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Biomedical subjects

P Iyer

Publications and source records attributed to P Iyer.

At least 19 recordsLinked to original sources
PubMed2000

Comparative study of the clinical efficacy of two dosing regimens of flutamide.

PURPOSE: We performed a randomized trial to compare the efficacy and toxicity of a new dose of flutamide (500 mg QD) with the currently recommended dose (250 mg q8h) in the treatment of advanced prostate cancer. The primary endpoints were percent of patients having normalization of prostate specific antigen (PSA), time to normalization, and percent change from baseline. Secondary endpoints were quality of life and toxicity. PATIENTS: Altogether, 440 men aged 46 to 94 years (mean 71 years) with confirmed stage M(1) disease, documented PSA rise >0.2 ng/mL, ECOG status 0 to 2, no second neoplasm, no liver function tests > or = 1.5-fold normal values, and no previous treatment for metastatic disease were entered in the trial. RESULTS: The PSA normalized by week 12 in 71% of the patients receiving 500-mg dose and 75% of those receiving the standard dose. The percent change in PSA was 89% and 96%, respectively. The treatment groups were not significantly different with respect to the incidence of adverse events: 71% v 68% in the 500-mg and 250-mg arms, respectively (P = 0.337). CONCLUSIONS: When combined with castration, 500 mg of flutamide appears to be equally effective in lowering serum PSA and is not significantly more toxic than conventional dosing. The use of 500 mg QD instead of the standard 250 mg q8h would result in a cost savings of 30%.

Aged↗
PubMed1999

Characterization of maternal influence on teratogenicity: an assessment of developmental toxicity studies for the herbicide cyanazine.

The contribution of maternal toxicity to the teratogenic effects of the herbicide cyanazine has been assessed to determine whether it may be a hazard to development. Eye defects such as anophthalmia and microphthalmia were observed in rat fetuses and pups. Maternal toxicity was determined from body weight data and clinical signs. Two approaches were used. First, the timing of maternal toxicity was correlated with the specific period of gestation during which the observed fetal defect was most likely to have occurred. Second, individual dams, as well as mean values for each group, were evaluated. The data at the individual level, i.e., in dams with affected litters, did not support conclusions based on the group means. Instead, it is suggested that the developmental effects were not a direct result of maternal toxicity of cyanazine. Data from a rabbit developmental toxicity study supported the findings from the Fischer 344 rat studies. The strategy employed may thus enable direct toxicity to the fetus to be distinguished from developmental toxicity arising as a secondary consequence of maternal toxicity.

Abnormalities, Drug-Induced↗
PubMed1999

Chemotaxis of Rhizobium sp.S2 towards Cajanus cajan root exudate and its major components.

The chemotactic response of Rhizobium sp. S2, a slow-growing Cajanus cajan isolate, towards its host root exudate was examined. Two classes of mutants, one nonchemotactic towards nutrients (amino acids and sugars) and signal compounds like flavonoids and the other, nonchemotactic towards amino acids and sugars but positive towards naringenin, the flavonoid present in Cajanus cajan root exudate, were obtained. The plasmid-cured derivative of the parent showed positive response towards amino acids and sugars but was nonchemotactic towards naringenin. A possible presence of dual chemotaxis pathways, one towards nutrients and the other for sensing signal compounds, was thus demonstrated. The possible involvement of naringenin as a chemoattractant in the preliminary stages of this Rhizobium-legume interaction was also established.

Amino Acids↗
PubMed1996

Anomalies in hepatobiliary excretion of technetium-99m-MAG3 preparations.

Technetium-99m-MAG3 is accepted as a renal tubular function agent. However, sporadic liver and gall bladder visualisation during its clinical use is clearly a disadvantage. HPLC-purified 99mTc-MAG3 samples exhibited appreciable hepatobiliary uptake (7%), and an elevated level of such uptake was observed in unpurified kit preparations, which was stated to be associated with the excretory property of the radiolabeled kit impurities. To verify this we attempted to quantitate the hepatobiliary uptake of the kit preparations with that of its radiolabeled components. The contribution of each component toward hepatobiliary uptake of the sample was calculated from their abundance in the chelate mixture and the individual biodistribution of the isolated components. However, the anticipated hepatobiliary uptake of different preparations of 99mTc-MAG3 calculated in this way was always lower than that of the experimental value determined directly. Further work is needed to explain the anomaly.

Animals↗
PubMed1996

Accuracy of pulse oximetry in hypothermic neonates and infants undergoing cardiac surgery.

