Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise

To test the hypothesis that delayed onset muscular soreness (DOMS) following intense eccentric muscle contraction could be due to increased production of prostaglandin E2 (PGE2), ten healthy male subjects were studied. Using a double-blind randomized crossover design, each subject performed two isokinetic tests separated by a period of at least 6 weeks: once with placebo, and once with piroxicam (Feldene®). They were given one capsule containing either placebo or piroxicam (20 mg) per day for 6 days with initial doses given starting 3 days prior to isokinetic testing. Exercise consisted of eight stages of five maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases, on a Kin Trex device at 60°/s angular velocity. The subjective presence and intensity of DOMS were evaluated using a visual analogue scale immediately after, and 24 and 48 h after each test. The mean plasma concentration of PGE2 measured at rest and after exercise was significantly lower in the group treated with piroxicam (p < 0.05). However, statistical analysis (two-way ANOVA test) revealed that exercise did not cause any significant change of mean plasma PGE2 over time in either of the two groups. Eccentric work was followed by severe muscle pain in extensor and flexor muscle groups. Maximal soreness was noted 48 h postexercise. Serum creatine kinase activity and the serum concentration of myoglobin increased significantly, and reached peak values 48 h after exercise in both experimental conditions (p < 0.001). By paired t-test, it appeared that there were no significant differences in the serum levels of these two markers of muscle damage between the two groups at any time point. We conclude that: (1) oral administration of piroxicam fails to reduce muscle damage and DOMS caused by strenuous eccentric exercise; and (2) the hypothetical role of increased PGE2 production in eccentric exercise-induced muscle damage, DOMS, and reduced isokinetic performance is not substantiated by the present results

Lipid Profiles in HIV-Infected Patients Receiving Combination Antiretroviral Therapy: Are Different Antiretroviral Drugs Associated with Different Lipid Profiles?

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC:HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC:HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC:HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapin

Granulomatous hepatitis due to Bartonella henselae infection in an immunocompetent patient

<p>Abstract</p> <p>Background</p> <p><it>Bartonella henselae </it>(<it>B. henselae</it>) is considered a rare cause of granulomatous hepatitis. Due to the fastidious growth characteristics of the bacteria, the limited sensitivity of histopathological stains, and the non-specific histological findings on liver biopsy, the diagnosis of hepatic bartonellosis can be difficult to establish. Furthermore, the optimal treatment of established hepatic bartonellosis remains controversial.</p> <p>Case presentation</p> <p>We present a case of hepatic bartonellosis in an immunocompetent woman who presented with right upper quadrant pain and a five cm right hepatic lobe mass on CT scan. The patient underwent a right hepatic lobectomy. Surgical pathology revealed florid necrotizing granulomatous hepatitis, favoring an infectious etiology. Despite extensive histological and serological evaluation a definitive diagnosis was not established initially. Thirteen months after initial presentation, hepatic bartonellosis was diagnosed by PCR studies from surgically excised liver tissue. Interestingly, the hepatic granulomas persisted and <it>Bartonella henselae </it>was isolated from the patient's enriched blood culture after several courses of antibiotic therapy.</p> <p>Conclusion</p> <p>The diagnosis of hepatic bartonellosis is exceedingly difficult to establish and requires a high degree of clinical suspicion. Recently developed, PCR-based approaches may be required in select patients to make the diagnosis. The optimal antimicrobial therapy for hepatic bartonellosis has not been established, and close follow-up is needed to ensure successful eradication of the infection.</p

Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles?

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC