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Biomedical subjects

K Wolski

Publications and source records attributed to K Wolski.

14 recordsLinked to original sources

Ticlopidine pretreatment before coronary stenting is associated with sustained decrease in adverse cardiac events: data from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) Trial.

BACKGROUND: Platelet inhibition at the time of a percutaneous coronary intervention has consistently been shown to decrease the risk of thrombotic adverse events but not restenosis. The role of enhanced antiplatelet protection through pretreatment with the platelet ADP-receptor antagonist ticlopidine in preventing both the early and late complications of coronary stenting has not previously been explored. METHODS AND RESULTS: In the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, approximately 1600 patients were randomized to stenting with either placebo or abciximab in addition to aspirin and heparin. All stented patients also received ticlopidine after the procedure, but 58% of these patients were given ticlopidine before stenting at the discretion of the investigating physician. Among patients randomized to placebo, ticlopidine pretreatment was associated with a significant decrease in the incidence of the composite end point of death, myocardial infarction, or target vessel revascularization (TVR) at 1 year (adjusted hazard ratio, 0.73; 95% CI, 0.54 to 0.98; P:=0.036). Ticlopidine pretreatment did not significantly influence the risk of death or myocardial infarction in patients randomized to abciximab. Controlling for patient characteristics and for the propensity of being on ticlopidine, Cox proportional hazards regression identified ticlopidine pretreatment as an independent predictor of the need for TVR at 1 year (hazard ratio, 0.62; 95% CI, 0.43 to 0.89; P:=0.010) in both placebo-treated and abciximab-treated patients. CONCLUSIONS: In the EPISTENT trial, among patients randomized to stenting, starting ticlopidine before the percutaneous coronary intervention was associated with a significant decrease in the incidence of the 12-month composite end point for patients not receiving abciximab and the need for TVR among all patients.

Cardiovascular Diseases↗

Effect of smoking status and abciximab use on outcome after percutaneous coronary revascularization: Pooled analysis from EPIC, EPILOG, and EPISTENT.

BACKGROUND: Tobacco use has been studied in relation to the development of atherosclerotic heart disease and outcome after acute coronary syndromes, though outcome data after percutaneous coronary intervention (PCI) are limited. Tobacco use has been associated with increased fibrinogen levels, thrombin generation, and increased platelet aggregation, and these factors may cause ischemic events after PCI. METHODS: We assessed whether smokers undergoing PCI have more ischemic events and if glycoprotein IIb/IIIa receptor blockade is particularly beneficial in preventing ischemic events in this cohort. We examined clinical outcomes for smokers and nonsmokers by using pooled analysis from 3 large, placebo-controlled trials of the glycoprotein IIb/IIIa antagonist abciximab during PCI. RESULTS: Among 6519 patients, 34% were smokers. The primary end point of death, myocardial infarction, or urgent revascularization within 30 days was reduced by abciximab from 12.3% to 6.4% (relative risk reduction, 48%; P <.001) in smokers and from 11.3% to 5.9% (relative risk reduction, 48%; P <.001) in nonsmokers treated with abciximab. At 6 months, death, myocardial infarction, or urgent revascularization was reduced from 14.4% to 8.5% (relative risk reduction, 41%; P <.001) in smokers and from 14.6% to 8.8% (relative risk reduction, 40%; P <.001) in nonsmokers. Adjusting for baseline differences, smoking was an independent predictor of poor outcome at 30 days (odds ratio, 1.22; 95% confidence interval, 1.02, 1.47; P =.03). CONCLUSIONS: This pooled analysis demonstrates that after PCI, smokers had worse 30-day outcomes than did nonsmokers. However, both groups had a comparable degree of benefit with platelet inhibition through the use of abciximab.

Abciximab↗

Cardiac exercise hemodynamics late after partial left ventriculectomy.

BACKGROUND: Although some patients report favorable activity levels late after partial left ventriculectomy (PLV), their exercise physiology has not been well described. METHODS AND RESULTS: We performed upright bicycle hemodynamics in 10 patients (9 men) aged 56+/-12 years at 1.7 years after PLV. Ejection fraction was 25+/-4%. Patients biked 10+/-7 minutes. With exercise, the mean pulmonary arterial pressure rose from 36+/-12 to 52+/-10 mm Hg (P:=0.0003). The mean pulmonary capillary wedge pressure rose from 25+/-14 to 36+/-9 mm Hg (P:=0.0566), and the cardiac index rose from 2.2+/-0.5 to 3.8+/-1.6 L. min(-1). m(-2) (P:=0.0077). The mixed venous oxygenation with exercise declined from 44+/-9% to 24+/-17% (P:=0. 0220), and the pulmonary vascular resistance increased from 2.0+/-0. 9 to 2.3+/-1.1 Wood units (P:=0.5566). CONCLUSIONS: In late follow-up after PLV with exercise, the cardiac index is significantly augmented. However, there are further rises in pulmonary artery and pulmonary capillary wedge pressures, suggesting abnormal compliance, with marked decline in mixed venous oxygenation. Elucidating late physiology after PLV may help pave the way for future innovative heart failure surgeries.

