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Biomedical subjects

S Nag

Publications and source records attributed to S Nag.

At least 109 records · Page 6Linked to original sources
PubMed1993

Consensus guidelines for high dose rate remote brachytherapy in cervical, endometrial, and endobronchial tumors. Clinical Research Committee, American Endocurietherapy Society.

PURPOSE: A large number of medical centers have recently instituted the use of High Dose-Rate Afterloading Brachytherapy (HDRAB). There is wide variation in treatment regimens, techniques, and dosimetry being used and there are no national standard protocols or guidelines for optimal therapy. METHODS AND MATERIALS: The Clinical Research Committee (CRC) of the American Endocurietherapy Society (AES) met to formulate consensus guidelines for HDRAB in cervical, endometrial, and endobronchial tumors. CONCLUSION: Each center is encouraged to follow a consistent treatment policy in a controlled fashion with complete documentation of treatment parameters and outcome including efficacy and morbidity. Until further clinical data becomes available, the linear quadratic model can be used as a guideline to formulate a new HDR regimen exercising caution when changing from a Low Dose Rate (LDR) to a HDRAB regimen. The treatments should be fractionated as much as practical to minimize long term morbidity. As more clinical data becomes available, the guidelines will mature and be updated by the Clinical Research Committee of the AES.

Brachytherapy↗
PubMed1993

Aggressive chemotherapy, organ-preserving surgery, and high-dose-rate remote brachytherapy in the treatment of rhabdomyosarcoma in infants and young children.

BACKGROUND: External beam radiation therapy often is avoided in the treatment of rhabdomyosarcoma (RMS) in young children because of the long-term sequelae. Conventional brachytherapy can reduce these problems, but its use is limited in young children because of radiation exposure to parents and care-givers. This is the first reported use of high-dose-rate remote brachytherapy (HDR) to treat RMS in young children. METHODS: Seven young children with RMS were treated from January 1990 through September 1991 with multiagent chemotherapy, organ preserving surgery, and HDR. The primary tumor sites included the tongue, buccal mucosa, chest wall, vagina, and clitoris. A minimum peripheral dose of 36 Gy HDR was administered in 12 fractions (twice a day) at 3 Gy per fraction for a period of 3 days. The treatment was given on an outpatient basis without requiring prolonged patient sedation or immobilization. Each treatment lasted 2-5 minutes. RESULTS: All seven children are alive and without evidence of tumor with a median follow-up of 30 months (range, 18-35 months) from diagnosis. The treatments have been reasonably well tolerated with some acute skin toxicity. There has been relatively good organ growth and function during this short follow-up period. CONCLUSION: The use of HDR radiation in these patients eliminated radiation exposure to care-givers and permitted constant nursing care and interaction among the parents, nursing personnel, and child. Treatments can be given on an outpatient basis, without requiring prolonged patient sedation or immobilization. Local control of tumor with preservation of organ function was achieved. HDR in young children should be restricted to controlled clinical trials until long-term morbidity and efficacy results are obtained from pilot studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Potent metabolic stimulation of septal gray and cerebral white matter in vivo by intraventricular endothelin and nitric oxide.

Endothelin-1 (ET) and sodium nitroprusside (SNP, which liberates nitric oxide, NO) were given alone or together into a lateral cerebral ventricle (icv) of anesthetized rats to assess their potential interaction on cerebral rates of glucose metabolism (autoradiographic [14C]deoxyglucose technique). ET (9 pmol) produced hypermetabolic effects ipsilaterally in the septal nuclei and periventricular white matter. NO lesioned the septum, which displayed neuronal damage and diminished metabolic activity, and evoked potent increases in glucose metabolism bilaterally in commissural and projection white matter tracts. Together, ET and NO had synergistic hypermetabolic effects in the hippocampal fimbria, but were antagonistic on the metabolic rate of the lateral septal nucleus and choroid plexus. The results reveal an extraordinary sensitivity in the metabolic rate of septal gray matter to ET and of white matter fibers to NO in vivo. Icv administration offers a useful approach for examination of the metabolic and toxicological properties of the novel neurotransmitter substances ET and NO on septal neurons, myelinated fibers, and choroidal epithelia.

Animals↗
PubMed1993

Alterations in spliced and unspliced HIV-1-specific RNA detection in peripheral blood mononuclear cells of individuals with varying CD4-positive lymphocyte counts.

