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Biomedical subjects

R Sankar

Publications and source records attributed to R Sankar.

At least 19 recordsLinked to original sources
PubMed1997

GABA metabolism during status epilepticus in the developing rat brain.

The rate of synthesis of GABA, the major inhibitory neurotransmitter, was determined in parietal cortex and hippocampus during SE induced by systemic administration of lithium (3 mEq/kg) followed 20 h later by pilocarpine (100 mg/kg) in 1-4-week-old rats. Our results show that the immature hippocampus is better capable of maintaining GABA synthesis in the face of SE at the earliest stages of development studied (74.1% of basal in 1-week-old) and that development results in a progressive decline in the ability to maintain GABA synthesis in the face of SE (44.1% of basal by 4 weeks) that may parallel the ontogeny of self-sustaining seizures. Our data describe an aspect of developmental GABA neurochemistry which may in part explain the relative resistance of the immature hippocampus to seizure spread and of certain types of seizure-induced damage.

Age Factors↗
PubMed1997

Induction of brain derived neurotrophic factor mRNA by seizures in neonatal and juvenile rat brain.

Seizures have been shown to regulate neurotrophin expression in adult mammalian brain. However, there has been some controversy as to whether seizures affect neurotrophin expression in very immature brain. In the present study, we have examined the effects of seizures induced by pilocarpine following lithium pretreatment or by kainic acid on the expression of brain derived neurotrophic factor (BDNF) mRNA in developing rat brain by in situ hybridization. In adult brain, lithium/pilocarpine treatment resulted in dramatic elevations of hybridization to BDNF cRNA in neocortical and limbic brain structures. In developing brain, lithium/pilocarpine induced elevations of BDNF mRNA in the hippocampus, piriform and entorhinal cortex as early as postnatal day 7 (P7). By P12, the pattern of enhanced expression was similar to that of the adult. Maximal elevations of hybridization were present 2 to 4 h following pilocarpine injection. Electrophysiological recording demonstrated that lithium/pilocarpine treatment resulted in electrographic seizures. Pretreatment with diazepam blocked the seizures as well as the elevation of BDNF mRNA. Kainic acid induced elevations of BDNF mRNA in the CA3 subfield of the hippocampal pyramidal cell layer, but not in other brain areas in pups as young as P7. These data indicate that seizures during the neonatal and early juvenile period of brain development induce elevated BDNF mRNA expression, and that different methods of seizure induction yield different patterns of elevations in hybridization. Furthermore, BDNF may be capable of playing a role in the development of seizure susceptibility in the immature brain.

Animals↗
PubMed1997

Serum neuron-specific enolase is a marker for neuronal damage following status epilepticus in the rat.

We determined the serum concentrations of neuron-specific enolase (s-NSE) in rat pups of 1, 2, 3, and 4 weeks of age and in adult rats that were subjected to lithium-pilocarpine status epilepticus (SE). Damage to brain regions was rated on a scale of 0 (no damage) to 5 (> 50% cell loss). Rat pups of 1-2 weeks of age had a higher baseline s-NSE than the adults. Following SE, 1 week old rat pups had no elevation of s-NSE and no histologic evidence of damage. At older ages the increases in NSE ranged from 18.9 +/- 0.8 ng/ml in the 2 week old (vs. 11.5 +/- 0.5 control) to 35.8 +/- 2.1 ng/ml in the 3 week old (vs. 12.1 +/- 0.8 control). In the adult rats s-NSE increased from 5.4 +/- 0.4 in the control animals to 30.4 +/- 1.3 after SE. The different brain regions examined had distinctive ontogenic profiles for SE-induced damage. Elevation of s-NSE after SE correlated with overall histologic evidence for damage.

Animals↗
PubMed1997

Vigabatrin.

Vigabatrin is a structural analogue of gamma amino butyric acid (GABA), which binds irreversibly to GABA-transaminase causing increased brain levels of GABA. It is an important advance in the medical management of children with epilepsy. It appears to be particularly effective in the treatment of infantile spasms, especially when caused by tuberous sclerosis. It is also effective in the treatment of partial seizures and some generalized seizures including those of the Lennox-Gastaut syndrome. However, myoclonic seizures may be made worse by vigabatrin. It is not yet approved for use in the United States but it is approved throughout most of the rest of the world including Canada and Mexico. Release in the United States is expected in the near future.

