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Biomedical subjects

B G Brown

Publications and source records attributed to B G Brown.

At least 19 recordsLinked to original sources

Filovirus clearance in non-human primates.

There has been concern in the USA and Europe about filovirus outbreaks in recently imported monkeys, and possible transmission to human beings. Healthy monkeys have been found to have low-titre immunofluorescence antibody (IFA) to Asian filoviruses (Reston and Pennsylvania viruses) as well as to the African filoviruses that caused fulminating human outbreaks in the 1970s (Ebola [Zaire] and Sudan viruses). We have assessed whether such monkeys are a risk to man. We studied 42 non-human primates; 31 were experimentally infected with African and Asian filoviruses, 6 were infected during a documented Reston filovirus outbreak, and 5 had serological evidence suggestive of recent filovirus infection. During the first 15 days after infection, virus could be routinely recovered from serum or biopsy or necropsy tissue, and Asian filovirus RNA could be detected by polymerase chain reaction. 20 to 600 days after challenge, filovirus could no longer be recovered nor viral RNA detected in 141 serum, liver, spleen, or kidney specimens. Animals surviving filovirus infection develop high-titre, cross-reacting filovirus-specific antibody 14 to 21 days after infection, and this coincides with virus clearance. Healthy monkeys with low-titre filovirus antibody may be regarded as uninfected.

Animals

Detection of simian T-lymphotropic virus type I using the polymerase chain reaction.

To develop the polymerase chain reaction (PCR) for the detection of simian T-lymphotropic virus type I (STLV-I) infection, cell lines or peripheral-blood mononuclear cells (PBMC) from 2 non-human primate species [African green monkeys (AGM), Cercopithecus aethiops; baboon, Papio cynocephalus] were evaluated for their STLV-I status using oligonucleotide primer pairs and probes specific for the tax and pol gene regions of the closely related human T-lymphotropic virus type I (HTLV-I). These PCR results were compared with serologic (Western blot assay) and viral culture (p24-antigen capture assay) data. PCR products for both gene regions were detected in established baboon, Japanese macaque and rhesus macaque STLV-I-producing cell lines. STLV-I tax and pol products were also detected in PBMC from 4 of 4 infected AGM and 4 of 4 infected baboons, each of which were also Western-blot-positive and p24-antigen-capture-positive. Of the remaining AGM (n = 7) and baboon (n = 1) which were PCR-negative, each was also Western-blot-negative and p24-antigen-capture-negative. Two seronegative and virus-culture-negative AGM were classified as PCR indeterminate with weak reactivity using tax primers. These primer pairs failed to amplify DNA from uninfected human PBMC, an uninfected human lymphoid cell line, a simian immunodeficiency virus macaque (SIVmac251)-infected cell line and a simian-retrovirus-type-D(SRV-D)-infected cell line. HTLV-II-pol-specific primer pairs failed to amplify DNA from STLV-I-infected cell lines and PBMC from STLV-I-infected monkeys. Further, HTLV-I pol and tax primer pairs successfully amplified RNA from HTLV-I- and STLV-I-infected cell lines by reverse transcriptase (RT)-PCR. We have demonstrated excellent specificity in the detection of STLV-I by PCR using these HTLV-I-derived primers and probes. Additionally, our data suggest that the tax and pol gene regions are conserved between HTLV-I and STLV-I strains found among these diverse species of non-human primates.

Animals

DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or heat tobacco.

