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Biomedical subjects

C A Boucher

Publications and source records attributed to C A Boucher.

At least 163 records · Page 9Linked to original sources

Antibody response to human immunodeficiency virus type 1 protease according to risk group and disease stage.

Three groups with different routes of human immunodeficiency virus type 1 (HIV-1) transmission (homosexual men, hemophiliacs, and children) were studied for serum antibodies to a recombinant form of the HIV-1 protease using an enzyme-linked immunoassay. At 1 year after seroconversion, defined as the moment antibodies to HIV-1 proteins were first detected, 56% (34/61) of the homosexual men had antibodies to protease, and 2 years after seroconversion this percentage was 63% (24/38). Within this 2-year period these antibodies were no longer detected in 16% (9/56). A similar pattern was observed in 20 hemophiliacs who seroconverted after exposure to HIV-1-contaminated blood products. We found that 63% (160/255) of homosexual men in Centers for Disease Control stage II or III, 60% (9/15) of patients with acquired immunodeficiency syndrome (AIDS)-related complex, and 36% (14/39) of patients with AIDS had antibodies to protease. In 255 homosexual men in Centers for Disease Control stage II or III, antibodies to protease were significantly more frequently found in samples lacking HIV-1 antigen (P less than 0.001) and possessing antibodies to HIV-1 core proteins (P less than 0.001). Twenty-four persons who developed AIDS were studied longitudinally: 58% (14/24) had antibodies to protease 1 year before developing symptoms; 29% (7/24) showed a decline and 29% (7/24) showed a loss of antibodies to protease at the onset of symptoms. Within a group of 47 HIV-1-infected children, 90% (18/20) with a stable disease course were persistently protease antibody positive, versus 4 of 27 children (15%) with an unstable disease course (P = 0.0001). These data indicate that HIV-1 protease is expressed and antigenic in most HIV-1-infected individuals and that a decline or absence of antibodies to protease is strongly associated with unstable disease in children and AIDS in adults.

Acquired Immunodeficiency Syndrome↗

Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging.

The biodistribution, dosimetry, and safety of a new myocardial imaging agent, 99mTc-hexakis-2-methoxyisobutyl isonitrile (HEXAMIBI), was evaluated in 17 normal volunteers at rest and exercise (Phase I studies). Technetium-99m HEXAMIBI clears rapidly from the blood with good myocardial uptake and favorable myocardial-to-background ratios for myocardial imaging. Dosimetry allows for administration of up to 30 mCi (1, 110 Bq) of [99mTc]HEXAMIBI. The myocardial images were of good quality and appeared less granular with sharper myocardial walls compared to 201T1 images. The clinical efficacy of [99mTc]HEXAMIBI planar stress and rest imaging was evaluated in a multicenter Phase II clinical trial involving 38 patients. Of 36 patients with significant coronary artery disease, 35 patients (97%) had abnormal 201T1 stress images, and 32 (89%) had abnormal [99mTc]HEXAMIBI stress images (P = N.S.). Technetium-99m HEXAMIBI images correlated in 31/35 patients (86%) who had either scar or ischemia on 201T1 images. By segmental myocardial analysis, exact concordance was obtained in 463/570 myocardial segments (81%). This multicenter Phase I and II study indicates that planar [99mTc]HEXAMIBI stress imaging is safe and compares well with 201T1 stress imaging for detection of coronary artery disease.

Adult↗

Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi's sarcoma.

The effectiveness and antiretroviral activities of interferon-alpha in AIDS-related Kaposi's sarcoma was assessed in a non-randomised, phase-II clinical trial. 28 patients were treated with high-dose (27-36 MU) human recombinant interferon-alpha 2a subcutaneously every day for 8 weeks. In patients with stable disease or showing a response, treatment was continued three times weekly until a complete response was achieved or there was progression. 12 of the 26 evaluable patients achieved a major response; 5 of these showed histologically confirmed complete responses. There was a significant increase in OKT4-positive cells in the responders and a significant decrease in HIV antigen (HIV-Ag) in the 7 responders with initially detectable HIV-Ag. Interferon-alpha is thus an effective treatment. The increase in OKT4-positive cells and the decrease in HIV-Ag seem to be significantly related to patients with tumour responses.

