Variability of bacterial vaginosis over 6- to 12-month intervals

OBJECTIVES: To examine variability in bacterial vaginosis (BV) over 6- to 12-month intervals. STUDY DESIGN: One thousand one hundred ninety-three women were followed for a median of 3 years with serial vaginal swab Gram stains for BV. Discrete time hazard models were fit to identify independent risk factors for BV. RESULTS: Women with BV at study entry were categorized as having normal flora at the next visit 20% of the time, and women with normal flora at study entry were categorized as having BV at the next visit 20% of the time. Among women with initially normal flora, factors associated with BV were black race, lower education, a history of BV, a history of chlamydial/gonococcal cervicitis, and lack of monogamy. CONCLUSION: About one fifth of women with normal flora develop BV over a given 6- to 12-month interval, and the modifiable risk factors of cervicitis and lack of monogamy contribute to the development of BV.     

Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis

The pathogenic mechanisms underlying acute pancreatitis are not clear. Two key pathologic acinar cell responses of this disease are vacuole accumulation and trypsinogen activation. We show here that both result from defective autophagy, by comparing the autophagic responses in rodent models of acute pancreatitis to physiologic autophagy triggered by fasting. Pancreatitis-induced vacuoles in acinar cells were greater in number and much larger than those induced with fasting. Degradation of long-lived proteins, a measure of autophagic efficiency, was markedly inhibited in in vitro pancreatitis, while it was stimulated by acinar cell starvation. Further, processing of the lysosomal proteases cathepsin L (CatL) and CatB into their fully active, mature forms was reduced in pancreatitis, as were their activities in the lysosome-enriched subcellular fraction. These findings indicate that autophagy is retarded in pancreatitis due to deficient lysosomal degradation caused by impaired cathepsin processing. Trypsinogen activation occurred in pancreatitis but not with fasting and was prevented by inhibiting autophagy. A marker of trypsinogen activation partially localized to autophagic vacuoles, and pharmacologic inhibition of CatL increased the amount of active trypsin in acinar cells. The results suggest that retarded autophagy is associated with an imbalance between CatL, which degrades trypsinogen and trypsin, and CatB, which converts trypsinogen into trypsin, resulting in intra-acinar accumulation of active trypsin in pancreatitis. Thus, deficient lysosomal degradation may be a dominant mechanism for increased intra-acinar trypsin in pancreatitis.     

The usefulness of direct ethanol metabolites in assessing alcohol intake in nonintoxicated male patients in an emergency room setting

Background: A major part of medical pathology in internal medicine is associated with chronic alcoholism. The aim of the current study was to investigate whether screening for Alcohol Use Disorders (AUD) can be improved through determination of direct ethanol metabolites compared to traditional biological state markers, the Alcohol Use Disorders Identification Test (AUDIT) and additional self‐reports beyond the detection time period of a positive blood alcohol concentration (BAC). Methods: A total of 74 blood alcohol negative male patients who presented at the emergency room with either thoracic or gastrointestinal complaints were included. Phosphatidylethanol (PEth) was determined in whole blood, and ethyl glucuronide (EtG) in serum and urine samples. Traditional biological state markers [carbohydrate deficient transferrin (%CDT), gamma glutamyl transpeptidase (GGT), mean corpuscular volume (MCV)] were determined. The AUDIT was obtained and furthermore, all patients completed an additional self‐report of alcohol consumption. Patients were divided into two (2) groups: AUDIT scores < 8 and AUDIT scores ≥ 8. Results: After assessment of the AUDIT, patients were allocated to one of the following groups: patients with AUDIT scores < 8 (n = 52) and with AUDIT scores ≥ 8 (n = 22). Twenty‐five percent of the patients with AUDIT scores below the cut‐off (n = 13/52) were tested positive for both PEth and UEtG. Of the patients who declared to be sober during the past 12 months, 38.5% were tested positive for PEth and UEtG. PEth discriminated similarly as %CDT for AUDIT scores ≥ 8 (AUC: 0.672; 95%CI 0.524 to 0.821). Self‐reports of alcohol consumption were unreliable. Conclusion: Determination of direct ethanol metabolites such as PEth and UEtG provides additional evidence in screening for AUD in an ER setting. Determination of PEth might be considered complementary with or alternatively to %CDT.     

