Adrenaline in local anesthetic solutions.
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Biomedical subjects
Publications and source records attributed to B Scott.
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T cell receptor (TCR) gene segments begin to rearrange in CD4-8-thymic lymphoblasts. In severe combined immune deficiency (scid) mice the development of T cells is arrested at this early stage as the scid thymus does not contain any CD4+ or CD8+ lymphocytes. This block in T cell development can be overcome by introducing productively rearranged TCR genes into the scid strain which results in the formation of CD4+8+ lymphocytes. While this early differentiation step requires TCR's of any specificity, later developmental stages depend on the specificity of the TCR: in scid mice, a transgenic TCR restricted by Db class I major histocompatibility complex (MHC) antigens allows the formation of CD4-8+ but not CD4+8- lymphocytes in Db positive but not Db negative animals. Thus, a TCR-MHC interaction in the absence of nominal antigen is required for the generation of mature T cells, and this interaction determines the CD4/CD8 phenotype. If both nominal antigen and presenting MHC antigen are present developing T cells are deleted at an immature CD4+8+ stage preventing the formation of more mature and functional autoaggressive T cell progeny. These experiments indicate that the immune system first learns about self by positive and negative selection of self recognizing lymphocytes from a continuously turning over pool of lymphocytes without requirement for idiotypic network interactions.
In view of the well known cytotoxic effects of hydrogen peroxide, it was decided to investigate the neurotoxic effects of this oxygen metabolite on the electric membrane properties of neurons. Neural cell cultures of adult mouse dorsal root ganglia were chronically exposed to H2O2 and electrical properties of the neurons determined using intracellular recordings. Chronic H2O2 exposure caused a variety of alterations in EMP including increased overshoot, afterhyperpolarization and duration of the action potential. The prolongation of the action potential was due to a shift to a more biphasic type of repolarization and to a decreased rate of fall of the initial phase of repolarization. The observed pattern of EMP alterations in conjunction with previous investigation of ionic dependence in these neurons suggested that hydrogen peroxide may exert its toxic effect, at least in part, by increasing the calcium dependence of the action potential ionic mechanism.
This study compared canine cardiovascular responses observed after endotracheally administered atropine, isoproterenol, and propranolol to those observed following IV administration. Acetylcholine and isoproterenol dose response curves for arterial pressures and heart rate were established following IV boluses of each drug. Once the dose response curves were established, atropine and propranolol were administered endotracheally and intravenously in different groups to alter the established dose response curves. The time required for endotracheally and intravenously administered atropine and propranolol to inhibit 50% of the mean arterial pressure response following an IV infusion of acetylcholine and isoproterenol, respectively, was determined. Atropine and propranolol administered by either route significantly altered the arterial pressure response to acetylcholine and isoproterenol (P less than .05), respectively. Atropine altered the heart rate response to acetylcholine when administered by either route (P less than .05). IV-administered propranolol altered the heart rate response to isoproterenol (P less than .05); endotracheally administered propranolol did not. Atropine administered IV inhibited 50% of the mean arterial pressure response during an acetylcholine infusion within 21 seconds, and within 48 seconds following endotracheal administration. Propranolol administered intravenously inhibited 50% of the mean arterial pressure response during an isoproterenol infusion within 23 seconds, and within 49 seconds following endotracheal administration. The arterial pressure and heart rate responses immediately following endotracheally and intravenously administered isoproterenol also were measured and compared. The arterial pressure and heart rate responses after endotracheally administered isoproterenol were much less than those following IV administration (P less than .005). In dogs the pharmacological effects following endotracheally and intravenously administered atropine and propranolol are similar, while the effects of endotracheally and intravenously administered isoproterenol differ greatly.
Two children with leukaemia are described who successfully underwent oversewing of perforated duodenal ulcers which probably were secondary to immunosuppression and steroid therapy. This is only the second report of ulceration in childhood leukaemia. Stress ulceration in children responds favourably to conservative surgery and removal of the insult. Ulcer prophylaxis with antacids or Cimetidine should be initiated in patients being subjected to combined immunosuppression and high-dose steroids, particularly during bone marrow transplantation.