Reverse transcriptase-polymerase chain amplification reactions (RT-PCR) were used to identify transcripts for HIV-1 structural and regulatory proteins in peripheral blood mononuclear cells of a cohort of 48 patients. At least one set of PCR primers was capable of detecting HIV-1 transcripts in 94% of patients. Unspliced gag-pol transcripts were detected with gag or pol primer sets in 60 and 63% of samples, respectively. A significant inverse correlation was noted between transcript identification with the gag primer set and the number of CD4-positive lymphocytes in the blood sample and the clinical stage of infection. Single-spliced env transcripts were identified in 44% of individuals. Multiple-spliced tat or nef transcripts were detected in 6.2 and 53% of individuals, respectively. These findings indicate that viral transcripts are expressed throughout the course of HIV-1 infection.

Base Sequence↗
PubMed1993

A syndrome of acute severe muscle necrosis in intensive care unit patients.

Four septic patients and one asthmatic patient are described who developed a severe paralytic disorder in an intensive care unit (ICU), associated with a rise in serum creatine kinase and a severe necrotizing myopathy. All cases had received non-depolarizing muscle blocking agents and large intravenous doses of glucocorticoids. Three patients developed myoglobinuria. No improvement or very little improvement in muscle function was noted in the four fatal cases. The single survivor recovered his strength after 6 months. This syndrome ("necrotizing myopathy of intensive care") provides one of the differential diagnoses for ICU-acquired weakness. The myopathy appears to have several interdependent causes and it is proposed that these should be classified as myonecrosis "priming" factors (glucocorticoids, myotropic infections, sepsis) and "triggering" factors (non-depolarizing muscle blocking agents).

Acute Disease↗
PubMed1992

Vascular changes in the spinal cord in N-methyl-D-aspartate-induced excitotoxicity: morphological and permeability studies.

Our previous studies have demonstrated toxicity in spinal cord neuronal systems of middle-aged rats with continuous intrathecal infusion of N-methyl-D-aspartate (NMDA). The present study was undertaken to determine when during the course of excitotoxicity vascular changes occur. The model used was intrathecal infusion of NMDA in the region of the lumbar enlargement of the spinal cord. Horseradish peroxidase (HRP) was used as a marker of vascular permeability alterations occurring in this model. Pathological changes were observed in the cord gray matter of all rats infused with 30-60 micrograms/min NMDA for 30 or 60 min. The changes consisted of swelling of dendrites which gave the neuropil a vacuolated appearance. There was expansion of the extracellular spaces in these areas and neurons were shrunken with pyknotic nuclei. These changes were more frequently encountered in the posterior than anterior horns and were specific for NMDA since they did not occur in NMDA-infused rats pretreated with MK-801, a specific NMDA antagonist. Endothelial dysfunction manifested as increased permeability to HRP. This was a consistent finding in all rats infused with the higher dose of NMDA and was less frequent in those infused with 30 micrograms/min and no vascular changes were observed in rats infused with NMDA for 30 min despite the presence of tissue changes. Increased permeability affected all types of vessels but principally, capillaries and venules. There was no evidence of endothelial necrosis or vascular occlusion. This study demonstrates that in excitotoxin-mediated tissue damage, breakdown of the blood-brain barrier follows the development of nervous tissue damage. Thus, edema is not a significant feature of early lesions in excitotoxin-induced brain injury.

Animals↗
PubMed1992

Cervical paravertebral leiomyosarcoma mimicking a nerve sheath tumor.

A rare case of leiomyosarcoma attached to the C6 nerve root with extension through the intervertebral foramen into the spinal canal is described. Clinically and at the time of frozen section, this was considered to be a nerve sheath tumor. A definitive histologic diagnosis was made on the basis of the ultrastructural features of the tumor. Complete remission was achieved following extensive surgical removal and postoperative radiotherapy. The possible origin of this neoplasm is discussed.

Adult↗
PubMed1992

Cerebral hypermetabolism produced by intraventricular endothelin-1 in rats: inhibition by nimodipine.

Injection of endothelin-1 (9 pmol) into the lateral cerebral ventricle of rats produced barrel-rotations, convulsions, tonic hindlimb extensions, facial clonus, and kinetic ataxia for up to 45 min. Quantitative metabolic autoradiographs produced from the [14C]deoxyglucose method and analyzed over 60 individual brain structures or subregions revealed intense hypermetabolism in periventricular tissues close to the injection site and in many of their efferent projection sites. Histological examination of these areas proved that this dose of endothelin was without toxic or ischemic effects on neurons or glial cells. Structures metabolically affected ipsilateral to injection were caudate nucleus (+164%), lateral septal nucleus (+270%), and two white matter tracts--corpus callosum (+236%) and hippocampal fimbria (+318%). Distant stimulated structures included cerebellar cortical layers, but not cerebellar nuclei or white matter. Increased rates of glucose metabolism among many other nuclei, particularly distinct subunits of the hippocampal formation and structures in contact with the ventricular system, signify that endothelin induced widespread metabolic stimulation over much of the neuraxis. Furthermore, although the 9 pmol concentration of endothelin produced convulsive movements and diverse metabolic stimulation, it did not evoke detectable electroencephalographic seizure activity assessed by intra- or extracerebral electroencephalography. Both the convulsions and hypermetabolic activation were inhibited by intraventricular pretreatment with the dihydropyridine calcium-channel antagonist, nimodipine. The results identify endothelin-1 as a calcium-mediated 'convulsive' peptide with selective stimulatory effects on cerebral glucose metabolism.

