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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 937 records · Page 52Linked to original sources
PubMed1980

Abnormal gastrocolonic response in patients with ulcerative colitis.

The purpose of these studies is to determine the colonic myoelectrical and contractile response after eating a 1000 calorie meal in patients with active ulcerative colitis. During fasting, slow waves are identifiable significantly more in patients with ulcerative colitis than in normal subjects (p < 0 . 01). The predominant slow wave frequency is 6 . 1 +/- 0 . 2 cycles/min, which is similar to the normal subjects. The slow waves are not altered by eating in either group. Minimal spike or contractile activity occurs during the fasting period both in patients with ulcerative colitis and in normal subjects. In patients with ulcerative colitis, spike activity increases rapidly after eating the 1000 calorie meal (P < 0 . 01), but the maximal response is decreased and shorter in duration than in normal subjects. There is no simultaneous increase in colonic contractility above fasting levels after the meal in patients with ulcerative colitis. This is strikingly different from the simultaneous increase in contractile and spike activity (P < 0 . 01) that occurs after eating in normal subjects. These studies suggest that in ulcerative colitis (1) the colonic smooth muscle slow wave activity is intact; and (2) a disturbance in the normal colonic contractile response to eating is present despite an adequate spike response. This lack of colonic contractility may contribute to the increase in diarrhoea that occurs in these patients after eating.

Adult↗
PubMed1980

Effect of deoxycholic acid on colonic motility in the rabbit.

The purpose of the study was to determine the effect of the bile salt, deoxycholic acid, on colonic myoelectrical and contractile activity recorded from a loop of proximal colon in the anesthetized rabbit. Myoelectrical activity was recorded from bipolar electrodes attached to the serosal surface of the proximal colon. Contractile activity of the circular smooth muscle was measured with a strain gauge attached in the circular direction on the serosal surface of the colonic loop. The colonic slow wave frequency was 12.5 +/- 1.1 cycles/min. The slow wave frequency throughout the loop was homogeneous with a low coefficient of variation of the slow wave frequency (5.8 +/- 0.3). There were spike potentials superimposed on 78.1 +/- 3.4% of the slow waves. The addition of 8 or 16 mM deoxycholic acid did not change the slow wave or spike activity. However, deoxycholic acid stimulated a dose-dependent increase in migrating action potential complexes. These complexes were associated with a forceful contraction of the circular smooth muscle that propelled luminal contents in the direction of the burst. Deoxycholic acid also stimulated an increase in luminal fluid content.

Action Potentials↗
PubMed1980

Does rigidity in structure of muscarinic agonists and antagonists reflect drug specificity?

The present work is an attempt to elucidate: (1) whether highly rigid structural analogs of acetylcholine are still capable of activating the muscarinic receptor; (2) whether such analogs, be they agonists or antagonists, discriminate among the various ACh-mediated functions, thereby providing a tool for the study of a possible receptor heterogeneity; (3) whether structural rigidity is a significant factor in the kinetics of drug-receptor interaction. To this end, we investigated some properties of drugs in the spiro-(1,3-dioxolane-4,3')-quinuclidine system (SDQ) which embodies the muscarinic pharmacophore in a framework of utmost rigidity. Wherever possible, these properties were compared with those of a closely related but more flexible analog. Variation in effect between members of a rigid-flexible pair or among drugs of varying rigidity is considered to reflect varying affinities towards various sites of action. 2-Methyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-30) is a weak but selective muscarinic agonist. It can be viewed as a highly rigid version of 3-acetoxyquinuclidine (3-AcQ) and it can be used as a probe for detection of heterogeneity among muscarinic receptors. AF-30 is equipotent with 3-AcQ in causing tremors (mice), but has 1/17th the activity of 3-AcQ in the guinea-pig ileum, 1/30th in lowering blood pressure (cats) and 1/10th in inducing analgesia (mice). 2-Diphenylmethyl-spiro(1,3-dioxolane-4',3)-quinuclidine (AF-41) and 2.2-diphenyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-32 are potent antagonists and possess KD values in the same range as those of the more flexible congener 3-diphenylacetoxy-quinuclidine (AF-43) and atropine (0.6--2 nM) but with koff = 0.1 msec-1 (AF-41) and koff = 1 msec-1 (AF-43) (carp atrium). Thus, duration of drug action of drug action at the receptor is a function of structural rigidity in the drug molecule, termination of action being fastest with the flexible molecules. Differences in rigidity among various antagonists also find expression in an unequal distribution of potencies in various tests; thus the rigid antagonists differentiate between two central effects in mice, viz., prevention of oxotremorine-induced tremors and fall from the rotating rod by a factor of 1:20 (especially AF-41 versus AF-43), whereas the more flexible antagonists (AF-43, atropine or even 3-quinuclidinyl-benzilate) do not show such as a selectivity. The existence of heterogenous muscarinic receptors can be inferred from data presented. Both theoretical and practical implications are discussed.

Acetylcholine↗
PubMed1980

Pneumonitis caused by gold salt therapy: evidence for the role of cell-mediated immunity in its pathogenesis.

