United Kingdom recommendations for obstetric venous thromboembolism prophylaxis: Evidence and rationale.

Venous thromboembolism (VTE) is a leading cause of maternal death in the United Kingdom. To address this problem guidance from the Royal College of Obstetricians and Gynaecologists (RCOG) has been developed that recommends the assessment of a woman's risk of thrombosis at specific time-points during pregnancy and postnatally at the time of delivery. The RCOG guidelines provide clinicians with a framework to inform decision-making on the use of thromboprophylaxis and are based on the premise that the higher risk a woman has for VTE, the more likely she is to benefit from prophylaxis - determining her level of risk is based on the number and characteristics of the risk factors that she has. This article will address the pathophysiology of VTE in pregnancy, evidence behind the risk factors for VTE and the use of thromboprophylactic agents. Further, it will reflect on the rationale behind the RCOG guidance.

Frequency comb offset detection using supercontinuum generation in silicon nitride waveguides.

We present the first direct carrier-envelope-offset (CEO) frequency detection of a modelocked laser based on supercontinuum generation (SCG) in a CMOS-compatible silicon nitride (Si(3)N(4)) waveguide. With a coherent supercontinuum spanning more than 1.5 octaves from visible to beyond telecommunication wavelengths, we achieve self-referencing of SESAM modelocked diode-pumped Yb:CALGO lasers using standard f-to-2f interferometry. We directly obtain without amplification strong CEO beat signals for both a 100-MHz and 1-GHz pulse repetition rate laser. High signal-to-noise ratios (SNR) of > 25 dB and even > 30 dB have been generated with only 30 pJ and 36 pJ of coupled pulse energy from the megahertz and gigahertz laser respectively. We compare these results to self-referencing using a commercial photonic crystal fiber and find that the required peak power for CEO beat detection with a comparable SNR is lowered by more than an order of magnitude when using a Si(3)N(4) waveguide.

Comparison of a PCR serotyping assay, Check&Trace assay for Salmonella, and Luminex Salmonella serotyping assay for the characterization of Salmonella enterica identified from fresh and naturally contaminated cilantro.

Salmonella enterica isolated from fresh cilantro samples collected through the USDA/AMS Microbiological Data Program (MDP) were used to compare a PCR serotyping assay against the Check&Trace assay and the Luminex (BioPlex) Salmonella serotyping assay. The study was conducted to evaluate the effectiveness of the three methods for serotyping Salmonella from both enrichment broth cultures and pure Salmonella cultures. In this investigation, Salmonella spp. serotyping was conducted using 24 h enrichment broth cultures and pure Salmonella cultures from cilantro samples, with the PCR serotyping assay. Conversely, the Check&Trace and Luminex for Salmonella assays required pure cultures for Salmonella serotyping. The cilantro samples contained S. enterica serovar Montevideo, Newport, Saintpaul, and Tennessee, identified by the PCR serotyping assay and Check&Trace for Salmonella, but the Luminex assay only identified two of the four serotypes of the cilantro samples. The anticipated impact from this study is that the PCR serotyping assay provides a time- and cost-effective means for screening, identifying and serotyping Salmonella using DNA extracted from 24 h enrichment cilantro samples.

A randomised trial of weekend and evening breast screening appointments.

BACKGROUND: There is a need to research interventions that improve access to and convenience of breast cancer screening services. METHODS: We conducted a randomised trial comparing invitations to out-of-hours appointments with standard office hour appointments. Women who were to be invited for routine breast screening were randomised (3 : 1 : 1 : 1) to one of these screening invitations: standard office hour appointment, office hour appointment with the option to change to an out-of-hours appointment, weekday evening appointment, or weekend appointment. RESULTS: A total of 9410 women were invited to an office hour, 3519 to an office hour with the option to change, 3271 to a weekday evening, and 3162 to a weekend appointment. The offer of an initial out-of-hours appointment was associated with a non-significant decrease in attendance rates (73.7% vs 74.1%). The highest attendance was observed in the group offered an initial office hour appointment with the option to change to out-of-hours (76.1% vs 73.3% for standard office hour, P=0.001), with 7% of invitees exercising the option to change. CONCLUSION: The optimum strategy for improving attendance at breast screening is to offer a traditional office hour appointment and including in the letter of invitation an option to change to an evening or weekend appointment if wished.

