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Biomedical subjects

J Patel

Publications and source records attributed to J Patel.

At least 217 records · Page 12Linked to original sources

Gentamicin disposition kinetics in humans with spinal cord injury.

The disposition kinetics of gentamicin, an aminoglycoside antibiotic, were studied in seven tetraplegic and six paraplegic volunteers. The volume of distribution of gentamicin in l/kg of body weight varied in a statistically significant way from values of this parameter measured in normal subjects. The elimination of gentamicin in spinal man proceeded in a log-linear fashion accurately characterized by a one compartment open-model with a half-life of approximately 2 hours. The clinical significance of altered disposition kinetics and an increased intersubject variability in gentamicin disposition in spinal man as compared to normal subjects is unknown. The existence of these observed differences in pharmacokinetic parameters, however, emphasizes the need to define individual pharmacokinetic profiles and individualize dosing regimens in spinal man. The data presented are supportive of the hypothesis that spinal man constitutes a discreet therapeutic population.

Adult↗

Jejunal diverticulosis: medical and surgical management.

Jejunal diverticulosis, a marker of disordered small intestinal motility, presents varied clinical manifestations. It is important to consider this disorder in elderly patients with unexplained abdominal discomfort accompanied by signs of intermittent small bowel obstruction and malabsorption. Diagnosis can be made by a small bowel follow-through x-ray film obtained as part of the evaluation of diarrhea and obstructive symptoms. Medical therapy is helpful in controlling diarrhea and anemia, while surgical therapy can give excellent results in treating complications or refractory symptoms.

Aged↗

Autoradiographic localization of adenosine uptake sites in rat brain using [3H]nitrobenzylthioinosine.

The adenosine uptake site has been localized in rat brain by an in vitro light microscopic autoradiographic method, using [3H]nitrobenzylthioinosine ( [3H]NBI) as the probe. The binding characteristics of [3H]NBI on slide-mounted sections are comparable to those seen in studies performed on brain homogenates. A very high density of uptake sites occurs in the nucleus tractus solitarius, in the superficial layer of the superior colliculus, in several thalamic nuclei, and also in geniculate body nuclei. A high density of sites are also observed in the nucleus accumbens, the caudate putamen, the dorsal tegmentum area, the substantia nigra, and the central gray. The localization of the adenosine uptake site in brain may provide information on the functional activity of the site and suggests the involvement of the adenosine system in the central regulation of cardiovascular function.

Adenosine↗

Merkel cell tumor with liver metastases: presentation as fulminant hepatic failure.

This report demonstrates that hepatic metastases can present with fulminant hepatic failure and that liver enzyme abnormalities may not become prominent until there has been massive replacement of the liver. The CT scan of liver may not demonstrate diffuse liver metastases as seen in this patient. Merkel cell tumor or trabecular neuroendocrine skin tumor is a previously unreported cause for the development of the syndrome of hepatic failure due to liver metastases.

Adenocarcinoma↗

Phorbol esters inhibit agonist-induced [3H] inositol-1-phosphate accumulation in rat hippocampal slices.

In rat hippocampal slices, carbachol and norepinephrine induce an accumulation of [3H]-inositol-1-phosphate which is markedly amplified in the presence of lithium. The tumor-promoting agents phorbol 12,13-dibutyrate (PDB) and 4 beta phorbol, 12 beta-myristate, 13 alpha-acetate (PMA) have no effect on [3H] inositol-1-phosphate accumulation alone, but when preincubated with hippocampal slices significantly inhibit the accumulation of [3H]-inositol-1-phosphate induced by carbachol and norepinephrine. The IC50 values for PDB and PMA are 0.2 microM and 25 microM respectively. In contrast, the weak tumor promoting agents 4-O-methylphorbol 12 myristate 13 acetate (MPMA) and phorbol 13,20-diacetate (P 13,20 DA) only slightly attenuate the agonist-induced response at concentrations less than or equal to 100 microM, whereas 4 alpha-phorbol (4 alpha-PHR), a biologically inactive phorbol, has no effect. These data suggest that phorbol ester receptor-mediated events may be negatively coupled to agonist-induced phosphatidylinositol hydrolysis.

