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Biomedical subjects

S Siegel

Publications and source records attributed to S Siegel.

At least 19 recordsLinked to original sources
PubMed1978

The effectiveness of the short- and long-term use of crystallized theophylline in asthmatic children.

The bioavailability, duration of action, and efficacy of a crystallized tablet form of theophylline were studied in 16 nonsteroid-dependent asthmatic children. All required bronchodilator drugs daily for control of symptoms. Theophylline 125 mg, ephedrine SO4 30 mg, T + E, or placebo were given in a randomized, double-blind, crossover design on four separate days. Pulmonary function tests (FVC, FEV1, FEF25-75) and serum T levels were determined at 0, 4, 1, 2, 4, and 6 hours on both day one and after day 7 of a every-six-hour drug dosage schedule. Mean maximum T levels were achieved at two hours with a peak mean of 2.94 microgram/ml +/- 0.24 SEM on day one. On day 8, the maximum T levels were higher, with a peak mean at two hours of 4.69 microgram/ml +/- 0.49 SEM. Computer analyses for pharmokinetics are compatible with 100% absorption of this preparation. Pulmonary function tests were significantly improved (FEV1 20% and FEF25-75 15%) at T levels of 2 to 5 microgram/ml. Addition of E to the T regimen further improved pulmonary function only on day one and had no effect on the last study day.

Administration, Oral↗
PubMed1978

The role of predrug signals in morphine analgesic tolerance: support for a Pavlovian conditioning model of tolerance.

According to a model of morphine tolerance, which emphasizes Pavlovian conditioning principles, tolerance results from an association between predrug environmental cues and the systemic effects of the drug. To assess this model, groups of rats were administered morphine on either three or nine occasions, with a complex environmental stimulus either paired or not paired with each injection. Control groups had equivalent experience with the environmental cue and injection procedure, but the injected substance was physiological saline. Subsequently, the analgesic effect of the opiate was tested in all subjects following administration of the drug in conjunction with the environmental cue. As expected on the basis of the conditioning model of tolerance, subjects with a pretest history of paired morphine administrations displayed analgesic tolerance, but subjects with a pretest history of unpaired administration displayed no evidence of such tolerance. The results suggest that prior demonstrations that the display of morphine tolerance is specific to the drug administration environment may be readily interpreted by a conditioning analysis of tolerance.

Acoustic Stimulation↗
PubMed1978

Tolerance to the hyperthermic effect of morphine in the rat is a learned response.

The results of several experiments indicated that the hyperthermic effect of morphine in rats becomes attenuated over the course of successive administrations by a conditional, compensatory, hypothermic response elicited by cues present at the time of morphine administration, thus accounting for hyperthermic tolerance: (a) Rats with a history of morphine administration display a tolerant response to the hyperthermic effect of the drug and a compensatory hypothermia following a placebo if these substances are administered following cues that previously signaled morphine--neither the tolerant reaction to morphine nor the hypothermic response to the placebo results when animals are injected following cues that previously signaled injection of physiological saline (Experiments 1A and 1B); (b) presenting environmental cues previously associated with morphine, but without the drug, abolished established tolerance, that is, pyretic tolerance can be extinguished (Experiment 2); (c) placebo sessions interspersed between morphine sessions impeded the acquisition of tolerance, that is pyretic tolerance is retarded by partial reinforcement (Experiment 3). These findings, implicating a Pavlovian conditioning process in hyperthermic tolerance, are not readily interpretable by tolerance models that do not attribute any role to drug-associated environmental cues in the acquisition of tolerance.

Animals↗
PubMed1978

Treatment of chronic childhood asthma with beclomethasone dipropionate aerosols: II. Effect on pituitary-adrenal function after substitution for oral corticosteroids.