OBJECTIVES: To assess the accuracy of pulse oximetry under hypothermic conditions in neonates and infants undergoing cardiac surgery, and to assess the effect of probe site as well as probe site skin temperature on the reliability of pulse oximetry. DESIGN: Prospective Study. SETTING: Cardiac operating room and intensive care unit of children's hospital. PATIENTS: Twenty-five infants <3 months of age undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Pulse oximeter readings (Sp O2) from probes placed on the hand and foot were recorded at various skin temperatures and compared with hemoximeter oxygen saturations (Sa O2) obtained on simultaneously drawn arterial blood samples. Core temperature, arterial pressure and vasodilator use were recorded simultaneously. MEASUREMENTS AND MAIN RESULTS: Pulse oximetry bias (Sp O2 - Sa O2) increased to an unacceptable range (>+3% or <-3%) in 45.5% of the readings at foot probe site temperatures of <27 degrees. Pulse oximetry bias was within an acceptable range in 94.7% of the readings at temperatures >29 degrees. There was no significant difference between oximeter readings obtained from two probe sites (hand and foot). Administration of phenoxybenzamine improved the accuracy of pulse oximetry in ten infants at skin temperature of <27 degrees. CONCLUSIONS: Pulse oximetry readings in small infants are likely to be unreliable at skin temperatures of <27 degrees, irrespective of probe site. Intravenous phenoxybenzamine appeared to improve the accuracy of pulse oximetry at low temperatures.

Age Factors↗
PubMed1995

Chemotherapeutic activity of levofloxacin (HR 355, DR-3355) against systemic and localized infections in laboratory animals.

Ofloxacin, its optical isomers levofloxacin (HR 355, DR-3355) and D-ofloxacin (DR-3354) and ciprofloxacin were administered orally to mice and rats which had systemic and localized infections. Both levofloxacin and ciprofloxacin were equally effective in treating systemic murine infections caused by staphylococci. Enterobacteriaceae or Pseudomonas aeruginosa with ED50s ranging from 0.18 to 15.8 mg/kg and 0.42 to 16.3 mg/kg respectively and both these agents were twice as effective as ofloxacin which had an ED50 0.41 to 39.7 mg/kg. In contrast, D-ofloxacin was either inactive or exhibited only modest chemotherapeutic activity against the staphylococci and the Gram-negative organisms tested. When given to mice to treat staphylococcal abscesses and lung infections due to Klebsiella pneumoniae DT-S levofloxacin was up to four times more effective and produced a more pronounced bactericidal effect against the pathogens in vivo than the reference compounds. Despite possessing a similar, if not lesser, in-vitro activity against the infecting pathogens, levofloxacin was more effective than ofloxacin and ciprofloxacin in rats with localized infections caused by Enterobacteriaceae and P. aeruginosa.

Abscess↗
PubMed1995

Longitudinal changes in the diameter of the ductus arteriosus in ventilated preterm infants: correlation with respiratory outcomes.

This study aimed to examine the early natural history of ductal shunting in ventilated preterm infants (< 1500 g) and to document the association between this shunting and respiratory outcomes. The size of the ductal shunt was assessed in 48 infants using serial echocardiographic measurement of colour Doppler internal ductal diameter and pulsed Doppler postductal aortic diastolic flow (PADF). At all postnatal ages, normal antegrade PADF was invariably seen when the ductal diameter was 1.5 mm or less, and was usually abnormal (absent or retrograde) when more than 1.5 mm. Longitudinal progress of ductal diameter fell into three groups: (i) asymptomatic spontaneous closure (n = 31)--in 20 of these infants closure occurred within 48 hours; (ii) symptomatic PDA which enlarged after a postnatal constriction (n = 9); and (iii) symptomatic PDA that showed minimal postnatal constriction (n = 8). Infants in group 2 were significantly less mature and had PDAs which became symptomatic significantly later than those in group 3. Logistic regression showed that ductal shunting had a significant correlation with mean oxygenation index over the first five days but not with ventilator or oxygen days. Gestation had the most significant association with the latter two variables, with atrial shunting also being related to days in oxygen. The preterm duct displays a wide spectrum of postnatal constrictive activity. Symptomatic PDAs usually showed slower early postnatal constriction. Ductal shunting independently related to short term but not long term respiratory outcomes.

Diastole↗
PubMed1994

Assessment of ductus arteriosus shunt in preterm infants supported by mechanical ventilation: effect of interatrial shunting.

