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Biomedical subjects

H D White

Publications and source records attributed to H D White.

At least 37 records · Page 2Linked to original sources
PubMed2002

Slowed ST segment recovery despite early infarct artery patency in patients with Q waves at presentation with a first acute myocardial infarction. Implications of initial Q waves on myocyte reperfusion.

BACKGROUND: The presence of Q waves at presentation with a first acute myocardial infarction reflects a more advanced stage of the infarction process. When infarct-related artery patency (Thrombolysis in Myocardial Infarction 2 or 3 flow) is restored, resolution of ST segment elevation indicating successful myocyte reperfusion may differ according to how far the infarction process has progressed. METHODS AND RESULTS: In 144 patients with a first acute myocardial infarction treated with streptokinase in the first Hirulog Early Reperfusion Occlusion trial, information was obtained from continuous ST segment monitoring, the presenting electrocardiogram and early angiography performed at a median time of 99 min after the commencement of streptokinase (interquartile range 89-108 min). We determined how many patients had 50% ST recovery within 120 min and in how many cases it was sustained over 4h. In the 109 patients with patent infarct-related arteries, 50% ST recovery occurred in 95% of patients without vs 80% of those with initial Q waves (P=0.03), and sustained ST recovery occurred in 67% of patients without vs 47% of those with initial Q waves (P=0.03). On multivariate analysis including the time from symptom onset to streptokinase therapy, the presence of Q waves at presentation was the only predictor of failure to achieve 50% ST recovery (odds ratio 5.08, 95% confidence interval 1.29-20.01, P=0.02). TIMI 2 flow, as opposed to TIMI 3 flow, was the only predictor of failure to achieve stable ST recovery (odds ratio 2.63, 95% confidence interval 1.15-5.88,P =0.02). CONCLUSION: The presence of initial Q waves predicts slower and less complete ST recovery, reflecting reduced myocyte reperfusion, even in those with early infarct artery patency. These patients may be targeted for new therapeutic strategies to improve microvascular reperfusion.

Acute Disease↗
PubMed2002

Management and outcome of patients with atrial fibrillation during acute myocardial infarction: the GUSTO-III experience. Global use of strategies to open occluded coronary arteries.

OBJECTIVE: To investigate the use of antiarrhythmic agents and electrical cardioversion in the management of patients with atrial fibrillation complicating acute myocardial infarction, and their relation to 30 day and one year mortality. DESIGN: Prospective study of 1138 patients with atrial fibrillation from the GUSTO-III trial. INTERVENTIONS: Of the 1138 study patients, 317 (28%) received antiarrhythmic treatment, including class I antiarrhythmic agents (12%), sotalol (5%), and amiodarone (15%); electrical cardioversion was attempted in 116 (10%). RESULTS: Sinus rhythm was restored in 72% of patients receiving class I antiarrhythmic agents, 67% of those receiving sotalol, 79% of those receiving amiodarone, and 64% of those having electrical cardioversion. After adjusting for baseline characteristics and complications occurring before the onset of atrial fibrillation, there was no difference among the treatment groups in the incidence of sinus rhythm at the time of discharge or before deterioration to hospital death. However, the use of class I antiarrhythmic drugs or sotalol was associated with a lower unadjusted 30 day and one year mortality. After adjustment for baseline factors and pre-atrial fibrillation complications, the odds ratios for 30 day and one year mortality were 0.42 (95% confidence interval (CI) 0.19 to 0.89) and 0.58 (95% CI 0.33 to 1.04) with class I agents, and 0.31 (95% CI 0.07 to 1.32) and 0.31 (95% CI 0.09 to 1.02) with sotalol. In contrast, there was no association between the use of amiodarone or electrical cardioversion and 30 day or one year mortality. CONCLUSIONS: There was a strong trend towards lower mortality associated with the use of class I antiarrhythmic agents or sotalol in managing patients with atrial fibrillation after acute myocardial infarction. Randomised trials are indicated.

Aged↗
PubMed2001

Effects of substituting uridine triphosphate for ATP on the crossbridge cycle of rabbit muscle.

