Comparison of Arterial and Venous Interposition Grafting for Arterial Defects in a Rat Model.

BACKGROUND: Interposition microvascular grafting may be required to bridge arterial defects during digital replantation or revascularization and has traditionally been performed utilizing a venous autograft. Arterial interposition grafting has been shown to be superior in maintaining patency in large vessel surgery; there are case reports of its use in microsurgery. METHODS: Six fellowship-trained hand and microsurgeons performed arterial and venous interposition grafts on the femoral arteries of 40 Wistar rats. After sectioning one femoral artery a segment of the contralateral femoral artery or vein was obtained. The time was recorded per graft and patency tested 10 minutes following grafting by an independent assessor. Each surgeon also completed a questionnaire detailing regular microsurgical volume, technical ease, and conceptual preference for either graft. RESULTS: Time for arterial interposition (median time 51.7 minutes) was longer than venous grafting (median time 45.9 minutes, p = 0.075). Arterial grafts were more likely to be patent or questionably patent (odds ratio [OR] = 6.77, p = 0.031). All surgeons found arterial interposition grafting technically easier and preferred it conceptually. Improvements were noted in patency rates (OR = 11.29, p = 0.018) and avoidance of anastomotic leak (OR = 0.19, p = 0.029) when surgeons performed moderate levels or greater of microsurgery within their regular practice. CONCLUSION: Greater immediate patency was noted with arterial interposition grafting in a rodent model when compared to venous grafting, although procedural time was greater. All surgeons found arterial grafting technically easier. Arterial microvascular grafting may be useful in the setting of digital replantation or revascularization with an arterial defect.

Modification of obturator to femoral nerve transfer for femoral nerve palsy.

Postoperative femoral nerve palsy with nerve division is a potentially devastating complication with a poor prognosis, especially when there is a delay in diagnosis. We present a novel 'belt and braces' approach for managing this unusual injury, using a modification of a nerve transfer, which has only been previously reported in the literature three times to our knowledge.

Feminisation of UK General Practice: a challenge for the Defence Medical Services?

BACKGROUND: The Defence Medical Services (DMS) primarily recruits its trained General Practitioners (GPs) from the NHS and since 1970, the number of men entering medicine has doubled whereas the number of women has increased 10-fold; female GPs will outnumber their male counterparts by 2017. This study performs a quantitative assessment of the potential impact of feminisation of UK General Practice upon the DMS recruitment and workforce planning. METHODS: General Medial Council General Practice Certificate of Completion of Training (GMC GP CCT) data were analysed to identify any change in the percentage of male and female GP Specialty Training Registrars successfully completing GP vocational training between 2007 and 2012, thus becoming potentially recruitable into the DMS as independent GPs. RESULTS: A 3% increase was seen in the number of women achieving GMC GP CCT between 2007 and 2012 (p=0.015). The percentage of DMS GP Specialty Training Registrars (GPStRs) gaining their GMC GP CCT in 2012 who were women (25%) was about half that seen nationally (59%). A lack of 2007 by-sex GMC GP CCT data for DMS GPStRs prevented a comparison with 2012. CONCLUSIONS: The national increase of only 3% infers feminisation of UK General Practice is not an immediate challenge for the DMS. Nevertheless, as feminisation of the UK GP workforce is expected to continue, the future cohort from whom the DMS will recruit its GPs is likely to contain increasing numbers of women. With the return to contingency, the DMS may wish to consider the implications of increasing numbers of female GPs upon service delivery in the UK and overseas, and explore more flexible medical employment models.

Heterogeneity of parvalbumin expression in the avian cerebellar cortex and comparisons with zebrin II.

