Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)-coinfected individuals does not lead to HBV polymerase mutations and is associated with persistence of lamivudine HBV polymerase mutations

Objectives

The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV‐coinfected individuals receiving tenofovir (TDF).

Methods

This retrospective cross‐sectional study identified 28 HIV/HBV‐coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on‐TDF), and 24 also had samples available prior to treatment (pre‐TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (±3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR‐positive samples was sequenced and compared with reference HBV data.

Results

Of the pre‐TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on‐TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3–23 months). Lamivudine (3TC)‐resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF‐resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual.

Conclusions

Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC‐resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF.     

Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory

The prefrontal cortex (PFC), a key brain region controlling cognition and emotion, is strongly influenced by stress. While chronic stress often produces detrimental effects on these measures, acute stress has been shown to enhance learning and memory, predominantly through the action of corticosteroid stress hormones. We used a combination of electrophysiological, biochemical, and behavioral approaches in an effort to identify the cellular targets of acute stress. We found that behavioral stressors in vivo cause a long-lasting potentiation of NMDAR- and AMPAR-mediated synaptic currents via glucocorticoid receptors (GRs) selectively in PFC pyramidal neurons. This effect is accompanied by increased surface expression of NMDAR and AMPAR subunits in acutely stressed animals. Furthermore, behavioral tests indicate that working memory, a key function relying on recurrent excitation within networks of PFC neurons, is enhanced by acute stress via a GR-dependent mechanism. These results have identified a form of long-term potentiation of synaptic transmission induced by natural stimuli in vivo, providing a potential molecular and cellular mechanism for the beneficial effects of acute stress on cognitive processes subserved by PFC.     

The National Center on Indigenous Hawaiian Behavioral Health study of prevalence of psychiatric disorders in native Hawaiian adolescents

OBJECTIVES: The prevalence rates of disorders among a community-based sample of Hawaiian youths were determined and compared to previously published epidemiological studies. METHOD: Using a two-phase design, 7,317 adolescents were surveyed (60% participation rate), from which 619 were selected in a modified random sample during the 1992-1993 to 1995-1996 school years: 590 selected randomly and 29 at risk (i.e., Center for Epidemiologic Studies-Depression score of >or=35 and suicidal risk) from grades 9-12. The Diagnostic Interview Schedule for Children-Version 2.3, was used to determine DSM-III-R diagnoses. Prevalence rates, weighted for ethnicity, Center for Epidemiologic Studies-Depression scores, and suicide attempts, were calculated for any diagnosis and various disorders. Meta-analyses compared the Hawai'i sample to four community-based studies (randomly selected youths from community populations) and two high-risk studies (homeless, low-income, or high unemployment communities). RESULTS: Hawaiian females had the highest rate for any diagnosis (37.7%; 95% confidence interval [CI] 28.4%-48.0%) and non-Hawaiian males had the lowest rate (19.6%; 95% CI 14.8%-25.5%). Hawaiian males (26.8%; 95% CI 18.2%-37.5%) and non-Hawaiian females (27.9%; 95% CI 22.2%-34.4%) had intermediate and comparable rates. Overall, Hawaiians had significantly higher rates (32.7%; 95% CI 26.1%-40.1%) than non-Hawaiians (23.7%; 95% CI 19.9%-28.0%) when controlling for gender, and girls had significantly higher rates (30.8%; 95% CI 25.8%-36.3%) than boys (21.1%; 95% CI 16.8%-26.1%) when controlling for ethnicity. These findings were primarily the result of the significant differences in rates regarding anxiety disorders. Meta-analyses showed the Hawaiian youth rate for any diagnosis was comparable to high-risk studies and nearly three times higher than the community studies. CONCLUSIONS: Hawaiian youths, especially females, are at high risk. Research on the sociocultural factors that underpin both the genesis of and protection from psychopathology is imperative for Hawaiian and non-Hawaiian mixed-ethnicity youths.     

Loss of nitroglycerin from aqueous solution into plastic intravenous delivery systems.

The mechanism of potential loss of nitroglycerin stored in plastic and glass containers was studied from an equilibrium and kinetic approach. Plastic strips equilibrated with dilute aqueous solutions of neat nitroglycerin showed that the drug was lost by absorption. Drug loss was followed by an electron-capture GLC assay. The same assay of control solutions in glass showed no drug loss in 48 hr at pH 5.7. The kinetics of nitroglycerin absorption and desorption were determined using synthesized 14C-labeled drug. Absorption can be quantified using a diffusion model, where the concentration in the aqueous phase falls with time. Curve fitting yielded an average diffusion coefficient in plastic of 2.05 x 10(-9) cm2/sec and a partition coefficient of 104 (plastic-water) at 30 degrees. Temperature-dependence studies of absorption showed that the diffusion coefficient followed an Arrhenius relationship with an energy requirement of 19.6 kcal/mole, whereas effects on the partition coefficient were negligible. Nitroglycerin desorption from plastic disks under sink conditions into water can be quantified by assuming a diffusion model where the concentration at the surface of a plane sheet remains constant. Nonlinear least-squares curve fitting generated a diffusion coefficient of 1.14 x 10(-9) cm2/sec for the desorption process at 30 degrees.     

Lymphomas of the head and neck.

Lymphomas of the head and neck arise in Waldeyer's ring, the salivary glands, nasal cavity, paranasal sinuses, thyroid gland, and orbit. Though anatomically in close proximity, lymphomas arising in these sites have distinct clinical characteristics. Factors that appear to influence the pattern of disease include concurrent conditions, such as Sj?gren's syndrome, and geographic factors, particularly with regard to nasal lymphomas. The treatment and prognosis of patients with head and neck lymphoma depends on the histologic grade of disease and extent of involvement at time of presentation. Most lymphomas are of intermediate-grade histology and early stage at presentation. A thorough understanding of clinical disease patterns and treatment options will allow the optimum management of these patients.     

Polymicrobial outbreak of intermittent peritoneal dialysis peritonitis during external wall renovation at a dialysis center.

OBJECTIVE: To investigate an outbreak of peritonitis in intermittent peritoneal dialysis (IPD) patients. DESIGN: An outbreak investigation was performed to identify the etiology of the polymicrobial outbreak, and a retrospective case-control study was conducted to assess the risk factors for development of peritonitis. SETTING: Renal dialysis center. PATIENTS: Ten episodes of peritonitis occurred in 8 of 61 patients over a 6-month period in which 669 IPD procedures were analyzed. INTERVENTIONS: Field visit to renal dialysis center to examine the entire IPD procedure, inspect the hospital environment, and perform air bacterial count. MAIN OUTCOME MEASURES: The environmental factors and risk factors contributing to the polymicrobial peritonitis outbreak in IPD patients. The incidence of IPD peritonitis was determined before and after interventions. RESULTS: The causative organisms included Acinetobacter baumanii (6), Stenotrophomonas maltophilia (2), Pseudomonas aeruginosa (1), Candida albicans (1), C. tropicalis (1), Enterococcus (3), and Enterobacteriaceae (2). Four episodes of peritonitis involved infection by more than one organism. Air sampling of the environment detected a median of 110 colony forming units of bacteria per cubic meter of air, 10% of which were found to be Acinetobacter baumanii. The source of this polymicrobial outbreak was attributed to the bamboo scaffolding structure covering the external wall of the hospital during renovation. A retrospective case-control study indicated that the absence of the flush-before-fill step was a risk factor for development of peritonitis. CONCLUSION: In addition to invasive aspergillosis in transplant or oncology patients, Acinetobacter peritonitis in dialysis patients should be considered another microbial cause of outbreak associated with hospital renovation.