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Biomedical subjects

H Teitelbaum

Publications and source records attributed to H Teitelbaum.

At least 19 recordsLinked to original sources

Fetal hypothalamic brain grafts reduce the obesity produced by ventromedial hypothalamic lesions.

Bilateral destruction of the rat ventromedial hypothalamus (VMH) produces a syndrome characterized by hyperphagia and obesity. In the present study we examined whether grafts of fetal hypothalamus could reverse the effects of this lesion. Three groups of adult rats received bilateral electrolytic lesions of the VMH. The first group of animals was then implanted with embryonic day 14-16 hypothalamic tissue by stereotaxic injection into the lesion sites. The second series of animals received comparable-sized grafts from a variety of non-hypothalamic regions of the fetal CNS. The third group experienced similar VMH lesions but did not receive any tissue grafts. After surgery, body weight and food consumption were recorded daily for up to 8 weeks. These measures were compared with similar ones obtained from non-operated rats. Hyperphagia and obesity were consistently observed in all of the lesioned animals not bearing transplants. An initial period of weight gain was also observed in animals receiving hypothalamic grafts, but the duration of the 'dynamic' phase of this syndrome was reduced. Consequently, these graft recipients exhibited significantly less weight gain. This depressed weight gain, however, did not coincide with a statistically significant decrease in hyperphagia. Transplantation of non-hypothalamic tissue also caused an attenuation of the VMH-lesion effect but this was more modest than that induced by homotopic grafts. The results of this experiment show that homotopic transplants can alter the dynamics of weight gain induced by bilateral VMH lesions. However, lesion-induced hyperphagia was not completely reversed in these grafted animals. The fact that other regions can exert a similar effect, though of lesser magnitude, suggests that a more general property of fetal CNS tissue may be involved.

Animals

Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants.

From May, 1979 to March, 1981, 76 leukemia patients were prepared for bone marrow transplantation (BMT) with a new hyperfractionated total body irradiation (TBI) regimen (1320 cGy in 11 fractions, 3x/day), followed by cyclophosphamide, 60 mg/kg, for two days. Partial lung shielding was done on each treatment, with supplemental electron beam treatments of the chest wall to compensate, and of the testes, a sanctuary site. This regimen was initiated to potentially reduce fatal interstitial pneumonitis as well as decrease leukemic relapse. These patients were analyzed in May, 1982, for a minimum follow-up of 14 months. Overall actuarial survival at 1 year for acute non-lymphocytic leukemia (ANLL) patients is 63%, while relapse-free survival at 1 year is 53%. For those ANLL patients who underwent BMT while in remission (first, second, and third combined), relapse-free survival is 61% at 1 year compared with 40% for those patients who had their BMT at the time of relapse (greater than or equal to 10% blasts in marrow). On the other hand, for acute lymphocytic leukemia (ALL) patients, there is no significant difference between relapse or remission patients with regard to overall survival or relapse-free survival, when relapse is defined as greater than 5% blasts in the marrow at the time of cytoreduction. Overall actuarial survival at 1 year for ALL is 61% and relapse-free survival is 45% at 1 year. Patients with ALL who had their BMT cytoreduction at the time of relapse have a survival equal to that of our remission patients, and greater than that of patients in relapse cytoreduced with a single dose as reported by others. However, patients with greater than or equal to 10% blasts have not fared as well, having only a 22% 1 year relapse-free survival compared with a 68% 1 year relapse-free survival for patients with less than 10% blasts. Fatal interstitial pneumonitis has dropped to 18% compared with 50% in our previous single-dose TBI regimen (1000 cGy), in which the same doses of cyclophosphamide were given prior to TBI. In conclusion, not only has fatal interstitial pneumonitis been reduced by hyperfractionation and partial lung blocking, but there may be a survival advantage in ALL patients in relapse, who have a survival equal to that of remission patients. This may indicate a greater cell kill with the higher dose (1320 cGy) attained with this regimen, in these patients with a higher leukemic cell burden.

Adolescent

Yohimbine blocks lateral hypothalamus-mediated behaviors.

There exist behavioral and physiological similarities between rats injected with yohimbine and those with lesions of the lateral hypothalamus. The present study sought to determine if behaviors mediated by the lateral hypothalamus would be significantly altered by yohimbine. Deficits in performance of an active avoidance task have been observed after lateral hypothalamic lesions. Likewise, in the present experiment, yohimbine significantly reduced the ability of trained rats to perform in a similar paradigm. Systemic injections of yohimbine caused decrements in lateral hypothalamic self-stimulation behaviors as well as in locomotor activity produced by lateral hypothalamic stimulation. Similar behaviors mediated by the substantia nigra were relatively unaltered by yohimbine. A final experiment revealed that yohimbine reduces the enhanced glucose utilization normally observed at the lateral hypothalamus during electrical stimulation. These data support the view that the lateral hypothalamus may be an important target of yohimbine's CNS actions.

