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Biomedical subjects

C A Boucher

Publications and source records attributed to C A Boucher.

At least 109 records · Page 6Linked to original sources
PubMed1993

Variables associated with a poor prognosis in patients with an ischemic thallium-201 exercise test.

To determine the exercise workload, ECG, and thallium-201 image parameters that are most closely associated with a poor prognosis from ischemic heart disease, the test results of 268 patients were reviewed. Only patients with unequivocal thallium-201 redistribution were selected. A multivariate analysis was performed to find the variables that were most strongly associated with the outcomes of coronary revascularization, myocardial infarction, and cardiac death during a follow-up period of 25 +/- 19 months. Patients who underwent early elective revascularization had poorer exercise tolerance and more thallium image abnormalities than those with no events. In the remaining patients myocardial infarction was most closely related to the extent and severity of thallium ischemia (p = 0.0086), whereas cardiac death was associated with abnormal thallium lung uptake (p = 0.0082) and an inability to exercise to 9.6 MET (p = 0.0144). Thus unlike myocardial infarction, cardiac death is best predicted by variables that reflect poor left ventricular function rather than those that indicate ischemia.

Aged↗
PubMed1993

Antigenic variation of the dominant gp41 epitope in Africa.

OBJECTIVE: To determine the value of (combinations of) synthetic peptides representing immunodominant sites on HIV-1/HIV-2 transmembrane proteins for the detection and discrimination between HIV-1 and HIV-2 infection in various populations. DESIGN AND METHODS: Two 24-mer synthetic peptides derived from immunodominant sites on the HIV-1 and HIV-2 transmembrane proteins were used separately, in combination (env 1/2), and in combination with recombinant p24 (p24/env) in enzyme-linked immunosorbent assays. RESULTS: Positive reactions with env-1 were found in 150 out of 150 (100%) samples from Dutch AIDS patients, 60 out of 60 (100%) samples from Dutch homosexual men obtained 1 year after HIV-1-antibody seroconversion, 29 out of 30 (96.7%) samples from these men obtained at the time of HIV-1-antibody seroconversion, 40 out of 41 (97.6%) samples from East Africans with AIDS-related symptoms, and three out of 29 (10.3%) samples from West Africans with HIV-2 infection (including a sample from an individual infected with both HIV-1 and HIV-2). Positive reactions with env-2 in these study populations were 11 out of 150 (7.3%), nine out of 60 (15%), none out of 30 (0%), 25 out of 41 (60.9%) and 29 out of 29 (100%), respectively. In the samples with dual reactivity, true versus cross-reactivity could generally be differentiated on the basis of large differences in optical density values in the respective assays. All samples reacted positively with p24/env; 308 out of 310 (99.3%) were positive in the env 1/2 assay. Four East African samples that had negative or only weakly positive reactions with env-1 showed a noticeably stronger reaction with variant peptides derived from Central African isolate sequences. In all samples from HIV-1-infected Dutch homosexual men, the strongest signal was detected using the env-1 peptide sequence, which is derived from European and American isolates. CONCLUSIONS: Small peptide antigens may permit the detection of strain-specific antibodies, allowing serological characterization of HIV isolates.

Africa↗
PubMed1993

Greater diversity of the HIV-1 V3 neutralization domain in Tanzania compared with The Netherlands: serological and genetic analysis.