We studied 51 preterm infants (< 1500 gm) with serial color Doppler echocardiography to determine the impact of incompetence of the foramen ovale on the hemodynamic implications of shunting through a patent ductus arteriosus. Doppler and two-dimensional echocardiographic measures included left atrial/aortic root ratio, right (RVSV) and left ventricular stroke volumes (LVSV), and outputs to determine relative ventricular outputs (RVSV/LVSV) and to calculate the pulmonary/systemic flow ratio (Qp/Qs), the diameter of the color flow Doppler mapping of interatrial and ductal shunts, pulsed Doppler pattern, and velocity of those shunts. The dominant direction of shunting at the ductal and atrial levels was left to right. In studies with minimal atrial shunting, there was a weak but significant correlation between RVSV/LVSV (1/(Qp/Qs)) and the left atrial/aortic root ratio, LVSV, and output index, but there was a close correlation with the diameter of the color flow Doppler of the shunt within the ductus (r = -0.8). With this diameter used as a constant, increasing color flow Doppler diameter of atrial shunt significantly reduced LVSV and increased RVSV/LVSV (1/(Qp/QS)). In infants with large ductal and atrial shunts, right ventricular output was often greater than left ventricular output. We conclude that atrial shunting has a significant impact on the hemodynamic implications of ductal shunting in many very preterm infants. This renders use of the relative ventricular outputs to calculate Qp/Qs inaccurate as a single measure of shunt size in patent ductus arteriosus. If the shunt is predominantly left to right, the most accurate assessment is provided by color flow ductal shunt diameter.

Atrial Function, Left↗
PubMed1994

Incompetence of the foramen ovale in preterm infants supported by mechanical ventilation.

Fifty-one preterm infants (< 1500 gm) who were supported by mechanical ventilation were studied by use of serial color Doppler echocardiography to determine the hemodynamic impact of incompetence of the foramen ovale. Right and left ventricular stroke volume, measured by two-dimensional and Doppler echocardiography, were used to determine the ratio of pulmonary to systemic flow (Qp/Qs). The diameter of the color flow mapping of any interatrial shunt was measured together with pattern and velocity of that shunt. Ductal patency status was established. Most infants had some atrial shunting. The dominant direction of shunting was left to right within a bidirectional shunt pattern (75%). When the ductus was closed, there was a significant correlation between color Doppler diameter of the atrial shunt and Qp/Qs (r = 0.71). When this diameter was less than 2 mm, there was minimal impact on Qp/Qs. Measurable effects on Qp/Qs were usually seen at diameters > 3 mm when Qp/Qs ratios of up to 2:1 were recorded. Longitudinally, atrial shunting could be divided into four groups. Group 1 (n = 23) had minimal shunt or small shunts (< 3 mm) that resolved early, group 2 (n = 11) had small shunts that persisted, group 3 (n = 9) had large shunts (> 3 mm) that resolved, and group 4 (n = 6) had large shunts that persisted. Clinically there were no significant differences between the groups except that patients in groups 2 to 4 tended to having worse acute lung disease than patients in group 1 and had significantly more chronic lung disease. We conclude that many preterm infants have left-to-right atrial shunts that have a noninvasively measurable hemodynamic impact. This may have an effect on acute and chronic respiratory outcome and is likely to affect assessments of ductal shunting.

Atrial Function, Left↗
PubMed1994

Re-evaluation of the left atrial to aortic root ratio as a marker of patent ductus arteriosus.

The aim of this study was to re-examine the accuracy of the left atrial aortic root ratio (LA:Ao) as a marker of significant patent ductus arteriosus (PDA) in the preterm infant by comparison with direct Doppler echocardiographic assessment. Fifty six infants (< 1500 g) had 463 serial echocardiograms. Firstly the LA:Ao was measured, then the duct was imaged and classified as wide open, restricting, or closed according to two dimensional and Doppler criteria. Probability analysis was performed to test the ability of the LA:Ao to discriminate between a wide open PDA and a restricting or closed duct. Mean LA:Ao was 1.17 and 1.21 when the duct was respectively closed or restricting compared with 1.61 when wide open. Using a LA:Ao of 1.5 as a cut off gives a sensitivity of 79% and specificity of 95% and increases the accuracy over the recommended levels of 1.3 and 1.4. With this cut off there were 20/94 false negatives, these were associated with scans on day 1 and large interatrial shunts. The sensitivity of the LA:Ao increased to 88% if only scans performed after day 1 were analysed. For diagnosing a PDA after day 1, the positive likelihood ratio of an LA:Ao of 1.5 or more was 17.5, and the negative likelihood ratio of an LA:Ao < 1.5 was 0.13. The LA:Ao is still a useful tool in the diagnosis of PDA. It is a simple method which needs less skill and resources than direct PDA imaging and is feasible on neonatal units without direct access to echocardiographic expertise. Its use on the first postnatal day is not recommended.

