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Biomedical subjects

J M Wright

Publications and source records attributed to J M Wright.

At least 73 records · Page 4Linked to original sources
PubMed1998

The role of l-thyroxine and hepatic reductase activity in isoniazid-induced hepatotoxicity in rabbits.

There is evidence that hydrazine, a metabolite of isoniazid, plays an important role in the mechanism of isoniazid-induced hepatotoxicity. Hydrazine has been reported to be metabolised by NADPH cytochrome P-450 reductase (reductase) to reactive and potentially toxic intermediates. The present study was designed, using a model of isoniazid-induced hepatotoxicity in rabbits, to determine whether or not reductase plays a role in this toxicity. Although pretreating rabbits with l-thyroxine increased hepatic reductase activity (54% greater than controls), the severity of isoniazid-induced hepatic cell damage (plasma argininosuccinic acid lyase activity) was lower in thyroxine pre-treated animals than in animals treated with isoniazid alone (31.3+/-20 vs 56.0+/-20 Takahara Units, respectively). In addition, pre-treatment with l-thyroxine completely prevented isoniazid-induced hepatic steatosis. In conclusion, contrary to our hypothesis, an increase in reductase activity achieved by pre-treatment with l-thyroxine was associated with a decrease in the severity of isoniazid-induced hepatic cell damage and steatosis in rabbits.

Animals↗
PubMed1998

Laboratory investigation and comparison of Salmonella Brandenburg cases in New Zealand.

An apparent increase in the incidence of S. Brandenburg in New Zealand, coupled with the possibility that the virulence of the organism may also be changing, prompted this study. Three typing methods: macro-restriction fragment length polymorphism (MRFLP) profiling using pulsed field gel electrophoresis (PFGE), plasmid profiling and antimicrobial susceptibility profiling were used to determine strain diversity amongst 115 recent and historical isolates of S. Brandenburg from both human cases and non-human sources. Antimicrobial resistance was noted only in three isolates. Plasmids of varying sizes were found in 31 isolates. MRFLP analysis resulted in 13 different patterns. Combining the three sets of typing data yielded 24 composite types. Comparison of composite type, isolation date and geographical location of case allowed the retrospective recognition of seven potential clusters during the 5-year study period. Composite types of 24 (80%) of the non-human isolates tested were indistinguishable from human isolates, suggesting that human infection may be via a number of vehicles. Although not cost-effective for routine use on all salmonella isolates, the methods used in this study are an important adjunct to serotyping for discrimination within an emerging serotype.

DNA, Bacterial↗
PubMed1998

Molecular cytogenetic analysis of heterochromatin in the chromosomes of tilapia, Oreochromis niloticus (Teleostei: Cichlidae).

The structure of the heterochromatic bands in mitotic chromosomes of the important tropical aquaculture species of tilapia, Oreochromis niloticus, was investigated by the combination of the C-banding technique, chromosomal digestion with two restriction endonucleases and fluorescence in situ hybridization (FISH) of two satellite DNAs (SATA and SATB). The tilapia chromosomes presented heterochromatic bands in the centromeres and in the short arms of almost all chromosomes that were differentially digested by the restriction endonucleases HaeIII and EcoRI. FISH of SATA showed that this satellite sequence is distributed in the centromeric region of all chromosomes of tilapia. FISH also revealed an intense hybridization signal for SATB in only one chromosome pair, but less intense signals were also present in several other pairs. The digestion of tilapia chromosomes by HaeIII and EcoRI was positively correlated with the position of SATA and SATB in chromosomes as revealed by FISH. The results obtained may be useful in future molecular and genetic studies of tilapias.

Animals↗
PubMed1998

Male mating success in an aquatically mating pinniped, the harbour seal (Phoca vitulina), assessed by microsatellite DNA markers.

Similar to many other pinniped species, harbour seals (Phoca vitulina) mate exclusively at sea. Here we present the first attempt to measure male mating success in an aquatically mating pinniped. Male mating success was estimated by paternity analysis in two cohorts of pups born at Sable Island, Nova Scotia, Canada, using microsatellite DNA markers. The genotypes of 275 pups born in 1994 and 1995 were compared to those of 90 candidate males at six microsatellite loci using a likelihood approach to resolve paternity. Paternity could be assigned for two, 22, 40 and 85 pups at confidence levels of 95, 80, 65 and 50%, respectively. Most successful males were assigned the paternity of a single offspring, suggesting a low variance in male mating success relative to most pinniped species. The proportion of paternal half sibs within cohorts and between maternally related sibs estimated by maximum likelihood were not significantly different from zero. It is thus unlikely that most offspring were sired by a small number of highly successful unsampled males, and that female harbour seals do not usually exhibit fidelity to the same male in sequential breeding seasons. A low level of polygyny in Sable Island harbour seals is consistent with predictions based on their breeding ecology, as females are highly mobile and widely dispersed in the aquatic mating environment at Sable Island.

