The metabolic effects of lopinavir/ritonavir in HIV-negative men

BACKGROUND: Therapy with HIV protease inhibitors (PI) has been shown to worsen glucose and lipid metabolism, but whether these changes are caused by direct drug effects, changes in disease status, or body composition is unclear. Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects. METHODS: A dose of 400 mg lopinavir/100 mg ritonavir was given twice a day to 10 HIV-negative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance, insulin sensitivity by euglycemic hyperinsulinemic clamp, and body composition were determined before and after lopinavir/ritonavir treatment for 4 weeks. RESULTS: On lopinavir/ritonavir, there was an increase in fasting triglyceride (0.89 +/- 0.15 versus 1.63 +/- 0.36 mmol/l; P = 0.007), free fatty acid (FFA; 0.33 +/- 0.04 versus 0.43 +/- 0.06 mmol/l; P = 0.001), and VLDL cholesterol (15.1 +/- 2.6 versus 20 +/- 3.3 mg/dl; P = 0.05) levels. There were no changes in fasting LDL, HDL, IDL, lipoprotein (a), or total cholesterol levels. Fasting glucose, insulin, and insulin-mediated glucose disposal were unchanged, but on a 2 h oral glucose tolerance test glucose and insulin increased. There were no changes in weight, body fat, or abdominal adipose tissue by computed tomography. CONCLUSION: Treatment with 4 weeks of lopinavir/ritonavir in HIV-negative men causes an increase in triglyceride levels, VLDL cholesterol, and FFA levels. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 h, but there is no significant change in insulin-mediated glucose disposal rate by euglycemic hyperinsulinemic clamp.     

Burkholderia cepacia infection and lung transplantation

Burkholderia cepacia has emerged as an important pathogen in patients with cystic fibrosis (CF) undergoing lung transplantation. Taxonomic analyses have divided B. cepacia into 7 closely related species called genomovars. The prevalence of B. cepacia infection ranges from 2% to 13% in CF patients with genomovar III being most prevalent. Risk factors for the acquisition of B. cepacia include greater severity of underlying CF, increasing age, having a sibling colonized with B. cepacia, and previous hospitalizations. One-year survival in patients with CF undergoing lung transplantation usually have been reported to be less than 70%. The antimicrobial resistance pattern of B. cepacia has correlated with inconsistent effect on survival. Presence of genomovar III also has been linked with survival of B. cepacia-infected patients; the survival rates were inferior for genomovar III as compared with non-genomovar III patients. Standard infection control techniques including isolation of both colonized and noncolonized individuals with frequent sputum culture have been recommended to prevent CF patients from acquiring B. cepacia infection. B. cepacia is inherently resistant to antipseudomonal antibiotics, colistin, and polymyxin.The combination of 2 or more antibiotics usually is recommended for the treatment of B. cepacia infections. Studies delineating the epidemiology and influence of B. cepacia infection on lung transplantation are warranted. This is a US government work. There are no restrictions on its use.     

Police AED programs: A systematic review and meta-analysis

Background

Approximately 359,400 out-of-hospital cardiac arrests occur in the United States every year, and around 60% of them are treated by emergency medical services (EMS) personnel. In order to alleviate the impact of this public health burden, some communities have trained police officers as first responders so that they can provide cardiopulmonary resuscitation and defibrillation to cardiac arrest patients. This paper is a review of the current literature on the impact of police automated external defibrillators (AEDs) programs in these communities.

Methods and results

A literature search of electronic journal databases was conducted to identify articles that evaluated police AED programs and quantified survival rates. The 10 articles that met the inclusion criteria were very heterogeneous in terms of study design, controlling for confounders, outcome definitions, and comparison groups. Two communities found a statistically significant difference in survival and 6 studies reported a statistically significant difference in time to defibrillation after the implementation of these programs. The weighted mean survival rate of the study groups was higher than that of the control groups (p < 0.001), as was the weighted mean survival rate of the group first shocked by police compared to those first shocked by EMS (39.4% vs. 28.6%, p < 0.001). The pooled relative risk of survival was 1.4 (95% CI: 1.3–1.6).

Conclusions

Though there are many challenges in initiating these programs, this literature review shows that time to defibrillation decreased and survival from out-of-hospital cardiac arrests increased with the implementation of police AED programs.     

Reversible regional wall motion abnormalities on exercise technetium-99m-gated cardiac single photon emission computed tomography predict high-grade angiographic stenoses

OBJECTIVES: We sought to determine the level of angiographic stenosis at which reversible regional wall motion abnormalities (RWMA) are present on exercise stress technetium-99m (Tc-99m)- gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and whether assessments of stress and rest RWMA add incremental diagnostic information. BACKGROUND: Stress and rest gated SPECT MPI enables the detection of post-exercise stunning. Although some studies have correlated RWMA to the severity of MPI defects, only one previous study correlated RWMA on gated MPI to angiographic findings. However, this correlation excluded patients with rest perfusion defects and did not involve gating of rest images. METHODS: One hundred patients undergoing angiography within six months of exercise stress Tc-99m (sestamibi)-gated SPECT MPI (in the absence of interim cardiac events or revascularization) were recruited. Images were acquired 15 to 30 min after stress and interpreted without knowledge of the Duke treadmill score, left ventricular ejection fraction and angiographic data. RESULTS: The sensitivity of reversible RWMA for angiographic stenoses >70% was 53%, with a specificity of 100%. The presence of reversible RWMA was able to stratify patients with angiographic stenoses of 50% to 79% and 80% to 99% with a high positive predictive value. A good correlation was noted between the presence of reversible RWMA and the coronary artery jeopardy score (R = 0.49, p < 0.0001). Multivariate analysis showed that the post-stress RWMA, Duke treadmill and reversible RWMA scores were significant predictors of angiographic severity. CONCLUSIONS: Post-stress and reversible RWMA, as shown by exercise stress Tc-99m-gated SPECT MPI, are significant predictors of angiographic disease and add incremental value to MPI for the assessment of angiographic severity.     

