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Biomedical subjects

S Datta

Publications and source records attributed to S Datta.

At least 181 records · Page 10Linked to original sources

Isoform specific reductions in Na+,K(+)-ATPase catalytic (alpha) subunits in the nerve of rats with streptozotocin-induced diabetes.

Na+,K(+)-ATPase activity in nerve is reduced in rats with streptozotocin-induced diabetes; three different isoforms of the alpha (catalytic) subunit of the enzyme are present in nerve. Using western blot to determine subunit isoform polypeptide levels in sciatic nerve, we found a substantial reduction in alpha 1-isoform polypeptide (88% at 3 weeks, 94% at 8 weeks) after induction of diabetes by streptozotocin. Reductions in alpha 2 and alpha 3 polypeptide were smaller and not statistically significant. The reduction in amount of all three isoform polypeptides in the nerve of 3-week diabetic animals was corrected by administration of insulin. Accumulation of alpha 1 polypeptide at a nerve ligature indicated that rapid transport of that polypeptide in nerve occurs with normal kinetics. The results implicate a specific marked deficit in alpha 1, much more than alpha 2 or alpha 3, catalytic subunit isoform of Na+,K(+)-ATPase in the pathogenesis of diabetic neuropathy.

Animals↗

Analgesics and ENT surgery. A clinical comparison of the intraoperative, recovery and postoperative effects of buprenorphine, diclofenac, fentanyl, morphine, nalbuphine, pethidine and placebo given intravenously with induction of anaesthesia.

1. Vomiting and restlessness following ENT and eye surgery are undesirable, and may be related to the emetic and analgesic effects of any analgesic given to augment anaesthesia during surgery. 2. To rationalise the choice of analgesic for routine ENT surgery we examined the intraoperative, recovery and postoperative effects following the administration of either buprenorphine (3.0 to 4.5 micrograms kg-1), diclofenac (1 mg kg-1), fentanyl (1.5 to 2.0 micrograms kg-1), morphine (0.1 to 0.15 mg kg-1), nalbuphine (0.1 to 0.15 mg kg-1), pethidine (1.0 to 1.5 mg kg-1) or saline (as control) given with the induction of anaesthesia in 374 patients. A standardised anaesthetic technique with controlled ventilation using 0.6-0.8% isoflurane in nitrous oxide and oxygen was employed. The study population constituted 7 similar groups of patients. 3. Intraoperatively, their effects on heart rate and blood pressure, airway pressure and intraocular pressure, were similar. This implies, most surprisingly, that neither their analgesic nor their histamine releasing effects were clinically evident during surgery. By prolonging the time to extubation at the end of anaesthesia, only buprenorphine, fentanyl, morphine and pethidine provided evidence of intraoperative respiratory depression. 4. Postoperatively, buprenorphine was associated with severe respiratory depression, prolonged somnolence, profound analgesia and the highest emesis rate. Diclofenac exhibited no sedative, analgesic, analgesic sparing, emetic or antipyretic effects. Fentanyl provided no sedative or analgesic effects, but was mildly emetic. Morphine provided poor sedation and analgesia, delayed the requirement for re-medication and was highly emetic. Nalbuphine and pethidine produced sedation with analgesia during recovery, a prolonged time to re-medication and a mild emetic effect. None provided evidence, from analysis of postoperative re-medication times and analgesic consumption, of any pre-emptive analgesic effect. 5. We conclude that nalbuphine (mean dose 0.13 mg kg-1) and pethidine (mean dose 1.35 mg kg-1), given individually as a single i.v. bolus during induction of anaesthesia, are the most efficacious analgesics for routine in-patient ENT surgery.

Adolescent↗

Effects of ephedrine and phenylephrine on maternal and fetal atrial natriuretic peptide levels during elective cesarean section.

The effects of ephedrine and phenylephrine on fetal and maternal plasma atrial natriuretic peptide (ANP) concentrations were studied during 30 elective cesarean sections. After induction of spinal anesthesia, reductions from baseline maternal blood pressure were corrected with one of these pressor agents administered in a double-blinded, randomized manner. Immediately following delivery, umbilical artery (UA) ANP concentrations were significantly higher than umbilical vein (UV) concentrations (pg/ml) for both groups (ephedrine, 120.8 +/- 64.0 vs. 86.8 +/- 40.8, phenylephrine, 125.0 +/- 54.2 vs. 72.4 +/- 31.7), but there were no differences between groups for UA and UV ANP levels. Postpartum maternal ANP concentrations were significantly higher than baseline values in both groups, but again there were no differences between groups. Correlations between total doses of ephedrine or phenylephrine and UA or UV ANP levels did not reach significance. Postpartum maternal (MV2), UA, and UV blood gas variables (pH, PCO2, and PO2) were also not different between groups. These data suggest that effects of pressor doses of ephedrine (beta and alpha agonist) and phenylephrine (alpha agonist) on maternal and fetal ANP levels are not different. Therefore, 1) assuming these pressor drugs stimulate ANP release, this stimulation is not solely mediated by beta receptors and 2) to the extent that fetal ANP influences feto-placental circulatory homeostasis, the effects of ephedrine and phenylephrine on this regulatory mechanism do not appear to be different.