The effects of beclomethasone, dipropionate aerosol (DBA) (400 microgram/day) on clinical course, pulmonary function, and pituitary-adrenal function was studied in 34 steroid-dependent asthmatic children. Asthma severity was assessed by daily symptom and medication scores, peak flow measured three times a day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal cortisol levels, cortisol responses to intravenous (IV) corticotropin (ACTH), and steroid responses to IV metyrapone. After 12 weeks of BDA therapy, 30 of 34 patients no longer required prednisone. Mean weekly symptom and medication scores and the number of attacks decreased significantly (P less than .01)). A significant improvement was demonstrated in the patients' peak flow (P less than .01), forced expiratory volume in one second, and maximum midexpiratory flow rates (P less than .01). Thirty of the 34 patients initially had abnormal metyrapone responses, 28 had abnormal diurnal cortisol levels, whereas only 14 had abnormal IV ACTH response tests. Although significant improvement was noted in the mean metyrapone and diurnal cortisol tests, only partial recovery of pituitary-adrenal function was observed in 20 patients, complete recovery in 5, and no change in 9. BDA was found to be therapeutically superior to oral steroids in the group of steroid-dependent asthmatic children and produced no serious adverse effects.

Administration, Oral↗
PubMed1978

Pavlovian conditioning analysis of morphine tolerance.

It has been demonstrated that many conditional responses to a variety of drugs are opposite in direction to the unconditional effects of the drug, and the conditioning analysis of morphine tolerance emphasizes the fact that subjects with a history of morphine administration display morphine-compensatory conditional responses when confronted with the usual administration procedure but without the drug. Thus, when the drug is presented in the context of the usual administration cues, these conditional morphine-compensatory responses would be expected to attenuate the drug-induced unconditional responses, thereby decreasing the observed response to the drug. Research has been summarized which supports this compensatory conditioning model of tolerance by demonstrating that the display of tolerance is specific to the environment in which the drug has been previously administered. Further evidence supporting this theory of tolerance has been provided by studies establishing that extinction, partial reinforcement, and latent inhibition--non-pharmacological manipulations known to be effective in generally affecting the display of conditional responses--similarly affect the display of morphine tolerance. Additional research has suggested many parallels between learning and morphine tolerance: Both processes exhibit great retention, both are disrupted by electroconvulsive shock and frontal cortical stimulation, both are retarded by inhibitors of protein synthesis, and both are facilitated by antagonists of these metabolic inhibitors.

Animals↗
PubMed1977

Morphine tolerance acquisition as an associative process.

The results of several experiments supported the proposal that morphine analgesic tolerance is a manifestation of an association between the drug administration ritual and the systemic effects of the drug: (a) Presenting environmental cues previously associated with morphine, but without the drug, attenuated established tolerance (i.e., morphine tolerance can be extinguished), (b) repeated presentations of the morphine administration procedure, prior to its pairing with the opiate, retarded the acquisition of tolerance (i.e., morphine tolerance is subject to "latent inhibition"), and (c) placebo sessions interspersed between morphine sessions deleteriously affected the development of tolerance (i.e., morphine tolerance is subject to the decremental effects of partial reinforcement). These findings appear inexplicable by most traditional theories of tolerance, which do not emphasize the role of drug-associated environmental cues in the development of tolerance. Additionally, it is suggested that the conditioning analysis of tolerance is congenial with a current view of habituation, and there may be a similar associative basis for the response decrement to both endogenous and exogenous iterative stimulation.

Animals↗
PubMed1976

Strong association between B-lymphocyte group-2 specificity and asthma.

30 families in which at least one member has asthma were tested for five new specificities of B lymphocytes as well as for twenty-five HLA antigens. 41 other asthmatic patients were also tested. HLA-B8 was slightly less common than normal in the 71 patients with asthma and there was a trend towards an increased frequency of HLA-A2 in these patients. However, 88% of the 30 asthma patients had B lymphocyte group 2 compared with 24% of the 109 controls. This strong association between asthma and B lymphocyte group 2 was not completely paralleled by linkage with a postulated susceptibility gene of the HLA complex in 9 families whose members were investigated in detail.

