Factors associated with sexual problems in HIV-positive gay men

Our objective was to determine factors associated with sexual problems in a sample of HIV-seropositive gay male clinic patients. Using a cross-sectional survey design a volunteer sample of 78 outpatient HIV-seropositive gay male service users completed a self-report questionnaire. This examined sexual problems, their perceived causes and associated factors including demographics, health status, sexual behaviour, self-justifications for sexual risk-taking and mood state (Hospital Anxiety and Depression Scale). Fifty (69%) of 78 HIV-positive gay men reported one or more sexual problems. Erectile dysfunction (ED) was reported by 38% rising to 51% in the context of trying to use condoms. Loss of interest in sex was reported by 41% and 24% experienced delayed ejaculation. The presence of sexual problems affected condom use in that 33 (90%) of the 37 gay men who had ED associated with condom use were inconsistent condom users in insertive sex compared to 28% of those not having this type of ED (P < 0.001). The presence of ED did not reduce the frequency of anal intercourse but those with ED associated with condoms were significantly more likely to have had receptive anal sex in the past three months (62%) compared to men without ED with condoms (38%) (P = 0.05). Risk cognitions such as wanting to lose oneself in sex, leaving responsibility for condom use to the active partner and perceptions that condoms interfere with pleasure were significantly more likely to be endorsed by those who report ED with condoms. Other factors associated with sexual problems included low T-cell counts (i.e. < 200). Psychological explanations were the most frequently cited causes of sexual problems, whether alone or in interaction with HIV disease itself, and combination therapy. A high incidence of sexual problems was found amongst this sample of HIV-positive gay men. Untreated sexual dysfunctions may contribute to sexual risk-taking and therefore HIV clinics need to address both issues. Further research is required to better understand the role of psychological factors, HIV disease itself and combination therapy in the incidence and treatment of sexual problems.     

Burning man 2011: mass gathering medical care in an austere environment

Abstract Introduction. Burning Man is a large weeklong outdoor arts festival held annually in the rugged and austere Black Rock Desert in northern Nevada. The 2011 event presented several unusual challenges in terms of emergency medical services (EMS) and medical care provision. Objective. This paper details the planning and subsequent emergency medical care for Burning Man 2011. Methods. This was a retrospective, observational review of the preparation, management, and medical care at Burning Man 2011. Results. Attendance at Burning Man 2011 was 53,735. Of these attendees, 2,307 were treated in the field hospital. While most patients had minor injuries, 33 were subsequently transported to a hospital (28 by ambulance and five by helicopter). The most common conditions treated were soft-tissue injuries, dehydration, eye problems, and urinary tract infections. There was one death (subarachnoid hemorrhage) and one patient in cardiac arrest (thoracic aortic dissection) who was successfully resuscitated and transferred. Burning Man 2011 presented numerous challenges in provision of EMS and medical care because of attendance size, the austere environment, and significant distance (150 miles) to definitive medical care. EMS operations included six dedicated ambulances, three quick-response vehicles, two first-aid stations, and a physician-staffed field hospital. The hospital had limited diagnostic capabilities (e.g., x-ray, ultrasound, basic laboratory analysis) and a limited formulary. We found that the use of physicians was necessary because much of the care provided was beyond the scope of paramedics. Conclusions. We describe the preparation and medical care for a large outdoor mass-gathering event held in a remote and austere environment. We met the stated goals of providing needed medical care while minimizing the need to transport attendees offsite for additional care. Our experience with Burning Man 2011 may aid planners with similar events.     

Pyrosequencing-based validation of a simple cell-suspension polymerase chain reaction assay for Campylobacter with application of high-processivity polymerase and novel internal amplification controls for rapid and specific detection

Although Campylobacter is an important food-borne human pathogen, there remains a lack of molecular diagnostic assays that are simple to use, cost-effective, and provide rapid results in research, clinical, or regulatory laboratories. Of the numerous Campylobacter assays that do exist, to our knowledge none has been empirically tested for specificity using high-throughput sequencing. Here we demonstrate the power of next-generation sequencing to determine the specificity of a widely cited Campylobacter-specific polymerase chain reaction (PCR) assay and describe a rapid method for direct cell suspension PCR to quickly and easily screen samples for Campylobacter. We present a specific protocol which eliminates the need for time-consuming and expensive genomic DNA extractions and, using a high-processivity polymerase, demonstrate conclusive screening of samples in <1 h. Pyrosequencing results show the assay to be extremely (>99%) sensitive, and spike-back experiments demonstrated a detection threshold of <10² CFU mL⁻¹. Additionally, we present 2 newly designed broad-range bacterial primer sets targeting the 23S rRNA gene that have wide applicability as internal amplification controls. Empirical testing of putative taxon-specific assays using high-throughput sequencing is an important validation step that is now financially feasible for research, regulatory, or clinical applications.     

