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Biomedical subjects

B E Smith

Publications and source records attributed to B E Smith.

At least 91 records · Page 5Linked to original sources
PubMed1990

Amitraz-induced glucose intolerance in rats: antagonism by yohimbine but not by prazosin.

Amitraz (N'-[2,4-dimethylphenyl]-N-[(2,4-dimethylphenyl)imino]-N- methylmethanimidamide) is a formamidine insecticide/acaricide that increases plasma glucose and decreases plasma insulin concentrations in dogs when applied topically. Because amitraz activates alpha 2-adrenoceptors in numerous tissues, in this study we used rats as a model to determine whether these effects of amitraz are mediated by alpha 2-adrenoceptors. The i.v. injection of amitraz (0.1, 0.3, and 1 mg/kg) followed by i.v. glucose injection (1 g/kg) induced a dose-dependent glucose intolerance characterized by hypoinsulinemia. At 1 mg/kg, amitraz completely blocked the insulin release induced by i.v. glucose administration. The alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, i.v.) prevented the effects of amitraz, but the alpha 1-adrenoceptor antagonist prazosin (0.3 mg/kg, i.v.) did not. The results suggested that one mechanism by which amitraz prolongs glucose-induced hyperglycemia is via inhibition of insulin release and this effect is mediated by alpha 2-adrenoceptors.

Animals↗
PubMed1990

Universities and the clinical monitoring industry: feckless independents or fruitful partners?

Since 1955 clinical monitoring in anesthesia care and critical care has improved markedly. However, both industry and academia find temptation to congratulate themselves on this achievement. Reflection, however, might suggest that, in comparison with analogous unrelated fields, the process of progress has been tardy, wasteful, expensive, and inefficient. 'State of the art' clinical monitoring may actually be viewed as woefully inadequate when measured by the yardstick of the possible. Analysis suggests that industry sometimes fails to grasp opportunities for progress by shared effort while academia, sometimes guilty of aloofness and isolation, may occasionally fail to cooperate actively to promote progress by sharing its experience with industry. To hasten the more efficient development of clinical monitoring by a new alliance of the clinical monitoring and computing industry and those universities, professors, and physicians with interests in clinical monitoring and computing is here proposed. A Foundation for Research, Development, and Advancement of Clinical Monitoring and Computing Devices should be established, to promote basic and practical research and development (R&D), sponsor shared specialized clinical testing facilities, special scholarships for physicians training as specialists in development of clinical monitoring devices, and promote and expand continuing medical education programs. By this multidisciplinary, cooperative activity, it is asserted that progress in the introduction of useful new clinical monitoring devices can be accelerated.

Critical Care↗
PubMed1990

Prophylactic administration of histamine1 and histamine2 receptor blockers in the prevention of protamine-related haemodynamic effects.

We studied the effects of the prophylactic administration of histamine1 and histamine2 receptor blockers on haemodynamic changes, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MBP), central venous pressure (CVP), and heart rate (HR, beats.min-1) before and after the administration of protamine in two groups of patients having coronary artery bypass graft surgery. Group I patients received no histamine blockers, whereas patients in Group II were treated prophylactically with both H1 (diphenhydramine) and H2 (cimetidine) receptor blockers. The mean SBP, DBP, MBP, CVP, and HR before (and after) administration of protamine in group I patients were 114 +/- 16 (90 +/- 16) mmHg, 64 +/- 11 (51 +/- 8) mmHg, 81 +/- 11 (65 +/- 10) mmHg, 10 +/- 3 (11 +/- 7) mmHg, and 92 +/- 10 (87 +/- 13) before (and after) protamine administration. Group II patients had mean SBP, DBP, MBP, CVP, and HR of 113 +/- 19 (113 +/- 17) mmHg, 61 +/- 12 (62 +/- 11) mmHg, 79 +/- 15 (80 +/- 13) mmHg, 9 +/- 3 (9 +/- 2) mmHg, and 88 +/- 6 (86 +/- 4) before (and after) protamine administration. Our data show that only in Group I patients who did not receive histamine receptor blockers, were there significant haemodynamic changes following protamine administration (P less than 0.05). We conclude that the prophylactic administration of histamine receptor blockers prevents some of the adverse haemodynamic effects associated with protamine administration.