The cerebellar cortex has a fundamental parasagittal organization that is reflected in the physiological responses of Purkinje cells, afferent and efferent connections, and the expression of several molecular markers. The most thoroughly studied of these molecular markers is zebrin II (ZII; a.k.a. aldolase C). ZII is differentially expressed in Purkinje cells, resulting in a pattern of sagittal stripes of high expression interdigitated with stripes of little or no expression. In this study, we examined the expression of the calcium binding protein parvalbumin (PV) in the cerebellum of several avian species (pigeons, hummingbirds, zebra finches) and compared it to the expression of ZII. We found that PV immunoreactivity was distributed across the cerebellar cortex such that there were sagittal stripes of PV immunopositive (PV+) Purkinje cells alternating with PV immunonegative (PV-) Purkinje cells. Although most Purkinje cells in the anterior lobe were PV+, there were several thin (i.e. only a few Purkinje cells wide) PV- stripes spanning the folia. In the posterior lobe, PV+ and PV- stripes were also apparent, but the PV- stripes were much wider than in the anterior lobe. In sections processed for both ZII and PV, the expression was generally complementary: PV+ stripes were ZII-, and vice-versa. This complementary expression was most apparent in folia II-IV and VIII-IXcd. The complementary expression was not, however, absolute; some Purkinje cells co-expressed PV and ZII whereas others lacked both. These novel findings relate to the complex neurochemical organization of the cerebellum, and are likely important to issues regarding cerebellar plasticity.

Amine Terminated SAMs: Investigating Why Oxygen is Present in these Films.

Self-assembled monolayers (SAMs) on gold prepared from amine-terminated alkanethiols have long been employed as model positively charged surfaces. Yet in previous studies significant amounts of unexpected oxygen containing species are always detected in amine terminated SAMs. Thus, the goal of this investigation was to determine the source of these oxygen species and minimize their presence in the SAM. The surface composition, structure, and order of amine-terminated SAMs on Au were characterized by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), sum frequency generation (SFG) and near edge X-ray absorption fine structure (NEXAFS) spectroscopy. XPS determined compositions of amine-terminated SAMs in the current study exhibited oxygen concentrations of 2.4 ± 0.4 atomic %, a substantially lower amount of oxygen than reported in previously published studies. High-resolution XPS results from the S(2p), C(1s) and N(1s) regions did not detect any oxidized species. Angle-resolved XPS indicated that the small amount of oxygen detected was located at or near the amine head group. Small amounts of oxidized nitrogen, carbon and sulfur secondary ions, as well as ions attributed to water, were detected in the ToF-SIMS data due to the higher sensitivity of ToF-SIMS. The lack of N-O, S-O, and C-O stretches in the SFG spectra are consistent with the XPS and ToF-SIMS results and together show that oxidation of the amine-terminated thiols alone can only account for, at most, a small fraction of the oxygen detected by XPS. Both the SFG and angle-dependent NEXAFS indicated the presence of gauche defects in the amine SAMs. However, the SFG spectral features near 2865 cm(-1), assigned to the stretch of the methylene group next to the terminal amine unit, demonstrate the SAM is reasonably ordered. The SFG results also show another broad feature near 3200 cm(-1) related to hydrogen-bonded water. From this multi-technique investigation it is clear that the majority of the oxygen detected within these amine-terminated SAMs arises from the presence of oxygen containing adsorbates such as tightly bound water.

Model for DNA hairpin denaturation.

We investigate the thermal denaturation of DNA hairpins using molecular dynamics simulations of a simple model describing the molecule at a scale of a nucleotide. The model allows us to analyze the different interacting features that determine how an hairpin opens, such as therole of the loop and the properties intrinsic to the stem.

Self-assembled organic monolayers terminated in perfluoroalkyl pentafluoro-lambda(6)-sulfanyl (-SF5) chemistry on gold.

Recently synthesized (Winter, R.; Nixon, P. G.; Gard, G. L.; Radford, D. H.; Holcomb, N. R.; Grainger, D. W. J. Fluorine Chem. 2001, 107, 23-30) SF5-terminated perfluoroalkyl thiols (SF5(CF2)nCH2CH2SH, where n = 2, 4, and 6) and a symmetric SF5-terminated dialkyl disulfide ([SF5-CH=CH-(CH2)8-S-]2) were assembled as thin films chemisorbed onto gold surfaces. The adsorbed monolayer films of these SF5-containing molecules on polycrystalline gold were compared using ellipsometry, contact angle, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and infrared spectroscopy (FTIR) surface analytical methods. The resulting SF5-dialkyl disulfide monolayer film shows moderate angle dependence in depth-dependent XPS analysis, suggesting a preferentially oriented film. The SF5-terminated perfluoroalkyl thiols exhibit angular-dependent XPS compositional variance depending on perfluoroalkyl chain length, consistent with improved film assembly (increasingly hydrophobic, fewer defects, and more vertical chain orientation increasing film thickness) with increasing chain length. Tof-SIMS measurements indicate that both full parent ions for these film-forming molecules and the unique SF5 terminal group are readily detectable from the thin films without substantial contamination from other adsorbates.

