The emerging importance of chronic hepatitis C infection in Asian Americans

OBJECTIVES: To study the demographics, epidemiology, and natural history of chronic hepatitis C in Asian Americans. METHODS: This retrospective survey describes 260 Asian Americans with chronic hepatitis C referred to one tertiary center. RESULTS: Ninety-two percent of patients were born in Asia. Fifty-one percent reported a history of unsafe therapeutic injections, which was a risk factor only in those with exposure outside the United States (p < 0.0001). A history of transfusion was reported in 41% of patients and was more frequent in those with exposure within the Unites States (p < 0.0001). Only 3.8% reported a history of intravenous drug abuse, which was more frequent in those with exposure within the United States (p < 0.0001). Hepatitis C genotype 1 was detected in 64.2% of patients, genotype 2 in 18.3%, and genotype 6 in 11.3%. Genotype 1 had a significantly lower sustained virologic response rate (32.8%) to interferon treatment, compared with genotype 2 (77.8%) or 6 (69.2%). During a mean follow-up of 6 yr, 26 patients developed hepatocellular carcinoma (HCC). Logistic regression model revealed fibrosis stage 4 (odds ratio [OR] 8.87, 95% confidence interval [CI] 2.97-26.48, p < 0.0001), age at presentation (55 vs 35 yr--OR 3.45, 95% CI 1.22-9.75, p= 0.0194), and baseline albumin level (3.0 vs 4.0 mg/dL--OR 3.47, 95% CI 1.02-11.76, p= 0.0464) were independent predictive factors for HCC development. CONCLUSIONS: Asian Americans with a history of unsafe therapeutic injections must be screened for chronic hepatitis C. Antiviral treatment should be initiated prior to development of cirrhosis. Surveillance for HCC must be routinely performed in cirrhosis patients.     

Hepatic tuberculosis in absence of disseminated abdominal tuberculosis

Liver involvement in tuberculosis in absence of miliary tuberculosis is rare. This study was performed to analyse the spectrum and response to treatment of hepatic tuberculosis in the absence of miliary abdominal tuberculosis. Retrospective analysis of seven cases of hepatic tuberculosis without miliary abdominal tuberculosis who presented at the single tertiary referral center were analyzed. All patients presented with fever and hepatomegaly. Five of them had pain in upper abdomen and vomiting. HIV serology was positive in one patient. All patients had normocytic normochromic anaemia, raised erythrocyte sedimentation rate (Mean 65). Mild elevation of liver enzymes and low albumin (Mean 2.4 gm%) with reversal of albumin globulin ratio (Mean 0.6) were seen in all. Two had jaundice. Prothrombin time was normal in all and lactate dehydrogenase values were elevated in all (Mean 794 IU/L). On ultrasonography, 2 had multiple hypodense lesion, 1 had coarse echotexture of liver, 1 had hyperechoic pattern and 3 had just hepatomegaly. Complete resolution of liver lesions on treatment with 4-drug anti-tuberculosis drug chemotherapy was seen. In conclusion, liver tuberculosis has protean manifestations with nonspecific alteration of liver function tests and is best diagnosed on liver biopsy. Overall response to therapy is satisfactory.     

Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients

Introduction

Delirium occurs in most ventilated patients and is independently associated with more deaths, longer stay, and higher cost. Guidelines recommend monitoring of delirium in all intensive care unit (ICU) patients, though few data exist in non-ventilated patients. The study objective was to determine the relationship between delirium and outcomes among non-ventilated ICU patients.

Method

A prospective cohort investigation of 261 consecutively admitted medical ICU patients not requiring invasive mechanical ventilation during hospitalization at a tertiary-care, university-based hospital between February 2002 and January 2003. ICU nursing staff assessed delirium and level of consciousness at least twice per day using the Confusion Assessment Method for the ICU (CAM-ICU) and Richmond Agitation-Sedation Scale (RASS). Cox regression with time-varying covariates was used to determine the independent relationship between delirium and clinical outcomes.