Cardiorenal syndrome in acute decompensated heart failure

Cardiorenal syndrome (CRS) commonly occurs during treatment of acute decompensated heart failure (ADHF) and is associated with poor clinical outcome. The pathophysiology of CRS entails a complex interaction between hemodynamic alterations, including reduced renal perfusion, increased venous pressure and activation of multiple neurohormonal systems. Attempts to effectively treat congestion while preserving renal function in ADHF are often met with limited clinical success and often require therapeutic decisions that reflect a compromise between potential benefits and harm. At present, there is no evidence-based intervention specifically targeted at renal function. Recent Phase III randomized trials, using novel agents in patients with ADHF, have largely failed to demonstrate any benefits of therapy on renal and clinical outcomes. Early diagnosis of CRS using novel markers of tubular injury may allow for timely interventions and attenuate progression. Future studies are needed to further elucidate the pathophysiology of this complex syndrome and identify new potential targets for effective evidence-based treatments.     

Novel therapies in acute and chronic heart failure

Despite past advances in the pharmacological management of heart failure, the prognosis of these patients remains poor, and for many, treatment options remain unsatisfactory. Additionally, the treatments and clinical outcomes of patients with acute decompensated heart failure have not changed substantially over the past few decades. Consequently, there is a critical need for new drugs that can improve clinical outcomes. In the setting of acute heart failure, new inotrops such as cardiac myosin activators and new vasodilators such as relaxin have been developed. For chronic heart failure with reduced ejection fraction, there are several new approaches that target multiple pathophysiological mechanism including novel blockers of the renin-angiotensin-aldosterone system (direct renin inhibitors, dual-acting inhibitors of the angiotensin II receptor and neprilysin, aldosterone synthase inhibitors), ryanodine receptor stabilizers, and SERCA activators. Heart failure with preserved ejection fraction represents a substantial therapeutic problem as no therapy has been demonstrated to improve symptoms or outcomes in this condition. Newer treatment strategies target specific structural and functional abnormalities that lead to increased myocardial stiffness. Dicarbonyl-breaking compounds reverse advanced glycation-induced cross-linking of collagen and improve the compliance of aged and/or diabetic myocardium. Modulation of titin-dependent passive tension can be achieved via phosphorylation of a unique sequence on the extensible region of the protein. This review describes the pathophysiological basis, mechanism of action, and available clinical efficacy data of drugs that are currently under development. Finally, new therapies for the treatment of heart failure complications, such as pulmonary hypertension and anemia, are discussed.     

Early-phase transmission of Yersinia pestis by cat fleas (Ctenocephalides felis) and their potential role as vectors in a plague-endemic region of Uganda

In recent decades, the majority of human plague cases (caused by Yersinia pestis) have been reported from Africa. In northwest Uganda, which has had recent plague outbreaks, cat fleas (Ctenocephalides felis) have been reported as the most common fleas in the home environment, which is suspected to be a major exposure site for human plague in this country. In the past, C. felis has been viewed as only a nuisance-biting insect because limited laboratory studies suggested it is incapable of transmitting Y. pestis or is an inefficient vector. Our laboratory study shows that C. felis is a competent vector of plague bacteria, but that efficiency is low compared with another flea species collected in the same area: the oriental rat flea, Xenopsylla cheopis. On the other hand, despite its low vector efficiency, C. felis is the most common flea in human habitations in a plague-endemic region of Uganda (Arua and Nebbi Districts), and occasionally infests potential rodent reservoirs of Y. pestis such as the roof rat (Rattus rattus) or the Nile rat (Arvicanthis niloticus). Plague control programs in this region should remain focused on reducing rat flea populations, although our findings imply that cat fleas should not be ignored by these programs as they could play a significant role as secondary vectors.     

Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B

This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment-naive and treatment-experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to <18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA <1,000 copies/mL and normal alanine aminotransferase) compared to placebo-treated subjects (23% versus 0%; P = 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P = 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA <1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P = 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to <18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg+ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups. CONCLUSION: ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB, but was not different from placebo in subjects aged 2 to 11 years.     

A high-throughput, near-saturating screen for type III effector genes from Pseudomonas syringae

Pseudomonas syringae strains deliver variable numbers of type III effector proteins into plant cells during infection. These proteins are required for virulence, because strains incapable of delivering them are nonpathogenic. We implemented a whole-genome, high-throughput screen for identifying P. syringae type III effector genes. The screen relied on FACS and an arabinose-inducible hrpL sigma factor to automate the identification and cloning of HrpL-regulated genes. We determined whether candidate genes encode type III effector proteins by creating and testing full-length protein fusions to a reporter called Delta79AvrRpt2 that, when fused to known type III effector proteins, is translocated and elicits a hypersensitive response in leaves of Arabidopsis thaliana expressing the RPS2 plant disease resistance protein. Delta79AvrRpt2 is thus a marker for type III secretion system-dependent translocation, the most critical criterion for defining type III effector proteins. We describe our screen and the collection of type III effector proteins from two pathovars of P. syringae. This stringent functional criteria defined 29 type III proteins from P. syringae pv. tomato, and 19 from P. syringae pv. phaseolicola race 6. Our data provide full functional annotation of the hrpL-dependent type III effector suites from two sequenced P. syringae pathovars and show that type III effector protein suites are highly variable in this pathogen, presumably reflecting the evolutionary selection imposed by the various host plants.     

Increased renal hypertrophy in diabetic mice genetically modified at the haptoglobin locus

BACKGROUND: The human haptoglobin (Hp) gene is polymorphic with two functional classes of alleles, denoted 1 and 2. We have demonstrated in three longitudinal studies and several cross-sectional studies that the Hp genotype is an independent risk factor for diabetic vascular disease. These studies have presented a compelling argument that diabetic individuals homozygous for the Hp 1 allele are at decreased risk of vascular complications as compared to diabetic individuals with the Hp 2 allele. METHODS: The naturally occurring (wild type) mouse Hp is a class 1 Hp allele. We examined renal hypertrophy in wild-type mice, Hp knockout mice (Hp 0), and in mice with the Hp 2 allele (Hp 2) with and without diabetes. RESULTS: In the absence of diabetes, we found that renal hypertrophy was significantly increased in Hp 0 mice and that this could be prevented with vitamin E. There was no difference between wild type and Hp 2 mice with regard to renal hypertrophy in the absence of diabetes. However, in the presence of diabetes, Hp 2 mice demonstrated a significant increase in renal hypertrophy as compared to wild-type mice. CONCLUSIONS: These results support a direct linkage between diabetic vascular disease and the Hp genotype. These Hp-modified mice may serve as a platform on which to test a variety of pharmacological agents in order to decrease diabetic vascular disease.     

The impact of GP IIb/IIIa inhibitors during primary percutaneous coronary intervention in acute myocardial infarction patients

The use of glycoprotein (GP) IIb/IIIa inhibitors during percutaneous coronary interventions (PCI) in the acute phase of myocardial infarction (AMI) is still a matter of debate. The aim of the present study was to compare the outcomes of patients with acute ST-segment elevation myocardial infarction who underwent primary PCI and were concomitantly treated with GP IIb/IIIa inhibitors with those who were not treated with these drugs. Between January 1996 and November 2003, a total of 418 consecutive patients underwent PCI in the setting of ST-segment elevation AMI. At the operator's discretion, 287 patients were concomitantly treated with GP IIb/IIIa inhibitors and 115 patients were not. Angiographic success and final TIMI 3 flow in the infarct-related artery was achieved more frequently in patients treated with GP IIb/IIIa inhibitors (90% vs. 77%; p=0.001). The in-hospital composite endpoint of death, reinfarction and bleeding complications was significantly better in patients treated with GP IIb/IIIa inhibitors (4% vs. 12%; p=0.005). Furthermore, the adjusted 12-month survival rate was significantly better in these patients (RR: 2.99, CI: 1.29-6.9; p=0.01). Therefore, adjunctive therapy with GP IIbIIIa inhibitors during primary PCI is associated with improved short-term outcomes and one-year survival without an increased risk of bleeding.