotocographs

Summary. Each of three scoring systems, and oscillatory frequency, had significantly poorer correlation with fetal outcome than reporting the cardiotocograph (CTG) as either 'reactive' or 'non-reactive'. There was no significant difference in the intra- and inter-observer variability when the CTG was reported in this way.     

The structure of fucosylated blood group substances in fetal rat skin. The combined use of monoclonal antibodies and glycosyl hydrolases

Cell surface carbohydrates are thought to be important during embryonic development. We have studied a group of defined cell surface carbohydrates during the differentiation of fetal rat skin by the use of immunocytochemical techniques. We used monoclonal antibodies to the LeX and human blood group H type II haptens. The structure of the molecules carrying these haptens has been inferred by the sensitivity of the immune reactions to digestion by glycosyl hydrolases. The primitive ectoderm expressed the LeX hapten. The differentiating epidermis carries the H type II antigen, but this was only detected following cleavage of a terminally modified portion of the carbohydrate containing linear poly-N-acetyl lactosamine chains. These carbohydrates on epidermal cells are carried N linked to glycoproteins.     

An assessment of the reproducibility of combined glottography in a clinical setting

Although combined glottography has potential as a clinical tool, it has had limited use in the monitoring of laryngeal function before and after treatment. There is no data about the standardization nor reproducibility of the procedure. An indication of the reproducibility of combined glottography is paramount if changes in laryngeal function are to be measured accurately. Using a standardized technique, two complimentary studies examined the reproducibility of combined glottography within one sitting (Study 1) and over time (Study 2). The components of variance were analysed (ANOVA). In Study 1 the variance under controlled conditions for Open Quotient (OQ) and Speed Quotient (SQ) was only 13% and 18% respectively of the total, whilst in Study 2 the variance over time for OQ and SQ was 55% and 58% respectively. Under controlled conditions combined glottography is a reproducible technique.     

Pregnancies in women with hyperprolactinaemia: obstetric and endocrinological management of 50 pregnancies in 37 women

Summary. Fifty pregnancies occurred in 37 women with hyperprolactinaemia. Thirty women (81%) initially attended with infertility and 24 (65%) had secondary amenorrhoea. Twelve women (31%) had pituitary macroadenomas, of whom seven (19%) were treated with neurosurgery and/or external radiotherapy before conception. Fortyone conceptions (82%) followed treatment with bromocriptine. There were no unusual obstetric or endocrinological complications. Scrum prolactin measured at least 6 months post partum when under basal conditions, without bromocriptine and not breast feeding, showed no significant trends compared with initial values. Tumour growth was not stimulated by the high oestrogen levels of pregnancy.     

Preschool language intervention: a follow-up study

A follow-up study was undertaken of 38 children who had attended a preschool language unit with detailed assessments of 25 by speech therapists and an educational psychologist. The subjects were assessed in a number of areas (language, learning and social skills) using standardized tests and rating schedules completed by teachers and parents. The initial results are presented in terms of group characteristics. At a mean age of 8.3 years the children were still making progress in all areas of development. Although some 16% of the children were attending specialist schools or classes (language unit, physically handicapped unit, schools for children with severe speech and language problems), the majority (84%) were within the mainstream of education. A continuing language difficulty was apparent on standardized tests. Reading and spelling were slightly depressed, but not significantly so. However, parents and teachers saw the children as differing little from their peers. The conclusion is reached that preschool intervention can prevent later educational failure.     

Atrial Fibrillation After Implantable Cardioverter Defibrillator Implantation

Atrial fibrillation is a reported complication of automatic defibrillator implantation. Its incidence, risk factors, time-course, and complications have not been well-defined. Accordingly, data from 117 patients who underwent defibrillator implantation via a thoracotomy (n = 71) or nonthoracotomy (n = 46) approach were reviewed. To identify risk factors, 15 variables of potential predictive value were chosen and analyzed. Atrial fibrillation developed in 26/117 patients (22%) during the early postoperative period and all but one of these 26 patients had undergone thoracotomy (P < 0.001). Patients who developed atrial fibrillation tended to be older than those who did not (63 ± 2 vs 58 ± 2 years, P = 0.04) and more frequently had a prior history of paroxysmal atrial fibrillation (31 % vs 10%, P = 0.02). They were also less likely to be taking Class I or III antiarrhythmic drugs (1/26 vs 24/91, P = 0.01). By multivariate analysis, operative approach (P < 0.001), the absence of antiarrhythmic drug therapy (P = 0.006), and a prior history of atrial fibrillation (P = 0.003) were significant independent variables. Digoxin neither prevented the occurrence of atrial fibrillation nor slowed the maximal ventricular response. The mortality and complication rates did not differ between the two groups. The major adverse effect of postimplant atrial fibrillation was automatic defibrillator discharge; six patients received between 1 and 11 discharges for atrial fibrillation with rapid ventricular rates.