Twenty patients with severe tinnitus who had undergone behavioural treatment, including applied relaxation and perceptual restructuring, were re-assessed 9 months after completion of treatment. Among the self-recorded variables, tinnitus loudness, discomfort from tinnitus, depression, and irritation, discomfort from tinnitus was the only variable which was still significantly reduced. As part of the 9-month follow-up assessment, the patients' recall of the loudness and discomfort from their tinnitus was studied. Correlations between original recordings and recall data were low.
From a waiting list consisting of hearing-impaired patients waiting for hearing aids to be fitted, 39 subjects who at interview also stated that they had tinnitus took part in an experimental group study with the aim of investigating the effect of a hearing aid on tinnitus. No subject had any previous experience of hearing aids. The subjects were randomly allocated to a treatment and a waiting list control group. After an initial interview, the routine programme for the fitting of hearing aids started in the treatment group, while the waiting list control group had to wait for 6 weeks before starting the same hearing aid rehabilitation programme. The hearing aids were fitted exclusively for hearing purposes. As expected, the hearing aids improved the hearing capacity, but they did not reduce tinnitus as recorded on a visual analogue scale. According to information obtained at the final interview, there were significant differences in tinnitus between subjects who used their aid for more than 2 hours daily and those who used it for less than 2 hours. However, the results of scaling (pre- and post-fitting) did not support this finding. The discrepancy between the scaling and interview data is probably due to demand characteristics.
Familial polyposis coli has generally been considered a disorder of adulthood that is rarely identified in children. We report 3 affected kindreds in which the disorder was diagnosed in 6 of 11 potentially affected children between 8 and 16 years of age. Experience with these kindreds demonstrates that polyps frequently develop during childhood in affected individuals. Colonoscopy was found to be preferable to the air-contrast barium enema, in that it was as sensitive a technique for detection of adenomas, and in that it also permitted collection of biopsies for histologic confirmation. We recommend that colonoscopy be performed late in the first decade of life before symptoms develop. Total colectomy, rectal mucosectomy, and ileo-anal anastomosis eliminated the risk of malignancy, preserved anal sphincter function by both clinical and manometric assessment, and was readily adapted to by these children.
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A preliminary technique is described for freezing and thawing of intact neural cell cultures and neural cell suspensions of adult mouse dorsal root ganglia which permitted the neurons to retain to a remarkable degree their usual morphological and electrophysiological characteristics. Determination of ten electrical membrane properties (EMP) indicated significant quantitative alterations including increased specific membrane resistance and duration of the action potential and decreased resting membrane potential. The pattern of altered EMP was discussed in terms of the possible ionic site of freezing damage.
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We examined the effect of nutritional rehabilitation in cystic fibrosis patients with severe disease. Thirteen malnourished patients (seven males, six females, age 7-27 yr) were studied over 7-16 mo. Oral supplementation was attempted initially in 12 patients (mean duration 6.7 mo); only 2 patients gained weight, 2 withdrew, and 1 died. The remaining 7 patients failed to achieve adequate weight gain and were commenced on nasogastric supplementation with a semisynthetic formula. An additional patient was entered without a prior period of oral supplementation because of the severity of malnutrition. Weight gain was achieved in 7 of 8 patients with nasogastric supplementation (mean duration 6.4 mo). Weight gain was associated with an increase in lean body mass, total body fat, and height velocity. While pulmonary function and biochemical parameters were unchanged, patient well-being improved and episodes of pneumonia decreased.