Aged↗
PubMed1990

Nasopharyngeal carcinoma in children--a retrospective review and demonstration of Epstein-Barr viral genomes in tumor cell cytoplasm: a report of the Pediatric Oncology Group.

Twenty-seven nasopharyngeal carcinomas were entered in the Pediatric Oncology Group Rare Tumor Registry from 1973 to 1988 (15 males, 12 females; 10 white, 15 black, two unknown; aged 8 to 17 years). Eight tumors were non-keratinizing carcinomas (World Health Organization 2) and 19 were undifferentiated (World Health Organization 3). The overall 3-year survival rate was 70% (SE 11%). Nine children developed distant metastases and two were salvaged. We found that localized tumor (P = .02) and black race (P = .05) were associated with a better outcome. In situ hybridization using a biotinylated probe demonstrated Epstein-Barr virus DNA in the cytoplasm of the neoplastic epithelial cells in nine of 11 tumors examined, firmly establishing the presence of Epstein-Barr virus within the malignant cells of nasopharyngeal carcinomas of both World Health Organization 2 and World Health Organization 3 histology, rather than in the surrounding lymphocytes.

Adolescent↗
PubMed1990

Blood levels of bupivacaine after arthroscopy of the knee joint.

Toxic levels of bupivacaine have been reported in other types of surgery, but have not been previously noted in arthroscopic procedures. The purpose of this study was to evaluate bupivacaine levels after an intraarticular bolus of bupivacaine administered after arthroscopic surgery. Blood levels of bupivacaine were found to be significantly higher in patients in whom synovial surgery had been performed compared with those patients in whom the procedure involved only meniscal or articular cartilage surgery. A reduction in the bupivacaine dosage when the synovium has been resected or divided is recommended to keep the serum level below the potentially toxic range.

Adult↗
PubMed1990

Relationship between resonance and gas exchange during high frequency jet ventilation.

We have studied the relationship between gas exchange and mechanical frequency response during high frequency jet ventilation (HFJV) at 0.5-5.0 Hz in anaesthetized pigs. The mechanical gain curve showed a minimal "anti-resonant" response at 0.8 Hz (f1) and a maximal "resonant" response at 5.0 Hz (f2). This finding may be explained by modelling the thorax and abdomen as a system of coupled masses and compliances which undergo two different modes of forced oscillation in the frequency range studied. Gas exchange was optimal in the frequency range between the minimal and maximal responses. The tidal volumes produced were greater than anatomical deadspace, suggesting that gas transport was mainly convective in this range.

Animals↗
PubMed1990

Xylazine enhances porcine myometrial contractility in vitro: possible involvement of alpha 2-adrenoceptors and Ca2+ channels.

The effects of xylazine on porcine myometrial contractility were studied in vitro using uterine strips to determine the alpha 2-adrenergic influences during the diestrous stage of the estrous cycle. Xylazine (10(-8)-10(-5) M) caused a dose-dependent increase in the amplitude of myometrial contractility. The alpha 2-adrenoceptor antagonists idazoxan and yohimbine (10(-8)-10(-6) M) blocked the effects of xylazine in a dose-dependent manner. Yohimbine was approximately 10 times more potent than idazoxan in this regard. In contrast, an alpha 1-adrenoceptor antagonist prazosin (10(-7) and 10(-6) M) did not block the xylazine-induced increase in myometrial contractility, but a higher dose of prazosin (10(-5) M) did reduce the effects of xylazine. When the porcine uterine strips were pretreated with Ca2(+)-free Tyrod's solution or verapamil, a Ca2+ channel blocker, the effects of xylazine on myometrial contractility were completely abolished, whereas those of carbachol were only moderately reduced. The results suggest that the xylazine-induced myometrial contractility is mediated by alpha 2-adrenoceptors and that this effect is mediated, at least in part, by Ca2+ channels, whereas the effect of carbachol is attributed to an increase in both Ca2+ entry and release of Ca2+ from intracellular pools.

Adrenergic alpha-Antagonists↗
PubMed1990

Peripheral neuropathy in the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion.

