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Biomedical subjects

Andrew Smith

Publications and source records attributed to Andrew Smith.

At least 55 records · Page 3Linked to original sources

YeastHub: a semantic web use case for integrating data in the life sciences domain.

MOTIVATION: As the semantic web technology is maturing and the need for life sciences data integration over the web is growing, it is important to explore how data integration needs can be addressed by the semantic web. The main problem that we face in data integration is a lack of widely-accepted standards for expressing the syntax and semantics of the data. We address this problem by exploring the use of semantic web technologies-including resource description framework (RDF), RDF site summary (RSS), relational-database-to-RDF mapping (D2RQ) and native RDF data repository-to represent, store and query both metadata and data across life sciences datasets. RESULTS: As many biological datasets are presently available in tabular format, we introduce an RDF structure into which they can be converted. Also, we develop a prototype web-based application called YeastHub that demonstrates how a life sciences data warehouse can be built using a native RDF data store (Sesame). This data warehouse allows integration of different types of yeast genome data provided by different resources in different formats including the tabular and RDF formats. Once the data are loaded into the data warehouse, RDF-based queries can be formulated to retrieve and query the data in an integrated fashion. AVAILABILITY: The YeastHub website is accessible via the following URL: http://yeasthub.gersteinlab.org.

Biology↗

A multicenter phase II study of "adjuvant" irinotecan following resection of colorectal hepatic metastases.

OBJECTIVES: This study evaluates the efficacy and toxicity of single-agent irinotecan following hepatectomy for metachronous colorectal metastases, and examines the predictive value of p27 and p53 expression and of microsatellite instability (MSI) status. METHODS: Twenty-nine patients, previously treated with 5-fluorouracil, with operable hepatic colorectal metastases underwent hepatectomy and received adjuvant irinotecan (thrice weekly) for 6 planned cycles. Metastases were examined for p53 and p27 expression by immunohistochemistry and for MSI using mono- and dinucleotide markers. RESULTS: The starting dose of irinotecan was 350 mg/m2 (in 3 patients), 300 mg/m2 (n = 14), and 250 mg/m2 (n = 12). Four patients failed to complete 6 cycles (2 progressive disease and 2 toxicity). Grade > or =3 toxicity was experienced in 8% of cycles (13 of 165). The estimated median relapse-free survival (RFS) was 45.2 months. RFS at 18 months was estimated to be 59% (95% confidence interval [CI], 43-80), 2-year overall survival (OS) was 85% (95% CI, 72-99.8), and the median follow-up was 27.9 months. Six patients (21%) have died; median OS has not been reached. In univariate analyses, p27 and MSI status were not predictive for RFS while p53 approached statistical significance (P = 0.051). Duration of chemotherapy was the only significant predictive factor (P = 0.006). CONCLUSION: The tolerability of this regimen after major liver resection supports further evaluation of irinotecan-based adjuvant chemotherapy in this group of patients.

Adenocarcinoma↗

Management of complex groin wounds: preferred use of the rectus femoris muscle flap.