Adult↗

Indicators of quality medical care for the terminally ill in nursing homes.

PURPOSE: To identify medical care indicators for nursing home terminal care. DATA SOURCES: Studies examining care of terminally ill patients were identified using computer, bibliography, and expert searches; input from nursing home medical directors in Maryland; and input from expert geriatricians. STUDY SELECTION: More than 900 articles, books, and abstracts from meetings covering medical care for terminally ill patients were reviewed. Information from more than 100 publications is included. DATA EXTRACTION: Indicators of medical care for terminally ill patients, which can be used to quantify performance with respect to standards, guidelines, and options, were identified initially through review of the literature. DATA SYNTHESIS: Indicators were refined by input from medical directors of Maryland long-term care facilities and subsequent review by expert geriatricians. CONCLUSIONS: Minimum standards for which 100% performance is expected are communication of advance directives, attention to pain control, and attention to relief of dyspnea. Performance indicators for medical care guidelines and options in terminal care of nursing home patients are also described.

Home Care Services↗

Neuronal activity in the caudolateral peribrachial pons: relationship to PGO waves and rapid eye movements.

1. The present study was performed to examine the hypothesis that the caudolateral peribrachial area (C-PBL) may be directly involved in shifting the brain from the nonpontogeniculooccipital (non-PGO)-related states of waking (W) and slow-wave sleep (S) to the PGO-related states of slow-wave sleep with PGO waves (SP) and rapid eye movement (REM) sleep. 2. To test this hypothesis at the cellular level, we have recorded a sample of 226 spontaneously discharging units of the C-PBL during natural sleep-waking cycles in unanesthetized head-restrained cats and have correlated the action-potential data with the PGO waves. 3. Of these 226 cells, 67.26% (n = 152) were called PGO state-on units because they increased or began firing 15-5 s before the first PGO wave of SP and maintained their high firing rate throughout SP (31.30 +/- 6.0 Hz, mean +/- SD) and REM sleep (39.46 +/- 6.70 Hz); their firing rates in W (0.45 +/- 0.85) and S (0.70 +/- 1.26) were much lower. Among these PGO state-on neurons, 28.94% (n = 44) discharged high-frequency (> 500 Hz) spike bursts on the background of tonically increased firing rates during the PGO-related states. Contrastingly, 14.16% (n = 32) of the cells (called PGO state-off units) fired tonically during W (11.54 +/- 4.15) and S (9.43 +/- 3.87) but stopped or decreased firing 25-15 s before the first PGO wave of SP; their activity remained suppressed throughout SP (0.19 +/- 0.44) and REM sleep (0.03 +/- 0.17). The remaining 18.58% (n = 42) cells fired (9-10 Hz) tonically but were unrelated to the wake-sleeping cycle. 4. During SP and REM sleep, primary PGO waves were found to appear with equal frequency in each lateral geniculate body (LGB). During REM sleep these primary waves were ipsilateral to the direction of phasic rapid eye movements as previously reported by Nelson et al. (1983). 5. During SP and REM sleep PGO state-on burst cells fired high-frequency bursts on a background of tonic activity in association with each ipsilateral primary LGB PGO wave. The first spike of a burst preceded the beginning of the negative component of the ipsilateral LGB PGO waves by 25 +/- 7.5 ms. On the basis of their sustained firing and the latency of their PGO-related bursting, we call these neurons long-lead PGO-on burst-tonic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

The role of continuous background infusions in patient-controlled epidural analgesia for labor and delivery.

The use of a background infusion with intravenous patient-controlled analgesia (IV-PCA) increases drug consumption without any additional contribution to analgesia. There are no data on the potential advantage of a background infusion administered with patient-controlled epidural analgesia (PCEA) for labor and delivery. Sixty women were randomized to one of four groups and received either: (a) demand dose PCEA (demand dose = 3 mL; lockout interval = 10 min); (b) continuous infusion plus demand dose PCEA (two separate infusion rates: 3 mL/h and 6 mL/h); or (c) a fixed-rate continuous epidural infusion (CEI) at 12 mL/h. All patients received 0.125% bupivacaine with 2 micrograms/mL of fentanyl. The study protocol was double-blind and placebo-controlled. Visual analog pain scores, motor strength, and bilateral pinprick analgesia were assessed every half hour by a blinded observer. Pain scores, cephalad extent of sensory analgesia, and motor block were no different among the study groups during the first and second stages of labor. Cumulative hourly bupivacaine use was similar among all PCEA study groups. However, use of PCEA (in whatever mode) provided a 35% dose-sparing effect in comparison to CEI. The PCEA groups receiving no background infusion or a 3-mL/h background infusion had a greater need for physician-administered supplemental bupivacaine during the first stage of labor. While not statistically significant, a trend toward increased need for supplementation was seen in these same patient groups over the entire course of labor and delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurements of protein binding of lidocaine throughout pregnancy.

