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Biomedical subjects

R Ramanathan

Publications and source records attributed to R Ramanathan.

At least 19 recordsLinked to original sources
PubMed2001

Cardiorespiratory events recorded on home monitors: Comparison of healthy infants with those at increased risk for SIDS.

CONTEXT: Home monitors designed to identify cardiorespiratory events are frequently used in infants at increased risk for sudden infant death syndrome (SIDS), but the efficacy of such devices for this use is unproven. OBJECTIVE: To test the hypothesis that preterm infants, siblings of infants who died of SIDS, and infants who have experienced an idiopathic, apparent life-threatening event have a greater risk of cardiorespiratory events than healthy term infants. DESIGN: Longitudinal cohort study conducted from May 1994 through February 1998. SETTING: Five metropolitan medical centers in the United States. PARTICIPANTS: A total of 1079 infants (classified as healthy term infants and 6 groups of those at risk for SIDS) who, during the first 6 months after birth, were observed with home cardiorespiratory monitors using respiratory inductance plethysmography to detect apnea and obstructed breathing. MAIN OUTCOME MEASURES: Occurrence of cardiorespiratory events that exceeded predefined conventional and extreme thresholds as recorded by the monitors. RESULTS: During 718 358 hours of home monitoring, 6993 events exceeding conventional alarm thresholds occurred in 445 infants (41%). Of these, 653 were extreme events in 116 infants (10%), and of those events with apnea, 70% included at least 3 obstructed breaths. The frequency of at least 1 extreme event was similar in term infants in all groups, but preterm infants were at increased risk of extreme events until 43 weeks' postconceptional age. CONCLUSIONS: In this study, conventional events are quite common, even in healthy term infants. Extreme events were common only in preterm infants, and their timing suggests that they are not likely to be immediate precursors to SIDS. The high frequency of obstructed breathing in study participants would likely preclude detection of many events by conventional techniques. These data should be important for designing future monitors and determining if an infant is likely to be at risk for a cardiorespiratory event.

Airway Obstruction↗
PubMed2001

A note on the use of the analytic hierarchy process for environmental impact assessment.

Environmental impact assessment (EIA) is an intrinsically complex multi-dimensional process, involving multiple criteria and multiple actors. Multi-criteria methods can serve as useful decision aids for carrying out the EIA. This paper proposes the use of a multi-criteria technique, namely the analytic hierarchy process (AHP), for the purpose. AHP has the flexibility to combine quantitative and qualitative factors, to handle different groups of actors, to combine the opinions expressed by many experts, and can help in stakeholder analysis. The main shortcomings of AHP and some modifications to it to overcome the shortcomings are briefly described. Finally, the use of AHP is illustrated for a case study involving socio-economic impact assessment. In this case study, AHP has been used for capturing the perceptions of stakeholders on the relative severity of different socio-economic impacts, which will help the authorities in prioritizing their environmental management plan, and can also help in allocating the budget available for mitigating adverse socio-economic impacts.

Animals↗
PubMed2001

Acute, subacute, and subchronic oral toxicity studies of 1,1-dichloroethane in rats: application to risk evaluation.

1,1-Dichloroethane (DCE) is a solvent that is often found as a contaminant of drinking water and a pollutant at hazardous waste sites. Information on its short- and long-term toxicity is so limited that the U.S. EPA and ATSDR have not established oral reference doses or minimal risk levels for the volatile organic chemical (VOC). The acute oral LD(50) in male Sprague-Dawley (S-D) rats was estimated in the present study to be 8.2 g/kg of body weight (bw). Deaths appeared to be due to CNS depression and respiratory failure. In an acute/subacute experiment, male S-D rats were given 0, 1, 2, 4, or 8 g DCE/kg in corn oil by gavage for 1, 5, or 10 consecutive days. The animals were housed in metabolism cages for collection of urine and sacrificed for blood and tissue sampling 24 h after their last dose. There were decreases in body weight gain and relative liver weight at all dosage levels, as well as increased renal nonprotein sulfhydryl levels at 2 and 4 g/kg after 5 and 10 days. Elevated serum enzyme levels, histopathological changes, and abnormal urinalyses were not manifest. For the subchronic study, adult male S-D rats were gavaged with 0.5, 1, 2, or 4 g DCE/kg 5 times weekly for up to 13 weeks. Animals receiving 4 g/kg exhibited pronounced CNS depression, with more than one-half dying by week 11. The 2-g/kg rats exhibited moderate CNS depression. One 2-g/kg rat died during week 6. There were very few manifestations of organ damage in animals that succumbed or in survivors at any dosage level. Decreases in bw gain and transient increases in enzymuria were noted at 2 and 4 g/kg. Serum enzyme levels and blood urea nitrogen were not elevated, nor were glycosuria or proteinuria present. Chemically induced histological changes were not seen in the liver, kidney, lung, brain, adrenal, spleen, stomach, epididymis, or testis. Hepatic microsomal cytochrome P450 experiments revealed that single, high oral doses of DCE did not alter total P450 levels, but did induce CYP2E1 levels and activity and inhibit CYP1A1 activity. These effects were reversible and regressed with repeated DCE exposure. There was no apparent progression of organ damage during the 13-week subchronic study, nor appearance of adverse effects not seen in the short-term exposures. One g/kg orally (po) was found to be the acute, subacute, and subchronic LOAEL for DCE, under the conditions of this investigation. In each instance, 0.5 g/kg was the NOAEL.

