The safety and efficacy of clindamycin phosphate foam 1% versus clindamycin phosphate topical gel 1% for the treatment of acne vulgaris

Clindamycin phosphate is the most widely used topical antibacterial agent for acne treatment. Treatment of patients with mild to moderate acne vulgaris with a new foam formulation (clindamycin foam, CF) for 12 weeks was at least as effective as clindamycin gel (CG) based on the Investigator's Static Global Assessment (ISGA) score. CF was superior to CG based on the reduction from baseline in total (P = .0014), inflammatory (P = .0478), and noninflammatory (P = .0037) acne lesion counts. Additionally, CF achieved efficacy that was superior to that of vehicle foam based on ISGA score (P = .0025) and all 3 lesion counts (all P < .05). Adverse experiences in the active treatment groups were mild or moderate and transient in nature. Thus the foam formulation of clindamycin is a safe and effective acne treatment; the unique foam delivery vehicle may offer cosmetic benefits to the patient and thus increase compliance.     

Peripheral kappa-opioid agonist, ICI 204448, evokes hypothermia in cold-exposed rats

ICI 204448, a selective kappa-opioid agonist with limited CNS access, can be used to discriminate central and peripheral opioid actions on physiological systems such as pain and thermoregulation. Therefore, we investigated the effect of ICI 204448 (2.5, 5, and 10 mg/kg, s.c.) on male Sprague-Dawley rats exposed to ambient temperatures of 5, 20, or 32 degrees C. ICI 204448 did not alter the body temperature of rats maintained at 20 or 32 degrees C. However, 5 and 10 mg/kg of ICI 204448 evoked significant hypothermia in rats exposed to 5 degrees C. The i.c.v. administration of nor-BNI, a kappa-opioid antagonist, did not affect the hypothermia produced by the systemic injection of ICI 204448. Thus, an involvement of brain kappa-opioid receptors in ICI 204448-evoked hypothermia is unlikely. The present data demonstrate for the first time that ICI 204448 produces hypothermia in cold-exposed rats and suggest that the role of peripheral kappa-opioid receptors in thermoregulation becomes more significant at cold ambient temperatures.     

A key role for transmembrane prolines in calcitonin receptor-like receptor agonist binding and signalling: implications for family B G-protein-coupled receptors

Calcitonin receptor like-receptor is a family B G-protein coupled receptor (GPCR). It requires receptor activity modifying protein (RAMP) 1 to give a calcitonin gene-related peptide (CGRP) receptor. Little is known of how members of this receptor family function. Proline residues often form important kinks in alpha-helices. Therefore, all proline residues within the transmembrane helices of the receptor (Pro241, Pro244 in helix 4, Pro275 in helix 5, Pro321 and Pro331 in helix 6) were mutated to alanine. Pro241, Pro275, and Pro321 are highly conserved throughout all family B GPCRs. The binding of CGRP and its ability to stimulate cAMP production were investigated in mutant and wild-type receptors after transient transfection into COS-7 cells with RAMP1. The P321A mutation significantly decreased the pEC(50) for CGRP and reduced its affinity but did not change cell-surface expression. Antagonist binding [CGRP(8-37) and 1-piperidinecarboxamide, N-[2-[[5amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl) (BIBN4096BS)] was little altered by the mutation. Adrenomedullin-mediated signaling was disrupted when P321A was coexpressed with RAMP1, RAMP2, or RAMP3. The P331A mutant produced a moderate reduction in CGRP binding and receptor activation. Mutation of the other residues had no effect on receptor function. Thus, Pro321 and Pro331 are required for agonist binding and receptor activation. Modeling suggested that Pro321 induces a bend in helix 6, bringing its C terminus near that of helix 3, as seen in many family A GPCRs. This is abolished in P321A. P321A-I325P, predicted to restore this conformation, showed wild-type activation. Modeling can also rationalize the effects of transmembrane proline mutants previously reported for another family B GPCR, the VPAC(1) receptor.     

Integration of gene expression profiling and clinical variables to predict prostate carcinoma recurrence after radical prostatectomy

BACKGROUND: Gene expression profiling of prostate carcinoma offers an alternative means to distinguish aggressive tumor biology and may improve the accuracy of outcome prediction for patients with prostate carcinoma treated by radical prostatectomy. METHODS: Gene expression differences between 37 recurrent and 42 nonrecurrent primary prostate tumor specimens were analyzed by oligonucleotide microarrays. Two logistic regression modeling approaches were used to predict prostate carcinoma recurrence after radical prostatectomy. One approach was based exclusively on gene expression differences between the two classes. The second approach integrated prognostic gene variables with a validated postoperative predictive model based on standard variables (nomogram). The predictive accuracy of these modeling approaches was evaluated by leave-one-out cross-validation (LOOCV) and compared with the nomogram. RESULTS: The modeling approach using gene variables alone accurately classified 59 (75%) tissue samples in LOOCV, a classification rate substantially higher than expected by chance. However, this predictive accuracy was inferior to the nomogram (concordance index, 0.75 vs. 0.84, P = 0.01). Models combining clinical and gene variables accurately classified 70 (89%) tissue samples and the predictive accuracy using this approach (concordance index, 0.89) was superior to the nomogram (P = 0.009) and models based on gene variables alone (P < 0.001). Importantly, the combined approach provided a marked improvement for patients whose nomogram-predicted likelihood of disease recurrence was in the indeterminate range (7-year disease progression-free probability, 30-70%; concordance index, 0.83 vs. 0.59, P = 0.01). CONCLUSIONS: Integration of gene expression signatures and clinical variables produced predictive models for prostate carcinoma recurrence that perform significantly better than those based on either clinical variables or gene expression information alone.     