Anthropometry↗
PubMed1993

Change in blood pressure after treatment of patent ductus arteriosus with indomethacin.

The effect of indomethacin treatment of patent ductus arteriosus (PDA) on blood pressure was studied in 24 preterm infants. PDA was diagnosed clinically and confirmed by echocardiography; the effect of treatment was monitored echocardiographically. Hourly intra-arterial recordings of systolic, diastolic, and mean blood pressure were averaged for the 48 hours before the first dose of indomethacin and for each of the three 24 hour periods after the first dose. In the 16 infants in whom treatment was successful, the average mean blood pressure increased significantly over the three days after the first dose. On the third day after beginning treatment with indomethacin the average increase in mean blood pressure was 10.4 mm Hg. Fourteen of 16 infants showed an increase of 4 mm Hg or more. Systolic and diastolic blood pressure increased significantly by similar amounts, so the pulse pressure did not change. In the eight infants treated unsuccessfully, there was no consistent change in any of the blood pressure parameters. The maximum increase in mean blood pressure was 3 mm Hg. These findings confirm that PDA is one of the determinants of blood pressure in preterm infants. The effect is general and there is no consistent change in pulse pressure when a PDA is closed. A general increase in blood pressure is a useful additional indicator of successful medical ductal closure.

Blood Pressure↗
PubMed1992

In vitro embryotoxicity of petroleum creosote monitored via mouse preimplantation embryo culture.

A mouse preimplantation embryo culture system was utilized to characterize the in vitro embryotoxicity of petroleum creosote (PC), a complex mixture of aliphatic and polycyclic aromatic hydrocarbons. ICR mouse embryos, collected on d 3.5 of gestation (blastocyst stage), were exposed for 1 h to varying concentrations of petroleum creosote in serum-supplemented culture medium. Parallel embryo cultures were exposed to PC in medium supplemented with rodent hepatic S9 microsomal fractions to monitor the role of bioactivation in PC-induced embryotoxicity. Embryos were subsequently cultured in control medium for 72 h and observed for viability as well as specific, time-dependent developmental end points--hatching and attachment to the culture dish at 48 h, and trophoblastic outgrowth with a distinct inner cell mass at 72 h. Embryonic viability varied in inverse proportion to PC concentration. Petroleum creosote caused embryolethal effects at concentrations of 33 micrograms/ml of culture medium and 54 micrograms/ml. Embryotoxicity was not observed at 22 micrograms/ml. Culture supplementation with rodent hepatic S9 fractions did not modify, either qualitatively or quantitatively, the embryotoxicity of PC in vitro. These findings implicate PC as a prenatal toxicant and support environmental and human health concerns regarding PC exposure from PC-containing chemical waste sites.

Animals↗
PubMed1992

Diltiazem potentiates angiotensin II-mediated renal prostacyclin synthesis.

Diltiazem (DIL), a calcium antagonist, has variable effects on renal hemodynamics, and has been considered to act independently of renal prostaglandins (PGs). Angiotensin II (AII) constricts renal vasculature but also increases renal vasodilator PG synthesis. We examined interactions between AII and DIL on [14C]p-aminohippurate ([14C]PAH) clearance, mean arterial pressure (MAP), and urine 6-ketoprostaglandin F1 alpha excretion (U6k) in groups of seven to nine conscious Sprague-Dawley rats. We calculated the renal vascular resistance (RVR) as the ratio of MAP/[14C]PAH clearance. AII infusion (10 ng/kg/min i.v.) increased the RVR by 50-80% for at least 120 min. DIL (1 mg/kg plus 2 micrograms/kg/min) reversed this vasoconstriction but adding indomethacin to DIL prevented the reversal. DIL alone did not change the RVR at 30-60 min after starting an infusion but increased it by 22% at 90-120 min. Adding AII to the DIL infusion actually decreased the RVR and this decrease was abolished by indomethacin. DIL alone had no effect on U6k while AII increased it slightly (1.36 +/- 0.12 to 1.86 +/- 0.22 ng/30 min, n = 6, p less than 0.05), and adding DIL to AII increased it further (3.19 ng/30 min, n = 6, p less than 0.05). We conclude that DIL enhances AII-induced renal prostacyclin synthesis and that this is functionally relevant. This mechanism may explain the reported variability of the renal hemodynamic effects of DIL. Furthermore, DIL-enhanced renal vasodilator PG synthesis may help protect the kidney during vasoconstrictor stress.

6-Ketoprostaglandin F1 alpha↗