Biomedical subjects
H Fisher
Publications and source records attributed to H Fisher.
Evaluation of deoxycoformycin in patients with advanced renal cell carcinoma. An ECOG pilot study.
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Quantification of the in vitro activity of some compounds with spermicidal activity.
The in vitro spermicidal activity of the commonly used surfactant spermicides and the antiseptic chlorhexidine, were quantified in a statistically reproducible manner, using donor semen and image capture analysis. The spermicidal activity was expressed as the ED50 under defined assay conditions. Using these parameters, the order of spermicidal activity was: Menfegol > nonoxynol-9 approximately benzalkonium chloride > sodium docusate > chlorhexidine. These differences were statistically significant.
Ethanol intake of chickens treated with fenfluramine, fluoxetine, and dietary tryptophan.
Male, white leghorn chickens fed a standard diet with or without tryptophan supplementation were treated with single injections of 8 mg/kg fenfluramine in one series of experiments, or 8 mg/kg fluoxetine in another series. The birds had been food- and water-deprived prior to injection. They were offered, following the drug or saline injection, water, a 5% ethanol solution, or an isocaloric sucrose solution (8.75%) for 1 hr. Both fluoxetine and fenfluramine significantly reduced consumption of the ethanol solution, an effect exacerbated by tryptophan supplementation. Water or sucrose solution intake was also significantly reduced, but significantly less so than ethanol after fenfluramine injection. Since the birds drank significantly more of the sucrose solution after saline injection than of water, the consumption decrease caused by fenfluramine resulted, nevertheless, in a higher intake than that of either water or ethanol. Body temperature was decreased by ethanol intake and/or fluoxetine injection. Fenfluramine injection had an opposite, body temperature-increasing effect. It appears that both fenfluramine and fluoxetine decrease ethanol intake in a manner more specific than for water or sucrose, and that this effect is amplified by dietary tryptophan supplementation.
Low-calcium diets enhance phytate-phosphorus availability.
This study showed that, in chickens, the negative effects of phytate-phosphorus in a low inorganic phosphorus diet could be completely reversed through the additive effects of reduced dietary calcium and increased cholecalciferol. In the future, perhaps greater reliance on more readily available plant phosphorus sources may be instituted in developing countries, where cheap sources of inorganic phosphorus are difficult to obtain.
High-dose carboplatin and etoposide with autologous bone marrow transplantation in refractory germ cell cancer: an Eastern Cooperative Oncology Group protocol.
PURPOSE: A phase II trial was undertaken to assess the feasibility, toxicity, and efficacy of high-dose carboplatin and etoposide with autologous bone marrow transplantation in patients with relapsed or refractory germ cell tumors. PATIENTS AND METHODS: Forty patients with recurrent germ cell cancer received carboplatin 500 mg/m2 and etoposide 400 mg/m2 given at 7, 5, and 3 days before marrow infusion. Autologous marrow infusion (day 0) was accomplished using one half of the bone marrow harvested before chemotherapy. Patients who achieved a complete or partial response with the first cycle of treatment received a second identical cycle of chemotherapy followed by infusion of the remaining cryopreserved bone marrow. RESULTS: Objective responses were obtained in 17 of the 38 patients (45%) assessable for response, including eight partial and nine complete remissions. Five of these patients remain in continuous complete remission with minimal follow-up of 1 year. Toxicity encountered was primarily hematologic, and five patients (13%) died of treatment-related complications. Significant toxicities often seen with high-dose cisplatin (ototoxicity, neurotoxicity, and renal toxicity) were manageable in this regimen of high-dose carboplatin. CONCLUSIONS: This trial confirms the curative potential of high-dose carboplatin and etoposide in highly refractory germ cell cancer.
Roles of in vitro- and in vivo-administered histamine and serotonin in compound 48/80-induced gastric acid secretion in isolated, perfused rat stomach.
In this investigation, an isolated, perfused rat stomach system was used to elucidate the roles of histamine, serotonin, and the action of cimetidine, methysergide, and propranolol in relation to the in vivo and in vitro administration of compound 48/80. While histamine administered both in vivo and in vitro stimulated acid secretion in the perfused rat stomach, serotonin, added in vitro, inhibited histamine-induced gastric acid secretion. Cimetidine, given either in vivo or in vitro, blocked histamine-induced acid secretion, and methysergide, but not propranolol, reversed the serotonin-induced inhibition of histamine-stimulated acid secretion. Compound 48/80, given in vitro, caused gastric acid secretion that was blocked by pretreatment with cimetidine. Administered in vivo, however, compound 48/80 inhibited both basal and histamine-stimulated acid secretion. This inhibition was partially reversed by pretreatment with methysergide. The absence of inhibition of acid secretion by in vitro-administered compound 48/80 may be related to the timing of the serotonin effect. When serotonin was given prior to histamine, it blocked acid secretion, whereas no inhibition occurred when serotonin was administered together with histamine. None of the other agents investigated affected basal acid secretion.
In vitro response of peripheral blood mononuclear cells to phytohemagglutinin and interleukin-2.
