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Biomedical subjects

D Reynolds

Publications and source records attributed to D Reynolds.

At least 19 recordsLinked to original sources
PubMed1995

Steroid elution improves the stimulation threshold in an active-fixation atrial permanent pacing lead. A randomized, controlled study. Model 4068 Investigators.

BACKGROUND: Prior work suggests that the addition of a steroid-eluting reservoir to a passive-fixation permanent pacemaker lead improves the stimulation threshold; however, no large randomized study has addressed this tissue. Over the last several years, there has been an increase in enthusiasm for the use of active-fixation permanent pacemaker leads for various reasons in spite of the generally accepted notion that active-fixation leads have higher stimulation thresholds. METHODS AND RESULTS: This multicenter, randomized, controlled study examined the difference in performance between a standard active-fixation atrial lead (Medtronic model 4058) and a steroid-eluting lead (Medtronic model 4068). Stimulation thresholds were obtained in a four-point strength-duration fashion. Evaluations of sensing and impedance were performed as well. These evaluations were performed at implantation, at weeks 1 through 4, and at weeks 6, 12, 24, and 52. Stimulation thresholds were significantly better in the steroid lead than in the nonsteroid lead at each measurement point from 1 week to 12 months. The mean 1.6-V stimulation threshold at 12 months was 0.19 +/- 0.2 ms in the steroid lead and 0.41 +/- 0.30 ms in the control lead. No acute peaking was observed with the steroid lead, whereas significant peaking was observed with the control lead. There was no difference in long-term sensing or impedance. CONCLUSIONS: Inclusion of a steroid-eluting reservoir in an active-fixation permanent pacing lead improved stimulation thresholds in both the subacute and chronic periods and therefore should extend pulse-generator longevity.

Aged↗
PubMed1995

Pharmacokinetics and pharmacodynamics of the monoamine oxidase B inhibitor mofegiline assessed during a phase I dose tolerance trial.

The safety, pharmacokinetics, and pharmacodynamics of single oral doses of up to 48 mg and daily (for 28 days) doses of up 24 mg mofegiline were investigated in healthy male volunteers. Plasma pharmacokinetics indicated rapid absorption and elimination: time to reach maximum concentration occurred at about 1 hour; half-life ranged from 1 to 3 hours. Maximal plasma concentration and area under the plasma concentration-time curve increased and oral clearance decreased disproportionately with dose. Mofegiline rapidly and markedly inhibited platelet monoamine oxidase B (MAOB) activity, which returned to baseline within 14 days. Urinary excretion of phenylethylamine increased proportionately with doses up to 24 mg. No changes in urinary elimination of catecholamines, blood pressure, heart rate, or ECG were observed. A classic maximum tolerated dose was not achieved in these studies. However, the 48 mg single dose and the 24 mg multiple daily dose far exceeded the dose (1 mg) that was associated with > 90% platelet MAOB inhibition.

Administration, Oral↗
PubMed1995

The use of a zinc based bioceramic as an osteoconductive agent in the rat model.

The many complications and risks of autograft and allograft bone have resulted in the search for an effective synthetic bone graft substitute [1,2]. The purpose of this study is to determine the effectiveness of ZCAP (zinc calcium phosphate) ceramic organic acid composite as an osteoconductive agent, including its possible benefits or risks for patients requiring bone grafting. A solid control model has been developed with an isolated mid-diaphyseal femur fracture immobilized by intramedullary threaded K-wire fixation. Two trials were performed in which two formulations of ZCAP composite ceramic were tested. The first, used in eighteen rats will be referred to as ZCAP1, the second, used in six rats will be referred to as ZCAP2. In the first trial rat femurs were augmented with 0.1 g ZCAP1 composite ceramic which varied in pore size. One pore size performed better than the others, so that pore size along with some minor changes in the composite design to increase resistance to the stresses inherent in our weight bearing model resulted in ZCAP2, which was tested in the second trial. The rats were sacrificed at ten weeks, during which time all rats remained viable. Blood work was done prior to sacrifice and radiography was done on all femurs. After sacrifice, gross morphological exam showed filling of the defect. Sections of the femurs from each group were analyzed by decalcified histological examination, electron microscopy, and tensile strength testing. The ZCAP composite ceramic had no significant effect on blood chemistry or body weight. Initial histological studies were consistent with endochondral ossification which was confirmed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

A large focus of alveolar echinococcosis in central China.

