Adolescence: a time of risk taking.
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Biomedical subjects
Publications and source records attributed to A J Robinson.
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This document is a first response to the need to develop sexual health services for young people on a single site whilst awaiting research from pilot studies of 'one stop shops' suggested in the Sexual Health and HIV strategy. It is a document which is intended to be a tool to use for those wishing to set up a service providing testing for sexually transmitted infections and provision of contraceptive services for those under 25 years. It is not intended that such a service would replace existing specialist or general practice care but complement it, allowing clients to choose the service most appropriate and acceptable to them, with close links and clear pathways of care for referral between services. This paper should be used as a template when initiating and monitoring a clinic but some of the standards may not be achievable without significant financial input. However, economic limitations should not detract from striving to achieve the best possible care for those most at risk from sexually transmitted infections and unwanted pregnancies. For example, not all clinics will be able to provide the recommended tests for the diagnosis for gonorrhoea and chlamydia immediately, but should work towards achieving them. Although the upper age limit in this document is defined as 25 years, some providers may wish to limit clinics to those under 20 depending on local needs. Detailed information on specific issues such as consent and confidentiality, provision of contraception, investigation of non-sexually transmitted vaginal infections and sexually transmitted infection management and diagnosis are referenced and we recommend these are accessed by the users of this document. Many of the references themselves are live documents available on the worldwide web, and are constantly updated. The Sexual Health and HIV Strategy has now been published and these standards are aimed at those who wish to provide a level 2 sexual health service for young people wherever the setting e.g. genitourinary outreach clinic, contraceptive services, general practice. This document is a starting point to be reviewed and updated as new research becomes available, as the Sexual Health Strategy is implemented and with further input from providers of care (family planning, general practice, genitourinary medicine, gynaecology and paediatrics) and service users. All service providers must maintain a high quality of care and have networks both with those who provide more specialized services (Level 3) and Level 1 services. This document is an initial attempt to ensure that there is equity of clinical provision wherever a Level 2 sexual health service is provided and should be a useful tool for those setting up or monitoring services.
Rh-DuPhos-catalyzed asymmetric hydrogenation of alpha,beta-diamidoacrylates provides a highly efficient and enantioselective route to chiral alpha,beta-diaminopropanoic acid derivatives. The mechanistic course of the hydrogenation was studied using isotopically enriched enamide complexes and phosphorus and carbon NMR. Addition of methyl alpha-N-benzoyl-beta-N-acetyl-diaminopropenoate to the solvated catalyst gave a single 1:1 enamide complex and demonstrated the binding of the olefin and alpha-amide carbonyl group; the carboxylate and beta-N-acyl groups did not bind to the metal. Changes to the electronic and steric properties of the beta-N-acyl group were well tolerated; however, small changes to the binding alpha-N-acyl group were found to significantly affect hydrogenation yields.
2,3-Diaminobutanoic acid (DAB) is found in several peptide antibiotics, toxins, and biologically active molecules. This paper describes the practical and highly enantioselective synthesis of all four N,N'-protected DAB stereoisomers using an asymmetric Rh(I)-phosphine-catalyzed hydrogenation of isomeric enamides as the key step. Thermal and photochemical isomerization of the enamide hydrogenation substrates coupled with catalyst-geometric isomer pairing allows targeted synthesis of single DAB isomers in maximum yield.
