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.     

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.     

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.     

Genetic mapping of modifier loci affecting malignant hypertension in TGRmRen2 rats.

BACKGROUND: Genetic background has a major influence on the manifestation of multifactorial diseases such as hypertension in which severe complications may be caused through an interaction with additional factors, which may be genetically determined. We have previously described a genetic model of malignant hypertension (MH) in rats carrying the mouse Ren2 gene (TGRmRen2-27), in which the phenotype is dependent on the genetic background. METHODS: Using a single homozygous TGRmRen2-27 male as transgene donor, we produced two F1 populations with (a) 100% penetrance of MH in progeny heterozygous for the Fischer F344 genetic background and (b) 58.5% penetrance in progeny heterozygous for the Lewis genetic background. To identify the modifier loci affecting the phenotype, a cohort of 252 males was produced by breeding the same single male with Fischer-Lewis F1 females. The progeny were phenotyped for clinical and pathological features of MH. RESULTS: Genome-wide screening and quantitative trait loci (QTL) analysis identified two loci, on chromosome 10 (LOD 4.4) and on chromosome 17 (LOD 3.9) close to the Ace and At1 genes, respectively, which contribute to the lethal MH phenotype. Their influence on mortality was consistent with a multiplicative effect of the two loci. In addition, we found higher plasma angiotensin-converting enzyme activity in progeny receiving the Fischer allele than in progeny receiving the Lewis allele (123.5 +/- 9.5 vs. 91.8 +/- 4.9 U/liter, P < 0.01), suggesting the association of angiotensin-converting enzyme and MH. CONCLUSIONS: Our study demonstrates the application of a transgene as a "major gene" to facilitate the identification of modifier loci, which can affect the phenotype of MH, and reveals Ace and At1 as candidate genes involved in the manifestation of the MH phenotype.     

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     

The Effect of Calcium Channel Antagonists on Spontaneous and Evoked Epileptiform Activity in the Rat Neocortex In Vitro

Calcium influx through voltage-activated calcium channels may play a crucial role in the propagation and maintenance of seizure activity. We have examined the contribution of various types of calcium currents to epileptogenesis by studying the effects of various calcium channel blockers on epileptiform activity. N-methyl-d-aspartate receptor-mediated epileptiform activity was induced by removal of magnesium ions superfusing the cortex, or by low-frequency stimulation of the underlying white matter. CoCl2, CdCl2 and omega-conotoxin, acting at the N- and L-type calcium channels, significantly reduced epileptiform activity. L-channel antagonists nifedipine and verapamil, and the agonist BAY K 8644, increased spontaneous bursting in cortical wedges, but had no effect upon evoked activity. The T-channel blocker NiCl2 had variable effects on epileptiform activity, whereas phenytoin consistently reduced such activity. These results suggest that calcium influx underlying epileptiform activity in the rat neocortex may occur at least partially via the activation of the N-type calcium channel. However, contributions from other calcium channel types cannot be excluded.     

The effect of temperature on copper tolerance ofParamecium

Summary The copper tolerance ofParamecium tetraurelia decreases with increased temperatures over the range of 12 C to 34 C. The relationship is linear and the correlation=–0.98. The regression equation has an intercept of 16 M Cu⁺⁺ at 0 C, and tolerance is reduced by 0.33 M for each degree increase in temperature.