Gold salt-related pneumonitis is now an established clinical entity, but the mechanism for the induction of the pulmonary disease is not known. In 2 patients with this disorder, we observed elaboration of the lymphokines, migration inhibition factor (MIF) and macrophage chemotactic factor (MCF), by peripheral blood lymphocytes after incubation with gold salt. Incorporation of [3H]thymidine was not seen with several different dosages of gold salt. Control lymphocytes from normal subjects, from patients with rheumatoid arthritis but not receiving gold salt, and from patients with rheumatoid arthritis receiving gold salt but without hypersensitivity manifestations, were all unresponsive to the drug. These results suggested that the pneumonitis associated with chrysotherapy is also associated with a specific cellular immune response to the drug. Further, they point to the necessity of evaluating multiple parameters of cellular immunity, because in these patients there was a dissociation between blast transformation and mediator production. In addition, they underscored the need for further observations of cellular responsiveness in patients receiving gold salt therapy with and without overt pulmonary disease.

Female↗
PubMed1980

A preclinical study of EO-122, a new lidocaine-like antiarrhythmic drug.

The 2,6-dimethylanilide of quinuclidine-3-carboxylic acid hydrochloride (EO-122), a new structural analog of lidocaine, has been shown to possess potent antiarrhythmic activity in experimentally induced arrhythmias in animals. Restoration of normal sinus rhythm and suppression of ouabain-induced arrhythmia in cats and dogs, and of coronary occlusion-induced arrhythmia in dogs, followed a single IV injection of 1--3 mg/kg, with an onset of 2 minutes and a duration of 20--240 minutes. Occlusion-induced arrhythmia was likewise suppressed after an oral dose of 10--20 mg/kg, with an onset of 11--65 minutes and a duration of 25--120 minutes. Under similar conditions, lidocaine was either totally ineffective or of ultra-short duration. The bioavailability of EO0122 by the oral route exceeded 80% of the oral dose. Therapeutic blood concentrations were in the range 0.5--7 microgram/ml. At about 5 microgram/ml there was a slight depression of cardiac function in the anesthetized cat, but not in the conscious dog. In cats, complete A-V block occurred at concentrations of 60--70 microgram/ml. The IV LD50 in mice was 22 mg/kg, and in rabbits 8.5 mg/kg. No overt signs of neurotoxicity could be observed at any dose of EO-122. The pharmacokinetic profile of the drug fits a two-compartment open model, with t1/2 congruent to 150 min and Vd (SS) congruent to 1.5 l/kg.

Animals↗
PubMed1980

GM1 ganglioside concentration in the cerebrospinal fluid of neonates and children.

GM1 ganglioside concentration was measured by radioassay technique in individual samples of lumbar cerebrospinal fluid from 20 neonatal and 17 older pediatric patients. The lumbar CSF GM1 ganglioside concentration of neonates (76.6 +/- 27.4 ng/ml) is greater than that of older infants and children (31.9 +/- 22.2 ng/ml). The lower range of GM1 ganglioside concentration of CSF from older pediatric patients is similar to the previously reported adult CSF values. The mean CSF GM1 ganglioside concentration in pediatric patients with active neurologic disease (53.1 +/- 30.0 ng/ml) is greater than that of children without central nervous system pathology. The temporal evolution and magnitude above baseline values of lumbar CSF GM1 ganglioside concentration in three neonates was correlated with the clinical status of these patients.

Adolescent↗
PubMed1980

Abnormal gastrocolic response in patients with intestinal pseudo-obstruction.

Gastrointestinal motility disturbances after endogenous stimuli have been demonstrated only in the esophagus and small intestine in patients with chronic idiopathic pseudo-obstruction. The 1,000-calorie meal stimulated a significant increase in spike and contractile activity in normal subjects. No increase in colonic spike or contractile activity occurred in patients with chronic idiopathic pseudo-obstruction even though colonic motility increased normally following the administration of neostigmine methylsulfate. These findings suggest that the normal response to eating is absent in patients with chronic idiopathic intestinal pseudo-obstruction even though their smooth muscle has been shown to be responsive to cholinergic stimulation. This loss of a gastrocolic response is further evidence for a disorder of the neurohumoral control mechanisms in patients with chronic idiopathic intestinal pseudo-obstruction.

Adult↗
PubMed1980

The gastrointestinal manifestations of scleroderma: pathogenesis and management.

This case exemplifies the severe gastrointestinal manifestations of scleroderma. Esophageal, gastric, small intestinal, and colonic motility disorders were present. The patient was unable to survive on oral feedings or tube feedings. He was clinically resistant to the pharmacologic stimulation of gastrointestinal motility. After considerable discussion the patient was begun on intravenous hyperalimentation to be performed at home. Approximately 1 hr later, he has done remarkably well. He has maintained his weight and has had only one brief hospitalized for a sepsis most likely related to the intravenous feedings. He is still unable to take oral feedings. Other organs have remained clinically uninvolved, and the skin and joint disease have remained stable. It is our feeling that intravenous home alimentation has provided a useful adjunct to management in this patient with severe gastrointestinal involvement of scleroderma. It is hoped that the newer therapeutic modalities described by Dr. Jimenez may be effective in patients with this disease who can now be nourished parenterally.

Action Potentials↗