Thioridazine effect on desipramine plasma levels.
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Biomedical subjects
Publications and source records attributed to J A Bennett.
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Of one hundred patients with velopharyngeal incompetence subjected to a pharyngoplasty selected on the results of endoscopic and radiological examination 97% were cured of unacceptable nasal escape and 93% of unacceptable nasal resonance on the criteria described. It was considered that this provided a vindication of the system of treatment. Critical examination of the morbidity revealed an unacceptably high proportion of hyponasality. This appeared to be due to ignoring the criteria for selection for pharyngoplasty and opting for the more radical operation resulting in over-treatment in some cases. With the numbers available in the smaller treatment groups it was not possible to state that there was no significant difference in the results between the different pharyngoplasties in the groups for which they were selected. It is expected that there will be a larger proportion of patients receiving less radical treatment without detriment to the success rate, but with a lower morbidity. Assuming that it is accepted that as much accurate information as possible prior to operation is needed for the correct selection of operation, simultaneous endoscopic and radiological examination provide a time- and cost-efficient system the benefit of which becomes overwhelming for revision of the failed pharyngoplasty.
Immunological function was analyzed in mice that received daily inoculations of 5'-amino-5'-deoxythymidine (1000 mg/kg/day, i.p.) or 5-iodo-2'-deoxyuridine (100 mg/kg/day, i.p.) following antigenic stimulation. 5' Amino-5'-deoxythymidine did not suppress the development of: (1) delayed type hypersensitivity response to sheep red blood cells, (2) cell-mediated cytotoxicity response to allogeneic tumor cells, and (3) IgM and IgG antibody response to sheep red blood cells. In contrast 5-iodo-2'-deoxyuridine suppressed the development of all of these responses.
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The location, within the brain stem, of vagal efferent neurones with axons in the cardiac and pulmonary branches of the cat, and the cardiac branch of the dog, have been defined. Horseradish peroxidase was applied to the cut central ends of these vagal branches and, after an appropriate time, sections of the brain stem were examined for labelled cell bodies. Labelled cell bodies were found ipsilaterally in the dorsal motor vagal nucleus, the nucleus ambiguus and in the reticular formation between these two nuclei. We suggest that the dual location for cell bodies of vagal axons may represent a separation of somata with myelinated and non-myelinated vagal axons to the nucleus ambiguus and the dorsal motor vagal nucleus respectively.
Intravenous inoculation of BCG into C57 B1/6 mice activated natural suppressor cells in the bone marrow and induced suppressor cells in the spleen. The suppressor activity of these cell populations was determined by co-cultivating them with normal lymphocytes being immunized against allogeneic P815 cells in vitro. Six million cells from the spleen or bone marrow of BCG treated mice inhibited by more than 50% the alloimmunization of twenty million normal syngeneic lymphocytes. The suppressor cells were found in the nylon wool adherent population in spleen and in both the nylon wool adherent and non-adherent populations in bone marrow. Indomethacin, at a concentration of 10(-6)M, completely blocked the suppression generated by unfractionated spleen or adherent spleen from BCG treated mice. However, 10(-6)M and higher concentrations of indomethacin only partially blocked the suppression generated by unfractionated marrow or adherent marrow from BCG treated mice. The suppression generated by non-adherent marrow from BCG treated mice was completely insensitive to indomethacin.
Ten anaesthetists were asked to make judgments on fitness for elective operation on data derived from 200 patients. The extent of their agreement was measured using a kappa statistic, and clusters of anaesthetists who agreed well with each other were identified. Using an alternative technique, the "true" fitness category of each patient was estimated using a maximum likelihood method which estimated the error involved in making judgments on limited amounts of information. It was possible to compare the performance of each anaesthetist against the consensus and to measure deviation on an "optimism--pessimism" continuum. A simple questionnaire predicted fitness for operation by all 10 anaesthetists in 96% of cases.
