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Biomedical subjects

E Ryan

Publications and source records attributed to E Ryan.

At least 55 records · Page 3Linked to original sources
PubMed1998

A respiratory challenge model for infection with Bordetella pertussis: application in the assessment of pertussis vaccine potency and in defining the mechanism of protective immunity.

The evaluation of vaccines for human use usually requires the development of appropriate animal models and the definition of laboratory correlates of immunity. Traditionally whole cell pertussis vaccines have been controlled by using an active mouse protection test, which measures protection following intracerebral challenge with Bordetella pertussis. However, this test is unsuitable for assessing the potency of the new generation acellular pertussis vaccines. In the present study we demonstrate that a murine respiratory challenge model for infection with B. pertussis is suitable for assessing the potency of acellular and whole cell pertussis vaccines. To allow standardization of different vaccines we have expressed the area under the clearance curve for immunized mice as a ratio of that for non-immunized controls to obtain a potency index. A comparison of estimated vaccine efficacy in children with potency in the murine model results in a highly significant correlation (r = 0.976, p < 0.001). Furthermore, we have used this model to define the protective mechanism of immunity against respiratory infection with B. pertussis and demonstrate a requirement for both specific T and B cells. In accordance with studies in humans, no clear relationship was observed between monotypic serum antibody responses against the putative protective antigens of B. pertussis and protection. In contrast, the most potent protection was observed when the T cell response is polarized to the Th1 subtype.

Animals↗
PubMed1997

Melatonin modulates vascular smooth muscle tone.

The molecular cloning of a family of melatonin receptors has created a renewed interest in the diverse actions of the hormone melatonin. The radioligand 2-[125I]iodomelatonin has identified potential sites of action for melatonin throughout the central nervous system and periphery of numerous species. Interestingly, in addition to the suprachiasmatic nucleus (the "biological clock"), 2-[125I]iodomelatonin binding sites have been localized to the rat caudal and cerebral arteries. Furthermore, in vitro, melatonin has been shown to induce a concentration-dependent vasoconstriction of rat caudal and cerebral arteries, and pig and human coronary arteries. The lack of melatonin receptor subtype-selective agonists and antagonists prevents the full pharmacological characterization of these responses. The physiological significance of the in vitro vasoconstrictive properties is far from clear, however; in rats, melatonin has been shown to reduce cerebral blood flow. The widespread use of melatonin warrants appropriately designed studies to probe the role of melatonin and its receptors in the modulation of in vitro vascular tone.

Animals↗
PubMed1997

Building an effective corporate compliance plan.

Corporate compliance plans are essential for healthcare organizations to cope with, and perhaps even stave off, investigations arising from allegations of illegal business practices. Initial development and implementation of a corporate compliance plan can be facilitated through four steps: determining the content of the code of conduct, determining how the code will be distributed, assigning responsibility for implementing the plan, and appointing a compliance task force to guide the implementation process. Special attention should be paid to education requirements of the United States Sentencing Guidelines to see that all employees understand and can apply provisions of the plan.

Employee Discipline↗
PubMed1995

Professional needs of palliative care nurses in New South Wales.

A survey of 108 palliative care nurses practising in New South Wales, Australia, was undertaken to explore their professional needs and clinical knowledge. Opportunity for improved training was the most frequently nominated professional need. Only 12% of the sample had postgraduate qualifications in palliative care and fewer than 20% were currently undertaking postgraduate training. Sixty-three per cent of nurses indicated that a lack of opportunity for formal study was a problem for them. The results of the knowledge survey revealed a need for additional training. Many nurses did not have the clinical knowledge identified as minimal by an expert committee. Those nurses who had a postgraduate qualification in oncology scored more highly on the knowledge questionnaire than did those whose general nursing training was undertaken outside Australia. The implications of these findings for training and other professional support are discussed.

Adult↗
PubMed1995

Fructosamine concentrations in hyperglycemic cats.

The aims of this study were 1) to establish a reference range for fructosamine in cats using a commercial fructosamine kit; 2) to demonstrate that the fructosamine concentration is not increased by transient hyperglycemia of 90 min duration, simulating hyperglycemia of acute stress; and 3) to determine what percentage of blood samples submitted to a commercial laboratory from 95 sick cats had evidence of persistent hyperglycemia based on an elevated fructosamine concentration. Reference intervals for the serum fructosamine concentration were established in healthy, normoglycemic cats using a second generation kit designed for the measurement of the fructosamine concentration in humans. Transient hyperglycemia of 90 min duration was induced by IV glucose injection in healthy cats. Multisourced blood samples that were submitted to a commercial veterinary laboratory either as fluoride oxalated plasma or serum were used to determine the percentage of hyperglycemic cats having persistent hyperglycemia. The reference interval for the serum fructosamine concentration was 249 to 406 mumol/L. Transient hyperglycemia of 90 min duration did not increase the fructosamine concentration and there was no correlation between fructosamine and blood glucose. In contrast, the fructosamine concentration was correlated with the glucose concentration in sick hyper- and normoglycemic cats. It is concluded that the fructosamine concentration is a useful marker for the detection of persistent hyperglycemia and its differentiation from transient stress hyperglycemia. Fructosamine determinations should be considered when blood glucose is 12 to 20 mmol/L and only a single blood sample is available for analysis.

