Do all men attending departments of genitourinary medicine need to be screened for non-gonococcal urethritis?

We investigated the influence of symptoms and signs on the detection of Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum organisms (ureaplasmas) in men with non-gonococcal urethritis (NGU). Two hundred and forty-two men attending the Jefferiss Wing at St Mary's Hospital for a sexual health assessment were evaluated, of whom 169 had NGU. Urethral inflammation was diagnosed if there were either > or =5 polymorphonuclear leucocytes (PMNLs) per high-power field (HPF) in five or more microscope fields of a Gram-stained urethral smear, or > or =10 PMNLs per HPF in five or more fields of a Gram-stained thread from 15-20 mL of a first-passed urine (FPU) specimen. C. trachomatis was diagnosed by direct immunofluoresence, M. genitalium by a polymerase chain reaction assay and ureaplasmas by culture. On multivariate analysis, to control for potential confounding by age, ethnicity, sexual lifestyle and co-infection, an urethral discharge remained significantly associated with the detection of C. trachomatis and M. genitalium in men with acute urethritis [OR 12.3, 95% CI (2.39-63.5) and OR 35.2, 95% CI (3.9-319.6), respectively], but dysuria or penile irritation did not. The detection of ureaplasmas was not associated with any clinical feature. In addition, on multivariate analysis men with NGU who were either symptomatic or had an observable discharge were more likely to have C. trachomatis or M. genitalium detected [(OR 6.92, 95% CI 1.41-33.9) and (OR 5.18, 95% CI 0.99-27.1), respectively], but not ureaplasmas (OR 1.19, 95% CI 0.33-4.35). The findings suggest that in men with acute NGU, symptoms or signs, and in particular a urethral discharge, are associated with the detection of C. trachomatis and M. genitalium, but not ureaplasmas. Currently, there is no precise answer to the question of whether all men attending a GUM clinic need to be screened for NGU, but if clinically asymptomatic NGU is found not to be associated with a sexually transmitted pathogen, the UK clinical guidelines requiring the preparation of a urethral smear from such men would need to be revised.     

Inflammatory bowel disease: A survey of the epidemiology in Asia

Inflammatory bowel disease (IBD) has long been considered a disease that affects predominantly a Western population. The incidence and prevalence rates from Asian populations are much lower in comparison. More recent data, however, have shown significantly higher rates in Asians and time trend studies have shown an increase in the incidence of ulcerative colitis (UC) and a similar but lower rise in Crohn's disease (CD). The epidemiological changes that are taking place mirror that of the Western experience seen 50 years previously and seem to occur in parallel with the rapid socioeconomic development taking place in Asia. It appears that certain racial groups are more prone than others to develop IBD. For instance, Indians in South‐East Asia have higher rates compared to Chinese and Malays. While there is host genetic predisposition, environmental factor(s) may be responsible for this difference. Migrant studies of South Asians in the UK, where second‐generation immigrants have assumed incidence rates as high as the indigenous whites and Asian Jews who develop high incidence rates comparable to Jews from Europe or North America in Israel point to the role of environmental factors. It is unclear which specific factors are responsible. Studies have suggested a change in diet to a more Westernized one may underlie this epidemiological change in the Asian population. It is likely that there are racial groups amongst Asians who are more susceptible to IBD and who will demonstrate a higher frequency of IBD when exposed to putative environmental factors.     

盐酸帕罗西汀治疗胃肠疾病433例分析

常见胃肠疾病的临床症状常是非特异性及多样性,其中或多或少受到精神因素的影响［１］。为探索针对调整神经功能失调药物在治疗胃肠疾病中的作用,自１９９７年５月至１９９８年７月,我们在常规药物治疗的基础上加用盐酸帕罗西汀（赛乐特）治疗常见胃肠疾病４３３例,疗效满意,现报告如下。材料与方法一、研究对象４３３例胃肠疾病均依据临床表现、内镜、实验室及影象学检查明确诊断,其表１　主要胃肠道症状及治疗效果（例）恶心呕吐腹痛腹胀暖气大便次数及习惯改变吞咽障碍或吞咽不协调病例数１５６１２８８２４３１０有效数１３２１１…     

A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales,Australia

Four hundred and twenty‐one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross‐sectional study to assess sexual dysfunction and infertility post‐transplant. Survey instruments included the Sydney Post‐Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) – BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft‐versus‐Host Disease (cGVHD) Activity Assessment‐ Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post‐Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61·6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3·3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10·3% reporting success. This study is the largest to date exploring sexual function in survivors of allo‐HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre‐ and post‐transplant.     