Animals↗
PubMed1997

Developmental outcomes in children receiving resection surgery for medically intractable infantile spasms.

Two-year postsurgical developmental outcomes were assessed in 24 children with infantile spasms who underwent resective surgery. The mean age of onset of infantile spasms was 12.0 weeks and the mean age at surgery was 20.8 months. Developmental outcomes were assessed using the Vineland Adaptive Behavior Scales (VABS). There was a significant increase in developmental level at 2 years postsurgery compared with presurgical levels. At 2 years postsurgery only one of the children in this series was severely retarded. The developmental outcomes of patients in the series were better than those in prior studies of symptomatic patients receiving medical treatment for infantile spasms. It is surprising that the children in the UCLA series frequently had developmental outcomes equal to and sometimes superior to other groups of children with infantile spasms, since all the UCLA patients were symptomatic, had neurologic deficits and had failed to respond to adrenocorticotrophic hormone (ACTH) and antiepileptic drugs. The 2-year postsurgery developmental outcomes were best for the children who received surgery when they were relatively young and who had the highest level of developmental attainments presurgically.

Activities of Daily Living↗
PubMed1996

Hemispherectomy for intractable seizures in children: a report of 58 cases.

Fifty-eight children who underwent anatomical, functional, or modified anatomical hemispherectomy for intractable seizures from 1986 to 1995 were evaluated for seizure control, motor function, and complications. Age at surgery ranged from 0.3 to 17.3 years (median 2.8 years). Twenty-seven anatomical, 27 functional, and 4 modified anatomical hemispherectomies were performed. Seizure control and motor function in the 50 patients with more than 1 year follow-up revealed a 90% or better reduction in seizure frequency in 44/50 (88%) overall: 19/22 (86%) anatomical, 23/26 (89%) functional, and 2/2 modified anatomical. Motor function of the preoperatively hemiparetic extremities was improved or unchanged postoperatively in 38/50 (76%) of the patients. Complications included one intraoperative death, one late death from shunt obstruction managed elsewhere, late postoperative seizure breakthrough requiring reoperation and further disconnection in 5/27 functional hemispherectomy patients, mild cerebrospinal fluid infections in 3/27 anatomical hemispherectomy patients, and hydrocephalus requiring shunting in 3/27 functional hemispherectomy patients. A review of the literature and comparison of techniques is presented.

Adolescent↗
PubMed1996

Signal processing methods for pulse oximetry.

Current signal processing technology has driven many advances in almost every aspect of life, including medical applications. It follows that applying signal processing techniques to pulse oximetry could also provide major improvements. This research was designed to identify and implement one or more techniques that could improve pulse oximetry oxygen saturation (SpO2) measurements. The hypothesis was that frequency domain analysis could more easily extract the cardiac rate and amplitude of interest from the time domain signal. The focus was on the digital signal processing algorithms that had potential to improve pulse oximetry readings, and then test those algorithms. This was accomplished using the Fast Fourier Transform (FFT) and the Discrete Cosine Transform (DCT). The results indicate that the FFT and DCT computation of oxygen saturation were as accurate without averaging, as weighted moving average (WMA) algorithms currently being used, and directly indicate when erroneous calculations occur.

Algorithms↗
PubMed1995

Landau-Kleffner syndrome with continuous spikes and waves during slow-wave sleep.