Results

Of 261 patients, 125 (48%) experienced at least one episode of delirium. Patients who experienced delirium were older (mean ± SD: 56 ± 18 versus 49 ± 17 years; p = 0.002) and more severely ill as measured by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (median 15, interquartile range (IQR) 10–21 versus 11, IQR 6–16; p < 0.001) compared to their non-delirious counterparts. Patients who experienced delirium had a 29% greater risk of remaining in the ICU on any given day (compared to patients who never developed delirium) even after adjusting for age, gender, race, Charlson co-morbidity score, APACHE II score, and coma (hazard ratio (HR) 1.29; 95% confidence interval (CI) 0.98–1.69, p = 0.07). Similarly, patients who experienced delirium had a 41% greater risk of remaining in the hospital after adjusting for the same covariates (HR 1.41; 95% CI 1.05–1.89, p = 0.023). Hospital mortality was higher among patients who developed delirium (24/125, 19%) versus patients who never developed delirium (8/135, 6%), p = 0.002; however, time to in-hospital death was not significant the adjusted (HR 1.27; 95% CI 0.55–2.98, p = 0.58).

Conclusion

Delirium occurred in nearly half of the non-ventilated ICU patients in this cohort. Even after adjustment for relevant covariates, delirium was found to be an independent predictor of longer hospital stay.     

Real-Time Adherence Monitoring for HIV Antiretroviral Therapy

Current adherence assessments typically detect missed doses long after they occur. Real-time, wireless monitoring strategies for antiretroviral therapy may provide novel opportunities to proactively prevent virologic rebound and treatment failure. Wisepill, a wireless pill container that transmits a cellular signal when opened, was pilot tested in ten Ugandan individuals for 6 months. Adherence levels measured by Wisepill, unannounced pill counts, and self-report were compared with each other, prior standard electronic monitoring, and HIV RNA. Wisepill data was initially limited by battery life and signal transmission interruptions. Following device improvements, continuous data was achieved with median (interquartile range) adherence levels of 93% (87–97%) by Wisepill, 100% (99–100%) by unannounced pill count, 100% (100–100%) by self-report, and 92% (79–98%) by prior standard electronic monitoring. Four individuals developed transient, low-level viremia. After overcoming technical challenges, real-time adherence monitoring is feasible for resource-limited settings and may detect suboptimal adherence prior to viral rebound.     

Differential dynamics and activity-dependent regulation of alpha- and beta-neurexins at developing GABAergic synapses

Neurexins (NRXs) and neuroligins are key synaptic adhesion molecules that also recruit synaptic signaling machineries. Neurexins consist of α- and β-isoforms, but how they couple synaptic transmission and adhesion to regulate activity-dependent synapse development remains unclear, in part because of poor understanding of their cell biology and regulation in the relevant neurons. Here, we examined the subaxonal localization, dynamics, and regulation of NRX1α and NRX1β in cortical perisomatic inhibitory synapses. Both isoforms are delivered to presynaptic terminals but show significant and different turnover rate at the membrane. Although NRX1α is highly diffuse along developing axons and filopodia, NRX1β is strictly anchored at terminals through binding to postsynaptic ligands. The turnover rate of NRX1β is attenuated by neural activity and presynaptic GABA(B) receptors. NRXs, thus, are intrinsically dynamic but are stabilized by local transmitter release. Such an activity-adjusted adhesion system seems ideally suited to rapidly explore and validate synaptic partners guided by synaptic transmission.     

