Identification of a novel circulating recombinant form (CRF) 36_cpx in Cameroon that combines two CRFs (01_AE and 02_AG) with ancestral lineages of subtypes A and G

An array of CRFs have been identified in Cameroon, the most notable being CRF02_AG. HIV-1 in the East Province of Cameroon is particularly diverse: in a recent study, we found a high proportion of unique recombinant forms (URFs). Herein we describe the analysis of the full-length sequences of two of these URFs, which, after preliminary analysis of gag, pol, and env fragments, appeared to be a novel CRF. This novel strain, CRF36_cpx, contains fragments that can be assigned to the CRF01_AE, CRF02_AG, and subtype A and G radiations. Forty percent of the genome can be classified as CRF02_AG, including regions in gag, pol, env, and the accessory genes. Twenty-seven percent is CRF01_AE, comprising the majority of gag, the beginning of env, and the end of env into the 3' LTR. Twenty percent of the genome can be assigned to subtype A, with segments in pol and env. The remaining 13% of the sequence is classifiable as subtype G, in pol and vpu. The subtype A and G lineages formed by the CRF36_cpx sequences are unique and appear ancestral in nature. CRF36_cpx is both the first to combine more than one CRF and the first to include fragments of CRF02_AG. The ancestral sequences present in CRF36_cpx represent a link to extinct strains, and, potentially, insight into the evolution of HIV-1.     

Comparative analysis of cell culture and prediction algorithms for phenotyping of genetically diverse HIV-1 strains from Cameroon

Background  

With the advent of entry inhibitors, monitoring of viral tropism in the clinical setting is important. Conventional methods are cell-based and lengthy, therefore V3 sequence based prediction algorithms are becoming increasingly attractive as monitoring tools. Here we report a comparative analysis of viral tropism of strains circulating in Cameroon where diverse and emerging variant strains are prevalent.     

Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice

In humans, hereditary inactivation of either p22(phox) or gp91(phox) leads to chronic granulomatous disease (CGD), a severe immune disorder characterized by the inability of phagocytes to produce bacteria-destroying ROS. Heterodimers of p22(phox) and gp91(phox) proteins constitute the superoxide-producing cytochrome core of the phagocyte NADPH oxidase. In this study, we identified the nmf333 mouse strain as what we believe to be the first animal model of p22(phox) deficiency. Characterization of nmf333 mice revealed that deletion of p22(phox) inactivated not only the phagocyte NADPH oxidase, but also a second cytochrome in the inner ear epithelium. As a consequence, mice of the nmf333 strain exhibit a compound phenotype consisting of both a CGD-like immune defect and a balance disorder caused by the aberrant development of gravity-sensing organs. Thus, in addition to identifying a model of p22(phox)-dependent immune deficiency, our study indicates that a clinically identifiable patient population with an otherwise cryptic loss of gravity-sensor function may exist. Thus, p22(phox) represents a shared and essential component of at least 2 superoxide-producing cytochromes with entirely different biological functions. The site of p22(phox) expression in the inner ear leads us to propose what we believe to be a novel mechanism for the control of vestibular organogenesis.     

Excretion of methamphetamine and amphetamine in human sweat following controlled oral methamphetamine administration

BACKGROUND: Understanding methamphetamine (MAMP) and amphetamine (AMP) excretion in sweat is important for interpreting sweat and hair testing results in judicial, workplace, and drug treatment settings. METHODS: Participants (n = 8) received 4 10-mg (low) oral doses of sustained-release S-(+)-MAMP HCl (d-MAMP HCl) within 1 week in a double-blind, institutional review board-approved study. Five participants also received 4 20-mg (high) doses 3 weeks later. PharmChek sweat patches (n = 682) were worn for periods of 2 h to 1 week during and up to 3 weeks after dosing. The mass of MAMP and AMP in each patch was measured by GC-MS, with a limit of quantification of 2.5 ng/patch. RESULTS: MAMP was measurable in sweat within 2 h of dosing. After low and high doses, 92.9% and 62.5% of weekly sweat patches were positive, with a median (range) MAMP of 63.0 (16.8-175) and 307 (199-607) ng MAMP/patch, respectively; AMP values were 15.5 (6.5-40.5) and 53.8 (34.0-83.4) ng AMP/patch. Patches applied 2 weeks after the drug administration week had no measurable MAMP following the low doses, and only 1 positive result following the high doses. Using criteria proposed by the Substance Abuse Mental Health Services Administration, 85.7% (low) and 62.5% (high) weekly sweat patches from the dosing week were positive for MAMP, and all patches applied after the dosing week were negative. CONCLUSIONS: These data characterize the excretion of MAMP and AMP after controlled MAMP administration and provide a framework for interpretation of MAMP sweat test results in clinical and forensic settings.     