OBJECTIVE: To compare variation in the HIV-1 V3 neutralization domain in Tanzania and The Netherlands. METHODS: For serologic analysis, the specificity of anti-V3 antibodies (immunoglobulin G) for a panel of V3 peptides was determined in sera from 55 symptomatic HIV-1-infected Tanzanians and 51 Dutch AIDS patients. For genetic analysis, viral RNA was isolated from 15 of the Tanzanian sera and six of the Dutch sera. The V3 encoding region was reverse-transcribed, polymerase chain reaction-amplified and bacterially cloned, and sequences were determined over a stretch of at least 207 nucleotides. RESULTS: Thirty-five per cent of the Tanzanian sera, versus 2% of the Dutch sera, showed the highest reactivity to a V3 sequence of Zairian origin (RKSIHVGPGQAFYATG). Twenty-nine per cent of the Tanzanian sera, versus 82% of the Dutch sera, showed the highest reactivity to V3 sequences of US/European origin (RKSIXIGPGRAFYTTG; X = H, P or N). The Tanzanian RNA sequences showed greater diversity (mean distance, 19%) than the Dutch RNA sequences (10%). The measured anti-V3 specificities of the Tanzanian sera did not match accurately with the V3 sequences recovered from these sera. However, reactivity to the Zairian V3 peptide was associated with the sequence GPGQ, found in the centre of the V3 in 50% of the Tanzanian sequences. Sera from both countries that showed similar reactivities to the peptide panel contained RNA sequences that were relatively distant. CONCLUSIONS: The diversity of the HIV-1 population in Tanzania is much greater than that in The Netherlands. An indication of the HIV-1 V3 variation in a particular geographic region can be obtained by serological methods, but sequence analysis should not be omitted.

Adolescent↗
PubMed1993

Use of competitive polymerase chain reaction to determine HIV-1 levels in response to antiviral treatments.

OBJECTIVE: To develop a competitive polymerase chain reaction technique with which to evaluate the usefulness of HIV-1 level as a marker of response to antiviral treatment. DESIGN: HIV-1 sequences were assessed by competitive polymerase chain reaction in four subjects participating in a double-blind study of monotherapy versus combination therapy with nucleoside analogues. METHODS: We inserted a mutant construct of the HIV-1 pol sequence into a commercial vector, enabling us to generate known amounts of mutant DNA and RNA for competitive polymerase chain reaction. To measure HIV-1 DNA copies in cells, the mutant DNA fragments were allowed to compete in a 10-fold dilution series with a constant amount of nucleic acid from the subject. To measure HIV-1 RNA copies in plasma, in vitro synthesized mutant RNA was added in a 10-fold dilution series to a constant amount of subject RNA and copy DNA was synthesized. DNA and copy DNA were used as the input for nested pol polymerase chain reaction. Mutant and wild-type amplimers were discriminated by size. RESULTS: The competitive polymerase chain reaction technique has been validated in model experiments and can be used over a broad range (at least 6 logs) of levels. Three of the four subjects showed a decline of 1 log in proviral DNA levels in cells after beginning antiviral treatment. All four showed a decline of at least 1 log in viral RNA levels in plasma, but this decline was transient in one subject. CONCLUSION: The HIV-1 sequence level is a useful marker in antiviral treatment studies.

Antiviral Agents↗
PubMed1993

Bepridil improves left ventricular performance in patients with angina pectoris.

Patients with coronary artery disease and angina pectoris have abnormalities of left ventricular (LV) diastolic performance. These abnormalities, which exist when the patients are at rest and not experiencing angina, are presumably secondary to abnormalities of intracellular calcium metabolism. Twenty-three patients with chronic exertional angina pectoris participated in a placebo-controlled, randomized, cross-over trial of bepridil hydrochloride. Angina frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were assessed, and each patient underwent first-pass radionuclide cineangiography while receiving placebo or bepridil to assess LV performance. Bepridil decreased angina frequency from 8.5 +/- 0.6 to 4.4 +/- 1.5 episodes per week (p < 0.01) and NTG consumption from 7.2 +/- 2.4 to 3.6 +/- 1.5 tablets per week (p < 0.01). Total treadmill exercise time, time to onset of angina, and time to 1-mm ST segment depression increased significantly during bepridil therapy. Cardiac output (CO), stroke volume (SV), and ejection fraction (EF) increased at rest and during peak upright bicycle exercise. Peak ejection rate and peak filling rate increased, and time to peak ejection rate and time to peak filling rate decreased at rest and at peak exercise during bepridil therapy. In addition, early diastolic filling fraction increased and atrial filling volume decreased during bepridil treatment. Bepridil is effective as monotherapy for treatment of patients with exertional angina; its use is associated with increased exercise capacity and decreased angina frequency and NTG consumption as well as improved LV systolic and diastolic performance at rest and during peak exercise.