Animals

Differential effects of localized lesions of n. accumbens on morphine- and amphetamine-induced locomotor hyperactivity in the C57BL/6J mouse.

Mice of the C57BL/6J strain became hyperactive to increasing doses of morphine sulfate. This response was similar to locomotor hyperactivity induced by amphetamine. Lesions and chemical blockade of posterior n. accumbens abolished amphetamine-induced hyperactivity and reduced but did not abolish the morphine response. These experiments demonstrate that the response to the two drugs is mediated by overlapping but noncongruent neural systems.

Amphetamine

Movement induced in cataleptic rats: differential effects produced by electrical stimulation of the lateral hypothalamus, substantia nigra, and reticular formation.

Haloperidol catalepsy can be countered by electrical stimulation of the lateral hypothalamus (LH) and, to a lesser extent, the reticular formation (RH). Substantia nigra (SN) stimulation proved to be least effective in this regard. Dissociation between behavioral arousal and cortical EEG during stimulation of the RF in cataleptic rats was observed.

Animals

Persistence of lateral hypothalamic-mediated behaviors after a supralethal dose of ionizing radiation.

After exposure to 10 krad of high-energy electrons, rats experience an early transient incapacitation characterized by symptoms similar to those associated with lateral hypothalamic lesions: akinesia and decrements in various motivated behaviors. Experimenter-imposed electrical stimulation of the lateral hypothalamus in akinetic, irradiated animals produced a locomotor response similar to that seen in unexposed rats. Furthermore, when allowed to self-stimulate, the irradiated subjects persisted in vigorous self-stimulation of the lateral hypothalamus while self-stimulation rates of other subcortical sites showed marked attenuation. The lateral hypothalamus is apparently less sensitive to ionizing radiation than are the other subcortical structures sampled.

Animals

Classical conditioning of hippocampal theta patterns in the rat.

Electrical stimulation (88 HZ) of the lateral hypothalamus elicited a sustained theta response at hippocampal recording sites of rats immobilized with succinylcholine. By pairing this unconditioned stimulus with a 10-sec presentation of a light, conditioned theta responses were demonstrated in as few as 40 trials. Spectral analysis of hippocampal bioelectric patterns during acquisition, extinction, and reconditioning indicated that the earliest change as a result of conditioning is a loss of power in EEG frequency below 8 HZ, followed by the development of a peak at 8 HZ with further conditioning. Extinction was associated with an increase in power in the frequencies below 8 HZ. When the conditioned rats were tested in the absence of the neuromuscular blocking agent, the conditioned stimulus elicited a theta response that was associated with slow motor activity on 70% of the trials.

Animals

Behaviorally evoked hippocampal theta waves: a cholinergic response.

Forced running in a treadmill results in the instantaneous appearance of a synchronous electroencephalographic pattern in the dorsal hippocampus of the rat. A similar bioelectric response in the absence of movement is induced by physostigmine. Both responses are blocked with scopolamine. Lesions of the medial septal nucleus abolish hippocampal theta waves induced by forced running or physostigmine.

Acetylcholine

Relationship between hippocampal theta activity and running speed in the rat.

The frequency of occurrence and amplitude of hippocampal theta waves induced by forced locomotion is proportional to speed of movement on a treadmill. Although induction of hippocampal theta waves is related to the initiation of movement, it is not dependent upon proprioceptive feedback because it persists in the resting animal after a bout of running. It is possible to obtain cortical theta waves in the absence of hippocampal theta activity.

Animals

A comparison of pediatric interviewing skills using real and simulated mothers.

In order to allay concerns about using simulators as opposed to real mothers for teaching and evaluating interviewing skills, a study was designed to test for differences in students' approaches when interviewing simulated and real mothers. Three mothers were trained to give their own children's histories consistently and two mothers trained to simulate a history. Thirty third-year medical students conducted two interviews which were audiotaped. Students were told the nature of the study and whether the mother was real or simulated. One half of the time the mothers were presented as simulators and one half of the time the simulators were presented as mothers. The variable of order was controlled. An objective checklist containing 70 to 80 bits of organic and personal data per case and an interaction analysis (with an average of 285 interactions per interview) were utilized to measure the content material gathered and the approach used by the students. The data were analyzed using an analysis of variance (ANOVA) technique. All but 1 of the 55 null hypotheses were accepted, i.e., no significant differences were found. The Use of Simulation for Teaching and Evaluating Interviewing Skills Provides a Valid Experience.

Child