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Biomedical subjects

S L Jones

Publications and source records attributed to S L Jones.

At least 37 records · Page 2Linked to original sources

The predictive value of exhaled nitric oxide measurements in assessing changes in asthma control.

Exhaled nitric oxide (eNO) levels are increased in untreated or unstable asthma and measurements can be made easily. Our aim was to assess the usefulness of eNO for diagnosing and predicting loss of control (LOC) in asthma following steroid withdrawal. Comparisons were made against sputum eosinophils and airway hyperresponsiveness (AHR) to hypertonic saline (4.5%). Seventy-eight patients with mild/moderate asthma had their inhaled steroid therapy withdrawn until LOC occurred or for a maximum of 6 wk. Sixty (77.9%) developed LOC. There were highly significant correlations between the changes in eNO and symptoms (p < 0.0001), FEV(1) (p < 0.002), sputum eosinophils (p < 0.0002), and saline PD(15) (p < 0.0002), and there were significant differences between LOC and no LOC groups. Both single measurements and changes of eNO (10 ppb, 15 ppb, or an increase of > 60% over baseline) had positive predictive values that ranged from 80 to 90% for predicting and diagnosing LOC. These values were similar to those obtained using sputum eosinophils and saline PD(15) measurements. We conclude that eNO measurements are as useful as induced sputum analysis and AHR in assessing airway inflammation, with the advantage that they are easy to perform.

Adolescent↗

Neodymium:yttrium-aluminum-garnet laser ablation of a urethral web to relieve urinary outflow obstruction in a horse.

An 8-year-old Hanoverian gelding was examined because of urine dribbling and urethral obstruction. Mild proprioceptive deficits of the left hind limb were evident during neurologic examination. Ultrasonography per rectum revealed dilatation of the pelvic portion of the urethra. Endoscopy of the urethra revealed 2 webs of tissue: 1 was located 10 cm proximal to the external urethral opening; the other was located 65 cm proximal to the external urethral opening and prevented passage of the endoscope into the urinary bladder. The mass was ablated with a neodymium:yttrium-aluminum-garnet laser, using a transendoscopic noncontact technique. On follow-up examination 6 months after laser surgery, an endoscope could easily be passed into the bladder, and no urethral web was seen. The horse was able to void a stream of urine but continued to dribble urine intermittently. The proximal location of the urethral lesion in this horse would have made use of traditional surgical methods problematic, whereas transendoscopic laser photoablation was easy and effective.

Animals↗

The future of antiinflammatory therapy.

The cells and mediators that make up the inflammatory response have the potential to injure tissues and contribute to the pathophysiology of many inflammatory diseases. Strategies to reduce neutrophil migration into sites of inflammation and subsequent activation by inhibiting integrin-mediated adhesion hold promise for successful treatment of a variety of inflammatory diseases. New pharmacologic agents that specifically target prostanoid mediators of inflammation by specifically inhibiting the activity of cyclooxygenase 2 are potent antiinflammatory agents with fewer gastrointestinal side effects than nonspecific cyclooxygenase inhibitors. These areas of antiinflammatory research are rapidly yielding drugs with diverse future applications in equine medicine.

Animals↗

BOVIGAM: an in vitro cellular diagnostic test for bovine tuberculosis.

BOVIGAM which is based on the detection of gamma interferon (IFN- gamma) is a rapid, laboratory assay of a cell mediated immune response that may be used for the detection of tuberculosis (TB) infection in animals. Whole blood is first incubated overnight with bovine PPD, avian PPD or negative control antigens, and IFN- gamma in the supernatant plasma is then measured by EIA. TB infection is indicated by a predominant IFN- gamma response to bovine PPD. Since 1988, BOVIGAM has been extensively trialed on more than 200 000 cattle in Australia, Brazil, Ireland, Northern Ireland, Italy, New Zealand, Romania, Spain and the USA. Sensitivity has varied between 81.8% and 100% for culture-confirmed bovine TB and specificity between 94% and 100%. The IFN- gamma assay detects M. bovis infection earlier than the skin test and in New Zealand is applied to detect skin-test negative cattle with TB, where after slaughter a significant number of IFN- gamma reactors have TB. BOVIGAM is also approved in New Zealand for serial testing skin test positive cattle when non-specificity is suspected. Cattle are tested 7-30 days after a positive caudal fold test. The boosting effect of the skin test on T-cell activity allows blood to be cultured with PPD up to 30 h after collection without effecting accuracy. The BOVIGAM results are not affected by poor nutritional condition and are only mildly and briefly affected by dexamethasone treatment and parturition. IFN- gamma responses of cattle vaccinated with BCG are dose-dependent and short-lived. The BOVIGAM kit is now used routinely in many countries for the detection of M. bovis infected cattle, buffalo and goats.