Adult↗
PubMed1976

Morphine analgesic tolerance: its situation specificity supports a Pavlovian conditioning model.

Rats were made tolerant to morphine in either of two environments and then assessed for morphine-induced alteration of pain sensitivity in both environments. Analgesic tolerance was displayed when rats were tested in that environment in which they previously received morphine, but not in the alternative environment. The results indicate than an association between environmental cues and the systemic effects of morphine is crucial to tolerance development.

Analgesia↗
PubMed1976

Relationship of allergy, enuresis, and urinary infection in children 4 to 7 years of age.

A group of 234 children, 4 to 7 years old, in a middle- to upper-middle-class Caucasian population, were divided into four groups and matched for age and sex. Group 1 consisted of 50 children previously treated for urinary infection: control group 1 contained 55 well children; group 2 consisted of 69 children treated for respiratory allergy; and control group 2 contained 60 well children. There was no statistical difference in persistent enuresis (night wetting every week), persistent day wetting (every week), allergy, or family history of enuresis, when group 1 and control group 1 were compared. A family history of urinary infection was higher (P less than .05) in group 1. There was no statistical difference in persistent enuresis, persistent day wetting, previous urinary infection, or family history of enuresis or urinary infection when group 2 and control group 2 were compared. This study suggests that there is no relationship between respiratory allergy, enuresis, and urinary infection.

Child↗
PubMed1975

Evidence from rats that morphine tolerance is a learned response.

It is proposed that the direct analgesic effect of morphine becomes attenuated over the course of successive administrations of the narcotic by a conditioned, compensatory, hyperalgesic response elicited by the administration procedure, the net result being analgesic tolerance. Using the "hot plate" analgesia assessment situation with rats, this conditioning view of tolerance is supported by several findings: (a) It is necessary to have reliable environmental cues predicting the systemic effects of morphine if tolerance is to be observed, (b) a hyperalgesic conditioned response may be observed in morphine-tolerant subjects when drug administration cues are followed by a placebo, and (c) merely by repeatedly presenting environmental cues previously associated with morphine (but now presented with a placebo), morphine tolerance can be extinguished.

Analgesics, Opioid↗
PubMed1975

Reactions of kidney cells with cytotoxic antisera: possible evidence of kidney-specific antigens.

HL-A typing of cadaver kidney cell suspension by fluorochromasia cytotoxicity was successful in 76 out of 124 cases. In the 44 cases with confirmed phenotypes, 24 had identical results for lymphocytes and kidney cells. Twenty kidney cells had HL-A antigens not detected on that donor's lymphocytes, most commonly HL-A7 and HL-A8. In eight of these 20 cases, the additional kidney antigens brought the total to more than two per segregant sereis, in disagreement with an earlier report from this laboratory. The discrepancy was traced to a change in the method of complement preparation. The complement was successfully deprived of the resulting non-specific cytotoxicity for kidney cells by absorption with human red blood cells. Prior to absorption, the complement had rendered kidney cells susceptible to the lytic effect of anti-A and B red cell antibodies. Using the absorbed complement, a patient who had hyperacutely rejected two cadaver kidneys provided sera with an antibody reacting with, and absorbed by, the kidney cells but not the lymphocytes of the donors.

Antigen-Antibody Reactions↗
PubMed1975

A bias for life.

Explore the source record for details and available documents.

Christianity↗
PubMed1975

Conditioning insulin effects.

It has previously been demonstrated that after a number of insulin injections in rats, an injection of a placebo leads to an elevation in blood sugar. It has been suggested that this apparent conditioned compensatory response is an artifact resulting from stressing the subject (when large doses of insulin are used) or represents a nonassociative phenomenon (when small doses of insulin are used). These two suggestions were rejected on the basis of the results of Experiments 1 and 2, respectively. Experiments 3 and 4 demonstrated that although the behavioral effects of insulin can be conditioned to the injection procedure, such conditioned insulinlike behaviors (contrary to suggestions of many investigators) are not mediated by a pypoglycemic state.

Animals↗