1. Substituting uridine triphosphate (UTP) for ATP as a substrate for rabbit skeletal myosin and actin at 4 degrees C slowed the dissociation of myosin-S1 from actin by threefold, and hydrolysis of the nucleotide by sevenfold, without a decrease in the rates of phosphate or uridine diphosphate dissociation from actomyosin. 2. The same substitution in skinned rabbit psoas fibres at 2-3 degrees C reduced the maximum shortening velocity by 56 % and increased the force asymptote of the force-velocity curve relative to force (alpha/P(o)) by 112 % without altering the velocity asymptote, beta. It also decreased isometric force by 35 % and isometric stiffness by 20 %, so that the stiffness/force ratio was increased by 23 %. 3. Tension transient experiments showed that the stiffness/force increase was associated with a 10 % reduction in the amplitude of the rapid, partial (phase 2) recovery relative to the isometric force, and the addition of two new components, one that recovered at a step-size-independent rate of 100 s(-1) and another that did not recover following the length change. 4. The increased alpha/P(o) with constant beta suggests an internal load, as expected of attached crossbridges detained in their movement. An increased stiffness/force ratio suggests a greater fraction of attached bridges in low-force states, as expected of bridges with unhydrolyzed UTP detained in low-force states. Decreased phase 2 recovery suggests the detention of high-force bridges, as expected of slowed actomyosin dissociation by nucleotide. 5. These results suggest that the separation of hydrolysed phosphates from nucleotides occurs early in the attached phase of the crossbridge cycle, near and possibly identical to a transition to a firmly attached, low-force state from an initial state where bridges with hydrolysed nucleotides are easily detached by shortening.

Actins↗
PubMed2001

Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes.

BACKGROUND: Diabetes mellitus is a major risk factor for adverse outcomes after acute coronary syndromes (ACS). Because this disease may be associated with increased platelet aggregation, we investigated whether diabetic patients with ACS derive particular benefit from platelet glycoprotein (GP) IIb/IIIa receptor inhibition. METHODS AND RESULTS: We performed a meta-analysis of the diabetic populations enrolled in the 6 large-scale platelet GP IIb/IIIa inhibitor ACS trials: PRISM, PRISM-PLUS, PARAGON A, PARAGON B, PURSUIT, and GUSTO IV. Among 6458 diabetic patients, platelet GP IIb/IIIa inhibition was associated with a significant mortality reduction at 30 days, from 6.2% to 4.6% (OR 0.74; 95% CI 0.59 to 0.92; P=0.007). Conversely, 23 072 nondiabetic patients had no survival benefit (3.0% versus 3.0%). The interaction between platelet GP IIb/IIIa inhibition and diabetic status was statistically significant (P=0.036). Among 1279 diabetic patients undergoing percutaneous coronary intervention (PCI) during index hospitalization, the use of these agents was associated with a mortality reduction at 30 days from 4.0% to 1.2% (OR 0.30; 95% CI 0.14 to 0.69; P=0.002). CONCLUSIONS: This meta-analysis, including the entire large-scale trial experience of intravenous platelet GP IIb/IIIa inhibitors for the medical management of non-ST-segment-elevation ACS, shows that these agents may significantly reduce mortality at 30 days in diabetic patients. Although not based on a randomized assessment, the survival benefit appears to be of greater magnitude in patients undergoing PCI. Therefore, the use of platelet GP IIb/IIIa inhibitors should be strongly considered in diabetic patients with ACS.

Diabetes Complications↗
PubMed2001

Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status: the paragon-B troponin T substudy.

BACKGROUND: Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. METHODS AND RESULTS: We prospectively studied 1160 patients with non-ST-segment elevation ACS randomized in PARAGON-B to receive lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (>/=0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P=0.01) among TnT-positive patients but not among TnT-negative patients (11.2% for placebo versus 10.8% for lamifiban, P=0.86; P=0.08 for test of interaction between TnT status and treatment assignment). This pattern held for the end points of death alone and death or myocardial (re)infarction at 30 days. Peak TnT level at 48 hours did not differ with lamifiban treatment. CONCLUSIONS: TnT predicts poor short-term outcomes in non-ST-segment elevation ACS. Treatment benefit with lamifiban is limited almost exclusively to TnT-positive patients, reducing 30-day adverse outcomes to a rate nearly identical to that of negative patients.

Acetates↗
PubMed2001

Human immunodeficiency virus-specific and CD3-redirected cytotoxic T lymphocyte activity in the human female reproductive tract: lack of correlation between mucosa and peripheral blood.

