The stress cascade and schizophrenia: etiology and onset

Psychosocial stress is included in most etiologic models of schizophrenia, frequently as a precipitating factor for psychosis in vulnerable individuals. Nonetheless, the stress-diathesis model has not been tested prospectively in prodromal patients as a predictor of psychosis. The biological effects of stress are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, which governs the release of steroids, including cortisol. The past few decades have witnessed an increased understanding of the neural effects of stress and cortisol, including both normal and abnormal diatheses. As few biological markers have been evaluated as risk factors for psychosis in prodromal patients, the HPA axis and its interaction with intervening life events are apt candidates for study. In this article, we review the HPA axis and its neural effects, present a model for how stress might precipitate psychosis in vulnerable individuals, review the empirical evidence of a link between stress and schizophrenia symptoms, and propose a research design and appropriate statistical models to test the stress-diathesis model for psychosis onset in prodromal patients.     

Coping and psychological distress among symptomatic HIV+ men who have sex with men

This study evaluated relations among indicators of latent coping factors and psychological distress while incorporating measures of life stress and HIV illness related factors simultaneously among 211 symptomatic, HIV+ men who have sex with men (MSM). Participants were all assessed at a single time point. A structural equations model with latent factors for approachoriented coping, avoidant-oriented coping, and psychological distress showed adequate fit. Furthermore, significant associations were identified among latent factors for approach-oriented coping, avoidance coping, and psychological distress; specifically, greater use of approach-oriented coping strategies and less use of avoidant-oriented coping were associated with lower levels of psychological distress. The model was revised to incorporate variables significantly associated with psychological distress (i.e., personal loss-total events, personal loss-controllability, and HIV-related symptoms). Relations among the coping and psychological distress latent factors remained significant. The results suggest that HIV+ MSM who do not have the coping skills or resources necessary to use adequate coping strategies to face the chronic burdens associated with HIV illness are likely to experience higher levels of psychological distress, independent of life stress and ongoing HIV-related symptoms. This work was supported by grants from the National Institute of Mental Health, including PO1 MH49548, and T32 MH18917.     

Computerized reaction time battery versus a traditional neuropsychological battery: detecting HIV-related impairments.

In recent years, interest in the use of computerized neuropsychological (NP) assessment measures has increased. However, there are limited data regarding how performance on these measures relates to performance on more traditional, clinical instruments. In the present study, 82 HIV+ men, who were all believed on clinical grounds to have neurobehavioral impairment, completed a traditional NP battery (TNB) and the California Computerized Assessment Package (CalCAP, a collection of computerized reaction time tests). Summary scores based on a TNB, as well as those based on the CalCAP, demonstrated significant associations with both degree of immunosuppression (CD4 count) and detectable viral load in cerebrospinal fluid, but not with detectable viral load in plasma. Established norms on the TNB and CalCAP batteries resulted in classifying 57% and 49% of the HIV+ sample as impaired, respectively. When using the TNB as the "gold standard," impairment classifications based on CalCAP summary scores exhibited a sensitivity of 68% and a specificity of 77%. Overall agreement on impairment classifications between batteries was low (kappa = .44). Data from this study suggest that traditional NP batteries and computerized reaction time tests do not measure the same thing, and are not interchangeable in examining HIV-related NP impairments.     

An economic assessment of inhaled formoterol dry powder versus ipratropium bromide pressurized metered dose inhaler in the treatment of chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is debilitating and costly to manage. A recent clinical trial concluded that formoterol, a long-acting beta(2)-adrenoceptor agonist, was more clinically effective than inpratropium bromide in the management of COPD. OBJECTIVE: The aim of this study was to perform an economic assessment of the management of COPD with formeterol versus ipratropium bromide. METHODS: Assessment were based on the results of a previously published 12-week, multicenter, double-masked, randomized, parallel-group, placebo-controlled clinical trial comparing inhaled formoterol dry powder 12 and 24 microg BID with ipratropium bromide 40 microg QID pressurized metered dose inhaler and with placebo in 780 COPD patients. Treatment costs for study drugs and rescue medications were estimated from resource utilization and average wholesale prices. Costs were assessed with respect to forced expiratory lung volume in 1 second (FEV(1)) and patient-reported quality of life (QOL) as assessed via the St. George's Respiratory Questionnaire. Cost-effectiveness ratios were calculated for each treatment arm and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment relative to the next best alternative. Economic efficiency frontiers were identified. Sensitivity analysis was conducted. RESULTS: Cost analysis with respect to FEV(1) revealed an economic efficiency frontier formed by placebo, ipratropium bromide 40 microg, and formoterol 12 microg at their respective FEV(1) levels, with cost-effectiveness ratios of $30.18, $53.50, and $142.04, respectively, per FEV(1). The ICER for ipratropium over placebo was $273.03; for formoterol 12 microg over ipratropium, $1611.32. Cost analysis with respect to QOL showed an economic efficiency frontier formed by placebo and formoterol 12 microg at their respective QOL outcomes, with cost-effectiveness ratios of $25.96 and $32.56, respectively, per QOL score change. The cost-effectiveness ratio for ipratropium was $69.40,which was not on the QOL economic efficiency frontier. The ICER for formoterol 12 microg over placebo was $34.51 per QOL score point. CONCLUSIONS: Formoterol 12 microg provided greater QOL outcome than ipratropium bromide at an additional cost of $554.28 per year. Further research would be necessary to assess whether the differences in outcomes, particularly QOL, observed in the short term with formoterol would lead to favorable long-term health and economic outcomes.     