Acquired Immunodeficiency Syndrome↗

Simultaneous low level treadmill exercise and intravenous dipyridamole stress thallium imaging.

Intravenous dipyridamole-thallium imaging unmasks ischemia in patients unable to exercise adequately. However, some of these patients can perform limited exercise, which, if added, may provide useful information. Treadmill exercise combined with dipyridamole-thallium imaging was performed in 100 patients and results compared with those of 100 other blindly age- and sex-matched patients who received dipyridamole alone. Exercise began after completion of the dipyridamole infusion. Mean +/- 1 standard deviation peak heart rate (109 +/- 19 vs 83 +/- 12 beats/min, p less than 0.0001) and peak systolic and diastolic blood pressure (146 +/- 28/77 +/- 14 vs 125 +/- 24/68 +/- 11 mm Hg, p less than 0.0001) were higher in the exercise group compared with the nonexercise group. There was no difference in the occurrence of chest pain, but more patients in the exercise group developed ST-segment depression (26 vs 12%, p less than 0.0001). The exercise group had fewer noncardiac side effects (4 vs 12%, p less than 0.01) and a higher target (heart) to background (liver) count ratio (2.1 +/- 0.7 vs 1.2 +/- 0.3; p less than 0.01), due to fewer liver counts. There were no deaths, myocardial infarctions or sustained arrhythmias in either group. Combined treadmill exercise and dipyridamole testing is safe, associated with fewer noncardiac side effects, a higher target to background ratio and a higher incidence of clinical electrocardiographic ischemia than dipyridamole alone. Therefore, it is recommended whenever possible.

Aged↗

Diagnostic value for coronary artery disease of chest pain during dipyridamole-thallium stress testing.

Intravenous dipyridamole with thallium imaging permits stress testing for coronary artery disease (CAD) without exercise. Chest pain may occur with dipyridamole-thallium testing, but its diagnostic significance is uncertain. Forty-five patients who had coronary angiography, no revascularization and chest pain during dipyridamole-thallium testing were identified. These patients were matched blindly by sex and age to 45 patients who had coronary angiography, no revascularization and no chest pain reported during the dipyridamole-thallium test. In the groups with versus without chest pain, 9 versus 24% had no CAD, 16 versus 16% had 1-vessel disease, 38 versus 29% had 2-vessel CAD and 38 versus 29% had 3-vessel CAD. These differences did not achieve statistical significance. Also, there were no evident differences in the severity of angiographic CAD by vessel or by percent of stenosis (p greater than 0.50). There was only a moderate association with ischemic ST changes (40 versus 16%, p less than 0.02). Chest pain with concurrent ischemic ST changes also failed to predict any difference in distribution or severity of angiographic stenoses. We conclude that chest pain during dipyridamole-thallium testing is not closely related to the severity of CAD and has little diagnostic value.

Adult↗

The effects of stress on left ventricular ejection fraction.

The left ventricular ejection fraction (EF) was studied in 17 healthy volunteers with a new ambulatory left ventricular function monitor. Heart rate, EF, and blood pressure measurements were made during rest, a psychiatric stress interview, cold exposure, exercise, and eating. An increase in EF was seen during emotional stress (from 0.45 +/- 0.09 to 0.51 +/- 0.13, P less than 0.001). This increase was comparable to that observed during exercise (0.52 +/- 0.14) and eating (0.52 +/- 0.10, P less than 0.001). In contrast, cold exposure caused a decrease in EF (0.43 +/- 0.13, P less than 0.05). These observations demonstrate the powerful hemodynamic consequences of common behaviors as well as the utility and feasibility of studying such behavioral factors in ambulatory subjects.