High bit rate all-optical signal processing in a fiber photonic wire.

We report the first demonstration of high bit rate signal processing by a fiber-based photonic wire. We achieve 160 Gb/s demultiplexing via four wave mixing in a 1.9 microm diameter photonic wire tapered from As(2)S(3) chalcogenide glass single mode fibre, with very low pump power requirements ( < 20 mW average power, 0.45 W peak power), enabled by a very high nonlinearity (gamma approximately 7850 W(-1) km (-1) ) and greatly reduced dispersion.

Long-term survival and occasional regression of distant melanoma metastases after adrenal metastasectomy.

BACKGROUND: Human melanoma cells express high-affinity glucocorticoid receptors, and adrenalectomy has been shown to have antimelanoma effects in animal models. Long-term regression of distant metastatic melanoma was observed in one patient after bilateral adrenalectomy, prompting a review of adrenalectomy for melanoma metastases performed at this center. METHODS: A retrospective study in which all patients treated at the Sydney Melanoma Unit and recorded as having adrenal gland metastases between January 1987 and January 2004 were identified and their survival analyzed. RESULTS: One hundred eighty-six patients with adrenal gland metastases were identified. Adrenalectomy was performed in 23 patients; the other 163 patients were treated nonsurgically. The adrenal glands were the sole site of disease in five patients. All symptomatic patients were free of pain after recovery from the surgical procedure. Thirteen patients were rendered clinically and radiologically disease-free by their surgery. There was no postoperative mortality within 30 days. Median overall survival after adrenalectomy was 16 months (2-year survival, 39%), compared with 5 months for patients with documented adrenal metastases treated nonsurgically (P < .00001). In one patient, nonresected visceral metastases elsewhere regressed completely after bilateral adrenalectomy; he remained well and free of disease 80 months after adrenalectomy. Regression of distant visceral metastatic disease also occurred in a second patient after unilateral adrenalectomy. CONCLUSIONS: Adrenalectomy for melanoma metastatic to the adrenal gland provides good palliation of symptoms and is associated with prolonged survival in a selected cohort of patients. We report for the first time sustained complete regression of distant metastatic melanoma after bilateral adrenalectomy, suggesting a possible role for adrenal hormones in modifying melanoma progression in certain patients.

Role of luteal glucocorticoid metabolism during maternal recognition of pregnancy in women.

The human corpus luteum (hCL) is an active, transient, and dynamic endocrine gland. It will experience extensive tissue and vascular remodeling followed by 1) demise of the whole gland without any apparent scarring or 2) maintenance of structural and functional integrity dependent on conceptus-derived human chorionic gonadotropin (hCG). Because cortisol has well-characterized roles in tissue remodeling and repair, we hypothesized that it may have a role in controlling luteal dissolution during luteolysis and would be locally produced toward the end of the luteal cycle. Glucocorticoid-metabolizing enzymes [11beta-hydroxysteroid dehydrogenase (11betaHSD) types 1 and 2] and the glucocorticoid receptor (GR) were assessed in hCL and cultures of luteinized granulosa cells (LGC) using immunofluorescence and quantitative RT-PCR. Furthermore, the effect of cortisol on steroidogenic cell survival and fibroblast-like cell activity was explored in vitro. The hCL expressed 11betaHSD isoenzymes in LGC and nuclear GR in several cell types. hCG up-regulated the expression and activity of 11betaHSD type 1 (P < 0.05) and down-regulated type 2 enzyme (P < 0.05) in vitro and tended to do the same in vivo. Cortisol increased the survival of LGC treated with RU486 (P < 0.05) and suppressed the activity of a proteolytic enzyme associated with luteolysis in fibroblast-like cells (P < 0.05). Our results suggest that, rather than during luteolysis, it is luteal rescue with hCG that is associated with increased local cortisol generation by 11betaHSD type 1. Locally generated cortisol may therefore act on the hCL through GR to have a luteotropic role in the regulation of luteal tissue remodeling during maternal recognition of pregnancy.

Enhanced Kerr nonlinearity in sub-wavelength diameter As(2)Se(3) chalcogenide fiber tapers.