Animals↗

Comparison of purified protein derivatives and effect of skin testing on results of a commercial gamma interferon assay for diagnosis of tuberculosis in cattle.

Purified protein derivatives (PPD) prepared in the USA were compared with those prepared in Australia by a private company (CSL Veterinary) for use with a commercial gamma interferon (gamma-IFN) assay for diagnosis of bovine tuberculosis. The effect of skin testing on results of the gamma-IFN assay was determined, and results were compared when blood samples were stimulated with PPD within 2 hours and after 24 hours of sample collection. Twenty cattle that were sensitized by subcutaneous injection of heat-killed Mycobacterium bovis were randomly divided into 3 groups. Cattle in group A were tested with the caudal fold skin test (CFT) on day 0 and the comparative cervical skin test (CCT) on day 7. Cattle in group B were tested with the CFT on day 0 and the CCT on day 63, and group C cattle were not skin tested. Blood samples for the gamma-IFN assay were collected at various times throughout the study period. Optical density (OD) values for the gamma-IFN assay were not significantly different when blood samples were stimulated with US avian PPD and CSL avian PPD. However, OD values were significantly higher for US bovine PPD than for CSL bovine PPD. However, the final interpretation of the gamma-IFN assay was usually the same when using either US or CSL PPD. In addition, OD values for the gamma-IFN assay were significantly higher for blood samples collected after sensitized cattle were skin tested than for samples collected from the same cattle before skin testing or from cattle not skin tested. The OD values for blood samples stimulated within 2 hours of sample collection were significantly higher than for samples stimulated 24 hours after sample collection. However, OD values for all PPD-stimulated samples from sensitized cattle were significantly higher in samples collected 3 days after skin testing and stimulated 24 hours after collection than for samples from the same animals collected before skin testing and stimulated within 2 hours of sample collection. Results of this study indicate that PPD prepared in the USA or Australia can be used to stimulate blood samples for the gamma-IFN assay. Skin testing cattle prior to collection of blood for the gamma-IFN assay boosts production of gamma-IFN by lymphocytes from cattle that have had prior exposure to M. bovis antigens. Use of the gamma-IFN assay in conjunction with skin testing may improve detection of cattle infected with M. bovis. In addition, the increase in production of gamma-IFN after skin testing will permit greater flexibility in conducting the assay because samples can be stimulated after they have been shipped overnight rather than only on the day of sample collection.

Animals↗

Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol.

Continuous treatment with a short-acting beta2-agonist can lead to reduced bronchodilator responsiveness during acute bronchoconstriction. This study evaluated bronchodilator tolerance to salbutamol following regular treatment with a long-acting beta2-agonist, formoterol. The modifying effect of intravenous corticosteroid was also studied. Ten asthmatic subjects (using inhaled steroids) participated in a randomised, double-blind, placebo-controlled, cross-over study. Formoterol 12 microg b.i.d. or matching placebo was given for 10-14 days with >2 weeks washout. Following each treatment, patients underwent a methacholine challenge to induce a fall in forced expired volume in one second (FEV1) of at least 20%, then salbutamol 100 microg, 100 microg, and 200 microg was inhaled via a spacer at 5 min intervals, with a further 400 microg at 45 min. After a third single-blind formoterol treatment period, hydrocortisone 200 mg was given intravenously prior to salbutamol. Dose-response curves for change in FEV1 with salbutamol were compared using analysis of covariance to take account of methacholine-induced changes in spirometry. Regular formoterol resulted in a significantly lower FEV1 after salbutamol at each time point compared to placebo (p<0.01). The area under the curves (AUCs) for 15 (AUC0-15) and 45 (AUC0-45) min were 28.8% and 29.5% lower following formoterol treatment (p<0.001). Pretreatment with hydrocortisone had no significant modifying effect within 2 h of administration. It is concluded that significant tolerance to the bronchodilator effects of inhaled salbutamol occurs 36 h after stopping the regular administration of formoterol. This bronchodilator tolerance is evident in circumstances of acute bronchconstriction.

Acute Disease↗

Induction of HIV-1-specific T-helper responses and type 1 cytokine secretion following therapeutic vaccination of macaques with a recombinant fowlpoxvirus co-expressing interferon-gamma.