Animals↗
PubMed1991

Effect of atrial natriuretic factor on permeability of the blood-cerebrospinal fluid barrier.

The demonstration of 125I-labelled atrial natriuretic factor (ANF)-binding sites on choroid plexus suggests a physiological role of ANF on the blood-cerebrospinal fluid barrier. This ultrastructural study was undertaken to determine whether ANF (0.5 microgram) alters the permeability of rat blood-cerebrospinal fluid barrier under steady states. Horseradish peroxidase (HRP) was used as a marker of protein permeability and ionic lanthanum as a marker of ionic permeability. HRP was not observed in the walls of choroid plexus vessels of control rats at 3 or 6 min, while at 12 min HRP was present in vessel walls and occasionally in continuity in the adjacent intercellular space between choroidal epithelial cells. In ANF-treated rats, HRP was observed in vessel walls and in the intercellular space between the choroidal epithelial cells up to the apical tight junctions at 3 min, indicating an accelerated passage of tracer. Although HRP was never observed beyond the apical tight junctions in control or test animals, at 6 min test rats showed ionic lanthanum within these junctions in focal areas and in continuity in the adjacent ventricular cavity. These studies demonstrate that ANF causes accelerated passage of both HRP and ionic lanthanum from blood into choroid plexuses with passage of ionic lanthanum into the ventricular cavity through the apical tight junctions of choroidal epithelial cells. The latter is in keeping with the known function of ANF in regulating water and electrolyte fluxes.

Animals↗
PubMed1991

Protective effect of flunarizine on blood-brain barrier permeability alterations in acutely hypertensive rats.

BACKGROUND AND PURPOSE: Increased cerebrovascular permeability to protein is a well-documented finding in acute and chronic hypertension. In this study, we examined the effect of pretreatment with a calcium entry blocker, flunarizine, on the increased cerebrovascular permeability to protein that develops in norepinephrine-induced acute hypertension. METHODS: Protein transfer was assessed qualitatively with Evans blue dye and quantitatively with iodine-125-labeled serum albumin. RESULTS: Brains of hypertensive rats showed increased permeability to both tracers. The number and size of the areas of Evans blue extravasation were smaller in the hypertensive groups pretreated with flunarizine intravenously. This was supported by the quantitative studies, which demonstrated a significant decrease in protein transfer in total brain of hypertensive rats pretreated with intravenous flunarizine, 1 mg/kg (p less than 0.005) and 2.5 mg/kg (p less than 0.001). Data from individual brain regions showed that pretreatment with flunarizine resulted in significant reduction of protein transfer in most brain regions. CONCLUSIONS: These data support the hypothesis that calcium plays a role in increased cerebral endothelial permeability in hypertension.

Animals↗
PubMed1990

Presence of transendothelial channels in cerebral endothelium in chronic hypertension.

In this model hypertension developed as early as 1 wk. post-surgery and was associated with reduction in Ca2(+)-ATPase activity in cerebral vessels indicating that abnormalities in ionic calcium in vessel walls occur early in the evolution of hypertension. This study supports previous observations that cerebral cortical arterioles develop increased permeability to endogenous plasma proteins in chronic hypertension. The principal mechanism resulting in this increased permeability is enhanced pinocytosis. Ca2(+)-ATPase localisation in endothelial pinocytotic vesicles helped to localise transendothelial channels in occasional vessels of hypertensive rats. The latter findings reinforce the concept that in pathologic states associated with cerebral oedema, pinocytotic vesicles fuse to form transendothelial channels which transport plasma proteins into brain.

Animals↗
PubMed1990

Cerebrovascular permeability in acute hypertension: effect of flunarizine.

