Biomedical subjects

S Krishnaswami

Publications and source records attributed to S Krishnaswami.

At least 19 recordsLinked to original sources

PubMed1999

Pharmacokinetic-pharmacodynamic profile of systemic nitric oxide-synthase inhibition with L-NMMA in humans.

AIMS: It has been demonstrated that inhibition of endothelium derived nitric oxide with NG-monomethyl-L-arginine (L-NMMA) results in a different cardiac and peripheral vascular response. The purpose of this study was to investigate the pharmacokinetic-pharmacodynamic profile of L-NMMA and pharmacokinetic interactions with L-arginine in healthy subjects. METHODS: Plasma pharmacokinetics were analysed from two different studies: In study 1, 3 mg kg-1 L-NMMA was administered i.v. over 5 min and systemic haemodynamics, cardiac output (CO), fundus pulsation amplitude (FPA), and NO-exhalation (exhNO) were measured at baseline and 15, 65, 95, 155, and 305 min after start of drug administration (n=7). In study 2, 17 mg kg-1 min-1 of the physiologic substrate for nitric oxide synthase, L-arginine, was coinfused i.v. over 30 min with a primed constant infusion of 50 microg kg-1 min-1 L-NMMA (n=8). RESULTS: Bolus infusion of L-NMMA resulted in a maximum plasma concentration of 12. 9+/-3.4 microg ml-1 (mean+/-s.d.) with elimination half-life of 63. 5+/-14.5 min and clearance of 12.2+/-3.5 ml min-1 kg-1 and caused a small hypertensive response, decreased CO by 13%, FPA by 26%, exhNO by 46% and increased systemic vascular resistance by 16% (P<0.05 each) 15 min after start of drug administration. Although only limited data points were available in the L-NMMA plasma concentration range between 0 and 4 microg ml-1, drug effects over time were in good agreement with an Emax model (r2>0.98 each), which also suggested that concentrations producing half-maximum effects were higher for FPA than for CO and exhNO. The coinfusion with L-arginine caused a nearly two-fold increase in plasma L-NMMA levels, indicating a pharmacokinetic interaction. CONCLUSIONS: In the absence of a systemic hypertensive response, L-NMMA significantly decreased CO, exhNO, and FPA. The concentration calculated to produce a half maximal effect was equivalent for exhNO and CO, but markedly higher for FPA. Furthermore, measurement of FPA is susceptible to changes in L-NMMA levels at small plasma concentrations.

Adult↗

PubMed1998

Pharyngeal colonisation, ADNB response and development of cardiac lesions in mice following intranasal inoculation with group A beta haemolytic streptococcus M type 18.

Swiss albino mice from a randomly bred colony were inoculated intranasally with 1.6, 2 or 2.4 x 10(7) colony forming units of a mid-logarithmic phase culture of group A beta haemolytic streptococcus M type 18 for 3 days, 6 days or once a week respectively for three weeks. Pharyngeal colonisation could be observed in 67 (59.8%) of 112 mice on 4th day after inoculation and 14 (38%) of the 37 mice on 21st day. Out of 27 mice tested for determination of antibodies to deoxyribonuclease B at regular intervals for 98 days, 15 (55.5%) showed responses, with maximum titers varying from 50 units to 4800 units in individual mice. Histopathological evidence for cardiac lesions were seen in five (3.03%) of the 165 animals studied. These included one case of severe endocarditis, two cases of endocarditis with valvular lesions and one case with non-specific lymphocyte infiltration in the heart. One other animal showed subendocardial oval nodular aggregates. Although the cellular nature of these lesions were not determined, this study shows that Swiss albino mice can serve as suitable animal models to study experimental streptococcal infections. However these are preliminary observations and are to be confirmed and revalidated by further controlled experiments.

Animals↗

PubMed1997

Transseptal approach to aortography and carotid artery stenting in pulseless disease.

We report on a patient with pulseless disease (Takayasu's arteritis) in whom access to the central circulation by extremity arterial cannulation was not possible due to absent pulses in all four limbs. The transseptal approach was used for aortography, bilateral selective carotid angiography, and successful elective stent deployment in the right common carotid artery.

Adult↗

PubMed1997

Mechanisms of cardiac perforation leading to tamponade in balloon mitral valvuloplasty.