The mitogen-activated protein kinase (MAPK) family consists of the p42/p44 MAPKs and the stress-activated protein kinases, c-Jun N-terminal kinase (JNK) and p38 MAPK. We have previously reported that the human adenosine A(1) receptor stimulates p42/p44 MAPK in transfected Chinese hamster ovary cells. In this study, we have investigated whether the endogenous adenosine A(1) receptor in the smooth muscle cell line, DDT(1)MF-2 activates p42/p44 MAPK, JNK and p38 MAPK. The adenosine A(1) receptor agonist N(6)-cyclopentyladenosine stimulated time and concentration-dependent increases in p42/p44 MAPK and p38 MAPK phosphorylation in DDT(1)MF-2 cells. No increases in JNK phosphorylation were observed following adenosine A(1) receptor activation. N(6)-cyclopentyladenosine-mediated increases in p42/p44 MAPK and p38 MAPK phosphorylation were blocked by the selective adenosine A(1) receptor antagonist 1,3-dipropylcyclopentylxanthine and following pretreatment of cells with pertussis toxin. Furthermore, adenosine A(1) receptor-mediated increases in p42/p44 MAPK were sensitive to the MAPK kinase 1 inhibitor PD 98059 (2'-amino-3'-methoxyflavone), whereas p38 MAPK responses were blocked by the p38 MAPK inhibitor SB 203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole). The broad range protein tyrosine kinase inhibitors genistein and tyrphostin A47 (alpha-cyano-(3,4-dihydroxy)thiocinnamide) did not block adenosine A(1) receptor stimulation of p42/p44 MAPK. For comparison, insulin-mediated increases in p42/p44 MAPK were blocked by genistein and tyrphostin A47. The Src tyrosine kinase inhibitor PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and the epidermal growth factor receptor tyrosine kinase inhibitor AG1478 (4-(3-chloroanilino)-6,7-dimethoxyquinazoline) also had no effect on adenosine A(1) receptor stimulation of p42/p44 MAPK. Furthermore, the protein kinase C inhibitors Ro 31-8220 (3-[1-[3-(2-isothioureido) propyl]indol-3-yl]-4-(1-methylindol-3-yl)-3-pyrrolin-2,5-dione), chelerythrine and GF 109203X (2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide) were without effect on adenosine A(1) receptor-induced p42/p44 MAPK phosphorylation. In contrast, wortmannin and LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), inhibitors of phosphatidylinositol 3-kinase, attenuated adenosine A(1) receptor stimulation of p42/p44 MAPK phosphorylation. In conclusion, the adenosine A(1) receptor stimulates p42/p44 MAPK through a pathway which appears to be independent of tyrosine kinase activation but involves phosphatidylinositol 3-kinase. Finally, adenosine A(1) receptor stimulation in DDT(1)MF-2 cells also activated p38 MAPK but not JNK via a pertussis toxin-sensitive pathway.
1. The mitogen-activated protein kinases (MAPKs) consist of the p42/p44 MAPKs and the stress-activated protein kinases, c-Jun N-terminal kinase (JNK) and p38 MAPK. In this study we have examined the effect of histamine H(1) receptor activation on MAPK pathway activation in the smooth muscle cell line DDT(1)MF-2. 2. Histamine stimulated time and concentration-dependent increases in p42/p44 MAPK activation in DDT(1)MF-2 cells. Responses to histamine were inhibited by the histamine H(1) receptor antagonist mepyramine (K(D) 3.5 nM) and following pre-treatment with pertussis toxin (PTX; 57% inhibition). 3. Histamine-induced increases in p42/p44 MAPK activation were blocked by inhibitors of MAPK kinase 1 (PD 98059), tyrosine kinase (genistein and tyrphostin A47), phosphatidylinositol 3-kinase (wortmannin and LY 294002) and protein kinase C (Ro 31-8220; 10 microM; 41% inhibition). Inhibitors of Src tyrosine kinase (PP2) and the epidermal growth factor tyrosine kinase (AG1478) were without effect. Removal of extracellular Ca(2+), chelation of intracellular Ca(2+) with BAPTA and inhibition of focal adhesion assembly (cytochalasin D) had no significant effect on histamine-induced p42/p44 MAPK activation. 4. Histamine stimulated time and concentration-dependent increases in p38 MAPK activation in DDT(1)MF-2 cells but had no effect on JNK activation. Histamine-induced p38 MAPK activation was inhibited by pertussis toxin (74% inhibition) and the p38 MAPK inhibitor SB 203580 (95% inhibition). 5. In summary, we have shown the histamine H(1) receptor activates p42/p44 MAPK and p38 MAPK signalling pathways in DDT(1)MF-2 smooth muscle cells. Interestingly, signalling to both pathways appears to involve histamine H(1) receptor coupling to G(i)/G(o)-proteins.
