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Biomedical subjects

D W Johnson

Publications and source records attributed to D W Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Alkyldimethylaminoethyl ester iodides for improved analysis of fatty acids by electrospray ionization tandem mass spectrometry.

The development of a new class of derivatives, the alkyldimethylaminoethyl ester iodides, for the analysis of fatty acids by electrospray ionization tandem mass spectrometry is described. They are prepared by quaternization of dimethylaminoethyl esters with alkyl iodides. The trimethylaminoethyl (choline) ester iodide affords between 8 and 12 times greater signal intensity than the corresponding dimethylaminoethyl ester used in the analysis of long to very long chain fatty acids in plasma samples. It is a superior derivative for unsaturated and monohydroxylated long chain fatty acids but unsuitable for bile acids and dicarboxylic acids.

Adult↗
PubMed2000

Glucocorticoids for croup.

BACKGROUND: Since the last meta-analysis in 1989, a number of randomised trials on the benefit of glucocorticoids have been published, resulting in an increasing interest in the use of glucocorticoids to treat outpatients with croup. The objective of this review was to provide evidence to guide clinicians in their treatment of patients with croup, to examine the effectiveness of glucocorticoids in these patients, and to identify areas of uncertainty for future research. OBJECTIVES: To determine the effect of glucocorticoids for children with croup. SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register, MEDLINE (January 1966 to August 1997) and Excerpta Medica/EMBASE (January 1974 to August 1997). We also contacted (by mail) authors of identified croup trials published in the last five years to inquire about other trials, published or unpublished. SELECTION CRITERIA: Meta-analysis of randomised controlled trials that examine the effectiveness of glucocorticoid treatment in children with croup. DATA COLLECTION AND ANALYSIS: Data were extracted using a structured form, which captured patient status (inpatient or outpatient), intervention and control, with the name of the drug, route of administration and dose. Data were also collected on the primary outcome measures comprised of a clinical croup score at baseline (as well as any other subsequent assessment times), length of stay (hours), patients status improved (yes/no), and use of co-interventions. The quality of the trials was assessed using empirically derived items that involved scales and components. Two researchers (TPK, MA) then selected studies as being potentially relevant based on a review of the titles and abstracts, if available. The complete text of these studies was then retrieved. All studies that had been retrieved were reviewed independently by two reviewers (AS, TPK). Data were extracted by one reviewer (MA) and checked for accuracy by a second reviewer (TPK). Two observers independently assessed quality (MA, JK), and inter rater agreement was measured by the intra class correlation. Differences were resolved by consensus. MAIN RESULTS: Twenty-four studies were deemed relevant for inclusion (N=2221). Glucocorticoid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of -1.0 (95% confidence interval -1.5 to -0.6) and at 12 hours -1.0 (-1.6 to -0. 4); at 24 hours this improvement was no longer significant (-1.0, -2. 0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with glucocorticoids: a decrease of 9% (95% confidence interval 2 to 16%) among those treated with budesonide and of 12% (4 to 20%) among those treated with dexamethasone. There was also a decrease in the length of time spent in accident and emergency (-11 hours, 95% confidence interval -18 to 4 hours), and for inpatients hospital stay was reduced by 16 hours (-31 to 1 hour). Publication bias seems to play a part in these results. REVIEWER'S CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer co-interventions are used and the length of time spent in hospital is decreased in patients treated with glucocorticoids.

Croup↗
PubMed2000

Decreased accumbens dopamine release after cocaine challenge in behaviorally sensitized female rats.

