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Biomedical subjects

W Smith

Publications and source records attributed to W Smith.

At least 19 recordsLinked to original sources
PubMed2006

Retinal vascular calibre and the risk of coronary heart disease-related death.

OBJECTIVE: To examine whether retinal vascular calibre independently predicts risk of coronary heart disease (CHD) -related death. METHODS: In a population-based cohort study of 3654 Australians aged > or = 49 years, retinal arteriolar and venular calibres were measured from baseline retinal photographs and the arteriole to venule ratio (AVR) was calculated. CHD-related death was confirmed from the Australian National Death Index. RESULTS: Over nine years, 78 women (4.1%) and 114 men (7.8%) had incident CHD-related deaths. In people aged 49-75 years, wider venules were associated with CHD death, with relative risk (RR) 1.8 (95% confidence interval (CI) 1.1 to 2.7) and RR 2.0 (95% CI 1.1 to 3.6) per standard deviation (SD) increase in venular calibre for men and women, respectively, after adjustment for traditional risk factors. Additionally, in women aged 49-75 years, smaller AVR and narrower arterioles were associated with CHD death (RR 1.5, 95% CI 1.1 to 2.2, and RR 1.9, 95% CI 1.0 to 3.5 per SD decrease in AVR and arteriolar calibre, respectively, after adjustment). These associations were not observed in people aged > 75 years. CONCLUSIONS: These findings suggest that microvascular disease processes may have a role in CHD development in middle-aged people, particularly in women. Retinal photography may be useful in cardiovascular risk prediction.

Aged↗
PubMed2006

A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion.

OBJECTIVE: To compare changes in weight in obese patients who received long-acting octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg) or placebo over 6 months and to identify the lowest dose of octreotide LAR that safely achieved optimal weight loss. DESIGN: Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels. PATIENTS: A total of 172 adults (28 men and 144 women) with at least moderate obesity (body mass index (BMI) range 30-65 kg/m2) and evidence of insulin hypersecretion were enrolled. Patients were predominantly either Caucasian (50.0%) or African American (45.3%). The mean age (38 +/- 11 year), weight (110.7 +/- 23 kg), and BMI (39.8 +/- 6.5 kg/m2) were similar across the four treatment groups. MEASUREMENTS: Efficacy measures included weight, BMI, fasting serum glucose; triglycerides; percentage of total body fat and abdominal fat as measured by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip circumference; leptin; percentage of carbohydrates, fat, and protein ingested; nutritional evaluation (including dietary analysis--3-day food record); quality of life (QoL; using the Impact of Weight on Quality of Life-Lite); Beck Depression Inventory; and Carbohydrate Craving Questionnaire. Safety measures included medical history, vital signs, physical examinations, hematology, blood chemistries, thyroid function tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and adverse events. RESULTS: After 6 months of treatment, patients receiving 40 or 60 mg of octreotide LAR experienced statistically significant weight loss compared to baseline, with mean differences from placebo in percent weight change of -1.98 and -1.87%, respectively. This finding was accompanied by statistically significant mean decreases in BMI compared to baseline, that is, a mean decrease of 0.73 and 0.79 kg/m2 for the 40 and 60 mg treatment arms, respectively. The observed weight loss was progressive during the 6-month treatment in the two higher dose groups. The lowest dose to reach statistical significance in weight loss after 6 months' treatment was 40 mg. Post hoc analysis revealed a 3.5-3.8% weight loss at month 6 in the two higher dose groups among Caucasian patients having insulin secretion greater than the median of the cohort, defined as CIR(gp) (corrected insulin response at the glucose peak) > or = 1.43. There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake. Mean changes of blood glucose AUC(0-180 min) during an oral glucose tolerance test in patients taking octreotide LAR were 39-40 mg/dl h higher than those on placebo. A total of 7-21% of the patients taking octreotide LAR reached a 5% or greater decrease in body weight from Baseline, compared to 11% for the placebo group. This was not statistically significant. The most common adverse events included diarrhea, headache, cholelithiasis, nausea, and abdominal pain. CONCLUSION: Octreotide LAR given at 40 or 60 mg resulted in statistically significant weight loss. A post hoc analysis stratifying patients by race and CIR(gp) indicated that Caucasian patients with the greater degree of insulin hypersecretion appeared to derive the most benefit from treatment. The observed safety profile was consistent with the known effects of octreotide from previous studies.

Adult↗
PubMed2006

How we do it: laser reduction of peri-tubal adenoids in selected patients with otitis media with effusion.