The pattern of Evans blue extravasation in the brain in norepinephrine-induced acute hypertension is similar to our previous observations using horseradish peroxidase as a tracer. Pretreatment with flunarizine IV resulted in significant reduction of RISA leakage in all regions of the brains of acutely hypertensive rats. The reduction in RISA leakage in the drug-treated hypertensive group is not attributable to differences in the blood pressure elevations which were not significantly different in both groups. These studies suggest a role for calcium in the increased endothelial permeability occurring in cerebral vessels in acute hypertension. Further morphological studies are required to determine whether flunarizine reduces permeability by decreasing pinocytosis.

Acute Disease↗
PubMed1990

Ultracytochemical localisation of Na+, K(+)-ATPase in cerebral endothelium in acute hypertension.

This ultracytochemical study was undertaken to determine whether increased arteriolar permeability in acute hypertension is accompanied by altered localisation of the ouabain-sensitive, K(+)-dependent p-nitrophenyl-phosphatase (K(+)-NPPase), a component of the Na+, K(+)-ATPase system. Rats were injected with horseradish peroxidase (HRP) intravenously and acute hypertension was induced by a 2-min infusion of angiotensin amide. Rats were killed at 3 and 15 min, following which brains were sliced and reacted for demonstration of K(+)-NPPase and HRP reaction product. Vessels of normotensive and hypertensive rats that were nonpermeable to HRP showed discontinuous distribution of K(+)-NPPase on the outer plasma membranes of endothelial and adventitial cells of arterioles and endothelial cells and pericytes of capillaries. Arterioles of the hypertensive rats which were permeable to HRP showed marked reduction of K(+)-NPPase localisation in their walls at 3 min while at 15 min when the blood pressure had returned to resting levels the enzyme localisation was similar to controls. This study demonstrates transient alteration of the NA+, K(+)-ATPase system during increased endothelial permeability in acute hypertension. The implication of this finding and our previous observation of reduced Ca2(+)-ATPase localisation in endothelial plasma membranes in acute hypertension has been discussed.

Animals↗
PubMed1990

Primary spinal leptomeningeal astrocytoma.

This autopsy case report describes a clinically aggressive, histologically well-differentiated, diffuse, primary leptomeningeal astrocytoma. This rare tumour produced a meningitic clinical picture associated with hydrocephalus, focal spinal cord necrosis, and signs of spinal and cranial nerve root irritation. Despite the microscopic features, death occurred approximately 7 weeks after the first meningeal symptoms.

Adult↗
PubMed1990

Spinal neuronal pathology associated with continuous intrathecal infusion of N-methyl-D-aspartate in the rat.

Continuous intrathecal infusion of N-methyl-D-aspartate (NMDA) at the level of the lumbar enlargement of the spinal cord in middle-aged rats produced dose-dependent toxicity of spinal cord neuronal systems. Toxicity was enhanced by coadministration of glycine, but was significantly reduced when NMDA was co-administered with the competitive inhibitor DL-2-amino-5-phosphovaleric acid or the noncompetitive inhibitor MgSO4. The toxic effects of NMDA were manifest most dramatically and at the lowest concentrations in the neuropil, while neuronal loss was obvious at higher concentrations. The distribution and intensity of reactive astrocytosis was consistent with the known regional and subcellular distribution of NMDA receptors in the spinal cord of rats. The increase in ribosomes and rough endoplasmic reticulum observed in anterior horn cells suggested an increase of cell metabolism reflecting either a nonspecific response to injury or a specific increase in cell metabolism secondary to sustained activation of NMDA receptors. The present studies implicate excitatory amino acid receptors of the NMDA type in producing toxicity to selected neuronal populations of the spinal cord. This model provides a system for studies of the protective effects and rescue of neuronal populations susceptible to the toxic effects of excitatory amino acids.

2-Amino-5-phosphonovalerate↗
PubMed1989

Myelopathy: an unusual presentation of toxoplasmosis.

Central nervous system toxoplasmosis is a well known disease of immunocompromised patients. Neuropathologic examinations have only rarely demonstrated spinal cord involvement. This report describes a fatal case of toxoplasmosis that presented with a subacute myelopathy. Toxoplasmosis should be considered in immuno-compromised patients, including patients with the acquired immune deficiency syndrome, that develop intramedullary lesions of the spinal cord.

Autoimmune Diseases↗
PubMed1989

Effect of atrial natriuretic factor on blood-brain barrier permeability.

Recent studies have demonstrated receptors for atrial natriuretic factor on endothelium of intracerebral vessels. The physiological role of these receptors is not known. The present study was undertaken to determine whether atrial natriuretic factor has an effect on blood-brain barrier permeability to protein and ions using horseradish peroxidase and lanthanum as markers of permeability alterations. This study does not demonstrate a significant effect of atrial natriuretic factor on blood-brain barrier permeability mechanisms in steady states.

Animals↗