The effects of the competitive NMDA receptor antagonist CPP on the initiation of behavioral sensitization to acute cocaine and basal and acute cocaine-induced dopamine (DA) release in the nucleus accumbens (NAC) were assessed in female Sprague-Dawley rats. Cocaine pretreated rats (30 mg/kg IP, once daily for 7 days) challenged with cocaine (10 mg/kg) on day 8 displayed increased motor activity relative to controls challenged with cocaine on day 8. This effect was blocked in rats receiving CPP (2 mg/kg) 15 min prior to all cocaine pretreatments. Basal DA levels in the NAC of both cocaine-pretreated and CPP plus cocaine-pretreated rats were higher on day 8 compared to controls. Acute cocaine challenge on day 8 resulted in increased extracellular DA concentrations in the NAC in control rats, no increase in rats pretreated with CPP plus cocaine, and a decrease in rats pretreated with cocaine only. These data demonstrate that development of behavioral sensitization to cocaine in female Sprague-Dawley rats can be completely blocked by a peripherally administered competitive NMDA receptor antagonist and that an increase in DA release in the NAC after a cocaine challenge is not an absolute requirement for expression of motor sensitization to cocaine in female rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

A rapid screening procedure for the diagnosis of peroxisomal disorders: quantification of very long-chain fatty acids, as dimethylaminoethyl esters, in plasma and blood spots, by electrospray tandem mass spectrometry.

A rapid method with potential to screen for many of the peroxisomal disorders using 5 microl of plasma or a 3-mm blood spot (3.6 microl blood impregnated on filter paper) is described. Fatty acids are liberated from plasma or blood spots and converted to dimethylaminoethyl esters. Trideuterated fatty acids, added as internal standards, are used to quantify eicosanoic (C20:0), docosanoic (C22:0), tetracosanoic (C24:0) and hexacosanoic (C26:0) acids by electrospray tandem mass spectrometry. The C26:0/C22:0 and C24:0/C22:0 ratios are significantly greater in the plasma of patients with peroxisomal disorders compared to controls. The C20:0/C22:0 ratio is elevated in the plasma of peroxisomal patients who accumulate phytanic acid. Blood spots collected from four peroxisomal patients between 2 and 10 days after birth and stored for up to 17 years, were shown to give between 33% and 233% higher C26:0/C22:0 ratios compared to age-matched controls.

Blood Chemical Analysis↗
PubMed2000

Use of the Personality Assessment Inventory to assess psychopathy in offender populations.

The authors investigated the validity of the Antisocial Features (ANT) scale of the Personality Assessment Inventory (PAI; L. C. Morey, 1991) with respect to assessments of psychopathy in 2 offender samples. Study 1 included 46 forensic psychiatric inpatients who were administered the Screening Version of the Hare Psychopathy Checklist (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995). In Study 2, 55 sex offenders were administered the Hare Psychopathy Checklist--Revised (PCL-R; R. D. Hare, 1991). ANT scores correlated highly with the PCL:SV total score (r = .54) and moderately with the PCL-R total score (r = .40). ANT tapped primarily behavioral symptoms of psychopathy rather than interpersonal and affective symptoms. Also, ANT had low to moderate diagnostic efficiency regarding diagnoses of psychopathy, suggesting that it may be better used as a dimensional rather than categorical measure of this construct.

Adult↗
PubMed2000

Enalaprilat directly ameliorates in vitro cyclosporin nephrotoxicity in human tubulo-interstitial cells.

