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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 631 records · Page 35Linked to original sources
PubMed1988

Susceptibility to pilocarpine-induced seizures in rats increases with age.

Systemic administration of high doses of the cholinergic agonist pilocarpine induces motor limbic seizures in rats. Susceptibility to the convulsant effects of pilocarpine increases during adult life: the threshold dose for generalized seizures is essentially constant from age 30 to 70 days, but decreases thereafter, particularly beyond age 100 days. The increase in seizure susceptibility continues up to at least age 200 days, (the oldest age studied).

Acetylcholine↗
PubMed1988

Do selenium and glutathione inhibit the toxic effects of mercury in marine lamellibranchs?

The effect of selenium (SeO2) and glutathione (GSH) on the bioaccumulation of mercury (HgCl2) and on the activities of lysosomal enzymes in four species of tropical estuarine lamellibranchs is reported. A definite correlation between mercury levels in the external medium and tissue uptake and physiological behaviour--opening and closing of shell valves, response to mechanical stimulus, mucus secretion, and incidence of bleeding--was evident. In the clams exposed to Hg (range 0.1-5.0 mg l-1), bioaccumulation was dependent on the ambient concentration of Hg. The highest bioaccumulation of Hg occurred during the initial 24 h exposure period. Further exposure of up to 7 days did not increase the body burden of Hg. Of the four bivalve species exposed to 0.1 mg Hg l-1, Perna viridis showed the highest levels of Hg (approximately 47 ppm) followed by Anadara granosa, A. rhombea (approximately 25 ppm) and Meretrix casta (approximately 9 ppm). The uptake of Hg by A. granosa was greatly reduced by GSH, whereas Se enhanced it by 50% when administered in combination with Hg. However, the presence of Hg did not influence the uptake of Se. Exposure to combined GSH and Hg resulted in almost complete inhibition of Hg uptake in all four bivalve species. Prior exposure to GSH, however, did not have the same influence on their uptake of Hg. Nevertheless, exposure of clams to GSH following initial exposure to Hg resulted in complete depuration of accumulated Hg. The activities of lysosomal enzymes--arylsulfatase, acid phosphatase, beta-galactosidase and beta-glucuronidase--varied considerably. Treatment with Hg and GSH, separately and in combination, significantly enhanced the levels of beta-galactosidase (P less than 0.05) and beta-glucuronidase (P less than 0.001) in the digestive gland after 96 h exposure. Although Se increased beta-glucuronidase activity (P less than 0.001), it had no effect on beta-galactosidase. On exposure to Hg + Se the activity of both enzymes decreased, except in P. viridis where it increased by 39%. The results show unequivocally that Se does not offer any protection against the toxic effects of mercury in marine lamellibranchs, whereas in many marine vertebrates it does. GSH, a thiol-rich tripeptide, on the other hand, completely nullifies the toxic effects of Hg, both in vivo and in vitro.

Animals↗
PubMed1988

Clinical comparison of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy in treating renal calculi.

STUDY OBJECTIVE: To compare extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for efficacy in treating renal calculi. DESIGN: Non-randomised multicentre cohort study with 3 month follow up and 13 month data collection period. SETTING: Lithotripter centre in London, tertiary referral hospital, and urological clinics in several secondary and tertiary care centres. PATIENTS: 933 of 1001 patients treated by lithotripsy at the lithotripter centre were compared with 195 treated by nephrolithotomy. Missing patients were due to incomplete collection of data. Age and sex distributions and characteristics of the stones were similar in the two treatment groups. Two patients died in the lithotripsy group. Three month follow up was achieved in about 84% of both groups (783/933 for lithotripsy; 163/195 for nephrolithotomy). INTERVENTIONS: The nephrolithotomy group had surgical nephrolithotomy alone. In the lithotripsy group 83% (774/933) had lithotripsy alone, 11% (103/933) had combined lithotripsy and nephrolithotomy, and 6% (56/933) had lithotripsy plus ureteroscopy. Single and combined lithotripter treatments were analysed as one group and compared with nephrolithotomy. END POINT: Presence of stones three months after treatment. MEASUREMENTS AND MAIN RESULTS: Presence of residual stones was assessed by plain radiography, ultrasonography, or intravenous urography. After adjustment for age and size and position of stone for patients with single stones the likelihood of being free of stones three months after treatment was significantly greater in the nephrolithotomy group than the lithotripsy group (odds ratio 6.6; 95% confidence interval 3.0 to 14.6) and the response was particularly pronounced with staghorn calculi (62% (8/13) v 15% (141/96) patients free of stones after nephrolithotomy and lithotripsy, respectively). OTHER FINDINGS: 19%(146/775) of patients who had had lithotripsy had to be readmitted within three months after treatment compared with 14%(23/162) who had nephrolithotomy; and 64%(94/146) of readmissions after lithotripsy were for complications compared with 30%(7/23) of readmissions after nephrolithotomy. CONCLUSIONS: Nephrolithotomy may be preferable to lithotripsy for treating renal stones and it may not be wise to invest heavily in lithotripsy facilities.