There is a well-recognized association between the inflammatory dermatomyopathy, dermatomyositis, and underlying visceral malignancy in adults. It is most commonly found in association with malignancies arising in the lung, breast and stomach. We report a case found in association with transitional cell carcinoma of the bladder, a site where there have only been a handful of previous reports.
Conjunctivitis due to Chlamydiaceae other than Chlamydia trachomatis is rarely reported because of infrequent occurrence or inadequate investigation. A case of chronic non-trachomatis chlamydial conjunctivitis is described. After full clinical information was supplied to the laboratory, a non-trachomatis chlamydia was recovered from the patient's eye. This organism, and a subsequent isolate from one of the patient's cats, were shown to be indistinguishable examples of the recently described species Chlamydophila felis. The infection was most likely acquired from the patient's cats. A prolonged course of doxycycline was required to eradicate the infection.
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ELISA techniques developed for the veterinary diagnosis of Rabbit Haemorrhagic Disease (RHD) in domestic rabbits were used for studying the epidemiology of RHD in Australian wild rabbits. The combination of ELISA techniques that distinguished IgA, IgG and IgM antibody responses and a longitudinal data set, mainly based on capture-mark-recapture of rabbits, provided a reliable basis for interpreting serology and set the criteria used to classify rabbits' immunological status. Importantly, young with maternal antibodies, immune rabbits and rabbits apparently re-exposed to RHD were readily separated. Three outbreaks of RHD occurred in 1996-7. The timing of RHD outbreaks was mainly driven by recruitment of young rabbits that generally contracted RHD after they lost their maternally derived immunity. Young that lost maternal antibodies in summer were not immediately infected, apparently because transmission of RHDV slows at that time, but contracted RHD in the autumn when conditions were again suitable for disease spread.
It is known that while the programs used to predict genes are good at determining coding nucleotides, there are considerable inaccuracies in the determination of the gene structural elements. Among them, the most notable is that of the exact boundaries of exons. In order to assess this, we had earlier reviewed various programs that predict potential splice sites and exons. The results led to the following two observations: (i) a high proportion of false positive splice sites from computational predictions occur in the vicinity of real splice sites; and (ii) current algorithms are misled to predict wrong splice sites more often when the coding potential ends within +/-25 nucleotides from real sites than when it ends at farther positions. In this report, we review decision tree models for human splice sites and the resultant software tool, namely SpliceProximalCheck, that discriminates such'proximal' false positives from real splice sites. Further presented is an integrated system (MZEF-SPC) with Splice ProximalCheck (SPC) as a front-end tool operating on the results of Michael Zhang's exon finder program. Examination of the output of the integrated program on an illustrative gene set revealed that as much as 61 of 93 MZEF-predicted false positive exons could be eliminated by SPC for a loss of only 3 out of 33 MZEF-predicted true positive exons.
Clinicians treating concurrent gonococcal and chlamydial infections have a variety of drugs to choose from. Neisseria gonorrhoeae is adept at developing resistance and the choice of antibiotic must be dictated to some extent by the patterns of resistance in the locality of the clinician. In contrast, resistance of Chlamydia trachomatis to some classes of drugs has been shown in vitro but does not appear to be clinically important at present. The success of treatment depends on patient compliance with the drug administration schedule. With these organisms, which can be carried asymptomatically, many patients are unlikely to comply with courses of antibiotics. Although single-dose therapy with azithromycin is available and established for chlamydial genital infection, it is more expensive and difficult to justify in a cash limited Healthcare system, and its efficacy for treating concurrent gonococcal infection requires further study. In patients where compliance is likely to be of concern, its use may be justified. Another major deterrent for completing antibiotic courses is the adverse effect profile. Most of the available drugs cause only minor adverse effects, in particular gastrointestinal. Ofloxacin has a better profile than doxycycline but is considerably more expensive. Newer fluoroquinolones, found to be effective in vitro, are being assessed in clinical studies. However, more evidence is required before recommending these over the tried and tested therapies.
