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Biomedical subjects

M A Quinones

Publications and source records attributed to M A Quinones.

At least 19 recordsLinked to original sources
PubMed2001

Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease characterized by cardiac hypertrophy, myocyte disarray, interstitial fibrosis, and left ventricular (LV) dysfunction. We have proposed that hypertrophy and fibrosis, the major determinants of mortality and morbidity, are potentially reversible. We tested this hypothesis in beta-myosin heavy chain-Q(403) transgenic rabbits. METHODS AND RESULTS: We randomized 24 beta-myosin heavy chain-Q(403) rabbits to treatment with either a placebo or simvastatin (5 mg. kg(-1). d(-1)) for 12 weeks and included 12 nontransgenic controls. We performed 2D and Doppler echocardiography and tissue Doppler imaging before and after treatment. Demographic data were similar among the groups. Baseline mean LV mass and interventricular septal thickness in nontransgenic, placebo, and simvastatin groups were 3.9+/-0.7, 6.2+/-2.0, and 7.5+/-2.1 g (P<0.001) and 2.2+/-0.2, 3.1+/-0.5, and 3.3+/-0.5 mm (P=0.002), respectively. Simvastatin reduced LV mass by 37%, interventricular septal thickness by 21%, and posterior wall thickness by 13%. Doppler indices of LV filling pressure were improved. Collagen volume fraction was reduced by 44% (P<0.001). Disarray was unchanged. Levels of activated extracellular signal-regulated kinase (ERK) 1/2 were increased in the placebo group and were less than normal in the simvastatin group. Levels of activated and total p38, Jun N-terminal kinase, p70S6 kinase, Ras, Rac, and RhoA and the membrane association of Ras, RhoA, and Rac1 were unchanged. CONCLUSIONS: Simvastatin induced the regression of hypertrophy and fibrosis, improved cardiac function, and reduced ERK1/2 activity in the beta-myosin heavy chain-Q(403) rabbits. These findings highlight the need for clinical trials to determine the effects of simvastatin on cardiac hypertrophy, fibrosis, and dysfunction in humans with hypertrophic cardiomyopathy and heart failure.

Animals↗
PubMed2000

End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography.

OBJECTIVES: The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (T1-201) scintigraphy. BACKGROUND: Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS: Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution T1-201 tomography before revascularization and a repeat resting echocardiogram > or =2 months later. RESULTS: Global wall motion score index decreased from 2.38 +/- 0.73 to 1.94 +/- 0.82 after revascularization (p < 0.001). Thirty-eight percent of severely dysfunctional segments recovered resting function. Compared to segments without recovery of resting function, those with recovery had greater EDWT (0.94 +/- 0.18 cm vs. 0.67 +/- 0.22 cm, p < or = 0.0001) and a higher T1-201 uptake (78 +/- 13% vs. 59 +/- 21%; p < 0.0001). An EDWT >0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a T1-201 maximal uptake of > or =60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum T1-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS: End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to T1-201 scintigraphy. Importantly, a simple measurement of EDWT < or =0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Aged↗
PubMed1998

Behavioral and demographic risk factors for transmission of human immunodeficiency virus type 1 in heterosexual couples: report from the Heterosexual HIV Transmission Study.

We compared 224 heterosexual couples who were discordant for human immunodeficiency virus (HIV) type 1 infection (one partner HIV infected) with 78 HIV-concordant couples (both partners HIV infected) to identify demographic and behavioral risk factors for HIV transmission. Among the 229 couples whose male partner was first infected, HIV-concordant couples had engaged in anal sex more frequently before and after knowing that the male was infected than had HIV-discordant couples. Pap smears of grade 2 or higher (inflammation) were more prevalent among the second-infected female partners in HIV-concordant couples than among uninfected women in discordant couples (58% vs. 23%; P < .001). Anal sex and unprotected vaginal sex after knowledge of a male partner's infection were significant correlates of concordance in a multivariate logistic model, as were ethnicity, marital status, and antiviral therapy. Ethnicity strongly predicted concordance, even after controlling for sexual risk behaviors and stage of disease.

Adult↗
PubMed1996

Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry.

Diabetes is an independent predictor of morbidity and mortality in patients with symptomatic heart failure, patients with asymptomatic left ventricular dysfunction (defined as an ejection fraction of 35% or less), and in a broader registry population with less stringent entry criteria. Although the SOLVD Trials made a major clinical contribution by proving the value of enalapril, diabetes remains a significant predictor of outcome even after adjusting for treatment with enalapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy.