Acetylglucosamine↗
PubMed2001

Towards the control of a powered orthosis for people with muscular dystrophy.

The paper describes the development of a passive/active orthosis for people with limited anti-gravity strength in their arms. This is symptomatic of conditions such as muscular dystrophy and spinal muscular atrophy. A passive orthosis was designed and developed using linear elastic elements. The system is being tested with children with disabilities and preliminary results are encouraging. An RT200 robot was also used as a test-bed for an active orthosis. The robot was instrumented with a six-axis force/torque sensor at the end-effector. The force acted as the input to the robot. The robot kinematics and dynamics were modelled. A number of control schemes were implemented on the test-bed including force proportional to velocity and acceleration; these schemes were evaluated with two subjects.

Arm↗
PubMed2000

Liquid chromatography/mass spectrometry methods for distinguishing N-oxides from hydroxylated compounds

This study describes the application of liquid chromatography/mass spectrometry (LC/MS) methods for distinguishing between aliphatic and aromatic hydroxylations and between hydroxylations and N-oxidations. Hydroxylations and N-oxidations are common biotransformation reactions of drugs. Electrospray (ESI) and atmospheric pressure chemical ionization (APCI) were used to generate ions from liquid chromatographic effluents. ESI-MS, ESI-MS/MS, APCI-MS, and APCI-MS/MS experiments were performed on several metabolites and derivatives of loratadine (a long-acting and nonsedating tricyclic antihistamine) using an ion trap mass spectrometer (LCQ) and a triple-quadrupole mass spectrometer (TSQ). The observations are as follows: (1) LC/ESI-MS produced predominantly [M + H]+ ions with minor fragmentation. (2) LC/ESI-MS/MS data, however, showed a predominant loss of water from metabolites with aliphatic hydroxylation while the loss of water was not favored when hydroxylation was phenolic. N-Oxides (aromatic and aliphatic) showed only a small amount of water loss in the MS/MS spectra. (3) Under LC/APCI-MS conditions, aliphatic hydroxylation could be readily distinguished from aromatic hydroxylation based on the extent of water loss. In addition, N-oxides produced distinct [M + H - O]+ ions. These [M + H - O]+ ions were not produced in the APCI-MS spectra of hydroxylated metabolites. (4) Similar to the ESI-MS/MS spectra, the APCI-MS/MS spectra from the (M + H)+ ions of N-oxides yielded a small amount of water loss but no [M + H - O]+ ions. These results indicate that LC/APCI-MS can be used to distinguish between hydroxylated metabolites and N-oxides.

Journal Article↗
PubMed2000

High frequency ventilation: basic concepts and clinical application.

High frequency ventilation (HFV) is a mode of therapy that improves gas exchange with pressure fluctuations much lower than that required for conventional ventilation. HFV is efficacious in the "rescue" management of infants with respiratory failure. Although each HFV system has functional characteristics that are design related, it now appears that when used with similar treatment strategies and within functional limitations, similar outcomes can be achieved. Ideally, the clinician or the operator should be familiar with the basic concepts of different high frequency ventilators to achieve maximal benefits from using these devices in infants with respiratory failure.

High-Frequency Ventilation↗
PubMed2000

Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity.

OBJECTIVE: To evaluate the short-term outcomes for laparoscopic Roux-en-Y gastric bypass in 275 patients with a follow-up of 1 to 31 months. SUMMARY BACKGROUND DATA: The Roux-en-Y gastric bypass is a highly successful approach to morbid obesity but results in significant perioperative complications. A laparoscopic approach has significant potential to reduce perioperative complications and recovery time. METHODS: Consecutive patients (n = 275) who met NIH criteria for bariatric surgery were offered laparoscopic Roux-en-Y gastric bypass between July 1997 and March 2000. A 15-mL gastric pouch and a 75-cm Roux limb (150 cm for superobese) was created using five or six trocar incisions. RESULTS: The conversion rate to open gastric bypass was 1%. The start of an oral diet began a mean of 1.58 days after surgery, with a median hospital stay of 2 days and return to work at 21 days. The incidence of early major and minor complications was 3.3% and 27%, respectively. One death occurred related to a pulmonary embolus (0.4%). The hernia rate was 0.7%, and wound infections requiring outpatient drainage only were uncommon (5%). Excess weight loss at 24 and 30 months was 83% and 77%, respectively. In patients with more than 1 year of follow-up, most of the comorbidities were improved or resolved, and 95% reported significant improvement in quality of life. CONCLUSION: Laparoscopic Roux-en-Y gastric bypass is effective in achieving weight loss and in improving comorbidities and quality of life while reducing recovery time and perioperative complications.

Adult↗
PubMed2000

Analysis of arm trajectories of everyday tasks for the development of an upper-limb orthosis.

Spatiotemporal arm and body movements of able-bodied subjects performing nine everyday tasks were recorded for the purpose of guiding the development of an upper-limb orthosis. To provide a user the opportunity to carry out these tasks with natural movements, the orthosis should allow replication of the measured trajectories. We outline the orthosis architecture, which supports the user's upper arm and forearm, and analyze the movement data to obtain orthosis design specifications. Trajectories were obtained using six-degree-of-freedom magnetic position sensors affixed to the wrist, elbow, shoulder, trunk and head. Elbow trajectory data were decomposed into ranges along the principle Cartesian axes to provide a generally useful envelope measure. The smallest Cartesian parallel-piped that contained the elbow trajectories for most tasks was approximately 30 cm front/back, 15 cm side/side, and 17 cm up/down. A rough lower bound estimate obtained by asking subjects to repeat the tasks while minimizing elbow movement substantially reduced movement in the up/down and side/side dimensions. Elbow angles were generally in the range 50 degrees-150 degrees, and the angle of the forearm with respect to vertical was 10 degrees-110 degrees. Raw trajectory data may be downloaded from www://asel.udel.edu/robotics/orthosis/range.h tml.

Activities of Daily Living↗
PubMed2000

Bioactive transforming growth factor-beta in the lungs of extremely low birthweight neonates predicts the need for home oxygen supplementation.

Transforming growth factor-beta (TGF-beta) is a peptide implicated in tissue injury and repair but its role in the premature human lung remains unclear. In the present study, we used a TGF-beta responsive-promoter-luciferase construct in mink lung epithelial cells to quantify levels of biologically active TGF-beta (BA-TGF-beta) in the endotracheal aspirate (ETA) fluid from 16 extremely low birthweight neonates [6 M/10 F, mean GA 26 weeks (range 23-30), mean BW 774 g (range 555-1,075)]. ETA fluid was obtained on day 1 and then every 4 days up to 32 days. BA-TGF-beta levels were low (92 +/- 19 pg/ml) in the first 24 h of life and then increased 5- to 10-fold with peak BA-TGF-beta levels (400 +/- 50 pg/ml) on day 20-25. BA-TGF-beta levels were higher in male than female infants (p = 0.0056). Prenatal steroids decreased significantly the amount of BA-TGF-beta recovered. High initial levels of BA-TGF-beta persisted over time and were predictive of the need for oxygen therapy at home. We conclude that abundant BA- TGF-beta is present in the lungs of preterm infants and speculate that it may be involved in inflammatory and repair processes encountered in acute and chronic lung disease.

Bronchoalveolar Lavage Fluid↗
PubMed2000

Systemic to pulmonary collaterals in very low birth weight infants: color doppler detection of systemic to pulmonary connections during neonatal and early infancy period.