Animals↗
PubMed1993

Simultaneous measurement of monoamines, metabolites and amino acids in brain tissue and microdialysis perfusates.

A high-performance liquid chromatographic method with coulometric array electrochemical detection is described for the simultaneous analysis of monoamines, their metabolites and o-phthalaldehyde (OPA)-derivatized amino acids. This method has been used to examine metabolite levels in both striatal tissue homogenates and striatal microdialysis perfusates. An aliquot of sample was initially analyzed for monoamines and metabolites by isocratic elution and electrochemical detection on a serial electrode array of eight coulometric flow-through graphite electrodes (0 to 490 mV; 70-mV increment). The remaining sample was derivatized pre-column with OPA-beta-mercaptoethanol and after column switching was analyzed for amino acids on a second isocratic system with electrochemical detection on four electrodes. Metabolites were then identified based on their retention time as well as electrochemical behavior across the arrays. The analysis, derivatization procedure, column switching, data reduction and peak identification were fully automated. The limit of detection for striatal tissue homogenates was approximately 1.38 ng/g wet weight for the monoamines and 8.25 ng/g wet weight for amino acids. The limit of detection for striatal perfusates was approximately 2.5 pg per 20-microliters sample for the monoamines and 15 pg per 20-microliters sample for the amino acids with analysis completed within 25 min making it ideal for microdialysis samples.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Analysis of phenolic and flavonoid compounds in juice beverages using high-performance liquid chromatography with coulometric array detection.

Analysis of phenolics and flavonoids in juice beverages using reversed-phase HPLC with coulometric array detection is described. Sixteen serial coulometric detectors were used for on-line resolution of co-eluting compounds and generation of voltammetric data. Within each class of compounds, oxidation potential corresponded to specific substitution patterns where: catechol < methoxycatechol < monohydroxyl < methoxyl. Twenty-seven standard compounds were resolved in a 45-min run. The limits of detection were in the low ng/ml range with a linear response range of at least three orders of magnitude. Intra-run retention time variation was < 1% (R.S.D.) and adjacent sensor response ratios varied by < 5% (R.S.D.). The utility of this technique in generating multivariate data for differentiation of juices and juice mixtures is shown.

Analysis of Variance↗
PubMed1993

Evidence for bimodal distribution of breast carcinoma ER and PgR values quantitated by enzyme immunoassay.

Breast carcinoma oestrogen receptor (ER) and progesterone receptor (PgR) values obtained by radioligand binding assays have commonly been observed to have approximate log-normal distributions. We examined the distribution of log-transformed receptor values obtained by enzyme immunoassay for 5468 primary breast carcinomas in five Ontario laboratories. In each laboratory, it was found that the frequency histograms for the log transformed receptor values were not unimodal, and generally were suggestive of bimodality. This was not affected by stratification by age or inferred menopausal status (< or = 49, > or = 50 years), and could not be explained by kit characteristics. However, the low point in the distribution varied from 5 to 63 fmol/mg cytosol protein, depending on the receptor, patient age and laboratory. The tendency towards biomodality was more distinct for ER than for PgR. It remains to be determined whether the low points on the frequency histograms have clinical relevance for discriminating between hormone-sensitive and hormone-insensitive tumours.

Adult↗
PubMed1993

Cutaneous epithelioid hemangioendothelioma without systemic involvement.

Epithelioid hemangioendothelioma (EH) is a unique vascular tumor characterized histologically by epithelioid endothelial cells. A case of EH arising from the dermis and presenting as a nodule of the palm is described. To our knowledge, this is the third report of a cutaneous presentation of EH and the first report of a patient with this rare neoplasm with solitary cutaneous involvement. A review of the literature is also presented.

Adult↗
PubMed1993

Determination of amino acids and monoamine neurotransmitters in caudate nucleus of seizure-resistant and seizure-prone BALB/c mice.

Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separated by isocratic reverse-phase chromatography and detected by a coulometric electrode array system. In situ activity of tyrosine hydroxylase and tryptophan hydroxylase were determined by measuring the accumulation of L-DOPA and 5-hydroxytryptophan after administration of the decarboxylase inhibitor NSD-1015. Highly significant decreases in concentrations of both excitatory (glutamate and aspartate) and inhibitory amino acids (GABA and taurine) were observed in extracts of caudate nucleus of seizure-prone mice. Substantial decreases in concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were also noted. Decreased accumulation of L-DOPA after NSD-1015 administration provided evidence for decreased tyrosine hydroxylase activity and decreased DA synthesis in striatum of seizure-prone mice compared with seizure-resistant mice. Decreased concentrations of the DA metabolite 3-methoxytyramine (after NSD-1015 administration) suggested that DA release was also compromised in seizure-prone mice. No significant difference in 5-hydroxytryptophan accumulation in striatum of seizure-prone and seizure-resistant mice suggested that tryptophan hydroxylase activity and serotonin synthesis were not affected. The data suggest that seizure-prone BALB/c mice have a deficiency in intracellular content of both excitatory and inhibitory amino acids. The data also raise the issue of whether GABAergic interactions with the nigrostriatal DA system are important in the regulation of audiogenic seizure susceptibility.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Heart rate/stroke volume relationship during upright exercise in long-term diabetics.

The changes in stroke volume (SV) during upright exercise were studied in 20 insulin-dependent diabetics (IDDM) and 20 age- and sex-matched controls. None of the diabetics had any cardiovascular symptoms. In addition, tests of autonomic function were conducted in the diabetics, assessing changes in heart rate (HR) during deep breathing and the Valsalva maneuver. During exercise the SV in the controls gradually increased and then remained essentially unchanged until maximum HR was achieved. Seven of the diabetics failed to sustain an initial increase in SV (fall > 15%), eight showed a "delayed" increase in SV, and the remaining five demonstrated an increasing SV over the range from rest to peak exercise. Abnormal autonomic function results were found during deep breathing (four diabetics) and the Valsalva maneuver (four diabetics). Findings indicate that cardiac function could be abnormal in IDDM without evidence of autonomic dysfunction. This abnormality could be due to a specific cardiomyopathy.

Adult↗
PubMed1992

The cost of neonatal care.

A medical and financial assessment of the Neonatal Unit at Groote Schuur Hospital showed that the emphasis was on high care provided at a cost of R265 per patient per day. Intensive care cost R530 and low care R88 per day. The average was R172 per day. Infants of very low birth weight (< 1,500 g) accounted for 58% of expenditure. Half of this amount was spent on infants of below 1,000 g; the cost was R14 621 per survivor and R344 per quality-adjusted life-year. The cost declined progressively for infants of greater birth weight. There are a paucity of comparable local data, but the cost of the care was very reasonable.

Costs and Cost Analysis↗
PubMed1991

Normoglycaemia after transplantation of freshly isolated and cryopreserved pancreatic islets in type 1 (insulin-dependent) diabetes mellitus.

Purified islets of Langerhans and a kidney were transplanted into a 36-year-old patient who suffered from renal failure secondary to a 25 year history of Type 1 (insulin-dependent) diabetes mellitus. The islet graft contained 243,000 fresh islets (mean islet diameter 150 microns) that were syngeneic with the kidney graft and 368000 cryopreserved islets that had been collected from four other donors. The total of 10,000 islets/kg body weight was infused into the liver via the umbilical vein. Immunosuppression was induced with antilymphocyte globulin and maintained with prednisone, cyclosporine and azathioprine. Serum C-peptide levels (ng/ml) during fasting and after standard mixed meal feeding (Sustacal) were less than 0.12 preoperatively. Postoperatively, insulin secretion was restored: fasting C-peptide rose during the first 4 weeks to levels of 4 to 5 and Sustacal elicited a further rise to 6 to 7. Transplant renal function was stable. Daily fasting glucose (mmol/l, mean +/- SD) was 5.6 +/- 1 and 5.3 +/- 0.6 during the first and second months respectively and post-Sustacal glucose was 5.7 +/- 0.8. Exogenous insulin therapy was progressively withdrawn and stopped during the ninth week. Thereafter, fasting glucose was 4.7 +/- 0.5, 24 h mean glucose was 6.6 +/- 0.5, and normoglycaemia was maintained after Sustacal. These data show that this mass of freshly isolated and cryopreserved islets from multiple donors provided sustained function (3 months) that reversed insulin-dependence in an immunosuppressed Type 1 diabetic patient treated with simultaneous islet-kidney transplantation.

