Biomedical subjects
Publications and source records attributed to J M Lipton.
The concentration of MSH per unit protein is reduced on average in several sites within the brains of aged squirrel monkeys. This decrease may account for alterations in CNS functions mediated via MSH but perhaps does not account for reduced fever in these aged subhuman primates.
Explore the source record for details and available documents.
Controversy surrounds the management of a residual chest mass in patients treated for Hodgkin's disease. Between 1971 and 1985, we treated 22 children, aged 7-18 years, with pathologically proven Hodgkin's disease. Nine had radiographic evidence of mediastinal and/or pulmonary involvement. Following treatment, a residual or new chest mass occurred in three patients, prompting surgical exploration. No histologic subtype of Hodgkin's disease predominated in this group. Two patients had received radiotherapy and chemotherapy, and one had received chemotherapy alone. The erythrocyte sedimentation rate (ESR), uniformly elevated at diagnosis, was normal prior to surgery in all three patients. Gallium scans, also uniformly positive at diagnosis, were negative in two patients but positive in a third, suggesting possible relapse. At operation, however, no patient had recurrent Hodgkin's disease. Pathologic findings were thymic fibrosis, mediastinal pseudocyst, and normal thymus, respectively. We conclude that a chest mass following treatment for Hodgkin's disease may be benign, particularly if disease markers such as ESR have normalized. Moreover, a positive gallium scan does not necessarily indicate recurrent Hodgkin's disease. Although surgical exploration is a prudent policy when there is persistent evidence of residual or recurrent chest mass, our experience suggests that immediate exploration is not mandatory and may be deferred for a period of close continued observation.
The effects on fever of central administration of alpha-melanocyte-stimulating hormone (alpha-MSH) and its antiserum, the specific increase in central concentration of alpha-MSH during fever, and related results indicate that this neuropeptide is important to central nervous system (CNS) regulation of the febrile response. The present experiments were designed to establish whether alpha-MSH is released from septal tissue during fever and, if so, in what temporal course relative to the febrile response. alpha-MSH release at localized push-pull perfusion sites within the septum during fever induced by intravenous interlukin-1 occurred in two basic patterns: prolonged or repeated release over sequential 10-min sample periods or a more discrete pulse largely confined to a single 10-min period. The greatest increases in concentration and the greatest number of increases occurred during the chill phase of fever, when temperature was rising rapidly, rather than during the plateau phase. Such episodic release is similar to that known to occur in neuroendocrine and other physiological systems, and it provides further support for a physiological role of alpha-MSH in CNS control of fever.
Thirty patients undergoing craniotomies were given infusions of fentanyl 1 microgram X kg-1 X hr-1, sufentanil 0.1 microgram X kg-1 X hr-1, or normal saline in a double-blind study of cerebral relaxation. Significantly better relaxation scores were achieved in patients given a narcotic infusion, but there was no difference between the scores with the two narcotics. Infusions of narcotics at these low rates did not delay recovery or alter the requirement for other anesthetic agents. Narcotic infusion rates that do not delay recovery or alter depth of anesthesia significantly improve cerebral relaxation.
The latency to movement of an ear exposed to radiant heat was prolonged after intravenous administration of morphine to rabbits. The quantification of this response in a relatively inactive species that is especially suited for long term and repeated tests suggests that the rabbit ear-withdrawal test will be useful for screening analgesic/anesthetic compounds.
This survey continues a second series of compilations of data regarding changes in body temperature induced by drugs and related agents. The information listed includes the species used, the route of administration and dose of drug, the environmental temperature at which experiments were performed, the number of tests, the direction and magnitude of change in body temperature and remarks on the presence of special conditions, such as age or brain lesions. Also indicated is the influence of other drugs, such as antagonists, on the response to the primary agent. Most of the papers were published from 1980 to 1984 but data from many earlier papers are also tabulated.
Thirty patients having postpartum tubal ligation under extradural anaesthesia were studied. All received bupivacaine at 4 degrees C initially and the incidence of shivering (47%), and the extradural temperatures measured with a small thermistor threaded into the extradural catheter, were recorded. To eight patients in whom the resultant shivering was marked, further bupivacaine warmed to 41 degrees C was injected. In four of these patients, shivering was stopped. The results suggest that thermosensitive tissue within the spinal canal contributes to the shivering observed in association with extradural anaesthesia.