Adolescent↗
PubMed1988

Type C Niemann-Pick disease. Lysosomal accumulation and defective intracellular mobilization of low density lipoprotein cholesterol.

The intracellular accumulation of unesterified cholesterol was examined during 24 h of low density lipoprotein (LDL) uptake in normal and Niemann-Pick C fibroblasts by fluorescence microscopy with filipin staining and immunocytochemistry. Perinuclear fluorescence derived from filipin-sterol complexes was observed in both normal and mutant cells by 2 h. This perinuclear cholesterol staining reached its peak in normal cells at 6 h. Subsequent development of fluorescence during the remaining 18 h of LDL incubation was primarily limited to the plasma membrane region of normal cells. In contrast, mutant cells developed a much more intense perinuclear fluorescence throughout the entire 24 h of LDL uptake with little enhancement of cholesterol fluorescence staining in the plasma membranes. Direct mass measurements confirmed that internalized LDL cholesterol more readily replenishes the plasma membrane cholesterol of normal than of mutant fibroblasts. Perinuclear filipin-cholesterol fluorescence of both normal and mutant cells was colocalized with lysosomes by indirect immunocytochemical staining of lysosomal membrane protein. Abnormal sequestration of LDL cholesterol in mutant cells within a metabolically latent pool is supported by the finding that in vitro esterification of cellular cholesterol could be stimulated in mutant but not in normal cell homogenates by extensive disruption of the intracellular membranous structures of cells previously cultured with LDL. Deficient translocation of exogenously derived cholesterol from lysosomes to other intracellular membrane sites may be responsible for the delayed homeostatic responses associated with LDL uptake by mutant Niemann-Pick Type C fibroblasts.

Cell Membrane↗
PubMed1988

Stress/catecholamine-induced cardiac necrosis. Reduction by beta 1-selective blockade.

Catecholamine-induced cardiac necrosis is a well-described phenomenon. Patients with severe head injury are known to be in a marked hyperadrenergic state and can experience cardiac morbidity; this was confirmed in a pilot study. A further study was then undertaken to examine a possible relationship between plasma catecholamine concentration and cardiac morbidity in patients with severe head injury and to assess the effect of intervention with the beta 1-selective agent atenolol. The study involved 114 hemodynamically stable patients with acute head injury who were randomized, double blind, to either placebo or atenolol given intravenously (10 mg every six hours) for three days and then orally (100 mg once a day) for four days. Both groups were equally stressed in terms of raised arterial norepinephrine levels. In patients receiving placebo, but not in those given atenolol, there was a significant (P less than 0.01) positive correlation between arterial level of norepinephrine and plasma level of cardiac-specific isoenzyme CK-MB. Thirty percent of the placebo group, in contrast to 7.4% of the atenolol group (P less than 0.05), had pathologically elevated CK-MB levels (ie, greater than 3% of total CK, a value compatible with acute myocardial infarction). Atenolol appeared to significantly reduce the likelihood of supraventricular tachycardia and ST-segment and T-wave changes and prevented cardiac necrosis (as determined post mortem). The finding that beta 1-selective blockade significantly inhibits catecholamine-induced necrosis has possible broad clinical implications.

Adolescent↗
PubMed1988

Preliminary communication: neuroanatomical variations of the posterior fossa in men with the fragile X (Martin-Bell) syndrome.

