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Biomedical subjects

Ian Wilson

Publications and source records attributed to Ian Wilson.

12 recordsLinked to original sources

Ethyl glucoside in human urine following dietary exposure: detection by 1H NMR spectroscopy as a result of metabonomic screening of humans.

Metabonomic screening of human urine samples using 1H NMR spectroscopy has revealed the presence of signals resulting from the excretion of ethyl glucoside. Experiments in volunteers have demonstrated that this ethyl glucoside results from dietary exposure to the compound, which is present in beverages such as rice wine and sake, rather than representing a new route for the metabolism of ethanol by humans. The limited studies undertaken in volunteers indicate that ethyl glucoside has a longer biological half life than ethanol itself. The potential problems associated with using this glucoside metabolite as a marker of ethanol consumption are considered.

Chromatography, High Pressure Liquid↗

A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation.

AIMS: The efficacy of cardioversion (DCCV) for restoration of sinus rhythm (SR) in persistent atrial fibrillation (AF) is limited by a high relapse rate. Relapse may be reduced by amiodarone but no placebo-controlled trials of efficacy have been performed and the appropriate duration of therapy is unknown. METHODS AND RESULTS: In this double-blind study, 161 subjects with persistent AF were randomized to one of three groups-placebo (n=38); amiodarone 400mg BD for 2 weeks prior to DCCV and 200mg daily for 8 weeks followed by placebo for 44 weeks (n=62, short-term amiodarone); amiodarone 400mg BD for 2 weeks then 200mg daily for 52 weeks (n=61, long-term amiodarone). Spontaneous reversion to SR occurred before DCCV in 21% (26/123) patients on amiodarone and none of the 38 patients on placebo (absolute difference 21%, 95% confidence interval (CI): 10 to 29%, P=0.002). At 8 weeks following DCCV, 51% (63/123) patients on amiodarone remained in SR compared to 16% (6/38) taking placebo (difference-35% 95% CI: -48 to -18%, P<0.001). At 1 year, 49% (30/61) patients on long-term amiodarone were in SR compared to 33% (21/62) taking short-term amiodarone (difference-15%, 95% CI: -31 to 2%, P=0.085). There was no difference in adverse event rate or quality of life scores between groups. CONCLUSIONS: Amiodarone pre-treatment before electrical DCCV for persistent AF allows chemical conversion in one-fifth of patients without altering the efficacy of subsequent DC conversion. Amiodarone is more effective than placebo in the maintenance of SR when continued for 8 weeks following successful DCCV. More patients taking long-term amiodarone remained in SR at 52 weeks, but more had serious adverse effects requiring discontinuation of therapy. Eight weeks of adjuvant therapy with amiodarone following successful DCCV may be the preferred option.

Aged↗

Psychiatric comorbidity in general practice.

BACKGROUND: Much of teaching and research has concentrated on single disease entities. In general practice, however, many patients suffer from a number of interacting illnesses at the same time. It is unlikely we will ever have randomised controlled trials to guide the management of such patients. OBJECTIVE: This article aims to develop a framework that will assist general practitioners in day-to-day clinical work with patients presenting with concurrent multiple physical and mental health problems. DISCUSSION: A positive, caring, patient centred approach is required and multiple diagnoses need to be managed within an integrated treatment plan. The quality of the therapeutic relationship is central to patient outcomes. Assessing and managing risk issues is a priority and coordinating care with other health professionals is essential. Set realistic goals, don't make changes too quickly or all at once, and don't assume that because a patient is taking a particular medication the associated diagnosis is correct.

Adult↗

Directed evolution of N-acetylneuraminic acid aldolase to catalyze enantiomeric aldol reactions.

Expanding the scope of substrate specificity and stereoselectivity is of current interest in enzyme catalysis. Using error-prone PCR for in vitro directed evolution, the Neu5Ac aldolase from Escherichia coli has been altered to improve its catalytic activity toward enantiomeric substrates including N-acetyl-L-mannosamine and L-arabinose to produce L-sialic acid and L-KDO, the mirror-image sugars of the corresponding naturally occurring D-sugars. The first generation variant containing two mutations (Tyr98His and Phe115Leu) outside the (alpha,beta)(8)-barrel active site exhibits an inversion of enantioselectivity toward KDO and the second generation variant contains an additional amino acid change Val251Ile outside the alpha,beta-barrel active site that improves the enantiomeric formation of L-sialic acid and L-KDO. The X-ray structure of the triple mutant epNanA.2.5 at 2.3A resolution showed no significant difference between the wild-type and the mutant enzymes. We probed the potential structural 'hot spot' of enantioselectivity with saturation mutagenesis at Val251, the mutated residue most proximal to the Schiff base forming Lys165. The selected variant had an increase in k(cat) via replacement with another hydrophobic residue, leucine. Further sampling of a larger sequence space with error-prone PCR selected a third generation variant with significant improvement in L-KDO catalysis and a complete reversal of enantioselectivity.

Aldehydes↗

A 5-year follow-up of general practice patients experiencing depression.