This study reviews our experience with the rectus femoris muscle flap for complex groin wound reconstruction. Over the past 5 years, the rectus femoris has become our routine method of groin wound reconstruction. The rectus femoris is harvested through a midanterior incision extending over the distal two-thirds of the thigh. The muscle is elevated on its pedicle and transposed into the groin wound defect either directly or through an intervening skin bridge. Hospital and outpatient records were reviewed for all patients undergoing groin wound reconstruction with this technique from 1999 through 2003. Thirty-seven rectus femoris muscle flaps were performed in 33 patients. The mean patient age was 65.3 years (range, 25 to 88 years). Thirty groin wounds (81.1 percent) occurred after infrainguinal revascularization, 23 (76.7 percent) of which contained prosthetic material. Five (21.7 percent) of these wounds had their prosthetic material removed at the time of reconstruction. The remaining seven groin wounds (18.9 percent) occurred after femoral vessel cannulation for either cardiac or transplant surgery. There were no intraoperative mortalities and no anastomotic hemorrhages. There were no flap losses. Thirty-five of the 37 treated wounds healed (94.6 percent), 26 primarily (70.3 percent) and nine (24.3 percent) after delayed healing and contracture. Reoperation was performed in one patient for flap readvancement and in three patients for prosthetic graft removal after initial flap reconstruction. Two patients (6.1 percent) died during their hospitalization with persistent open groin wounds after flap reconstruction. All muscle flap donor incisions healed, with only two (5.4 percent) experiencing minimal delayed healing. There were no donor-site wound infections and no donor sites required reoperation. Thirty-three groin wounds (89.2 percent) demonstrated culture-positive microbial infection, 15 (45.5 percent) of which were polymicrobial. The 30-day mortality rate was 15.2 percent and the 6-month mortality rate increased to 27.2 percent, with multisystem organ failure as the most common cause. The rectus femoris muscle flap is an effective and reliable means of complex groin wound reconstruction. The muscle flap is dependable and the donor site is not problematic, even in the presence of peripheral vascular disease. On the basis of our clinical results, we believe that the rectus femoris muscle flap is the flap of choice for groin wound reconstruction.

Adult↗

Access, boundaries and their effects: legitimate participation in anaesthesia.

The distribution of work, knowledge and responsibilities in the delivery of anaesthesia has attained particular significance recently as attempts to meet the demands of the European Working Times Directive intensify existing pressures to reorganise anaesthetic services. Using Lave and Wenger's (1991) notions of 'legitimate peripheral participation' in 'communities of practice' (and Wenger 1998) to analyse ethnographic data of anaesthetic practice we illustrate how work and knowledge are currently configured, and when knowledge may legitimately be taken as the basis for action. The ability to initiate action, to prescribe healthcare interventions, we suggest, is a critical element in the organisation of anaesthetic practices and therefore central to any attempts to reshape the delivery of anaesthetic services.

Anesthesiology↗

The information needs of perioperative staff: a preparatory study for a proposed specialist library for theatres (NeLH).

AIMS/OBJECTIVES: To undertake an information-needs analysis of operating theatre staff in order to inform the development of a specialist library of the National Electronic Library of Health (NeLH). SETTING: Three hospitals in an NHS Trust in a rural county in the north of England. METHODS: In-depth interviews, during which staff were questioned in regard to their job roles and information needs, information-seeking behaviour, access to computers, use and perceptions of the NeLH, and what they would like from a specialist library. RESULTS: Information needs were found to concern direct care, professional and academic development, medical devices knowledge and administration. Currency and speed of delivery were the key information requirements. Poor communication appeared to be a major problem for many staff and inhibited efficient information exchange. When using the Web, both clinical and non-clinical staff searched in a similar fashion to health consumers generally, despite their need for highly specialist information. Most respondents reacted warmly to the idea of the proposed National Electronic Library for Theatre Staff (NeLTS) and made several practical suggestions for suitable material. However, access was problematic for nurses and might prove to be an obstacle to take-up of the Specialist Library. CONCLUSIONS: Communication difficulties, the fragmentation of data in the field and the consequent difficulties of finding information point to the need for an NeLTS. However, for this library to embrace and succeed with all the various groups that constitute the operating theatre staff, issues of access and digital literacy need to be addressed.

England↗

Importance of organosulfur utilization for survival of Pseudomonas putida in soil and rhizosphere.

The sulfur present in both agricultural and uncultivated soils is largely in the form of sulfonates and sulfate esters and not as free, bioavailable inorganic sulfate. Desulfurization of the former compounds in vitro has previously been studied in Pseudomonas putida, a common rhizosphere inhabitant. Survival of P. putida strains was now investigated in three sulfur-deficient Danish soils which were found to contain 60 to 70% of their sulfur in sulfonate or sulfate ester form, as determined by X-ray near-edge spectroscopy. The soil fitness of P. putida S-313 was compared with that of isogenic strains with mutations in the sftR and asfA genes (required for in vitro desulfurization of sulfate esters and arylsulfonates, respectively) and in the ssu locus (required in vitro for the desulfurization of both sulfonates and sulfate esters). asfA or sftR mutants showed significantly reduced survival compared to the parent strain in bulk soil that had been enriched with carbon and nitrogen to mimic rhizosphere conditions, but this reduced survival was not observed in the absence of these additives. In a tomato rhizosphere grown in compost, survival of sftR and ssu mutants was reduced relative to the parent strain. The results demonstrate that the ability to desulfurize sulfonates and sulfate esters is critical for survival of bacteria in the rhizosphere but less so in bulk soils outside the influence of plant roots, where carbon is the limiting nutrient for growth.

