Mental health services and the city: a neighbourhood-level epidemiological study

Journal of Public Health - Neighbourhood composition is considered a social determinant of mental health that can be addressed by policymakers to improve outcomes. Deprived neighbourhoods typically...     

Influence of HRT on prognostic factors for breast cancer: a systematic review after the Women's Health Initiative trial

INTRODUCTION: Mortality due to breast cancer has been reported to be the same or even lower in HRT users than in non-users. This has been attributed to earlier diagnosis and to better prognosis. Nevertheless, more advanced disease in HRT users was reported recently by the Women's Health Initiative (WHI) study. The objective of this study was to assess, using a systematic review of current literature, whether the data of the WHI study are in contradiction to observational data. METHODS: We selected 25 studies, for which we evaluated the methodology, the characteristics of the studied populations, confounding breast cancer risk factors and prognostic indicators. RESULTS: The WHI study, showing a worsening of some prognostic parameters, is in contradiction to most published observational studies. Most observational studies are retrospective, not well matched and did not consider most confounding factors. Their methodology and selection criteria varied considerably and the number of patients was often small. No differences in the distributions of histology, grade or steroid receptors were observed in the WHI trial, while this was the case in some of the observational studies. Other parameters (S phase, protein Neu, Bcl-2 gene, protein p53 and E-cadherin, cathepsin D) were not reported in the WHI trial. CONCLUSIONS: In view of these data, the current clinical message to patients should be changed: one can no longer declare that breast cancers developed while using HRT are of better prognosis.     

Adaptations in skeletal muscle capillarity following changes in oxygen supply and changes in oxygen demands

Summary The effects of changes in oxygen supply and oxygen demands on fiber cross-sectional areas, capillary dersities and capillary to fiber ratios were determined in three skeletal muscles of rat. The muscles examined were the vastus lateralis, soleus, and diaphragm. Reduced oxygen supply was produced by subjecting rats to ambient hypoxia, and increased oxygen demands were produced by subjecting rats to low ambient temperatures or treatment with thyroxin. Capillaries were visualized by injecting fluorescent dyes into the circulation. Muscles were quick frozen at resting lengths to preserve normal fiber geometry and were subsequently sectioned on a cryostat. All of the muscles sampled from animals in the experimental groups had elevated capillary densities. However, capillary to fiber ratios were not increased significantly in any muscle, for any experimental condition. Thus, all of the observed differences in capillarity were due to changes in the intrinsic rate of muscle fiber growth. Further, the relations of capillary density and capillary to fiber ratio to fiber area were the same as those obtained during normal maturation, suggesting that capillary growth is closely linked to the intrinsic rate of fiber growth.     

Comparative evaluation of surface deposits on high water content hydrogel contact lens polymers

Twenty soft contact lens wearers were fit with a high water content, non-HEMA (ofilcon A) lens (Durasoft 4; Wesley-Jessen) on the test eye. Patients subsequently wore one of the following four lenses on the same eye: a high-water content non-HEMA (surfilcon A) lens (Permaflex 74; CooperVision); a modified mid-water content HEMA (bufilcon A) lens (Hydrocurve Elite; Sola/Barnes-Hind); a low-water content HEMA (polymacon) lens (O4; Bausch & Lomb); or a low-water content non-HEMA (crofilcon A) lens (CSI; Sola/Barnes-Hind). All lenses were worn on a daily wear basis for one month and then evaluated with the scanning electron microscope (SEM). The amount of surface deposition was measured in terms of the area of lens covered by deposit as visualized on a standard series of SEM photographs. When control was obtained for patient, eye, technique, care system, and wearing time, similar amounts of deposit were found on the two high water content soft lenses. A significantly greater amount of deposit was found on the non-HEMA high water content ofilcon A lens compared to the mid-water content modified HEMA material. However, when the patient's tendency to produce "heavy" or "light" deposits on a soft lens surface is taken into account, then for the lighter depositors the high water content non-HEMA material was found to be as acceptable as the low water content HEMA and non-HEMA materials. But for heavy depositors the high water content non-HEMA material is not recommended.     

Isolation of the ERG2 gene,encoding sterol Δ8Δ→7 isomerase,from the rice blast fungus Magnaporthe grisea and its expression in the maize smut pathogen Ustilago maydis

The Magnaporthe grisea ERG2 gene, encoding ⁸⁷ sterol isomerase, was isolated from a genomic library by heterologous hybridization to a fragment of the Ustilago maydis ERG2 gene. The isolated gene contained a reading frame of 745 bp which encoded a protein of 221 amino acids. The coding region was interrupted by a single putative 79-bp-long intron. The deduced amino-acid sequence exhibited similarity to the ERG2 gene products of U. maydis and of Saccharomyces cerevisiae, particularly in the central region of the proteins. The NH₂-terminal of all three proteins contained a long stretch of amino acids that were strongly hydrophobic, suggesting that they may function by anchoring the protein to a membrane surface. The M. grisea ERG2 gene complemented a U. maydis deletion mutant in which the ERG2 gene had been removed using a one-step gene replacement procedure. The ⁸⁷ sterol isomerase produced by the M. grisea ERG2 gene exhibited a level of sensitivity to the sterol biosynthesis inhibitor, tridemorph, similar to that of the enzyme derived from the U. maydis ERG2 gene.     

