Syndrome X in women is associated with oestrogen deficiency

This study was undertaken to ascertain whether gynaecologicalhistory or a reduction in ovarian hormones are triggers of anginain menopausal women with a positive exercise test and normalcoronary arteries. The majority of patients with angina pectoris,a positive exercise test and normal coronary arteries are female,suggesting that the female gender may be important in the aetiology.We studied the gynaecological features of 107 women (age 53±9 years) with syndrome X, taken from a population of134 patients including 27 males. Cardiological investigationswere undertaken and detailed gynaecological history obtainedfrom all the female patients. Menopausal status was confirmedby plasma levels of oestradiol-17ß100 pmol. l^–1. In 95 of the 107 female patients, chest pain began either duringthe perimenopausal period (32) or after the menopause (63).Of the 63 menopausal patients, 43 had undergone hysterectomyat an average of 8 ± 6 years prior to the onset of chestpain. The incidence of hysterectomy in the study population(40%) was four times greater than that of an age-matched population.These findings confirm that the majority of patients with syndromeX are women in whom the chest pain began after the onset ofmenopause. Ovarian hormone deficiency may, therefore, play arole in the onset of syndrome X in female patients.     

SULPHASALAZINE-INDUCED AUTOIMMUNE ABNORMALITIES IN PATIENTS WITH RHEUMATIC DISEASE

Sulphasalazine is a commonly used second line agent in rheumatoidarthritis (RA) and other inflammatory joint diseases and isreported to be one of the least toxic of this group of drugs.Recently a severe allergic reaction and cases of lupus-likedisease have been described in patients with RA after treatmentwith sulphasalazine. We describe five patients, all with inflammatoryarthropathy who developed cutaneous vasculitis, lupus-like diseaseor atypical serology after exposure to sulphasalazine. Threeof four cases investigated were found to have the slow acetylatorphenotype. These reactions can complicate the diagnosis anddelay discontinuation of the drug. Moreover, present guidelinesfor the diagnosis of drug-induced lupus do not apply to themajority of patients with sulphasalazine-induced lupus. KEY WORDS: Sulphasalazine-induced lupus, Rheumatoid arthritis, dsDNA antibodies, Vasculitis     

1,1,1,2-Tetrafluoroethane: Repeat Exposure Inhalation Toxicity in the Rat, Developmental Toxicity in the Rabbit, and Genoxicity in Vitro and in Vivo

Subchronic and chronic studies were carried out in the rat anda developmental toxicity study in the rabbit with exposuresto 1,1,1,2-tetrafluoroethane (HFC 134a) by inhalation. In therat repeated exposure to 50,000 ppm HFC 134a for 13,52, and104 weeks elicited no effect on clinical condition, growth,and survival, or on a variety of hematological, clinical chemistry,and urinary parameters. Treatment-related pathological changeswere seen only at study termination at 2 years and were confinedto increased incidence of Leydig cell hyperplasia and adenomain male rats exposed to 50,000 ppm. The tumors, which were alsoseen in control animals, were benign and not life-threatening.A battery of in vitro and in vivo tests gave no evidence ofgenotoxic activity. With exposure to pregnant rabbits, the onlytreatment-related effects were of minimal maternal toxicityat high exposure concentrations; there were no effects on fetaldevelopment. It is concluded that HFC 134a is of very low toxicityand should be an acceptable alternative to CFCs.     

The representation of pleasant touch in the brain and its relationship with taste and olfactory areas

Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.     

Clozapine as a drug of dependence

Rationale: In schizophrenics, clozapine has been reported to induce various withdrawal signs and rapid onset relapse to psychosis on cessation of chronic treatment. Objective: The study was designed to develop an animal model of one aspect of clozapine tolerance and withdrawal using core body temperature measures. Methods: Two groups of 15 female Wistar rats were treated chronically (b.i.d.) with clozapine at 6 or 12 mg/kg per injection for 21 days prior to cessation of drug treatment, withdrawal being studied over 4 consecutive days. Body temperatures were assessed daily throughout the study. Results: Acutely, clozapine induced dose-related hypothermia, to which complete tolerance developed in both groups, the development of tolerance being more rapid in the group treated with 6 mg/kg per injection of clozapine. During withdrawal only the group treated chronically with 12 mg/kg per injection of clozapine showed rapid onset significant hyperthermia. This dissipated progressively over days, and was completely absent after 4 days of withdrawal. Conclusions: Clozapine induced a clear somatic withdrawal sign after chronic treatment. It is suggested that, in future research in both humans and animals, it is important to attempt to differentiate between clozapine withdrawal and clozapine withdrawal-induced relapse to psychosis. It is also important to characterise the clozapine withdrawal syndrome fully in animals; to establish the neurochemical mechanisms involved in such withdrawal; and to determine which novel antipsychotics are most efficacious in inducing clozapine-like withdrawal effects, in suppressing clozapine withdrawal, and in preventing relapse to psychosis in patients being transferred from clozapine to novel atypical antipsychotic drugs. Received: 14 May 1998/Final version: 14 September 1998     

