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Biomedical subjects

P Jain

Publications and source records attributed to P Jain.

At least 19 recordsLinked to original sources

Reemergence of the fetal pattern of L-type calcium channel gene expression in non infarcted myocardium during left ventricular remodeling.

The cardiac L-type voltage-dependent calcium channel (VDCC) is a critical component of cardiac action potential and excitation-contraction coupling. The objective of the present study was to examine the changes in expression in Motif IV, an alternatively spliced region of the alpha-1 subunit of the VDCC channel in postmyocardial infarction (MI) remodeled rat left ventricle. RNase protection assay was used to determine alteration in isoform expression in the noninfarcted hypertrophied ventricular myocardium 21 days post myocardial infarction. Our study demonstrates that cardiac hypertrophy is associated with significant increase in the mRNA level of the fetal isoform, with the reversion of fetal:adult isoform ratio to the fetal phenotype. Changes in isoform expression in the post-MI remodeled ventricle, not previously reported, is a pertinent genetic marker of cardiac hypertrophy.

Alternative Splicing

Overuse of the indwelling urinary tract catheter in hospitalized medical patients.

BACKGROUND: The indwelling urinary tract catheter (IUTC) is an important aspect of medical care. We studied the prevalence of the unjustified use of the IUTC in hospitalized medical patients and identified situations associated with its unjustified use. METHODS: This prospective study involved 202 patients admitted to either the medical intensive care unit (n = 135) or the medical floors (n = 67) of a tertiary care university hospital who were catheterized during the hospital admission. An independent observer assessed the indication of initial catheterization by chart review and interview with the patient and the nurse. The need for continued catheterization was assessed daily by the same observer. The proportion of unjustified IUTC placement was determined using the study guidelines. Complications as a direct consequence of catheter use were recorded. RESULTS: Of the 202 patients who were studied, the initial indication for the placement of an IUTC was found to be unjustified in 21% (95% confidence interval [CI], 15% to 27%). Continued catheterization was unjustified in 47% (95% CI, 42% to 57%) of 912 patient-days with IUTC studied. In the medical intensive care unit, 64% (95% CI, 58% to 70%) of the total unjustified patient-days with IUTC resulted from its excessively prolonged use for monitoring urine output. Urinary incontinence was found to be the major cause of unjustified initial ([52%] 95% CI, 32% to 74%) and continued ([56%] 95% CI, 50% to 62%) use of IUTC in the noncritical care areas. Catheter-related urinary tract infection requiring intravenous antibiotics or continuous bladder irrigation with amphotericin B was observed in 5% of the patients. CONCLUSIONS: The IUTCs are significantly overused in hospitalized medical patients and careful attention to this aspect of medical care may reduce catheter-related complications by primary prevention.

Catheters, Indwelling

Increased expression of messenger RNA for collagen type I, collagen type III, and fibronectin in myometrium of pregnancy.

OBJECTIVE: To determine the expression of the extracellular matrix proteins collagen type I, collagen type III, and fibronectin by immunohistochemistry, and the messenger RNA (mRNA) for these proteins by Northern blot analysis in the myometrium of pregnancy compared with myometrium from normal premenopausal women. METHODS: Myometrial tissue was obtained from seven pregnant women undergoing elective cesarean delivery and eight nonpregnant premenopausal women undergoing hysterectomy. Tissue was paraffin embedded and processed for RNA. Antibodies to collagen type I, collagen type III, and fibronectin were used to examine protein expression by immunohistochemistry. Complimentary DNA probes for the same proteins were used to examine mRNA expression by Northern blot analysis. RESULTS: Increased staining was seen for all three proteins in the myometrium of pregnancy. Densitometric analysis of Northern blots showed increased levels of collagen type I mRNA (P < .003), collagen type III mRNA (P < .005), and fibronectin mRNA (P < .04) in the myometrium of pregnancy compared with myometrium from nonpregnant premenopausal women. CONCLUSION: There is increased expression of both protein and mRNA for collagen type I, collagen type III, and fibronectin in the myometrium of pregnancy.

Blotting, Northern

Silent myocardial ischemia in diabetics with normal autonomic function.

