Fipronil and two of its transformation products in water and European eel from the river Elbe.

Fipronil is an insecticide which, based on its mode of action, is intended to be predominantly toxic towards insects. Fipronil bioaccumulates and some of its transformation products were reported to be similar or even more stable in the environment and to show an enhanced toxicity against non-target organisms compared to the parent compound. The current study investigated the occurrence of Fipronil and two of its transformation products, Fipronil-desulfinyl and Fipronil-sulfone, in water as well as muscle and liver samples of eels from the river Elbe (Germany). In water samples total concentrations of FIP, FIP-d and FIP-s ranged between 0.5-1.6ngL(-1) with FIP being the main component in all water samples followed by FIP-s and FIP-d. In contrast, FIP-s was the main component in muscle and liver tissues of eels with concentrations of 4.05±3.73ngg(-1) ww and 19.91±9.96ngg(-1) ww, respectively. Using a physiologically based toxicokinetic (PBTK) model for moderately hydrophobic organic chemicals, the different distributions of FIP, FIP-d and FIP-s in water and related tissue samples could be attributed to metabolic processes of eels. The measured concentrations in water of all analytes and their fractional distribution did not reflect the assumed seasonal application of FIP and it seems that the water was constantly contaminated with FIP, FIP-d and FIP-s.

A national audit on the management of pelvic inflammatory disease in UK genitourinary medicine clinics.

The prompt and effective treatment of pelvic inflammatory disease (PID) may reduce the risk of complications such as infertility, ectopic pregnancy and pelvic pain. We conducted a national audit to investigate the treatment of women diagnosed with PID and associated rates of partner notification in genitourinary (GU) medicine clinics during 2008 and compared our results with the British Association of Sexual Health and HIV (BASHH) 2005 national guideline. Among a total of 1,105,587 female attendees, national data showed 18,421 cases of PID diagnosed in GU medicine clinics, giving an incidence of 167 cases per 10,000 attendences. We audited a national sample of 1132 PID cases for review. Of those, 504 (44.5%) received a recommended treatment regimen and 447 (39%) of named male contacts were treated. Adherence to recommended treatment and partner notification did not reach national standards.

How do UK medical graduates rate their knowledge and skills in sexual health and HIV medicine? A national survey.

The objectives of this study are to determine self-assessed knowledge and skills in sexual health and HIV medicine in preregistration house officers and to explore undergraduate experiences of teaching and assessment in these subjects prior to the launch of National Core Learning Outcomes in Sexual and Reproductive Health and HIV. The study was designed as a postal questionnaire survey. The participants were all UK medical graduates of August 2004. The response rate 1737/4746 (36%). The main outcome measures were Doctors' views on their preparedness to manage patients with sexual health and HIV-related problems. Since graduation, 90% of respondents had seen at least one patient with a sexually transmitted infection or HIV-related issue. Seventy-six percent felt confident to take a sexual history. In all, 63% and 53% felt competent in male and female genital examination, respectively. Forty-three percent felt they could conduct an appropriate HIV pretest discussion and 59% felt they could recognize clinical indicators suggestive of HIV. Seventy-eight percent had been formally assessed in sexual health and 55% in HIV medicine. Increased confidence in sexual history taking, HIV pretest discussion and recognition of HIV indicators was associated with a longer duration of teaching and formal examination. In conclusion, although the proportion of recent graduates confident in sexual history taking is encouraging, their lack of skill in discussing HIV testing, risk assessment and recognition of possible HIV presentations must be addressed. Integration of National Core Learning Outcomes into all undergraduate curricula is a key step in reducing inconsistencies in undergraduate training.

Non-consultant career grade doctors in genitourinary medicine - are they up to the job? National survey 2007.

Non-consultant career grade doctors in genitourinary (GU) medicine have been called 'a reliable silent backbone of the specialty' and 'a spare pair of hands' [Hiscock E. Non-consultant career grade staff in GU medicine; a reliable backbone or, a spare pair of hands? Int J STD AIDS 1996;7:375-7]. But are they adequate pairs of hands? This survey, conducted in July 2007, examined the work, qualifications and experience of these doctors. A summary of the 154 (19%) responses is presented. Respondents contributed 773 sessions per week, including 164 special interest sessions; 30 (19.5%) were doing regular HIV work. Non-clinical work was described by 134 (87%), especially teaching (132 [86%]) and management roles (26 [17%]). Postgraduate qualifications were cited by 148 (96%), including DipGUM or Dip Ven (51 [33%]), contraception qualifications such as DFFP, MFFP or FFFP (110 [71%]), MRCGP (43 [8%]) and qualifications in psychosexual medicine/therapy (10 [6.5%]). Over half were trained in general practice. Certificate of completion of specialist training or equivalent was held by 55 (36%), including two in GU medicine. These doctors are well qualified, and an asset to the specialty.