Mechanisms of cardiac perforation in 10 cases of cardiac tamponade encountered in a single-center series of 903 balloon mitral valvuloplasty procedures were elucidated by precise localization of the site of perforation at subsequent surgery. These mechanisms were perforation of the aortic root and adjacent right atrium by sliding up of the transseptal set (2), apical tears by straight-tip balloon catheters driven distally during mitral valve dilatation (3), apical perforations by guidewires introduced through catheters wedged in the apex (2), tear of the posterior right atrial wall by dilatation of the track produced by very low septal punctures (2), and right ventricular perforation by a pacing catheter (1). Multivariate analysis showed cardiac perforation to be significantly related to the total experience at the center (inversely) and to patient age (directly). Left ventricular perforation occurred exclusively in patients > 40 yr of age. Understanding these mechanisms has enabled formulation of effective strategies to prevent cardiac perforation.

Adolescent↗

PubMed1997

Combined brachial and femoral approach to balloon angioplasty in coarctation of aorta.

Transfemoral balloon angioplasty of native aortic coarctation was initially not feasible in two patients, because of inability to cannulate the femoral artery percutaneously in one, and to cross the coarctation in the other. The percutaneous brachial approach helped overcome both these problems, after which utilization of intravascular snares allowed successful transfemoral completion of angioplasty.

Adult↗

PubMed1997

Transjugular approach to transseptal balloon mitral valvuloplasty.

The feasibility of a transjugular approach to septal puncture and Inoue-balloon mitral valvuloplasty (BMV) was studied in 20 patients with severe mitral stenosis and varying degrees of anatomic atrial distortion. Left atrial entry by transjugular septal puncture was achieved without difficulty and BMV completed in all patients. In all of 16 patients who had high septal punctures, crossing the mitral valve with the Inoue-balloon was consistently simple and quick. In one patient, septal dilation after very high septal puncture led to a tear extending to the atrial free wall, resulting in cardiac tamponade requiring surgery. Another patient developed severe mitral regurgitation after BMV and required mitral valve replacement. Excellent results were obtained in 16 patients. The transjugular approach simplifies BMV procedure significantly in patients with distorted atrial anatomy and allows rapid patient mobilization. Its safety and efficacy need to be established in larger studies.

Adolescent↗

PubMed1997

Do behavior changes herald physical illness in adults with mental retardation?

A longitudinal study of 62 individuals with profound mental retardation was conducted to determine if direct care staff can identify behavior change prior to identifying symptoms of acute illness. Results indicate that staff were able to notice changes in sluggishness prior to the onset of illness. Self-care behavior was of borderline significance and there was no significant change in eight behavior dimensions (vocalizations, peer conflict, stereotypy, aggression, self injurious behavior, restlessness, distractibility, and depression). This finding should alert physicians and caregivers to the importance of prompt response to symptoms. Reliance on behavioral observation of direct care staff is not always sensitive enough to pick up changes in health status in less restrictive residential environments.

Activities of Daily Living↗

PubMed1997

Combination treatment with trimetazidine and diltiazem in stable angina pectoris.

OBJECTIVE: To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina. DESIGN: Double blind, randomised, placebo controlled trial of four weeks duration. SETTING: Outpatient department of two Indian hospitals. SUBJECTS: 64 male patients with stable angina, uncontrolled on diltiazem alone. INTERVENTIONS: Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily. MAIN OUTCOME MEASURE: Change in exercise time to 1 mm ST segment depression. RESULTS: 33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5) v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1) v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/ week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05). CONCLUSIONS: Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects.

Angina Pectoris↗

PubMed1997

Are individuals with mental retardation at high risk for chronic disease?

BACKGROUND AND OBJECTIVES: Family physicians are responsible for the health and illness care of individuals with mental retardation (MR) in many community practices. Therefore, it is important to determine the special disease patterns for this group. This study determined if individuals with MR are at increased risk for selected chronic diseases. METHODS: We analyzed 366 individuals, living in the community, with a primary diagnosis of MR. The two comparison groups without MR were 427 individual Medicaid recipients and 746 privately insured individuals. RESULTS: Individuals with MR had higher rates of neurophysical conditions (eg, seizures, central nervous system conditions, and sensory loss) compared to the other two groups. However, they had lower rates of some chronic conditions and health behaviors (eg, hypertension, migraines/chronic headaches, diabetes, depression or anxiety, obesity, substance abuse, and smoking) compared to other Medicaid and insured patients. CONCLUSIONS: Individuals with MR have lower rates of many chronic conditions, compared with other Medicaid recipients. This finding should reduce concerns among family physicians that treatment of this special population involves higher rates of chronic illness.

