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Biomedical subjects

A Aggarwal

Publications and source records attributed to A Aggarwal.

At least 55 records · Page 3Linked to original sources

beta-blockers, angiotensin II, and ACE inhibitors in patients with heart failure.

Blood concentrations of angiotensin II are often raised in patients with heart failure, despite treatment with angiotensin-converting-enzyme (ACE) inhibitors. We compared concentrations of angiotensin II in two groups of matched patients, receiving ACE inhibitor therapy with or without concomitant administration of beta-blockers. Concentrations of angiotensin II were lower in individuals taking beta-blockers than in those who were not (geometric mean 1.1 [95% CI 0.4-2.7] vs 15.5 [4.6-52.6] fmol/mL, 95% CI for difference 3-59). Our findings indicate that a reduction in angiotensin II concentrations might contribute to the therapeutic benefits of beta-blockade in heart failure, especially in patients who simultaneously receive ACE inhibitor treatment.

Adrenergic beta-Antagonists↗

Acute effects of continuous positive airway pressure on cardiac sympathetic tone in congestive heart failure.

BACKGROUND: Depressed ventricular performance and neurohormonal activation are key pathophysiological features of congestive heart failure (CHF). Although angiotensin-converting enzyme inhibitors and beta-adrenoceptor blockers exert beneficial effects in CHF, mortality remains unacceptably high, and the development of further therapeutic approaches is warranted. Recent data suggest that continuous positive airway pressure (CPAP) may be of benefit in the treatment of CHF, although the mechanism for this action is incompletely understood. METHODS AND RESULTS: In the present study, we examined the effect of short-term CPAP (10 cm H(2)O for 10 minutes) on hemodynamics (Swan Ganz catheter) and total systemic and cardiac sympathetic activity (norepinephrine spillover method) in 14 CHF patients in New York Heart Association class III. The application of CPAP was associated with a fall in cardiac output (4.8+/-0.3 to 4.4+/-0.2 L/min; P<0.05) and a significant reduction in cardiac norepinephrine spillover (370+/-58 to 299+/-55 pmol/min; P<0.05), although total systemic norepinephrine spillover was unchanged. CONCLUSION: The short-term application of CPAP results in an inhibition of cardiac sympathetic nervous activity. Further investigation into the potential value of long-term CPAP in CHF patients is warranted.

Heart↗

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Algorithms↗

Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21.

One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to>81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes,with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.

Animals↗

Typhoid vaccines.

Typhoid fever continues to be a major public health problem in developing countries with about 33 million cases per year. Protective efficacy of traditional acetone/phenol killed vaccines is similar to newer typhoid vaccines (Ty21A and Vi antigen vaccine) but side effects of these newer vaccines are considerably less. Though the mortality is low, typhoid fever causes considerable morbidity and loss of working days. Problems during treatment are increasing due to emergence and spread of multidrug resistant S. typhi. Hence to decrease the incidence of typhoid fever in addition to ensuring safe water supply and excreta disposal a typhoid vaccine needs to be introduced in the National Immunization Schedule.

Administration, Oral↗

Postcoital vaginal laceration in a patient presenting with signs of small bowel perforation: report of a case.

Postcoital vaginal rupture or tear is a well-known entity to the gynecologist, albeit unusual; however, such cases are rarely encountered by the general surgeon. The index case is reported to highlight the rare situation wherein a middle-aged woman underwent laparotomy for a suspected small bowel perforation, which revealed a vaginal tear as the cause of pneumoperitoneum. This case emphasizes the importance of taking a gynecological history and performing a gynecological examination when the clinical diagnosis is uncertain.

Coitus↗

Exercise rehabilitation of older patients with cardiovascular disease.

As the population of elderly patients with cardiovascular disease continues to increase, much research needs to be done with the goal of maintaining physical functioning and personal independence in this population. It is of particular importance to determine whether training programs can improve physical functioning in the most severely disabled older coronary patients. Effects of cardiac rehabilitation programs on other outcome measures, including psychosocial outcomes, lipid levels, insulin levels, and body composition require better study. Finally, the economic benefits of cardiac rehabilitation in the older coronary patients has received little attention, although early reports are promising. In summary, the older population with coronary disease is characterized by high rates of disability. Exercise training has been demonstrated to be safe and to improve strength, aerobic fitness capacity, endurance and physical function. It remains to be seen whether exercise training can reverse or prevent disability in a broad population of older patients with cardiovascular disease. If successful, cardiac rehabilitation programs will pay great medical, social, and economic dividends in this population.