Potential health risks of complementary alternative medicines in HIV patients.

OBJECTIVES: To determine the prevalence and purpose of complementary alternative medicines (CAMs) use in people receiving treatment for HIV infection. To identify and quantify potential health risks of CAM use in this population and to explore options for improved pharmacovigilance. METHODS: Cross-sectional questionnaire survey of 293 patients receiving antiretroviral (ARV) therapy at three specialist HIV out-patient clinics in central London, UK. The use of herbal medicines and supplements was explored, and potentially adverse side effects or significant drug interactions with conventional therapies were identified. RESULTS: Of the 293 patients included, 61% (n=179) were taking herbal remedies or supplements and 35% (n=103) were using physical treatments. Twenty-seven per cent (n=80) used a combination of both. Twenty per cent (n=59) potentially compromised their HIV management through using CAM therapy. Ten per cent (n=29) were advised to stop their CAMs and 15% (n=43) were made aware of potential drug interactions and adverse effects and were advised to monitor their care. CONCLUSIONS: There are potentially significant health risks posed by the concomitant use of CAMs in patients taking ARV therapy. Medical practitioners need to be able to identify CAM use in HIV-positive patients and recognize potential health risks. Patients should be encouraged to disclose CAM use to their clinicians and other healthcare professionals.

Simian immunodeficiency virus lentivector corrects human X-linked chronic granulomatous disease in the NOD/SCID mouse xenograft.

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the phagocyte nicotinamide dinucleotide phosphate oxidase catalytic subunit gp91(phox). Gene therapy targeting hematopoietic stem cells (HSCs) can correct CGD, but permanent correction remains a challenge. Lentiviral vectors have become attractive tools for gene transfer, and they may have the potential to transduce very primitive HSCs. We used a self-inactivating RD114/TR-pseudotyped simian immunodeficiency virus (SIVmac)-based vector encoding human gp91(phox) for ex vivo transduction of peripheral blood-mobilized stem cells (PBSCs) from patients with X-CGD. In PBSCs from two patients, ex vivo transduction efficiencies of 40.5 and 46% were achieved, and correction of oxidase activity was observed in myeloid cells differentiating in culture. When transduced PBSCs from these patients were transplanted into nonobese diabetic/severe combined immunodeficient mice and compared to normal control, 10.5 and 7.3% of the human myeloid cells in bone marrow developing at 6 weeks from the human xenografts expressed the gp91(phox) transgene. Sustained functional correction of oxidase activity was documented in myeloid cells differentiated from engrafted transduced PBSCs. Transgene marking was polyclonal as assessed by vector integration site analysis. These data suggest that RD114/TR SIVmac-based vectors might be suitable for gene therapy of CGD and other hereditary hematologic diseases.

Genitourinary medicine clinic KC60 coding for first episode genital herpes: a lesson from north of the border?

A survey of the accuracy of applying the KC60 diagnostic code for genital herpes: first attack (C10A) was undertaken by non-consultant career-grade doctors working in genitourinary (GU) medicine in England, Wales and Northern Ireland. In total, 148 forms were returned (58% response). Overall, 88/148, 59.5% (95% confidence interval 51.5-67.4%) applied the correct codes for all the clinical scenarios presented. Of doctors who personally assigned codes to clinical episodes, 57/104 (54.8%), were correct compared with 31/44 (70.5%) who did not personally apply codes. There was no difference between these two groups (P=0.08). The main error was assigning code C10A on clinical grounds only when there was no laboratory confirmation of herpes simplex virus. The authors suggest that the KC60 C10A code for first attack genital herpes should be simplified to accept a clinical diagnosis rather than insisting on viral confirmation. Alternatively, consideration could also be given to adopting a more comprehensive system (such as the Scottish example) for first attack genital herpes. We believe that either option would help improve the accuracy of GU clinic data relating to genital herpes.

Expression of heat shock protein 70 in a permanent cell line (EPC) exposed to sediment extracts from the North Sea and the Baltic Sea.