Four men with fragile X (fra (X], or Martin-Bell, syndrome were studied by magnetic resonance imaging (MRI) to determine whether detectable abnormalities of the cerebellum were present. The cerebellum was chosen because of the apparently increased tendency for fra (X) patients to demonstrate autistic behavior and accumulating evidence implicating cerebellar abnormalities in autism. Compared with a control group of four normal men, fra (X) patients had a significantly decreased area of the cerebellar vermis, particularly the posterior portion, on planimetric analysis in the midsagittal plane. The pons and fourth ventricular areas also were decreased and increased, respectively, in the fra (X) men. Neuroanatomical and animal research increasingly implicates the cerebellar vermis as an important component in functional brain systems subserving sensory and motor integration, learning, and modulation of affect, motivation, and social behavior. Thus, vermis dysfunction could account for many of the behavioral and cognitive abnormalities observed in fra (X) males, particularly those which overlap with the behavioral syndrome of autism.

Adult↗
PubMed1988

Development of a lymphocyte transformation assay for rotavirus in whole blood and breast milk.

A multivariate assay was developed for detecting lymphoproliferative responses to rotavirus in whole blood and breast milk. Detection of lymphocyte transformation in samples from healthy uninfected adults required an assay incorporating a large number of antigen and cell concentrations and several incubation periods before pulsing. In contrast, lymphoproliferation to rotavirus was observed over a wider range of these variables in blood collected from a kidney recipient nine days post-rotavirus infection. Lymphoproliferation to rotavirus was detected in 32.5% of breast milk samples tested. The magnitude of lymphoproliferation to rotavirus did not correlate with rotavirus-specific IgG ELISA antibody titres in sera or with rotavirus-specific IgA ELISA antibody titres in breast milk.

Adult↗
PubMed1988

The involvement of excitatory amino acid receptors within the prepiriform cortex in pilocarpine-induced limbic seizures in rats.

The prepiriform cortex (PPCx) shows high sensitivity to the epileptogenic action of chemo-convulsants and to the protective action of the NMDA receptor antagonist, 2-amino-7-phosphono-heptanoate (APH) against pilocarpine-induced (motor) limbic seizures in rats. In this study the interaction between agonists acting selectively on the three main excitatory amino acid receptor subtypes in the PPCx and the muscarinic agonist, pilocarpine, within the PPCx have been investigated. Kainate (KA) or quisqualate (QUIS) injected focally into the PPCx (100 pmoles or 5 nmoles per side respectively) induced motor limbic seizures when administered after a subconvulsant dose of pilocarpine (250 mg/kg, i.p.). KA, 100 pmoles injected into the same site in olfactory-bulboectomized rats (bulbectomy results in protection against pilocarpine-induced seizures) also facilitated seizures. However, activation of the NMDA receptor in the PPCx by focal injection of NMDA (250 fmoles-10 nmoles) failed to produce seizures after a subconvulsant dose of pilocarpine. Moreover NMDA in the same range of doses injected into the PPCx protected rats against the seizures induced by a fully convulsant dose of pilocarpine.

Animals↗
PubMed1988

Anti-epileptic effects of focal micro-injection of excitatory amino acid antagonists.

The role of excitatory synaptic activity at various brain regions in the development and spread of seizure activity has been investigated by the focal microinjection of 2-amino-7-phosphono-heptanoate (2-APH), a selective antagonist at the N-methyl-D-aspartate preferring receptor, or gamma-D-glutamyl-aminomethyl sulphonate (GAMS), a partially selective antagonist at the kainate receptor. In genetically epilepsy prone rats the seizure response to a loud sound in most effectively suppressed by focal injections of 2-APH, 0.1-1.0 nmol, in the inferior colliculus. Protection is also seen after injections of 2-APH, 25 nmoles, in the substantia nigra (pars reticulata) or the midbrain reticular formation. Motor limbic seizures induced by pilocarpine, 380 mg/kg intraperitoneally, are prevented by prior injection into the substantia nigra, pars reticulata, or the entopeduncular nucleus, of 2-APH, 10 nmol or 10 pmol, respectively. Similar protection follows the injection of 2-APH, 1-5 pmol in the piriform cortex. The convulsant effects of pilocarpine are also blocked by the focal injection of GAMS, 10 nmol in the entopeduncular nucleus. This experimental approach can indicate critical sites at which seizure activity is initiated in particular models (e.g., inferior colliculus in sound-induced seizures, and piriform cortex in limbic seizures) and the pathways controlling seizure expression, such as the basal ganglia outputs. It also identifies specific receptors at which anticonvulsant drugs may operate.