Arylsulfonates↗

Assessment of 100 live potential renal donors for laparoscopic nephrectomy with multi-detector row helical CT.

PURPOSE: To retrospectively review the authors' experience with multi-detector row helical computed tomography (CT) in assessing 100 consecutive live potential renal donors. MATERIALS AND METHODS: Hospital ethical committee approval was obtained; informed patient consent was not required. One hundred potential renal donors underwent multi-detector row CT assessment. Nonenhanced, arterial phase, and nephrographic phase examinations were performed. Delayed topograms were acquired to visualize the collecting system anatomy. A vascular radiologist prospectively interpreted the multi-detector row CT images. A second vascular radiologist, blinded to the initial results, retrospectively reviewed the images. Eighty candidates subsequently underwent donor nephrectomy, including 70 laparoscopic donor nephrectomies (LDNs) and 10 open donor nephrectomies (ODNs). Surgical findings served as the reference standard for 80 kidneys. The imaging findings in all 100 candidates (200 kidneys) were reviewed, although these findings were considered observational data only because there was no reference standard for 120 kidneys. RESULTS: Multi-detector row CT findings predicted uncomplicated LDN in 67 of 70 patients. Small upper-pole capsular arteries arising from the distal main renal artery in two patients were not described in the multi-detector row CT report: In one patient, the arising vessels resulted in conversion to ODN because of bleeding; in the other patient, arterial reconstruction was performed. In another patient, conversion to ODN was necessary because of ongoing bleeding from an avulsed large lumbar venous tributary to the left renal vein. Observational data revealed that multiple renal arteries--most of which were accessory renal arteries--were seen in 52 (26%) kidneys. Early branching of the main renal artery was seen in 24 (12%) kidneys, and main renal arterial abnormalities were identified in six (3%). Capsular arteries were detected in 10 (5%) kidneys. Major variations in the anatomy of the main renal veins--including multiple right renal veins, a retroaortic left renal vein, and a circumaortic left renal vein--were seen in 28 (14%) kidneys. Large (>5 mm in diameter) systemic tributaries to the left renal vein were seen in 25 (25%) kidneys. There was no significant interobserver disagreement between the vascular radiologists. CONCLUSION: Multi-detector row CT findings can predict successful LDN in live potential renal donors.

Adult↗

Effects of repeated doses of caffeine on mood and performance of alert and fatigued volunteers.

Evidence for behavioural effects of caffeine is well documented in the literature. It is associated with increased subjective alertness, improved reaction time and enhanced encoding of new information. These effects are most prominent in low arousal situations. However, there is an ongoing debate as to whether such changes are in fact improvements or merely a reversal of the negative effects of a period of caffeine withdrawal (e.g. overnight abstinence). To avoid such a confound this study included multiple doses of caffeine which were administered under double-blind conditions to participants who had ingested their normal daily quota of caffeine. In the present study participants were fatigued by carrying out a prolonged testing schedule in the evening. Sixty volunteers, all regular caffeine consumers, took part in the study. They attended for three sessions on separate days. They were instructed to consume normal amounts of caffeinated beverages. Consumption was measured by a diary and saliva samples were taken and caffeine assays conducted. A baseline test session was carried out at 18.00h and following this a double blind placebo controlled caffeine challenge (1.5mg/kg) conducted. The test battery was repeated twice approximately 30 minutes after the caffeine challenge. Following this another drink was administered and the test battery repeated twice more. On one test session volunteers had placebo in both drinks, in another they had caffeine in both drinks and another caffeine in the first and placebo in the second. Order of conditions was balanced across subjects. The results showed that caffeine led to a more positive mood and improved performance on a number of tasks. Different effects of caffeine were seen depending on the person's level of arousal. Linear effects of caffeine dose were also observed. This is evidence against the argument that behavioural changes due to caffeine are merely the reversal of negative effects of a long period of caffeine abstinence. The findings are discussed in relation to both noradrenergic and cholinergic neurotransmitter systems.