Adult↗
PubMed1993

High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase.

Passage of human immunodeficiency virus type 1 in the presence of increasing 2'-deoxy-3'-thiacytidine (3TC) concentrations results in high-level (> 100-fold) 3TC-resistant viruses. All 3TC-resistant viruses possess a substitution at the second codon (from a methionine into an isoleucine) at position 184 within the highly conserved motif (YMDD) of human immunodeficiency virus type 1 reverse transcriptase. 3TC-resistant viruses were cross-resistant to the (-) enantiomer of the fluorinated derivative of BCH-189 but remained susceptible to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. The susceptibilities of the 3TC-resistant viruses to the (+) enantiomers of BCH-189 and the fluorinated derivative of BCH-189 demonstrate an enantiomeric specificity for viruses selected under these conditions. Introduction of an isoleucine substitution at codon 184 into a background of two known 3'-azido-3'-deoxythymidine resistance mutations (amino acids 41 and 215) restored the susceptibility of this virus to 3'-azido-3'-deoxythymidine.

Antiviral Agents↗
PubMed1993

Effects of discontinuation of zidovudine treatment on zidovudine sensitivity of human immunodeficiency virus type 1 isolates.

Zidovudine treatment of individuals infected with human immunodeficiency virus type 1 (HIV-1) results in HIV-1 isolates with a reduced zidovudine sensitivity in vitro. This reduction is due to mutations causing amino acid substitutions at five codons (41, 67, 70, 215, and 219) on the reverse transcriptase enzyme of HIV. HIV-1 isolates were obtained 8 to 69 weeks after therapy discontinuation from 10 patients at different stages of disease. Zidovudine sensitivity was determined by the HeLa CD4+ plaque assay. The presence of the resistance-conferring mutations was determined by using a selective polymerase chain reaction. Sensitivity could be determined for six isolate pairs: one showed a decline in the 50% inhibitory zidovudine concentration after therapy discontinuation; four pairs did not show a change. The majority of changes in the five codons in isolates from all 10 patients were the result of a relative increase in the wild-type sequence. Complete changes from mutant to the wild type were seen for only two codons in isolates from two patients. This study of isolates from a small group of individuals at different stages of disease, who had been taking zidovudine for 1 to 2 years, shows that a period of 1 year without zidovudine may be required to achieve a change from a mutant or mixed virus population to a wild-type virus population.

CD4-Positive T-Lymphocytes↗
PubMed1993

Two highly antigenic sites in the human immunodeficiency virus type 1 reverse transcriptase.

Antibodies to human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) are found in the serum of the majority of infected individuals, and inhibition of RT polymerase activity by HIV-1-positive sera can be demonstrated in vitro. The binding sites of human antibodies on the protein have not yet been identified. We synthesized overlapping peptides covering the entire RT protein of HIV-1 and used them in an enzyme-linked immunosorbent assay system to map the reactivities of HIV-1 and HIV-2 antibody-positive sera. Two highly antigenic regions were identified by both HIV serotypes. One region was found in the central part of the RT protein (amino acids 261 to 280) and another was found at the carboxy terminus in the RNase H portion of RT (amino acids 517 to 536). Comparison of the serological results with the crystal structure of the RT revealed that the antigenic region in the RNase H portion is located at the surface of the protein. The other antibody-binding site (amino acids 261 to 280) was located in the "thumb" region of the polymerase domain of RT. Polyclonal antibodies to either of the antibody-binding sites do not affect the polymerase activity of the RT protein.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Usefulness of dipyridamole-thallium scanning for preoperative evaluation of cardiac risk for nonvascular surgery.