OBJECTIVE: Angiographic visualization of systemic to pulmonary collaterals (SPC) has been documented in premature infants needing prolonged ventilatory support. Noninvasive identification of such communications in premature infants was reported recently. The purpose of this study was to describe: 1) incidence, 2) clinical findings and implications, and 3) short-term follow-up of SPC diagnosed by echocardiography in very low birth weight (VLBW) infants admitted to the neonatal intensive care unit. METHODS: From December 1, 1994 to August 31, 1996, 196 infants with birth weight <1500 g were admitted to the neonatal intensive care unit; 133 of them received serial echocardiographic evaluations at 1 to 2 days, at 2 weeks, and at 1, 2, and 3 months of life. Follow-up echocardiograms were scheduled at 6 months and 1 year of age for patients with SPC persisting at 3 months of age. RESULTS: SPC were demonstrated in 88 patients (66%) at 1 to 90 days of life (mean 28 days). In most cases, the SPC originated at the distal aortic arch or the proximal descending aorta. Ten patients (11%) were treated for congestive heart failure. The symptoms improved and anticongestive therapy was discontinued in 9. One patient with persistent congestive heart failure underwent therapeutic cardiac catheterization and 1 prominent SPC was embolized. CONCLUSIONS: The incidence of SPC in VLBW infants is much higher than previously reported. We postulate that SPC are bronchopulmonary communications that enlarge and/or proliferate in response to a given stimulus. These communications are associated with increased time on positive pressure ventilation and length of stay in the hospital. SPC may lead to pulmonary edema and should be searched for in VLBW infants with a more complicated course. Echocardiographic examination with color Doppler performed in premature infants to evaluate left to right shunts should include careful search for systemic to pulmonary collaterals.echocardiography, systemic to pulmonary collaterals, aortopulmonary collaterals, prematurity, pulmonary edema.

Aorta, Thoracic↗
PubMed1999

A randomized trial of nasopharyngeal-synchronized intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants after extubation.

OBJECTIVE: To prospectively compare the incidence of respiratory failure in premature infants randomized to receive either nasopharyngeal continuous positive airway pressure (NPCPAP) or nasopharyngeal-synchronized intermittent mandatory ventilation (NP-SIMV) in the immediate postextubation period. STUDY DESIGN: This is a prospective study of very low birth weight (VLBW) infants randomized at the time of extubation to receive either NPCPAP or NP-SIMV in a university-based level III neonatal intensive care unit. Statistical analysis were performed with the Mann-Whitney U test for continuous and ordinal variables, and with the chi-squared test or Fisher's exact test for categorical variables. RESULTS: A total of 41 VLBW infants were studied; 19 were in the NPCPAP group, and 22 were in the NP-SIMV group. Respiratory failure after extubation in the NP-SIMV group was significantly lower that in the NPCPAP group (5% vs 37%, respectively (p = 0.016). No statistically significant differences between groups with regard to demographics, severity of initial illness and associated complications, time to extubation, ventilatory management before extubation, weight, age, or nutritional status at the time of extubation were noted.

Female↗
PubMed1999

Real-time t(11;14) and t(14;18) PCR assays provide sensitive and quantitative assessments of minimal residual disease (MRD).

Non-Hodgkin's lymphoma (NHL) arises as a clonal transformation of normal B and T cell differentiation and is often characterized by a higher incidence of specific chromosomal translocations. We have developed real-time TaqMan PCR assays directed toward two of these tumor-associated DNA markers, the t(14;18)(q32;q21.3) at the major breakpoint region of the bcl-2 gene and the t(11;14)(q13;q32) at the bcl-1 major translocation cluster. During analysis of serial dilutions of t(14;18)-positive DNA, the t(14;18) real-time PCR was at least as sensitive as nested PCR and demonstrated enhanced quantitative potential. Moreover, in a blinded comparison of the t(14;18) real-time PCR and a clinically validated nested PCR protocol using 134 cell line and patient DNA samples, the real-time PCR detected the translocation in 30.0% more cases than nested PCR. Both the t(14;18) and t(11;14) real-time PCR assays were used to quantitate minimal residual disease (MRD) in an NHL clinical trial assessing the safety and efficacy of a tumor-purging protocol in autologous stem cell transplantation. The assays were also used to evaluate disease depletion in an ex vivo tumor spiking model in which normal peripheral blood was spiked with tumor cell lines and processed according to the clinical purging method. PCR data from both the clinical trial and the ex vivo model demonstrated a 4 to 6 log reduction in tumor cells during CD34+ and CD34+ Thy-1+ enrichment. Because the t(14;18) and t(11;14) real-time PCR assays are very sensitive, quantitative, rapid, and require no post-PCR manipulation, they may serve as practical alternatives to nested PCR.