A comparison of two pre-enrichment media prior to immunomagnetic separation for the isolation of E. coli O157 from bovine faeces.

AIMS: To compare the sensitivity of two pre-enrichment broth media prior to immunomagnetic separation for the isolation of Escherichia coli O157 from cattle faeces. METHODS AND RESULTS: One-gram portions of 721 cattle faeces collected from 43 farms were pre-enriched in buffered peptone water containing vancomycin, cefixime and cefsulodin (BPW-VCC) and buffered peptone water without additives (BPW-WOA), respectively. A total of 137 samples were positive for E. coli O157: 127 pre-enriched with BPW-WOA and 89 pre-enriched in BPW-VCC. Representative isolates were tested for phage type, verotoxin and eae (E. coli attaching and effacing) gene sequences, resulting in the recognition of eight different types. All the E. coli O157 types recognized were isolated by both methods except for three different strains, each of which were isolated only on a single occasion: two by BPW-WOA and another by BPW-VCC. CONCLUSIONS: The results clearly demonstrate, under the conditions of this study, that BPW without antibiotics was the superior pre-enrichment medium for the isolation of E. coli O157 from cattle faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of BPW-WOA in preference to BPW-VCC for the isolation of E. coli O157 from cattle faeces in future research and outbreak studies should lead to a higher number of positive isolates.

Liver enzyme monitoring in patients treated with troglitazone.

CONTEXT: Soon after initial marketing in March 1997, troglitazone, the first thiazolidinedione antidiabetic agent, was found to cause life-threatening acute liver failure. The drug was removed from the market in March 2000. OBJECTIVE: To evaluate the effect of US Food and Drug Administration (FDA) risk management efforts, including repeated labeling changes and "Dear Healthcare Professional" letters, on periodic liver enzyme monitoring of patients taking troglitazone. DESIGN, SETTING, AND PARTICIPANTS: Claims data from a large, multistate managed care organization were used to establish 4 cohorts of patients (N = 7603) with at least 90 days of health plan enrollment before first troglitazone prescription during 4 consecutive periods spanning April 1997 to September 1999 and representing 4 progressively stringent liver monitoring recommendations. MAIN OUTCOME MEASURES: Percentage of eligible troglitazone users in each cohort with baseline, monthly (for up to 6 months of continuous use), and complete (baseline and monthly) enzyme monitoring, based on computerized records of laboratory claims. RESULTS: Baseline testing increased from 15% before any FDA monitoring recommendations (cohort 1) to 44.6% following 4 separate FDA interventions (cohort 4; P<.001). In cohort 4, 33.4% of users had follow-up testing after 1 month of therapy, falling to 13% after 5 months of continuous use. In all cohorts, less than 5% received all recommended liver enzyme tests by the third month of continuous use. CONCLUSIONS: The FDA risk management efforts did not achieve meaningful or sustained improvement in liver enzyme testing. Evaluation of the impact of regulatory actions is needed before such actions can be regarded as effective or sufficient.

Inhibition of endothelial cell migration by cigarette smoke condensate.

Cigarette smoking is among the leading risk factors in the etiology of atherosclerotic vascular disease. The mechanism, however, that links cigarette smoking to an increased incidence of atherosclerosis is poorly understood. Endothelial cell (EC) integrity is critical in preventing vascular lesion formation, and after a loss of EC integrity reendothelialization must be rapid and complete. We therefore investigated whether cigarette smoke affected the ECs ability to migrate or altered the intracellular signals generated during migration. The DMSO-soluble fraction of cigarette smoke condensate (CSC), derived from the standard research cigarette, was tested on cultured ECs (HUVEC) derived from human umbilical vein. The addition of CSC caused a dose-dependent decrease in the ability of EC to migrate as measured over a 24-h time period. Nicotine and cadmium sulfate, two constituents of cigarette smoke, individually or in combination, had no effect on migration. Examination of the tyrosine phosphorylation state of various intracellular proteins by Western blot analysis showed that CSC caused the hyperphosphorylation of a 130-kDa protein. In addition, other intracellular proteins showed changes in their phosphorylation states after CSC addition. These results support the hypothesis that CSC is detrimental to normal EC function in maintaining vascular integrity and suggest that smokers are more likely to develop complications of vascular disease due to delayed or incomplete reendothelialization as a consequence of decreased EC migration.