The ability to stratify cardiac risk before nonvascular surgery using clinical markers and dipyridamole-thallium scanning (DTS) was assessed for patients with known or suspected coronary artery disease unable to exercise. Of 100 consecutively studied patients who proceeded to nonvascular surgery, 9 (9%) experienced greater than or equal to 1 perioperative cardiac ischemic event, including death in 2 patients (2%) and nonfatal myocardial infarction in 2 (2%). Logistic regression identified 2 clinical predictors (age greater than 70 years and history of heart failure), and 1 DTS (thallium redistribution) predictor of events. Of 45 patients with neither clinical variable, none (0%; 95% confidence intervals [CI] 0 to 8%) had events. Of 55 patients with greater than or equal to 1 clinical marker, 9 (16.4%; 95% CI 7 to 26%) had events. Within this subgroup, 1 of 31 patients (3.2%; 95% CI 0 to 16%) without thallium redistribution had events compared with 8 of 24 (33.3%; 95% CI 14 to 52%) with redistribution. An algorithm combining 5 independent clinical and 2 DTS predictors, derived previously in vascular surgery patients, was validated in the 100 nonvascular surgery patients. It is concluded that preoperative planar DTS is most useful to stratify selected nonvascular surgery patients at intermediate or high risk by clinical assessment. However, for almost half of those patients with known or suspected coronary artery disease, DTS may be unnecessary because of sufficiently low predictive value based on simple clinical descriptors.

Aged↗
PubMed1992

Effects of antianginal therapy on left ventricular systolic and diastolic performance: comparison of the response to bepridil, propranolol, and diltiazem.

Abnormalities of left ventricular (LV) systolic performance develop during exercise in patients with coronary artery disease (CAD) as a result of ischemia-induced regional wall motion abnormalities. Like patients with hypertension and those with hypertrophic cardiomyopathy, patients with CAD display abnormalities of LV diastolic performance under basal conditions in the absence of ischemia. The purpose of these studies was to compare the effects of bepridil versus those of propranolol or diltiazem in patients with exertional angina pectoris. LV systolic and diastolic performance were assessed at rest and during peak upright bicycle exercise by first-pass radionuclide ventriculography. Compared with propranolol, bepridil increased exercise capacity, cardiac output, and stroke volume and decreased systemic vascular resistance. Compared with diltiazem, bepridil increased exercise capacity, peak filling rate, and early diastolic filling fraction and decreased systemic vascular resistance, heart rate, time to peak filling rate, and atrial filling volume. Bepridil therapy is associated with improved exercise capacity and decreased anginal frequency and nitroglycerin consumption. In addition, its use is accompanied by favorable changes in LV systolic and diastolic function at rest and during exercise. These changes are consistent with benefits resulting from resolution of myocardial ischemia as well as from positive lusitropic effects of bepridil on the ventricular myocardium.

Angina Pectoris↗
PubMed1992

Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine.

It is recognized that high-level resistance to 3'-azido-3'-deoxythymidine (AZT, zidovudine, or Retrovir) is conferred by the presence of four mutations in the human immunodeficiency virus (HIV) reverse transcriptase [RT; deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase (RNA-directed), EC 2.7.7.49] coding sequence. However, a number of clinical isolates have been observed that exhibit high-level resistance but contain only three of the four identified mutations (Asn-67, Arg-70, and Tyr-215). Construction of a molecular clone with this genotype gave rise to only a partially resistant virus, raising the possibility that an additional mutation existed in some clinical isolates. Using an HIV marker rescue system, we have mapped and identified a fifth mutation conferring resistance to zidovudine, namely, methionine to leucine at codon 41 of HIV RT. An infectious molecular clone containing this mutation together with three previously identified mutations in the RT coding sequence yielded highly resistant HIV after transfection of T cells. Direct detection of the fifth mutation in DNA samples from cocultured peripheral blood lymphocytes by the PCR revealed that it occurred relatively early in the development of zidovudine resistance. However, this mutation was only detected after the appearance of the codon 215 change in the RT coding sequence. Identification of this mutation in addition to the other known mutations conferring resistance enables rapid and direct correlation between an RT genotype and sensitivity of the virus.

Amino Acid Sequence↗
PubMed1992

Technetium-99m sestamibi myocardial imaging at rest for assessment of myocardial infarction and first-pass ejection fraction. Multicenter Cardiolite Study Group.

