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Biomedical subjects

S R Wilson

Publications and source records attributed to S R Wilson.

At least 37 records · Page 2Linked to original sources

Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial.

OBJECTIVE: To compare the effectiveness and safety of low-dose unfractionated heparin and a low-molecular-weight heparin as prophylaxis against venous thromboembolism after colorectal surgery. METHODS: In a multicenter, double-blind trial, patients undergoing resection of part or all of the colon or rectum were randomized to receive, by subcutaneous injection, either calcium heparin 5,000 units every 8 hours or enoxaparin 40 mg once daily (plus two additional saline injections). Deep vein thrombosis was assessed by routine bilateral contrast venography performed between postoperative day 5 and 9, or earlier if clinically suspected. RESULTS: Nine hundred thirty-six randomized patients completed the protocol and had an adequate outcome assessment. The venous thromboembolism rates were the same in both groups. There were no deaths from pulmonary embolism or bleeding complications. Although the proportion of all bleeding events in the enoxaparin group was significantly greater than in the low-dose heparin group, the rates of major bleeding and reoperation for bleeding were not significantly different. CONCLUSIONS: Both heparin 5,000 units subcutaneously every 8 hours and enoxaparin 40 mg subcutaneously once daily provide highly effective and safe prophylaxis for patients undergoing colorectal surgery. However, given the current differences in cost, prophylaxis with low-dose heparin remains the preferred method at present.

Anticoagulants↗

A controlled trial of an environmental tobacco smoke reduction intervention in low-income children with asthma.

STUDY OBJECTIVES: To determine the effectiveness of a cotinine-feedback, behaviorally based education intervention in reducing environmental tobacco smoke (ETS) exposure and health-care utilization of children with asthma. DESIGN: Randomized controlled trial of educational intervention vs usual care. SETTING: The pediatric pulmonary service of a regional pediatric hospital. PARTICIPANTS: ETS-exposed, Medicaid/Medi-Cal-eligible, predominantly minority children who were 3 to 12 years old and who were seen for asthma in the hospital's emergency, inpatient, and outpatient services departments (n = 87). INTERVENTION: Three nurse-led sessions employing behavior-changing strategies and basic asthma education and that incorporated repeated feedback on the child's urinary cotinine level. MEASUREMENTS: The primary measurements were the urinary cotinine/creatinine ratio (CCR) and the number of acute asthma medical visits. The secondary measurements were number of hospitalizations, smoking restrictions in home, amount smoked, reported exposures of children, and asthma control. RESULTS: The intervention was associated with a significantly lower odds ratio (OR) for more than one acute asthma medical visit in the follow-up year, after adjusting for baseline visits (total visits, 87; OR, 0.32; p = 0.03), and a comparably sized but nonsignificant OR for one or more hospitalization (OR, 0.34; p = 0.14). The follow-up CCR measurement and the determination of whether smoking was prohibited inside the home strongly favored the intervention group (n = 51) (mean difference in CCR adjusted for baseline, -0.38; p = 0.26; n = 51) (60; OR [for proportion of subjects prohibiting smoking], 0.24; p = 0.11; n = 60). CONCLUSIONS: This intervention significantly reduced asthma health-care utilization in ETS-exposed, low-income, minority children. Effects sizes for urine cotinine and proportion prohibiting smoking were moderate to large but not statistically significant, possibly the result of reduced precision due to the loss of patients to active follow-up. Improving ETS reduction interventions and understanding their mechanism of action on asthma outcomes requires further controlled trials that measure ETS exposure and behavioral and disease outcomes concurrently.

Acute Disease↗

Radiology reports: examining radiologist and clinician preferences regarding style and content.