The serological determination of class II antigens is still a mandatory test prior to allotransplantation. It is known that these antigens are normally expressed on B lymphocytes and monocytes. The B lymphocytes that constitute 10% to 15% of total blood lymphocytes are the cells currently used for HLA-DR typing. To avoid HLA-DR typing difficulties, or even impossibilities that are frequently encountered among some patient groups, we studied the response of peripheral blood mononuclear cells--as an alternative source of cells for class II antigen typing--to in vitro mitogen and interleukin-2 activation and propagation. Although the patients included in this study were selected having previously known HLA-DR typing difficulties, all could be adequately typed by this method.
Suppression of ethanol intake in chickens by fenfluramine and dietary tryptophan.
Two groups of 10-week-old White Leghorn cockerels were fed a commercial grower diet with or without an L-tryptophan (0.5%) supplement. After a 24-hr water deprivation and 13 to 14 hr without food, the birds were randomly injected with 0 (saline) 4, 8, or 12 mg of fenfluramine/kg body weight. Thirty minutes after injections, water or a 5% ethanol solution was offered, no choice, to the birds and fluid consumption as well as skin and rectal temperature before and after fluid availability were measured. The ethanol solution in otherwise untreated animals was consumed in similar amounts as water was. Fenfluramine (8 mg/kg) significantly reduced ethanol consumption and tryptophan further significantly reduced ethanol intake. At 12 mg/kg fenfluramine, both water and ethanol intake were sharply reduced. Ethanol decreased body temperature, an effect that was reversed by both tryptophan alone and fenfluramine + tryptophan in a dose-dependent manner. These observations are discussed in reference to the effects of central serotonergic manipulations and ethanol consumption.
Mobilization of renal carnosine and histidine to histamine during compound-48/80-induced shock.
Recently the presence of carnosine in the kidney has been established, and several potential roles for histamine have been proposed in renal metabolism. Histamine is known to occur in relatively high concentrations in renal tissue of several species and has been implicated in the autoregulation of renal blood flow and glomerular filtration. This study was designed to evaluate the effect of shock produced by compound 48/80 on the mobilization of renal carnosine to histamine and the effects of various blocking agents such as lodoxamide, diphenhydramine and cimetidine on this mobilization. Our results showed that compound-48/80-induced shock causes significant mobilization of renal carnosine and histidine to histamine and that this response can be blocked by administration of lodoxamide and diphenhydramine, but not cimetidine.
Client confidentiality and the family's need to know: strategies for resolving the conflict.
Vital supports for individuals disabled by mental illness are often provided by their families. The ability of these families to help is dependent on their knowledge of their relative's illness and treatment regime. However, practitioners wishing to provide such information feel a conflict between the family's interest in the information and their client's right to confidentiality. This article presents strategies to enhance information sharing with families while still protecting the client's confidentiality.
The presence and significance of carnosine in histamine-containing tissues of several mammalian species.
Histamine is known to exert profound effects on the cardiovascular system in many mammals. Carnosine (beta-alanyl-L-histidine) is a dipeptide previously known to be present only in a few tissues. It is our hypothesis that carnosine serves as a non-mast cell reservoir for histidine, available for histamine synthesis during periods of physiologic stress. To validate this hypothesis, we demonstrated the existence of carnosine in multiple histamine-rich tissues in several mammalian species; documented a metabolic link between carnosine and histidine, histamine and 3-methylhistamine (a degradation product of histamine) in unstressed animals, and showed that tissue carnosine is decreased simultaneously with an increase in tissue histamine during stress.
Effect of histamine antagonists on myocardial carcinine metabolism during compound 48/80-induced shock.
Carcinine (beta-alanylhistamine) is an imidazole dipeptide that exists in mammalian hearts, increases cardiac contractility, and is metabolically linked to carnosine (beta-alanylhistidine), a non-mast cell histidine and histamine precursor during stress. We have previously shown that tissue carnosine levels are regulated by H1 and H2 receptors. This study evaluated the effects of H1, H2, and mast cell degranulation blockers on metabolism of carcinine and related imidazoles during shock induced by compound 48/80, a mast cell degranulator. Fifty 125-g male Sprague-Dawley rats were divided into nine ip treatment groups: saline, 48/80, lodoxamide (LOD, mast cell degranulation inhibitor), diphenhydramine (DPH, H1 antagonist), cimetidine (CIM, H2 antagonist), LOD + 48/80, CIM + 48/80, DPH + 48/80, or DPH + CIM + 48/80. Heart tissue was analyzed at 30 min by HPLC. 48/80 caused decreases in myocardial carnosine (P less than 0.01) and histidine (P less than 0.0001) levels and concomitant increases in carcinine (P less than 0.01), histamine (P less than 0.01), and 3-methylhistamine (P less than 0.05) compared to those of controls. These changes were inhibited by LOD or DPH. Treatment with CIM significantly increased myocardial carcinine levels compared to 48/80 alone (P less than 0.001) without an additional effect on the other compounds. These data indicate that carcinine is involved in the cardiac response to stress via the carnosine-histidine-histamine pathway. Compound 48/80-induced shock increases histamine metabolism via this pathway resulting in mobilization of myocardial carnosine and histidine to carcinine and histamine; this effect is increased by H2 receptor blockade.