We experimentally demonstrate enhanced Kerr nonlinear effects in highly nonlinear As(2)Se(3) chalcogenide fiber tapered down to sub-wavelength waist diameter of 1.2 mum. Based on self phase modulation measurements, we infer an enhanced nonlinearity of 68 W(-1)m(-1). This is 62,000 times larger than in standard silica singlemode fiber, owing to the 500 times larger n(2) and almost 125 times smaller effective mode area. We also consider the potential to exploit the modified dispersion in these tapers for ultra-low threshold supercontinuum generation.

Use of a staff administered structured questionnaire to identify relevant life-style issues and social-health determinants in a sexual and reproductive health service.

OBJECTIVE: To evaluate a staff-administered questionnaire to identify life-style issues and social-health determinants. DESIGN: Structured questionnaire administered by a health professional after dealing with the primary reason for attendance. SETTING: Community-based UK sexual and reproductive health service. POPULATION: First 1329 selected clinic patients comprising 1018 women attending Family Planning and 161 women plus 150 men attending Genitourinary Medicine; 47% were aged under 25. MAIN OUTCOME MEASURES: Identification of relevant health-risk taking, life-style issues, and unaddressed health concerns. Participants were offered appropriate support, information and referrals. RESULTS: Two hundred and sixty-four (23%) of the Family Planning women and 83 (52%) of the Genitourinary Medicine women [plus 103 (69%) of the men] reported two or more sexual partners in the last year. A third of participants denied regular condom use. Six per cent of women and 5% of men questioned had previously been forced to have sex. Eleven per cent of men admitted to having paid for sex and 9% of women disclosed physical assault (one-quarter in the home). Eight per cent of women and 7% of men had unresolved issues relating to previous miscarriage, termination, or stillbirth. CONCLUSIONS: It is possible to identify relevant life-style issues and social determinants of health during routine practice using a staff-administered questionnaire. The resulting information may not otherwise have been disclosed and may impact significantly on health and care delivery. The information collected provides opportunities for both individuals and service planners to address wider health needs.

Everyday memory following traumatic brain injury.

Residual memory deficits may represent a problem to the everyday functioning of a large number of people, including those who have sustained traumatic brain injury (TBI). The present exploratory study sought to investigate the interrelationships between subjective memory reports, performance on traditional memory tests, and performance on tests of prospective memory. These interrelationships were contrasted between a group of 24 adults who had sustained TBI and a group of 24 matched control subjects. Prospective memory was hypothesized to be indicative of everyday memory functioning. The results provided preliminary evidence that prospective memory tests are sensitive to TBI-related neurological impairment and, in comparison to traditional tests, may be better indicators of functional memory capacity. This pattern was particularly true for control subjects, possibly because TBI subjects had difficulties in evaluating their memory functioning.

Delayed neuropathy in pigs induced by isofenphos.

In 1990 an outbreak of ataxia occurred in over 700 pigs in the north of England. Epidemiological studies demonstrated that the disorder was associated with the consumption of feed from a particular supplier and that one component (wheat screenings) was common to the batch of feed with which the ataxia was associated. An analysis of the feed demonstrated the presence of an organophosphorus pesticide, later identified as isofenphos, a pesticide not approved for use in the United Kingdom. The wheat screenings had been imported from France and the warehouse in which they had been stored was contaminated with isofenphos, which is approved for restricted use in France. Isofenphos is known to cause delayed neuropathy. The dose to which the pigs were theoretically exposed would be expected to have resulted in neuropathy (manifested as ataxia).

The effect of oral omeprazole on the disposition of lignocaine.

The effects of the gastric antisecretory drug, omeprazole, on the disposition of lignocaine were studied in 10 healthy male volunteers in a double-blind, randomised, placebo-controlled, two-period crossover trial. Omeprazole 40 mg or placebo was taken daily for one week before administration of lignocaine 1 mg.kg-1 (3.7 mumol.kg-1) given intravenously over 10 min. Venous concentrations of lignocaine and its metabolite monoethylglycinexylidine were measured in plasma with reversed phase liquid chromatography. The mean (95% CI) areas under the curve at infinity for lignocaine after pretreatment with omeprazole or placebo were 6.67 (4.90-8.45) mumol.h.l-1 and 6.14 (5.05-7.23) mumol.h.l-1, respectively (p = 0.44). The respective areas for monoethylglycinexylidine were 1.85 (1.25-2.45) mumol.h.l-1 and 1.79 (1.44-2.14) mumol.h.l-1 (p = 0.78). Similarly, omeprazole had no significant effect on the half-lives of lignocaine or methylglycinexylidine.