Aged↗

Evidence for functional presynaptic alpha-2 adrenoceptors and their down-regulation in human heart failure.

OBJECTIVES: The aim of this study was to investigate the role of peripheral presynaptic alpha-2 adrenergic receptors in modulating norepinephrine (NE) release in congestive heart failure (CHF). BACKGROUND: Activation of the sympathetic nervous system is a hallmark of CHF. Clonidine, an imidazoline and adrenergic agonist with high selectivity for the alpha-2 adrenoceptor, has been shown to reduce generalized sympathetic activity in heart failure after parenteral administration. If it could be shown that peripheral presynaptic alpha-2 adrenoceptors are inhibitory to NE release, then they could be targeted for future therapy, and as a corollary, potentially circumvent unwanted side effects arising from stimulation of alpha-2 adrenoceptors in the brain. Additionally, it could be concluded that these receptors form the basis for an auto-inhibitory feedback to further NE release. METHODS: Fifteen healthy volunteers and 10 patients with heart failure received intra-arterial clonidine via the brachial artery (0.05 microg and 0.48 microg/100 ml forearm/min). Radio-tracer techniques were employed for studying NE kinetics. RESULTS: Intra-arterial clonidine caused a dose-dependent decrease in forearm spillover of NE in healthy individuals (low dose, high dose: 26%, 49%: p < 0.05, p < 0.001, respectively). In the patient group, no decrease in forearm spillover was demonstrated after local administration. The difference in response between the two groups was statistically significant (p = 0.004). CONCLUSIONS: Peripheral sympathoneural alpha-2 adrenoceptors are functionally important in inhibiting NE release in the healthy human. In heart failure, this function is lost. This finding offers further insights into the mechanisms responsible for high circulating levels of NE in patients with heart failure. In addition, it suggests that selective targeting of peripheral presynaptic alpha-2 adrenoceptors will not achieve sympathoinhibition in heart failure.

Aged↗

Improved outcomes from a comprehensive management system for heart failure.

AIMS: Congestive heart failure (CHF) is associated with a high readmission rate after diagnosis. We assessed the ability of a comprehensive management program (CMP) for CHF to reduce readmissions with secondary endpoints of improving quality of life, exercise capacity and targeted drug doses. METHODS AND RESULTS: Patients (pts) with: New York Heart Association Class (NYHA) III or IV CHF; left ventricular ejection fraction <40%; and stable outpatient therapy were assigned to a CMP of cardiology assessment intensive education and referral to a tailored exercise program. Forty-two pts (35 M, 7 F, mean age 54 years, S.D. 12 years) were enrolled. Two pts were transplanted, two died during follow-up and two were lost to follow-up. Hospital admissions were reduced by 87.2%, (mean 1.05, S.D. 0.98, admissions per pt to mean 0.08, S.D. 0.28, admissions per pt at 6-month follow-up; P<0.0001). ACE-inhibitor dose increased by 42% (P<0.0008) and beta-blocker dose increased by 61% (P<0.0001). NYHA Class, 6-min walk and quality of life scores all improved significantly (P<0.0001). CONCLUSION: A CMP improves QOL and exercise capacity as well as substantially reducing hospital admissions in CHF pts. This study validates the benefit of intensive outpatient care of CHF.

Aged↗

Mechanism of action of disease modifying anti-rheumatic agent, gold sodium thiomalate (GSTM).

GSTM has been used for long in the treatment of rheumatoid arthritis (RA). However, its mechanism of action is still poorly understood. In the last decade, tumor necrosis factor-alpha (TNF-alpha) has emerged as the major pro-inflammatory cytokine in the pathogenesis of RA. We studied the effect of GSTM on spontaneous and LPS-stimulated TNF-alpha production by human peripheral blood mononuclear cells (PBMCs) of normal volunteers. PBMCs were isolated from 20 normal volunteers and cultured in the presence of absence of lipopolysaccharide (LPS 10 ng/ml) and GSTM (1 microgram/ml). TNF-alpha level was measured using commercial enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). The TNF-alpha response to LPS was heterogeneous. PBMCs of 24 subjects showed high LPS-stimulated TNF-alpha production (LPS-responsive group), whereas that of six individuals had low LPS-stimulated TNF-alpha production (LPS-non-responsive group). GSTM-stimulated spontaneous TNF-alpha production and inhibited LPS-stimulated TNF-alpha production in 16 of 24 (75%) individuals of LPS-responsive group and one of six individuals (17%) of LPS-non-responsive group. The suppression of TNF-alpha by GSTM was also demonstrated at the mRNA level. We conclude that there is a heterogeneity among normal population for TNF-alpha production in response to LPS, and GSTM inhibits LPS-stimulated TNF-alpha production, primarily in LPS responders. Further study is needed to establish the relationship between LPS responsiveness and GSTM suppression.