Anogential warts are much less common in children than in adults. In children the presence of anogenital warts have been suggested as an indicator for sexual abuse because of the association of genital warts with sexual activity. Difficulties of establishing mode of transmission arise because of the long latency of human papillomavirus and possibility of vertical and non-sexual transmission. A multidisciplinary approach is advised for the proper care of children with anogenital warts.
Development of immunocontraceptives for wild rabbit populations requires selection of both effective antigens and effective delivery systems. Recombinant rabbit zona pellucida glycoprotein B (ZPB) produced in eukaryotic cells in vitro was an effective antigen and induced sustained infertility in 70% of female rabbits. This required two boosts and serum antibody titers of 12 800 or greater. Antibody titers in females were low after the initial immunization, as might be expected with a self-antigen; however, male rabbits had a strong antibody response, indicating that the protein was immunologically foreign. To develop a delivery system, ZPB was delivered by infection with a recombinant myxoma virus. In contrast to the results with ZPB protein, infection of rabbits induced a similar serum antibody response to ZPB in both sexes. This indicated that presentation of ZPB in the context of a virus infection was able to overcome tolerance in females. However, the antibody titers were lower than 12 800, and only 25% of female rabbits were infertile. This antibody response was boosted by injections of recombinant ZPB protein, after which 80% of female rabbits were infertile. Infertility was associated with antibody binding to zonae and varying degrees of ovarian pathology characterized by follicular degeneration and substantial depletion of primordial follicles. Oocyte and follicular degeneration appeared to be the principal mechanism of infertility and may be primarily induced by antibodies to ZPB.
The only method of assessing the virulence of myxoma virus is to record survival times of rabbits inoculated with the virus. This raises ethical concerns about using animals in experiments where death is the end point. We investigated whether or not the opioid analgesic buprenorphine could be used in rabbits without compromising the myxoma virus virulence assay and on the presumption that animals may suffer pain during the course of the disease. Thirty, 5-month-old New Zealand White rabbits were divided into two groups stratified for weight and gender, and inoculated intradermally with 100 pfu of the Standard Laboratory Strain (SLS) of myxoma virus. At day 6 post infection (p.i.), when eyelid swelling was first seen, each animal in one group was treated with 0.03 mg/kg buprenorphine, subcutaneously, morning and evening until death. Animals in the other group were untreated. Animals were weighed daily and rectal temperatures taken morning and evening. Intake of food and water was assessed as was general demeanor including respiratory effort. There was no significant difference in mean survival time, weight change, or demeanor between the two groups. Increased respiratory effort was seen from day 10 p.i. in animals surviving up to and beyond that time but again there was no difference between groups. Animals treated with buprenorphine refused food and water a day earlier than untreated animals, and had lower temperatures immediately prior to death. It was concluded that the opiate analgesic buprenorphine can be used without compromising the current virulence assay for the SLS of myxoma virus in New Zealand White rabbits but that the clinical signs of myxomatosis that could be attributed to pain were not abrogated.
The aim of this study was to evaluate the sensitivity and acceptability of self-taken vulval-introital (VI) samples, first-catch urine (FCU) samples and clinician-obtained cervical samples for the presence of genital Chlamydia trachomatis infections in women using the ligase chain reaction (LCR) assay. One hundred and four patients were enrolled, of whom 54 patients had chlamydial DNA in at least one of the samples tested. The sensitivity of the cervical sample was 96.3%, vulval-introital sample in LCR buffer 92.6%, vulval-introital swab collected dry 88.9%, FCU stored at +2-8 degrees C 81.5%, FCU stored at room temperature 77.8% and FCU stored with 2% w/v boric acid at room temperature 87.0%. Self-taken vulval-introital LCR samples were shown to be an acceptable alternative to a clinician-obtained LCR sample. The addition of boric acid may overcome the need for a continuous cold chain for FCU samples.
This article reviews the evidence available to guide practitioners when advising patients with genital warts, by seeking to answer the questions most commonly asked in medical practice. It highlights where evidence is lacking and is intended to inform patients about their condition, and to identify areas where further research is warranted.