Blood Gas Analysis↗

Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration.

Adjunctive immunotherapy with heat-killed Mycobacterium vaccae was studied in a randomized, placebo-controlled trial of 120 non-human immunodeficiency virus-infected adults with newly diagnosed pulmonary tuberculosis. Patients were randomized to a single dose of M. vaccae or placebo 1 week after beginning chemotherapy and were followed up for 1 year. M. vaccae was safe and well tolerated. The rate of sputum culture conversion after 1 month of tuberculosis treatment was 35% in the M. vaccae group and only 14% in the placebo group (P=.01) but was comparable at 2 months and thereafter. Patients receiving M. vaccae had greater improvement on chest radiography at 6 months (91% vs. 77% for placebo recipients; P=.04) and 12 months (94% vs. 80%; P=.04) after initiation of tuberculosis treatment. These data provide evidence of an early increase in sputum culture conversion and greater radiographic improvement among patients who received M. vaccae. Further studies are warranted.

Adult↗

Clinical correlates and course of thrombocytopenia during percutaneous coronary intervention in the era of abciximab platelet glycoprotein IIb/IIIa blockade.

BACKGROUND: Thrombocytopenia is infrequently associated with abciximab therapy but may contribute to hemorrhagic risk. Factors associated with development of thrombocytopenia, the role of weight-adjustment in concomitant heparin administration, and clinical outcomes in patients with thrombocytopenia are not well defined. METHODS AND RESULTS: Pooled data from 3 placebo-controlled, randomized trials (EPIC, EPILOG, and EPISTENT) of abciximab therapy during percutaneous coronary intervention identified 178 patients (2. 4% of 7290 patients) in whom thrombocytopenia (platelet count <100 x 10(9)/L) developed after enrollment. Multivariate regression analysis identified age (>65 years; P <.001), weight (<90 kg; P =. 023), baseline platelet count (<200 x 10(9)/L; P <.001), abciximab therapy (P =.002), and enrollment into the EPIC trial (P <.001) to be associated with development of thrombocytopenia. Major and minor nonsurgical hemorrhage and transfusion were more frequent (all P <. 001) in thrombocytopenic patients. Although the primary composite clinical end point of these trials (death, myocardial infarction, or urgent revascularization to 30 days) was observed with similar frequency in patients with (11.2%) and those without (7.9%; P =.114) thrombocytopenia, 30-day mortality rate was higher in thrombocytopenic patients (8.4% vs 0.6%, respectively; P <.001). This excess mortality rate persisted after excluding patients in whom thrombocytopenia was first noted after the performance of coronary bypass surgery (4.8% vs 0.6%; P <.001). Among patients in whom thrombocytopenia developed during these trials, those who received prophylactic abciximab had fewer primary end point events (7.1% vs 23.1%; P =.056) and had a lower 30-day mortality rate (3.5% vs 15.4%; P =.048) than patients with thrombocytopenia who had received prophylactic placebo. CONCLUSIONS: Thrombocytopenia associated with abciximab therapy for percutaneous coronary intervention was more frequent in older, lighter-weight patients, those with lower baseline platelet counts, and in those patients who were enrolled into the EPIC trial. Both bleeding and transfusion events occur more frequently in patients with thrombocytopenia. Patients in whom thrombocytopenia developed during these trials had increased mortality rates to 30 days not attributable to the performance of coronary bypass surgery. Among patients with thrombocytopenia, those who received prophylactic abciximab had better clinical outcomes including survival than those who did not.

Abciximab↗

Exercise hemodynamic findings in patients with exertional dyspnea.

To determine whether upright bicycle exercise could provide useful information about disabling exertional dyspnea in the absence of severe abnormalities (as shown by traditional testing methods), we evaluated 13 such patients. There were 3 men and 10 women with a mean age of 49+/-15 (SD) years. We used pulmonary artery catheterization at rest and during upright bicycle exercise to evaluate these patients. All patients had normal left ventricular function except for 1, who had an ejection fraction of 45%. The mean duration to peak exercise was 9+/-6 minutes. Normal systolic pulmonary artery pressure was defined as 25+/-5 mmHg. Four patients had normal systolic pulmonary pressure, and 9 exhibited pulmonary hypertension with exercise. In those 9, the mean mixed pulmonary venous oxygen saturation at rest was 61%+/-9% and fell to 32%+/-9% at peak exercise. Six of the 9 patients also had some degree of resting pulmonary hypertension that worsened with exercise: their mean pulmonary artery systolic pressure at rest was 47+/-14 mmHg and rose to 75+/-25 mmHg at peak exertion (P = 0.01). The other 3 patients showed no pulmonary hypertension at rest; their mean pulmonary artery systolic pressure was 27+/-6 mmHg. However, this level rose to 53+/-4 mmHg at peak exertion (P = 0.04). In this pilot study of patients with dyspnea, 9 of 13 (69%) displayed marked pulmonary hypertension with exercise. The resting hemodynamic levels were normal in 3 (33%) of those with exercise pulmonary hypertension. We conclude that hemodynamic data from bicycle exercise tests can provide additional information regarding the mechanisms of exertional dyspnea.