Pregnancy-related anatomic and physiologic changes result in altered pharmacologic and toxicologic responses to local anesthetics. Reductions in serum protein binding have been implicated in enhanced toxic effects. Previous studies have demonstrated these reductions in protein binding only in the term parturient. The present study defines the pattern of protein binding changes of lidocaine throughout gestation. Venous samples were obtained from pregnant patients of varying gestational age, as well as from nonpregnant control patients. The percent free drug at a fixed concentration (2 micrograms/mL) was determined for each sample using an ultrafiltration technique. The free concentration of lidocaine increased significantly throughout gestation, reflecting a corresponding decrease in protein binding. However, these changes were small compared to those in the nonparturient, which suggests that toxicity to lidocaine should not vary during pregnancy.

Adult↗

Differential axonal transport of individual Na,K-ATPase catalytic (alpha) subunit isoforms in rat sciatic nerve.

Three isoforms of the Na,K-ATPase catalytic (alpha) subunit are present in neurons, demonstrated by in situ hybridization of neurons and Western blot of nerve. We used Western blot with antibodies specific for alpha 1, alpha 2 and alpha 3 peptides to measure the accumulation of individual peptides at a ligature on the sciatic nerve. alpha 1 peptide accumulated with kinetics suggesting rapid axonal transport of that isoform within nerve. alpha 2 and alpha 3 peptides did not accumulate at the ligature. These studies provide insight into the dynamics of axonal Na,K-ATPase isoforms.

Animals↗

Synthesis and characterization of fluorescently labeled bovine brain G protein subunits.

G proteins play an important role in transmitting hormonal signals, and fluorescence techniques would be useful to study their cellular distribution and mechanisms. To prepare active fluorescent G protein Go/Gi or beta gamma subunits were reacted with fluorescein isothiocyanate (FITC) to label the alpha (F-alpha) and gamma (F-gamma/beta) subunits or with (iodoacetamido)tetramethylrhodamine (TMR-IAA) to label the beta subunit (TMR-beta gamma). Unreacted dye was removed from the labeled proteins by ultrafiltration, followed by further purification using HPLC gel filtration. The molar ratios of dye to protein were 0.96 +/- 0.15, 0.59 +/- 0.07, and 1.37 +/- 0.09 for labeled alpha,beta, and gamma subunits, respectively. GTP gamma S binding to F-alpha and ADP-ribosylation by pertussis toxin of F-alpha were reduced to 63% and 78% of control, respectively. F-alpha was a heterogeneous population of alpha subunits. Active F-alpha containing less than one (0.7) label/subunit (F-alpha-Mono Q) was separated from unlabeled and multiply labeled F-alpha by Mono Q anion-exchange chromatography. F-alpha-Mono Q displayed reduced GTPase activity (turnover number was 46% of control), while GTP gamma S binding and ADP-ribosylation by pertussis toxin were only decreased to 78% and 82% of control, respectively. TMR-beta gamma and F-gamma/beta retain full function compared to native beta gamma, as measured by three methods: (1) TMR-beta gamma and F-gamma/beta are able to form heterotrimers with alpha o subunits, (2) TMR-beta gamma and F-gamma/beta support the ADP ribosylation of alpha o subunits by pertussis toxin, and (3) TMR-beta gamma and F-gamma/beta inhibit forskolin-stimulated adenylyl cyclase activity. The fluorescent G protein subunits will be valuable tools to study G protein mechanisms in reconstituted membranes and intact cells.

Animals↗

Enhancer detector analysis of the extent of genomic involvement in nervous system development in Drosophila melanogaster.

We conducted a survey of the patterns of gene expression in the central nervous system (CNS) of larvae of the fruitfly Drosophila melanogaster to identify genes that may be important in the development of the CNS, aid in the recognition of basic organizing features that might underlie CNS development, and estimate the extent of the use of information encoded in the genome in the construction of the nervous system. A so-called enhancer detector strategy was used to generate many thousands of lines containing a beta-galactosidase reporter gene. These lines were screened as third-instar larvae for patterns of expression in the developing optic lobes and other portions of the CNS. Most of the lines recovered which evidence staining within the CNS could be included in one of a relatively small number of patterns. A random sample of 594 lines from the larger population screened was selected to quantify the relative frequencies of these patterns, and a more careful analysis of the changes in the patterns of expression with developmental time was done for representative lines of nine of the patterns. These studies demonstrated great variability in the pattern of gene expression as a function of developmental stage. Few, if any, lines showed beta-galactosidase activity limited to the optic lobes; similarly, few lines were identified in which staining was limited to only a small number of cells. Together with the limited number of patterns of gene expression seen, this suggests that in the larval CNS developmental pathways may be controlled by a combinatorial process of gene activity that involves the majority of the genome rather than by having a specific gene specify the fate of only a few neuronal precursors.

Animals↗