Human alveolar echinococcosis (AE) is a rare and highly pathogenic helminthic zoonosis due to infection with the intermediate stage of the small fox tapeworm, Echinococcus multilocularis. Parasite transmission is restricted to northern latitudes, including central and north China, from where few clinical and no detailed community studies have been reported. In August, 1991, 65 (5%) of 1312 people residing in three rural communes of Zhang County, Gansu Province, China were diagnosed as having hepatic AE after mass ultrasound scanning with serological back-up. This represents one of the highest prevalence rates of AE ever recorded. It is also the first time that mass ultrasound scanning and serology have been used together in an AE endemic region. The region was selected one year earlier, when a preliminary serosurvey on 606 unselected people in the same locality resulted in an 8.8% serum antibody positive rate with a 76% rate of confirmation of hepatic AE in 37 individuals who could be followed up in 1991. Seropositivity rates varied for villages between 0 and 20.5%. Overall, females (7.8%) had a significantly greater risk of infection than males (2.5%), especially in the 31-50 age group, a difference which may be related to contact with dogs and dog faeces over many years. Age-specific prevalence of AE increased from 0% in the under 5-year group to 8.2% in those aged 31-50. The youngest case was 11 years and the mean age of diagnosis was 40 years. Adult tapeworms of E multilocularis were identified from the small intestines of 10% of domestic dogs. Sylvatic animal hosts of the parasite have not yet been identified. The high prevalence of human AE in this region of central China is most probably due to semi-domestic transmission of E multilocularis between wild rodents and dogs, together with the poverty and poor hygiene in these rural communities.

Adolescent↗
PubMed1992

Introducing beer sales at a Canadian ball park: the effect on motor vehicle accidents.

The impact of introducing the legal sale of beer in a Toronto stadium on drinking-driving accidents is investigated. The results suggest that a greater proportion of accidents in the postgame time are alcohol-related when compared to pregame times and to control times. No significant effect was found, however, for the introduction of legal beer sales, suggesting that drinking was common before the public sales policy.

Accidents, Traffic↗
PubMed1992

MHC restriction of synovial fluid lymphocyte responses to the triggering organism in reactive arthritis. Absence of a class I-restricted response.

Synovial fluid mononuclear cells (SFMC) from patients with reactive arthritis (ReA) show marked proliferative responses to preparations of the organism triggering the arthritis. Initial studies with MHC-specific MoAbs have indicated that a significant element of these proliferative responses is mediated by class II MHC-restricted CD4+ T cells. It is imperative to establish the presence or absence of a class I-restricted response, for two reasons. Firstly, the association of ReA with the MHC class I molecule, HLA B27, raises the possibility of there being a B27-restricted response to the triggering organism. Secondly, a number of the organisms associated with ReA are intracellular pathogens, whose antigens might be expected to be presented by class I MHC molecules. In an effort to identify a class I MHC-restricted pathogen-specific response in the SFMC of ReA patients, we have assessed the proliferative responses of SFMC depleted of CD4+ T cells. Responses were grossly diminished by CD4+ T cell depletion. We also investigated Chlamydia-specific cytotoxicity in the SFMC of patients with sexually acquired ReA in a system using productive chlamydial infection to produce both targets and effectors. Significant antigen specific cytotoxicity was not seen. These experiments do not provide evidence to support the existence of pathogen-specific responses by CD8+, class I-restricted synovial fluid T cells in ReA.

Arthritis, Reactive↗
PubMed1991

Cytokine mRNA are preferentially increased relative to secretory granule protein mRNA in mouse bone marrow-derived mast cells that have undergone IgE-mediated activation and degranulation.