The Landau-Kleffner syndrome is sometimes associated with continuous spike-waves during slow-wave sleep. The clinical significance of this association is unclear. In order to investigate differences in glucose metabolic patterns between awake and sleep states in two children with Landau-Kleffner syndrome and continuous spike-waves during slow-wave sleep, fluorodeoxyglucose positron-emission tomographic (PET) studies were performed in each state. In the first patient, the awake interictal PET study revealed moderate hypometabolism in the thalamus and frontal and temporal cortex and mild hypometabolism in the parietal and anterior cingulate cortex bilaterally. Occipital cortex was severely hypometabolic bilaterally. In a repeat PET study performed during sleep in which continuous spike-waves during slow-wave sleep were present, the only difference noted compared to the awake study was a marked bilateral increase in temporal cortex metabolism. The awake interictal PET in the second child was normal, except for mildly increased relative glucose metabolism in the left inferior temporal cortex. The sleep PET study with continuous spike-waves during slow-wave sleep in this child showed hypermetabolism in both temporal lobes; however, this was more pronounced, with a wider distribution in the left temporal cortex. In normal subjects, PET studies performed during awake and sleep states have not revealed such differences. Whether the temporal lobes are involved in the generation of continuous spike-waves during slow-wave sleep remains to be confirmed in a larger group of patients. The first child was treated surgically with multiple subpial transection, following which continuous spike-waves during slow-wave sleep disappeared and language function improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1995

Thyroid function in a goitre endemia.

A study was conducted to determine the thyroid function in a goitre endemia. Sadam is small village in the south district of Sikkim. Severe iodine deficiency exist in this village (prevalence of goitre 73.5%, cretinism prevalence 4%; mean urinary iodine exeretion 4.13 ng/dl - SD 3.1). Total of 72 out pf 142 households were randomly selected. All the inmates of the households above 14 years of age were examined for goitre and blood samples were collected from them for estimation of concentration of thyroid stimulating hormones (triiodothyroine T-3, thyroixe T-4) and thyroid stimulating hormone (TSH). Total of 244 subjects were examined, (137 males and 107 females). Goitre was detected in 149 (61.1%) individuals. The mean T-3, T-4 and TSH concentrations in the non-goitrous groups were (SD in parenthesis) 110.13 ng/dl (26.19), 10.12 ug/dl (2.38) and 1.01 uu/ml (0.52). The corresponding values for the goitrous group were, 132.22 ng/dl (46.25), 9.06 ug/dl (2.04) and 1.33 uu/ml (1.19). The differences in the mean concentrations between the goitrous and non-goitrous groups were statistically significant. An inverse correlation between the goitre size and T-4 on the one hand, and TSH and T-4 on the other hand was noticed. The result of the study show that functional decompensation of the thyroid occur in the majority of goitrous subjects.

Adolescent↗
PubMed1993

Pathophysiological mechanisms of brain damage from status epilepticus.

Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.

Animals↗
PubMed1993

Clinical study of endemic cretinism in south Sikkim.

One hundred individuals suffering from Endemic Cretinism were studied. There were 55 males and 45 females. 62% of the cretins had visible goitre. Thirty nine (62.9%) goitrous cretins had grade II goitre. Neurological cretinism was the predominant type encountered (99%) and Myxoedematous cretinism was seen in only one patient. The most salient neurological feature was deaf-mutism seen in 74%. Findings in the motor system were, apart from deaf-mutism, the most characteristic feature of the condition on clinical examination. 58% had exaggerated deep tendon reflexes and 31% had extensor plantar response. Squint was noticed in 29%. Familial aggregation was noticed and was striking. Endemic cretinism is a distinctive and easily identifiable clinical entity and is an important indicator of the severity of iodine deficiency in a community.

Adolescent↗
PubMed1993

Strategies for diagnosis and treatment of childhood epilepsy.

Recent developments in neuroimaging have advanced our capability to diagnose and perform presurgical evaluations in a large proportion of children without recourse to invasive monitoring techniques. Functional imaging is also providing us with novel insights into the mechanism of certain childhood epileptic syndromes. The role of anatomic (computed tomography, magnetic resonance imaging) and functional (single photon emission computed tomography, positron emission tomography) imaging modalities in the diagnosis and therapeutic decision making in major epileptic syndromes of childhood is reviewed.

Child↗
PubMed1992

Infantile spasms: II. Lenticular nuclei and brain stem activation on positron emission tomography.