BACKGROUND: Studies of Left Ventricular Dysfunction (SOLVD) demonstrated that enalapril therapy significantly improved the clinical course of patients with left ventricular (LV) dysfunction. The goals of this substudy were to evaluate changes in LV structure and function in SOLVD patients and to test the hypothesis that enalapril inhibits remodeling in patients with LV dysfunction. METHODS AND RESULTS: Patients entering both the prevention and treatment arms of SOLVD from 5 of the 23 clinical centers were recruited for this substudy. The 301 patients who participated underwent Doppler-echocardiographic evaluation according to standard protocol before randomization to either enalapril or placebo and again after 4 and 12 months of therapy. Recorded data were analyzed in a blinded fashion at a central core laboratory. Analysis of baseline clinical characteristics showed that patients enrolled in the substudy were generally representative of the SOLVD population, although prevention arm patients were slightly overrepresented in the substudy group (69.8% compared with 61.9% of remaining SOLVD patients). The enalapril group demonstrated significant reductions in the mitral annular E-wave-to-A-wave velocity ratio (due predominantly to a reduction in E-wave velocity), and this response was different from that seen in the placebo group (P = .030). Changes in the E-to-A ratio in the enalapril group correlated significantly with changes in plasma atrial natriuretic peptide (r = .56; P < or = .01). LV end-diastolic and end-systolic volumes increased in placebo but not enalapril-treated patients, and the differences in response between the treatment groups were significant (P = .025 and .019, respectively). LV mass tended to increase in placebo patients and to be reduced in enalapril-treated patients, and the difference in response between the groups was highly significant (P < or = .001). CONCLUSIONS: These data demonstrate that enalapril attenuates progressive increases in LV dilatation and hypertrophy in patients with LV dysfunction. The results support the possibility that the favorable effects of enalapril reported in the SOLVD trials were related to inhibition of LV remodeling.

Adult↗
PubMed1995

Myocardial contrast echocardiography: relation of collateral perfusion to extent of injury and severity of contractile dysfunction in a canine model of coronary thrombosis and reperfusion.

OBJECTIVES: This study sought to determine whether myocardial contrast echocardiography could be used to detect and quantitate collateral blood flow capable of limiting the effects of ischemia in an experimental model of coronary thrombosis and reperfusion. BACKGROUND: Myocardial contrast echocardiography has been used to assess collateral blood flow in humans, but this technique has not been extensively validated in the experimental laboratory. METHODS: Myocardial ischemia occurred after electrically induced left circumflex coronary artery thrombosis in a canine model. Ischemia was intensified by administration of vasodilators. Reperfusion was induced with recombinant tissue-type plasminogen activator. Myocardial perfusion was assessed with contrast echocardiography and radiolabeled microspheres. Infarct size was determined by histochemical staining methods. Myocardial samples were evaluated histologically. RESULTS: The dogs were classified into two groups on the basis of contrast echocardiographic detection of perfusion in the ischemic region: those with (n = 13) and without collateral flow (n = 10). Collateral perfusion detected by contrast echocardiography paralleled changes detected by radiolabeled microspheres during thrombosis and vasodilator administration. A 91% agreement was observed between the two techniques in detecting collateral flow > 0.3 ml/min per g (p < 0.0001). Collateral perfusion correlated directly with radial shortening fractions of the ischemic myocardium (p < 0.01). Recovery of function after reperfusion was faster, infarct size was smaller (mean [+/- SD] 4 +/- 1% vs. 11 +/- 3%, p = 0.05), and histopathologic injury was less in dogs with than without collateral flow, respectively (p < 0.05). CONCLUSIONS: Myocardial contrast echocardiography can identify physiologically significant collateral vessels capable of limiting the degree of ischemic damage during coronary thrombosis. The magnitude of collateral flow and the change in flow induced by vasodilators can be assessed and compares favorably with the microsphere standard.

Animals↗
PubMed1993

Comparative neurohormonal responses in patients with preserved and impaired left ventricular ejection fraction: results of the Studies of Left Ventricular Dysfunction (SOLVD) Registry. The SOLVD Investigators.