Adult↗
PubMed1991

Unique modulation of central 5-HT2 receptor binding sites and 5-HT2 receptor-mediated behavior by continuous gepirone treatment.

The effect of continuous treatment with the selective 5-HT1A agonist gepirone upon 5-HT2-mediated behavior and cortical 5-HT2 receptor binding sites was examined in naive rats or rats receiving noradrenergic (DSP4) or serotonergic (5,7-DHT) lesions. Continuous administration of gepirone in non-lesioned rats for 3, 7, or 14 days enhanced the head shake response to the 5-HT agonist quipazine. This enhancement of 5-HT2-mediated behavior occurred despite concomitant down-regulation of cortical 5-HT2 binding sites. However, 28 days of gepirone administration significantly reduced behavioral responsiveness to quipazine. The gepirone-induced facilitation of 5-HT2-mediated behavior observed after 7 days of continuous treatment was blocked in both DSP4 and 5,7-DHT-lesioned rats. However, both noradrenergic and serotonergic denervation failed to modify the down-regulation of 5-HT2 receptor binding sites produced by continuous gepirone administration. These results suggest that the curious dissociation of behavioral and biochemical indices of 5-HT2 receptor function produced by continuous gepirone treatment may be the result of a dual yet separate action of the drug on central presynaptic noradrenergic and serotonergic mechanisms and postsynaptic 5-HT receptors. Furthermore, the postsynaptic action of gepirone which reduces the maximal number of cortical 5-HT2 receptor binding sites may be the result of gepirone's agonist action at postsynaptic 5-HT1A receptors.

Analysis of Variance↗
PubMed1991

Involvement of excitatory amino acid receptors in long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices.

The present article reviews studies from our laboratory, which have shown that excitatory amino acids receptors of the N-methyl-D-aspartate type are involved in the induction of long-term potentiation in the Schaffer collateral-commissural pathway of rat hippocampal slices. The nature of the excitatory amino acid receptors that mediate the response that is modified by the induction of long-term potentiation is also considered. The mechanism of induction of long-term potentiation is discussed, as are some possible stages that are required for the maintenance of this process. Some new data are presented concerning the ability of N-methyl-D-aspartate to potentiate synaptic transmission and to depress the amplitude of the presynaptic fibre volley. Concerning the potentiation, it is shown that brief (1-2 min) perfusion of slices with N-methyl-D-aspartate is sufficient to potentiate synaptic transmission for at least 3 h. The N-methyl-D-aspartate induced depression of the presynaptic fibre volley is shown to be transient and independent of synaptic transmission.

Animals↗
PubMed1990

Review of an Irish cervical smear service.

Cervical cytology material from 5,815 women who presented to General Practitioners throughout Ireland for routine cervical smears were referred to our Pathology Laboratory. The smears were reviewed retrospectively in order to report on the incidence of dyskaryosis and other abnormalities diagnosed on cervical cytology. Evidence of dyskaryosis was found in a total of 2.2% and "borderline" changes in a total of 0.3% of smears. Cytology and subsequent histology were compared in cases of significant cervical intraepithelial neoplasia. Comparison in cases of moderate and severe dyskaryosis showed precise correlation between the diagnosis of cervical intraepithelial neoplasia on biopsy and its prediction on cytology in 30 of 33 cases. Over a third of women screened were in their 4th decade and the highest incidence of dyskaryosis was in this age group. Only 10% of those screened were 50 years or over and a third were aged 40 years and over. These facts are of relevance with regard to the problem of targeting the population at risk in the long term planning of routine cytology screening services in this country.

Adolescent↗
PubMed1987

Prevalence of antibody to Chlamydia trachomatis in spontaneous abortion and infertility.

A higher prevalence of Chlamydia trachomatis antibody occurred in 57.6% of women with recurrent abortion, but not in their male partners, compared to 33.7% of normal pregnant women (p less than 0.01) and 44.2% of infertile women (NS). The mean titer for the recurrent abortion group was not significantly elevated, compared to controls. Women with blocked fallopian tubes had the highest prevalence of elevated titers (p less than 0.01) and the highest mean titer (p less than 0.001). Despite multiple testing, no women or men were chlamydia culture-positive. The lack of isolation among patients with antibody could be due to cryptic infection at a site not amenable to culture or to inhibition by secretory IgA. There could also be nonspecific stimulation of chlamydial antibody caused by other infections such as mycoplasma. The presence, though at a low level, of antibody in culture-negative patients suggests chlamydia may not be directly associated with recurrent abortion but reflect previous exposure to chlamydia or an altered immune system.

Abortion, Habitual↗