Heat shock proteins 70 (hsp70) are known to be induced by a great variety of chemical stressors. The effects of different environmental contaminants, which were identified in sediments of the North Sea and the Baltic Sea as main contaminants or as contaminants of special toxicological interest, on the extent of expression of hsp70 in a permanent cell line Epithelioma papulosum cyprini (EPC) were investigated. Concentrations of the single contaminants leading to elevated hsp70 levels were compared to the respective concentrations of these contaminants encountered in the sediment extracts thus allowing an assessment of their contribution to the toxicity of these sediments. Analysis of hsp70 was performed using western blotting techniques with subsequent comparative quantification by densitometry. Eleven of thirteen contaminants have shown a dose-dependent increase in hsp70 levels. An expression of hsp70 was observed in most cases between 0.1 and 10 microg/mL test solution. Some of the investigated stressors led to extremely high hsp70 contents even at low concentrations. However, in most cases contaminant concentrations in sediments were too low to cause an effect. For this reason, effects of the tested sediments are attributed to other contaminants or rather to mixtures of stressors.

Brominated indoles and phenols in marine sediment and water extracts from the north and baltic seas-concentrations and effects.

This work presents results from analytical as well as ecotoxicologic investigations of sediment and water samples from the North and Baltic Seas. A bioassay-directed procedure was used to investigate cause-effect relationships between observed effects in acute laboratory bioassays (luminescent bacteria assay with Vibrio fischeri and embryo test with Danio rerio) and analyte concentrations in extracted samples. Brominated phenols and indoles-including 4-bromophenol; 2,4-dibromophenol; 4- and 6-bromoindole; 3,4-, 4,6-, and 3,6-dibromoindole; and tribrominated compounds-were identified in partly remarkable concentrations (up to 40,000 ng g(-1) total organic carbon TOC for 4-bromophenol) in North Sea sediment samples and water samples (913 ng L(-1) 3,6-dibromoindole) from the German Bight. The toxicity of some of the identified brominated substances was low, with median effect concentration levels (EC(50)) ranging from 0.08 to 21.7 mg/L for V. fischeri and 4.3 to 46.3 mg/L for D. rerio. Comparison of the concentrations of analytes with ECs showed a toxicity contribution of brominated phenols and indoles to overall toxicity of the fraction. In the case of one water sample from the German Bight, brominated phenols and indoles accounted for the observed toxicity. Brominated phenols and indoles, which are assumed to be of biogenic origin, have rarely been discussed so far in the context of ecotoxicologic effects in marine ecosystems.

Primary care and the National Strategy for Sexual Health and HIV: an evaluation of one primary care trust.

Windsor, Ascot, Maidenhead (WAM) primary care trust (PCT) currently has no specialist sexual health services. We researched the level of sexual health service provision in WAM compared with targets set out in the National Strategy for Sexual Health and HIV and assessed support for level 2 service expansion. We found practices were already providing much of level 1 and parts of level 2 services. Gaps centred on male and asymptomatic female screening and sexual health promotion. Ten out of 22 practices expressed interest for service development within the PCT, but obstacles cited included lack of resources, training and prioritization of the strategy. The study has identified strengths and weaknesses across the PCT that have guided recent initiatives. This model could be used by other PCTs to ascertain their needs and acknowledge their achievements.

Delivering results to clients: a question of satisfying needs or desires?

Demand for genitourinary (GU) medicine services is outstripping supply. Improving efficiency can modulate the supply side of the equation, e.g. decreasing the number of clients having to return for their results. This survey explored how clients at two central London GU medicine clinics would like to receive their results and their views were reflected against what was offered by London GU medicine clinics. There was a significant difference between the result delivery services that the clients wanted and what the clinics provided (P <0.0001, chi(2)). Of the clients, 92% wanted to know their results regardless of outcome whereas 22% of London clinics would only inform clients of positive results. This study questions the importance and feasibility of patient choice, an important aspect of the National Strategy for Sexual Health and HIV. Clinics may not individually be able to provide choice but between them, they do provide a wide range of alternatives for the client.

Non-consultant career grade doctors in genitourinary medicine: as revalidation approaches, are some jobs at risk?

The Genitourinary Medicine Non-Consultant Career Grade Group (GUM NCCG Group) was established for the purpose of looking at training and contractual issues for this heterogeneous group of doctors. In June 2003, 700 questionnaires were posted to NCCG doctors in the UK to enquire about various aspects of working conditions. A summary of the 244 replies (35% response) is presented. Eighty-four (34%) had a job plan and 81 (33%) had had an appraisal. Just over one-third (38%) had time allocated for continuing medical education (CME), audit and administration. The response of employers to attempts by NCCGs to upgrade was poor. In all, 195 (80%) said they were registered for the purpose of continuing professional development (CPD), 43 (18%) were not and six people did not know whether they were registered or not. These results give cause for real concern at this point regarding revalidation pathways. Our survey highlights that NCCGs are disadvantaged in terms of appraisal, CPD and career progression and some jobs will be at risk as revalidation approaches.