Commentary on why national epidemiological estimates of substance abuse by race should not be used to estimate prevalence and need for substance abuse services at community and local levels

Large-scale epidemiological studies suggest substantially lower prevalence rates of substance abuse disorders in Black Americans than in White Americans. This is counterintuitive since indicators of socioeconomic status, which on an average are lower in Blacks than Whites, are inversely associated with the prevalence of psychiatric disorders. Herein, we recommend against the use of race-specific national epidemiological data to estimate prevalence of substance abuse disorders and need for services at community/local levels. This is important so that catchment areas with high proportions of minorities receive equitable levels of substance abuse prevention and treatment resources. We illustrate our recommendation through observations and potential biases (e.g., reporting bias) identified from large-scale epidemiological studies of the prevalence of substance use disorders between Black and White Americans.     

Recent trends in the percutaneous treatment of chronic total coronary occlusions

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) has a lower success rate than PCI for non-CTO lesions. We sought to determine trends in the treatment of CTOs within the current interventional era. Using 4 sequential recruitment waves of the National Heart, Lung, and Blood Institute Dynamic Registry, we assessed the relative prevalence and success rates in treating CTO (n=371) versus non-CTO (n=4,802) lesions over a 7-year period (1997 to 2004). Characteristics of attempted lesions and factors associated with PCI outcome were evaluated. CTO lesion attempts decreased by 41% over time, from 9.6% (1997 to 1998) to 5.7% (2004, p<0.0001 for trend). More contemporary CTO lesions were longer (22.4 vs 17.0 mm, p=0.006 for trend), had thrombus less often (21.3% vs 35.4%, p=0.03 for trend), and were more often treated with stents (69.8% vs 45.4% p=0.02). The rate of successful intervention for CTO lesions decreased nonsignificantly during this time, from 79.7% to 71.4% (p=0.18). Using multivariable analysis, female gender (adjusted odds ratio 0.42, 95% confidence interval 0.20 to 0.88, p=0.02), and thrombus (adjusted odds ratio 0.31, 95% confidence interval 0.15 to 0.61, p=0.0008) were associated with higher success rates, whereas the presence of severe noncardiac disease (adjusted odds ratio 1.91, 95% confidence interval 1.05 to 3.45, p=0.03) was associated with a higher risk for PCI failure. Recruitment wave and patient age were not independently related to lesion success. In conclusion, during the PCI period of 1997 to 2004, CTO lesions were attempted less frequently and success rates did not increase, indicating a need for new operator techniques or device technologies to treat this important lesion subset by a percutaneous approach.     

Percutaneous coronary intervention of moderate to severe calcified coronary lesions: Insights from the National Heart,Lung, and Blood Institute Dynamic Registry

Objectives: To evaluate the efficacy and safety of drug eluting stents (DES) when compared with bare metal stents (BMS) in patients with moderate to severe calcified coronary lesions. Background: Calcified coronary lesions present unique technical challenges during percutaneous coronary intervention (PCI) and it is not known if DES are as safe and as effective in the presence of calcium, as randomized trials typically exclude this common patient subset. Methods: We evaluated patients with PCI of a single calcified lesion enrolled across five recruitment waves in the National Heart, Lung, and Blood Institute Dynamic Registry between 1997 and 2006. Patients were divided into two groups based on the stent type‐ BMS and DES. The primary efficacy outcome was the need for repeat revascularization at 1 year and the primary safety outcome was a composite of death and myocardial infarction at 1 year. Results: Among the 1,537 patients included in the analysis, 884 (57%) underwent PCI with BMS and 653 (43%) with DES. DES use was associated with a significant reduction in the risk of repeat revascularization (10.0% vs. 15.3%; P = 0.003) with no significant higher risk of primary safety outcome (9.3% vs. 10.5%; P = 0.45) when compared to the BMS group. In a propensity score adjusted analysis, DES use was associated with a significantly lower risk in repeat revascularization (HR = 0.57; 95% CI 0.40–0.82; P = 0.002) and no significant difference in the risk of death and myocardial infarction (HR = 0.78; 95% CI 0.53–1.15; P = 0.20) compared to BMS group. Conclusion: In this large multicenter registry of patients with a moderate to severe calcified coronary lesion, use of DES compared to BMS was associated with significant reduction in the risk of repeat revascularization without any increase in death and myocardial infarction. © 2010 Wiley‐Liss, Inc.     