OBJECTIVES: The aim of this study was to determine the differences in neurohumoral responses between patients with pulmonary congestion with and without impaired left ventricular ejection fraction. BACKGROUND: Previous studies have established the presence of neurohumoral activation in patients with congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to the impairment in systolic contractility. METHODS: The 898 patients recruited into the Studies of Left Ventricular Dysfunction (SOLVD) Registry substudy were examined to identify those patients with pulmonary congestion on chest X-ray film who had either impaired (< or = 45%, group I) or preserved (> 45%, group II) left ventricular ejection fraction. Plasma norepinephrine, plasma renin activity, arginine vasopressin and atrial natriuretic peptide levels were measured in these two groups of patients and compared with values in matched control subjects. RESULTS: Distribution of the New York Heart Association symptom classification was the same in the two groups of patients. Compared with control subjects, patients in group II with pulmonary congestion and preserved ejection fraction had no activation of the neurohumoral mechanisms, except for a small but statistically significant increase in arginine vasopressin and plasma renin activity. Compared with patients in group II, those in group I with pulmonary congestion and impaired ejection fraction had significant increases in plasma norepinephrine (p < 0.002), plasma renin activity (p < 0.02) and atrial natriuretic peptide levels (p < 0.0007). When we controlled for baseline differences between groups I and II, the between-group differences in plasma norepinephrine (p < 0.02) and atrial natriuretic peptide (p < 0.002) remained significant. However, plasma renin activity was not significantly different between groups I and II. When the effects of diuretic agents and angiotensin-converting enzyme inhibitors were adjusted, patients with lower ejection fraction were found to have significantly higher plasma norepinephrine and atrial natriuretic peptide levels. CONCLUSIONS: The results point to the importance of the decrease in left ventricular ejection fraction as one of the mechanisms for activation of neurohormones in patients with heart failure.

Adult↗
PubMed1992

Doppler echocardiographic evaluation of pseudoaneurysms complicating composite grafts of the ascending aorta.

BACKGROUND: Pseudoaneurysms of the ascending aorta is a rare and serious complication after composite graft surgery for combined disorders of the aortic valve and ascending aorta. METHODS AND RESULTS: Echocardiographic and Doppler findings are described in eight patients (seven men, one woman; mean age, 45 +/- 12 years) with documented pseudoaneurysm of the ascending aorta and are compared with those by aortography and at surgery. The diameter of the ascending aorta ranged from 6 to 14 cm. Pseudoaneurysm was diagnosed by echocardiography in seven cases (six transthoracic, one transesophageal), by aortography in five, and by both methods in all patients. All three patients not diagnosed by aortography had a single dehiscence at the aortic annulus anastomosis. Five patients had more than one site of origin of the pseudoaneurysm. Periannular dehiscence (n = 7) was identified by color flow Doppler in six cases and by aortography in only one, and coronary artery dehiscence (n = 6) was detected by echocardiography in three and by aortography in two arteries. Of the three patients with distal graft dehiscence, one was identified by aortography and none by echocardiography. In cases of dehiscence at the aortic annulus, continuous wave Doppler further supported the diagnosis by demonstrating two distinct jets, one through the prosthetic valve and another with higher velocity through the communication. CONCLUSIONS: Echocardiography with Doppler can diagnose the presence of pseudoaneurysms complicating composite grafts and identify their proximal sites of origin. Furthermore, it complements aortography in the overall evaluation of patients with suspected pseudoaneurysm, particularly in those with single dehiscence of the graft at the aortic annulus anastomosis.

Adult↗
PubMed1991

AIDS education in drug user treatment programs.

This paper presents the results of an AIDS educational intervention for intravenous drug users (IVDUs) who participated in the New Jersey State Department of Health's Coupon program. An examination of the data showed that those with high pre-intervention test scores were more likely to have been White and to have been in treatment since 1981. Furthermore, the 1-hour AIDS educational intervention produced significantly higher post-intervention test scores (overall and for 27 of the 31 individual test items). Finally, none of the demographic and drug history variables used in this analysis were found to contribute significantly to the effectiveness of the educational session.

Acquired Immunodeficiency Syndrome↗
PubMed1991

New Jersey high school students' knowledge, attitudes, and behavior regarding AIDS.