The levels of mRNA that encode a number of cytokines have been reported by several laboratories to be increased in mouse mast cells after their IgE-bearing receptors have been cross-linked with Ag. In this study, we have compared the mRNA levels for Fc epsilon RI alpha, three cytokines (IL-6, granulocyte-macrophage CSF, and TNF-alpha), actin and three secretory granule-localized proteins (carboxypeptidase A, proteoglycan peptide core, and a generic serine protease) in mouse bone marrow-derived mast cells (BMMC) before and after IgE-mediated activation and degranulation to determine the kinetics and specificity of mRNA induction. An antigen concentration of approximately 10 ng/ml was optimal for the release of histamine from IgE-sensitized BMMC and for the generation and release of a cytokine that was functionally and immunochemically identical to TNF-alpha. In kinetic experiments, the levels of TNF-alpha, IL-6, and granulocyte-macrophage CSF mRNA increased greater than 23-fold 0.5 to 1 h after activation. As assessed by in situ hybridization, virtually all BMMC contained detectable proteoglycan peptide core mRNA before and after exposure to Ag, but only approximately one-half of the Ag-treated cells in the culture contained IL-6 mRNA 1 h after activation. There was a slight transient increase at 4 h in the level of proteoglycan peptide core mRNA, but no increase in the levels of those highly expressed mRNA that encode actin, Fc epsilon RI alpha, carboxypeptidase A, and serine protease. Thus, despite the remarkable increment in the levels of the transcripts that encode cytokines in BMMC after IgE-mediated, Ag-dependent activation, the levels of those transcripts that encode a plasma membrane-localized recognition receptor and several constituents of the secretory granule remain essentially unchanged. The failure to increase substantially the level of protease and proteoglycan peptide core mRNA in mast cells after the activation/secretion response suggests that regranulation of mast cells is a slow process.

Animals↗
PubMed1989

The proliferation and life-span of rat large granular lymphocytes: effects of cytokines.

Pulse labeling of large granular lymphocytes (LGL) with [3H]thymidine for 1 h in vitro showed that 1%-7% of LGL were in S phase in the blood, spleen and liver of unstimulated euthymic and athymic rats as scored with autoradiography. Repetitive injections of [3H]thymidine over 2-7 days revealed that about half of the blood and spleen LGL had formed by division of precursors during this week. Stimulation of rats with the interferon inducer poly(I).poly(C) increased the proportion of S phase LGL rapidly and simultaneously in the blood, spleen and liver, so that by 20 h after stimulation ca 30% of LGL were in the S phase in these organs. This LGL proliferation was accompanied by an increased number of LGL in all three compartments 48-96 h after poly(I).poly(C) injection. Blood LGL cultured in cell impermeable diffusion chambers in the peritoneal cavity of poly(I).poly(C)-stimulated rats exhibited enhanced natural killer (NK) activity but no proliferative response, indicating that mature LGL were not induced to undergo blastogenesis by poly(I).poly(C) in vivo. Pretreatment of NK cells with rat interferon (IFN-alpha/beta) and with human recombinant interleukin 2 (rIL 2) in vitro, showed that these two cytokines, when combined, had opposing effects on NK activity and proliferation: whereas rIL 2 inhibited the IFN-induced augmentation in NK activity, IFN inhibited the rIL 2-induced LGL proliferation.

Animals↗
PubMed1988

Synthesis of O-alpha-L-fucopyranosyl-(1----3)-O-beta-D-galactopyranosyl-(1----4)-2- acetamido-2-deoxy-D-glucopyranose (N-acetyl-3'-O-alpha-L-fucopyranosyllactosamine).

