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Biomedical subjects

D Reynolds

Publications and source records attributed to D Reynolds.

At least 55 records · Page 3Linked to original sources

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↗

Treatment of patients with prior exit block using a novel steroid-eluting active fixation lead. Model 4068 Investigators.

An increased interest has developed in active fixation leads for several reasons. Exit block is an uncommon complication that is seen with both active and passive fixation leads. Exit block has not been a significant problem with passive fixation steroid-eluting leads and has been treated with these leads. A new steroid-eluting active fixation lead was examined for its performance in patients in whom exit block had previously occurred. The lead function was evaluated prospectively in 24 patients with a history of exit block (15 ventricular and 9 atrial). The results in patients with atrial exit block are encouraging with an average chronic stimulation threshold of 0.19 msecs at 2.5 volts. Results in the ventricle are less encouraging with 3 occurrences of recurrent exit block in 15 patients; however, the remaining patients had a good mean threshold of 0.21 +/- 0.11 msecs at 2.5 volts. There were a remarkable number of non-lead related complications suggesting that this is a substantially different group than routine implantations.

Cardiac Pacing, Artificial↗

The geographic variation of cancer incidence in Ontario.

OBJECTIVES: Our objectives were (1) to describe an analysis of the spatial pattern of cancer incidence in Ontario and (2) to discuss the quality of data in the Ontario Cancer Registry with respect to the accuracy of local cancer rates. METHODS: Cancer incidence rates were calculated for 22 cancer sites in 49 counties of Ontario during 1976 to 1986. Capture-recapture methods were used to estimate completeness of case registration, and completeness of residence information was also assessed. Spatial autocorrelation was used in measuring the geographic pattern of incidence rates. Comparisons were also made between sexes and with earlier data from 1966 to 1975. RESULTS: The quality of the geographic data in the registry appeared good, and corrections for incomplete or inaccurate registration had little impact. About one third of the sex-site combinations showed some evidence of spatial patterning in the cancer rate. Particularly strong regional variation was noted for cancers of the stomach, lung, uterus, and prostate. CONCLUSIONS: The analysis revealed a number of cancers with significant spatial patterning of risk. Further work is needed to relate the cancer data to other information on potential life-style and environmental factors.

Female↗

A "partnership"--a case study.

The Misericordia and The General Hospital (Grey Nuns) of Edmonton (two sites) have formed a partnership and established one board and management structure responsible for the three sites. Described are the processes and techniques used during the assessment stage to determine the viability and desirability of such an action. To study the issue, a task force was formed, drawing equally from the boards of the two hospitals, and involving the participation of the Catholic Archbishop of Edmonton. The responsibilities and actions of the task force are described, along with the observations of the other participants--the owners, management, medical staff, employees and the community.

Alberta↗

The population health impact of arthritis. POHEM Workshop Group.

The workshop was convened to develop quantitative estimates of the incidence of progressional musculoskeletal diseases in order to estimate the population health impact of arthritis. Estimates were developed for (a) the prevalence of arthritis, (b) a weighting strategy to adjust for the quality of life for the range of health states associated with arthritis, and (c) transition probabilities to represent the likelihood of disease onset and progression through the range of possible health states. A simulation "game" was designed to follow the progression of a cohort of 200 healthy persons or persons with arthritis, creating the basis for the estimation of transition probabilities and thus generating simulated longitudinal data that allow calculation of the quantitative estimate of the burden of illness from musculoskeletal diseases within the Canadian population.

Arthritis↗

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↗

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↗

Hospital reimbursement in Alberta: outcomes management is on the way.

The Alberta government has initiated a process to alter fundamentally the way it pays hospitals. As with most provinces, Alberta has been paying hospitals for what they spend. The new Alberta model will initially pay hospitals for what they do and ultimately will pay hospitals for what they ought to do; that is, for the outcomes that should be achieved. This article describes the initial step of what is expected to be a lengthy journey. The principles underlying the model are: it should be a prospective case-based system; there should be performance linkages between types of hospitals; severity should be incorporated into the model; and cost or cost proxies should be used where possible in weight development and clinical concerns, both nursing and medical, should be addressed. For the past two years funding adjustments have been made on the basis of the calculation of a Hospital Performance Index (HPI). The HPI is the average predicted cost per case divided by the unweighted average actual cost per case. The HPI is intended as an interim measure only. Ultimately, the system will evolve into a true prospective case-based system with volume controlled via role statements and linked to clinical outcomes.

Alberta↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