Animals↗

Adenosine uptake sites in dog heart and brain; interaction with calcium antagonists.

[3H] Nitrobenzylthioinosine (NBI) binding is characterized in dog heart and brain. Evidence is presented suggesting that [3H]NBI is binding to the adenosine uptake site in both tissues. Physiologic studies in open-chested dogs clearly demonstrate that NBI acts as a coronary vasodilator, consistent with an action at the adenosine uptake site. The binding is reversible, saturable and of high affinity (KD = 0.78 +/- .06 nM for heart and 0.52 +/- .05 nM for brain). Both dipyridamole and hexobendine are high potency inhibitors of [3H]NBI binding in heart and brain while other antihypertensives and vasodilators such as propranolol and nitroglycerin have no effect. The inhibition of [3H]NBI binding observed with dipyridamole was competitive indicating that both agents are acting at the same site. The dihydropyridine calcium antagonists also inhibited binding with a lower potency than the adenosine uptake blockers. Non-dihydropyridine calcium antagonists were much less potent in this regard. The inhibition of [3H]NBI binding observed with the dihydropyridine calcium antagonists was non-competitive suggesting that the calcium channel and adenosine uptake site may be coupled to each other.

Adenosine↗

Tamoxifen (Nolvadex) versus adrenalectomy in metastatic breast cancer.

The relative efficacy of adrenalectomy and tamoxifen (Nolvadex) was evaluated in a randomized study of 51 patients with metastatic breast cancer. In 25 patients undergoing adrenalectomy, there were 13 responders. There were 9 responders of 26 patients receiving tamoxifen. There was no statistically significant difference. In the crossover phase, 15 patients received tamoxifen following adrenalectomy and 3 responded, one of the 6 previous adrenalectomy responders and 2 of the 9 adrenalectomy nonresponders. Nine patients underwent adrenalectomy following tamoxifen, and there were five responders, one of two tamoxifen responders and four of seven tamoxifen nonresponders. Both tamoxifen and adrenalectomy were effective modalities, and appear to retain effectiveness in crossover trials. The frequency of remission was similar in both groups treated by both modalities in different sequences. Response rates to adrenalectomy, considered as both primary and secondary therapy, were significantly higher, since 18 of 34 patients (53%) responded to this therapy, whereas 12 of 41 (29%) responded to tamoxifen as either primary or secondary therapy.

Adrenalectomy↗

Effects of chronic caffeine on brain adenosine receptors: regional and ontogenetic studies.

The effect of chronic caffeine treatment on three different binding sites in five brain areas of mice is characterized. The sites studied were the adenosine receptor, using [3H] diethylphenylxanthine, the benzodiazepine receptor, using [3H] diazepam and the adenosine uptake site, using [3H] nitrobenzylthioinosine. Significant increases were only observed in adenosine receptors with the greatest degree of change seen in the cerebellum and brain stem at both 16 and 23 days of caffeine treatment. The lack of significant effects of chronic caffeine on benzodiazepine receptors and adenosine uptake sites indicates that the caffeine effect is specific. The effect of chronic caffeine treatment on the ontogeny of adenosine receptors was also studied with the result showing a significantly accelerated development of the receptor in the caffeine treated animals. The adult adenosine receptor levels were 20-30% higher than those observed in control animals. The observed alterations in adenosine receptor number which occur as a consequence of caffeine consumption may underlie some of the behavioral effects of this cortical stimulant as well as provide insights concerning the mechanisms of tolerance to and dependence on caffeine.

Adenosine↗

Ontogeny of calcium antagonist binding sites in chick brain and heart.