Preventive and/or therapeutic vaccines against Human Immunodeficiency Virus (HIV-1) are urgently required. Induction of cellular immunity is favoured since these responses correlate with control of HIV-1. Recombinant fowlpoxvirus (FPV) vaccines encoding both HIV-1 gag/pol and interferon-gamma (FPV gag/pol-IFNgamma) were hypothesised to enhance HIV-specific cellular immunity and were further evaluated in macaques previously infected with HIV-1. A novel assay to detect IFNgamma secretion following HIV antigen stimulation of whole blood was developed to further assess the safety and immunogenicity of the FPV gag/pol-IFNgamma vaccine. Immunisation with FPV gag/pol-IFNgamma safely enhanced HIV-specific IFNgamma secretion following ex vivo stimulation of whole blood, greater than that observed following FPV gag/pol vaccination not co-expressing IFNgamma. Both HIV-specific IFNgamma-spot-forming cells by ELISPOT and CD69 expression by CD4+ lymphocytes were also enhanced following FPV gag/pol-IFNgamma vaccination. Hence, the FPV-HIV vaccine co-expressing IFNgamma stimulated HIV-specific T cell responses in macaques, and should be further evaluated as a therapeutic or preventive HIV vaccine.

AIDS Vaccines↗

Sensitivity and specificity of two serological tests for the detection of ovine paratuberculosis.

OBJECTIVE: To determine the sensitivity and specificity of an absorbed ELISA and an AGID test for the detection of clinical and subclinical paratuberculosis in sheep. DESIGN: By testing a panel of sera from 1257 Australian Merino and crossbred sheep greater than 1 year of age, of which 1137 sheep were not infected with Mycobacterium avium subsp paratuberculosis and 120 sheep had paratuberculosis. PROCEDURE: Sera were collected from 457 sheep in Victoria and 800 sheep in Western Australia. Presence of M a paratuberculosis infection in Victorian sheep was determined by histological examination of intestinal tissues, whereas sheep from Western Australia were presumed to be free of Johne's disease. The ability of an absorbed ELISA to discriminate between infected and uninfected sheep was described by test sensitivity and specificity, the distribution of ELISA OD, and the area under a receiver operating characteristic curve. RESULTS: The absorbed ELISA had a specificity of 98.2 to 99.5% (CI) and a sensitivity of 35 to 54% (CI). In sheep from infected flocks in Victoria, the AGID test had a specificity of 99 to 100% (CI) and a sensitivity of 38 to 56% (CI). The sensitivity of serological tests was higher in sheep with a body condition representative of the lower quintile of their flock of origin. CONCLUSION: The AGID test and absorbed ELISA are useful tests for the detection of ovine paratuberculosis. Although the tests had a similar accuracy, they detected different subpopulations of infected sheep with only moderate overlap. The AGID test had a higher specificity than the absorbed ELISA.

Animals↗

Knowledge, attitudes, and practices of parents of asthmatic children in Cape Town.

To obtain information useful to asthma care in a relatively poor, high asthma prevalence population, a focus group study was undertaken with 72 parents of children with asthma or recurrent wheezing. There was a reasonable level of understanding of the causes of asthma, although variable acceptance of the diagnosis. Willingness to undertake home management of acute episodes and environmental control measures was high. Reported treatment was characterized by reliance on syrups, use of home remedies, resistance to inhaled therapy, and relatively low compliance with prescribed treatment. There was agreement on the poor level of service offered by doctors and public sector clinics. Asthma education in this population needs to build on what parents know and accept, but stress the relative safety of inhaled therapy, the need for maintenance therapy, and the value of pre-exercise prophylaxis, house dust mite control, and smoking cessation. There is an urgent need to improve the quality of asthma care provided by public sector clinics.

Adult↗

Electronic journals: are they a paradigm shift?

Ejournals are becoming an accepted and necessary means of meeting the demands for the dissemination of knowledge. This introductory article discusses the recent "explosion" of ejournals and provides an explanation of what is meant by an "ejournal." Ejournals are explored within the traditional context of scholarship and a discussion of the "serials crisis" that promoted the inception of ejournals is presented. After laying the groundwork for discussing scholarship in this new age of dissemination of scholarly information, the article discusses whether this digital form of publication can be called a "paradigm shift" in Kuhn's (1970) traditional sense of the word.

Periodicals as Topic↗

Excessive use of inhaled salbutamol: the potential benefits of dose-reduction. A case report.

Inhaled, short-acting, beta-agonist medications are widely used in the treatment of asthma. It is recommended in current asthma management guidelines that these medications should only be used "as required" for relief of asthma symptoms. Despite this, there are still a number of asthmatic patients who are using excessive amounts. In occasional patients this may be detrimental to the control of asthma. We report the case of a 43-year-old, steroid-dependent asthmatic, with unstable asthma, using salbutamol up to 30 times a day. Following reduction of her beta-agonist use she had a dramatic improvement in her asthma control and was able to successfully stop her oral steroids.

Administration, Inhalation↗

Effects of ephedrine enantiomers on conditioned taste aversion and kaolin intake in rats.