Eosinophilia, brawny induration, and tenderness of the skin and deeper tissues, and eosinophilic and lymphocytic infiltration of skin, deep fascia, and muscle characterize the acute eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan. Many patients have a florid inflammatory myopathy. We evaluated 10 patients with this syndrome in whom peripheral neuropathy was a prominent or the only presenting feature. Two of these patients with severe neuromuscular disease required mechanical ventilation, and 1 died. Clinical severity appeared to be positively associated with the total dose of L-tryptophan ingested. Although the inflammation is generally thought to be more severe in skin, fascia, and muscle, inflammation, especially in the epineurium of sural nerve, was sometimes striking and often accompanied by vasculopathy and angioneogenesis. These cases draw attention to a new preventable syndrome with peripheral nerve involvement, emphasize the value of tissue biopsy for its diagnosis, and raise issues related to pathogenesis.

Adult↗
PubMed1990

Effects of tetramethylpyrazine on heart rate and pupil diameter in rats.

The alpha-adrenergic nature of tetramethylpyrazine (TMPZ), a commonly used cardiovascular drug in China, was studied with a combined bradycardia and mydriasis model in the pentobarbital anesthesized rat. Intravenous injections of TMPZ at 1-30 mg/kg failed to change heart rate or pupil size, whereas iv injections of both clonidine (alpha 2-adrenoceptor agonist, 1-30 micrograms/kg) and methoxamine (alpha 1-adrenoceptor agonist, 10-300 micrograms/kg) caused dose-dependent bradycardia and mydriasis. Pretreatment of rats with TMPZ (30 mg/kg) did not significantly change clonidine- or methoxamine-induced bradycardia or mydriasis. However, when TMPZ was injected 2 min after clonidine administration (30 micrograms/kg), while the mydriasis reached a maximum, it slightly but significantly reversed the clonidine-induced mydriasis for 15-20 s. In contrast, the alpha 2-adrenoceptor antagonist idazoxan (6 micrograms/kg) caused the same degree of reduction of the clonidine-induced mydriasis for greater than 2 min. Our results suggested that TMPZ at the doses studied did not have alpha-adrenoceptor agonistic activities, but may have slight alpha 2-adrenoceptor antagonistic activities.

Animals↗
PubMed1990

Analysis of site-directed mutations in the alpha- and beta-subunits of Klebsiella pneumoniae nitrogenase.

Using directed mutagenesis, amino acid substitutions have been made in the alpha- and beta-subunits of the klebsiella pneumoniae nitrogenase component 1 at positions normally occupied by conserved cysteine or tyrosine residues. Nif+, Nif- and intermediate phenotypes have been obtained. To extend our earlier biochemical characterization (Kent et al., 1989) the electrophoretic mobility of component 1 of the mutant and wild-type nitrogenases has been analysed by non-denaturing gel electrophoresis. The major and minor forms of component 1 separated by this methodology have been probed for by using both polyclonal and monoclonal antibodies. All Nif+ mutants exhibited a distribution of electrophoretic forms of component 1 comparable to the wild type, and the abundance of the major form found in purified nitrogenase correlated approximately with the specific activity of the extract. In contrast, after electrophoresis, component 1 from Nif- mutants exhibited either a major low-mobility form or a fast-moving form. Analysis of nitrogenase polypeptides synthesized in the absence of co-factor (FeMoco) allowed us to conclude that changing cysteine 275 to alanine in the alpha-subunit produces component 1 defective in its interaction with FeMoco. Substitution of other conserved cysteine residues by alanine appears to prevent early steps in nitrogenase assembly or to promote degradation. Two single mutations (cysteine 89 to alanine in the alpha-subunit and cysteine 94 to alanine in the beta-subunit) which are tightly Nif- can be combined to produce a weakly active nitrogenase, indicating regions involved in the interaction between subunits.

Electrophoresis, Polyacrylamide Gel↗
PubMed1989

Site-directed mutagenesis of the Klebsiella pneumoniae nitrogenase. Effects of modifying conserved cysteine residues in the alpha- and beta-subunits.