In 1988 a questionnaire was administered to 1,793 urban and suburban New Jersey high school students to survey their knowledge, attitudes, and behavior related to the acquisition of acquired immunodeficiency syndrome (AIDS). Knowledge about the disease was high, but exaggeration of risk from social contacts was common. Although fear was associated with misperceptions, it was not always dispelled by knowledge. Nearly half (49%) of all participants reported having used condoms, indicating that condom use is somewhat familiar and acceptable to them. Over 80% thought that condoms offer some protection against AIDS. However, knowledge did not always result in recognition or practice of risk-reduction behaviors. Student suggestions for slowing the spread of AIDS stressed personal responsibility and education. Follow-up assemblies that used survey results to address gaps in knowledge appeared necessary to counter misperceptions that might have arisen from the survey.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Functional significance of myocardial perfusion defects induced by dipyridamole using thallium-201 single-photon emission computed tomography and two-dimensional echocardiography.

The mechanisms responsible for inhomogeneous myocardial blood flow after oral administration of a large dose (300 mg) of dipyridamole were assessed in 27 patients with serial thallium-201 single-photon emission computed tomography (SPECT) and simultaneous 2-dimensional echocardiograms. Myocardial tomographic images were obtained 50 minutes and 3 to 4 hours after administration of dipyridamole. Two-dimensional echocardiograms were recorded at baseline and then every 15 minutes for 60 minutes. Dipyridamole caused only a mild reduction in blood pressure (from 129 +/- 18 to 126 +/- 16 mm Hg) and a mild increase in heart rate (from 69 +/- 15 to 73 +/- 4 beats/min). Sixteen patients had perfusion defects after dipyridamole by SPECT, which underwent partial or total filling-in. Fourteen of these patients (87.5%) had either a new abnormality or further deterioration of a preexisting wall motion abnormality by 2-dimensional echocardiography, and thus were considered to have developed transient ischemia during dipyridamole administration. Ten of 11 patients (91%) with normal perfusion or fixed defects by SPECT had no further deterioration in wall motion after oral dipyridamole, and were thus considered to have no evidence of myocardial ischemia. In conclusion, most patients with transient thallium-201 defects after dipyridamole develop transient worsening of resting wall motion by 2-dimensional echocardiography, suggestive of true myocardial ischemia. Because myocardial oxygen demand, as indicated by the heart rate-blood pressure product, did not change significantly, the mechanism of myocardial ischemia in these patients is likely to be diminished regional blood flow related to a "subendocardial steal" induced by dipyridamole.

Angina Pectoris↗
PubMed1990

Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results.

Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models. To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to +3, with 0 indicating an absence of contrast effect and +3 indicating full opacification of the cavities examined. All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opacification greater than or equal to +2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Doppler assessment of right ventricular filling in a normal population. Comparison with left ventricular filling dynamics.

To examine whether alterations in right ventricular filling dynamics occur with increasing age and to compare right and left ventricular filling in normal subjects, pulsed Doppler echocardiographic studies were performed at the tricuspid and mitral anuli in 50 normal volunteers (23 males and 27 females) with an age range of 5-66 years. An age-related decrease in peak early filling velocity, increase in peak late velocity, and augmentation in the late/early ratio of peak velocities at the tricuspid anulus were observed (r = -0.68, 0.63, and 0.84, respectively). Significant correlations were also found between age and first third, first half, and atrial filling fractions (r = -0.60, -0.72, and 0.69, respectively). Weaker relations were observed between heart rate and Doppler-derived diastolic parameters (r = 0.18-0.54). Right ventricular filling indexes related significantly to those of the left ventricle (r = 0.58-0.88), the best being for the late/early ratio of peak velocities. With inspiration, an increase in early and late right ventricular filling occurred, whereas a reduction in filling occurred in the left ventricle. Thus, careful consideration for age, heart rate, and respiration is necessary in examining the effect of disease states or therapeutics on the filling dynamics of either the right or left ventricle.

Adolescent↗
PubMed1989

Assessment of regional myocardial perfusion by contrast echocardiography. II. Detection of changes in transmural and subendocardial perfusion during dipyridamole-induced hyperemia in a model of critical coronary stenosis.