The ontogeny of chick brain and heart ventricle calcium antagonist binding sites was determined, using [3H]nitrendipine ([3H]NDP), as the ligand. The binding of [3H]NDP to adult heart and brain was kinetically very similar, with the former displaying a KD of 0.28 +/- 0.02 nM and a Bmax of 138 +/- 17 fmol/mg protein, and the latter a KD of 0.30 +/- 0.02 nM and a Bmax of 160 +/- 12 fmol/mg protein. The binding site in both brain and heart was highly specific for dihydropyridine calcium antagonists, such as nifedipine, nimodipine, and nisoldipine, since these drugs were several orders of magnitude more potent as inhibitors of [3H]NDP binding than verapamil, methoxyverapamil, or diltiazem. The developmental appearance of [3H]NDP binding sites in brain was rather gradual, with adult levels being attained just prior to birth. This was in contrast to the profile in heart ventricle which showed essentially adult levels at seven days gestation. The acquisition of [3H]NDP binding sites in chick brain roughly paralleled the onset of neuronal maturation and functional activity. In both chick brain and heart, verapamil and methoxyverapamil were weak inhibitors of [3H]NDP binding. However, the inhibition of binding in both tissues was markedly biphasic, with only 50% of the binding sites being susceptible to inhibition by each agent, suggesting that multiple calcium antagonist binding sites may exist in both tissues.

Animals↗

Increased phosphorylation of a membrane protein consequent to amygdaloid kindling.

The phosphorylation of both particulate and soluble proteins in the amygdala was examined in electrically kindled rats. In animals receiving electrical stimulation in the left amygdala for 5-6 days that displayed electrical after-discharges but no motor seizures, no changes were observed in the phosphorylation of either particulate or soluble proteins. In animals stimulated for 20-21 days where major motor seizures were produced, the phosphorylation of a protein having a molecular weight of 45,000 ( 45K ) was markedly increased. The phosphorylation of this protein was increased in both the right (unstimulated) and left (stimulated) amygdala. Major motor seizures induced by electroconvulsive shocks, however, did not alter phosphorylation of this protein. Phosphorylation of the 45K protein was stimulated by calcium and calmodulin. The 45K protein is a major phosphoprotein of amygdala, representing 3.2% of the total particulate phosphoproteins in control animals and 7.4% in the kindled animals. In the presence of calcium-calmodulin, 16.2% of net protein phosphorylation was accounted for by the 45K protein.

Amygdala↗

Giant fibrovascular polyp of the esophagus.

An adult patient with a giant fibrovascular esophageal polyp, measuring 17 cm in length, is described in this report. The patient presented with dysphagia and intermittent partial regurgitation of a fleshy mass in the mouth, only after the polyp had attained giant proportions. The polyp appeared as a large polypoid filling defect on a barium swallow and the findings were confirmed at endoscopy. The stalk was attached just below the cricopharyngeus muscle, and the club-shaped polyp extended almost up to the gastroesophageal junction. Because of the vascularity of this large structure and the proximity of respiratory passages to the site of attachment of the stalk, surgical resection of the polyp was undertaken.

Deglutition Disorders↗

Specific and potent interactions of carbamazepine with brain adenosine receptors.

Carbamazepine, a drug effective in pain, seizure, and affective disorders, was screened for its ability to interact with a variety of neurotransmitter and neuromodulator binding sites on brain membranes. The most potent effect was observed on adenosine antagonist ( [3H]DPX) binding to the adenosine receptor (KI = 3.5 +/- 0.4 microM) followed by adenosine agonist ( [3H]CHA) binding (KI = 24.5 +/- 3.6 microM). Lower potency effects were observed on benzodiazepine receptors, and no inhibition was seen in a variety of other systems. The inhibition of adenosine receptor binding by carbamazepine was competitive. No correlation was observed between the potency of a series of carbamazepine analogs as inhibitors of either ( [3H]DPX, [3H]CHA or [3H]diazepam binding and their ability to inhibit electroshock-induced convulsions, suggesting that the anticonvulsant properties of these agents are not mediated by the adenosine receptor, but raising the possibility that other clinical effects of carbamazepine may relate to its ability to act at the adenosine receptor.

Animals↗