Adult↗

No predictive value of GC phenotypes for HIV infection and progression to AIDS.

The genetic polymorphism of group-specific component (GC) was investigated with isoelectric focusing in 351 homosexual men at risk for HIV infection, 96 male patients with AIDS, and 86 heterosexual controls. No significant differences in GC phenotype distribution were seen between controls and any of the at risk groups or patients, neither between HIV-Ab-positive/Ag-negative and HIV-Ab-positive/Ag-positive homosexual men nor between HIV-Ab-positive/Ag-positive homosexual men and AIDS patients, suggesting that the GC system is not involved in the infective susceptibility or progression of HIV infection to AIDS-related complex and AIDS.

Acquired Immunodeficiency Syndrome↗

Transmission of HIV and AIDS by plasmapheresis for Guillain-Barré syndrome.

A 58-year-old patient suffering from Guillain-Barré syndrome was successfully treated with plasma exchange therapy. Two- and half year later she developed AIDS. The only risk factor of this patient was plasmapheresis and it appeared, retrospectively, that one of the plasma donor samples contained antibodies to HIV. Knowing the exact moment of infection of our patient we documented the transfer of HIV antibodies from donor to patient, a HIV antigen peak two weeks after transmission (reflecting the initial virus replication in the patient) and subsequently the occurrence of patients' HIV antibodies and the reoccurrence of HIV antigen at the moment AIDS was diagnosed.

Acquired Immunodeficiency Syndrome↗

Superiority of quantitative exercise thallium-201 variables in determining long-term prognosis in ambulatory patients with chest pain: a comparison with cardiac catheterization.

The purpose of this study was to determine the prognostic utility of quantitative exercise thallium-201 imaging and compare it with that of cardiac catheterization in ambulatory patients. Accordingly, long-term (4 to 9 years) follow-up was obtained in 293 patients who underwent both tests for the evaluation of chest pain: 89 had undergone coronary artery bypass graft surgery within 3 months of testing and were excluded from analysis, 119 experienced no cardiac events and 91 had an event (death in 20, nonfatal myocardial infarction in 21 and coronary artery bypass operations performed greater than 3 months after cardiac catheterization in 50). When all variables were analyzed using Cox regression analysis, the quantitatively assessed lung/heart ratio of thallium-201 activity was the most important predictor of a future cardiac event (chi 2 = 40.21). Other significant predictors were the number of diseased vessels (chi 2 = 17.11), patient gender (chi 2 = 9.43) and change in heart rate from rest to exercise (chi 2 = 4.19). Whereas the number of diseased vessels was an important independent predictor of cardiac events, it did not add significantly to the overall ability of the exercise thallium-201 test to predict events. Furthermore, information obtained from thallium-201 imaging alone was marginally superior to that obtained from cardiac catheterization alone (p = 0.04) and significantly superior to that obtained from exercise testing alone (p = 0.02) in determining the occurrence of events. In addition, unlike the exercise thallium-201 test, which could predict the occurrence of all categories of events, catheterization data were not able to predict the occurrence of nonfatal myocardial infarction. The exclusion of bypass surgery and previous myocardial infarction did not alter the results. In conclusion, data from this study demonstrate that exercise thallium-201 imaging may be superior to data from both exercise testing alone and cardiac catheterization data alone for predicting future events in ambulatory patients who have undergone both exercise thallium-201 imaging and catheterization for the evaluation of chest pain.

Adult↗

Continuous monitoring of left ventricular function by an ambulatory radionuclide detector in patients with coronary artery disease.