The ability of technetium (Tc)-99m sestamibi myocardial perfusion imaging at rest to evaluate myocardial infarction and first-pass ejection fraction was studied in a trial involving 18 institutions. Protocol I compared regional perfusion with occurrence of infarction by Q wave or by gated blood pool scan wall motion abnormality in 146 patients. Protocol II assessed first-pass right and left ventricular ejection fraction in 85 patients. In protocol I, Tc-99m sestamibi images were abnormal in 104 of 111 patients (94%) with both a Q wave and a gated scan wall motion abnormality and was normal in 23 of 25 patients (92%) in whom both were normal. Therefore, concordance existed in 105 (94%) patients. Of 115 patients with a Q wave, 107 (93%) had an abnormal Tc-99m sestamibi study. Of 115 patients with a gated scan wall motion abnormality, 108 (94%) had an abnormal Tc-99m sestamibi study. Tc-99m sestamibi imaging showed corresponding perfusion abnormalities in 81% of 69 anterior Q-wave infarcts, 73% of 55 inferior Q-wave infarcts and 88% of 8 posterior infarcts. Specificity in normal regions on electrocardiography and wall motion was 91, 100 and 100%, respectively, for anterior, inferior and posterior regions, respectively, between wall motion and perfusion. Of 17 myocardial segments per patient, there was concordance in 74% of patients. First pass Tc-99m sestamibi imaging of ejection fraction agreed well with conventional first-pass imaging for the right and left ventricle. It is concluded that Tc-99m sestamibi myocardial imaging at rest reliably diagnoses and localizes infarction and assesses ejection fraction by first-pass imaging.

Adult↗
PubMed1992

Relationship between septal perfusion, viability, and motion before and after coronary artery bypass surgery.

The etiology of abnormal interventricular septal motion occurring after open-heart surgery using cardiopulmonary bypass has not been clarified. Intraoperative ischemic septal injury has been proposed as one explanation for this finding. To examine this possibility, resting septal perfusion and viability were studied using rest and redistribution thallium-201 scintigraphy in 16 patients before and after coronary artery bypass surgery. The results were compared with septal motion on preoperative and postoperative resting gated blood pool scans. Preoperatively, septal thallium uptake was normal in 10 of 16 patients, and septal motion was normal in 14 of 16. Postoperatively, septal thallium uptake was normal in 11 of 16 patients, while septal motion was abnormal in all. Thus abnormal postoperative septal motion is usually associated with normal septal perfusion and viability on thallium scans and therefore is not the result of septal ischemic injury in a majority of patients.

Adult↗
PubMed1992

Effects of atrial natriuretic peptide on myocardial contractile and diastolic function in patients with heart failure.

Atrial natriuretic peptide alters left ventricular performance in patients with heart failure. To assess the direct effects of this hormone on myocardial function, its actions were compared with those of the pure vasodilator nitroprusside in 10 patients with heart failure. Simultaneous left ventricular micromanometer pressure and radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during atrial natriuretic peptide infusion. The baseline end-systolic pressure-volume relation was generated in nine patients from pressure-volume loops obtained during the two baseline periods and during afterload reduction with nitroprusside. Mean arterial pressure decreased with atrial natriuretic peptide (89 +/- 3 to 80 +/- 2 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (90 +/- 4 to 73 +/- 3 mm Hg, p less than 0.05). Left ventricular end-diastolic pressure also decreased with atrial natriuretic peptide (24 +/- 2 to 16 +/- 3 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (24 +/- 2 to 13 +/- 3 mm Hg, p less than 0.05). Cardiac index increased during infusion of each agent from 2.0 +/- 0.2 to 2.4 +/- 0.2 liters/min per m2 (p less than 0.01). Heart rate increased slightly with nitroprusside but did not change with atrial natriuretic peptide. Peak positive first derivative of left ventricular pressure (dP/dt), ejection fraction and stroke work index were unchanged by either agent. The relation between end-systolic pressure and volume during atrial natriuretic peptide infusion was shifted slightly leftward from the baseline value in four patients, slightly rightward in four and not at all in one patient, indicating no consistent inotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Positive inotropic and lusitropic effects of intravenous flosequinan in patients with heart failure.