OBJECTIVE: The introduction of picture archiving and communication systems (PACS) frequently includes the option of computer-generated itemized reports. This motivated us to reassess the merits of traditional prose dictated reports. This study examines radiologist and clinician preferences regarding report style and content. MATERIALS AND METHODS: The study was conducted in two parts. The first part was a retrospective audit of existing medical imaging prose reports to determine their content. The second part comprised a questionnaire containing three mock clinical scenarios. Three pairs of reports were provided for each scenario, with only essential information in the first pair, some optional information in the second, and the most complete report in the third. Each pair consisted of a prose and itemized report with identical content. Participants ranked reports by preference and were asked specific questions regarding report content. The questionnaires were mailed to referring clinicians and administered during an interactive forum to staff radiologists, radiology fellows, and radiology residents. RESULTS: The audit of existing reports showed a wide variation in all fields with consistency limited to a given radiologist. Responses to the questionnaire showed that, in general, a majority of radiologists and referring clinicians preferred itemized reports. The itemized report with the most detailed content was ranked highest of all three scenarios. CONCLUSION: Prose reports foster a lack of standardization of content among different radiologists. Itemized reports facilitate complete documentation of information and measurements and are more popular with both radiologists and referring clinicians.

Attitude of Health Personnel↗

Tissue harmonic imaging: is it a benefit for bile duct sonography?

OBJECTIVE: Our purpose was to compare tissue harmonic imaging with conventional sonography of the biliary tract. SUBJECTS AND METHODS: Eighty patients with suspect biliary disease had conventional sonography and tissue harmonic imaging with an ATL 3000 or 5000 scanner in a 6-month interval. Final diagnoses included malignant biliary obstruction (n = 30), choledocholithiasis (n = 16), sclerosing cholangitis (n = 4), normal or nonobstructed ducts (n = 16), and miscellaneous conditions (n = 14). Similar images were taken with each technique in terms of projection, field of view, focal zone selection, and evidence of disease. Two separate observers blinded to patient data and technique reviewed and graded images individually for the appearance of the lumen of the bile ducts, the length of the visible duct, the appearance of the duct wall, the presence of any intraluminal masses, and the appearance of associated acoustic shadows. Images were graded from zero to 3, with 3 being the best. RESULTS: The median of the 546 tissue harmonic images was one grade higher than the median for the corresponding conventional images (p < 0.0001). Improvements with tissue harmonic imaging included better sharpness of the duct walls (p < 0.01), a clearer lumen (p < 0.0001), identification of a longer length of the common bile duct (p < 0.0001), and improved detection of intraluminal masses (p < 0.006). Acoustic shadows were better defined and blacker with tissue harmonic imaging (p < 0.007). CONCLUSION: Improvement in contrast and reduction of side lobe artifacts with tissue harmonic imaging enhance visualization of the biliary ducts. Tissue harmonic imaging is now our routine technique for bile duct examination.

Artifacts↗

Transperineal and transvaginal sonography of perianal inflammatory disease.

OBJECTIVE: Perianal infection arises in small intersphincteric anal glands predominantly located at the dentate line. Documentation of fluid collections and the relationship of inflammatory tracts to the sphincter mechanism is important for surgical treatment. Transanal sonography for assessment of perianal inflammatory disease is limited because placement of the rigid probe into the anal canal does not allow assessment of disease in the perineal region. The purpose of this study was to validate the use of transperineal sonography in men and both transvaginal and transperineal sonography in women for evaluation of perianal inflammatory disease. SUBJECTS AND METHODS: Fifty-four patients, 28 men and 26 women, were imaged with transperineal and a combination of transperineal and transvaginal sonography, respectively. All patients were examined in the supine lithotomy and left lateral position with a transvaginal 8-to 4-MHz probe or a linear 12- to 7-MHz transducer. All fluid collections, sinus tracts, and fistulas were described by their location in relation to the sphincter mechanism and perineum. RESULTS: Forty-six of 54 patients had perianal fistulas or sinus tracts: 33 transphincteric, seven intersphincteric, and six extrasphincteric. Fifteen patients had an associated abscess. In the eight remaining patients, there were two anovaginal fistulas, one rectovaginal fistula, one prolapsed internal hemorrhoid, two perianal complex masses, and two vascular perianal or perirectal inflammatory masses. Twenty-six patients underwent surgical procedures involving the anorectal canal or perirectal region, and of these, preoperative sonographic findings were confirmed in 22 (85%) of 26 patients. Three patients refused surgery, and six are awaiting surgery at this writing. Fifteen patients were treated conservatively. CONCLUSION: Transperineal and transvaginal sonography are accurate, painless, and cost-effective methods for documenting perianal fluid collections and fistulas or sinus tracts or both.

