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Biomedical subjects

S Ravi

Publications and source records attributed to S Ravi.

At least 19 recordsLinked to original sources

Safety and potential cost savings of same-setting electrophysiologic testing and placement of transvenous implantable cardioverter-defibrillators.

BACKGROUND: Separately, electrophysiologic study (EPS) and placement of a transvenous implantable cardioverter-defibrillator (ICD) can be performed safely in the majority of patients. The safety and potential cost savings of same-setting procedures have not been evaluated. HYPOTHESIS: Electrophysiologic study and placement of transvenous ICDs can be performed safely in the same setting at reduced cost. METHODS: In all. 160 (mean age 65 +/- 10 years, 75% men) and 41 (mean age 66 +/- 11 years, 73% men) consecutive patients who underwent same- versus separate-setting procedures, respectively, were prospectively evaluated. RESULTS: The two groups had similar clinical characteristics and indications for EPS and ICD therapy. Complications occurred in eight patients (5.0%, 95% confidence interval [CI] 2.3-10.3) who had same-setting procedures (one hypotension during ICD testing, one pocket hematoma, two lead dislodgments, two pneumothoraces, one stroke, and one infection) and in two (4.9%, CI 0.60-16.5) who had separate-setting procedures (one pocket hematoma and one infection). There were no procedure-related deaths or long-term ICD-related complications in either group. The mean time from ICD implantation to hospital discharge was similar in the two groups (2.5 +/- 2.4 vs. 2.7 +/- 2.2 days, p = NS). The combined procedure cost was higher in patients who had separate-setting procedures ($12,403 +/- 1,386 vs. $10,242 +/- 2.256, p = < 0.001). who incurred an additional hospital cost of $2,121 +/- $2,125 for the waiting period (1.7 +/- 1.6 days) between EPS and ICD implantation. CONCLUSIONS: In patients deemed candidates for ICD therapy based on EPS results, placement of transvenous defibrillators in the same setting as EPS is as safe as separate-setting procedures and, if adopted, could further reduce the cost of providing ICD therapy.

Aged↗

Dose-rate effects of ethylene oxide exposure on developmental toxicity.

In risk assessment, evaluating a health effect at a duration of exposure that is untested involves assuming that equivalent multiples of concentration (C) and duration (T) of exposure have the same effect. The limitations of this approach (attributed to F. Haber, Zur Geschichte des Gaskrieges [On the history of gas warfare], in Funf Vortrage aus den Jahren 1920-1923 [Five lectures from the years 1920-1923], 1924, Springer, Berlin, pp. 76-92), have been noted in several studies. The study presented in this paper was designed to specifically look at dose-rate (C x T) effects, and it forms an ideal case study to implement statistical models and to examine the statistical issues in risk assessment. Pregnant female C57BL/6J mice were exposed, on gestational day 7, to ethylene oxide (EtO) via inhalation for 1.5, 3, or 6 h at exposures that result in C x T multiples of 2100 or 2700 ppm-h. EtO was selected because of its short half-life, documented developmental toxicity, and relevance to exposures that occur in occupational settings. Concurrent experiments were run with animals exposed to air for similar periods. Statistical analysis using models developed to assess dose-rate effects revealed significant effects with respect to fetal death and resorptions, malformations, crown-to-rump length, and fetal weight. Animals exposed to short, high exposures of EtO on day 7 of gestation were found to have more adverse effects than animals exposed to the same C x T multiple but at longer, lower exposures. The implication for risk assessment is that applying Haber's Law could potentially lead to an underestimation of risk at a shorter duration of exposure and an overestimation of risk at a longer duration of exposure. Further research, toxicological and statistical, are required to understand the mechanism of the dose-rate effects, and how to incorporate the mechanistic information into the risk assessment decision process.

Administration, Inhalation↗

Abnormal estrous cyclicity after disruption of endothelial and inducible nitric oxide synthase in mice.