. The literature supports the benefit of adenoidectomy in patients with otitis media with effusion (OME). . It is difficult to clear adenoid tissue from around the Eustachian tubes using curettes and this conventional method of adenoidectomy is contra-indicated in patients with cleft palates. . Laser reduction of peri-Eustachian adenoid tissue without myringotomies or grommet insertion was performed in three patients with OME. Two patients had previous adenoidectomies performed with curettes and one patient had a cleft palate. . In all three patients, the OME resolved and all had closure of the air-bone gap that was maintained during long-term follow-up (14 months-4 years). . This technique resolved OME without the need for myringotomies or grommet insertion and should be considered particularly in patients who have peri-tubal recurrence of adenoidal tissue following conventional adenoidectomy or in patients with cleft palate where there is concern with regards to palatal incompetence.

Acoustic Impedance Tests↗
PubMed2006

The in vitro activity of selected defensins against an isolate of Pseudomonas in the presence of human tears.

BACKGROUND/AIMS: Pseudomonas aeruginosa is a major cause of severe bacterial keratitis and remains a difficult clinical entity to treat successfully with the current arsenal of antimicrobial agents. Defensins are small cationic peptides with broad in vitro antimicrobial activity and are potential ocular therapeutic agents. The authors characterised the in vitro activity of defensins NP-1 and NP-3a against P aeruginosa in the presence of human tears. METHODS: A clinical Pseudomonas isolate was grown to mid-log phase, and 1 x 10(6 )colony forming units were exposed to the peptides (200 microg/ml) for up to 2 hours in the presence of varying concentrations (10-70%) of human tears. RESULTS: For both peptides in the presence of 10% tears, >3 log units of killing was achieved within 30 minutes. In 70% tears, NP-1 produced >1 log unit of killing at 2 hours, indicating that, although reduced, its activity remained significant. In 20% tears, NP-3a demonstrated 2 log units of killing at 2 hours; however, the antimicrobial activity of this defensin was completely inhibited in the presence of 70% tears. CONCLUSION: These in vitro data suggest that while the microbicidal activity of some defensins may be diminished at the ocular surface in vivo, significant activity is still possible with certain peptides.

Animals↗
PubMed2006

The utility of DynaCT in neuroendovascular procedures.

The authors present 3 patients who underwent neuroendovascular procedures in which DynaCT produced by a flat-panel detector facilitated management of complications. As part of a combined CT/angiography suite, DynaCT offered the major advantage of immediate detection or exclusion of intracranial complication without patient transfer. The quality of cone-volume CT-generated images produced by DynaCT was sufficient to make a diagnosis.

Adult↗
PubMed2005

Topical and oral CAM in acne: a review of the empirical evidence and a consideration of its context.

INTRODUCTION: Acne is one of the commonest diseases to afflict humanity. Anecdotally, the use of CAM in acne is widespread. In this review the empirical evidence for the efficacy of CAM modalities is examined and the context for their use discussed. METHODS: Searches were made of the MEDLINE, EMBASE, AMED (Allied and Complementary Medicines), Cochrane, and DARE databases using the search terms "acne" and "acne vulgaris" together with "alternative" and "complementary". RESULTS: The identified studies examined a broad range of CAM modalities but were of generally poor methodological quality. Evidence suggests that many of these therapies are biologically plausible. DISCUSSION AND CONCLUSION: Complementary therapies in acne should be viewed in a wider context than that of the very limited empiric evidence base that exists for their use. Further rigorously conducted trials should be conducted to define efficacy and adverse effect profiles of currently used CAM acne therapies.

Acne Vulgaris↗
PubMed2005

Retinal microvascular signs and risk of stroke and stroke mortality.

OBJECTIVE: The purpose of this study was to assess the relation of retinal microvascular signs and incident stroke and stroke mortality in an older population. METHODS: The authors took retinal photographs on baseline participants (3,654 patients aged 49+ years) of the Blue Mountains Eye Study (1992 to 1994). They assessed the presence of retinopathy (microaneurysms, retinal hemorrhages) in participants without diabetes and retinal arteriolar signs in all participants using standardized grading protocols. Incident stroke/TIA/cerebrovascular death (combined stroke events) were identified at follow-up examinations during 1997 to 1999. RESULTS: During a 7-year period, 859 participants died, 97 (11.3%) of which died of cerebrovascular causes. Of survivors, 24 had confirmed incident stroke, and 11 had incident TIA. Combined stroke events were more frequent in participants with retinopathy (5.7%), with moderate/severe arteriovenous nicking (4.2%), or with focal arteriolar narrowing (7.2%) compared with those without (1.9%). After controlling for age, sex, systolic blood pressure, smoking, and self-rated health, retinopathy was significantly associated with combined stroke events (relative risk [RR] 1.7, 95% CI 1.0 to 2.8) in persons without diabetes. This association was stronger in those without severe hypertension (RR 2.7, CI 1.2 to 6.2) or in persons with two or more retinal microvascular signs (RR 2.7, CI 1.5 to 5.2). Generalized or focal arteriolar narrowing or arteriovenous nicking was not independently associated with combined stroke events after multivariate adjustment. CONCLUSIONS: In older Australians without diabetes, retinopathy signs predict stroke or stroke-related death independent of traditional stroke risk factors.