CYP450-derived oxylipins mediate inflammatory resolution

Resolution of inflammation has emerged as an active process in immunobiology, with cells of the mononuclear phagocyte system being critical in mediating efferocytosis and wound debridement and bridging the gap between innate and adaptive immunity. Here we investigated the roles of cytochrome P450 (CYP)-derived epoxy-oxylipins in a well-characterized model of sterile resolving peritonitis in the mouse. Epoxy-oxylipins were produced in a biphasic manner during the peaks of acute (4 h) and resolution phases (24–48 h) of the response. The epoxygenase inhibitor SKF525A (epoxI) given at 24 h selectively inhibited arachidonic acid- and linoleic acid-derived CYP450-epoxy-oxlipins and resulted in a dramatic influx in monocytes. The epoxI-recruited monocytes were strongly GR1⁺, Ly6c^hi, CCR2^hi, CCL2^hi, and CX3CR1^lo. In addition, expression of F4/80 and the recruitment of T cells, B cells, and dendritic cells were suppressed. sEH (Ephx2)^−/− mice, which have elevated epoxy-oxylipins, demonstrated opposing effects to epoxI-treated mice: reduced Ly6c^hi monocytes and elevated F4/80^hi macrophages and B, T, and dendritic cells. Ly6c^hi and Ly6c^lo monocytes, resident macrophages, and recruited dendritic cells all showed a dramatic change in their resolution signature following in vivo epoxI treatment. Markers of macrophage differentiation CD11b, MerTK, and CD103 were reduced, and monocyte-derived macrophages and resident macrophages ex vivo showed greatly impaired phagocytosis of zymosan and efferocytosis of apoptotic thymocytes following epoxI treatment. These findings demonstrate that epoxy-oxylipins have a critical role in monocyte lineage recruitment and activity to promote inflammatory resolution and represent a previously unidentified internal regulatory system governing the establishment of adaptive immunity.Monocytes and monocyte-derived macrophages play a critical role in chronic inflammation, in part via the production and release of lipid mediators (1). One such lipid precursor, arachidonic acid, is metabolized into families of biologically active mediators by the cyclooxygenase, lipoxygenase, and cytochrome P450 (CYP) pathways (2, 3). CYPs metabolize arachidonic acid by: (i) an epoxygenase activity that catalyzes the conversion of arachidonic acid to epoxyeicosatrienoic acids (EETs); (ii) a lipoxygenase-like activity that metabolizes arachidonic acid to midchain hydroxyeicosatetraenoic acids (HETEs); and (iii) ω- and ω-1-hydroxylase activity, which produces ω-terminal HETEs (3). In addition to arachidonic acid, CYPs with epoxygenase activity can also metabolize alternative polyunsaturated fatty acids such as linoleic acid and docosahexaenoic acid into a series of products including epoxyoctadacamonoenoic acids (EpOMEs) and 19,20-epoxydocosapentaenoic acid (EpDPE), respectively, whose functions remain poorly understood (3–5).The main polyunsaturated fatty acid-metabolizing CYPs belong to the CYP2 family, in particular the CYP2J and CYP2C subfamilies (3, 4, 6, 7). Moreover, these CYP-lipid–metabolizing enzymes are the primary sources of eicosanoids in small blood vessels, the kidney, liver, lung, intestines, heart, and pancreas (3, 7). In most organs, EETs and related epoxygenase products are metabolically unstable and are rapidly metabolized. The major pathway that regulates EET metabolism is that catalyzed by epoxide hydrolases (8), which convert EETs to less biologically active dihydroxyeicosatrienoic acids (DHETs) (9). EpOMEs similarly get converted into dihydroxyoctadecenoic acids (DiHOMEs), whereas 19,20-EpDPE gets converted into 19,20-dihydroxydocosapentaenoic acid (DiHDPA). Elevating the levels of endogenous CYP products by disrupting (knockout) or inhibiting soluble epoxide hydrolase (sEH) reduces neointima formation (10), atherosclerosis, abdominal aortic aneurysm, dyslipidemia (11), hypertension (12), and diabetes (13) in different mouse models, all of which to some extent one could argue have a degree of nonresolving inflammation.Over the last 15 y there has been a vast increase in our knowledge of fatty acid mediators that regulate inflammatory processes, particularly newly identified mediators such as the resolvins that mediate the resolution of inflammation (14–16). However, unlike cyclooxygenase and lipoxygenase products, the roles of CYP450 pathways in chronic inflammation remain unclear. The arachidonic acid products of the CYP epoxygenases, the EETs, can regulate vascular tone, smooth muscle cell mitogenesis, platelet aggregation, steroidogenesis, and endothelial and vascular smooth muscle cell activation (4, 5, 7, 17–19). We recently published that in human monocytes and macrophages, epoxygenases and some of their arachidonic acid products were antiinflammatory through their ability to activate the peroxisome proliferator-activated receptor (PPAR), in particular PPARα (20, 21). Overexpression of epoxygenase enzymes CYP2J2 and CYP2C8 or genetic disruption of sEH (sEH^−/−) inhibits LPS-induced pulmonary inflammation (22, 23), and sEH^−/− mice or treatment with sEH inhibitors is highly effective against inflammatory and neuropathic pain (24–27).Monocytes are heterogeneous in mice and in humans (28). In mice, monocyte subsets can be divided based on the expression of Ly6c, Gr1, CC-chemokine receptor 2 (CCR2), and CX3C-chemokine receptor 1 (CX3CR1). Ly6c^hi monocytes are Gr1⁺, CCR2⁺, and CX3CR1^lo, whereas Ly6c^lo monocytes are Gr1⁻, CCR2⁻, and CX3CR1^hi (29, 30). Lipid mediators that regulate the recruitment and phenotype of monocytes are poorly understood.Herein, using a sterile model of inflammatory resolution dependent on monocyte recruitment, we found that CYP-epoxygenase products not only accumulate in a temporal manner with monocyte recruitment but also limit proinflammatory monocyte recruitment and promote a proresolution phenotype in cells of the monocyte lineage.     