Chronic Disease↗

PubMed1996

Triglyceride expression.

Current epidemiologic reports claim an important role for triglycerides in coronary artery disease (CAD). By cross-sectional data analysis, the role of triglycerides was assessed in 1726 consecutive patients investigated for chest pain, 1119 with CAD and 607 with normal coronaries. Besides study of male and female patients as separate groups, the males were divided into age groups of below 40 years, 41 to 50 years, 51 to 60 years and over 61 years. The female patients were divided into those below 50 years and over 51 years because of smaller numbers. Using the mean value for cholesterol, triglyceride, HDL cholesterol, LDL cholesterol and body mass index for normals as the demarcation line, logistic regression analysis was carried out to study their association in the patients with CAD and normals. Results showed that while the odds ratio for total cholesterol were higher for the younger age groups, the odds ratio for triglycerides were consistently higher for the groups over 51 years both male and female. It is speculated that there may be a difference in the relative importance of lipid fractions with reference to age in the development of atherosclerotic plaque with cholesterol playing a more important role in younger people and triglycerides being equally or more important in older people, on the basis of metabolic handling of lipid fractions.

Adult↗

PubMed1996

A population-based analysis of behavior problems in children with cerebral palsy.

Used the National Health Interview Survey, Child Health Supplement for 1981 and 1988, to analyze parent-reported behavior problems of children, ages 4-17 years, with cerebral palsy (n = 47), with mental retardation (n = 50), with other chronic conditions (n = 6,038), and with no known health problem (n = 5,930), using the Behavior Problem Index (developed by Zill & Peterson). Behaviors with scores greater than the 90th percentile of the entire sample were considered problem behaviors. Parent-reported behavior problems were 5 times more likely in children with cerebral palsy (25.5%) compared with children having no known health problem (5.4%). The adjusted odds ratio for behavior problems of children with cerebral palsy without mental retardation was 4.9 and of children with mental retardation without cerebral palsy was 7.9. Specific behaviors that were most problematic for children with cerebral palsy were identified as dependency, headstrong, and hyperactive.

Adolescent↗

PubMed1996

Coronary angiographic findings in patients with diabetes: an exercise in cardiovascular epidemiology.

A study of 516 patients with diabetes mellitus who presented with chest pain and an equal number of matched controls without diabetes examined by selective coronary arteriography was undertaken. Detailed analysis of the angiograms showed that prevalence of CAD in diabetics with symptoms was 86.6%. This prevalence increased with age. Multivessel disease was more common in diabetics that in controls (p < 0.01). In diabetic patients disease involvement of proximal and distal segments in the same vessel was more common (p < 0.01). The Gensini score of quantitative expression of severity of CAD was higher in diabetics (p < 0.05). The number of occluded segments in the coronary tree was higher in diabetics (p < 0.01). No correlation could be established between severity of disease and age, body mass index or duration of diabetes. It is concluded that diabetes affects the coronary arteries of Indian patients more adversely than those of non-diabetics. The prevalence of CAD among diabetics increases linearly with age.

Adult↗

PubMed1994

Lack of correlation between coronary risk factors and CAD severity.

The coronary arterial lesions seen by angiography in 1666 consecutive male patients were converted to a score by the standardized scoring system advocated by Gensini. The resulting score, which allowed the disease to be expressed as a continuous variable, was effectively utilized to see the correlations between the severity of coronary arterial disease (CAD) and individual risk factors/risk markers. Significant correlations were seen between severity and age (P < 0.001), with a very low coefficient of correlation of 0.0873. On univariate analysis, no correlation was found between CAD severity and diabetes, smoking, positive family history of CAD, hypertension and other lipid fractions. On multiple regression analysis, significant correlations were found between severity and LDL Cholesterol, family history and total cholesterol after adjusting for other factors. The R2 for all these risk factors was only 14.1%. It is concluded that, although strong associations exist between risk factors and the occurrence of CAD, the small quantitative association detected between the presence of risk factors and the severity of disease is weak.