Patients' and doctors' perception of long-term morbidity in patients with testicular cancer clinical stage I

Patient-based questionnaires were designed with the aim to identify and rank long-term somatic and psychosocial morbidity in patients with low-stage testicular cancer. A further intention was to compare patients' assessments with experienced doctors' general opinion on quality of life items in cured testicular cancer patients. In pilot study I, 103 tumour-free patients ranked items of physical and psychosocial morbidity after having had various kinds of treatment. Though the ranking procedure appeared to cause some difficulties amongst the patients and subsequently was abandoned, the results indicated considerable differences between the patients' and doctors' evaluations. In pilot study II patients were asked to score the different items. The questionnaire of pilot study II was completed by 107 patients from the Norwegian Radium Hospital (NRH) and 99 relapse-free patients from the Royal Marsden Hospital (RMH) with testicular cancer stage I at least 1 year after infradiaphragmatic radiotherapy (n = 94) or adjuvant chemotherapy (2 cycles,n=26), or patients who had been followed on the surveillance program (n = 86). A total of 93 doctors completed a similar questionnaire, thereby expressing their general opinion on long-term morbidity in comparable testicular cancer patients as seen during routine clinical follow-up. Both the irradiated patients and those on the surveillance program reported slight degrees of Raynaud-like phenomena, neurotoxicity and ototoxicity, most probably representing background morbidity in an age-matched general male population. Doctors tended to underestimate their patients' somatic morbidity, but often overestimated the degree of psychological distress, in particular in patients on the surveillance program. Significant differences between RMH and NRH patients with regard to sexual problems and to leisure time activity may be explained by cultural differences in the two countries. The items presented in the questionnaire used identify important issues for patients cured of testicular cancer which may be used in future multicentre trans-cultural studies assessing these patients' quality of life. This will provide sufficient data for psychometric testing and, together with the findings from patients' free comments, support the final design of a testicular cancer quality of life module.     

The effect of organizational type and hierarchical level on nurses' perceptions of hospital issues

Managers in four acute care hospitals in southeast Florida described the resource, management, outcome, and external issues confronting their organizations. Eight major issues and four contributing and resulting subissues associated with each were identified from the 746 separate issue statements the managers made. Nurses in the same four hospitals were asked to evaluate the impact of the eight issues on their organization and their work, as well as the extent to which the subissues had either contributed to or resulted from the main ones. Overall perceptual patterns are discussed, as well as the differential effects of both hospital type and level of employment on perceptions. It is suggested that differential perceptions among such a key component of the care delivery system as nurses will need to be better understood as hospitals seek to survive in a turbulent environment.     

Genetic manipulation of mammary epithelium by transplantation

Genes can be introduced into mammary epitheliumin vivo by the tissue reconstitution method. Primary cultures of mammary epithelial cells are prepared, a gene introduced using retrovirus vectors, and the cells transplanted into a mammary fat pad from which the normal epithelium has been removed. The cells reform an epithelium in which some cells express the introduced gene. The technique is reviewed and compared with the mammary-specific expression of genes in transgenic mice. To model the development of neoplasia, particularly the preneoplastic changes caused by a single oncogene alone, several oncogenes have been expressed this way—myc, Ha-ras, erbB, erbB2,Wnt-1, andhst/FGF-4. Each caused a different alteration to the growth pattern of the epithelium, such as altered branching, premature alveolus development, distorted duct structure, or altered hormone sensitivity. Insights into normal development have also been obtained by inappropriate expression of genes such asWnt-4.