Existence of carcinine, a histamine-related compound, in mammalian tissues.
Carcinine (beta-alanylhistamine) was synthesized in vitro from histamine and beta-alanine. It was detected quantitatively using an HPLC method previously described for the quantification of the related compounds histamine, histidine, carnosine and 3-methylhistamine. Carcinine was identified in several tissue of the rat, guinea pig, mouse and human, and was then shown to be metabolically related in vivo to histamine, histidine, carnosine and 3-methylhistamine through radioisotopic labeling. The results demonstrate that carcinine may be concurrently quantitated using the same HPLC method as that used to measure histamine, histidine, carnosine and 3-methylhistamine. These findings suggest a role for carcinine in the carnosine-histidine-histamine metabolic pathway and in the mammalian physiologic response to stress.
Positive inotropic effect of carcinine in the isolated perfused guinea pig heart.
Carcinine (beta-alanylhistamine) is a recently discovered compound that is present in the hearts of several mammalian species, including man. Although the function of carcinine is unknown, its structural similarity to histamine, a compound known to have profound effects on the mammalian heart, and to carnosine (beta-alanylhistidine), a compound which we have previously shown to serve as a histamine source, led to the hypothesis that carcinine may play a role in mammalian cardiac physiology. We therefore administered several doses of carcinine (10, 25, 50, 75, and 100 micrograms) to isolated, perfused guinea pig hearts in a Langendorff apparatus. Carcinine exerted a dose-dependent positive inotropic effect, similar to that of histamine. Comparable doses of carnosine yielded no measurable change in contractility. We conclude that carcinine appears to be a positive inotrope in the mammalian heart, and may play a role in cardiac physiology via its metabolic link to histamine.
Effect of H1 and H2 receptor blockers on mobilization of myocardial carnosine to histamine during compound 48/80-induced shock in young rats.
Histamine exerts profound effects on the cardiovascular system during shock mediated by H1 and H2 receptors. The source of histamine is uncertain. It is our hypothesis that carnosine serves as a nonmast-cell reservoir for histidine, utilized for histamine synthesis during shock. We have shown that treatment of older rats with compound 48/80, a mast cell degranulator, produces age-dependent lethal stress, which is prevented by lodoxamide (LOD), a mast cell degranulation inhibitor, is exacerbated by H2 receptor blockade, and is accompanied by increased mobilization of myocardial carnosine to histidine and histamine. This study was designed to evaluate the effects of H1 and H2 blockers on carnosine mobilization to histamine during 48/80-induced shock in young rats. Fifty male SD rats (125 g) were divided into nine groups: saline; LOD; H1 blocker diphenhydramine (DPH); H2 blocker cimetidine (CIM); 48/80; LOD + 48/80; DPH + 48/80; CIM + 48/80; and DPH + CIM + 48/80. All rats were sacrificed 30 min after final injections and hearts were analyzed via HPLC. There was a reduction in myocardial carnosine (P less than or equal to 0.01) and histidine (P less than or equal to 0.001) and a simultaneous increase in histamine (P less than or equal to 0.01, P less than or equal to 0.001) in animals receiving 48/80 or CIM + 48/80, respectively, compared to controls or groups pretreated with LOD, DPH, or DPH + CIM. These results indicate that 48/80-induced shock increases mobilization of myocardial carnosine and histidine to histamine, which supports a role for carnosine as a nonmast-cell histamine source.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of histamine receptor antagonists on mortality in compound 48/80-induced shock.
The roles of histamine and H1 and H2 receptors in shock are uncertain. We have found that treatment of aged rats with compound 48/80 (a mast cell degranulator) produced lethal (LD99) shock which was completely prevented by lodoxamide (LOD), a mast cell degranulation inhibitor. This study evaluated the effect of H1 and H2 receptors and age on mortality of 48/80-induced shock in rats. To assess survival, 65 young male (125 g), 65 mature male (250 g) and 30 aged male (500 g) SD rats were placed in groups and treated intraperitoneally with saline; 48/80; LOD + 48/80; the H1 blocker diphenhydramine (DPH) + 48/80; the H2 blocker cimetidine (CIM) + 48/80; or DPH and CIM + 48/80. Rats were observed for 30 min or until death. All 125 g rats survived. Of the 250 g rats, 50% of 48/80-treated and 100% of CIM + 48/80-treated rats died; all others survived. All 500 g 48/80- and CIM + 48/80-treated rats died; all other 500 g rats survived. For all ages, survival differences between saline-, 48/80-, and CIM + 48/80-treated rats were highly significant (P less than or equal to 0.0001). In addition, both 48/80 and CIM + 48/80 greatly reduced mean survival time in the 250 g and 500 g groups (P less than or equal to 0.0001) compared to all other treatments. Both LOD and DPH were protective against 48/80, and DPH was also protective against CIM + 48/80, for both absolute survival and mean survival time (P less than or equal to 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Melatonin mediates the antidyskinetic effects of naloxone in tardive dyskinesia.
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