Comparison of the prognostic effect of left versus right versus no bundle branch block on presenting electrocardiogram in acute myocardial infarction patients treated with primary angioplasty in the primary angioplasty in myocardial infarction trials

The presence of bundle branch block (BBB) has been associated with poor outcomes in patients who have acute myocardial infarction. Whether this is true in the angioplasty era is not known. We sought to evaluate the outcome of patients with acute myocardial infarction and BBB who were treated with primary angioplasty. We evaluated 3,053 patients who underwent emergency catheterization in the PAMI trials. Patients who had left BBB (n = 48, 1.6%) on presenting electrocardiogram were compared with patients who had right BBB (n = 95, 3.1%) or no BBB (n = 2,910, 95.3%). Patients who had BBB were older and more frequently had diabetes mellitus, peripheral vascular disease, and previous coronary artery bypass grafting. They had lower ejection fraction and more multivessel disease. There were no significant differences in door-to-balloon time, final Thrombolysis In Myocardial Infarction flow grade or stent use. In-hospital major adverse cardiac events (death, ischemic target vessel revascularization, and reinfarction) were higher in patients who had BBB due primarily to increased in-hospital death (left BBB 14.6%, right BBB 7.4%, no BBB 2.8%, p < 0.0001). In multivariate logistic regression analysis, left BBB was an independent predictor of in-hospital death (odds ratio 5.53, 95% confidence interval 1.89 to 16.1, p = 0.002). In conclusion, patients who have acute myocardial infarction and BBB have increased co-morbidities and higher mortality rates despite treatment with primary angioplasty. Despite early identification of multivessel disease with triage to angioplasty or coronary artery bypass grafting, if necessary, similar treatment times, and final Thrombolysis In Myocardial Infarction grade 3 flow, the presence of left BBB on admission electrocardiogram in patients who have acute myocardial infarction is an independent predictor of in-hospital mortality. Because 85% of deaths in patients who have left BBB occur within the first week, these patients should be recognized early and receive prompt and aggressive treatment.     

Team communications in the operating room: talk patterns, sites of tension, and implications for novices.

PURPOSE: Although the communication that occurs within health care teams is important to both team function and the socialization of novices, the nature of team communication and its educational influence are not well documented. This study explored the nature of communications among operating room (OR) team members from surgery, nursing, and anesthesia to identify common communicative patterns, sites of tension, and their impact on novices. METHOD: Paired researchers observed 128 hours of OR interactions during 35 procedures from four surgical divisions at one teaching hospital. Brief, unstructured interviews were conducted following each observation. Field notes were independently read by each researcher and coded for emergent themes in the grounded theory tradition. Coding consensus was achieved via regular discussion. Findings were returned to insider "experts" for their assessment of authenticity and adequacy. RESULTS: Patterns of communication were complex and socially motivated. Dominant themes were time, safety and sterility, resources, roles, and situation. Communicative tension arose regularly in relation to these themes. Each procedure had one to four "higher-tension" events, which often had a ripple effect, spreading tension to other participants and contexts. Surgical trainees responded to tension by withdrawing from the communication or mimicking the senior staff surgeon. Both responses had negative implications for their own team relations. CONCLUSIONS: Team communications in the OR follow observable patterns and are influenced by recurrent themes that suggest sites of team tension. Tension in team communication affects novices, who respond with behaviors that may intensify rather than resolve interprofessional conflict.     

Prostate cancer risk and ESR1 TA, ESR2 CA repeat polymorphisms.