CD8(+) T cell phenotype and function were assessed in the female reproductive tracts (FRTs) of 3 human immunodeficiency virus (HIV)-positive patients who had undergone hysterectomy. FRT cytotoxic T lymphocyte (CTL) lytic activity from 1 patient (patient 872) was detected by using CD3-dependent redirected-lysis assay and HIV-specific assay, concomitant with the presence of CD8(+) cells. In contrast, samples from the 2 other HIV-positive patients (patients 1356 and 1364), who also were asymptomatic for HIV-associated illnesses, demonstrated no CTL activity in any solid tissue tested by either assay, despite activity by autologous peripheral blood mononuclear cells (PBMC). This absence of CTL activity was correlated with a relative absence of CD8(+) cells in the FRT, whereas CD8(+) cells were present in PBMC. Thus, CTL activity in PBMC may fail to correlate with mucosal activity. The finding of CTL activity in the FRT of patient 872 represents the first description of CTL in upper and lower FRT tissues of an HIV-positive woman.

Adult↗
PubMed2001

Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project.

BACKGROUND: Stroke is a leading cause of death and disability. Although clinical trials of the early lipid-lowering therapies did not demonstrate a reduction in the rates of stroke, data from recently completed statin trials strongly suggest benefit. METHODS AND RESULTS: The effect of pravastatin 40 mg/d on stroke events was investigated in a prospectively defined pooled analysis of 3 large, placebo-controlled, randomized trials that included 19 768 patients with 102 559 person-years of follow-up. In all, 598 participants had a stroke during approximately 5 years of follow-up. The 2 secondary prevention trials (CARE [Cholesterol And Recurrent Events] and LIPID [Long-term Intervention with Pravastatin in Ischemic Disease]) individually demonstrated reductions in nonfatal and total stroke rates. When the 13 173 patients from CARE and LIPID were combined, there was a 22% reduction in total strokes (95% CI 7% to 35%, P:=0.01) and a 25% reduction in nonfatal stroke (95% CI 10% to 38%). The beneficial effect of pravastatin on total stroke was observed across a wide range of patient characteristics. WOSCOPS (West of Scotland Coronary Prevention Study, a primary prevention trial in hypercholesterolemic men) exhibited a similar, although smaller, trend for a reduction in total stroke. Among the CARE/LIPID participants, pravastatin was associated with a 23% reduction in nonhemorrhagic strokes (95% CI 6% to 37%), but there was no statistical treatment group difference in hemorrhagic or unknown type. CONCLUSIONS: Pravastatin reduced the risk of stroke over a wide range of lipid values among patients with documented coronary disease. This effect was due to a reduction in nonfatal nonhemorrhagic strokes.

Anticholesteremic Agents↗
PubMed2001

One-year survival following early revascularization for cardiogenic shock.

CONTEXT: Cardiogenic shock (CS) is the leading cause of death for patients hospitalized with acute myocardial infarction (AMI). OBJECTIVE: To assess the effect of early revascularization (ERV) on 1-year survival for patients with AMI complicated by CS. DESIGN: The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) Trial, an unblinded, randomized controlled trial from April 1993 through November 1998. SETTING: Thirty-six referral centers with angioplasty and cardiac surgery facilities. PATIENTS: Three hundred two patients with AMI and CS due to predominant left ventricular failure who met specified clinical and hemodynamic criteria. INTERVENTIONS: Patients were randomly assigned to an initial medical stabilization (IMS; n = 150) group, which included thrombolysis (63% of patients), intra-aortic balloon counterpulsation (86%), and subsequent revascularization (25%), or to an ERV group (n = 152), which mandated revascularization within 6 hours of randomization and included angioplasty (55%) and coronary artery bypass graft surgery (38%). MAIN OUTCOME MEASURES: All-cause mortality and functional status at 1 year, compared between the ERV and IMS groups. RESULTS: One-year survival was 46.7% for patients in the ERV group compared with 33.6% in the IMS group (absolute difference in survival, 13.2%; 95% confidence interval [CI], 2.2%-24.1%; P<.03; relative risk for death, 0.72; 95% CI, 0.54-0.95). Of the 10 prespecified subgroup analyses, only age (<75 vs >/= 75 years) interacted significantly (P<.03) with treatment in that treatment benefit was apparent only for patients younger than 75 years (51.6% survival in ERV group vs 33.3% in IMS group). Eighty-three percent of 1-year survivors (85% of ERV group and 80% of IMS group) were in New York Heart Association class I or II. CONCLUSIONS: For patients with AMI complicated by CS, ERV resulted in improved 1-year survival. We recommend rapid transfer of patients with AMI complicated by CS, particularly those younger than 75 years, to medical centers capable of providing early angiography and revascularization procedures.