The role of databases in drug postmarketing surveillance.

This paper describes the role of databases used for postmarketing surveillance of drugs at the United States Food and Drug Administration (FDA). First we describe the Adverse Event Reporting System (AERS), the largest database of adverse event reports in the world. Next, we explain the methods we have used for assembling these adverse event reports into a case series and analysing them, as well as techniques for employing drug use databases to construct reporting rates in the evaluation of drug safety issues. Finally, we discuss the FDA's use of the databases it accesses through its Cooperative Agreement Program to conduct high priority studies to support regulatory decision-making.

Surface characterization of hydroxyapatite and related calcium phosphates by XPS and TOF-SIMS.

The surfaces of six biologically interesting calcium phosphate (CaP) phases (hydroxyapatite, dibasic calcium phosphate dihydrate, dibasic calcium phosphate, monobasic calcium phosphate, beta-tribasic calcium phosphate, octacalcium phosphate) have been examined by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The intensity of an O(1s) shake-up satellite correlates with the phosphate oxygen content. Together with the Ca/P and O/Ca XPS peak ratios, this feature helps provide identification of the CaP phase(s) present in the surface of unknown samples and establish their mole fractions, as proven with a bone sample. Contributions from carbonate impurities can be quantified using its C(1s) peak at 279.9 eV and subtracted from the O(1s) line shape to aid identification. Principal component analysis (PCA) has been applied successfully to analyze TOF-SIMS spectra of these six CaP phases. Multivariate analysis can help differentiate these CaP phases using the first two PCs, which are dominated by the relative intensities of only a few key ions: PO3-, O-, Ca+, CaOH+, PO2-, and OH-.

Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting.

OBJECTIVE: The goal of this study was to determine the prevalence of Clostridium difficile diarrhea (CDD) and the risk for CDD associated with different oral antibiotics commonly used in the ambulatory care setting. METHODS: The prevalence of CDD was determined for enrollees in 4 UnitedHealth Group-affiliated health plans between January 1, 1992, and December 31, 1994. Cases were identified based on the presence of an inpatient or outpatient claim with a primary diagnosis of diarrhea, a pharmacy claim for a prescription drug used to treat CDD, or a physician or facility claim for the C. difficile toxin test, and were confirmed using full-text medical records. Within a retrospective cohort design, periods of risk for CDD were defined on the basis of duration of antibiotic therapy. To control for potential selection bias created by heterogeneous rates of C. difficile testing and to limit confounding due to multiple antibiotic exposures, we used a nested case-control design, restricting eligibility to subjects who underwent screening for C. difficile and who had been exposed to only 1 antibiotic risk period with a single antibiotic. RESULTS: The global prevalence of CDD in 358,389 ambulatory care enrollees was 12 per 100,000 person-years. In the nested case-control study, after controlling for other risk factors, 2 antibiotics demonstrated an increased association with CDD: cephalexin (odds ratio [OR] = 7.5, 95% CI = 1.8 to 34.7) and cefixime (OR = 6.4, 95% CI = 1.2 to 39.0). CONCLUSIONS: Although CDD is thought to occur primarily in hospitalized patients, it was found to be present in an ambulatory care population, but at a low frequency. In this population, it appeared to be associated with 2 cephalosporins but not with other types of antibiotics usually linked with nosocomial CDD. Because the frequency of C. difficile testing was shown to be more common with high-risk antibiotics, CDD may be underdiagnosed in the ambulatory care setting.

Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy.