The five conserved cysteine residues present in the alpha-subunit and the three conserved cysteine residues present in the beta-subunit of nitrogenase component 1 were individually changed to alanine. Mutations in the alpha-subunit at positions 63, 89, 155 and 275 and in the beta-subunit at positions 69, 94 and 152 all resulted in a loss of diazotrophic growth and component 1 activity and loss of the normal e.p.r. signal of the component 1 protein. Component 2 activity was retained. Replacement of cysteine-184 in the alpha-subunit with alanine greatly diminished, but did not eliminate, diazotrophic growth and component 1 activity. Substitution of serine for cysteine at position 152 in the beta-subunit, in contrast with the substitution of alanine at this position, resulted in the formation of active component 1. Replacement of the non-conserved cysteine-112 in the beta-subunit with alanine did not greatly perturb diazotrophic growth or the activity of component 1. Extracts prepared from a mutant, with cysteine-275 of the alpha-subunit replaced by alanine, complemented extracts of a mutant unable to synthesize the iron-molybdenum cofactor of nitrogenase, indicating that the alanine-275 substitution increases the availability of cofactor. Furthermore extracts of this mutant exhibited an e.p.r. signal similar to that of extracted iron-molybdenum cofactor. These data suggest a role for cysteine-275 as a ligand to the cofactor.

Acetylene↗
PubMed1989

Vanadium K-edge X-ray-absorption spectroscopy of the functioning and thionine-oxidized forms of the VFe-protein of the vanadium nitrogenase from Azotobacter chroococcum.

Vanadium K-edge X-ray-absorption spectra were collected for samples of thionine-oxidized, super-reduced (during enzyme turnover) and dithionite-reduced VFe-protein of the vanadium nitrogenase of Azotobacter chroococcum (Acl*). Both the e.x.a.f.s and the x.a.n.e.s. (X-ray-absorption near-edge structure) are consistent with the vanadium being present as part of a VFeS cluster; the environment of the vanadium is not changed significantly in different oxidation states of the protein. The vanadium atom is bound to three oxygen (or nitrogen), three sulphur and three iron atoms at 0.215(3), 0.231(3) and 0.275(3) nm respectively.

Azotobacter↗
PubMed1989

Reduction of cyclopropene by NifV- and wild-type nitrogenases from Klebsiella pneumoniae.

The nitrogenase from wild-type Klebsiella pneumoniae reduces cyclopropene to cyclopropane and propene in the ratio 1:2 at pH 7.5. We show in this paper that the nitrogenase from a nifV mutant of K. pneumoniae also reduces cyclopropene to cyclopropane and propene, but the ratio of products is now 1:1.4. However, both nitrogenases exhibit the same Km for cyclopropene (2.1 x 10(4) +/- 0.2 x 10(4) Pa), considerably more than the Km for the analogous reaction with Azotobacter vinelandii nitrogenase under the same conditions (5.1 x 10(3) Pa). Analysis of the data shows that the different product ratio arises from the slower production of propene compared with cyclopropane by the mutant nitrogenase. During turnover, both nitrogenases use a large proportion of the electron flux for H2 production. CO inhibits the reduction of cyclopropene by both K. pneumoniae proteins, but the mutant nitrogenase exhibits 50% inhibition at approx. 10 Pa, whereas the corresponding value for the wild-type nitrogenase is approx. 110 Pa. However, H2 evolution by the mutant enzyme is much less affected than is cyclopropene reduction. CO inhibition of cyclopropene reduction by the nitrogenases coincides with a relative increase in H2 evolution, so that in the wild-type (but not the mutant) the electron flux is approximately maintained. The cyclopropane/propene production ratios are little affected by the presence of CO within the pressure ranges studied at least up to 50% inhibition.

Binding Sites↗
PubMed1989

Histamine 2 receptor blocker in the treatment of protamine related anaphylactoid reactions: two case reports.

Two case reports are described of acute anaphylactoid reactions following the administration of protamine to reverse the anticoagulation effect of heparin in patients undergoing coronary artery bypass graft surgery. The administration of cimetidine seemed to reverse the anaphylactoid reaction after conventional treatment with epinephrine, H1 receptor blocker, and steroids had failed. We recommend that H2 receptor blockade be included with other drugs in the treatment of anaphylactoid reactions following protamine, and possibly after anaphylactoid reactions associated with other substances.

Adult↗