BACKGROUND/AIMS: Several recent studies have suggested that angiotensin-converting enzyme (ACE) inhibitors ameliorate chronic cyclosporin A (CyA) tubulo-interstitial disease by mechanisms independent of their antihypertensive effects. The aim of the present study was to determine whether ACE inhibition exerts a direct beneficial effect on the tubulo-interstitium in an in vitro model of chronic CyA nephropathy. METHODS: Primary cultures of human proximal tubular cells (PTC) and renal cortical fibroblasts (CF) were exposed for 24 h to CyA in the presence or absence of enalaprilat. Parameters of tubulo-interstitial nephrotoxicity were then measured including collagen synthesis (proline incorporation), tubular viability and function (thymidine incorporation, lactate dehydrogenase release, and apical sodium-hydrogen exchange), and secretion of insulin-like growth factor I, transforming growth factor beta 1 (TGFbeta1), and platelet-derived growth factor. RESULTS: CyA promoted CF collagen synthesis, PTC cytotoxicity (suppressed viability, growth and sodium transport), and tubulo-interstitial fibrogenic cytokine release (CF secretion of insulin-like growth factor I and PTC secretion of TGFbeta1 and platelet-derived growth factor). Enalaprilat completely reversed the stimulatory effects of CyA on CF collagen synthesis (CyA + enalaprilat 6.40 +/- 0.50% vs. CyA alone 8.33 +/- 0.56% vs. control 6.57 +/- 0.62% vs. enalaprilat alone 5.55 +/- 0.93%, p < 0.05) and PTC secretion of TGFbeta1 (0.71 +/- 0.11, 1.13 +/- 0.09, 0.89 +/- 0.07, and 0.67 +/- 0.09 ng/mg protein/day, respectively, p < 0.05). However, the other manifestations of CyA toxicity were not significantly reversed by concomitant enalaprilat administration. CONCLUSIONS: ACE inhibition directly prevents CyA-induced interstitial fibrosis, but not proximal tubule cytotoxicity, independently of haemodynamic and systemic renin-angiotensin system effects. Renoprotection may be partially afforded by directly preventing the tubular secretion of TGFbeta1.

Angiotensin II↗
PubMed1999

The effectiveness of glucocorticoids in treating croup: meta-analysis.

OBJECTIVE: To determine the effectiveness of glucocorticoid treatment in children with croup. DESIGN: Meta-analysis of randomised controlled trials that examine the effectiveness of glucocorticoid treatment in children with croup. MAIN OUTCOME MEASURES: Score on scale measuring severity of croup, use of cointerventions (adrenaline (epinephrine), antibiotics, or supplemental glucocorticoids), length of stay in accident and emergency or in hospital, and rate of hospitalisation. RESULTS: Twenty four studies met the inclusion criteria. Glucocorticoid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of -1.0 (95% confidence interval -1.5 to -0.6) and at 12 hours -1.0 (-1.6 to -0.4); at 24 hours this improvement was no longer significant (-1.0, -2.0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with glucocorticoids: a decrease of 9% (95% confidence interval 2% to 16%) among those treated with budesonide and of 12% (4% to 20%) among those treated with dexamethasone. There was also a decrease in the length of time spent in accident and emergency (-11 hours, 95% confidence interval -18 to 4 hours), and for inpatients hospital stay was reduced by 16 hours (-31 to 1 hour). Publication bias seems to play a part in these results. CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer cointerventions are used and the length of time spent in hospital is decreased in patients treated with glucocorticoids.

Anti-Bacterial Agents↗
PubMed1999

Metabolism of trideuterated iso-lignoceric acid in rats in vivo and in human fibroblasts in culture.

Saturated very long chain fatty acids (fatty acids with greater than 22 carbon atoms; VLCFA) accumulate in peroxisomal disorders, but there is little information on their turnover in patients. To determine the suitability of using stable isotope-labeled VLCFA in patients with these disorders, the metabolism of 22-methyl[23,23,23-2H3]tricosanoic (iso-lignoceric) acid was studied in rats in vivo and in human skin fibroblasts in culture. The deuterated iso-VLCFA was degraded to the corresponding 16- and 18-carbon iso-fatty acids by rats in vivo and by normal human skin fibroblasts in culture, but there was little or no degradation in peroxisome-deficient (Zellweger's syndrome) fibroblasts, indicating that its oxidation was peroxisomal. Neither the 14-, 20-, and 22-carbon iso-fatty acids nor the corresponding odd-chain metabolites could be detected. In the rat, the organ containing most of the iso-lignoceric acid, and its breakdown products, was the liver, whereas negligible amounts were detected in the brain, suggesting that little of the fatty acid crossed the blood-brain barrier. Our data indicate that VLCFA labeled with deuterium at the omega-position of the carbon chain are suitable derivatives for the in vivo investigation of patients with defects in peroxisomal beta-oxidation because they are metabolized by the same pathways as the corresponding n-VLCFA. Moreover, as iso-VLCFA and their beta-oxidation products are readily separated from the corresponding n-fatty acids by normal chromatographic procedures, the turnover of VLCFA can be more precisely measured.