The World Health Organization European Health in Prisons Project after 10 years: persistent barriers and achievements

The recognition that good prison health is important to general public health has led 28 countries in the European Region of the World Health Organization (WHO) to join a WHO network dedicated to improving health within prisons. Within the 10 years since that time, vital actions have been taken and important policy documents have been produced. A key factor in making progress is breaking down the isolation of prison health services and bringing them into closer collaboration with the country's public health services.However, barriers to progress remain. A continuing challenge is how best to move from policy recommendations to implementation, so that the network's fundamental aim of noticeable improvements in the health and care of prisoners is further achieved.     

Social and physical environments and disparities in risk for cardiovascular disease: the healthy environments partnership conceptual model

The Healthy Environments Partnership (HEP) is a community-based participatory research effort investigating variations in cardiovascular disease risk, and the contributions of social and physical environments to those variations, among non-Hispanic black, non-Hispanic white, and Hispanic residents in three areas of Detroit, Michigan. Initiated in October 2000 as a part of the National Institute of Environmental Health Sciences' Health Disparities Initiative, HEP is affiliated with the Detroit Community-Academic Urban Research Center. The study is guided by a conceptual model that considers race-based residential segregation and associated concentrations of poverty and wealth to be fundamental factors influencing multiple, more proximate predictors of cardiovascular risk. Within this model, physical and social environments are identified as intermediate factors that mediate relationships between fundamental factors and more proximate factors such as physical activity and dietary practices that ultimately influence anthropomorphic and physiologic indicators of cardiovascular risk. The study design and data collection methods were jointly developed and implemented by a research team based in community-based organizations, health service organizations, and academic institutions. These efforts include collecting and analyzing airborne particulate matter over a 3-year period; census and administrative data; neighborhood observation checklist data to assess aspects of the physical and social environment; household survey data including information on perceived stressors, access to social support, and health-related behaviors; and anthropometric, biomarker, and self-report data as indicators of cardiovascular health. Through these collaborative efforts, HEP seeks to contribute to an understanding of factors that contribute to racial and socioeconomic health inequities, and develop a foundation for efforts to eliminate these disparities in Detroit.     

Liver transplantation: teaching strategies used with patients waiting for surgery

This study aims to describe the learning results of the implementation of teaching strategies involving patients who will be submitted to liver transplantation. One of these strategies is to give the patients a manual with orientations and the subsequent application of a questionnaire related to the content of the manual. Authors analyzed 13 patients who were waiting for liver transplantation. With respect to the answers regarding the questionnaire, an average of 83.8% of correct responses was given and only one patient got all the questions right. During the correction and the time to clarify their doubts, authors concluded that the opportunity of reading the manual and applying the questionnaire allowed patients and families to get a better understanding about the surgery's most important aspects.     

Can we evaluate population screening strategies in UK general practice? A pilot randomised controlled trial comparing postal and opportunistic screening for genital chlamydial infection

STUDY OBJECTIVE: To assess whether opportunistic and postal screening strategies for Chlamydia trachomatis can be compared with usual care in a randomised trial in general practice. DESIGN: Feasibility study for a randomised controlled trial. SETTING: Three West of Scotland general medical practices: one rural, one urban/deprived, and one urban/affluent. PARTICIPANTS: 600 women aged 16-30 years, 200 from each of three participating practices selected at random from a sample of West of Scotland practices that had expressed interest in the study. The women could opt out of the study. Those who did not were randomly assigned to one of three groups: postal screening, opportunistic screening, or usual care. RESULTS: 38% (85 of 221) of the approached practices expressed interest in the study. Data were collected successfully from the three participating practices. There were considerable workload implications for staff. Altogether 124 of the 600 women opted out of the study. During the four month study period, 55% (81 of 146) of the control group attended their practice but none was offered screening. Some 59% (80 of 136) women in the opportunistic group attended their practice of whom 55% (44 of 80) were offered screening. Of those, 64% (28 of 44) accepted, representing 21% of the opportunistic group. Forty eight per cent (59 of 124) of the postal group returned samples. CONCLUSION: A randomised controlled trial comparing postal and opportunistic screening for chlamydial infection in general practice is feasible, although resource intensive. There may be problems with generalizing from screening trials in which patients may opt out from the offer of screening.     

Patient preferences for anesthesia outcomes associated with cesarean delivery

When deciding on neuraxial medication (e.g., spinal opioids) for cesarean delivery (CS) under regional anesthesia, anesthesiologists make treatment decisions that "trade off" relieving pain with the potential for increased risk of side effects. No previous studies have examined obstetric patients' anesthesia preferences. Researchers administered 100 written surveys to pregnant women attending our institutions' expectant parent class. We determined patients' preferences for importance of specific intraoperative and postoperative anesthesia outcomes using priority ranking and relative value scales. We also explored patients' fears, concerns, and tolerance regarding CS and analgesics. Eighty-two of 100 surveys were returned and analyzed. Pain during and after CS was the greatest concern followed by vomiting, nausea, cramping, pruritus, and shivering. Ranking and relative value scores were closely correlated (R2 = 0.7). Patients would tolerate a visual analog pain score (0-100 mm) of 56 +/- 22 before exposing their baby to the potential effects of analgesics they receive. In contrast to previous general surgical population surveys that found nausea and vomiting as primary concerns, we found pain during and after CS as parturients' most important concern. Common side effects such as pruritus and shivering caused only moderate concern. This information should be used to guide anesthetic choices, e.g., inclusion of spinal opioids given in adequate doses. IMPLICATIONS: Medical care can be improved by incorporating patients' preferences into medical decision making. We surveyed obstetric patients to determine their preferences regarding potential cesarean delivery anesthesia outcomes. Unlike general surgical patients who rate nausea and vomiting highest, parturients considered pain during and after cesarean delivery the most important concern.