A prototype cigarette that heats tobacco (test cigarette), developed by R.J. Reynolds Tobacco Company, has yielded consistently negative results in several in vivo and in vitro genetic toxicology tests. The objective of the present study was to evaluate the potential of cigarette smoke condensate (CSC) from the test cigarette to induce DNA adducts in mouse tissues and compare the results with those obtained with CSC from a reference tobacco-burning cigarette (1R4F). CD-1 mice were skin-painted with CSC from reference and test cigarettes three times a week for 4 weeks. The highest mass of CSC applied was 180 mg "tar" per week per animal for both reference and test cigarette. DNA adducts were analyzed in skin and lung tissues using the 32P-postlabeling method with the P1 nuclease modification. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from both skin and lung tissues of animals dosed with reference CSC, whereas no corresponding DRZ were observed from the DNA of animals dosed with either test CSC or acetone (solvent control). The relative adduct labeling (RAL) values of skin and lung DNA from reference CSC-treated animals were significantly greater than those of the test CSC-treated animals. The RAL values of the test CSC-treated animals were no greater than those of solvent controls. The negative results in DNA adduct assays with test CSC are consistent with all previous results of in vivo and in vitro genetic toxicology testing on this cigarette and provide additional evidence that smoke condensate from the test cigarette is not genotoxic.

Animals

Association of apolipoprotein B gene variants with plasma apoB and low density lipoprotein (LDL) cholesterol levels.

The contribution of the variants of the apolipoprotein (apo) B locus to the total variance in plasma apoB and cholesterol levels was examined in four independent populations, two that were composed of normal controls (n = 77 and 85) and two with coronary heart disease (n = 115 and 159). A correlation between genotype at the apoB-XbaI locus and apoB levels was observed. The effects of the (+; presence of restriction site) and (-) alleles were to increase or decrease the apoB and cholesterol levels by approximately 3.5 mg/dl, respectively. None of the 274 individuals in the coronary heart disease (CHD) groups was found to be a carrier of the apoB allele Arg3500----Gln, previously shown to be associated with an apoB protein defective in binding to the low density lipoprotein receptor (LDL-R). No DNA sequence variants were found in the region encoding amino acid residues 3129-3532 within the putative LDL-R binding domain among 35 individuals with apoB levels above the 94th percentile (141 mg/dl).

Adult

Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette. II. DNA adducts and alveolar macrophage cytogenetics.

The chemical constituents of cigarette smoke are greatly diluted in environmental tobacco smoke (ETS). In the typical indoor environment where cigarettes are smoked, the mean value of respirable suspended particles is approximately 0.1 mg/m3. In this study, we used aged and diluted sidestream smoke (ADSS) of 1R4F University of Kentucky research cigarettes as a surrogate for ETS and exposed Sprague-Dawley rats nose-only to 0, 0.1, 1.0, and 10 mg wet total particulate matter (WTPM)/m3 for 6 hr per day for 14 consecutive days. DNA from lung, heart, larynx, and liver was tested for adduct formation after 7 and 14 days of exposure and after 14 days of recovery. In addition, alveolar macrophages from animals exposed for 7 days were examined for chromosomal aberrations. Exposure-related DNA adducts were not observed in any of the animals at 0.1 or 1.0 mg WTPM/m3, which represent ambient and 10-fold exaggerated ETS concentrations, respectively. Slight diagonal radioactive zones, characteristic of adducts observed in human smokers and in animals exposed to mainstream smoke, were observed, but only in lung and heart DNA of animals exposed to the highest concentration of ADSS (10 mg WTPM/m3), a 100-fold exaggeration of typical field measurements of ETS. The mean relative adduct labeling values (+/- SE) were 8.7 (+/- 0.2) adducts per 10(9) nucleotides for lung DNA and 5.7 (+/- 0.7) adducts per 10(9) nucleotides for heart DNA after 14 days of exposure. No elevation in chromosomal aberrations was observed in alveolar macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Effect of lovastatin or niacin combined with colestipol and regression of coronary atherosclerosis.