Animals↗
PubMed1999

Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.

OBJECTIVE: In children with mild acute asthma, to compare treatment with a single dose of albuterol delivered by a metered dose inhaler (MDI) with a spacer in either a weight-adjusted high dose or a standard low-dose regimen with delivery by a nebulizer. STUDY DESIGN: In this randomized double-blind trial set in an emergency department, 90 children between 5 and 17 years of age with a baseline forced expiratory volume in 1 second (FEV1 ) between 50% and 79% of predicted value were treated with a single dose of albuterol, either 6 to 10 puffs (n = 30) or 2 puffs (n = 30) with an MDI with spacer or 0.15 mg/kg with a nebulizer (n = 30). RESULTS: No significant differences were seen between treatment groups in the degree of improvement in percent predicted FEV1 (P =.12), clinical score, respiratory rate, or O2 saturation. However, the nebulizer group had a significantly greater change in heart rate (P =.0001). Our study had 93% power to detect a mean difference in percent predicted FEV1 of 8 between the treatment groups. CONCLUSION: In children with mild acute asthma, treatment with 2 puffs of albuterol by an MDI with spacer is just as clinically beneficial as treatment with higher doses delivered by an MDI or by a nebulizer.

Adolescent↗
PubMed1999

Does competition enhance or inhibit motor performance: a meta-analysis.

A meta-analysis was conducted on the relative impact of cooperative, competitive, and individualistic efforts on motor skills performance. Competition was divided into 3 groups: zero sum, appropriate, and unclear. The motor skills tasks were divided into means-interdependent and means-independent tasks. The dependent variables were achievement-performance, interpersonal attraction, social support, and self-esteem. A total of 64 studies met the criteria for inclusion. Effects sizes were computed, and confidence intervals were used to determine their significance. A fail-safe sample size was computed to determine how many additional studies were needed to change the significance of the results. Cooperation resulted in higher achievement for means-interdependent tasks in zero-sum competition, unclear competition, and individualistic efforts, and it promoted higher achievement for means-independent tasks for unclear competition and individualistic efforts. For all comparisons, cooperation resulted in greater interpersonal attraction, social support, and self-esteem.

Achievement↗
PubMed1999

Optic disc and retinal microvasculopathy after high-dose chemotherapy and autologous hematopoietic progenitor cell support.

The purpose of this study was to prospectively evaluate the retinal and optic nerve changes in patients undergoing high-dose chemotherapy (HDC) followed by autologous hematopoietic progenitor cell support (AHPCS). One hundred and forty patients undergoing HDC and AHPCS underwent extensive pre- and post-transplant ophthalmologic evaluations for development of retinal microvascular complications. One hundred and ten patients received high-dose cyclophosphamide, cisplatin and BCNU; thirty received identical doses of cyclophosphamide and cisplatin, but received paclitaxel instead of BCNU. Thirty-four patients (24%) had retinal findings of either cotton wool spots (CWS) (n = 20) or retinal hemorrhages (n = 18) during follow-up, which ranged from 1 to 12 months. Ten (7%) of these patients, all of whom received BCNU, showed ocular toxicity characterized by CWS 1 to 4 months post transplant (n = 10); optic disc edema (n = 3); and variable vision loss associated with the onset of BCNU-induced pulmonary toxicity. Retinal and optic disc microvascular complications may occur after high-dose chemotherapy followed by AHPCS. The association of ischemic retinal lesions and/or optic disc edema with BCNU-induced pulmonary toxicity and the lack of ocular toxicity in patients that did not receive BCNU may suggest that BCNU is the etiologic agent.

Adult↗