BACKGROUND: Depression is a common disease in primary care and produces significant morbidity in the community. Little is known about the outcomes of depression in general practice. OBJECTIVES: This research set out to explore both the longitudinal management and outcomes of depression as seen in general practice. METHODS: The Medic-GP database is a collection of the medical records of >50 000 people seen in nine Australian general practices. It was used to follow the management of depressed patients over 4-5 years. Records from 1994-1995 were searched for depression or similar words. Individual records of patients whose notes mentioned depression were randomly selected and examined to determine if they were diagnosed with depression. Records of patients who were diagnosed as suffering from depression were examined to determine progress over the ensuing 5 years. RESULTS: Six hundred of 5889 patients were examined in detail. A total of 382 patients (63.7%) were diagnosed with depression; 219 had been diagnosed during this time interval. The main findings were 64.7% of patients were female; 93.6% of patients received an antidepressant at some time during the study; 16% of patients were referred to a psychiatrist; 7.3% were hospitalized; 30% of patients who ceased antidepressants without a recurrence had courses of antidepressants of 3 months or less; and only 22.5% of patients had a single episode of depression. CONCLUSION: Unlike cross-sectional studies, this study has shown a high rate of prescription of antidepressants. GPs often prescribed short courses of antidepressants, and depression behaves as a chronic, recurrent disease.

Adolescent↗

Multilocus enzyme electrophoresis: a practical guide.

Multilocus enzyme electrophoresis (MEE) uses the relative electrophoretic mobilities of intracellular enzymes to characterize and differentiate organisms by generating an electromorph type (ET). This article presents the chemical conditions that may be useful, a guide to the successful practice of the electrophoretic technique, and analysis of the results.

Algorithms↗

Detection of Chlamydia pneumoniae by polymerase chain reaction-enzyme immunoassay in intestinal mucosal biopsies from patients with inflammatory bowel disease and controls.

BACKGROUND AND AIM: It has been suggested that Chlamydia is an organism that may have the potential to cause inflammatory bowel disease (IBD) in susceptible individuals. Chlamydia pneumoniae has emerged as an important human pathogen in the last decade. The objective of the present study was to investigate the frequency of the presence of C. pneumoniae DNA in intestinal biopsies from patients with IBD and from non-IBD controls. METHODS: The DNA was extracted from 222 colonoscopic biopsies, which were obtained from 11 patients with Crohn's disease (CD), 18 patients with ulcerative colitis (UC) and from 37 non-IBD control patients. The presence of the C. pneumoniae omp1 gene and C. trachomatis 16S rRNA gene was determined using a rapid and sensitive polymerase chain reaction-enzyme immunoassay (PCR-EIA). RESULTS: The C. pneumoniae-specific DNA was detected in 32 (14.4%) of 222 endoscopic biopsies. Among them, C. pneumoniae DNA were found in nine of 42 (21.4%) biopsies from patients with CD, nine of 59 (15.3%) biopsies from patients with UC, and 14 out of 122 (11.4%) biopsies from non-IBD control patients, respectively. Moreover, the percentage of patients with at least one biopsy positive for C. pneumoniae was higher, although not statistically significant, in CD (36.4%) and UC patients (38.9%) compared to non-IBD controls (16.2%). In contrast, C. trachomatis DNA was detected in only two of 222 (0.9%) biopsy samples. CONCLUSION: The C. pneumoniae DNA was detected in the intestine of both patients with IBD and in non-IBD control patients, probably reflecting the high prevalence of this organism in the environment. The moderate yield of positive biopsies in our IBD patients and the fact that the detection rate of C. pneumoniae DNA was similar in endoscopic biopsies from IBD patients and non-IBD controls does not support a direct role for this organism in the pathogenesis of IBD.

Adolescent↗

Activation of the mucosal immune system in irritable bowel syndrome.

BACKGROUND & AIMS: A role for the mucosal immune system in the pathogenesis of irritable bowel syndrome is suggested by its association with intestinal infections. METHODS: To investigate this, we performed histologic and immunohistologic studies on colonoscopic biopsy specimens from 77 patients with symptoms satisfying the Rome criteria and 28 asymptomatic control patients. RESULTS: Histologic assessment of biopsy specimens from symptomatic patients indicated 3 different groups. The first (38 of 77) had normal conventional histology; however, immunohistology showed increased intraepithelial lymphocytes (median, 1.8-fold; range, 1.74-1.86), lamina propria CD3(+) cells (2-fold; range, 1.55-2.91), and CD25(+) cells (6.5-fold; range, 4.98-8.13) compared with asymptomatic controls. The second group (31 of 77) had nonspecific microscopic inflammation and on immunohistology showed similar increases in lymphocyte populations (not significant vs. the uninflamed group) as well as increased numbers of neutrophil leukocytes and mast cells (P < 0.0001 vs. controls and the uninflamed group). The third group (8 of 77) fulfilled histologic and immunohistologic criteria for classic lymphocytic colitis. CONCLUSIONS: Examination of colonoscopic biopsy specimens from patients meeting the Rome criteria for a clinical diagnosis of irritable bowel syndrome showed subgroups with normal and abnormal conventional histology. All groups showed increased numbers of activated immunocompetent cells in the intestinal mucosa on quantitative immunohistology, implicating the mucosal immune system in pathogenesis.

Adult↗

Patterning of the vertebrate ventral spinal cord.

We review investigations that have lead to a model of how the ventral spinal cord of higher vertebrate embryos is patterned during development. Central to this model is the secreted morphogen protein, Sonic hedgehog. There is now considerable evidence that this molecule acts in a concentration-dependent manner to direct the development of the spinal cord. Recent studies have suggested that two classes of homeodomain proteins are induced by threshold concentrations of Sonic hedgehog. Reciprocal inhibition between the two classes acts to convert the continuous gradient of Sonic hedgehog into defined domains of transcription factor expression. However, a number of aspects of ventral spinal cord patterning remain to be elucidated. Some issues currently under investigation involve temporal aspects of Shh-signalling, the role of other signals in ventral patterning and the characterisation of ventral interneurons. In this review, we discuss the current state of knowledge of these issues and present some preliminary studies aimed at furthering understanding of these processes in spinal cord patterning.

Animals↗

Pathways to care.

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Australia↗