When aggressive lipid-altering therapy is compared with conventional therapy in patients at very high risk for CHD, i.e. those who have abnormal lipid profiles, established coronary disease, and symptomatic heart disease, aggressive therapy halves the expected frequency of progression, triples the frequency of regression, favours the net regression of disease, and reduces clinical events by nearly 75%. These benefits correlate with reductions in LDL cholesterol, systolic blood pressure and increases in HDL cholesterol, and are highly significant, not only statistically but also clinically. This finding is consistent with the observation that there is a persistent relationship between coronary morbidity and mortality across the spectrum of cholesterol levels, and that this risk can be reduced in men with CHD and abnormal lipid metabolism through aggressive lipid management.

Apolipoprotein A-I

Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain.

African filoviruses have caused outbreaks of fulminating hemorrhagic fever among humans. In 1989, related filoviruses were isolated from cynomolgus monkeys imported into the United States from the Philippines. The pathogenic potential of these new filoviruses was compared in 16 Asian monkeys (Macaca fascicularis-cynomolgus) and 16 African monkeys (Cercopithecus aethiops-African green) using African filoviruses from Zaire (Ebola virus) and Sudan or Asian filoviruses (Reston and Pennsylvania). African filovirus infections resulted in earlier death (P = .005), had a shorter duration of disease and median incubation period (3-4 vs. 7 days), and had earlier peak viremia (5-7 vs. 7-9 days). African green monkeys showed significantly higher survival than cynomolgus monkeys (P less than .01), and some were asymptomatic as have been humans accidentally infected with Asian filovirus. Rechallenge experiments showed that protection in survivors of filovirus infections against fatal challenge with Ebola (Zaire) virus is unpredictable. The minimal clinical disease observed in humans infected with the Reston strain is consistent with host- and virus-dependent pathogenicity.

Africa

Familial combined hyperlipidemia and abnormal lipoprotein lipase.

A previous study reported that heterozygotes for lipoprotein lipase (LPL) deficiency have reduced LPL, the lipoprotein pattern classified as familial combined hyperlipidemia (FCHL), elevated apolipoprotein (apo) B levels, and reduced high density lipoprotein (HDL) levels. These findings suggest that subjects with reduced LPL may form one subset of the FCHL population. The purpose of the present study is to determine whether a subset of patients with FCHL have reduced LPL. Three patient populations with FCHL were studied: 1) subjects with the diagnosis of FCHL (n = 9) established by previous family studies, 2) clinic patients with a tentative diagnosis of FCHL (n = 14), and 3) subjects undergoing angiography who had coronary artery disease (CAD) and a diagnosis of FCHL by family study (n = 33). Two of nine subjects with the established diagnosis of FCHL, five of the 14 FCHL clinic patients, and 13 of the 33 CAD subjects with FCHL had reduced LPL activity in the same range as do individuals who are obligate heterozygotes for LPL deficiency. Subjects with FCHL and reduced LPL had higher plasma triglyceride (p < 0.01) and lower HDL cholesterol (p < 0.025) levels than did the subjects with FCHL and normal LPL levels (327 +/- 201 versus 210 +/- 122 mg/dl [mean +/- SD] and 36 +/- 7 versus 44 +/- 13 mg/dl, respectively). Thus, in all three groups of patients with apparent FCHL, 20 of 56 subjects (36%) had reduced LPL, suggesting that one subset of the FCHL population may be identified by an abnormality in LPL activity that is associated with lipoprotein abnormalities.