Explore the source record for details and available documents.
alpha-Melanocyte-stimulating hormone (alpha-MSH) has a marked antipyretic action when given centrally or peripherally, and the concentration of this peptide within the septal region of the brain increases during fever. To assess the significance of endogenous central alpha-MSH in fever, antiserum was given to rabbits via a cannula implanted in the third cerebral ventricle. Each day for 3 days, the animals received 50 microliters of normal rabbit serum (NRS) or an equal volume of antiserum raised against alpha-MSH. Interleukin 1 (IL 1) was then injected intravenously to determine the effect of central immunoneutralization of alpha-MSH on the febrile response. Immunoneutralization markedly prolonged fever. The average rise in temperature and the area under the fever curve after IL 1 injection were also significantly increased. Antiserum treatment did not alter normal body temperature, and NRS had no effect on IL 1-induced fever. These results indicate that endogenous central alpha-MSH contributes to physiological limitation of fever and that the role of this peptide in temperature regulation is relevant to the febrile state but not to normothermia.
We prospectively documented the development of a fatal, secondarily acquired severe immunodeficiency in a 19-year-old man who underwent uncomplicated bone marrow transplantation. He had no graft v host disease (GVHD) and had normal recovery of his immune system as determined by lymphocyte phenotyping, mitogenic responses of his peripheral blood lymphocytes, and his ability to secrete immunoglobulin. This alteration in immunity was associated with the acquisition of antibody to HTLV-III. His only risk factor for the development of HTLV-III infection was the transfusions he had received during the transplant and recovery period. Two of his 54 transfusions were from an asymptomatic individual at high risk for acquired immunodeficiency syndrome (AIDS), who was subsequently found to be seropositive for anti-HTLV-III and from whom HTLV-III was isolated. The loss of immunocompetence in patients without chronic GVHD disease is unusual, and our data support the view that this patient's immunodeficiency was due to HTLV-III. When bone marrow transplant recipients without chronic GVHD develop late opportunistic infections, consideration should be given to transfusion-associated AIDS.
To explore the etiology of congenital hypoplastic or Diamond-Blackfan anemia (DBA) we investigated in vitro erythropoiesis in nine patients. Of the nine, seven were clinically responsive to prednisone. Four were infants evaluated at the time of diagnosis. Six were never or were only minimally transfused. Those for whom prednisone had been prescribed had discontinued the drug a minimum of five months prior to study. The bone marrows of these nine patients were compared with those of hematologically normal individuals and with those of four patients with transient erythroblastopenia of childhood (TEC) whose erythroid aplasia was as severe as that of the patients with DBA. Using the plasma clot semisolid culture technique to enumerate erythroid progenitors and to evaluate the growth characteristics of the colonies to which they give rise, we concluded that at the onset of DBA: (a) erythroid progenitor frequency does not correlate with the degree of anemia and erythroblastopenia; (b) erythroid progenitor differentiation may in some cases be abnormally insensitive to crude preparations of erythropoietin; and (c) progenitor erythropoietin insensitivity in vitro does not necessarily indicate prednisone insensitivity in vivo. Thus, DBA does not appear to be solely the result of deficient formation of erythroid progenitors but is, in addition, a disorder that is due to defective progenitor differentiation in vivo.
After injection of 5 micrograms into a lateral cerebral ventricle, 6 of 12 peptides induced mean changes of 0.3 degree C or more in rectal temperature of rabbits. When beta-endorphin was studied further with 1.25-5 micrograms in 10, 23 and 30 degrees C environments, it induced dose-related hypothermia in the cold, hyperthermia in the heat and progressively smaller increases in body temperature with increasing doses at 23 degrees C.