Brain natriuretic Peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases

Cardiac fibroblasts (CFs) produce extracellular matrix proteins and participate in the remodeling of the heart. It is unknown if brain natriuretic peptide (BNP) is synthesized by CFs and if BNP participates in the regulation of extracellular matrix turnover. In this study, we examined the production of BNP in adult canine CFs and the role of BNP and its signaling system on collagen synthesis and on the activation of matrix metalloproteinases (MMPs). BNP mRNA was detected in CFs, and a specific radioimmunoassay demonstrated that BNP(1-32) was secreted into the media at a rate of 11.2+/-1.0 pg/10(5) cells per 48 hours (mean+/-SEM). The amount of BNP secretion was significantly (P<0.01) augmented by 10(-7) mol/L tumor necrosis factor-alpha in a time-dependent manner. BNP significantly (P<0.01) inhibited de novo collagen synthesis as assessed by [3H]proline incorporation, whereas zymographic MMP-2 (gelatinase) abundance was significantly (P<0.05) stimulated by BNP between 10(-7) and 10(-6) mol/L. In addition, protein expression of MMP-1, -2, and -3 and membranous type-1 MMP was significantly increased by 10(-6) mol/L BNP. The cGMP analogue 8-bromo-cGMP (10(-4) mol/L) mimicked the BNP effect, whereas inhibition of protein kinase G by KT5823 (10(-6) mol/L) significantly (P<0.05) attenuated BNP-induced zymographic MMP-2 abundance. In summary, this study reports that BNP is present in cultured CFs and that BNP decreases collagen synthesis and increases MMPs via cGMP-protein kinase G signaling. These in vitro findings support a role for BNP as a regulator of myocardial structure via control of cardiac fibroblast function.     

Virus movement maintains local virus population diversity

Viruses are the largest reservoir of genetic material on the planet, yet little is known about the population dynamics of any virus within its natural environment. Over a 2-year period, we monitored the diversity of two archaeal viruses found in hot springs within Yellowstone National Park (YNP). Both temporal phylogeny and neutral biodiversity models reveal that virus diversity in these local environments is not being maintained by mutation but rather by high rates of immigration from a globally distributed metacommunity. These results indicate that geographically isolated hot springs are readily able to exchange viruses. The importance of virus movement is supported by the detection of virus particles in air samples collected over YNP hot springs and by their detection in metacommunity sequencing projects conducted in the Sargasso Sea. Rapid rates of virus movement are not expected to be unique to these archaeal viruses but rather a common feature among virus metacommunities. The finding that virus immigration rather than mutation can dominate community structure has significant implications for understanding virus circulation and the role that viruses play in ecology and evolution by providing a reservoir of mobile genetic material.     

Does race or socioeconomic status predict adverse outcome after out of hospital cardiac arrest: a multi-center study

Objective: To assess whether socioeconomic status (SES) or race is associated with adverse outcome after an out-of-hospital cardiac arrest (OHCA). Methods: A convenience sample of OHCA of presumed cardiac origin from seven suburban cities in Michigan, 1991–1996. Median household income (HHI), utilizing patient home address and 1990 census tract data, was dichotomized above and below 1990 state median income. Patient race was dichotomized as black or white. Outcome was defined as survival to hospital discharge (DC). Multiple logistic regression and Pearson’s χ² values were used for analysis. Results: Of 1317 cases with complete data for analysis, the average age was 67.3±16.0, 939 (71.1%) were white, 587 (44.4%) arrests were witnessed (WIT), and 65 (4.9%) were DC alive. There was no significant difference between races with respect to WIT arrests, V_T/V_F arrest rhythms, and a small difference in EMS response interval. Whites were more likely to be above median HHI (57.1 vs. 26.2%, P<0.001). Adjusted odds ratios for predictors of survival were WIT arrest (OR=3.76, 95% CI (1.7, 8.2)), V_T/V_F (OR=8.74, 95% CI (3.7, 10.8), but not race (OR=0.68, 95% CI (0.3, 1.4)) or SES (OR=1.51,95% CI 0.8, 2.8). Conclusion: In this population, neither race nor SES was independently associated with a worse outcome after OHCA.     

Cocaine and Marijuana Use Among Young Adults With Myocardial Infarction

Background

Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited.