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Biomedical subjects

B Subramaniam

Publications and source records attributed to B Subramaniam.

17 recordsLinked to original sources
PubMed2001

Autoxidation of substituted phenols catalyzed by cobalt Schiff base complexes in supercritical carbon dioxide.

This first study of O(2) oxidation (autoxidation) of substituted phenols catalyzed by a dioxygen carrier in supercritical carbon dioxide (scCO(2)) provides additional insights into the established mechanism of reactions that have been much studied in conventional solvents. As has been long believed, the cobalt(II) dioxygen carriers of the class represented by [[N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II)], Co(salen), show both oxidase and oxygenase activities during oxygenation of substituted phenols in scCO(2). The catalytic autoxidation of 2,6-di-tert-butylphenol (DTBP) and 3,5-di-tert-butylphenol (35-DTBP) in scCO(2) was studied by analysis of products in batch reactions with carefully controlled variables, in the presence of a large excess of O(2), at 207 bar of total pressure and a reaction temperature of 70 degrees C. The oxidation of 35-DTBP yielded only traces of products under the same experimental conditions that converted DTBP totally to a mixture of the oxygenation product 2,6-di-tert-butyl-1,4-benzoquinone (DTBQ) and the related product of radical coupling 3,5,3',5'-tetra-tert-butyl-4,4'-diphenoquinone (TTDBQ). The effects on conversion of DTBP to products and on selectivity between the two products were studied for variations in temperature and the concentrations of catalyst, oxygen, and methylimidazole. Selectivity in favor of the O-transfer product DTBQ over the self-coupling of the phenoxy radical was observed upon changing the oxygen concentration. In contrast, selectivity remained unaffected over a wide range of temperatures and catalyst concentrations. The oxygen dependence of both the conversion and selectivity showed saturation effects identifying the dioxygen complex as the effective oxidant in both the initial radical formation step and the oxygenation of that radical. No direct reaction is observed between the electrophilic phenoxy radical and O(2).

Journal Article↗
PubMed2001

Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery.

STUDY OBJECTIVE: To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Tertiary care referral and teaching hospital. PATIENTS: 46 ASA physical status I and II patients who underwent major upper abdominal procedures. INTERVENTIONS: Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively. MEASUREMENTS: A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups. RESULTS: Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups. CONCLUSIONS: The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects.

Abdomen↗
PubMed2001

Dexamethasone is a cost-effective alternative to ondansetron in preventing PONV after paediatric strabismus repair.

This study evaluated the antiemetic efficacy, cost-effectiveness and clinical utility of prophylactic ondansetron and dexamethasone compared with placebo in the prevention of postoperative nausea and vomiting (PONV) in 135 children (2-15 yr, ASA I-II) undergoing strabismus repair. After induction with halothane and nitrous oxide in oxygen or i.v. thiopental, the children received i.v. dexamethasone 1 mg kg(-1) to a maximum of 25 mg, ondansetron 100 microg kg(-1) to a maximum of 4 mg or placebo (n=45). Episodes of PONV were recorded for the first 24 h after the operation. True outcome measures (parental satisfaction score, duration of stay in the postanaesthesia care unit and fast tracking time), therapeutic outcome measures (number needed to prevent (NNTP) PONV) and the cost to benefit a child with each drug were analysed. The incidence and severity of PONV in the first 24 h were significantly less in the dexamethasone and ondansetron groups than in the placebo group (P<0.05). The incidence (P=0.04) and severity (P=0.03) of PONV at the 6-24 h epoch were significantly less in the dexamethasone group than in the ondansetron group. Recovery time (P=0.07), fast tracking time (P=0.6), parental satisfaction scores (P=0.08) and NNTP PONV were comparable (NNTP=2) in both the ondansetron and the dexamethasone group. The cost to benefit a child with dexamethasone was approximately 22 times less than that of ondansetron.

Adolescent↗
PubMed2001

Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect.

UNLABELLED: In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3-15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5-15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10-48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4-36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures. IMPLICATIONS: Ketamine added to epidural morphine given before surgery can decrease postoperative pain by its preemptive effect, opioid potentiation, and prevention of acute opioid tolerance. A single epidural bolus of 1 mg/kg of ketamine with morphine given before major upper-abdominal surgery did not result in a clinically relevant reduction in postoperative pain relief.

Abdomen↗
PubMed2001

Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy.

This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients.

Adolescent↗
PubMed2000

Balancing selection on a floral polymorphism.

The common morning glory, Ipomoea purpurea, exhibits a flower color polymorphism at the W locus throughout the southeastern North America. The W locus controls whether flowers will be darkly pigmented (WW), lightly pigmented (Ww), or white with pigmented rays (ww). In this report, we describe results of a perturbation, or convergence, experiment using five plots designed to determine whether balancing selection operates on the W locus. The pattern of gene frequency changes obtained are indicative of balancing selection operating at the W locus, providing direct evidence that both the alleles are actively maintained by selection.

Gene Frequency↗
PubMed2000

Pre-emptive analgesia with epidural morphine or morphine and bupivacaine.

Studies of preemptive analgesia in humans have shown conflicting results. The study design, patient population and the duration of assessment of postoperative pain are important in the evaluation of preemptive analgesia. We carried out a prospective, randomized, double-blind controlled study in 80 patients of physical status ASA 1-3 undergoing upper abdominal and thoracic surgery. Patients received two epidural injections, one 20 minutes before induction and the other at the end of surgery. Study solution was either morphine (50 micrograms/kg), with or without 0.1% bupivacaine in 10 ml of normal saline, or normal saline alone. The study groups (Pre M, Pre MB) were given either morphine or morphine-bupivacaine before induction and saline at the end of surgery. The control groups (Post M, Post MB) were given saline before induction and morphine or morphine-bupivacaine at the end of surgery. Postoperative pain was assessed with a Visual Analogue Scale (VAS) during coughing and deep breathing at six-hourly intervals for five days. Epidural morphine was given if the VAS exceeded 4. Pre MB compared to Post MB had a significantly increased interval between the analgesic top-ups (P < 0.01) and decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.001). Pre M and Post M were comparable. Pre MB compared to Pre M had significantly decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.0001). Epidural morphine plus bupivacaine is effective as a preemptive analgesic. Morphine plus bupivacaine has better efficacy than morphine given alone before the induction of anaesthesia.

Abdomen↗
PubMed2000

Tethered cord syndrome in children with anorectal malformations.

OBJECT: Anorectal malformations are known to be associated with neurological deficits, which may contribute to the disability suffered by patients with these malformations. This study was undertaken to determine the incidence and pattern of sacral abnormalities in children with anorectal malformations, the incidence and nature of the neurological deficits, and the incidence and nature of operable intraspinal abnormalities in patients with this condition. METHODS: Neurological evaluation was performed in 81 children with anorectal malformations. Plain x-ray films were obtained to identify the presence of sacral abnormalities. The patients with neurological deficits were evaluated for the presence of operable intraspinal anomalies, and when such anomalies were identified, correction of the same was undertaken. In 21% of these children radiographic evidence of sacral abnormalities was shown. Fifteen percent of patients harbored neurological deficits, and 10% harbored operable intraspinal anomalies. In addition, one patient had split notochord syndrome. Patients with operable intraspinal anomalies underwent surgical correction, with resultant neurological improvement. CONCLUSIONS: Bone abnormalities of the sacrum, neurological deficits, and operable intraspinal lesions are not uncommon in children with anorectal malformations. Because the neurological deficits can contribute to the disability suffered by these individuals, we recommend routine screening of patients with anorectal malformations and neurological deficits and/or sacral abnormalities for the early identification and treatment of potentially correctable intraspinal lesions.

Anal Canal↗
PubMed1998

Three-dimensional quantitative structure-activity relationship study of the cannabimimetic (aminoalkyl)indoles using comparative molecular field analysis.

The present study describes the implementation of comparative molecular field analysis (CoMFA) to develop two 3D-QSAR (quantitative structure-activity relationship) models (CoMFA models 1 and 2) of the cannabimimetic (aminoalkyl)indoles (AAIs) for CB1 cannabinoid receptor binding affinity, based on pKi values measured using radioligand binding assays that displace two different agonist ligands, [3H]CP-55940 and [3H]WIN-55212-2. Both models exhibited a strong correlation between the calculated steric-electrostatic fields and the observed biological activity for the respective training set compounds. In light of the basicity of the morpholine nitrogen in the AAIs, separate CoMFA models were built for the AAIs as unprotonated and protonated species. Comparison of the statistical parameters resulting from these CoMFA models failed to provide unequivocal evidence as to whether the AAIs are protonated or neutral as receptor-bound species. Although the training sets of CoMFA model 1 and CoMFA model 2 differed with respect to composition and to the choice of displacement radioligand in each biological assay, their CoMFA StDevCoeff contour plots reveal similarities in terms of identifying those regions around the AAIs that are important for CB1 cannabinoid receptor binding such as the sterically favored region around the C3 aroyl group and the sterically forbidden region around the indole ring. When the experimental pKi values for the training set compounds to displace the AAI radioligand [3H]WIN-55212-2 were plotted against the pKi values as predicted for the same compounds to displace the cannabinoid radioligand [3H]CP-55940, the correlation was moderately strong (r = 0.73). However, the degree of correlation may have been lowered by the structural differences in the compounds comprising the training sets for CoMFA model 1 and CoMFA model 2. Taken together, the results of this study suggest that the binding site region within the CB1 cannabinoid receptor can accommodate a wide range of structurally diverse cannabimimetic analogues including the AAIs.

Animals↗
PubMed1997

Pharmaceutical processing with supercritical carbon dioxide.

Replacement of traditional solvents with "environmentally benign" carbon dioxide is receiving increased attention in pharmaceutical processing. Among the reported applications, particle formation with dense carbon dioxide and the "clean" synthesis of drug compounds using carbon dioxide as a reaction medium hold immense potential for large-scale application in the pharmaceutical industry. This paper provides an overview of these rapidly emerging technologies along with examples of the wide variety of relatively contaminant-free pharmaceutical compounds that have been processed via these technologies on a laboratory scale. Challenges facing successful implementation in practice include demonstration of continuous production and harvesting of particles with desired and reproducible product characteristics. Mathematical models aimed at a better fundamental understanding of the underlying thermophysical phenomena are essential for rational design and scale-up of these technologies.

Carbon Dioxide↗
PubMed1997

Neuroanatomy in Rett syndrome: cerebral cortex and posterior fossa.

Rett syndrome (RS), a neurodevelopmental disorder of unknown etiology occurring almost exclusively in females, is characterized by autistic-like behavior, motor dysfunction, loss of language skills, dementia, and microcephaly. This study is a follow-up and extension of a previously reported neuroimaging study of patients with RS. We replicated previously reported findings with a larger patient population, and the volumetric MRI analysis was extended to include an analysis of neuroanatomy of the posterior fossa. Twenty girls with RS were compared with individually age- and gender-matched normal controls. Patients with RS showed global reduction in gray- and white-matter volumes. The prefrontal, posterior-frontal, and anterior-temporal regions showed the largest bilateral decrease in gray-matter volume, whereas white-matter volume was uniformly reduced throughout the brain. We found confirmation for the preferential reduction in caudate nucleus volume. However, we observed no preferential reduction in midbrain volume despite a preferential reduction in the midsagittal area of this region. We also present an individual case comparison between monozygotic twins discordant for RS.

Adolescent↗
PubMed1995

The role of visual attention in saccadic eye movements.

The relationship between saccadic eye movements and covert orienting or visual spatial attention was investigated in two experiments. In the first experiment, subjects were required to make a saccade to a specified location while also detecting a visual target presented just prior to the eye movement. Detection accuracy was highest when the location of the target coincided with the location of the saccade, suggesting that subjects use spatial attention in the programming and/or execution of saccadic eye movements. In the second experiment, subjects were explicitly directed to attend to a particular location and to make a saccade to the same location or to a different one. Superior target detection occurred at the saccade location regardless of attention instructions. This finding shows that subjects cannot move their eyes to one location and attend to a different one. The result of these experiments suggest that visuospatial attention is an important mechanism in generating voluntary saccadic eye movements.

Attention↗
PubMed1993

Structure-activity relationships for cannabinoid receptor-binding and analgesic activity: studies of bicyclic cannabinoid analogs.