Adolescent↗

When the drug of choice is a drug of confusion: embalming fluid use in inner city Hartford, CT.

This paper examines the use of a new illicit drug--embalming fluid mixtures--in Hartford, CT based on a recent assessment of drug consumption in an outreach-recruited sample of 242 not-in-treatment active drug users. Sociodemographic, drug use, and health and social problems of drug users who do and do not use embalming fluid mixture are presented, revealing some notable differences between these two groups of street drug users. Despite regular consumption, we report that embalming fluid mixture users are often uncertain about what is in this new drug, despite experiencing often powerful effects. Urine toxicology findings from a subsample of individuals who used embalming fluid mixtures in the last 48 hours, reveal the frequent presence of phencyclidine (PCP) as well as other drugs. The public health implications of this new wave of PCP use are assessed.

Acquired Immunodeficiency Syndrome↗

Significant morphological but little molecular differences between Trypanosoma of rodents from Alaska.

We examined blood smears of 173 rodents and 33 shrews captured at 4 sites in the Gates of the Arctic National Park, northern Alaska, in summer 2002. Trypanosoma spp. were detected in the plasma of 5 Microtus oeconomus, 4 Microtus miurus, and 1 Lemmus trimucronatus. The trypomastigote morphology from different individuals of M. oeconomus caught at the same site and of M. miurus from different sites varied significantly. The 4 DNA sequences obtained from the blood smear positive samples contained 2 different haplotypes very similar to each other and to that of Trypanosoma microti. Of possible vectors of blood parasites, the flea Amalaraeus dissimilis was collected from M. miurus.

Alaska↗

Physiogenomic analysis links serum creatine kinase activities during statin therapy to vascular smooth muscle homeostasis.

Statins are highly effective at reducing coronary disease risk. The main side effects of these medications are a variety of skeletal muscle complaints ranging from mild myalgia to frank rhabdomyolysis. To search for physiologic factors possibly influencing statin muscle toxicity, we screened for genetic associations with serum creatine kinase (CK) levels in 102 patients receiving statin therapy for hypercholesteremia. A total of 19 single nucleotide polymorphism (SNPs) were selected from ten candidate genes involved in vascular homeostasis. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. SNPs in the angiotensin II Type 1 receptor (AGTR1) and nitric oxide synthase 3 (NOS3) genes were significantly associated with CK activity. These results demonstrate a strong association between CK activity during statin treatment and variability in genes related to vascular function, and suggest that vascular smooth muscle function may contribute to the muscle side effects of statins.

Adult↗

Feasibility assessment of aortic valve area in patients with aortic stenosis using a pressure wire through a 4 French system and single femoral arterial access.

OBJECTIVE: We sought to determine the safety, success and accuracy of using a pressure wire through a 4 French catheter with single arterial access to determine the aortic valve area in patients with aortic stenosis. BACKGROUND: Conventional invasive techniques to assess aortic stenosis are associated with procedural risks secondary to bilateral femoral access or the sheath size and reduced accuracy using femoral sheath pressure to replace ascending aortic pressure. METHODS: Cardiac output was measured using a pulmonary artery catheter. With a 4 French catheter through single femoral access ascending aortic pressure and, with a pressure wire, left ventricular pressure were recorded simultaneously in four patients with aortic stenosis. Likewise, both pressures were recorded using the pullback method. Pressure gradients were determined by both methods and aortic valve area calculated with the Gorlin equation prior to correlation. Of note, patients with significant arrhythmias such as atrial fibrillation or frequent premature atrial or ventricular contractions were excluded to maintain accuracy of the pullback method. RESULTS: All hemodynamic parameters were successfully obtained in all four patients. The correlation between pressure wire and pullback method was highly significant in this case series (n = 4, r = 0.983, p = 0.017). There were no complications. CONCLUSION: The results suggest that the aortic valve area can be safely and accurately evaluated with a pressure wire using a 4 French system. This novel method could be the preferred method for patients with vascular access limitations.