Seeking and engaging in internet sex: a survey of patients attending genitourinary medicine clinics in Plymouth and in London.

We conducted a survey of patients attending two GUM clinics to evaluate the use of the internet for seeking sexual partners and for seeking on-line sexual health information. Prevalence of internet sex-seeking (ISS) was 11% (57/500) in Plymouth and 21% (50/237) in London. ISS was more common among men who have sex with men (MSM) (43/92 = 47%) than men who have sex with women (MSW) (38/280 = 14%, P < 0.0001) and more common amongst MSW than women who have sex with men (WSM) (25/350 = 7%, P = 0.007). In both samples, accessing sexual health information online was associated with ISS (Plymouth, P = 0.05 and London, P = 0.001), as was reporting more than 10 sexual partners per year (Plymouth and London, P < 0.001). It remains to be seen whether the potential sexual health promotion benefits of the internet could balance potential risks of STI acquisition.

Sexual health provision and the Sexual Health and HIV Strategy for England: a questionnaire survey of general practitioners' views.

An anonymous postal survey was used to assess the views of general practitioners (GPs) on the expected contents of the Department of Health National Sexual Health and HIV Strategy for England prior to release. One hundred and seventeen GPs in four London Primary Care Groups took part (response rate=50%). The majority felt they currently have about the right amount of involvement in patient care (HIV 70%: GUM 66%); 88% of GPs felt they offer general sexual health care (Level one), and most wished to continue with this (85%). However, a sizeable minority of GPs wanted to be involved in the development of care guidelines (HIV 17%; GUM 22%), and 10% considered that they might wish to offer more specialist services (Level two). To achieve a Strategy goal to integrate sexual healthcare services in England, it is likely that there will need to be local consultation and support for GPs.

Nonylphenols, nonylphenol-ethoxylates, linear alkylbenzenesulfonates (LAS) and bis (4-chlorophenyl)-sulfone in the German Bight of the North Sea.

Nonylphenols and nonylphenol-ethoxylates were detected in the water and sediment samples from the German Bight of the North Sea. Additionally bis (4-chlorophenyl)-sulfone and linear alkylbenzenesulfonates (LAS) were detected in marine waters. Proof of identification is given by comparison of spectral and chromatographic data from the compounds in sample extracts to those obtained from pure standards. In extracts obtained from water samples taken in 1990 and 1995 the concentrations of nonylphenols and bis-(4-chlorophenyl)-sulfone were compared for each year. The concentrations of nonylphenols in seawater varied from 0.7 to 4.4 ng/l while in the Elbe estuary about 33 ng/l were found. In water samples taken in 1998 nonylphenol-polyethoxylates could not be determined, whereas LAS concentrations of 30 ng/l were confirmed by HPLC-MS/MS. The concentrations of bis (4-chlorophenyl)-sulfone ranged from 0.18 to 2.2 ng/l. In sediment samples LAS concentrations of 39-109 ng/g dry weight were determined.

The occurrence of xenoestrogens in the Elbe river and the North Sea.

The xenoestrogens Bisphenol A (BPA), p-alkylphenols and p-alkylphenol ethoxylates were determined in water samples of the North Sea, the Elbe river, and its tributaries Schwarze Elster, Mulde, Saale and the Weisse Elster. The sampling sites of the Elbe river reached from Schmilka at the German-Czech border to Cuxhaven at the estuary. Samples of the North Sea were taken in the German Bight. Additionally, freshly deposed sediments of the River Elbe and its tributaries were analyzed. Partitioning coefficients of these compounds for the distribution between suspended particulate matter (SPM) and the aqueous phase were calculated for samples of the River Elbe at sampling site Geesthacht. The analytical procedure consisted of liquid-liquid extractions of the acidified water samples using dichloromethane. Sediments and SPM samples were extracted by Accelerated Solvent Extraction with n-hexane/acetone. Following a clean-up by HPLC, the analytes were derivatized with heptafluorobutyric acid anhydride and quantified using GC-MSD. The concentration ranges of the compounds analyzed in water samples of the Elbe river were as follows (in ng l(-1)): BPA 9-776, alkylphenols 10-221 and alkylphenol ethoxylates 18-302. In sediment samples the concentrations were (in microg kg(-1) dry mass): BPA 66-343, alkylphenols 17-1378 and alkylphenol ethoxylates 30-1797. In samples of the North Sea the concentrations were generally about 1 order of magnitude lower. As shown by the concentration profiles following the River Elbe into the North Sea, the Elbe river must be considered as a major pollution source for the North Sea concerning the compounds analyzed. The SPM/water-partitioning coefficients calculated (mean values) amounted to: BPA 4.50, alkylphenols 5.52-5.58 and alkylphenol ethoxylates 5.60-6.38. A comparison of the results with data from other surface waters showed that concentrations of these xenoestrogens in the River Elbe and its tributaries were relatively low. The evaluation of the data based on the lowest observable effect concentration (LOEC) for alkylphenols (endpoint: vitellogenin synthesis in male trout) indicated that the concentrations were well below the effectivity threshold.