Abscess↗

Influence of H2S and thiols on the binding of alkenes and alkynes to ReS4-: the spectator sulfido effect.

The three-component reaction of ReS4- (1), H2S, and unsaturated substrates (un = alkene, alkyne) affords the ReV derivatives Re(S)(S2un)(SH)2-. These adducts arise via the addition of H2S to intermediate dithiolates ReS2(S2C2R4)- and dithiolenes ReS2(S2C2R2)-. The species [ReS[S2C2(tms)2](SH)2]-, [ReS(S2C7H10)(SH)2]- (3), and [ReS(S2C2H4)(SH)2]- are prepared according to this route. Similarly, the selenolate-thiolate complex [ReS(S2C7H10)(SeH)(SH)]- (5) is produced by the reaction of [ReS2(S2C7H10)]- with H2Se. The corresponding reactions using benzenethiol in place of H2S afford the more thermally robust adducts [ReS[S2C2(tms)2](SH)(SPh)]-, [ReS(S2C7H10)(SH)(SPh)]- (7), and [ReS(S2C2H4)(SH)(SPh)]-. Norbornanedithiolato compounds 3, 5, and 7 are obtained as pairs of isomers that differ in terms of the relative orientation of the norbornane bridgehead relative to the Re=S unit. The reaction of [ReS(S2C7H10)(SD)2]- (3-d2) with H2S to give 3 is proposed to proceed via elimination of D2S and subsequent addition of H2S. Variable-temperature 1H NMR measurements on the equilibrium of [ReS(S2C6H12)(SPh)(SH)]- with 1,1-hexene, and PhSH gave the following results: deltaH = -7 (+/- 1) kJ x mol(-1); deltaS = 23 (+/- 4) J x mol(-1) x K(-1). Solutions of ethanedithiol and 1 react with C2(tms)2 and C2H4 to give [ReS[S2C2(tms)2](S2C2H4)]- and [ReS(S2C2H4)2]-, respectively, concomitant with loss of H2S. The pathway for the ethanedithiol reaction is examined using 2-mercaptoethanol, affording [ReS[S2C2(tms)2](SC2H4OH)]-, which does not cyclize. Treatment of a solution of diphenylbutadiyne and 1 with PhSH gives two isomers of the dithiolene [ReS(SH)(SPh)[S2C2Ph(C2Ph)]]-. The corresponding reaction of ethanedithiol, diphenylbutadiyne, and 1 affords the 1,4-diphenylbutadiene-1,2,3,4-tetrathiolate complex [[ReS(S2C2H4)]2(S4C4Ph2)]2-.

Journal Article↗

X-ray crystal structure of an anti-Buckminsterfullerene antibody fab fragment: biomolecular recognition of C(60).

We have prepared a monoclonal Buckminsterfullerene specific antibody and report the sequences of its light and heavy chains. We also show, by x-ray crystallographic analysis of the Fab fragment and by model building, that the fullerene binding site is formed by the interface of the antibody light and heavy chains. Shape-complementary clustering of hydrophobic amino acids, several of which participate in putative stacking interactions with fullerene, form the binding site. Moreover, an induced fit mechanism appears to participate in the fullerene binding process. Affinity of the antibody-fullerene complex is 22 nM as measured by competitive binding. These findings should be applicable not only to the use of antibodies to assay and direct potential fullerene-based drug design but could also lead to new methodologies for the production of fullerene derivatives and nanotubes as well.

Amino Acid Sequence↗

Alkaloid-fullerene systems through photocycloaddition reactions.