The roles of nitric oxide (NO) and nitric oxide synthase (NOS) in reproduction were studied by examining the estrous cycle of wild-type (WT) mice, inducible NOS (iNOS)-, and endothelial NOS (eNOS)-knockout mice. We observed an average estrous cycle of 4.8 +/- 0.2 days in WT mice. While we observed no significant influence of iNOS deficiency on cycle length, eNOS-knockout females showed a significantly longer estrous cycle (6.6 +/- 0.6 days; p < 0.03) than WT females, due to an extension of diestrus (p < 0.03). There was no influence of iNOS deficiency on ovulation rate compared with that in WT females; however, eNOS-knockout mice showed a significant reduction (p < 0.05) in ovulatory efficiency relative to WT or iNOS-knockout females. In contrast to WT females, in which the highest level of estradiol (E2) was observed at 1500 h of proestrus, iNOS-knockout females reached a peak of E2 at 1830 h of proestrus. In eNOS-knockout females, the peak of E2 occurred at 1830 h, as in iNOS-knockout mice; however, E2 levels were 5-fold and 3-fold higher (p < 0.05) than levels observed in WT and iNOS-knockout females, respectively. There was no effect of genotype on the plasma LH concentrations at proestrus. On the first day of diestrus, eNOS-knockout females showed significantly higher plasma E2 and progesterone levels (p < 0.05) relative to WT and iNOS-knockout females. The dysfunction in cyclicity, ovulation rate, ovarian morphology, and steroidogenesis in eNOS-knockout female mice strongly supports the concept that eNOS/NO plays critical roles in ovulation and follicular development.

Animals↗

Protein Z in healthy human individuals and in patients with a bleeding tendency.

Protein Z is a vitamin-K-dependent plasma glycoprotein; its physiological function is not clear. Low protein Z levels were found in patients with otherwise unexplained bleeding disorders. It was therefore suggested that low protein Z levels might be associated with a bleeding diathesis. In the present study we measured protein Z levels in plasma samples of 48 patients with a suspected bleeding disorder and in plasma samples of 200 healthy adult individuals. We found protein Z to have a wide normal range in healthy men and women. Significantly lower protein Z levels were observed in women compared to men, whereas no correlation was found with age or other vitamin-K-dependent coagulation proteins. None of the 48 patients with a bleeding disorder had a protein Z level below the normal range. However, protein Z was significantly lower in the group of male patients with a bleeding history as compared to healthy men. In conclusion, our data indicate that low-normal protein Z levels are not associated with a bleeding tendency. However, it remains to be determined whether a low protein Z level is a weak cofactor associated with an increased bleeding tendency and whether decreased or absent protein Z (conditions not detected in our patients) might constitute a haemorrhagic diathesis.

Adolescent↗

Cardiac metastasis from carcinoma breast--a case report.

Secondary neoplasms of the heart are more common than primary tumours. Metastasis occurs most commonly from bronchogenic carcinoma followed by lymphoma and carcinoma breast. Most often cardiac metastasis go undetected as they are asymptomatic and occurs as a terminal event. A 51 year old lady who developed cardiac metastasis from carcinoma breast diagnosed during life is reported with brief review of the literature.

Bone Neoplasms↗

Muscarinic regulation of Alzheimer's disease amyloid precursor protein secretion and amyloid beta-protein production in human neuronal NT2N cells.

The Alzheimer amyloid precursor protein (APP) undergoes complex processing resulting in the production of a 4-kDa amyloid peptide (A beta) which has been implicated in the pathogenesis of Alzheimer's disease. Recent studies have shown that cells can secrete carboxyl terminus truncated APP derivatives (APP-S) in response to physiological stimulus. We have used human central nervous system neurons (NT2N) derived from a teratocarcinoma cell line (NT2) to study the signal transduction pathways involved in APP-S secretion and A beta production. Muscarinic receptors (m2 and m3) as well as the heterotrimeric GTP-binding protein Gq and the beta 1 isoform of phospholipase C were present in NT2N neurons. Stimulation of the muscarinic receptor with carbachol resulted in phospholipase C activation as shown by a transient increase in the second messengers 1,2-diacyl-sn-glycerol and inositol 1,4,5-trisphosphate. Carbachol also caused an increase in intracellular Ca2+ levels measured in single NT2N neurons. Under these conditions, carbachol caused a time-dependent 2-fold increase in APP-S secretion into the medium. In contrast, prolonged treatment with carbachol caused a decrease in A beta production into the medium. These results suggest that APP-S secretion and A beta production in NT2N neurons are regulated by the muscarinic/phospholipase C signal transduction pathway. Furthermore, activation of this pathway results in dissociation of APP-S secretion and A beta production.