OBJECTIVES: This study was designed to assess the direct effects of flosequinan on myocardial function. BACKGROUND: Flosequinan has been shown to improve symptoms and exercise tolerance in patients with heart failure. Although previous studies have established that flosequinan is a vasodilator, it is not known to what extent direct actions of the drug on myocardial contractility or diastolic properties contribute to its beneficial hemodynamic effects. METHODS: Nitroprusside and intravenous flosequinan were administered sequentially to 18 patients with severe heart failure (New York Heart Association functional class III or IV, left ventricular ejection fraction 0.14 +/- 0.02). Micromanometer left ventricular pressure and radionuclide volume data were combined to construct pressure-volume loops during 1) a baseline period, 2) nitroprusside infusion, 3) a second baseline period, and 4) flosequinan infusion. RESULTS: The peak rate of left ventricular pressure development increased from 899 +/- 84 to 1,070 +/- 94 mm Hg/s (p less than 0.05) with flosequinan. The baseline left ventricular end-systolic pressure-volume relation was constructed in 15 patients from the two baseline pressure-volume loops and from that obtained during afterload manipulation with nitroprusside. During flosequinan administration, the relation between end-systolic pressure and volume was shifted upward and leftward, indicating enhanced contractility, in 14 of 15 patients (p less than 0.001). The maximal rate of decrease in left ventricular pressure during isovolumetric relaxation increased in magnitude with flosequinan from 882 +/- 63 to 1,026 +/- 68 mm Hg/s (p less than 0.05). CONCLUSIONS: These results indicate that intravenous flosequinan has positive inotropic and lusitropic effects in patients with heart failure. Further studies are needed to assess the direct myocardial effects of oral flosequinan.

Cardiac Catheterization↗
PubMed1992

Effects of fosinopril on cardiac function in patients with hypertension. Radionuclide assessment of left ventricular systolic and diastolic performance.

Numerous pharmacologic agents are capable of lowering the blood pressure of hypertensive patients; however, each drug has a characteristic side effect profile and effect on cardiac performance. In this study, the hemodynamic effects of the angiotensin converting enzyme inhibitor fosinopril were assessed at rest and at peak upright bicycle exercise by first-pass radionuclide cineangiography in 12 patients with essential hypertension. Fosinopril reduced blood pressure at rest in the seated position from 152/101 to 131/85 mm Hg (P less than .01) and at peak exercise from 206/103 to 184/91 mm Hg (P less than .01). Fosinopril therapy was associated with an increase in stroke volume and cardiac output and a decrease in systemic vascular resistance at rest and during peak exercise. Both peak ejection rate and peak filling rate increased significantly at rest during fosinopril therapy. The unique cardiotropic response to fosinopril may reflect its effects on the myocardial renin-angiotensin system, and suggests that this agent may offer a therapeutic advantage compared with other angiotensin converting enzyme inhibitors.

Adolescent↗
PubMed1992

Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects.

The order of appearance in the reverse transcriptase gene of four mutations implicated in the development of resistance to zidovudine was investigated by selective polymerase chain reaction. Serial human immunodeficiency virus isolates were studied from 18 initially asymptomatic individuals who had been treated with zidovudine for 2 years. Most subjects had similar patterns. The first mutation occurred transiently at codon 70; its disappearance was paralleled by the appearance of a mutation at codon 215. Subsequently, in some individuals, the mutation at codon 70 reappeared. During the 2 years of treatment, no mutations developed at codon 219 and only one at codon 67, suggesting that most individuals developed only partly resistant virus. This was confirmed by plaque-reduction assay. Six subjects progressed to AIDS within the 2-year study period, confirming that the development of highly resistant isolates is not required for progression in treated individuals. No clear temporal relationship was found between the development of partial resistance and progression.

Acquired Immunodeficiency Syndrome↗