Adult↗

Relaxation rate in the assessment of masseter muscle fatigue.

The aim of this study was to assess a simple method of measuring relaxation rate in the jaw-closing system for the purpose of quantifying jaw muscle fatigue. A summary of the various different methods of measuring relaxation rate is also provided. The rates of twitch contraction and relaxation were measured in 30 symptom-free subjects following bilateral direct electrical stimulation of the masseter muscles. The resulting twitch force was recorded via a force transducer placed between the anterior teeth. The transducer was held between the teeth with as little force as possible while four single stimuli were delivered at 5-s intervals. The stimulating electrodes were then removed and replaced and the experiment was repeated. The force records of the resulting twitches were averaged and the half-contraction time, twitch amplitude and half-relaxation time were measured. There was a significant difference in half-relaxation time between males and females, being faster in females (P=0.0045, independent t-test). No significant difference was found in twitch amplitude and half-contraction time between males and females. Half-relaxation time and half-contraction time were independent of twitch amplitude. This method of measuring the relaxation rate of the masseter muscles was found to be practical and the results were reproducible between sessions.

Adult↗

Interactions of herbal remedies with prescription cardiovascular medications.

Herbal medicinal use has increased dramatically in recent years. The increasing use of these products is of concern, and their use may not be recognized by the treating physicians. Many of these remedies have potential for adverse interactions with medications commonly prescribed for various cardiovascular disorders. Despite their widespread use, limited data exists regarding the efficacy of herbs such as echinacea, garlic, ginseng, gingko, ephedra, and St. John's wort. Of special concern is the ability of herbal remedies to potentiate effects of prescription drugs with a narrow margin of safety. An increasing awareness of the potential for harmful effects of herbal remedies has given the impetus for aggressive interventions to inquire about the use of these agents and systematic reporting of adverse events emanating from their use. This review briefly summarizes important adverse interactions of commonly used herbal remedies with prescription cardiovascular medications.

Cardiovascular Agents↗

Mushroom poisoning--from diarrhea to liver transplantation.

Mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common species. The typical symptoms of nausea, vomiting, abdominal pain, and diarrhea are nonspecific and can be mistaken for gastroenteritis. If not adequately treated, hepatic and renal failure may ensue within several days of ingestion. In this case series, patients poisoned with Amanita virosa are described with a spectrum of clinical presentations and outcomes ranging from complete recovery to fulminant hepatic failure. Although there are no controlled clinical trials, a few anecdotal studies provide the basis for regimens recommended to treat Amanita poisoning. Use of i.v. penicillin G is supported by most reports. Silibinin, although preferred over penicillin, is not easily available in the United States. In those with acute liver failure, liver transplantation can be life saving.

Adult↗

Normal complement of motor units in asymptomatic familial (SOD1 mutation) amyotrophic lateral sclerosis carriers.

OBJECTIVE: To understand the mechanisms causing neuronal death in amyotrophic lateral sclerosis (ALS), an electrophysiological technique of motor unit number estimation (MUNE) was used to examine the pattern of motor neuron loss in amyotrophic lateral sclerosis. The aim was to determine whether gradual lifelong loss of motor units precedes clinical disease or whether sudden, catastrophic loss of motor units occurs at the onset of the disease. METHOD: Using the statistical technique of motor unit number estimation, a cross sectional study was performed on a group of asymptomatic carriers of the Cu, Zn superoxide dimutase 1 (SOD1) gene. MUNE results were compared with those from age and sex matched family controls who did not carry the SOD1 mutation. A total of 87 subjects (45 men and 42 women) with an age range from 16-73 years of age were studied. RESULTS: There was no detectable difference in the number of motor units in SOD1 mutation carriers compared with SOD1 negative family controls or population controls. Symptomatic subjects showed a definite loss of motor units. The test-retest reproducibility of this technique yielded an average difference between MUNE results on separate occasions on the same subject of +/-5%. CONCLUSION: The finding that presymptomatic SOD1 mutation carriers have a full complement of motor neurons indicates that mutation carriers must have normal survival of motor neurons until rapid and widespread cell death of these neurons occurs, coinciding with the onset of clinical features. This implies that symptomatic ALS is not the end result of a slow attrition of motor neurons.

Adolescent↗