The photocycloaddition of tertiary amines to ¿60fullerene (C(60)) is an interesting and useful reaction. We wished to extend the applications of this type of reaction through an investigation of the photoaddition of alkaloids to C(60) for the purpose of synthesizing novel and complex photoadducts that are difficult to obtain by usual methods. Irradiation of tazettine (2) or gramine (3) with C(60) in toluene leads to formation of one monoadduct (6 or 7), whereas scandine (1a) or 10-hydroxyscandine (1b) reacts with C(60) photochemically to give two products, the expected ¿6,6 monoadduct (5a, 5b) and a new type of monoadduct with a bis-¿6, 6 closed structure (4a, 4b). These new structures were characterized by UV-vis, FT-IR, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, ROESY, HMQC (heteronuclear multiple-quantum coherence), and HMBC (heteronuclear multiple-bond connectivity) spectroscopy. The techniques of time-of-flight secondary ion MS (TOF-SIMS) and field desorption MS (FD-MS) were used for the mass determination. (3)He NMR analysis of the product mixture from photoaddition of 1a to C(60) containing a (3)He atom ((3)He@C(60)) led to two peaks at -9.091 and -11.090 ppm relative to gaseous (3)He, consistent with formation of a ¿6, 6-closed monoadduct and a bis-¿6,6 closed adduct. Presumably, the bis-¿6, 6 closed adducts are formed by an intramolecular ¿2 + 2 cycloaddition of the vinyl group to the adjacent 6,6-ring junction of C(60) after the initial photocycloaddition.

Alkaloids↗

Inhibition of nitric oxide synthase isoforms by tris-malonyl-C(60)-fullerene adducts.

C(3)-tris-malonyl-C(60)-fullerene and D(3)-tris-malonyl-C(60)-fullerene derivatives inhibit citrulline and NO formation by all three nitric oxide synthase isoforms in a manner fully reversible by dilution. The inhibition of citrulline formation by C(3)-tris-malonyl-C(60)-fullerene occurs with IC(50) values of 24, 17, and 123 microM for the neuronal, endothelial, and inducible nitric oxide synthase (NOS) isoforms, respectively. As measured at 100 microM l-arginine, neuronal NOS-catalyzed nitric oxide formation was inhibited 50% at a concentration of 25 microM C(3)-tris-malonyl-C(60)-fullerene. This inhibition was a multisite, positively cooperative inhibition with a Hill coefficient of 2.0. C(3)-tris-malonyl-C(60)-fullerene inhibited the arginine-independent NADPH-oxidase activity of nNOS with an IC(50) value of 22 microM but had no effects on its cytochrome c reductase activity at concentrations as high as 300 microM. The inhibition of nNOS activity by C(3)-tris-malonyl-C(60)-fullerene reduced the maximal velocity of product formation but did not alter the EC(50) value for activation by calmodulin. C(3)-tris-malonyl-C(60)-fullerene reduced the maximal velocity of citrulline formation by inducible NOS without altering the K(m) for l-arginine substrate or the EC(50) value for tetrahydrobiopterin cofactor. As measured by sucrose density gradient centrifugation, fully inhibitory concentrations of C(3)-tris-malonyl-C(60)-fullerene did not produce a dissociation of nNOS dimers into monomers. These observations are consistent with the proposal that C(3)-tris-malonyl-C(60)-fullerene inhibits the inter-subunit transfer of electrons, presumably by a reversible distortion of the dimer interface.

Animals↗

Precision trace gas analysis by FT-IR spectroscopy. 1. Simultaneous analysis of CO2, CH4, N2O, and CO in air.

We report the development of a method of trace gas analysis based on 1-cm-1 resolution Fourier transform infrared (FT-IR) spectroscopy, deployable in both laboratory and field applications. Carbon dioxide, methane, nitrous oxide, and carbon monoxide may be analyzed simultaneously in a single air sample using this method. We have demonstrated that the method can provide analytical precision of the order of +/- 0.15 mumol mol-1 for CO2, +/- 0.9 nmol mol-1 for CH4, +/- 0.3 nmol mol-1 for N2O, and +/- 0.3 nmol mol-1 for CO, expressed as mole fractions in dry air. The analytical precision is in all cases competitive with or superior to that of the more usual methods of analysis for these trace gases, namely, nondispersive infrared spectroscopy for CO2 and gas chromatography-based techniques for CH4, N2O, and CO. The novel FT-IR method relies on calibration using synthetically calculated absorbance spectra and a chemometric multivariate calibration algorithm, classical least squares.

Air↗

Precision trace gas analysis by FT-IR spectroscopy. 2. The 13C/12C isotope ratio of CO2.