Methyl 2-O-benzyl-beta-D-galactopyranoside (6) was obtained in five, good yielding steps from methyl beta-D-galactopyranoside (1). Treatment of 1 with tert-butylchlorodiphenylsilane in N,N-dimethylformamide in the presence of imidazole afforded a 6-(tert-butyldiphenylsilyl) ether, which was converted into its 3,4-O-isopropylidene derivative (3). Benzylation of 3 with benzyl bromide-silver oxide in N,N-dimethylformamide, and subsequent cleavage of its acetal and ether groups then afforded 6. On similar benzylation, followed by the same sequence of deprotection, benzyl 2-acetamido-3,6-di-O-benzyl-4-O-[6-O-(tert-butyldiphenylsilyl)-3,4 -O- isopropylidene-beta-D-galactopyranosyl]-2-deoxy-alpha-D-glucopyranoside gave the 2-O-benzyl derivative (10). Compound 10 was converted into its 4,6-O-benzylidene acetal (11). Glycosylation (catalyzed by halide-ion) of 11 with 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide afforded the fully protected trisaccharide derivative (13). Cleavage of the benzylidene and then the benzyl groups of 13 furnished the title trisaccharide (16). The structure of 16 was established by 13C-n.m.r. spectroscopy.

Benzyl Compounds↗
PubMed1988

Reactivity of catecholamines and related substances in the mouse lymphoma L5178Y cell assay for mutagens.

Using the L5178Y mouse lymphoma cell thymidine kinase locus and the Salmonella his locus assays, the mutagenic potentials of several catecholamines and related compounds were examined. No supplementary metabolic activation systems were used. In the mouse lymphoma assay, the dihydroxybenzenes catechol and hydroquinone had similar and appreciable mutagenic potentials, whereas resorcinol was less active. Derivatives of catechol, such as dopamine and epinephrine, were mutagenic, whereas the related monohydroxylated compounds tyramine and synephrine were inactive. The primary amine, arterenol, and the corresponding secondary amine, epinephrine, induced similar mutagenic responses. Carboxylation of the side chain of dopamine, giving L-dopa, reduced the maximum mutagenic response. The introduction of charged groups directly on to the aromatic ring also reduced mutagenic activity, while an intervening methylene reversed this effect. Thus, 3,4-dihydroxyhydrocinnamic acid was more active than 3,4-dihydroxybenzoic acid. The compound active at the lowest doses was 4-tert-butyl catechol. The activities of these compounds are highly dependent upon substituent groups. Experiments with superoxide dismutase gave circumstantial evidence for some of the mutagenic activity being due to superoxide anion. Active oxygen species might be responsible for some of the observed effects, but this cannot be concluded from the superoxide dismutase experiments. Mutagenic responses in Salmonella were very low but were significant for L-dopa in three strains and for epinephrine and arterenol in one strain. Limited DNA association studies of 14C-dopamine suggest interactions in L5178Y and Salmonella cells and in mouse liver. The mutagenicity of dopamine in L5178Y is reduced by high serum concentrations during the exposure period, while the apparent association with DNA is unaffected.

Animals↗
PubMed1988

Novel method for purification of staphylococcal enterotoxin A.

A novel single-step procedure for the purification of staphylococcal enterotoxin A (SEA), namely, dye ligand affinity chromatography with the triazine dye Red A, was developed. SEA purified by this method produced a single band when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The yield from 5 liters of culture supernatant was 0.113 g, corresponding to an overall yield of 55%. In some instances, purification of SEA from culture supernatants by dye ligand affinity chromatography produced two enterotoxin peaks that could be eluted from the column with 300 and 500 mM phosphate buffer (pH 6.8). Enterotoxin from these peaks produced a single band when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but multiple bands were observed on isoelectric focusing gels. This method of purification represents a significant improvement in time, yields, and purity of enterotoxin over previously published purification methods.

Chromatography, Affinity↗
PubMed1987

Atenolol for ventricular ectopy: a dose-response study.

The antiarrhythmic efficacy, safety, and tolerance of atenolol was evaluated in 32 patients with an average of at least 60 ventricular ectopic depolarizations/hr. Patients received, single-blind, the following treatments for 2 weeks each: placebo and atenolol, 50, 100, and 200 mg daily. A 24-hour ambulatory ECG recording was obtained each week. Reduction in ventricular ectopic frequency by at least 75% occurred in six of 32 patients receiving 50 mg daily, five of 30 patients receiving 100 mg daily, and three of 21 patients receiving 200 mg daily (P = not significant for any paired dose comparison). No patient who failed to respond to a lower dose responded to 200 mg daily. The frequency of ventricular tachycardia was reduced by at least 75% in eight of 17 patients receiving 50 mg daily, seven of 16 patients receiving 100 mg daily, and eight of 11 receiving 200 mg daily (P = not significant for any paired dose comparison). Atenolol was discontinued because of adverse effects in 12 patients. The results indicate that atenolol is more effective in suppressing ventricular tachycardia than in suppressing overall ventricular ectopy.

