PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation.

The PlA polymorphism (Leu33Pro) of the platelet glycoprotein (GP) IIIa gene has been suggested to play an important role in coronary thrombosis. In vitro studies have shown differences for this polymorphism in platelet sensitivity towards antiplatelet drugs (aspirin and abciximab), suggesting a pharmacogenetic modulation. The aim of the study was to assess the modulatory effect of the PlA polymorphism on clopidogrel-induced antiplatelet effects in 38 patients undergoing coronary stent implantation receiving a 300 mg clopidogrel loading-dose. Platelet reactivity was assessed as GPIIb/IIIa activation and P-selectin expression in platelets stimulated with 2 micromol/l adenosine diphosphate using whole blood flow cytometry. The distribution of the homozygous PlA1/A1 and heterozygous PlA1/A2 genotypes were 74 and 26%, respectively. PlA2 carriers had a higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P = 0.02) during the overall study time course and a lower antiplatelet effect to a 300 mg clopidogrel loading-dose up to 24 h following intervention (P < 0.05). In conclusion, the Pl polymorphism of the GPIIIa gene modulates platelet reactivity towards clopidogrel front loading in patients undergoing coronary stenting. This suggests the need for individualized antithrombotic regimens to optimally inhibit platelet reactivity.     

Coronary stenting versus balloon angioplasty in small vessels: a meta-analysis from 11 randomized studies

OBJECTIVES: A meta-analysis of 11 randomized trials was done to compare stenting versus balloon angioplasty (BA) in small coronary vessels. BACKGROUND: Randomized studies on coronary stenting (CS) in small vessels have yielded controversial results. METHODS: Eleven randomized trials on CS versus BA in small vessels, including angiographic re-evaluation at six months, were analyzed. RESULTS: The BeStent (Medtronic Instent, Minneapolis, Minnesota) was used in four studies, the Multi-Link (Guidant, Advanced Cardiovascular Systems Inc., Santa Clara, California) in three trials, and the NIR (Boston Scientific Corp., Boston, Massachusetts), JoStent (Jomed International AB, Helsingborg, Sweden), Tenax (Biotronik, Berlin, Germany), and BioDivysio (Abbott Vascular Devices, Redwood City, California) in the remaining four trials. Overall, 3,541 patients were included (1,672 allocated to BA and 1,869 to stent). The rate of cross-over from balloon to stent in the pooled population was 19%, and unsuccessful stent deployment occurred in 2% of the patients allocated to stent. The pooled rates of restenosis were 25.8% and 34.2% in patients allocated to stent and balloon, respectively (p = 0.003) (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.65 to 0.92). A smaller reference vessel diameter at baseline was associated with a higher risk reduction in the restenosis rate (y = -3.551 + 1.826 [x]; p = 0.012). Patients allocated to stent had lower rates of major adverse cardiac events (15.0% vs. 21.8%, p = 0.002; RR 0.70; 95% CI 0.57 to 0.87) and new target vessel revascularizations (12.5% vs. 17.0%, p = 0.004; RR 0.75, 95% CI 0.61 to 0.91). CONCLUSIONS: Elective stenting is superior to provisional stenting in small coronary arteries. This benefit is more evident in smaller coronary arteries.     

Effects of a Less-invasive Surgical Technique on Cement Mantle Quality in Total Knee Arthroplasty

The purpose of this study was to assess the effects of a less-invasive midvastus exposure during total knee arthroplasty (TKA) on cement mantle grade compared with a standard parapatellar arthrotomy and standard TKA. Fifty consecutive cemented minimally invasive TKAs using a midvastus approach, patellar subluxation without eversion, and less-invasive instrumentation were compared radiographically with a control cohort of 50 consecutive cemented standard TKAs. To eliminate patient selection bias, the standard cohort included consecutive surgeries completed before 2004, prior to the advent of minimally invasive techniques in TKA. Analog supine anteroposterior and lateral radiographs were evaluated using Ewald's criteria. Lucent lines, cement voids, and cement debris were recorded for each group.Radiographic analysis revealed compromised femoral component cement mantle grades in the minimally invasive group. The number of anterior femoral cement voids (zone 1) was significantly higher in the minimally invasive group, and peripatellar and tibial cement debris was also more common in the minimally invasive group. Based on these findings, the midvastus approach compromises the surgeon's ability to duplicate a consistent femoral cement mantle obtained using a standard exposure.     

Economic effects of community versus hospital-based faculty pneumonia care

To compare the length of stay and charges for patients with pneumonia admitted in 1995 to the teaching and nonteaching services of a Northeastern teaching hospital, we reviewed the charts of 237 patients. Patients cared for by hospital-based generalists working with housestaff (teaching service) were discharged more quickly and with lower or equivalent charges than patients cared for by community-based attending physicians working either with housestaff (private teaching service) or alone (nonteaching service). Academic teaching services staffed by general medicine faculty may provide efficient inpatient pneumonia care.     

Subacute toxicity of a halogenated pyrrole hydroxymethylglutaryl-coenzyme A reductase inhibitor in Wistar rats.

Wistar rats received an hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, a halogenated pyrrole designated PD 123244-15, orally by gavage for 14 days at 10, 50, 150, 300, and 600 mg/kg. Doses of 150-600 mg/kg caused death and marked systemic toxicity involving stomach, esophagus, liver, gonads, lymphoid tissues, and skeletal muscle. Histopathologic findings included hyperkeratosis in esophagus and forestomach, increased hepatic mitotic activity, ovarian follicular necrosis, testicular atrophy and arrested spermatogenesis, and skeletal muscle necrosis and regeneration. Elevated serum aspartate aminotransferase correlated with muscle necrosis and hepatocellular damage. Marked systemic effects associated with high plasma concentrations were consistent with toxicity defined for other HMG-CoA reductase inhibitors, with the exception of pathologic alterations in the esophagus and ovaries. Direct mucosal irritation may have contributed to forestomach and esophageal lesions induced by this halogenated pyrrole.     

Rotavirus infections in children (author's transl)]

In 43 out of 90 children suffering from acute gastroenteritis Rotaviruses could be identified in stool-specimens by electronmicroscopy. Symptoms were watery diarrhoea (100%), vomiting (88%), fever (77%), dehydration (47%) and upper respiratory tract infection (21%). In 3 out of 9 patients liver involvement could be documented. In 29 children i.v.-fluid therapy for 1-2 days was necessary. Only in 1 patient severe diarrhoea persisted for 11 days.