Global left ventricular function and a modified V5 electrocardiographic (ECG) lead were continuously monitored by a radionuclide recorder in 12 normal subjects and 39 patients with coronary artery disease while the subjects were performing various daily activities. The ambulatory studies revealed that walking on a level surface caused 11 of 12 normal subjects and 18 of 32 patients to increase their left ventricular ejection fraction by greater than 6% units. A transient decrease in left ventricular ejection fraction (6 to 18%) lasting greater than or equal to 1 min was observed on 36 occasions in 16 patients with coronary artery disease; 12 episodes were accompanied by chest pain or shortness of breath and 24 were asymptomatic. Electrocardiographic ST segment depression suggestive of ischemia was recorded in 6 of the 12 symptomatic and 5 of the 24 asymptomatic episodes. In 10 of the 12 symptomatic episodes, left ventricular ejection fraction began to decrease 30 to 90 s before the onset of symptoms. These studies suggest that continuous monitoring of both left ventricular function and the ECG may permit stratification of episodes of ST depression suggesting ischemia by the degree of left ventricular dysfunction they produce.

Activities of Daily Living↗

Thallium kinetics in rat cardiac transplant rejection.

Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection.

Animals↗

Fatty acid analogue accumulation: a marker of myocyte viability in ischemic-reperfused myocardium.

A 3-methyl substituted radioiodinated long chain fatty acid analogue was evaluated as an agent for the noninvasive detection of altered fatty acid uptake in reperfused, postischemic myocardium. This iodinated fatty acid analogue, 15-(para-iodophenyl)-3-methyl pentadecanoic acid, was given intravenously at 3 hours of reperfusion following 15 minutes (Group 1, n = 5 dogs) or 60 minutes (Group 2, n = 5 dogs) of left anterior descending coronary artery occlusion. Myocardial blood flow (MBF) was measured during occlusion and reperfusion with radiolabeled microspheres administered via the left atrium. Paired ultrasonic subendocardial crystals were placed in the ischemic perfusion bed to assess regional left ventricular systolic function at baseline, during ischemia and reperfusion. Electron microscopic analysis and staining with triphenyltetrazolium chloride (TTC) was performed. Groups 1 and 2 dogs had similar (p = NS) myocardial blood flows during occlusion. TTC positive 1 g endocardial segments from Group 1 (n = 98) and Group 2 (n = 71) had 37% greater fatty acid analogue activity (0.26 +/- 0.04 vs. 0.19 +/- 0.09 percent injected dose per gram; p less than 0.05) compared with TTC negative segments from Group 2 dogs (n = 37). When fatty acid analogue activity was related to near simultaneous reperfusion blood flow, this ratio was 27% greater (p less than 0.05) in TTC positive segments (0.38 +/- 0.1) compared with TTC negative (0.30 +/- 0.16) segments, and 9% greater than normal (0.35 +/- 0.09; p less than 0.05). While ischemic regions from both Groups 1 and 2 dogs became similarly dyskinetic during occlusion (systolic shortening, -11 +/- 6 vs. -11 +/- 2%; p = NS), TTC negative segments remained akinetic (= 1 +/- 7%) at 3 hours of reperfusion while TTC positive zones had recovered partial systolic function (8 +/- 22%). Electron microscopy confirmed the presence of reversible ultrastructural changes in TTC positive regions. A 60-minute occlusion, 3-hour reperfusion model adapted for in vivo single photon emission computed tomography showed a similar excess of 123I fatty acid activity over flow when compared to perfusion (as measured with 201Tl) in the ischemic border zone of 4/4 canine myocardial infarcts. We conclude that the accumulation of this non-beta-oxidized fatty acid analogue noninvasively identifies zones of discordance between fatty acid and flow distribution that are characteristic of ischemically "stunned" but viable myocardium.

Animals↗

Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition.