Adult↗

PubMed1993

Pseudohypertension in a child with Williams syndrome.

Pseudohypertension has often been reported in elderly subjects, but is an unusual phenomenon in children. We report the case of a 5-year-old child who presented with features of Williams syndrome (characterized by elfin facies, supravalvar aortic stenosis, and peripheral pulmonary artery stenosis). Repeated blood pressure recordings made with appropriately sized blood pressure cuffs were very high, while simultaneous intraarterial blood pressure was normal, confirming the presence of pseudohypertension. This was shown to be caused by excessively thickened arterial vessels.

Aortic Valve Stenosis↗

PubMed1993

Mitral valve replacement for an annular submitral aneurysm of the left ventricle.

Successful surgical repair of an annular submitral aneurysm of the left ventricle in two patients is described. In both cases the diagnosis was made at surgery and they were treated successfully by transatrial closure of the aneurysm with Teflon felted sutures and mitral valve replacement. This is the first report of the use of mitral valve replacement for this condition.

Adult↗

PubMed1993

Tetralogy of Fallot: intracardiac repair in 840 subjects.

Since 1967, when the first intracardiac repair was performed in this centre, until 1991, 840 symptomatic subjects with tetralogy of Fallot have undergone corrective surgery. Cardiac catheterization and angiocardiography were carried out in all patients. Cardinal findings on the clinical status of these subjects are outlined. A substantial number of patients (244; 29.0%) were > 15 years of age. Historically, a transannular pericardial gusset has been utilized in 578 (68.8%), and in 423 (93.0%) during the past decade. The incidence of residual interventricular septal defects has been 0.68% and occurrence of complete heart block after surgery 0.4%. Death occurred in 86 patients (10.2%) within 30 days of operation and later in 40 subjects (4.8%). Long-term results have been excellent with good haemodynamic status in > 90% of subjects in the follow-up period. Associated features including absent pulmonary valve, absent left pulmonary artery, and previous palliative shunts did not alter the outcome; however, a raised haematocrit (> 0.65) was associated with an increased mortality rate.

Adolescent↗

PubMed1992

Educational attainment, occupational history, and stratification: determinants of later-life economic outcomes.

Determinants of economic well-being among men 25-44, 45-64, and 65+ were examined using data from the 1984 panel of the Survey of Income and Program Participation. A path analysis explored race, education, and occupational history effects on income adjusted for annuitized assets, household composition, and underreporting of unearned income. Direct and total education effects were undiminished among elderly persons, whose income derived mainly from benefits and assets, as compared with the nonelderly subjects whose income was dominated by earnings; education explained more of the variance in adjusted income for the elderly group than for the nonelderly. While Social Security income exerts an equalizing effect across educational attainment groups, private pensions and other important retirement income sources were highly education-dependent, producing a high overall degree of stratification on early-established socioeconomic characteristics.

Adult↗

PubMed1992

Assessment of impaired left ventricular diastolic function in patients with coronary artery disease, using radionuclide angiography.

Left ventricular (LV) diastolic filling at rest was assessed in 76 patients with coronary artery disease (CAD) and 16 healthy subjects using radionuclide angiography. Peak LV filling rate (PFR), expressed in end diastolic volume per second (EDV/sec), was subnormal in CAD patients (1.95 +/- 0.51 as compared to the normal 3.11 +/- 0.36, P < 0.001) and time to PFR (TPFR) was prolonged (171.1 +/- 79 msec versus 106.6 +/- 25 msec normal, P < 0.001). These indices were also abnormal in 60 patients with normal resting LV ejection fraction (PFR 2.17 +/- 0.48 EDV/sec, TPFR 163.9 +/- 68 msec). Abnormal LV filling at rest (PFR EDV/sec or TPFR 160 msec) was found in 88 percent of all patients with CAD, 85 percent of patients with normal resting LV ejection fraction, and 83 percent of patients without Q waves on resting electrocardiogram. Thus, LV diastolic filling, evaluated non invasively by radionuclide angiography, appears to be abnormal in a high percentage of patients with CAD independent of LV systolic function or previous myocardial infarction.

Adult↗