OBJECTIVE: To determine whether the severity of valvulopathy was associated with the dosage of fenfluramine taken by fenfluramine-phentermine users with valvulopathy. DESIGN: Out of 105 suspected valvulopathy case reports received by the US Food and Drug Administration (FDA) among fenfluramine-phentermine users, 74 patients meeting FDA case definition for valvulopathy were included in this study. Patients with severe valvulopathy were classified as those either undergoing valve replacement surgery or having severe aortic or mitral regurgitation; all other patients were considered to have less severe valvulopathy. RESULTS: The proportion with severe valvulopathy increased from 20-66% with increasing fenfluramine dosage from /=60 mg/d. Compared with patients taking<40 mg/d fenfluramine, patients taking >/=60 mg/d had an adjusted odds ratio of 9.2 (95% confidence interval=2.1-40.8) for severe valvulopathy. CONCLUSION: Compared to patients with less severe valvulopathy, those with severe valvulopathy were substantially more likely to have taken >/=60 mg/d fenfluramine.

The adrenal incidentaloma: guidelines for evaluation and recommendations for management.

Adrenal masses are identified incidentally on up to 1.5% of all abdominal CT scans. The appropriate evaluation and management of these "incidentalomas" remains controversial and centers on questions of function and potential for malignancy. Functional evaluation includes consideration of the diagnoses of aldosteronoma, pheochromocytoma, and corticosteroid-producing adenoma. Potential for malignancy can be evaluated using a number of imaging modalities, although none is diagnostic. Size remains one of the best criteria for assessing potential for malignancy.

The risk for outpatient antibiotic-treated infections following a course of oral corticosteroids among children with asthma.

Short courses of oral corticosteroids are widely used to treat asthma. The objective of this study was to assess if one course of oral corticosteroids increases asthmatic children's risk for infections treated with outpatient antibiotics. Using New York State Medicaid claims data on asthmatic children 2-15 years old, we made cohorts of oral corticosteroid users and nonusers. We determined the percentage of children who filled antibiotic prescriptions in the 30 days after index dates. Index dates were dates oral steroids were started (for steroid users) or matched dates (for nonusers). Odds ratios were adjusted for age, month of index date, and prior antibiotic use. Among children not receiving antibiotics on index dates, antibiotic prescriptions were filled in the next 30 days for 438 (20%) of 2145 steroid nonusers and 130 (19%) of 698 steroid users (p=0.30); compared to nonusers, steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.92 (95% confidence interval [CI] 0.73-1.15). Among children receiving antibiotics on index dates, antibiotic prescriptions were filled in the next 30 days for 116 (26%) of 451 steroid nonusers and 50 (19%) of 260 steroid users (p=0.05); compared to nonusers, steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.65 (95% CI 0.53-0.97). We conclude that one course of oral corticosteroids does not increase asthmatic children's risk for infections treated with outpatient antibiotics.

The association of intra-abdominal infection and abdominal wound dehiscence.

Concurrent infection is a risk factor for abdominal wound dehiscence. We reviewed our experience with fascial dehiscence to determine the incidence and to identify prognostic factors for associated intra-abdominal infection. Over a 7-year period, 107 patients with abdominal wound dehiscence were identified. Seventeen were managed nonoperatively, and 90 underwent exploratory laparotomy, 43 of whom had no intra-abdominal pathology and 47 of whom had intra-abdominal infections. Demographic factors, comorbid diseases, and potential indicators of systemic infection did not distinguish patients with intra-abdominal infection from those without. Patients with an intra-abdominal infection were more likely to have undergone an emergency operation (74% vs 48%; P < 0.02), an operation on the colon (55% vs 25%; P < 0.005), or an operation with a higher wound classification (P < 0.02). Mortality was higher in patients with intra-abdominal infection than in those without (44% vs 20%; P < 0.02). Wound dehiscence after emergent operations, and operations with a higher wound classification, especially those involving the colon, should raise concern for intra-abdominal infection. Thorough abdominal exploration should be performed at the time of dehiscence repair. Before nonoperative management is chosen, intra-abdominal infection should be excluded.

A note on the time dependence of pineal gland research publications.

Counts of the number of publication titles containing the search truncation "pinea*" were compiled via Current Contents over the time period 1978-1994. These counts and their time dependence were examined for autocorrelations and frequency spectral components. Such analyses were carried out irrespective of either author, research laboratory, funding, or other factors. Interestingly, the results show the research publication rate in pineal studies to be linked to community history. In particular, the interactions affecting output among community members operate on a few characteristic time scales ranging from one to several years.