The association of Chlamydia trachomatis and Mycoplasma genitalium with non-gonococcal urethritis: observations on heterosexual men and their female partners

Our objectives were to study the distribution of Chlamydia trachomatis and Mycoplasma genitalium in men with or without non-gonococcal urethritis (NGU) and their respective female partners. A case-control study was carried out to which men with or without NGU and their female partners were recruited. All study participants were tested for the presence of C. trachomatis and M. genitalium. An analysis firstly of the distribution of each of these microorganisms among men with or without urethritis and their respective female partners was carried out. Furthermore, we examined the association of each of these microorganisms and NGU when the other had been excluded. Chlamydia trachomatis was present in 14 (36%) of 39 men with NGU compared to none of 12 men without NGU (P=0.022). The prevalence rates for female partners of men with NGU were 10 (26%) of 39 compared to none of 12 partners of men without NGU (P=0.092). M. genitalium was detected in 12 (33%) of 36 men with NGU compared to 1 (9%) of men without NGU (not significant; P=0.147). The prevalence rates for female partners of men with NGU were 10 (32%) of 31 women compared to none of 7 partners of men without NGU (not significant; P=0.156). There was a greater concordance than discordance of carriage of each of the 2 microorganisms among the study couples and each tended to be carried independently of the other by men. Analysis of the association between the presence of C. trachomatis in men and NGU was significantly improved by the exclusion of men with M. genitalium (P=0.0058). Likewise, the association between the presence of M. genitalium in men and NGU was significantly improved by the exclusion of couples in whom either the man or woman was C. trachomatis-positive (P=0.049). The independent carriage of C. trachomatis and M. genitalium by men with NGU, coupled with the improved association between each pathogen and NGU by exclusion of the other provides support for the separate role of each in the aetiology of NGU.     

Management guidelines for uninvestigated and functional dyspepsia in the Asia-Pacific region: First Asian Pacific working party on functional dyspepsia

Dyspepsia is most optimally defined as pain or discomfort centred in the upper abdomen. The symptom complex may be caused by peptic ulcer disease, gastro-oesophageal reflux, or gastric cancer but is most often due to functional (or non-ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the underlying cause of dyspepsia, it is expensive. A more pragmatic approach is needed in the Asia-Pacific region where health services are limited. A detailed treatment algorithm is given for managing patients presenting with new-onset dyspepsia and documented functional dyspepsia after endoscopy, and evidence to support this approach is reviewed. Prompt endoscopy is recommended for patients with alarm features. In patients without alarm features, treatment for 2–4 weeks with an empirical anti-secretory or prokinetic agent, followed by investigation using non-invasive Helicobacter pylori testing and treatment for patients who do not respond or relapse, is recommended. Trials of management strategies are now needed to establish the efficacy and cost-effectiveness of the approaches recommended.     

克泻灵片中苦参碱类生物碱的HPLC分析

目的:对克泻灵片中主要有效生物碱定性、定量。完善产品的质量控制及评价手段。方法:采用HPLC,紫外测定波长:220nm。结果:片剂中有有效生物碱以苦参碱类生物碱为主,其中苦参碱和槐定碱含量高,分别占总生物碱的14.2％～31.6％和22.6％～62.7％,其次为槐颗碱和槐胺碱,氧化苦参碱的含量很低。结论:建立了HPLC测定克泻灵片中主要生物碱,方法简便快捷,精密度好,回收率高,可用于制剂及原料的质量控制。