Treatment paradigm shift may improve survival of patients with high risk superficial bladder cancer

PURPOSE: Historically patients with recurrent T1 bladder tumors after bacillus Calmette-Guerin have been treated with bladder sparing approaches. Recently a paradigm shift has occurred since patients are increasingly offered radical cystectomy before disease progression to muscle invasion. In this study we explored the effect of this paradigm shift on progression rates and disease specific survival. MATERIALS AND METHODS: The historical cohort consisted of 307 patients from 3 prospective intravesical bacillus Calmette-Guerin protocols from 1980 to 1989. An institutional review board approved review identified 589 patients treated with bacillus Calmette-Guerin in a contemporary cohort from 1992 to 2004. RESULTS: In the historical cohort the 85 patients with documented T1 recurrence were initially treated with repeat transurethral resection and intravesical bacillus Calmette-Guerin. Of these 85 patients 60 had progression to muscle invasive disease. At 5 years after T1 recurrence, the cumulative incidence of progression to T2 disease was 71% (95% CI 61%, 81%) and the cumulative incidence of death from disease was 48% (95% CI 39%, 60%). In the contemporary cohort 129 patients had documented T1 recurrence. In this cohort 65 of the 129 patients with recurrent T1 underwent immediate radical cystectomy. At 5 years after T1 recurrence, the cumulative incidence of progression to muscle invasive disease was 28% (95% CI 20%, 38%) and the cumulative incidence of death from disease was 31% (95% CI 22%, 42%). CONCLUSIONS: Preemptive radical cystectomy performed for recurrent T1 disease following intravesical bacillus Calmette-Guerin therapy may be associated with better disease specific survival.     

Partial splenectomy for children with congenital hemolytic anemia and massive splenomegaly

Partial splenectomy is an alternative to total splenectomy for the treatment of congenital hemolytic anemias (CHAs) in children, although the feasibility of this technique in the setting of massive splenomegaly is unknown. This study was designed to evaluate the safety and efficacy of partial splenectomy in children with CHAs and massive splenomegaly. This retrospective study examined 29 children with CHAs who underwent partial splenectomy. Children were divided into 2 groups based on splenic size: 8 children had splenic volumes greater than 500 mL, whereas 21 children had splenic volumes less than 500 mL. Outcome variables included perioperative complications, transfusion requirements, hematocrits, reticulocyte counts, bilirubin levels, splenic sequestration, and splenic regrowth. All 29 children underwent successful partial splenectomy with 0.02 to 10 years of follow-up. After partial splenectomy, children overall had decreased transfusion requirements, increased hematocrits, decreased bilirubin levels, decreased reticulocyte counts, and elimination of splenic sequestration. Children with massive splenomegaly had similar outcomes compared with children without massive splenomegaly. Long-term complications included 3 mild infections, 4 cases of gallstones requiring cholecystectomy, and 1 child who required completion splenectomy. Partial splenectomy is a safe, effective, and technically feasible option for children with various CHAs, even in the setting of massive splenomegaly.     

Response to the 2004-2005 influenza vaccine shortage in veterans with spinal cord injuries and disorders and their providers

BACKGROUND/OBJECTIVES: To assess patient and provider behaviors regarding influenza vaccination, diagnosis, and testing strategies and the availability of influenza vaccine during the 2004-2005 nationwide influenza vaccine shortage. DESIGN/METHODS: Multisite, anonymous, cross-sectional surveys of patients and providers and qualitative interviews after the 2004-2005 influenza season. SETTING: Department of Veterans Affairs (VA) health care facilities with spinal cord injury centers or clinics. PARTICIPANTS: Stratified random sample of 3,958 veterans with spinal cord injuries and disorders (SCI & D; 31% response rate), 177 providers who treat persons with SCI&D, and 17 key informants. RESULTS: Most patient respondents (96.1%) reported awareness of a vaccine shortage (n = 938). When asked whether the shortage affected their ability to get the vaccine, 64.8% said they had no problem, whereas 12.1% reported an inability to get the vaccine. The vaccination rate was 71.8%; most veterans received the vaccine early (October-November) at the VA, and vaccination rates increased with age (P < 0.0001). Although vaccine shortages were reported by 47.5% of provider survey respondents (n = 177), most reported that the vaccine shortage did not affect availability of vaccine for patients with SCI&D. Few clinicians conducted diagnostic tests for influenza more often than in past years (4.9%). Although providers reported shortages at 12 centers (n = 23), patients with SCI&D had priority at 11 of 12 centers. CONCLUSIONS: Most patients were aware of the vaccine shortage, and the vaccination rate remained high and comparable with previous years. VA providers and facilities targeted SCI&D as a high-risk group and prioritized use of the limited vaccine supply for them.