BACKGROUND: Experimental evidence has suggested that estrogen receptor alpha (coded by the gene ESR1) might increase prostate cancer risk, whereas estrogen receptor beta (coded by the gene ESR2) might reduce prostate cancer risk. METHODS: We investigated the relationship with prostate cancer risk of both a TA repeat polymorphism in the ESR1 5' region, ESR1 (TA)(n), and with a CA repeat polymorphism in intron 5 of ESR2, ESR2 (CA)(n), in a case-control study (545 cases and 674 controls) nested in the Physicians' Health Study. RESULTS: Prostate cancer risk was highest for carriers of ESR1 (TA)(24) and ESR1 (TA)(25). Replacing one modal ESR1 (TA)(14) allele with one ESR1 (TA)(24) allele yielded an odds ratio of 1.42 (95% confidence interval, 1.00-2.00; P=0.05). Replacing one ESR1 (TA)(14) allele with one ESR1 (TA)(25) allele yielded an odds ratio of 2.10 (95% confidence interval, 1.15-3.84; P=0.02). ESR2 (CA)(n) showed no effects on prostate cancer risk. CONCLUSIONS: The ESR1 (TA)(n) polymorphism might play a role in prostate cancer risk.     

A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer.

PURPOSE: To define the toxicities, pharmacodynamics, and clinical activity of the proteasome inhibitor, PS-341 (bortezomib), in patients with advanced malignancies. PATIENTS AND METHODS: Twenty-eight patients (14 male and 14 female) received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity necessitated dose omissions on this schedule, 16 additional patients (12 male and 4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of 20S proteasome activity in peripheral blood mononuclear cells (PBMC) and accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated as pharmacodynamic markers of PS-341 activity. RESULTS: The most common toxicity was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6 mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a patient in schedule I. Grade > or =3 toxicities for schedule I were constipation, fatigue, myalgia, and sensory neuropathy. Grade > or =3 toxicities for schedule II were dehydration resulting from diarrhea, nausea and vomiting, fatigue, hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both schedules. Reversible dose-dependent decreases in 20S proteasome activity in PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75% at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in tumor samples after treatment with PS-341. A patient with multiple myeloma had a partial response. CONCLUSION: PS-341 given 1.5 mg/m2 twice weekly for 2 of every 3 weeks is well tolerated and should be further studied.     

Comparative pharmacokinetic study of continuous venous infusion fluorouracil and oral fluorouracil with eniluracil in patients with advanced solid tumors.

PURPOSE: To compare the pharmacokinetics of continuous venous infusion (CVI) fluorouracil (5-FU) with that of oral eniluracil/5-FU and to describe toxicities and clinical activity of prolonged oral administration of eniluracil/5-FU. PATIENTS AND METHODS: A randomized, open-label, cross-over study compared CVI 5-FU to an oral 5-FU/eniluracil combination. Seventeen patients (arm A) were randomly assigned to receive eniluracil/5-FU combination tablets (10:1 mg/m(2) BID for 7 days) during the first study period, followed by 5-FU (300 mg/m(2) CVI for 7 days) during period 2, with a 14-day washout between periods. Sixteen patients (arm B) received treatment in the opposite sequence. In period 3, all patients received eniluracil/5-FU tablets BID for 28 days. Plasma levels of 5-FU during CVI and oral administration were analyzed in periods 1 and 2. Dihydropyrimidine dehydrogenase (DPD) activity was determined by measuring plasma uracil, urinary alpha-fluoro-beta-alanine, and peripheral-blood mononuclear cell (PBMC) DPD activity. RESULTS: There were no grade 3 or 4 toxicities in either arm. Partial responses were observed in three patients. Another three patients had stable disease for > or = 3 months. Eniluracil and 5-FU pharmacokinetics were similar to those observed in previous studies and were unaffected by administration sequence. The mean +/- SD steady-state plasma concentration (C(P)) and area under the curve (AUC)(144-168h) for CVI 5-FU (104 +/- 45 ng/mL and 2,350 +/- 826 ng x h/mL, respectively) were three-fold greater than those for oral 5-FU (38.1 +/- 7.7 ng/mL and 722 +/- 182 ng x h/mL, respectively [P <.00001]). Individual 5-FU concentrations during CVI were highly variable, whereas those after eniluracil/5-FU were very reproducible. DPD activity in PBMCs before each study period was normal. CONCLUSION: Both CVI 5-FU and oral eniluracil/5-FU were well tolerated, with moderate activity in these heavily pretreated patients. However, 5-FU steady-state C(P) and AUCs achieved with oral eniluracil/5-FU were significantly less than with CVI 5-FU.