A randomized comparative study of the metabolic effects of two regimens of gestrinone in the treatment of endometriosis

OBJECTIVE: To study some of the metabolic effects of oral gestrinone on plasma lipoprotein risk markers for cardiovascular disease and on bone density, a risk marker for osteoporosis. DESIGN: Randomized double-blind study. SETTING: All patients were referred to Gynaecology Clinic of Royal Free Hospital Medical School. PATIENTS: Twenty premenopausal women with laparoscopically confirmed endometriosis. INTERVENTIONS: Subjects were randomized in a double-blind fashion to receive either 1.25 mg or 2.5 mg gestrinone two times per week for 6 months. MAIN OUTCOME MEASURE: Laparoscopy was performed before treatment, and clinical responses were determined by second laparoscopy after 6 months. Plasma lipid and bone density measurements during and after therapy were compared with baseline. RESULT: Median total endometriosis scores decreased from 7.5 to 1.0 in the 1.25-mg group and from 7.0 to 0 in the 2.5-mg group. There were no significant between-group differences in endometriosis scores. At both doses, bone density in the spine and the proximal femur was conserved, but plasma concentrations of low-density lipoproteins rose by 13% and those of high-density lipoproteins fell by 40%. CONCLUSIONS: Reducing the dose of gestrinone to 1.25 mg appeared to maintain the therapeutic effectiveness of this treatment but was still associated with potentially unfavorable effects on lipids and lipoproteins.     

Induction of atypical squamous metaplasia with benzo[a]pyrene in cultured hamster tracheas

Areas of hyperplasia were produced in hamster tracheal epithelium maintained in vitro by exposure to a suspension of benzo[a]pyrene (BP) in gelatin. Typical and atypical epiodermoid metaplasia were seen by 2 weeks. In atypical areas, cell nuclei were enlarged with prominent nucleoli, the cytoplasm contained dense bundles of tonofilaments and the cells were joined by numerous desmosomes. The peak response to the carcinogen was reached 4 weeks after the application of BP and consisted of extensive atypical epidermoid metaplasia. Tracheas treated with gelatin alone maintained a columnar epithelium for 6 weeks of culture. The characteristics of the metaplastic changes in vitro are essentially identical to those described after exposure of the hamster tracheobronchial epithelium to benzo[a]pyrene-ferric oxide in vivo.     

The apolipoprotein E epsilon 4 allele does not influence the clinical expression of the amyloid precursor protein gene codon 693 or 692 mutations

In 31 symptomatic and 5 asymptomatic carriers of the amyloid precursor protein (APP) gene codon 693 mutation, 10 family members without mutation, and 5 carriers of the APP gene codon 692 mutation (3 with early-onset Alzheimer dementia, 2 with cerebral hemorrhage), a high frequency of the apolipoprotein E epsilon 4 allele was found. Age at onset, age at death, occurrence of dementia, and number of strokes did not differ between APP gene mutation carriers with or without epsilon 4 allele, showing that the clinical expression of these APP mutations is not influenced by the apolipoprotein E gene.     

Does the choice of antihypertensive therapy influence haemodynamic responses to induction, laryngoscopy and intubation?

We have measured haemodynamic responses to induction of anaesthesia, laryngoscopy and intubation in 103 mild-moderate hypertensive patients (83 patients (diastolic pressures < or = 110 mm Hg) currently receiving one of four monotherapies (ACE inhibitors, group A; beta adrenoceptor blocking drugs, group B; calcium channel antagonists, group C; diuretics, group D) and 24 were untreated hypertensive patients). Anaesthesia was induced with fentanyl 1.5-2.0 micrograms kg-1 and thiopentone 3-5 mg kg-1. Tracheal intubation was facilitated by vecuronium 0.1 mg kg-1 and anaesthesia maintained with enflurane and nitrous oxide in oxygen. Systolic and diastolic pressures (SAP, DAP) were measured at 1-min intervals by a non-invasive oscillometric method and cardiac output (CO) and stroke volume (SV) by thoracic bioimpedance. Induction of anaesthesia was associated with a decrease in SAP, DAP and CO in groups A-D (P < 0.05). Heart rate (HR) decreased in groups A and D (P < 0.01) and systemic vascular resistance (SVR) decreased in groups A and B (P < 0.05). SAP and HR increased in all groups after laryngoscopy and intubation (P < 0.01) as did SVR in groups A, B and D (P < 0.02). CO was unaltered. Similar changes occurred in the untreated hypertensive patients, although nine of 24 patients exhibited HR > or = 100 beat min-1 after laryngoscopy and intubation. Comparison of the changes in SAP, DAP, CO and SVR with time showed no differences in the five treatment groups; changes in HR were significantly less in group B compared with the other groups (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular evolution of the family Camelidae: a mitochondrial DNA study

We report the first molecular evolutionary analysis of the family Camelidae by analysing the full DNA sequence of the mitochondrial cytochrome b gene. Estimates for the time of divergence of the Old World (Camelini) and New World (Lamini) tribes obtained from sequence data are in agreement with those derived from the fossil record. The DNA sequence data were also used to test current hypotheses concerning the ancestors of the domesticated llama and alpaca. The results show that hybridization has occurred in the ancestry of both domesticated camelids, obscuring the origin of the domestic species.     

A community-based public-academic liaison program

OBJECTIVE: The authors discuss obstacles and incentives associated with successful community-based public-academic liaison activities and illustrate their conclusions by describing their public-academic liaison program, which received the American College of Psychiatrists' first annual Award for Creativity in Psychiatric Education. METHOD: The first 8 years of a state/university collaboration are described in which the parties involved first developed a variety of innovative services designed to fill specific gaps in the public service delivery system and subsequently integrated academic research and training components. RESULTS: The carefully planned and monitored process resulted in the exponential growth of interest in public sector work, the realization of the university's primary goals of developing high quality training and research sites, a substantial increase in the number of graduates accepting positions in the public sector, several projects funded by the National Institute of Mental Health, and two national awards. CONCLUSIONS: These collaborations illustrate the highly complementary relationship of public-academic liaison activities and their potential capacity to improve access to services, substantially improve the quality of these services, generate extramural support for services research, and increase the number of well-trained professionals in the public sector.