Catheterization, Swan-Ganz↗

Chest pain--a strong predictor of adverse cardiac events following precutaneous intervention (from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial [EPISENT])].

Postprocedural chest pain remains a common problem, and irrespective of electrocardiographic changes, is associated with a higher incidence of early cardiac events. A return to the catheterization laboratory is unlikely to benefit patients with postprocedural chest pain without electrocardiographic changes with documented irreversible intraprocedural complications, or those with late postprocedural pain.

Abciximab↗

Measurement of sputum Mycobacterium tuberculosis messenger RNA as a surrogate for response to chemotherapy.

Effective treatment regimens for pulmonary tuberculosis are difficult to assess because of the slow growth rate of Mycobacterium tuberculosis in culture and its protracted clearance from sputum. A rapid method that reflects effective antimicrobial activity would markedly advance evaluation of treatment and promote the assessment of new antituberculosis drugs. Conventional methods measure the progressive reduction of numbers of acid-fast bacilli in the sputum smear and the clearance of organisms in sputum culture. In this study, we measured levels of M. tuberculosis 85B (alpha antigen) messenger RNA (mRNA), 16S ribosomal RNA (rRNA), and IS6110 DNA in patients' sputa to ascertain whether they could serve as potential surrogate markers of response to chemotherapy. Sputum specimens were sequentially collected for up to a year from 19 smear-positive pulmonary tuberculosis patients receiving an optimal drug treatment regimen. Nucleic acids were isolated from these specimens, and two M. tuberculosis molecular targets (mRNA, DNA) were quantified, using the ABI Prism 7700 Sequence Detection System. The Mycobacterium genus-specific 16S rRNA was quantified with a limiting dilution RT-PCR assay. Results show that levels of 85B mRNA declined after initiation of therapy, as did viable M. tuberculosis colony counts, with 90% of patients becoming negative for both markers after 2 mo of treatment. The rapid disappearance of M. tuberculosis mRNA from sputum suggests that it is a good indicator of microbial viability and a useful marker for rapid assessment of response to chemotherapy.

Adult↗

Induction of the antigen 85 complex of Mycobacterium tuberculosis in sputum: a determinant of outcome in pulmonary tuberculosis treatment.

Sputum quantitative culture, acid-fast smear, days-to-positive by BACTEC, and Mycobacterium tuberculosis antigen 85 complex were monitored during therapy in 42 patients with pulmonary tuberculosis (TB). By BACTEC, 4 patients were persistently positive on days 90-180, and treatment ultimately failed in 2 of these. Antigen 85 expression increased in subjects in whom disease persisted (persisters) from days 0 to 14 when the difference between persisters and nonpersisters was statistically significant (P = .002). Only antigen 85 complex values at day 14 suggested TB persistence at or after day 90. All subjects with day 14 antigen 85 complex values < 60 pg/mL responded rapidly to treatment and were cured. Of those with values > 60 pg/mL, in 33% TB persisted at or after day 90 and treatment failed in 17%. Biologic factors expressed early in therapy, not related to compliance or resistance, may exert a substantial influence on outcome. The antigen 85 complex is critical in cell wall biosynthesis and is induced by isoniazid in vitro. Its induction may represent an adaptive transition to a persistent state during therapy.

Adult↗

Impact of human immunodeficiency virus type-1 infection on the initial bacteriologic and radiographic manifestations of pulmonary tuberculosis in Uganda. Makerere University-Case Western Reserve University Research Collaboration.