Aged↗

The inhibition of LPS-induced splenocyte proliferation by ortho-substituted and microbially dechlorinated polychlorinated biphenyls is associated with a decreased expression of cyclin D2.

Immunological effects of polychlorinated biphenyls (PCBs) have been demonstrated in our laboratories with the peferential inhibition of lipopolysaccharide (LPS)-induced splenocyte proliferation by ortho-substituted PCB congeners. An investigation of the mechanism behind this immunotoxicity revealed an interruption in the progression of murine lymphocytes from G0/G1 into S phase by Aroclor 1242 and the di-ortho-substituted congener, 2,2'-chlorobiphenyl (CB), whereas, a non-ortho-substituted congener, 4,4'-CB, did not affect cell cycle progression. This interruption of cell cycle progression by 2,2'-CB and Aroclor 1242 was associated with a decreased expression of the cell cycle regulatory protein, cyclin D2, while expression was not affected by exposure to the non-ortho-substituted 4,4'-CB. These results suggest the preferential inhibition of LPS-induced splenocyte proliferation by ortho-substituted congeners is a result of a decreased expression of cyclin D2, which leads to an interruption in cell cycle progression. In addition, PCB mixtures with an increased percentage of chlorines in the ortho position following an environmentally occurring degradation process inhibited LPS-induced proliferation, interrupted cell cycle progression, and decreased cyclin D2 expression. This study provides evidence for a mechanism of action of the immunological effects of ortho-substituted individual congeners as well as environmentally relevant mixtures enriched in congeners with this substitution pattern.

Anaerobiosis↗

Evaluation of a point-of-care assay for cardiac markers for patients suspected of acute myocardial infarction.

BACKGROUND: Creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) are important biomarkers for the diagnosis and rule-out of acute myocardial infarction (AMI) of patients who presented to the emergency department (ED) with chest pain. With new rapid ED assessment protocols, there is increasing pressure to produce results with a short turnaround time (TAT), and point-of-care (POC) testing is one alternative for providing fast results. METHODS: In a multicenter study, we evaluated the analytical precision, sensitivity and specificity of the RAMP (Response Biomedical) CK-MB and cTnI POC assays and compared results against the Triage (Biosite) POC and the Dimension RxL (Dade Behring) central-laboratory assays on 365 subjects, including 185 patients suspected of AMI, and determined the normal range on 180 healthy individuals. At one site, the clinical sensitivity and specificity were estimated in 121 patients and healthy subjects with AMI using the European Society of Cardiology (ESC)/American College of Cardiology (ACC) definition of AMI. Results from healthy individuals and those with ST elevation and non-ST elevation AMI were included in a receiver operating characteristic (ROC) curve analysis. RESULTS: Intra- and total imprecision ranged from 7.2% to 11.4% for cTnI at 0.22, 1 and 5 ng/ml and 4.8% to 8.6% for CK-MB at 7, 14 and 25 ng/ml. The upper limit of linearity was 32 ng/ml with an average recovery of 105% for cTnI and 80 ng/ml with a 106% recovery for CK-MB. The lower limit of detection was 0.03 ng/ml (10% coefficient of variance [CV] = 0.21 ng/ml) for cTnI and 0.32 ng/ml for CK-MB. The upper reference limit (normal range) was < 0.03 ng/ml for cTnI and 0-3.7 ng/ml for CK-MB. Analytical correlation against Dimension RxL were RAMP=(0.456 x RxL) + 0.11 (r = 0.988, n = 364) for cTnI and RAMP=(0.966 x RxL) + 0.60 (r = 0.986, n = 363) for CK-MB and against Triage, RAMP=(0.626 x Triage) + 0.164 (r = 0.969, n = 364) for cTnI and RAMP=(0.845 x RxL) - 0.495 (r = 0.952, n = 363) for CK-MB. On 39 AMI and 67 non-AMI patients, the clinical sensitivity, specificity and diagnostic efficiency of the cTnI and CK-MB RAMP assays were not significantly different from predicate assays. CONCLUSIONS: The RAMP cardiac marker assays are alternatives to other FDA-cleared central laboratory and POC testing devices.