To determine the role of Thy-1 antigen in murine hematopoietic differentiation, bone marrow was treated with anti-Thy-1.2 antibody and complement or complement alone. Growth of immature hematopoietic progenitors, erythroid burst-forming units (BFU-E), and granulocyte/macrophage colony-forming units (CFU-GM) was greatly reduced following antibody and complement treatment and was not restored by mitogen-stimulated spleen cell supernatants. In contrast, more mature erythroid and myeloid progenitors, the erythroid colony-forming unit (CFU-E) and the macrophage progenitor stimulated by L-cell-conditioned media (LCM), were spared by anti-Thy-1.2 antibody and complement treatment. Here, to separate the effects of anti-Thy-1.2 antibody treatment on accessory cells from those on progenitors, splenic T cells and thymocytes were added to treated marrow at ratios of up to 200%. Growth of BFU-E and CFU-GM was not restored. To more precisely replace required accessory cells, male complement-treated marrow was cocultured with female anti-Thy-1.2 antibody and complement-treated marrow. Even marrow cells failed to restore female BFU-E and CFU-GM growth. Fluorescent-activated cell sorting (FACS) and immune sheep red cell rosetting with anti-Thy-1.2-labeled marrow were then performed to determine if immature hematopoietic progenitors bear Thy-1.2. These techniques revealed enrichment of BFU-E and CFU-GM in the Thy-1.2-positive fraction, demonstrating the presence of Thy-1.2 on early murine hematopoietic progenitors. CFU-E and CFU-M were present in the Thy-1.2-negative fraction following FACS separation. These data demonstrate that Thy-1.2 is a differentiation antigen, present on at least some murine BFU-E and CFU-GM and lost as they mature to CFU-E and CFU-M.
This survey continues a second series of compilations of data regarding changes in body temperature induced by drugs and related agents. The information listed includes the species used, the route of administration and dose of drug, the environmental temperature at which experiments were performed, the number of tests, the direction and magnitude of change in body temperature and remarks on the presence of special conditions, such as age or brain lesions. Also indicated is the influence of other drugs, such as antagonists, on the response to the primary agent. Most of the papers were published since 1979, but data from many earlier papers are also tabulated.
This survey begins a second series of compilations of data regarding changes in body temperature induced by drugs and related agents. The information listed includes the species used, the route of administration and dose of drug, the environmental temperature at which experiments were performed, the number of tests, the direction and magnitude of change in body temperature and remarks on the presence of special conditions, such as age or brain lesions. Also indicated is the influence of other drugs, such as antagonists, on the response to the primary agent. Most of the papers were published since 1978, but data from many earlier papers are also tabulated.
alpha-MSH-related compounds may prove to be clinically useful antipyretics since the parent peptide is extremely potent in reducing fever, it is effective when given orally, and it neither stimulates corticosteroid activity nor has marked melanotropic effects in man. To determine whether or in what doses alpha-MSH might cause harmful side-effects, we injected doses greatly exceeding those required to reduce fever into a lateral cerebral ventricle of afebrile rabbits. One hundred to seven hundred and fifty micrograms alpha-MSH caused large and prolonged reductions in body temperature and the dose-response relation was bell-shaped for both magnitude and duration. These doses caused no apparent injury to the animals. One mg alpha-MSH elicited hyperthermic responses that were variable in magnitude and duration. Animals that had previously received large doses of alpha-MSH (greater than or equal to 100 micrograms) did not develop hyperthermia, even when given 2 mg, indicating an acquired tolerance to this hyperthermic action of alpha-MSH. All animals, tolerant or previously uninjected, showed symptoms with doses greater than or equal to 1 mg alpha-MSH that included: increased salivation, agitation, ataxia, respiratory distress, and death (in 30% of the animals); those that recovered from these large doses resumed outwardly healthy appearance and behavior. Although alpha-MSH is toxic when given centrally in large doses, the 5000-fold difference between antipyretic and toxic doses indicates a wide safety margin should this peptide be used clinically as an antipyretic drug.
There has been little research on the cause(s) of postanesthetic shivering (PAS) and on specific interventions. Therefore, the authors investigated PAS in eight unoperated squirrel monkeys anesthetized with halothane-nitrous oxide mixture. Shivering developed in all monkeys in which body temperature was allowed to decrease (mean +/- SEM, 2.8 +/- 0.6 degrees C) during anesthesia. Shivering occurred in 25% of animals in which body temperature was actively maintained at preanesthetic levels during anesthesia. No shivering occurred in animals warmed both during and after anesthesia. Application of radiant heat to the skin stopped PAS immediately, even though deep body temperature remained low; shivering resumed within seconds after this heating was discontinued. Intracerebroventricular (0.1-2 mg) and intravenous (100 mg/kg) administration of the putative inhibitory neurotransmitter taurine also stopped the shivering in preliminary experiments, but central injection of alpha-melanocyte stimulating hormone (100-300 micrograms), an endogenous antipyretic, did not. The results implicate reduced body temperature and activation of central heat production pathways as major factors in PAS and suggest that halothane-nitrous oxide anesthesia per se, elevation of the thermal set-point, and surgical procedures are not essential to the shivering phenomenon. The results suggest for future study two methods to control PAS: application of radiant heat or administration of taurine.