In earlier work on malignant hyperthermia (MH) susceptible pigs the concentration of muscle metabolites differed from that found in normal control pigs. Therefore, in the present study these metabolites were measured in human muscle biopsies to find out whether normal individuals could be discriminated from MH-susceptible persons. Analysis of skeletal muscle metabolites was performed on skeletal muscle obtained from humans (n = 68) being screened to exclude or confirm susceptibility to MH. Three groups were identified based on the reaction pattern of a skeletal muscle sample exposed in vitro to caffeine or halothane 1% plus caffeine: 1) MH susceptible (MHS; n = 19); 2) normal humans, (controls; n = 31); and 3) intermediate-reaction type (K-type:n = 18). No significant differences were found in metabolite levels of phosphocreatine (normal, MHS, and K-type: 13.20 vs. 13.74 vs. 14.42 nmol/mg wet weight, respectively), creatine (16.30 vs. 16.94 vs. 15.06 nmol/mg wet weight, respectively), adenosine triphospate (3.75 vs. 3.98 vs. 3.89 nmol/mg wet weight, respectively) and lactate (3.73 vs. 3.65 vs. 3.79 nmol/mg wet weight, respectively). It is concluded that analysis of skeletal muscle metabolites cannot be used as a screening test to confirm or exclude MH susceptibility in humans.
Transcutaneous electrical stimulation was used in 5 consecutive patients suffering from troublesome tinnitus. The study included three parts. Part one constituted an open trial using the stimulation equipment. During this part, 2 patients reported a reduced subjective tinnitus loudness. These 2 patients proceeded to part two where the effect from the stimulation equipment was compared with the effect from a placebo apparatus in an experimental double-blind trial. One of these 2 patients reported similar effects from active stimulation and placebo, while the other patient reported a constant positive effect from the active stimulation and no effect at all from placebo. The latter patient continued to part three where the effect of the equipment was studied over a 3-month period. Throughout the study, continuous self-recordings of the complaints was used. The results show that the electrical stimulation had a genuine tinnitus-reducing effect in one patient, remaining over a 3-month period, a positive placebo effect in one patient, but no effect in 3 patients. To determine the applicability of this method in the clinical population, carefully designed outcome studies, with appropriate control conditions, are required.
In the present study, neural cell cultures of fetal and adult mouse dorsal root ganglia (DRG) were prepared, exposed to various concentrations of lead (Pb) for two different schedules, and dose survival curves obtained. For the late exposure (LE) to Pb, Pb was applied from 8 DIV to 20 DIV (12 day exposure) while for the early exposure (EE), Pb was applied from 2 DIV to 20 DIV (18 day exposure). For LE there was evidence for increased vulnerability of adult compared to fetal neurons and the LD50 for both was greater than 100 microM. For both LE and EE and for both adult and fetal tissue, the non-neuronal cells were much more sensitive to the toxic Pb effects than neurons. For the LE, the adult and the fetal non-neuronal cells had LD50s of 28 microM and 58 microM respectively. For EE the LD50 for adult neurons was 35 microM. The differential effect of Pb on fetal and adult non-neuronal cells observed for LE was reversed in direction for EE; the LD50 for adult non-neuronal cells being 5.5 microM and the LD50 for fetal non-neuronal cells being only 1.7 microM, making the fetal cells about three times more sensitive than adult non-neuronal cells. An explanation of the differential effects of Pb on neurons and non-neuronal cells and on adult and fetal cells was proposed which incorporated known cell dynamics in vitro.
Neural cell cultures of dissociated dorsal root ganglia (DRG) were used to investigate the effect of chronic ethanol exposure on the differential survival of fetal and adult neurons and non-neuronal cells. After 12 days of culture in ethanol (20 DIV), counts were made of both neurons and non-neural cells. Unexpectedly, the adult neurons showed a slightly greater degeneration with increasing ethanol than fetal neurons; the adult and the fetal neurons had LD50s of 1.78 and 2.08 gm% respectively. In contrast, for the non-neuronal cells the differential response was reversed; the fetal non neuronal cells were more affected than the adult non neuronal cells with LD50s of 0.7 gm% and 0.94 gm% for fetal and adult non-neuronal cells respectively. Also independent of developmental stage, the non-neuronal cells were 2 to 3 times more sensitive (in terms of survival) to increasing ethanol than the neurons. Electron microscopic examination suggested an increased amount of lipofuscin and dilated endoplasmic reticulum in the adult neurons exposed to ethanol. The possible significance of the results to fetal alcohol syndrome (FAS) is discussed.