Effects of fluid resuscitation on mesenteric microvascular blood flow and lymphatic activity after severe hemorrhagic shock in rats

We investigated the acute microcirculatory effects, including mesenteric lymphatic pumping, of volume replacement with different iso- or hypertonic/oncotic solutions after severe hemorrhage (mean arterial pressure [MAP] approximately 35 mmHg during 30 min) in halothane-anesthetized Wistar rats. Resuscitation was achieved 30 min after induction of shock with one of the following solutions: autologous blood (BL); 0.9% NaCl (IS), 7.5% NaCl (HS); 5% bovine serum albumin (BSA); 0.9% NaCl-6% hydroxyethyl starch (HES), or 7.5% NaCl-HES (HES 7.5). MAP was partially and transiently restored by infusion of IS or HS, whereas in the groups treated with BL, HES, HES 7.5, or BSA, there was a complete restoration of blood pressure in the 30-min period after infusion. Microvascular blood flow (MBF), measured by laser Doppler flowmetry, was reduced by 59% +/- 7% 10 min after bleeding. MBF was also transiently restored after infusion of IS, HS, BL, BSA, or HES. HES 7.5 was the only solution able to induce immediate and sustained (60 min) restoration of preshock levels of MBF. Volume replacement with IS or HES 7.5 resulted respectively in long-lasting or transient lymphatic pumping overload. On the other hand, resuscitation with all other solutions, except BSA, did not restore lymphatic activity to preshock levels. We also observed a significant reduction of the diameter of mesenteric terminal arterioles (15-30 microm) after bleeding, which was reversed temporarily in IS, BL, and HES groups, whereas resuscitation with HES 7.5 solution was able to maintain arterioles dilated until the end of the experimental period. Therefore, it is concluded that the association of hyperoncotic and hyperosmotic solutions, represented here by HES 7.5, induces positive effects with respect to the macro- and microhemodynamics accompanied by restoration and maintenance of the interstitial drainage system, being indicated for maintenance of postresuscitation cardiovascular and microvascular function.     

Efficacy and safety of HLA-B7/beta-2 microglobulin plasmid DNA/lipid complex (Allovectin-7) in patients with metastatic melanoma

Human leukocyte antigen (HLA)-B7/beta-2 microglobulin plasmid DNA/lipid complex, otherwise known as Allovectin-7 (Vical, Inc., San Diego, CA, USA), has been developed as a non-viral gene delivery product. After multiple laboratory and human trials, it appears that the concept of gene transfer has established itself as a clinical reality. While the manifestations of the gene transfer have not been as dramatic as one might have hoped, HLA-B7/beta-2 microglobulin plasmid DNA/lipid complex appears to be a promising agent with an extremely safe toxicity profile. Ongoing trials are further investigating potential clinical uses of Allovectin-7.     