Twenty male diabetic patients (age range, 40-60 years) with normal autonomic function were studied to determine the prevalence of silent myocardial ischemia on exercise as well as ambulatory electrocardiography. The presence and extent of silent myocardial ischemia was also correlated with the severity of atherosclerotic coronary artery disease as determined by coronary angiography. A cohort of 20 matched non-diabetic patients were also included in the study. Silent myocardial ischemia was detected in 50% of the diabetic patients on exercise electrocardiography and in 35% on ambulatory electrocardiography compared with 10% and 5% in non-diabetics by the two methods, respectively (P < 0.01 and P < 0.05, respectively). On exercise testing in diabetic patients, silent myocardial ischemia was detected in 64% of the patients with three-vessel disease, 50% of the patients with two-vessel disease and 20% of the patients with one-vessel disease whereas in non-diabetic patients silent myocardial ischemia was detected in only 18% of the patients with three-vessel disease (P < 0.05) and in none of the patients with two- or one-vessel disease. On ambulatory electrocardiography, only patients (both diabetic and non-diabetic) with three-vessel disease manifested silent myocardial ischemia. Total ischemic burden was similar in both the diabetic and non-diabetic patients. We conclude that silent myocardial ischemia occurs in diabetic patients with coronary artery disease more frequently even in the absence of autonomic dysfunction and the prevalence of silent myocardial ischemia is higher in patients with severe degree of coronary artery disease.

Adult

A new subclass of alkaloids from a dendrobatid poison frog: a structure for deoxypumiliotoxin 251H.

Deoxypumiliotoxin 251H [4], representing a new subclass of the pumiliotoxin-A class of alkaloids, has been isolated from a dendrobatid frog, Epipedobates tricolor. The structure, elucidated by nmr, gc-Ftir, and mass spectral analyses, is proposed to be an 8-methyl-6-(5-hydroxy-2-methylhexylidene)-1-azabicyclo[4.3.0]nonan e. The absolute stereochemistry and the relative configuration of the hydroxyl group are unknown.

Alkaloids

The myometrium of postmenopausal women produces prolactin in response to human chorionic gonadotropin and alpha-subunit in vitro.

OBJECTIVES: To examine the effect of equimolar concentrations of hCG and dissociated alpha-subunit on PRL production by leiomyoma and myometrial tissue obtained from different hormonal states and to examine changes in PRL messenger RNA levels as PRL protein levels increased. DESIGN: Explant cultures of leiomyomas and myometrium were established and cultured for 96 hours. Tissue was studied from normal cycling women, postmenopausal women, pregnant women, and women undergoing GnRH agonist (GnRH-a) therapy. Cultured medium was collected at 24, 48, and 96 hours and assayed for PRL. In selected experiments, tissue was processed at 0 and 96 hours to analyze messenger RNA (mRNA) levels. RESULTS: Human chorionic gonadotropin and alpha-subunit stimulated PRL secretion in [1] explant cultures of leiomyoma and myometrium from premenopausal women, [2] cultures of tissue treated in vivo with leuprolide acetate for both leiomyoma and myometrium, and [3] myometrium obtained from postmenopausal women. Postmenopausal myometrium was significantly more responsive to stimulation. Prolactin mRNA levels were documented to increase after hormone treatment in postmenopausal myometrium. CONCLUSION: Myometrium from postmenopausal women is very responsive to hCG and alpha-subunit. There is a difference in response between tissue obtained from menopausal women and that from women undergoing GnRH-a therapy to achieve a "medical menopause" and reproductive age women. The level of endogenous gonadotropins as well as the steroid milieu may modulate myometrial PRL secretion.

Antineoplastic Agents, Hormonal

Stalling by RNA polymerase II in the polyomavirus intergenic region is dependent on functional large T antigen.

RNA polymerase II encounters an elongation block and stalls in vivo during transcription of the late strand of polyomavirus DNA. In this study, we performed transcriptional run-on assays and localized the stalling site to a 164-nucleotide region (nt 11-175) that contains specific binding sites for polyomavirus large T antigen. The effect of large T antigen on elongation by RNA polymerase II through this region was examined in cells infected with a mutant polyomavirus (AT3-ts25E) which encodes a thermolabile large T antigen. Removal of functional large T antigen by shifting to the nonpermissive temperature (39 degrees) eliminated stalling by RNA polymerase in this region, although RNA polymerases transcribing other regions of the viral genome were unaffected. RNA polymerase resumed stalling when functional large T antigen was again allowed to accumulate by shifting back to the permissive temperature (32 degrees). We conclude that stalling by RNA polymerase II in vivo is dependent on the presence of functional large T antigen.

Animals

Myopotential inhibition of unipolar demand pacemakers: utility of provocative manoeuvres in assessment and management.

Fifty patients with permanent unipolar pacemakers (48 multiprogrammable, 2 non programmable) with protective insulating sheath placed against the muscular side of the pacemaker pocket were studied to determine the occurrence of inhibition of pacing by sensing of the myopotentials. All the patients were subjected to a combination of different provocative manoeuvres at their nominal R wave sensitivity settings. Myopotential inhibition was exhibited in 35 (70%) patients. Only 3 patients however had reported symptoms suggesting loss of pacing. The most useful provocative manoeuvre was shoulder flexion with adduction against resistance (94.3% positivity). Appropriate sensitivity adjustments resulted in amelioration of the problem in 86% of the patients while still retaining R wave sensing. Myopotential interference continues to be a frequently observed problem even in the present generation of unipolar pacemakers. Provocative tests and appropriate reprogramming should be done in all such patients as a routine.