Adult

Coronary angioplasty performed within the thrombolysis in Myocardial Infarction II study.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of the infarct-related artery was performed within 42 days of recombinant tissue-type plasminogen activator (rt-PA) administration in 1,414 of the 3,534 patients who participated in the Thrombolysis In Myocardial Infarction (TIMI) II study. Primary angiographic success was obtained in 88.7%, with bypass surgery within 24 hours in 3.3% and death within 24 hours in 0.7% of patients. By 1 year, 25.1% of the 1,414 patients had sustained one or more adverse outcomes including death (3.6%), reinfarction (8.4%), or the need for further revascularization (20%). METHODS AND RESULTS: Despite these generally favorable results, multivariate testing identified several anatomic and clinical subgroups as having an increased risk ratio (RR) for adverse outcome: Unsuccessful PTCA was more common in patients undergoing protocol-assigned PTCA within 2 hours of rt-PA administration (RR, 2.7; p less than 0.001) and in patients over age 70 years (RR, 1.7; p = 0.034). The need for further revascularization within 1 year was increased in the 30.4% of patients with multivessel disease (RR, 2.5; p less than 0.001), patients with prior angina (RR, 1.4; p less than 0.006), or those undergoing ischemia-driven PTCA within 15 hours of rt-PA administration (RR, 1.7; p = 0.022). The risk of death or recurrent infarction within 1 year was increased by the presence of multivessel disease (RR, 1.6; p = 0.007) or prior angina (RR, 1.5; p = 0.014). CONCLUSIONS: These observations do not necessarily apply to patients undergoing primary PTCA (or PTCA after other thrombolytic agents); however, they do offer a unique yardstick against which to evaluate the results of PTCA in myocardial infarction.

Angioplasty, Balloon, Coronary

Lumen diameter of normal human coronary arteries. Influence of age, sex, anatomic variation, and left ventricular hypertrophy or dilation.

BACKGROUND: Precise knowledge of the expected "normal" lumen diameter at a given coronary anatomic location is a first step toward developing a quantitative estimate of coronary disease severity that could be more useful than the traditional "percent stenosis." METHODS AND RESULTS: Eighty-three arteriograms were carefully selected from among 9,160 consecutive studies for their smooth lumen borders indicating freedom from atherosclerotic disease. Of these, 60 men and 10 women had no abnormalities of cardiac function, seven men had idiopathic dilated cardiomyopathy, and six men had left ventricular hypertrophy associated with significant aortic stenosis. Lumen diameter was measured at 96 points in 32 defined coronary segments or major branches. Measurements were scaled to the catheter, corrected for imaging distortion, and had a mean repeat measurement error of 0.12 mm. When sex, anatomic dominance, and branch length were accounted for, normal lumen diameter at each of the standard anatomic points could usually be specified with a population variance of +/- 0.6 mm or less (SD) and coefficient of variation of less than 0.25 (SD/mean). For example, the left main artery measured 4.5 +/- 0.5 mm, the proximal left anterior descending coronary artery (LAD) 3.7 +/- 0.4 mm, and the distal LAD 1.9 +/- 0.4 mm. For the LAD, lumen diameter was not affected by anatomic dominance (right versus left), but for the right coronary artery, proximal diameter varied between 3.9 +/- 0.6 and 2.8 +/- 0.5 mm (p less than 0.01) and for the left circumflex, between 3.4 +/- 0.5 and 4.2 +/- 0.6 mm (p less than 0.01). Women had smaller epicardial arterial diameter than men (-9%; p less than 0.001), even after normalization for body surface area (p less than 0.01). Branch artery caliber was unaffected by the anatomic dominance but increased with branch length, expressed as a fraction of the origin-to-apex distance (p less than 0.001). Lumen diameter was not affected by age or by vessel tortuosity but was significantly increased among men with left ventricular hypertrophy (+ 17%; p less than 0.001) or dilated cardiomyopathy (+ 12%; p less than 0.001). CONCLUSIONS: This is a reference normal data set against which to compare lumen dimensions in various pathological states. It should be of particular value in the investigation of diffuse atherosclerotic disease.

Adult

Plasmodium cynomolgi: immunization of a rhesus monkey with exoerythrocytic stages cultured in autologous hepatocytes.

To investigate the immune response to exoerythrocytic stages of malaria parasites, a rhesus monkey was immunized with autologous primary hepatocyte cultures infected with 7-day-old liver stage parasites of Plasmodium cynomolgi. A primary antibody response against EE stage antigens was obtained, and boosted after injection of homologous viable sporozoites. Antibodies directed against sporozoites and blood stages were also detected. The polyvalent immune response observed demonstrates the antigenicity of the liver stages and suggests their involvement in the general immune response against malaria.