Age Factors↗
PubMed2005

Basal ganglia calcification in BB/E rats with diabetes.

Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three sub-groups according to age (and duration of diabetes). Basal ganglia calcification (BGC) was present in the brains of more than 50% of diabetic animals, but not in any of 37 non-diabetic BB/E rats. BGC occurred more commonly in those animals which had the longest duration of diabetes (p=0.001), such that BGC was present in only 8% of animals with diabetes for 20 weeks, but in 100% of animals with diabetes for 60 weeks. There were no other significant light microscopic neuropathologic changes in diabetic animals. It will be important to investigate the mechanism of brain calcification, whether a similar process occurs in humans with diabetes, and its possible relationship to cognitive decline.

Actins↗
PubMed2005

Radiocontrast anaphylaxis with failure of premedication.

Radiocontrast media (RCM) is used commonly in clinical practice, and can be associated with significant adverse effects. We report a patient who experienced severe anaphylaxis after being given multiple drugs. Challenge testing established allergy to both RCM and ceftriaxone. Premedication did not prevent recurrence of anaphylaxis on repeat challenge with RCM. The haemodynamic and serum tryptase consequences of the challenges are discussed, and a summary of RCM allergy is provided.

Anaphylaxis↗
PubMed2005

Aspirin-sensitive asthma.

Aspirin-sensitive asthma is a common and often underdiagnosed disease affecting up to 20% of the adult asthmatic population. It is associated with more severe asthma, requires increased use of inhaled and oral corticosteroids, more presentations to hospital and a risk of life-threatening reactions with aspirin/non-steroid anti-inflammatory drug (NSAID) ingestion. Aspirin-sensitive asthma is often accompanied by severe rhinosinusitis and recurrent nasal polyposis, causing significant impairment of patients' quality of life. The pathogenesis of aspirin-sensitive asthma is complex and involves chronic eosinophilic inflammatory changes, with evidence of increased mast cell activation. The cyclo-oxygenase pathways play a major role in the respiratory reactions that develop after aspirin ingestion. The cysteinyl-leukotrienes have also been shown to play a role in the pathogenesis of aspirin-sensitive asthma. The clinical management of aspirin-sensitive asthma is complicated by the lack of diagnostic testing, other than challenge procedures. Other aspects of management include management of the underlying asthma and avoidance of NSAID in the majority of patients. Other considerations in the management of patients with aspirin-sensitive asthma include the role of leukotriene modifying agents, aspirin desensitization, and the use of other agents, such as roxithromycin. The management of nasal polyposis in patients with aspirin-sensitive asthma often needs to be considered as a separate issue, and requires a team approach.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease.

Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL(CR) = 50-80 mL/min), moderate (CL(CR) = 20-49 mL/min), and severe chronic renal disease (CL(CR) <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400-mg dose of posaconazole oral suspension with a standardized high-fat breakfast. For hemodialysis-dependent subjects, this dose was given on a nonhemodialysis day, and a second 400-mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis-dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, C(max), CL/F, and t1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only approximately 3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (approximately 98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single-dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.

Administration, Oral↗
PubMed2005

Brugada syndrome following tricyclic antidepressant overdose.

The Brugada syndrome, a pro-arrhythmogenic repolarization abnormality, is becoming increasingly recognised as a cause of collapse and sudden cardiac death. We report a case of a 48-year-old man with a tricyclic overdose and a delayed presentation of the Brugada pattern in the ICU. This case raises the need for clinicians to be aware of the Brugada pattern and those patients potentially at risk.

Antidepressive Agents, Tricyclic↗
PubMed2004

DL_POLY_3: the CCP5 national UK code for molecular-dynamics simulations.

DL_POLY_3 is a general-purpose molecular-dynamics simulation package embedding a highly efficient domain decomposition (DD) parallelization strategy. It was developed at Daresbury Laboratory under the auspices of the Engineering and Physical Sciences Research Council. Written to support academic research, it has a wide range of applications and will run on a wide range of computers; from single-processor workstations to multi-processor computers, with accent on the efficient use of multi-processor power. A new DD adaptation of the smoothed particle mesh Ewald method for calculating long-range forces in molecular simulations, incorporating a novel three-dimensional fast Fourier transform (the Daresbury Advanced Fourier Transform), makes it possible to simulate systems of the order of one million particles and beyond. DL_POLY_3 structure, functionality, performance and availability are described in this feature paper.

Algorithms↗