We report the development of a method of carbon stable isotope ratio analysis based on 1-cm-1 resolution Fourier transform infrared (FT-IR) spectroscopy, deployable in both laboratory and field applications. We demonstrate the determination of the 13C/12C ratio of CO2 (i.e., delta 13CO2) in air with an analytical precision of the order of +/- 0.1/1000 (i.e., +/- 0.01%). The FT-IR method relies on calibration using synthetically calculated absorbance spectra and a multivariate calibration algorithm. The method requires no sample preparation other than optional drying of the sample and may be applied directly to ambient air samples containing approximately 350 mumol mol-1 CO2 (molar mixing ratio). It may also be applied to samples more concentrated in CO2, such as human breath, approximately 5% CO2. We demonstrate the utility of the technique to the analysis of delta 13CO2 in air during an experimental field campaign and to the laboratory-based analysis of human breath. A similar method could also be used to determine the H/D ratio in atmospheric water vapor.

Air↗

Ultrasound for the visualization and quantification of tumor microcirculation.

Advances in ultrasound based methods for the non-invasive assessment of the tumor microcirculation are described. Two new ultrasound approaches are highlighted. The first method relies on commercially available ultrasound contrast agents in combination with specialized nonlinear imaging sequences. Nonlinear scattering by microbubble contrast agents provides a unique intravascular signature that can be distinguished from the echoes caused by surrounding tissues. Through destruction-reperfusion experiments it is possible to use microbubble contrast agents as a tracer revealing the kinetics of tumor blood flow. The second ultrasound method for examining the microcirculation involves the use of much higher frequencies. At frequencies on the order of 50 MHz, Doppler processing allows the direct assessment of flow dynamics in realtime in arterioles as small as 15 microm. Three dimensional Doppler maps of flow patterning are presented. The strengths and weaknesses of these new methods are discussed and the potential for their use in preclinical animal drug studies, clinical drug trials, and prognostic studies is described.

Animals↗

Evaluating linkage and linkage disequilibrium: use of excess sharing and transmission disequilibrium methods in affected sib pairs.

Two popular and robust approaches to analysing affected sib pair (ASP) data for linkage are the traditional excess sharing methods and the transmission/disequilibrium test (TDT). Here we derive an overall test of linkage for multi-allelic ASP marker data which comprises two component tests: one for excess sharing and one for transmission disequilibrium. This method has several advantages. Firstly the overall test of linkage is often more powerful than either of the two component tests. Secondly the method makes it possible to determine the contribution of linkage disequilibrium (LD), in addition to linkage, to an overall positive linkage result. This is useful because the presence of LD in addition to linkage may suggest that the marker locus is in very close proximity to a disease susceptibility gene. Thirdly the method provides estimates of the risk associated with transmission of the different marker alleles.

Genetic Diseases, Inborn↗

Testing for concordant equilibria between population samples.

A substantial body of theory has been developed to assess the effect of evolutionary forces on the distribution of genotypes, both single and multilocus, within populations. One area where the potential for application of this theory has not been fully appreciated concerns the extent to which population samples differ. Within populations, the divergence of genotype or haplotype frequencies from that expected under Hardy-Weinberg (HW) or linkage equilibrium can be measured as disequilibria coefficients. To assess population samples for concordant equilibria, an analytical framework for comparing disequilibria coefficients between populations is necessary. Here we present log-linear models to evaluate such hypotheses. These models have broad utility ranging from conventional population genetics to genetic epidemiology. We demonstrate the use of these log-linear models (1) as a test for genetic association with disease and (2) as a test for different levels of linkage disequilibria between human populations.

Animals↗

How important is DNA replication for mutagenesis?