Animals

Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators.

BACKGROUND: The influence of coronary collateral vessels on infarct size in humans remains controversial, partly because no previous study has examined the impact of collaterals present at the onset of acute myocardial infarction on infarct size. METHODS AND RESULTS: The present study used the data base of the Thrombolysis in Myocardial Infarction (TIMI) Phase I trial to correlate the presence or absence of angiographically documented collaterals in the initial hours of myocardial infarct evolution with the size of the infarct as assessed by serial measurements of serum creatine kinase (CK). To avoid the confounding effects of reperfusion on enzymatic estimates of infarct size, this report is limited to those 125 patients who failed to recanalize at 90 minutes after administration of tissue plasminogen activator or streptokinase. Patients with angiographically documented collaterals (group A, n = 51) had significantly lower values of peak serum CK than patients without collaterals (group B, n = 74) (1,877 +/- 216 versus 2,661 +/- 212 IU/l, respectively [mean +/- SEM], p = 0.004). Similarly, CK-derived infarct size estimates were significantly lower in group A than in group B (20.6 +/- 2.5 versus 31.4 +/- 2.8 CK gram equivalents, p = 0.001). The infarct size observed in patients with collaterals was less for anterior infarctions as well as for infarctions of other locations; thus, the beneficial effects of collaterals were independent of the site of the infarct. In 65 of the 125 patients who failed to reperfuse, left ventricular ejection fraction (LVEF) was assessed by contrast ventriculography both at initial cardiac catheterization (before thrombolytic therapy) and at hospital discharge. Among the patients who had both studies, global LVEF tended to increase from pretreatment to hospital discharge in group A (from 50.6 +/- 1.8% to 53.4 +/- 1.8%, p = 0.10) but decreased in group B patients (from 50.3 +/- 1.8% to 47.8 +/- 1.7%, p = 0.02). At hospital discharge, global LVEF was greater in patients with coronary collaterals (53.5 +/- 1.7% versus 49.6 +/- 1.7%, p = 0.01). CONCLUSIONS: The results demonstrate that, in patients in whom thrombolytic therapy fails to induce reperfusion, the presence of coronary collateral vessels at the onset of myocardial infarction is associated with limitation of infarct size as assessed enzymatically and with improved ventricular function on discharge as assessed by LVEF.

Collateral Circulation

Ribose facilitates thallium-201 redistribution in patients with coronary artery disease.

To investigate whether i.v. infusion of ribose, an adenine nucleotide precursor, postischemia facilitates thallium-201 (201Tl) redistribution and improves identification of ischemic myocardium in patients with coronary artery disease (CAD), 17 patients underwent two exercise 201Tl stress tests, performed 1-2 wk apart. After immediate postexercise planar imaging, patients received either i.v. ribose (3.3 mg/kg/min x 30 min) or saline as a control. Additional imaging was performed 1 and 4 hr postexercise. Reversible defects were identified by count-profile analysis. Significantly more (nearly twice as many) reversible 201Tl defects were identified on the post-ribose images compared to the post-saline (control) images at both 1 and 4 hr postexercise (p less than 0.001). Quantitative analyses of the coronary arteriogram was available in 13 patients and confirmed that the additional reversible defects were in myocardial regions supplied by stenosed arteries. We conclude that ribose appears to facilitate 201Tl redistribution in patients with CAD and enhances identification of ischemic myocardium.

Aged

Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease.