Action Potentials

Spectrum of right-sided infective endocarditis: an Indian experience.

We studied retrospectively 23 consecutive patients seen at our centre with right heart endocarditis. None of the patients had a history of intravenous drug abuse. All patients were found to have underlying congenital heart disease as a predisposing factor, of which ventricular septal defect (26%) and Fallot's tetralogy (26%) were the commonest. Postoperative endocarditis (26%) also constituted an important clinical subset. Fever (100%) and predominant pulmonary symptoms (69.5%) were the important presenting features. Congestive heart failure was present in 15 patients (65.2%) and predicted an adverse in-hospital outcome. Both the pulmonary and the tricuspid valves were affected equally with presence of vegetations at multiple sites in 10 patients (43.4%). Seven patients (30%) also had concomitant left-sided endocarditis. Medical therapy alone was successful in 15 patients (68.1%) with an overall in-hospital mortality of 31.8%. Five of 6 patients with postoperative endocarditis died, signifying an ominous prognosis of this subgroup when treated medically. The clinical spectrum of right-sided endocarditis in our country differs from the West. The frequent presence of underlying congenital heart disease, the rarity of drug abuse as a predisposing factor, equal involvement of the tricuspid and pulmonary valves and a greater incidence of congestive heart failure are some of these differences.

Adolescent

Fluorescein angiography in systemic hypertension.

This study evaluates the role of fluorescein angiography (FA) in detecting changes in the retinal and choroidal capillary bed in hypertension and defines its advantages over direct ophthalmoscopy. 37 patients with varying degree of severity of hypertension were studied. Direct ophthalmoscopy and FA was done in all cases. No significant difference was found in documenting vessel calibre and arteriovenous crossing changes with either of the methods. Hard exudates were not visualized on FA. Capillary bed and choroidal abnormalities could be better studied on FA which can be employed in selected patients of hypertension but its use is not advocated as a routine in all hypertensives.

Adult

Significance of ventricular late potentials in patients with myocardial infarction.

Fifty six patients (52 males, 4 females, mean age 53.6 +/- 8 years, range 35-75 years) were studied to determine the influence of clinical variables, site of myocardial infarction, thrombolytic therapy, documented arrhythmias and left ventricular ejection fraction (LVEF) on the incidence of ventricular late potentials (LP's). LP's were detected in 17 (30.3%) patients; in 6 (26%) patients with acute and in 11 (33.3%) patients with old healed myocardial infarction. 87.5% of the patients in whom LPs were detected had low LVEF. The presence of low LVEF correlated significantly with the presence of LP's (p = .02). LP's were also present in all patients with documented sustained ventricular tachycardia. Clinical variables (Killip and NYHA class), site of myocardial infarction, Q wave versus non-Q wave myocardial infarction and thrombolytic therapy did not relate to the presence of LP's (p > 0.5) Patients of myocardial infarction with low LVEF and a history of ventricular tachyarrhythmias should undergo signal averaged electrocardiography for LP detection. LP presence would identify patients at higher risk of future arrhythmic events within this subgroup.

Adult

Synthesis and biological evaluation of a series of gem-dichlorocyclopropanes as antitumor agents.

As part of our continuous effort to produce non-steroidal antiestrogens demonstrating less intrinsic estrogenicity and greater antagonism than those in use, a series of Analog II (1,1-dichloro-2,3-diphenylcyclopropanes) derivatives was synthesized. The compounds were tested for their ability to inhibit the growth-stimulating action of estradiol in the immature mouse uterus and estrogen receptor (ER) (+) MCF-7 human breast cancer cells in vitro. Like Analog II, the derivatives were found to have no intrinsic estrogenicity (except 30) and they antagonized estradiol action less completely than the lead compound. Polarity improved the ER binding affinity of Analog II, but was quite small for all compounds, except 30, for which it was comparable to tamoxifen. Six compounds (8, 10, 14, 23, 29 and 30) demonstrated antiproliferative activity toward MCF-7 cells, in vitro, and the mean inhibition period over 6 days ranged from 20 to 37%. Only compound 30 was reversed by estradiol.

Animals

Effects of milrinone on left ventricular remodeling after acute myocardial infarction.

BACKGROUND: Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction. METHODS AND RESULTS: Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals. CONCLUSION: Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation.

Animals