Antigens, CD34↗
PubMed1999

Reverse aortic arch flow secondary to severe pulmonary hypertension in the neonate.

The purpose of this study is to determine the incidence of reverse aortic arch flow in newborn infants with pulmonary hypertension, and no other identifiable cause for flow reversal, being considered for extracorporeal membrane oxygenation (ECMO) 2) compare the left ventricular output, and 3) outcomes, of these infants, with those in the group of patients with normal arch flow. We reviewed the medical records and echocardiograms of all infants referred to our institution for extracorporeal membrane oxygenation support for pulmonary hypertension, between August 1994 and April 1996. Neonates with pulmonary hypertension and reverse aortic arch flow had significantly lower left ventricular output (p = 0.005), and had significantly higher mortality (p = 0.04), than those with normal aortic arch flow. They required significantly higher ventilatory support (p = 0.01) and tended to need more inotropic support. Reverse aortic arch flow in newborn infants with pulmonary hypertension, and no other cause for the reverse flow, indicates significantly decreased left ventricular output, and may be a marker for a more difficult clinical course and poor prognosis. In this group of patients with pulmonary hypertension, the survival was significantly higher in infants with no PDA or with pure left to right shunt across a PDA.

Aorta↗
PubMed1998

Improved quantitation of minimal residual disease in multiple myeloma using real-time polymerase chain reaction and plasmid-DNA complementarity determining region III standards.

The complementarity determining region III of the rearranged immunoglobulin heavy chain gene has been the target for tumor-specific PCR assays for the detection and follow-up of B-cell malignancies. Previously, these assays have relied on gel-based end point data collection methods (i.e., band densitometry) and, thus, have provided at best a semiquantitative assessment of tumor levels. We show the development of a novel, real-time TaqMan PCR assay to quantitate residual multiple myeloma cells in clinical samples after high-dose chemotherapy and autologous stem cell transplantation. We provide evidence that real-time PCR is reproducible, sensitive, and quantitative. In a 40-replicate PCR experiment targeting the beta-actin gene, the coefficient of variation for threshold cycle data was 1.6%, whereas it increased to 13.6% and 31%, respectively, for end point fluorescence and gel densitometry. Moreover, in an experiment directly comparing standard curves obtained from band densitometry and threshold cycle data, the standard curve constructed from threshold cycle data had a multiple R2 value of 1.00 and demonstrated a dynamic range >4 logs, compared with the 2-log linear range of gel densitometry. Finally, we show that when a complementarity determining region III-specific PCR primer is used in conjunction with a consensus primer for the immunoglobulin heavy chain joining gene, plasmid DNA can be used as a readily available and effective substitute for clonal plasma-cell genomic DNA when preparing standards. By applying real-time PCR to the analysis of clinical samples, we are able to quantitate levels of tumor involvement with unparalleled reproducibility and statistical confidence. Real-time PCR technology may well provide the accuracy and reliability necessary for minimal residual disease detection to have real prognostic significance.

Base Sequence↗
PubMed1998

The effects of IL-10 on proinflammatory cytokine expression (IL-1beta and IL-8) in hyaline membrane disease (HMD).

Deficient expression of the counterregulatory cytokine IL-10 by lung inflammatory cells may facilitate chronic inflammation and the pathogenesis of hyaline membrane disease (HMD), in premature infants. To determine if pathways which regulate proinflammatory cytokines in response to human recombinant IL-10 (rIL-10) were functional in the lungs of these neonates, bronchoalveolar lavage (BAL)-derived lung inflammatory cells (predominantly macrophages and neutrophils) from infants with HMD were cultured in the presence of lipopolysaccharide (LPS) and increasing concentrations of (rIL-10). The expression of IL-1beta and IL-8 protein was assessed 24 h later. IL-10 protein was also measured from the BAL aspirates of these newborns at 4-day intervals over the first month of life. In cell culture IL-1beta expression was inhibited by rIL-10 in a dose-dependent fashion while IL-8 expression was inhibited by higher concentrations of rIL-10. IL-10 protein was undetectable from BAL fluid of the premature infants sampled over 28 days. The results demonstrate that lung inflammatory cells, which do not express IL-10 in vivo, are capable of responding to rIL-10 in cell culture with reduction of IL-1beta and IL-8 expression. These data support the rationale for the development of rIL-10 as a potential anti-inflammatory agent in the treatment of HMD.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Bioavailability of intranasal promethazine dosage forms in dogs.

Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

Administration, Intranasal↗