Alzheimer Disease↗

Relation between impedance and temperature during radiofrequency ablation of accessory pathways.

Temperature monitoring is a useful tool for radiofrequency ablation of accessory pathways. Impedance monitoring is also helpful, and an impedance fall of 20 ohm may predict coagulum formation. Therefore the purpose of this study was to prospectively quantitate the correlation between impedance and temperature during radiofrequency ablation. Thirty-three consecutive patients underwent radiofrequency ablation with a thermistor ablation catheter with continuous temperature and impedance monitoring during each energy application. The initial and final impedance and temperature measurements for 319 applications of radiofrequency energy were 109 +/- 17 ohm and 102 +/- 17 ohm (p < 0.0001), respectively, and 37 +/- 1 degree C and 57 degrees +/- 11 degrees C (p < 0.0001), respectively. Among the 319 applications of radiofrequency energy, 158 were associated with > or = 20 degrees C increase in tissue temperature, and 10 were associated with coagulum formation. A > or = 20 degrees C increase in tissue temperature was observed in 84 of 104 applications associated with a 5 to 10 ohm decrease in impedance (81% positive predictive value and 93% negative predictive value). The mean change in impedance for applications associated with and without coagulum formation was -19 +/- 7 ohm and -6 +/- 6 ohm (p < 0.0001), respectively, and coagulum formation never occurred with less than a 12 ohm decrease. In conclusions successful tissue heating without coagulum formation can be achieved by titrating the power to achieve a 5 to 10 ohm decrement in impedance. Impedance decrements beyond 10 ohm increase the likelihood of coagulum formation.

Adult↗

Ofloxacin-containing combined drug regimens in the treatment of lepromatous leprosy.

A total of 26 clinically diagnosed adult patients, with active untreated lepromatous leprosy, with a Bacteriological Index of 4+ or more, were admitted to the hospital of the Central Leprosy Teaching and Research institute, Chengalpattu, India, between 1989 and 1991. After prescribed investigations, the patients were randomly allocated in groups of 3 to 3 treatment regimens, namely: 1, clofazimine 50 mg daily and 300 mg once in 4 weeks + dapsone 100 mg daily (AA); 2, (AA)+ofloxacin 400 mg daily (BB); and 3, (AA)+ofloxacin 800 mg daily (CC). The drugs were administered for 56 days continuously under supervision. Sequential biopsy results on day 0, 7, 14, 28 and 56 in normal mouse footpad revealed no growth by day 28 and 56 in all patients treated with CC and BB regimens, respectively. Calculation of the proportion of viable Mycobacterium leprae through analysis of median infectious dose (ID50) showed significant differences on day 7 in the percentage of kill between the ofloxacin-containing regimens and the other. Moderate to marked clinical improvement has been observed in a significantly higher proportion of patients treated with ofloxacin-containing regimens. All the 3 regimens were well tolerated. No severe complications or side-effects to the drugs were noticed with any of the regimens that required any suspension of treatment or the administration of steroids. Addition of ofloxacin to the standard WHO recommended MDT regimen for multibacillary patients may reduce the present duration of therapy. Ofloxacin may also be considered as an alternative drug in rifampicin-resistant cases or where rifampicin is contraindicated.

Adult↗

Multibacillary leprosy presenting as a solitary skin lesion; report of three cases and its significance in control programs.

Three patients with solitary skin lesions showing the cardinal signs of leprosy were seen and clinically classified among the paucibacillary cases. Initially, they were treated with two drugs (rifampin and dapsone) as recommended by the WHO Expert Committee. On the first visit of their follow-up, they were seen to be histopathologically either in the borderline (BB) or borderline lepromatous (BL) group, and acid-fast bacilli were demonstrated in the sections. Later they were put on three drugs (rifampin, dapsone and clofazimine) as given for multibacillary cases, and therapeutically they also behaved like bacilliferous leprosy. Such cases are rare and the reasons for the occurrence are not clear. Further studies on the subtle relationship between the local host factors and the virulence of the organisms grown from these lesions may offer an explanation. In light of these cases and previous reports of even lepromatous leprosy presenting as a single skin lesion, field workers--including both medical and paramedical workers--should carefully perform and interpret slit-skin smears from clinically diagnosed paucibacillary cases so that such unusual presentations of the disease are treated appropriately and not missed.

Adolescent↗