The impact of body mass index on short- and long-term outcomes inpatients undergoing coronary revascularization. Insights from the bypass angioplasty revascularization investigation (BARI)

OBJECTIVES: We sought to investigate the impact of body mass index (BMI) on short- and long-term outcomes after initial revascularization with percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft surgery (CABG). BACKGROUND: Equivocal results exist on the impact of BMI on the risk of in-hospital complications after PTCA or CABG, and no long-term mortality data exist from a large series of revascularized patients. METHODS: From the randomized series and observational registry of the Bypass Angioplasty Revascularization Investigation (BARI), 2,108 patients who had PTCA and 1,526 patients who had CABG were evaluated by taking their BMI at study entry. They were classified as follows: low (< 20 kg/m(2)), normal (20 to 24.9 kg/m(2)), overweight (25 to 29.9 kg/m(2)), class I obese (30 to 34.9 kg/m(2)) and class II/III obese (greater-than-or-equal 35 kg/m(2)). In-hospital complications and short- and long-term mortalities were compared between levels of BMI within each mode of initial revascularization. RESULTS: Among patients who had PTCA, each unit increase in BMI was associated with a 5.5% lower adjusted risk of a major in-hospital event (death, myocardial infarction, stroke, coma); among patients who had CABG, no difference in the in-hospital outcome was observed according to BMI. In contrast, BMI was not associated with five-year mortality in the PTCA group; among the CABG group, adjusted relative risks of five-year cardiac mortality according to levels of BMI were 0.0 (low), 1.0 (normal), 2.02 (overweight), 3.16 (class I obese) and 4.85 (class II/III obese) (linear p < 0.001).CONCLUSIONS: Body mass index appears to have a differential impact on short- and long-term outcomes after coronary revascularization. These results underscore the need for further research to identify factors responsible for the apparent short-term protective effect of a higher BMI in patients undergoing PTCA and to study the impact of weight reduction on the long-term survival of obese patients undergoing CABG.     

Ca2+]i reduction increases cellular proliferation and apoptosis in vascular smooth muscle cells: relevance to the ADPKD phenotype

Cardiovascular complications are the leading cause of morbidity and mortality in autosomal dominant polycystic kidney disease. Pkd2+/- vascular smooth muscle cells (VSMCs) have an abnormal phenotype and defective intracellular Ca2+ ([Ca2+]i) regulation. We examined cAMP content in vascular smooth muscles from Pkd2+/- mice because cAMP is elevated in cystic renal epithelial cells. We found cAMP concentration was significantly increased in Pkd2+/- vessels compared with wild-type vessels. Furthermore, reducing the wild-type VSMC [Ca2+]i by Verapamil or BAPTA-AM significantly increased cellular cAMP concentration (mainly by phosphodiesterase [PDE] inhibition), the rate of VSMC proliferation (determined by direct cell counting, 3H-incorporation, FACS analysis of cells entering S phase, and quantitative Western PCNA and ERK1/2 analyses), and the rate of apoptosis (by Hoechst staining, FACS analysis of the Annexin-V positive cells, and quantitative Western Bax, cytochrome c, and activated caspase 9 and 3 analyses). The low [Ca2+]i induced VSMC proliferation was independent of cAMP/B-Raf signaling, while that of apoptosis was promoted by cAMP. In summary, Pkd2+/- VSMCs have elevated cAMP levels. This elevation can also be induced by reducing [Ca2+]i in wild-type VSMCs. The [Ca2+]i reduction and cAMP accumulation can cause an increase in both cellular proliferation and apoptosis, resembling Pkd mutant phenotype.