2-Amino-5-phosphonovalerate↗
PubMed1988

Decrease in excitatory transmission within the lateral habenula and the mediodorsal thalamus protects against limbic seizures in rats.

We have used limbic convulsions induced by systemic pilocarpine in rats combined with focal intracerebral injections concurrently to study the initiation and spread of seizure activity. Protection against pilocarpine-seizure development by antagonism of excitatory or facilitation of inhibitory neurotransmission at focal sites establishes the anatomical circuits involved in the propagation of seizures. The excitatory amino acid antagonist 2-amino-7-phosphonoheptanoate (APH, selective for the NMDA preferring glutamate receptor subtype) is potently anticonvulsant after bilateral focal injections into the habenula or mediodorsal thalamus. The dose of APH required to give sustained protection against pilocarpine-induced convulsions is 10 pmol for lateral habenula and 50 pmol for mediodorsal thalamus. The GABA agonist muscimol produces a similar sustained protection following focal injections (100 pmol/side) into either the lateral habenula or the mediodorsal thalamus. An overall decrease in the efferent neurotransmission of these two brain regions results in a strong anticonvulsant effect indicating their importance in modulating limbic seizure activity.

2-Amino-5-phosphonovalerate↗
PubMed1988

Regulation of seizure threshold by excitatory amino acids in the striatum and entopeduncular nucleus of rats.

The participation of excitatory neurotransmitter systems in the basal ganglia in the initiation and propagation of limbic seizures induced by pilocarpine has been investigated in the rat. Limbic seizures (electrographic and motor) occur in rats receiving bilateral microinjections into the entopeduncular nucleus of 12.5 nmol N-methyl-D-aspartate or 0.1 nmol kainate, 15 min prior to a subconvulsant dose of pilocarpine (150 mg/kg, intraperitoneally). N-Methyl-D-aspartate (12.5 nmol) or kainate (0.5 nmol), injected alone bilaterally into the entopeduncular nucleus, induce sniffing and grooming but no electrographic or behavioural seizures. Limbic seizures also occur after a subconvulsant dose of pilocarpine when it is preceded by injection of N-methyl-D-aspartate (12.5 nmol) or kainate (0.5 or 2 nmol) into the dorsal striatum. Behavioural and electrographic signs of limbic seizures following pilocarpine (380 mg/kg) are suppressed by the focal microinjection into the entopeduncular nucleus of the N-methyl-D-aspartate antagonist, 2-amino-7-phosphonoheptanoate (0.02 nmol) or the kainate antagonist, gamma-D-glutamylamino-methylsulphonate (40 nmol). Seizure threshold within the limbic system is modulated by excitatory systems controlling basal ganglia outputs. The relative importance of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor systems varies between different components of the basal ganglia.

Animals↗
PubMed1988

Effects of GABA compounds injected into the subpallidal regions of rat brain on nucleus accumbens evoked hyperactivity.

The effects of administration of gamma-aminobutyric acid (GABA) compounds into the ventral pallidum and substantia innominata on the locomotor hyperactivity induced by the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) in the nucleus accumbens were investigated in rats. Hyperactivity induced by ADTN was antagonized by the GABA receptor agonists muscimol, isoguvacine, and baclofen. The compounds were equally effective in both subpallidal regions. In contrast, the GABA antagonists picrotoxin and bicuculline injected into subpallidal sites had no effects on accumbens-evoked hyperactivity, although by themselves both antagonists caused a mild and transient locomotor stimulation. It is suggested that GABA receptors in the subpallidal areas are involved in locomotor stimulation elicited from the nucleus accumbens.

Animals↗
PubMed1988

Calcitriol synthesis is decreased in spontaneously hypertensive rats.