SETTING: TB Treatment Centre, Kampala, Uganda. OBJECTIVE: To evaluate the impact of human immunodeficiency virus (HIV) co-infection on the bacteriologic and radiographic presentation of pulmonary tuberculosis (TB) in Uganda, a nation with high rates of Mycobacterium tuberculosis and HIV infection. DESIGN: To compare baseline characteristics among HIV-infected and non-HIV-infected adults with initial newly-diagnosed episodes of culture-confirmed pulmonary TB screened for participation in a randomized prospective TB treatment trial. RESULTS: Negative and paucibacillary (very scanty or scanty) sputum acid fast bacilli (AFB) smears were more frequent in HIV-infected patients presenting with pulmonary TB (P = 0.007). More HIV-infected individuals also had sputum cultures that required 7-8 weeks incubation until positivity than non-HIV-infected patients (P < 0.01). Lower lung field and diffuse pulmonary infiltrates were more frequent among HIV-infected patients. Rates of atypical X-ray presentations and cavitary disease were comparable between HIV-seropositive and -seronegative patients; however, atypical disease was more frequent in HIV-infected patients with small tuberculin reactions or tuberculin anergy (PPD = 0 mm). CONCLUSION: HIV co-infection was associated with a higher frequency of negative and paucibacillary sputum AFB smears. The differences in the diagnostic yields of microscopy and culture between HIV-infected and non-HIV-infected individuals were small and do not, in our opinion, significantly affect the utility of these important diagnostic tests in developing countries. Examining more than one sputum specimen and monitoring cultured specimens for a full 8 weeks may assist in optimizing the diagnostic yield. Upper lobe infiltrates and cavitary disease are still the most frequent radiographic presentations of pulmonary TB in HIV-infected and non-HIV-infected adults in countries with a high prevalence of TB.

Adult↗

Risk factors for adverse drug reactions during thiacetazone treatment of pulmonary tuberculosis in human immunodeficiency virus infected adults.

SETTING: Prospective randomised clinical trial comparing the safety and efficacy of rifampicin- and thiacetazone-containing regimens in human immunodeficiency virus (HIV)-infected adults with pulmonary tuberculosis (TB) at the National Tuberculosis Treatment Centre, Kampala, Uganda. OBJECTIVE: To assess demographic, clinical and laboratory risk factors associated with toxicity during treatment with streptomycin, thiacetazone and isoniazid (STH) of HIV-1 infected adults with pulmonary TB. DESIGN: Nested case-control study of all subjects randomized to the STH treatment arm. Baseline demographic, clinical, microbiological, hematological and radiographic characteristics were compared between subjects who developed and those who did not develop adverse drug reactions (ADR). RESULTS: Of the 90 subjects randomized to STH, 13 developed ADR yielding an incidence rate of 19.6 events per 100 person years of observation (PYO). Eleven of the 13 ADR were cutaneous hypersensitivity reactions, including one fatal case of Stevens-Johnson syndrome. Eight of 13 patients who developed ADR were tuberculin anergic, compared to 12 of 77 patients who did not develop ADR (P < 0.001). An absolute lymphocyte count below 2000 cells/mm3 was also associated with ADR (P = 0.02). CONCLUSION: Initial anergy to tuberculin and lymphocytopenia, markers of advanced HIV infection and immunosuppression, were associated with increased risk for adverse drug reactions during STH chemotherapy.

AIDS-Related Opportunistic Infections↗

Dentinal bonding after chemomechanical caries removal--effect of surface topography.

A study was carried out to determine whether or not the topography of the dentinal surface that is left after caries removal affects bond strength. The caries was removed either by a rotating instrument and a bur or by the chemomechanical method using D,L,2-aminobutyric acid. The bond strength appeared to be enhanced on those specimens treated by the chemomechanical removal since the surface was characterized by lack of a smeared layer and by open dentinal tubules and numerous undercuts.

Aminobutyrates↗

Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada 1983.

We report a cohort study of fatal upper GI hemorrhage and/or perforation in relation to use of nonsteroidal anti-inflammatory drugs (NSAIDs) among the one million residents of Saskatchewan Canada in 1983. All hospitalized cases of GI hemorrhage and/or perforation with a fatal outcome were identified using the records linkage system of the Saskatchewan Department of Health. Discharge summaries and autopsy records were reviewed to select the cases of upper GI hemorrhage or upper GI perforation and to exclude cases in which known risk factors were present. The 134,060 residents who filled one or more prescriptions for an NSAID in 1983 were identified and individually linked to their hospital records by patient identification number. The age- and gender-specific incidence of fatal upper GI hemorrhage and/or perforation in the absence of risk factors in users was compared to that in nonusers, controlling for recent history of upper GI disease. Fatal upper GI hemorrhage or perforation in temporal association with NSAIDs is extremely rare in persons younger than 75 years of age. No temporally-related cases occurred in male NSAID users age 75 and older, but NSAID usage in this group was limited. Among women age 75 and older, the rate in users was higher than in nonusers, with the highest rate being in female NSAID users age 75 and older with a recent history of upper GI disease. Total mortality among women age 75 and older was slightly lower among users than among nonusers. Physicians who prescribe NSAIDs to patients age 75 and older should be aware of the potential risks, particularly in those with predisposing factors such as a history of upper GI disease.

Adult↗