Animals↗
PubMed1998

What is the plasma cofactor required by diuretics for direct vascular relaxant effect in vitro?

OBJECTIVE: To determine the plasma cofactor which is required by diuretics (hydrochlorothiazide, chlorthalidone, indapamide, and furosemide) for direct vasorelaxant effects in vitro. DESIGN: A randomized, double-blind, vehicle-control design was used to avoid experimenter bias. METHODS: We plotted concentration-response curves for responses to hydrochlorothiazide, chlorthalidone, indapamide, and furosemide of male Wistar rat aortic rings in the presence of different bath solutions containing various plasma factors. RESULTS: Plasma was found both to make possible and facilitate the vasodilator action of the diuretics tested by an action on the membrane and to decrease the action by binding the diuretics. The diuretics retained their vasorelaxant properties in Krebs solution alone, 30 min after having been incubated in a 50:50 solution of Krebs solution and plasma for 1 h. All four diuretics exerted significant vasorelaxant actions in Krebs solution-plasma, Krebs solution-serum, and Krebs solution plus human or bovine albumin (40 g/l) media. No vasorelaxant action was found in Krebs solution alone, Krebs solution plus denatured plasma, Krebs solution plus egg albumin, and Krebs solution plus insulin. CONCLUSION: Albumin is the main cofactor required by the diuretics tested for direct relaxant action in vitro, and these findings may explain some of the contradictory evidence concerning this action in the literature.

Animals↗
PubMed1998

Evidence-based pharmacotherapy: review of basic concepts and applications in clinical practice.

OBJECTIVE: To introduce concepts that may assist pharmacists in the use and application of scientific evidence in clinical practice. These concepts are followed by examples of clinical trials as well as case scenarios that guide the reader through solving clinical problems using the tools discussed in the article. BACKGROUND: The introduction of evidence-based practice in the 1990s has had a positive impact on the practices of medicine and pharmacy. Part of this impact has been in the area of drug therapy. Although much literature has been published on the principles of evidence-based practice in the past few years, most of this material was intended for practicing physicians. We are not aware of any articles on the use of the evidence-based principles intended for clinical pharmacists. We are also aware that discussing all of these principles is an enormous task and thus beyond the scope of this article. Therefore, we focused this discussion on a brief summary of different study designs, factors affecting the strength of scientific evidence, and interpretation of the data. An approach in the use of these concepts is discussed through the use of case scenarios. RECOMMENDATIONS: Clinical pharmacists must use concepts in evidence-based practice when making pharmacotherapeutic decisions.

Clinical Trials as Topic↗
PubMed1998

A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin.

The 4'-hydroxylation of the S-enantiomer of the anticonvulsant drug mephenytoin exhibits a genetic polymorphism in humans. This polymorphism shows marked interracial heterogeneity, with the poor metabolizer (PM) phenotype representing 2 to 5% of Caucasian and 13 to 23% of Asian populations. Two defective CYP2C19 alleles, CYP2C19*2 and CYP2C19*3, have been described which account for approximately 87% of Caucasian and > 99% of Oriental PM alleles. The present study identifies a new allele (CYP2C19*4) in Caucasian PMs which contains an A-->G mutation in the initiation codon. A new polymerase chain reaction-restriction fragment length polymorphism genotyping test was developed, and the incidence of this allele was examined in a European Caucasian population which had been phenotyped for mephenytoin metabolism. One of nine putative PMs was heterozygous for CYP2C19*2/CYP2C19*4, which suggests that CYP2C19*4 represents a defective allele. Six of the seven remaining putative PMs available for genotyping were explained by CYP2C19*2. The frequency of the CYP2C19*4 allele in Caucasians was 0.6%. An additional Caucasian PM from a separate study was also heterozygous for CYP2C19*2 and CYP2C19*4. To verify that CYP2C19*4 represented a defective CYP2C19 allele, the initiation codon of the normal CYP2C19*1 cDNA was mutated to a GTG, and both cDNAs were expressed in yeast. Recombinant CYP2C19 protein was detected by Western blot analysis of colonies transformed with CYP2C19*1 cDNA, but not in those transformed with CYP2C19*4 cDNA. The two cDNAs were also used in an in vitro coupled transcription/translation assay. CYP2C19 protein was translated only from the CYP2C19*1 allele. These data indicate that CYP2C19*4 represents a new PM allele.

Alleles↗
PubMed1998

ROn-1 SINEs: a tRNA-derived, short interspersed repetitive DNA element from Oreochromis niloticus and its species-specific distribution in Old World cichlid fishes.

A SINE-like repetitive element (ROn-1) has been cloned from the tilapiine cichlid fish Oreochromis niloticus. The element is 345 base pairs (bp) in length and consists of a transfer-RNA-like domain with putative RNA polymerase III recognition sequences, a tRNA-unrelated region, and a poly(A) tail. Approximately 6000 copies of ROn-1 occur in the haploid genome of O. niloticus. Southern blot analysis revealed that ROn-1 is an abundant element in the genomes of many African cichlid fishes, but absent from the genome of the Indian cichlid Etroplus.