Measurements of myocardial contrast (sonicated meglumine diatrizoate) intensity were compared with myocardial flow by radioactive microspheres before and after administration of dipyridamole (0.5 mg/kg body weight intravenously) in 10 open chest dogs with a critical stenosis in the left circumflex coronary artery. Computer measurements of contrast time-intensity curves corrected for background myocardial intensity were made along 12 transmural segments of the left ventricle at mid-papillary level and for the subendocardial and subepicardial half of each segment. After administration of dipyridamole, transmural flow in the control region increased significantly (p less than 0.001), resulting in a dipyridamole/baseline flow ratio (i.e., coronary reserve ratio) of 2.54 +/- 0.95. Similar changes (p less than 0.001) were seen by contrast echocardiography; the coronary reserve ratio was 2.10 +/- 0.60 with use of peak intensity and 3.48 +/- 1.58 with use of area under the time-intensity curve. In contrast, no significant changes were observed in myocardial flow, peak contrast intensity or area under the curve in the ischemic region after dipyridamole. In the control region the ratio of subendocardial to subepicardial flow was similar at baseline and after dipyridamole administration as assessed by microspheres (1.08 +/- 0.24 versus 1.17 +/- 0.25) or by area under the time-intensity curve (1.11 +/- 0.45 versus 1.11 +/- 0.56). In the ischemic region, the subendocardial/subepicardial flow ratio decreased significantly after dipyridamole administration as measured by microspheres (1.15 +/- 0.19 to 0.82 +/- 0.25; p less than 0.001) or by area under the curve (1.10 +/- 0.28 to 0.70 +/- 0.47; p less than 0.01). Thus, myocardial contrast echocardiography appears to be a sensitive technique with which to detect changes in myocardial flow induced by dipyridamole in the various myocardial layers of normal segments as well as of segments supplied by a critically stenotic coronary artery.

Animals↗
PubMed1989

A coupon program--drug treatment and AIDS education.

The New Jersey State Department of Health developed a program to test the following hypotheses: (1) numerous heroin addicts will respond to free detoxification treatment offered through a coupon program, (2) a substantial number of these patients will continue in treatment beyond the free detoxification attempt, and (3) participation in an AIDS education session can increase the knowledge level of intravenous drug abusers regarding this disease. Eighty-four percent of the 970 distributed coupons were redeemed for detoxification treatment. Twenty-eight percent of the program participants continued in treatment after the free detoxification period, and the AIDS information session significantly increased the knowledge of participating addicts.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients.

Hyperlipidemia, particularly hypercholesterolemia, occurs in cardiac transplant recipients both as a preexisting condition and as a consequence of immunosuppressive therapy. Lovastatin (Mevacor) has emerged as an agent that may effectively manage this condition. Few serious side effects of this drug have been observed. We describe two cardiac transplant recipients treated with lovastatin in conjunction with their other medications, including cyclosporine, who developed acute renal failure and rhabdomyolysis. Resolution of muscle damage followed discontinuation of cyclosporine and lovastatin therapy. We postulate that hepatic dysfunction secondary to cyclosporine predisposed these patients to lovastatin-induced muscle damage. Use of this drug in cardiac and other organ transplant recipients should be accompanied by close surveillance of creatine kinase, hepatic transaminases, and cyclosporine levels.

Acute Kidney Injury↗
PubMed1988

Accurate assessment of aortic stenosis severity by Doppler echocardiography independent of aortic jet velocity.

The present investigation was designed to derive an accurate pulsed Doppler method of assessing aortic stenosis severity that does not rely on measurement of aortic jet velocity. Left ventricular ET and SV were determined from pulsed Doppler recordings of flow velocity at the aortic anulus in 44 mostly normotensive patients with aortic stenosis. Aortic valve area at catheterization ranged between 0.3 and 2.13 cm2. A predicted ET was derived from Doppler-determined SV with the use of a regression equation previously described by Harley et al. A significant inverse quadratic relation was observed between the ET difference (delta ET), defined as measured ET minus predicted ET, and valve area at catheterization (r = -0.87; valve area = 1.4 - 15 delta ET + 60 delta ET2; SEE = 0.23 cm2). An ET difference of greater than or equal to 0.060 second was 88% sensitive, 89% specific, and 89% accurate for detecting critical aortic stenosis. Thus the ET difference, derived from measurements of SV and ET by pulsed Doppler, is a sensitive index for detection of critical aortic stenosis that is independent of determination of aortic jet velocity. This index should complement the Doppler evaluation of aortic stenosis, especially in cases where interrogation of the stenotic jet with continuous wave Doppler is inadequate.

Adult↗