Rates of mutation and substitution in mammals are generally greater in the germ lines of males. This is usually explained as resulting from the larger number of germ cell divisions during spermatogenesis compared with oogenesis, with the assumption made that mutations occur primarily during DNA replication. However, the rate of cell division is not the only difference between male and female germ lines, and mechanisms are known that can give rise to mutations independently of DNA replication. We investigate the possibility that there are other causes of male-biased mutation. First, we show that patterns of variation at approximately 5,200 short tandem repeat (STR) loci indicate a higher mutation rate in males. We estimate a ratio of male-to-female mutation rates of approximately 1.9. This is significantly greater than 1 and supports a greater rate of mutation in males, affecting the evolution of these loci. Second, we show that there are chromosome-specific patterns of nucleotide and dinucleotide composition in mammals that have been shaped by mutation at CpG dinucleotides. Comparable patterns occur in birds. In mammals, male germ lines are more methylated than female germ lines, and these patterns indicate that differential methylation has played a role in male-biased vertebrate evolution. However, estimates of male mutation bias obtained from both classes of mutation are substantially lower than estimates of cell division bias from anatomical data. This discrepancy, along with published data indicating slipped-strand mispairing arising at STR loci in nonreplicating DNA, suggests that a substantial percentage of mutation may occur in nonreplicating DNA.

Animals↗

Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast.

RATIONALE AND OBJECTIVES: To create a microbubble contrast image of vessels that lie below the resolution of an ultrasound system, a technique is required that detects preferentially the agent echo, rejecting that from tissue. Harmonic imaging exploits the nonlinear behavior of microbubbles but forces a compromise between image sensitivity and axial resolution. The authors describe and evaluate a new method that overcomes this compromise and improves contrast imaging performance: pulse inversion imaging. METHODS: Sequences of pulses of alternate phase are transmitted into tissue and their echoes summed. A prototype scanner equipped with pulse inversion was used to image phantoms and 16 patients with focal liver masses. RESULTS: Pulse inversion images show contrast sensitivity and resolution superior to that of harmonic images. Vessels can be imaged at an incident power sufficiently low to avoid destroying the agent, allowing unique visualization of tumor vasculature. Distinct patterns were seen in hemangiomas, metastases, and hepatocellular carcinomas. CONCLUSIONS: Pulse inversion imaging is an improved bubble-specific imaging method that extends the potential of contrast ultrasonography.

Adult↗

Harmonic hepatic US with microbubble contrast agent: initial experience showing improved characterization of hemangioma, hepatocellular carcinoma, and metastasis.

PURPOSE: To characterize blood flow in focal hepatic lesions with harmonic ultrasonographic (US) imaging and a microbubble contrast agent. MATERIALS AND METHODS: Thirty patients with known hepatic masses were examined after injection of a perfluorocarbon microbubble agent. Tumor vascularity was assessed with continuous, harmonic gray-scale imaging with a low mechanical index (MI). Tumor vascular volume was assessed with brief, high-MI insonation called interval-delay imaging, which caused microbubble destruction. As the total contrast agent volume in the liver reflects the total vascular volume, quantitation of lesion enhancement relative to normal hepatic enhancement helped determine the vascular volume of the tumor relative to that of normal parenchyma. RESULTS: Low-MI continuous harmonic imaging showed lesional vessels in hepatocellular carcinomas, minimal or no vessels in hemangiomas, and variable vascularization in metastases. High-MI interval-delay imaging showed greater enhancement in hepatocellular carcinomas than in normal liver (P <.02) and showed less enhancement in hemangiomas than in normal liver (P <.02). Enhancement in metastases was greater in the margins than in the center; as a result, the lesions appeared smaller (P <.03) and less well defined on the interval-delay images. CONCLUSION: Contrast-enhanced harmonic imaging appears superior to conventional Doppler US for hepatic mass characterization. Low-MI continuous and high-MI interval-delay imaging can help assess tumor vascular pattern and microvascular volume.

Adult↗

Appendicitis at the millennium.

Acute appendicitis is a common clinical problem. Accurate and prompt diagnosis is essential to minimize morbidity. While the clinical diagnosis may be straightforward in patients who present with classic signs and symptoms, atypical presentations may result in diagnostic confusion and delay in treatment. Helical computed tomography (CT) and graded compression color Doppler ultrasonography (US) are highly accurate means of establishing the diagnosis. These imaging modalities have now assumed critical roles in the treatment of patients suspected to have appendicitis. The purpose of this article is threefold: to provide an update on new information regarding the pathophysiology, clinical diagnosis, and laparoscopic treatment of acute appendicitis; to describe the state-of-the art use of CT and US in diagnosing this disease entity; and to address the role of medical imaging in this patient population.

Acute Disease↗