The ephedrine (EPH) enantiomers, (-)-EPH and (+)-EPH, have different biological activity in the rat, with the (-)-EPH enantiomer exerting a greater impact on suppression of feeding, induction of locomotion, and activation of brown adipose tissue thermogenesis. Recent studies document that (-)-EPH treatment produces an alteration of extracellular dopamine in the brain, an effect that is consistent with the locomotor-stimulating and reinforcing effects of this drug. Whether the EPH enantiomers exert aversive actions in the rat is unknown. Experiment 1 examined the impact of systemically administered (+)-EPH (0, 5, 10, or 20 mg/kg) or (-)-EPH (0, 5, 10, or 20 mg/kg) on conditioned taste aversion (CTA) in adult male rats relative to the effect of 32 mg/kg lithium chloride (LiCl). No dose of either enantiomer produced CTA, whereas strong CTA was evident for LiCl. In Experiment 2, consumption of kaolin (a nonnutritive clay) over a 24-h period was used to assess drug toxicity. Rats treated with either 0, 5, 10, 20, or 40 mg/kg (+)-EPH or 0, 5, 10, 20, or 40 mg/kg (-)-EPH did not exhibit alteration of kaolin intake. In contrast, systematic increases in kaolin intake were observed in rats after systemic administration of LiCl (0, 16, 32, 64, and 96 mg/kg). These findings suggest that the enantiomers of EPH do not exert aversive effects at behaviorally relevant doses.

Analysis of Variance↗

A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor that is widely used to treat neutropenia. In addition to stimulating polymorphonuclear neutrophil (PMN) production, G-CSF may have significant effects on PMN function. Because G-CSF receptor (G-CSFR)-deficient mice do not have the expected neutrophilia after administration of human interleukin-8 (IL-8), we examined the effect of the loss of G-CSFR on IL-8-stimulated PMN function. Compared with wild-type PMNs, PMNs isolated from G-CSFR-deficient mice demonstrated markedly decreased chemotaxis to IL-8. PMN emigration into the skin of G-CSFR-deficient mice in response to IL-8 was also impaired. Significant chemotaxis defects were also seen in response to N-formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, or macrophage inflammatory protein-2. The defective chemotactic response to IL-8 does not appear to be due to impaired chemoattractant receptor function, as the number of IL-8 receptors and chemoattractant-induced calcium influx, actin polymerization, and release of gelatinase B were comparable to those of wild-type PMNs. Chemoattractant-induced adhesion of G-CSFR-deficient PMNs was significantly impaired, suggesting a defect in beta2-integrin activation. Collectively, these data demonstrate that selective defects in PMN activation are present in G-CSFR-deficient mice and indicate that G-CSF plays an important role in regulating PMN chemokine responsiveness.

Actins↗

Genetic-based and assisted reproductive technology of the 21st century.

The scientific advances of human genetics and assisted reproductive technology are redefining the concepts of health and illness by revealing the mysteries of the human genome and the process of conception, implantation, and diagnostic testing of the human embryo. The effect of these discoveries and their clinical applications will move from the tertiary to primary care arena through the ability to readily screen, diagnose, and treat some disorders and offer cure as the end result for others. In addition, the ethical, legal, and social issues, along with the attendant implications for professional practice, will need to be identified. Only a small portion of nurses have had to address the knowledge and practice issues associated with these advances. "Brave new families" are being created. Perinatal nurses must be prepared to meet the emerging needs of these families through the art and science of nursing.

Education, Nursing, Continuing↗

A role for the actin-bundling protein L-plastin in the regulation of leukocyte integrin function.

Regulation of leukocyte integrin avidity is a crucial aspect of inflammation and immunity. The actin cytoskeleton has an important role in the regulation of integrin function, but the cytoskeletal proteins involved are largely unknown. Because inflammatory stimuli that activate integrin-mediated adhesion in human polymorphonuclear neutrophils (PMN) and monocytes cause phosphorylation of the actin-bundling protein L-plastin, we tested whether L-plastin phosphorylation was involved in integrin activation. L-plastin-derived peptides that included the phosphorylation site (Ser-5) rapidly induced leukocyte integrin-mediated adhesion when introduced into the cytosol of freshly isolated primary human PMN and monocytes. Substitution of Ala for Ser-5 abolished the ability of the peptide to induce adhesion. Peptide-induced adhesion was sensitive to pharmacologic inhibition of phosphoinositol 3-kinase and protein kinase C, but adhesion induced by a peptide containing a phosphoserine at position 5 was insensitive to inhibition. These data establish a novel role for L-plastin in the regulation of leukocyte adhesion and suggest that many signaling events implicated in integrin regulation act via induction of L-plastin phosphorylation.

Amino Acid Sequence↗