Cannabimimetic compounds, such as delta 9-tetrahydrocannabinol (delta 9-THC), evoke analgesia in addition to other behavioral responses in humans and animals. The cannabinoid receptor mediating this response has been characterized by its ability to bind the cannabinoid agonist [3H]CP-55,940 and to inhibit adenylyl cyclase via Gi. An investigation of structural requirements for antinociceptive activity of cannabinoid structures led to the development of a simple bicyclic cannabinoid agonist, CP-47,497, that possessed a spectrum of cannabinoid activities in animals that resembled that of delta 9-THC. The present investigation examines several series of CP-47,497 analogs for their binding affinity at the cannabinoid receptor and their ability to evoke analgesia in rodents. Analogs substituted at the C-3 alkyl side chain exhibited maximal affinity for the cannabinoid receptor with side chains of seven or eight carbons in length. Analgesic potency paralleled the receptor-binding affinity. The cyclohexyl ring was optimized as a six- or seven-membered ring structure for binding as well as analgesic activity. Cyclohexyl alkyl side chain extensions of up to four carbons in length had little influence on the affinity for the receptor or analgesic activity. Hydroxyalkyl side chains exhibited optimal binding affinity and antinociceptive activity at three or four carbon atoms in length; however, polar groups closer to the ring diminished binding to the receptor. The importance of the phenolic and cyclohexyl hydroxyl groups for binding affinity was demonstrated. In general, analgesic activity correlated well with the affinity of these analogs for the cannabinoid receptor. Exceptions could be explained by metabolic transformations likely to occur in vivo.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful for optimum scheduling of subsequent bolus injections in a multiple bolus dosing regimen. There are no reported applications of the FFT method to solve repeated input functions in either the chemical engineering or pharmaceutical science literature. Thus, the application of FFT method to solve multiple bolus injections is a unique one. Use of this FFT based analysis as a predictor tool can limit the number of costly experiments which are being done now to achieve this purpose. Even though the model in its present form is simplified, the analysis thereof has nevertheless led to a better understanding of the various factors that must be taken into account for rational design of drug therapy.

Drug Administration Routes↗
PubMedDate not supplied

Balanced interactions in ganglion-cell receptive fields.

Receptive fields of retinal ganglion cells in turtle have excitatory and inhibitory components that are balanced along the dimensions of wavelength, functional ON and OFF responses, and spatial assignments of center and surround. These components were analyzed by spectral light adaptations and by the glutamate agonist, 2-amino-4-phosphonobutyric acid (APB). Extracellular recordings to stationary and moving spots of light were used to map changes in receptive fields. ON spike counts minus OFF spike counts, derived from flashed stationary light spots, quantified functional shifts by calculating normalized mean response modulations. The data show that receptive fields are not static, but rather are dynamic arrangements which depend on linked, antagonistic balances among the three dimensions of wavelength, ON and OFF response functions, and center/surround areas.

Action Potentials↗
PubMedDate not supplied

Edge complexity and partial volume effects.

PURPOSE: The accuracy of MR brain image segmentation is limited by so-called partial volume effects. We hypothesized that "edge complexity" (i.e., tissue class interface border complexity) significantly influences the magnitude of such effects. METHOD: To investigate partial volume effects and provide a vehicle for validation of segmentation algorithm accuracy in brain MRI. We developed a computer simulation, the "gigabrain." The simulation is based on interpolated (supersampled) data from actual MR studies. The voxels are assigned to one of five compartments (gray matter, white matter, CSF, fat, or "background"), the compartment interfaces are "jittered" to add high frequency "signal" or "edge complexity," and the voxels are populated with appropriate values determined from human data, low pass filtered (based on the MR scanner's point spread function), and subsampled back to the sampling and voxel size of the original MR data set. RESULTS: In comparison studies with actual phantoms and human MR data, our simulation approach was able to produce images whose appearance and quantitative values were comparable with the actual data, but only when edge complexity was added to the original MR data. CONCLUSION: Edge complexity is a significant source of partial volume effects. MR simulations must include edge complexity to adequately test segmentation algorithms.

Adipose Tissue↗