Plasma high density lipoproteins (HDL) can be separated into two subpopulations of apolipoprotein A-I-containing particles: those that also contain apoA-II [Lp(AI w AII)] and those that do not [Lp(AI w/o AII)]. These particles were isolated by immunoaffinity chromatography from 17 men (9 normolipidemic (NL), 8 hyperlipidemic (HL) with symptomatic coronary artery disease (CAD), from 17 NL men without any symptoms of CAD (healthy controls), and from 10 NL men with entirely normal coronary arteriograms (CAD-free controls). The distributions of particle size in these two subpopulations were determined by gradient gel electrophoresis and densitometric scanning. Approximately half of the Lp(AI w AII) particles in all subjects were distributed in the 8.2-9.2 nm interval. For patients with CAD, a greater fraction of the particles were small, in the 7.0-8.2 nm interval [33% in CAD vs. 26% in CAD-free controls (P less than 0.01) and 19% in healthy controls (P less than 0.0001)], and a smaller fraction of the particles were in the 9.2-11.2 nm interval (14% in CAD vs. 24% in CAD-free control (P less than 0.002) and healthy control groups (P less than 0.001). The Lp(AI w/o AII) of both control groups were primarily composed of two discrete subpopulations in the 8.2-9.2 nm and the 9.2-11.2 nm intervals. In CAD patients there were fewer particles in the 9.2-11.2 nm size interval (23% in CAD vs. 33% in CAD-free controls (P less than 0.005) and 36% in healthy controls (P less than 0.0001), and more particles in the smallest 7.0-8.2 nm size interval (32% in CAD vs. 23% in CAD-free controls (P less than 0.01) and 18% in healthy controls (P less than 0.001]. Thus, the spectrum of HDL particle sizes in patients with CAD tends to be shifted toward the smaller particle when compared with the two control groups. This was observed in both NL and HL patients with HDL cholesterol (CH) values in the normal range. As a group, CAD patients had lower HDL (42 +/- 7 mg/dl) and HDL2 (6 +/- 4 mg/dl) CH than healthy (HDL: 49 +/- 7, HDL2: 12 +/- 6 mg/dl) and CAD-free (HDL: 51 +/- 9, HDL2: 12 +/- 6 mg/dl) controls. When controls and patients were compared for their frequencies of abnormal HDL CH levels and particle sizes, abnormalities in HDL and HDL2 CH levels were not significantly more frequent (twofold) among CAD patients than among controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

SIV, STLV-I and type D retrovirus antibodies in captive rhesus macaques and immunoblot reactivity to SIV p27 in human and rhesus monkey sera.

The prevalence of simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus type 1 (STLV-I), and type D retrovirus (SRV-D) antibodies was determined for 1229 rhesus monkeys (Macaca mulatta) from two research colonies. Serum samples were tested by using enzyme-linked immunosorbent assay (ELISA), immunoblot (IB), and radioimmunoprecipitation assay (RIPA). Seropositive results for the three retroviruses tested were 0 for SIV, 270 (22%) for STLV-I, and 103 (8.4%) for type D retrovirus. Of the rhesus monkey sera, 61 (5.0%) were reactive to SIV gag p27 only, when tested by IB, but were negative when further tested by RIPA. Virus isolation was attempted from cultured peripheral blood mononuclear cells of 35 monkeys whose sera contained only p27 reactivity and none were positive by reverse transcriptase and core antigen assays to detect SIV. No overt clinical signs of immunodeficiency disease or unexplained deaths were evident in either monkey colony. Additionally, 63 of 165 (38%) human sera from various groups (primate center workers, normal donors, health care workers) had weak to moderate IB reactivity only to SIV p27, but 31 of 31 sera tested were negative by RIPA. These sera remained reactive to SIV p27 following absorption with an uninfected cell lysate, after blocking IB strips with various blocking solutions and were reactive to different SIV antigen preparations while remaining negative to human immunodeficiency virus type 1 (HIV-1) by IB and negative to HIV-2 by ELISA. These data underscore the need to adopt criteria for a positive SIV serologic test requiring reactivity against more than one viral gene product. These results also illustrate a potential problem in the testing of human sera for antibodies against simian retroviruses and demonstrate the need for caution in the interpretation of immunoblot results.

Animals

Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial.

To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.

Aged