A permanent fish cell line (EPC) for genotoxicity testing of marine sediments with the comet assay.

Genotoxicity and cytotoxicity were evaluated in an in vitro system with a permanent cell line Epithelioma papulosum cyprini (EPC) derived from a skin tumour of carp (Cyprinus carpio L.). EPC cells were exposed to different concentrations of organic sediment extracts from the North Sea for 24h. After incubation the cells were analysed for viability and DNA strand breaks with the comet assay or single cell gel electrophoresis (SCGE). The results confirm the sensitivity of this assay. Out of 10 marine sediment samples from the North Sea, 9 showed a dose-dependent genotoxic effect. The EC(50) of sediment extracts ranged from 7 to 307 mg sediment dry weight/ml assay volume. Hepatic microsomal enzymes from dab (Limanda limanda L.) was proposed for enzymatic activation of benzo[a]pyrene (BAP) or sediment extracts, respectively. The suitability of this in vitro test system for assessing genotoxic and cytotoxic effects of marine sediment extracts on EPC cells could be demonstrated.

Human CD34+ cell preparations contain over 100-fold greater NOD/SCID mouse engrafting capacity than do CD34- cell preparations.

OBJECTIVE: The CD34 cell surface marker is used widely for stem/progenitor cell isolation. Since several recent studies reported that CD34(-) cells also have in vivo engrafting capacity, we quantitatively compared the engraftment potential of CD34(+) vs CD34(-) cell preparations from normal human placental/umbilical cord blood (CB), bone marrow (BM), and mobilized peripheral blood (PBSC) specimens, using the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model. METHODS: CD34(+) and CD34(-) cell preparations were purified by four different approaches in 14 individual experiments involving 293 transplanted NOD/SCID mice. In most experiments, CD34(+) cells were depleted twice (CD34(=)) in order to obtain efficient depletion of CD34(+) cells from the CD34(-) cell preparations. RESULTS: Dose-dependent levels of human hematopoietic cells were observed after transplantation of CD34(+) cell preparations. To rigorously assess the complementary CD34(-) cell preparations, cell doses 10- to 1000-fold higher than the minimum dose of the CD34(+) cell preparations necessary for engraftment were transplanted. Nevertheless, of 125 NOD/SCID mice transplanted with CD34(-) cell preparations purified from the same starting cells, only six mice had detectable human hematopoiesis, by flow cytometric or PCR assay. CONCLUSIONS: CD34(-) cells provide only a minor contribution to hematopoietic engraftment in this in vivo model system, as compared to CD34(+) cells from the same samples of noncultured human cells. Hematopoiesis derived from actual CD34(-) cells is difficult to distinguish from that due to CD34(+) cells potentially contaminating the preparations.

Genotoxic potential of marine sediments from the North Sea.

The alkaline comet assay is a method for detecting DNA strand breaks and alkali labile sites in individual cells. An in vitro system was used to investigate the genotoxic potential of complex mixtures such as organic extracts of marine sediments. DNA damage was induced in leukocytes isolated from carp (Cyprius carpio) by exposure to organic sediment extracts from the North Sea or hydrogen peroxide as positive control, respectively. The minimum concentration for significant effects ranged from 1 to 40 mg sediment dry weight per milliliter assay volume. The sensitivity of the method was enhanced by using the DNA repair inhibitor, 1-beta-D-arabinofuranosylcytosine (ara C). From the results, it can be suggested that total organic carbon (TOC) as well as the different compositions of contaminants present in the sediment extracts may contribute to the genotoxic effects observed. The comet assay can be applied successfully as an in vitro bioassay for investigations on genotoxicity of marine sediment extracts.