Infantile spasms are generalized seizures specific to early infancy, and are believed to result from complex cortical-subcortical interactions during a critical period of development. We used positron emission tomography (PET) to determine local cerebral metabolic rates for glucose (1CMRG1c) in 44 infants with spasms, in an attempt to define the neuroanatomical substrates that mediate these seizures. All infants were studied in the awake state during continuous electroencephalographic monitoring. The most consistent abnormality on PET, seen in 32 infants, was the symmetrical increase in 1CMRG1c in the lenticular nuclei, compared to age-matched normal infants (p less than 0.05). In 21 infants, even though the brain stem appeared to be visually more prominent compared to normal infants, statistically significant differences could not be demonstrated. Relative hypermetabolism of the lenticular nuclei (1) occurred irrespective of whether the spasms were cryptogenic or symptomatic, (2) was associated with focal cortical hypometabolism in 22 and focal cortical hypermetabolism in 5 of the 44 infants, and (3) was not characterized by any specific electroencephalographic abnormality during PET. These findings suggest that the lenticular nuclei may contribute to the pathophysiological state that predisposes to infantile spasms, and is consistent with the observation that spasms are clinically symmetrical even when focal cortical lesions are present. A scheme describing the neuronal circuitry likely to be involved in the generation of infantile spasms is proposed.

Brain Stem↗
PubMed1992

Automatic computer analysis of transients in EEG.

The electroencephalogram (EEG) is often used for the diagnosis of diseases and functional disturbances in the brain. In this paper, new algorithms developed for the automatic detection of transients in EEG are described. The single spike, and spike and wave bursts, both of which are abnormal phenomena associated with epileptic activity are considered. The algorithms for detecting these transients were tested using real EEG data. The transient detection is enhanced by two classification algorithms: patient-independent analysis and patient-dependent analysis. In the patient-independent analysis, multiple reference templates are generated from a patient population and for the patient-dependent analysis, the spikes from the patient's own EEG recording is used as reference. The description of the algorithms and their performances are presented.

Algorithms↗
PubMed1990

Alpha-tocopherol reduces doxorubicin-induced toxicity in rats--histological and biochemical evidences.

The beneficial effect of alpha-tocopherol on doxorubicin-induced toxicity was studied in rats. alpha-Tocopherol (400 mg/kg/day) was administered orally, daily for a period of 2 months along with/without doxorubicin (2.5 mg/kg, i v weekly once for 8 weeks). Histology showed liver necrosis, heart myocyte degeneration, glomerular and tubular degeneration, cellular infiltration and desquammation of intestinal mucosa in doxorubicin treated animals. There was a significant increase in lipid peroxide levels measured in terms of "TBA reactants" in all these organs. These changes were associated with elevated levels of serum enzymes such as transaminases, creatine kinase and lactate dehydrogenase. The pathological observations, were minimal in animals receiving both doxorubicin and alpha-tocopherol. The lipid peroxide levels were low with concomitant normal levels of serum and intestinal enzymes in those animals.

Alanine Transaminase↗
PubMed1990

Lipids and lipoprotein profile in doxorubicin treated rats: influence of alpha-tocopherol administration.

The effect of doxorubicin (DXR) on the levels of heart, liver and plasma lipids and plasma lipoproteins were studied in rats. Rats were treated with DXR (2.5 mg/kg body weight weekly for 8 weeks, iv) with or without alpha-tocopherol (alpha-TPL) (400 mg/kg body wt daily for 60 days) co-administration. DXR treated rats showed increase in plasma total cholesterol, triglycerides and phospholipids. The activities of lecithin cholesterol-acyl transferase and hepatic and extrahepatic lipoprotein lipase were lowered significantly with concomitant increase in liver and heart lipid peroxide levels in DXR treatment. HDL cholesterol level was found to be decreased significantly in DXR treated rats as a result of which there was an increase of LDLc/HDLc ratio. alpha-TPL coadministration brought back the enzyme activity to near normal and reduced the level of lipid peroxides. The lipid changes were minimum in rats treated with both alpha-TPL and DXR. This study suggests that the toxicity of DXR is reflected in lipids and lipoprotein profile.

Animals↗