Tolerance,cross-tolerance and dependence measured by operant responding in rats treated with triazolam via osmotic pumps

Previous research has found that drugs with affinity for (benzodiazepine) sites differ in their abilities to produce tolerance and dependence. The present study therefore investigated the effects of ligands of (BZ) sites in rats that had been rendered tolerant to a benzodiazepine. Two experiments were carried out in separate groups of rats. Behavioral changes induced by chronic infusion of triazolam (3 mg/kg/day, SC, for 14 days) via osmotic pumps were studied in animals trained on a fixed ratio 10 schedule of food presentation. Control animals were implanted with pumps containing the vehicle. Test drugs were administered IP using cumulative dosing. In one experiment triazolam decreased response rates on days 1, 2 and 3 after implantation of the pumps and tolerance developed to this depressant effect. In the other experiment, vehicle and triazolam treated rats differed in their responding during chronic infusion but differences were not statistically significant on any particular day. Flumazenil (3.0–30 mg/kg) greatly decreased rates of responding on day 11 in triazolam treated rats. This effect may represent a precipitated withdrawal syndrome. However, no withdrawal effects on operant performance were observed upon pump removal. Chronic infusion of triazolam did not affect the sensitivity of rats to alpidem on day 11 (10–100 mg/kg) whereas it abolished the stimulant effect of bretazenil (0.1–1.0 mg/kg). Chronic triazolam treatment produced tolerance to the depressant effects of triazolam (1.0–3.0 mg/kg), lorazepam (0.3–3.0 mg/kg) and zopiclone (10 mg/kg) but no tolerance to those of CL 218,872 (3.0–30 mg/kg) and zolpidem (0.3–3.0 mg/kg) when tested 3–14 days after pump removal. Differences between compounds highlighted with this model are in agreement with previous observations that these agents possess different pharmacological profiles and different potentials to induce tolerance and dependence.     

Level of use of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in humans correlates with EEG power and coherence

Rationale: Despite animal studies implicating 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of changes in neural function in humans who use MDMA as a recreational drug. Objective: The present study investigated whether there is a correlation between quantitative EEG variables (spectral power and coherence) and cognitive/mood variables, and level of prior use of MDMA. Methods: Twenty-three recreational MDMA users were studied. Resting EEG was recorded with eyes closed, using a 128-electrode geodesic net system, from which spectral power, peak frequency and coherence levels were calculated. Tests of intelligence (NART), immediate and delayed memory, frontal function (card sort task), and mood (BDI and PANAS scales) were also administered. Pearson correlation analyses were used to examine the relationship between these measures and the subject’s consumption of MDMA during the previous 12-month period. Partial correlation was used to control for the use of other recreational drugs. Results: MDMA use was positively correlated with absolute power in the alpha (8–12 Hz) and beta (12–20 Hz) frequency bands, but not with the delta (1–3 Hz) or theta (4–7 Hz) bands. MDMA use was negatively correlated with EEG coherence, a measure of synchrony between paired cortical locations, in posterior brain sites thought to overly the main visual association pathways of the occipito-parietal region. MDMA use did not correlate significantly with any of the mood/cognitive measures except the card sort task, with which it was weakly negatively correlated. Conclusions: Alpha power has been shown to be inversely related to mental function and has been used as an indirect measure of brain activation in both normal and abnormal states. Reduced coherence levels have been associated with dysfunctional connectivity in the brain in disorders such as dementia, white-matter disease and normal aging. Our results may indicate altered brain function correlated with prior MDMA use, and show that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of MDMA and other drugs. Received: 19 October 1998/Final version: 12 January 1999     

Antihyperglycaemic effect of saccharin in diabetic ob/ob mice

1. The effect of chronic saccharin (benzosulphimide) consumption on glucose homeostasis was examined in normal lean +/+ mice and genetically obese hyperglycaemic insulin-resistant ob/ob mice.
2. Consumption of a 5% (w/v) sodium saccharin solution for 7 weeks prevented the development of hyperglycaemia, improved glucose tolerance (area under curve decreased by 51%), reduced the extent of hyperinsulinaemia (by 21%), and reduced excessive weight gain (by 18%) in ob/ob mice.
3. Consumption of 5% (w/v) sodium saccharin temporarily decreased hyperphagia at the beginning of treatment, decreased hepatic glycogen content (by 47%), increased abdominal muscle glycogen content (by 82%), but did not significantly alter the hypoglycaemic response to exogenous insulin in ob/ob mice.
4. Consumption of a 1% (w/v) sodium saccharin solution did not prevent the development of hyperglycaemia in ob/ob mice.
5. Normal lean +/+ mice consuming 5% (w/v) sodium saccharin solution showed a marginal decrease (by 8%) in glycaemia, and glucose tolerance was improved (area under curve decreased by 30%) without a significant change in the insulin response to glucose or the hypoglycaemic effect of exogenous insulin.
6. The results suggest that chronic consumption of saccharin can defer the development of hyperglycaemia and improve glucose homeostasis in insulin-resistant ob/ob mice through a mechanism that is independent of insulin.