Africa↗
PubMed1997

BAPTA-AM and ethanol protect cerebellar granule neurons from the destructive effect of the weaver gene.

The mechanisms by which the weaver gene (Reeves et al., 1989; Patil et al., 1995) inhibits neurite extension and/or induces death of the granule neurons in homozygous weaver mouse cerebellum are not presently understood. Here we show that BAPTA-AM and ethanol, which either reduce cytosolic levels of free calcium or prevent calcium entry, promote neurite outgrowth of the weaver neurons similar to the L-type calcium channel blocker verapamil (Liesi and Wright, 1996). Importantly, BAPTA-AM, ethanol, and verapamil not only restore neurite outgrowth of the weaver neurons but adjust their depolarized resting membrane potentials to the levels of normal neurons. These results indicate that calcium-dependent mechanisms mediate the action of the weaver gene and that the weaver neurons can be normalized by blocking this calcium effect. We further report that BAPTA-AM and verapamil also have a neuroprotective effect on normal neurons exposed to high concentrations of ethanol. We suggest that verapamil should be evaluated as a drug for treatment of alcohol-induced brain damage and neurodegenerative disorders.

Animals↗
PubMed1997

The adduction distraction maneuver.

The adduction distraction maneuver is presented as an adjunct to the surgeon's technical skills to assist with the initial introduction of the shoulder arthroscope. Both novice and experienced arthroscopists can experience difficulty establishing access to the glenohumeral joint. Often this results in articular cartilage or soft tissue damage. The adduction distraction maneuver when used in the "beach chair" seated position for shoulder arthroscopy can facilitate posterior portal placement and minimize iatrogenic trauma.

Arthroscopy↗
PubMed1997

Prevalence of periodontal disease in patients with Sjögren's syndrome.

The periodontal status of 25 patients with Sjögren's syndrome was compared with that of an age-, sex-, and race-matched healthy controls. Clinical evaluation included determination of number of teeth, decayed/missing/filled surfaces, probing pocket depth, clinical attachment level, plaque index, gingival index, bleeding on probing, and measurement of alveolar bone level (examined with radiography). Results of the study suggest that patients with Sjögren's syndrome have a significantly higher plaque index score (p < 0.005), higher decayed/missing/filled surfaces scores (p < 0.05), increased alveolar bone loss (p < 0.05), deeper clinical attachment level (p < 0.05), and increased cementoenamel junction-alveolar bone crest distance (p < 0.005). Although no significant difference was found in the number of cases of "established periodontitis" between the Sjögren's syndrome and controls, odds ratio analysis suggests that patients with Sjögren's syndrome are at 2.2 times higher risk of having adult periodontitis than healthy controls.

Adult↗
PubMed1997

Antifungals: use in high-risk patients.

Advanced medical technology has resulted in a growing population of patients with altered defense mechanisms against nosocomial infections. Fungal infections, primarily Candida species, account for a significant proportion of hospital-acquired infections and are associated with increased morbidity and mortality. This article discusses current issues and controversies related to nosocomial fungal infections and summarizes optimal management strategies.

Antifungal Agents↗
PubMed1997

Mexiletine in the symptomatic treatment of diabetic peripheral neuropathy.

OBJECTIVE: To evaluate the efficacy and safety of mexiletine in the symptomatic treatment of diabetic peripheral neuropathy (DPN). METHODS: In this prospective, double-blind study, 29 patients were randomized to receive mexiletine 600 mg/d or matching placebo for 3 weeks. A four-item symptom score (FIS), which rated pain, dysesthesias, paresthesias, and nightly exacerbations of symptoms, and a 100-mm visual analog scale (VAS), which rated pain intensity, were completed by patients before and after treatment. At the end of treatment independent patient and investigator global assessments were made. Patients reported adverse effects after 1 and 3 weeks of treatment. RESULTS: Treatment groups were similar at baseline. The difference between the median changes in FIS scores (mexiletine = 5.5, placebo = 2) was not statistically significant. Overall symptom response was similar in both treatment groups as demonstrated by both global assessments (p = 0.19). The mean change in VAS score from baseline to posttreatment was determined for both groups and the difference between these mean scores was 16.5 mm (95% CI, -7.1 to 40.2 mm) (p = 0.16). Inadequate statistical power (1-beta = 0.40) may have resulted from small sample size, small magnitude of effect, or variability in the measured effect. Adverse effects were more common in the mexiletine group, though not statistically significant. One patient receiving mexiletine was hospitalized for palpitations. CONCLUSIONS: Because of conflicting reports of mexiletine's efficacy in the treatment of symptomatic DPN, this drug should be reserved for patients unresponsive or intolerant to standard therapy, without evidence of heart disease, and with sensations of burning heat, formication, or stabbing pain.

Adult↗