Color Change after 25% Hydrogen Peroxide Bleaching with Photoactivation: A Methodological Assessment Using Spectrophotometer versus Digital Photographs

This study aimed to evaluate the color change of teeth bleached with light activation using two different objective color measurement approaches after two years of clinical follow-up. A cross-sectional retrospective clinical study according to STROBE was followed including 30 participants. The 25% hydrogen peroxide gel (Philips Zoom) was applied with a supplementary LED light for 15 min in four cycles. Tooth color was assessed based on CIEL*a*b* values using a spectrophotometer (Spectroshade) at different time points (baseline, post bleaching, 1 week, 1 year, and 2 years). Standardized digital photographs were taken at each time point. The L*, a*, and b* values were measured from the digital photographs using Adobe Photoshop software. The color difference (ΔE) was separately calculated using the L*, a*, and b* values obtained with spectrophotometric and photographic analyses at each evaluation time. Data were analyzed with non-parametric tests (p < 0.05). A color regression was detected by both measurement approaches after 1 and 2 years (p < 0.05). Greater ΔE values were acquired with the spectrophotometer compared to the digital photographic analysis (p < 0.05). Although a greater color change was observed with the spectrophotometer, both approaches were able to detect the color rebound using the 25% hydrogen peroxide light-activated in-office system. Digital photographic analysis might therefore be used to assess color change after bleaching.     

Changes in beta 2-adrenoceptor and other signaling proteins produced by chronic administration of 'beta-blockers' in a murine asthma model

BACKGROUND: We have previously reported that chronic treatment with certain 'beta-blockers' reduces airway hyperresponsiveness (AHR) to methacholine in a murine model of asthma. METHODS: Airway resistance was measured using the forced oscillation technique in ovalbulmin-sensitized and ovalbulmin-challenged mice treated with several beta-adrenoceptor (beta-AR) ligands. We used the selective beta 2-AR ligand ICI 118,551 and the preferential beta 1-AR ligand metoprolol to investigate the receptor subtype mediating the beneficial effect. Expression of beta-ARs was evaluated using immunofluorescence. We evaluated several signaling proteins by western blot using lung homogenates, and measured the relaxation of the isolated trachea produced by EP2 and IP receptor agonists. RESULTS: Four findings were associated with the decreased AHR after chronic beta-blocker treatment: (1) the highly selective beta 2-AR antagonist/inverse agonist, ICI 118,551 produced the bronchoprotective effect; (2) beta 2-AR up-regulation resulted from chronic 'beta-blocker' treatment; (3) reduced expression of certain proteins involved in regulating bronchial tone, namely, Gi, phosphodiesterase 4D and phospholipase C-beta 1; and (4) an enhanced bronchodilatory response to prostanoid agonists for the IP and EP2 receptors. CONCLUSIONS: These data suggest that in the murine model of asthma, several compensatory changes associated with either increased bronchodilator signaling or decreased bronchoconstrictive signaling, result from the chronic administration of certain 'beta-blockers'.     

Disseminated trichosporonosis with atypical histologic findings in a patient with acute lymphocytic leukemia

We report a case of disseminated Trichosporon asahii in a patient on systemic antifungal therapy who presented with multiple cutaneous nodules suggestive of fungal infection. Histologic features resembled neutrophilic eccrine hidradenitis but staining with periodic acid‐Schiff and Gomori methenamine silver confirmed the clinical diagnosis. This case highlights the importance of maintaining suspicion for trichosporonosis and contextualizing histologic findings within the underlying clinical picture.     

Interobserver variation in the diagnosis and grading of dyskaryosis in cervical smears: specialist cytopathologists compared with non-specialists.

AIMS--To compare the assessment of dyskaryosis in cervical smears made by specialist consultant cytopathologists and consultant general histopathologists. METHODS--One hundred and ten cervical smears were circulated to 10 observers from five district general hospital histopathology departments and five major departments of cytopathology. Their responses were analysed by five consultant general histopathologists and five consultant specialist cytopathologists. In 54 of the 110 cases, the histology of a corresponding cervical biopsy specimen was compared with the smear assessments. RESULTS--Specialist cytopathologists were more consistent than non-specialists when diagnosing and grading dyskaryosis. They chose the higher grades of dyskaryosis more frequently than the non-specialists. The cytopathologists recommended referral for colposcopy more frequently, but if they asked for a repeat smear, they wanted it done within three months more frequently than the histopathologists. The specialists were more frequently in agreement with the biopsy grade of intra-epithelial neoplasia than the non-specialists, whose smear diagnoses tended to underestimate the severity of the histopathological abnormality. CONCLUSIONS--This study has shown major differences between specialist and non-specialist cytopathologists in the diagnosis and grading of cervical smears and in the recommended management of patients with abnormal smears. These differences may result in uneven clinical management of women with smear abnormalities. It is therefore important to explore possible strategies for standardising the reporting of cervical smears, such as centralisation of screening services, accreditation in cytopathology for non-specialist consultants, and the value of participation in external quality assessment schemes.