Aged↗
PubMed2001

Corrected TIMI frame counts correlate with stenosis severity and infarct zone wall motion after thrombolytic therapy.

BACKGROUND: The majority of patients with patent infarct-related arteries after thrombolytic therapy have slower than normal flow, which relates to myocardial perfusion. METHODS: To evaluate the relationships between blood levels of creatine kinase (CK) and the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC), infarct artery stenosis, and left ventricular function, we studied 397 patients with a first myocardial infarction who underwent angiography at 3 weeks. TIMI flow grades, the CTFC, infarct artery stenosis, and infarct zone wall motion (by contrast ventriculography using the centerline method) were assessed, and CK levels (in units per liter) were measured hourly for the first 4 hours after streptokinase (1.5 x 10(6) U over 30-60 minutes) and then every 4 hours over the next 20 hours, all blinded to treatment and outcome. RESULTS: Infarct artery stenosis and the CTFC, assessed as continuous variables, correlated in patients with patent infarct arteries (r = 0.33, P <.001). Also, there was a significant correlation between the CTFC and the sum of hypokinetic chords in the infarct zone (r = 0.15, P =.01). Patients with total occlusion or markedly slowed infarct artery flow (CTFC >100) had a higher fraction of chords with wall motion >2 SDs below normal (0.65 [0.41, 0.80] vs 0.37 [0.0, 0.67]) compared with patients with normal flow (CTFC < or =27) (P <.001). The rates of increase of median CK levels with respect to TIMI flow grades were 342 U/L/h for TIMI 3 versus 212 U/L/h for TIMI 2 versus 140 U/L/h for TIMI 0-1 (P <.0001). CONCLUSIONS: Prolonged corrected TIMI frame counts correlate with stenosis severity in the infarct artery after infarction, infarct zone regional wall motion, and CK levels.

Constriction, Pathologic↗
PubMed2000

Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. Main results of the GUARDIAN trial. Guard during ischemia against necrosis (GUARDIAN) Investigators.

BACKGROUND: The transmembrane sodium/hydrogen exchanger maintains myocardial cell pH integrity during myocardial ischemia but paradoxically may precipitate cell necrosis. The development of cariporide, a potent and specific inhibitor of the exchanger, prompted this investigation of the potential of the drug to prevent myocardial cell necrosis. METHODS AND RESULTS: A total of 11 590 patients with unstable angina or non-ST-elevation myocardial infarction (MI) or undergoing high-risk percutaneous or surgical revascularization were randomized to receive placebo or 1 of 3 doses of cariporide for the period of risk. The trial failed to document benefit of cariporide over placebo on the primary end point of death or MI assessed after 36 days. Doses of 20 and 80 mg every 8 hours had no effect, whereas a dose of 120 mg was associated with a 10% risk reduction (98% CI 5.5% to 23.4%, P=0.12). With this dose, benefit was limited to patients undergoing bypass surgery (risk reduction 25%, 95% CI 3.1% to 41.5%, P=0.03) and was maintained after 6 months. No effect was seen on mortality. The rate of Q-wave MI was reduced by 32% across all entry diagnostic groups (2.6% versus 1.8%, P=0.03), but the rate of non-Q-wave MI was reduced only in patients undergoing surgery (7.1% versus 3.8%, P=0.005). There were no increases in clinically serious adverse events. CONCLUSIONS: No significant benefit of cariporide could be demonstrated across a wide range of clinical situations of risk. The trial documented safety of the drug and suggested that a high degree of inhibition of the exchanger could prevent cell necrosis in settings of ischemia-reperfusion.

Aged↗
PubMed2000

Effects of pravastatin in 3260 patients with unstable angina: results from the LIPID study.

BACKGROUND: The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction. METHODS: 3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3-36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6.0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox's proportional hazards model. FINDINGS: Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20.6% in the myocardial infarction group and 26.3% in the unstable angina group (p=0.55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24.6% of the placebo group; 22.3% of the pravastatin group). INTERPRETATION: Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin.

Adult↗