PEPSCAN analysis, performed using 536 overlapping nonapeptides derived from the HTLV-III B nucleotide sequence of the region encoding the external envelope protein of 120 kDa (gp120), identified in the V3 region of gp120 a major binding site for antibodies of HIV-1-infected humans. The minimal amino acid sequence of this antibody binding site was demonstrated by multiple length scanning to be five to eight amino acids in length: (G)PGRAF(VT), i.e. amino acids 312-319. A peptide (Neu 21) containing this binding site for human antibodies (KSIRIQRGPGRAFVTIG) was synthesized and shown to induce HTLV-III B cell fusion-inhibiting antibodies in rabbits and mice. Antibodies binding to this HTLV-III B/LAV-1-specific peptide were shown to be primarily of the IgG 1 subclass, appeared within 6 months after HIV-1 antibody seroconversion in six out of 14 men studied, and persisted throughout the follow-up period of 10-24 months. The other eight seroconverting men did not develop antibodies to Neu 21 during the observation period. The appearance of antibodies to Neu 21 paralleled the capacity of the serum to inhibit HTLV-III B in cell fusion. HIV-1-infected men with Kaposi's sarcoma exhibited a similar frequency of antibodies to the synthetic peptide Neu 21 (14 out of 39, 36%) as asymptomatic HIV-1-infected men (112 out of 319, 35%). Adults with Pneumocystis carinii pneumonia had a significantly lower frequency (11 out of 78, 14%) of antibodies to Neu 21. Similarly, a low prevalence of antibodies to Neu 21 (8 out of 43, 19%) was observed among symptomatic HIV-1-infected children.

Amino Acid Sequence↗

Persistent human immunodeficiency virus type 1 antigenemia in children correlates with disease progression.

In a longitudinal study, human immunodeficiency virus type 1 (HIV-1) antigen (HIV-Ag) was measured in serum specimens from 54 children with HIV-1 infection followed for a median duration of 17 months. The persistent detection of free HIV-Ag in a group of 25 children was associated with clinical deterioration in 22 (88%) and a mortality of 52%, whereas the persistent nondetection of free HIV-Ag in a group of 18 children was associated with clinical deterioration in five (28%) and a mortality of 11% during the period of observation. Nine children had transient HIV-1 antigenemia and two children converted from HIV-Ag negative to positive during the study. Free HIV-Ag levels varied inversely with antibody reactivity to viral core proteins p24 and p17 determined by Western immunoblot, suggesting either the formation of immune complexes or a balance between viral expression and the host immune response. Five mother-infant pairs were studied for HIV-Ag expression in the perinatal period. In three of these pairs, both mother and infant were HIV-Ag negative, in one pair the mother had high levels of HIV-Ag and the infant was HIV-Ag negative. In the remaining mother-infant pair, the neonate became HIV-Ag positive but the mother was HIV-Ag negative prepartum and postpartum. These data suggest that HIV-Ag probably does not cross the placenta and that the detection of free HIV-Ag in the offspring of a HIV-1 infected mother most likely indicates viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Western↗

Increased exercise thallium-201 lung uptake: a noninvasive prognostic index in two-vessel coronary artery disease.

To determine the physiologic impact of two-vessel coronary artery disease and its effect on prognosis, a series of clinical, angiographic, exercise and quantitative thallium-201 (Tl-201) imaging parameters were analyzed in 85 consecutive two-vessel coronary artery disease patients followed for 52 +/- 27 months after coronary angiography and Tl-201 scintigraphy. End points were cardiac death (n = 3), myocardial infarction (n = 6) and coronary bypass graft surgery more than three months after testing (n = 16). Using Cox Hazards survival analysis, early cardiac events were not predicted by: myocardial infarction or anginal history; resting left ventricular function; exercise blood pressure response; angina or severity of ECG ST segment depression (mm); Tl-201 defect size; redistribution or clearance; angiographic patterns; or the presence of proximal left anterior descending disease. Significant predictors of adverse cardiac events were: increased exercise lung to heart Tl-201 ratio (0.59 +/- 0.12 versus 0.46 +/- 0.1; P less than 0.0001); ECG lead extent of ST segment depression (P less than 0.03); and exercise heart rate response (P less than 0.047). Event-free survival for patients with normal and abnormally increased lung to heart Tl-201 ratios at 48 months was 76% versus 63% (P less than 0.003). It was concluded that two-vessel coronary artery disease survival correlates with exercise Tl-201 uptake which reflects exercise induced left ventricular dysfunction.

Actuarial Analysis↗