To investigate the mechanisms of abnormal calcium metabolism, such as hypocalcemia, decreased intestinal calcium absorption and hypercalciuria in spontaneously hypertensive rats (SHR), we have measured the plasma concentration of calcitriol and its synthesis in 5-, 8-, 12-, 16-, and 20-week-old normotensive Wistar Kyoto rats (WKY) and SHR. Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were measured by the constant isotope infusion method. Plasma concentration of calcitriol and PR of calcitriol were decreased in SHR after 12 weeks of age. MCR of calcitriol, however, was not different between WKY and SHR in any age group. Therefore, the decreased synthesis of calcitriol accounts for the lower plasma level of calcitriol in SHR after 12 weeks of age. Metabolic acidosis or decreased renal function could not account for the decreased synthesis of calcitriol, since the blood pH and pCO2 and creatinine clearance were similar between WKY and SHR at times when the calcitriol synthesis was reduced in SHR. Plasma concentration of ionized calcium was also lower in SHR after 12 weeks of age. Plasma concentration of calcitonin was significantly higher in 16-week-old SHR (41.6 +/- 1.5 pg/ml) than in age-matched WKY (30.5 +/- 1.7, P less than 0.001). The values, however, were not different between 8- and 12-week-old WKY and SHR. We believe that the decreased synthesis of calcitriol could be the pathogenetic factor for the development of abnormal calcium metabolism in SHR. Age of animals should be considered when studying the calcium metabolism in SHR.

Aging↗
PubMed1988

Production and metabolic clearance of calcitriol in acute renal failure.

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol were studied three and seven days after ischemic acute tubular necrosis (ATN). Creatinine clearance was decreased three days after clamping the renal arteries (0.42 +/- 0.03 ml/min/100 g, N = 6 in ATN vs. 0.68 +/- 0.09, N = 7 in sham controls; P less than 0.001). Plasma concentrations (24.1 +/- 1.9 pg/ml) and PR of calcitriol (9.8 +/- 0.91 ng/kg/day) were significantly lower in ATN rats three days after ischemic insult when compared to sham control rats, respectively (76.6 +/- 7.3 pg/ml, and 29.6 +/- 3.3 ng/kg/day; both P less than 0.01). The MCRs of calcitriol were not different between ATN (0.28 +/- 0.02 ml/min/kg) and sham control rats (0.27 +/- 0.01). By the seventh day after ischemic injury, when creatinine clearance of ATN rats returned to normal, both the PR and plasma concentrations of calcitriol also returned to normal values in these animals. In order to assess the effect of uremia on calcitriol metabolism, MCR and PR of calcitriol were measured in rats with reinfusion of their urines for 24 hours. The PR of calcitriol was significantly decreased (9.42 +/- 1.21; vs. controls, 20.5 +/- 2.9 ng/kg/day, P less than 0.001) in uremic animals. Since decreased PR of calcitriol was also accompanied by decreased MCR of calcitriol, plasma concentrations of calcitriol of the uremic rats with intact kidneys remained within normal values. We conclude that the PR of calcitriol is decreased early in ATN rats. Although the MCR was not decreased in mild ATN rats, it may decrease in severe acute renal failure.

Acute Kidney Injury↗
PubMed1988

Visualization of a pseudomeningocele on isotope cisternography.

Pseudomeningocele, a hernial protrusion of the meninges, most commonly forms in wounds that have been incompletely closed at surgery. They are frequently seen with hydrocephalus, with or without increased intracranial pressure. The authors present a case of an incidental finding of a posterior fossa pseudomeningocele seen on cisternography that was performed because of postoperative hydrocephalus after removal of a cerebellar astrocytoma.

Craniotomy↗
PubMed1988

Diurnal variation in precorneal tear film stability.

The stability of the precorneal tear film as inferred from the tear thinning time (TTT) appears to vary over a single 12-h period. The form of this variation is subject dependent. For the average patient the stability is low early in the morning, and tends to rise to equilibrium level between 10:00 a.m. and 12 noon.

Adult↗
PubMed1988

Microsurgical removal of arteriovenous malformations of the basal ganglia.

Arteriovenous malformations in the basal ganglia region have been a problem in neurosurgical practice. We report six cases of deep-seated malformations fed mainly by the perforating branches of the middle cerebral artery. There were no deaths in the series. Four patients returned to their previous activities, and the other two patients had persistent hemiparesis and dysphasia, present preoperatively, with worsening in one case. Both of these patients improved and are independent. We show the feasibility of satisfactory microsurgical treatment of these lesions based on the knowledge of microanatomical studies.

Basal Ganglia↗