Modification of myocardial function parameters by L- and D-penbutolol--an echocardiography, placebo-controlled double-blind study

In order to study left ventricular contraction parameters of L-penbutolol and D-penbutolol (isopenbutolol) we evaluated TM-echocardiograms of 12 healthy volunteers at 30 and 60 minute intervals for 8 hours after oral administration of 40 mg L- and D-penbutolol and placebo. Three different observers determined end-systolic and end-diastolic dimensions, left ventricular shortening fraction (SF) as well as mean-, peak- and rate corrected circumferential fiber shortening (VCF) and calculated at each measuring point the difference from the control value (Delta). L-penbutolol demonstrated a typical beta-blocking effect with a significant (p less than 0.001) decrease of systolic (11.1 +/- 8.6 mm Hg) and diastolic blood pressure (6.7 +/- 4.6 mm Hg) and heart rate (10.0 +/- 7.4 bpm) as well as a significant (p less than 0.001) negative inotropic effect expressed by a decrease of SF (6.5 +/- 4.2%) and VCF-mean (0.40 +/- 0.15 circ/s), VCF-peak (1.04 +/- 0.61 circ/s) and rate corrected VCF (0.28 +/- 0.08 circ/s). However, we saw a similar but less distinct negative inotropic and chronotropic effect of D-penbutolol as compared to placebo. HR decreased by 5.3 +/- 6.2 bpm (p less than 0.001), SF decreased maximally by 5.0 +/- 3.2% (p less than 0.05), VCF-mean by 0.27 +/- 0.08 circ/s (p less than 0.001), VCF-peak by 0.71 +/- 0.31 circ/s (p less than 0.001) and rate corrected VCF by 0.22 +/- 0.04 circ/s (p less than 0.001). By means of TM echocardiography it was therefore possible to document a strong beta-blocking effect of L-penbutolol as well as a negative inotropic and negative chronotropic effect by the D-isomer of penbutolol.     

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents

Context  Traditionally, stent thrombosis has been regarded as a complication of percutaneous coronary interventions during the first 30 postprocedural days. However, delayed endothelialization associated with the implantation of drug-eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited regarding the risks and the impact of this phenomenon outside clinical trials. Objective  To evaluate the incidence, predictors, and clinical outcome of stent thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice. Design, Setting, and Patients  Prospective observational cohort study conducted at 1 academic hospital and 2 community hospitals in Germany and Italy. A total of 2229 consecutive patients underwent successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272 stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents between April 2002 and January 2004. Interventions  Implantation of a drug-eluting stent (sirolimus or paclitaxel). All patients were pretreated with ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for at least 6 months after paclitaxel-eluting stent implantation. Main Outcome Measures  Subacute thrombosis (from procedure end through 30 days), late thrombosis (>30 days), and cumulative stent thrombosis. Results  At 9-month follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and 20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13 died (case fatality rate, 45%). Independent predictors of stent thrombosis were premature antiplatelet therapy discontinuation (hazard ratio [HR],  89.78; 95% CI, 29.90-269.60; P<.001), renal failure (HR,  6.49; 95% CI, 2.60-16.15; P<.001), bifurcation lesions (HR,  6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR,  3.71; 95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR,  1.09; 95% CI, 1.05-1.36; P<.001 for each 10% decrease). Conclusions  The cumulative incidence of stent thrombosis 9 months after successful drug-eluting stent implantation in consecutive "real-world" patients was substantially higher than the rate reported in clinical trials. Premature antiplatelet therapy discontinuation, renal failure, bifurcation lesions, diabetes, and low ejection fraction were identified as predictors of thrombotic events.      

Collecting longitudinal data through childhood, adolescence, and young adulthood: methodological challenges

This article presents the proceedings of a workshop at the 2003 Research Society on Alcoholism meeting in Fort Lauderdale, Florida. The organizers and chairs were Vivian Faden and Nancy Day. The presentations were (1) Lessons Learned From the Lives Across Time Longitudinal Study, by Michael Windle and Rebecca Windle; (2) Methodological Issues in Longitudinal Surveys With Children and Adolescents, by Joel Grube; (3) The Pittsburgh ADHD Longitudinal Study: Methodological and Conceptual Challenges, by Brooke Molina, William Pelham, Elizabeth Gnagy, and Tracey Wilson; and (4) Lessons learned in Conducting Longitudinal Research on Alcohol Involvement: If Only I Had Known Before Hand! by Kristina Jackson and Kenneth Sher.     

Ingenamine G and cyclostellettamines G-I, K, and L from the new Brazilian species of marine sponge Pachychalina sp

The chemical investigation of the cytotoxic and antituberculosis active MeOH crude extract of the marine sponge Pachychalina sp. led to the isolation of six new nitrogenous metabolites, including ingenamine G (1), as well as a mixture of new cyclostellettamines G, H, I, K, and L (10-14) with the known cyclostellettamines A-F (4-9). Structural assignments of compound 1 were based on the analysis of MS and NMR data, while the structures of compounds 10-14 could be established by HPLC-MS/MS analysis. Ingenamine G displayed cytotoxic activity against HCT-8 (colon), B16 (leukemia), and MCF-7 (breast) cancer cell lines, antibacterial activity against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and four oxacilin-resistant S. aureus strains, and antimycobacterial activity against Mycobacterium tuberculosis H37Rv.     

ITIH5, a novel member of the inter-alpha-trypsin inhibitor heavy chain family is downregulated in breast cancer

The inter-alpha-trypsin inhibitor (ITI) family constitutes a group of proteins built up from one light chain and a variable set of heavy chains. Originally identified as plasma protease inhibitors, recent data indicate that ITI plays a role in extracellular matrix (ECM) stabilization and in prevention of tumor metastasis. Here we describe cloning as well as phylogenetic and expression analysis of a novel member of the heavy chain gene family, ITIH5. ITIH5 contains the two domains conserved in all known ITIHs, the vault protein inter-alpha-trypsin (VIT) domain and a von Willebrand type A (vWA) domain. However, ITIH5 diverged early from a common ancestor of the other subfamilies. We found strong downregulation of ITIH5 expression in breast tumors by real-time PCR and RNA in situ hybridization. While normal breast epithelial cells clearly express ITIH5, expression is consistantly lost or strongly downregulated in invasive ductal carcinoma. ITIH5 mRNA was neither detectable in cancerous nor benign breast cell lines. We propose that loss of ITIH5 expression may be involved in breast cancer development.     

Alcohol problem recognition as a function of own and others' perceived drinking

A self-regulation model was applied for predicting alcohol problem recognition. With the rate of others' alcohol use serving as a standard, problem recognition was predicted to increase the more one perceived one's drinking rate to be above others' use. Within the context of a classroom-administered survey, 707 nonabstaining undergraduates reported their drinking rates and estimated other students' drinking rates for annual drinking frequency, average weekly drinking quantity, and recent heavy drinking frequency. The independent roles of one's own and others' drinking rates, as well as the discrepancy between these two rates in predicting problem recognition, were examined. Findings were consistent with a self-regulation account. Across measures, only own drinking rate independently predicted problem recognition. Others' drinking rate interacted with own drinking rate in predicting problem recognition on the quantity measure. Specifically, the more heavy drinkers perceived their own quantity to be above others', the higher their problem recognition. Finally, gender effects were observed. Although men reported higher problem recognition than women, women reflected more on their drinking rates for problem recognition.