Adult↗
PubMed1986

Scaled-up production and purification of Clostridium perfringens type A enterotoxin.

Methods for small-scale production of Clostridium perfringens type A enterotoxin were unsuitable for large-scale culture of this organism. Rapid, efficient harvesting of 40 1 batch culture of Cl. perfringens was achieved by tangential flow micro-filtration with the Millipore Pellicon cassette system. Enterotoxin-containing extracts were prepared by passing concentrated suspensions of the harvested cells through a French pressure cell. The overall yield of purified enterotoxin was 38.8%. The toxin gave a single band on native polyacrylamide gels but formed high molecular weight aggregates in the presence of sodium dodecyl sulphate. These aggregates frequently occurred during storage of non-sterile enterotoxin preparations but could be separated from the monomer toxin by gel filtration on Sephadex G-100. Purified monomer enterotoxin had biological activities of 119.3 micrograms/kg mouse lethal dose when injected intraperitoneally and 3333 capillary permeability increasing units/mg protein in guinea pig skin. Thirty micrograms of the enterotoxin caused fluid accumulation in ligated rabbit ileal loops. Aggregated enterotoxin had no demonstrable biological or immunological activity.

Animals↗
PubMed1986

Slot machines: their use in rehabilitation after stroke.

A comparative study of a novel and entertaining motor function exercise and traditional motor function exercise was conducted in the therapy of stroke patients. Therapists rated patients in five dependent variables, including range of motion, muscle strength, fine motor coordination, gross motor coordination, and degree of depression in control and experimental groups. Multivariate analysis of the results showed significantly greater progress in the five dependent variables among patients in the experimental group. Follow-up procedures using stepwise discriminant function analysis produced a rank ordering of the impact of each of the five dependent variables. Demographic variables of age, sex, education level, and marital status showed no effect. Correlations between the dependent variables were performed.

Adult↗
PubMed1984

Effect of the air hammer on the hands of stonecutters. The limestone quarries of Bedford, Indiana, revisited.

In the limestone quarries of Indiana, USA, pneumatic percussive hammers replaced the mallet and hammer around 1900. By 1917 the air hammer was being used exclusively for periods of eight to ten hours a shift. In 1918 Alice Hamilton investigated an unusual "disease" in these stonecutters of Bedford, Indiana, who complained of "attacks of numbness and blanching of the fingers coming on suddenly under the influence of cold and then disappearing." The prevalence of vibration induced white finger (VWF) found in this population of 38 stonecutters was 89%, with decreased light touch, pain, and temperature appreciation in advanced cases. In 1978 a VWF research team revisited these limestone quarries. During the 60 year interval the stonecutting industry had contracted from 4000 workers in 40 quarries in 1918 to 3-400 in 10 quarries in 1978, with only 50 employees remaining in the Bedford area. In a population of 30 stonecutters the prevalence of VWF in 1978 was 80%, with similar sensory loss in light touch, pain, and temperature appreciation. Between 1918 and 1978 no change had taken place in the design of the air hammers used for stonecutting. Vibration levels of 4859 metres/s2 on the chisel, and 2010 metres/s2 on the barrel were measured over a frequency range 6.3 to 1000 Hz. The fundamental frequency was 75 Hz. These measured vibration levels are outside the ISO/DIS/5349 (1979) recommended limits for human exposure to vibration transmitted to the hand. The VWF data presented in this paper, and those originally reported by Hamilton in 1918, call for an immediate redesign of stonecutting pneumatic hammers in order to remove one cause of Raynaud's phenomenon of occupational origin.

Adult↗