Pretreatment of mice with three batches of BCG Phipps strain 10 days before in vitro immunization of their spleen cells with syngeneic or allogeneic tumor cells augmented the levels of antitumor cytotoxicity (compared to the levels exhibited by in vitro immunized spleen cells from normal mice), whereas pretreatment with another batch of BCG Phipps strain or with a batch of BCG Tice strain suppressed antitumor cytotoxicity. The suppressive effects of these BCG vaccines could not be attributed to route of administration, dose of BCG, or percentage of colony-forming units in an inoculum. The effect of the interval between BCG pretreatment and in vitro immunization on the generation of antitumor cytotoxicity was evaluated; one BCG batch was of special interest, inasmuch as augmented cytotoxicity was obtained when the interval was short and suppressed cytotoxicity was obtained when the interval was long.
Bacillus Calmette-Guérin (BCG) stimulated the proliferation of granulocyte-macrophage colony-forming cells (CFU) and activated suppressor cells that inhibit the immunization of T-lymphocytes in vitro. Increases in both CFU concentration and suppressor cell activity were moderate in the bone marrow and marked in the spleen of mice given BCG i.v. In the bone marrow, these increases were apparent 2 days after treatment with BCG, while in the spleen they did not occur until 7 days after BCG. A BCG strain that produced no increases in CFU concentration also produced no activation in suppressor cell activity. Fractionation of spleen cells through nylon wool and density gradients revealed that cell populations enriched in CFU were also enriched in suppressor cell activity. The paralelism in the response to CFU and suppressor cells to BCG indicates that there is a close relationship between these two cell populations.
Pretreatment of H-2b mice with KCl-extracts of an H-2d tumor (L1210) together with L1210 antibody rendered the mice incapable of mounting an effective immune response to viable L1210 tumor cells. This specific immunosuppression was associated with inhibition of macrophage functions, which could be used to quantitate the level of suppression. Lyt 1 cells (but not Lyt 2 cells) from either the spleen or thymus of mice pretreated with antigen-antibody complexes could adoptively transfer the suppressed state to normal mice. The Lyt 1 cells that transferred the suppression were resistant to low (20 mg/kg) doses of cyclophosphamide (Cy) but required a Cy-sensitive precursor and/or amplifier cell to be activated. Once activated, they required a Cy-sensitive Lyt 1 2 3 acceptor cell in the normal recipient to effectively suppress the adoptive host's macrophages. Our results indicative that immune complexes in concert with a Cy-sensitive T cell generate Cy-resistant Lyt 1 inducers of suppression. These in turn activate normal thymic or peripheral Lyt 1 2 3 acceptor cells, resulting in the generation of effector suppressor T cells. These suppressor cells are most likely the proximate cause of the inhibition of macrophages we have observed in vivo.
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Addition of normal C57BL/6 mouse bone marrow cells to an in vitro culture of normal C57BL/6 spleen cells and allogeneic P815-Y tumor cells inhibited the development of cell-mediated immunity. Bacillus Calmette-Guérin (BCG) enhanced the suppressive activity of these bone marrow cells as early as 2 days after its intravenous administration to donor mice and elicited similar activity in the spleen by 7 days. Concomitant with the appearance of suppressor cells in the spleen there was a decrease in bone cell number and an increase in spleen cell number. While normal spleen cells failed to inhibit immunization, spleen cells from thymectomized, irradiated, bone marrow-reconstituted mice were inhibitory. Administration of BCG further increased the suppressive activity of spleen cells in these T cell-deprived mice. From this evidence it appears that systemic administration of BCG activates natural suppressor cells in the bone marrow and elicits suppressor cells in the spleen through the migration and colonization of the spleen by bone marrow elements.
Following the report of the death of a patient concurrently taking fenfluramine, following routine general anaesthesia, a series of anaesthetised rabbits received injections of adrenaline or fenfluramine. There were abnormal electrocardiographic changes and phonocardiographic evidence of altered heart activity in both groups, but the changes seen with fenfluramine were greater in number and less readily reversed with beta blockers and resuscitative drugs. This evidence may support an interaction between halothane and fenfluramine in man, and it is suggested that the latter drug be discontinued for a week prior to anaesthesia for elective surgery.
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