Effects of selective antagonism of beta-adrenoceptor sub-types on responses to isoprenaline in rat distal colon in vitro.

1. The effects of the beta 1- and beta 2-adrenoceptor selective antagonists, CGP 20712A and ICI 118551 respectively, on responses to isoprenaline-induced relaxation of rat distal colon were investigated in order to determine the contributions of these subtypes to relaxation. In addition, the properties of ICI D7114, a novel putative stimulant of atypical beta-adrenoceptors, were investigated. Our preliminary experiments with ICI D7114 showed that this compound lacked agonist activity in rat distal colon and in fact antagonized responses to isoprenaline. We therefore studied the antagonism of isoprenaline by ICI D7114 in more detail. 2. Longitudinal segments of rat distal colon were suspended in Krebs solution at 37 degrees C for isometric recording. The Krebs solution contained EDTA (23 microM) and prazosin (0.1 microM) and was gassed with 95/5% O2/CO2. After an initial equilibration period, reproducible contractions to a submaximal concentration of methacholine (1 microM) were obtained before carrying out a concentration-response curve (CRC) to isoprenaline in a non-cumulative manner. Four consecutive CRCs to isoprenaline were carried out in each tissue with a 1 h interval between each curve. Antagonists were present in increasing concentrations during the intervals between CRCs. Control tissues received no antagonists to allow estimation of the magnitude of time-dependent changes. 3. Isoprenaline produced a concentration-dependent inhibition of methacholine-induced contractions. CRCs to isoprenaline were reproducible with no significant time-dependent changes. Propranolol produced no shift of the isoprenaline CRC at 0.01 microM and a 5 fold shift at 0.1 microM. No further shift was observed with 1 microM. CGP 20712A had no effect on the CRC to isoprenaline at 0.1, 1 and 3 microM. ICI118551 produced little or no shift at 0.1 microM and a six fold shift with 1 microM. No further shift was observed with 3 microM. ICI D7114 produced a concentration-dependent parallel rightward shift of the CRC to isoprenaline. Schild analysis gave a slope close to unity and a mean pA2 value of 7.29 for ICI D7114.4. The results with propranolol and ,l- and 132-adrenoceptor antagonists confirm the mainly atypical nature of beta-adrenoceptors in rat distal colon. There may also be a small contribution from beta2-adrenoceptors in the response to isoprenaline but beta1-adrenoceptors are absent. ICI D7114 has no agonist activity and behaves as a relatively high affinity reversible competitive antagonist of atypical beta-adrenoceptors in this preparation.

A family with X-linked deafness showing linkage to the proximal Xq region of the X chromosome.

Linkage analysis has been carried out in a family with severe congenital sensorineural deafness with a structural abnormality of the inner ear. Recombinations show the gene responsible for deafness in this family to lie between the loci DXS255 (Xp11.22) and DXS94 (Xq22). Close linkage was found to locus DXS159 (cpX289) in Xq12, with a LOD score of 3.155 and 0 recombination. This location is consistent with other linkage studies of X-linked deafness.

A study of the psychometric effects of chlormethiazole in healthy young and elderly subjects.

The pharmacokinetics and effects of chlormethiazole (91 mg intravenously together with 356 mg orally) on psychomotor performance were studied in 10 young (mean age 29 years) and 10 older (mean age 66.2 years) volunteers using an open design. Chlormethiazole affected psychomotor function and decreased subjective arousal in both age groups. The peak effect was found at approximately 30 min, i.e. at the end of the infusion, and performance returned to normal by 3 h. There was no evidence of increased sensitivity of the older subjects to the psychomotor or subjective effects of chlormethiazole. The incidence and type of reported symptoms was also similar in the two age groups. The volume of distribution of chlormethiazole was greater in the old than in the young subjects as was the elimination half-life after intravenous administration. Other pharmacokinetic variables showed no significant differences between young and old subjects.