Acute Disease↗

Optimum blood collection intervals for B-type natriuretic peptide testing in patients with heart failure.

Patients with congestive heart failure have increased concentrations of B-type natriuretic peptide (BNP) in blood. We determined the frequency of serial BNP measurements that exceeded the biologic variation of BNP of 100% as a function of days between blood collections. Samples collected 7 days apart were associated with the highest frequency (50%) of statistically different results (increased or decreased) compared with daily collections, where increased or decreased results occurred less often (22%).

Blood Specimen Collection↗

Electronic control of the regiochemistry in palladium-phosphine catalyzed intermolecular Heck reactions.

Density functional theory calculations of the transition-state structures and reaction barriers for the C-C coupling between monosubstituted eta(2)-olefins and eta(1)-vinyl for neutral [PdI(PH(3))(vinyl)(RCHCH(2))] and cationic [Pd(H(2)PCH(2)PH(2))(vinyl)(RCHCH(2))](+) (R = OMe, Me, and CN) depend mostly on the regiochemistry and not on the starting position of the olefin substituent. The regiochemistry is thus implicit in the electronic structure of the precursor complex. A selectivity index, Omega, based on electrostatic and frontier orbital interactions gives a good correlation with experiment for vinylations or arylations. The model correctly predicts that the regiochemistry for R = OMe, Me, and CN is the same for both neutral and cationic Pd complexes while for R = CH(2)OH the regiochemistry reverses. The latter is confirmed by explicit calculations of the transition-state energies. Selectivity indices are computed for 13 substituents: CO(2)Me, CN, CF(3), Ph, H, Me, CH(2)OH, CH(2)NMe(2), 2-pyrolidone, CH(2)SiMe(3), OAc, OMe, and F. Cationic conditions systematically give larger Omega values and thus tend to favor coupling at the alpha carbon on the olefin. The Omega values are approximately additive and can be used to predict the regiochemistry for disubstituted olefins.

Journal Article↗

Sex differences in age-related stiffening of the aorta in subjects with type 2 diabetes.

Hypertension and type 2 diabetes are associated with increased aortic pulse wave velocity (PWV), a measure of aortic stiffness and a powerful risk factor for cardiovascular events. The association of hypertension with type 2 diabetes may obscure the degree to which diabetes rather than hypertension contributes to an elevated PWV. The objective of this study was to determine whether the presence of type 2 diabetes is associated with an elevated PWV compared with nondiabetic subjects matched for mean arterial blood pressure. PWV was determined by measuring carotid to femoral transit time using applanation tonometry in 186 subjects (104 women) with (n=93) and without (n=93) type 2 diabetes. Diabetic and nondiabetic subjects were matched for age and mean arterial pressure (to +/-5 years and 5 mm Hg, respectively). PWV was strongly correlated with age and mean arterial blood pressure (R=0.59 and 0.29 respectively, each P<0.0001). PWV increased significantly more with age in women with diabetes (slope of regression line+/-SE: 0.19+/-0.03 m x s(-1) x year(-1)) than in nondiabetic women (0.08+/-0.02 m x s(-1) x year(-1), P<0.01 for difference). In men, however, the age-related increase in PWV was similar in diabetic (0.15+/-0.03 m x s(-1) x year(-1)) and nondiabetic subjects (0.13+/-0.03 m. s(-1) x year(-1), P=NS). The interaction of diabetic status with age and with sex was significant (P=0.01). Type 2 diabetes is associated with a greater age-related stiffening of the aorta in women compared with men, and this is not explained by hypertension.

Adult↗