Food habits are associated with lipid peroxidation in an elderly population

OBJECTIVE: The purpose of this study was to assess the association between dietary intake and lipid peroxidation. DESIGN: Cross-sectional population analysis from an ongoing prospective study. Malondialdehyde (MDA) was measured as a marker of lipid peroxidation. Diet was assessed through direct observation and food frequency questionnaire. SUBJECTS: Participants with no missing data were 162 nonsmoking elderly individuals residing in 7 institutions across Asturias (Spain). STATISTICAL ANALYSES PERFORMED: Comparisons of adjusted group means by tertiles of plasma MDA were made by analysis of variance. Stepwise regression analysis was done using MDA as a dependent variable and food intake as an independent variable. Food intakes were categorized into quartiles and logistic regression was applied to calculate the odds ratio for being in the highest tertile of plasma MDA. RESULTS: Consumption of potatoes had an independent direct effect and accounted for a sizeable proportion of the variation in plasma MDA levels (18%, P<.001). In addition to potatoes, other foods that had an apparently independent effect on plasma MDA were eggs, cooked vegetables, and red wine (R(2)=0.028, 0.023 and 0.018, respectively). In this study, dietary factors accounted for 25% of the variation in plasma MDA levels. CONCLUSION: Identifying nutritional determinants of oxidative stress is important because of its negative health effect. Consumption of cooked vegetables and moderate intake of wine has been shown to be appropriate for reducing the risk of oxidative damage. On the contrary, caution must be used with the intake of potatoes because we have found a positive association with MDA levels. Further studies are required to investigate the mechanism(s) of this association and whether it is related to the preparation method or to the potato itself.     

Evolution of the Old World Arenaviridae and their rodent hosts: generalized host-transfer or association by descent?

Ten scenarios optimizing the number of cospeciation events between the phylogenies of the Old World Arenaviridae (OWA) and their murine hosts are tested while attempting to answer the following questions. Does the coevolutionary model explain their respective distribution? What kind of evolutionary events could have most frequently contributed to the horizontal and/or vertical transmission of the OWA? How to define secondary hosts and to interpret their existence in the evolutionary process? Where are the geographical origins of the OWA? All scenarios support the "diffuse coevolution" hypothesis previously proposed for the OWA, in which parallel phylogeny and/or host switches on closely related hosts can be considered as the most common mechanisms of transmission. The scenarios allow defining more precisely the concepts of principal and secondary hosts. Such scenarios also suggest that the diversity of the viruses and their rodent hosts could be higher than currently expected and that cophylogeny could have been underestimated. The "diffuse coevolution" hypothesis permits to interpret the transfer of the viruses to distant hosts as a result of a disturbance in their regular mode of dispersion, which could match with the periods of emergence as human parasites. The comparison of the viral phylogeny with the host cladogram also suggests that the viruses parasitized the Murinae before several lineages became distinct and spread in Africa. This supposes that the origin of the arenaviruses has to be found out of Africa.     

Bone marrow transplantation retinopathy

Background: Bonemarrow transplantion (BMT) isthe treatment of choice for bothmalignant and nonmalignant disordersof the bone marrow. BMT retinopathy occurs aftera latent period of 6 months and usuallyrecovers after a few weeks.Methods: We present a case of BMTretinopathy (BMT) in a patient with a high-degreeof non-Hodgkin lymphoma. We analysed the funduscopic andangiographic findings, andthe evolution of the case.Results: and conclusions: After a period oftwo and a half years we observed thespontaneous complete resolution of the funduslesions and the recovery of visual acuityAll of this confirm the theory that BMTretinopathy does not progress beyond theischemic microvascular stage.     

Italian drug information centres: benchmark report

Objective: Pharmacistoperated Drug Information Centres (DICs) in Italy were surveyed to gather current information concerning the status, availability and scope of their services. Methods: 40 DICs were identified and a questionnaire was mailed to them. Topics covered in the questionnaire included staffing, resources, activities and services. The results were compared with previous survey results to identify trends. Results: Information from 36 DICs was analysed (response rate =90%). Almost all regions of the country are represented. Pharmacists, parttime or fulltime, are the most frequent employees working in the DICs. 91% of DICs participate in the P/T committee, 74% takes part in the technical scientific committee for clinical experimentation and/or to the Medical Ethics committee and 60% participate in the hospital infection committee. 90% of DICs produce newsletters and/or bulletins and are involved in research projects. Regarding the questionanswer service, requests are mainly concerned with clinical comparative efficacy, therapeutic use, adverse effects. The most frequent users are physicians (67%) followed by pharmacists (16%) while other professionals use DICs to lesser extent. The most frequently used information sources, include "Goodman and Gilman's the pharmacological basis of therapeutics", Martindale: the Extra Pharmacopeia and Physician's Desk Reference; journals such as the Medical Letter, Adverse Drug Reactions Bulletin and Drug and Therapeutic Bulletin, Micromedex, Medline and IOWA databases.Data collected through the questionnaire and details about organisation and activity of Italian DICs are available in "Eupharma", the website of the Italian Society of Hospital Pharmacy (SIFO) at the URL http://www.sifo.it.Conclusion: The results parallel the European and American trends. In future communication and collaboration at European level could help to identify best practice models that would result in the standardisation of the activities and in the harmonisation of programs in common areas of interest.