bluuebunny/crossref_metadata_2025 huggingface dataset:
The myeloproliferative disorder–associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3
Authors: Hookham Michelle B. , Elliott Joanne , Suessmuth Yvonne , Staerk Judith , Ward Alister C. , Vainchenker William , Percy Melanie J. , McMullin Mary Frances , Constantinescu Stefan N. , Johnston James A.
Published: February 2007

The somatic JAK2 valine-to-phenylalanine (V617F) mutation has been detected in up to 90% of patients with polycythemia and in a sizeable proportion of patients with other myeloproliferative disorders such as essential thrombocythemia and idiopathic myelofibrosis. Suppressor of cytokine signaling 3 (SOCS3) is known to be a strong negative regulator of erythropoietin (EPO) signaling through interaction with both the EPO receptor (EPOR) and JAK2. We report here that JAK2 V617F cannot be regulated and that its activation is actually potentiated in the presence of SOCS3. Instead of acting as a suppressor, SOCS3 enhanced the proliferation of cells expressing both JAK2 V617F and EPOR. Additionally, although SOCS1 and SOCS2 are degraded in the presence of JAK2 V617F, turnover of SOCS3 is inhibited by the JAK2 mutant kinase and this correlated with marked tyrosine phosphorylation of SOCS3 protein. We also observed constitutive tyrosine phosphorylation of SOCS3 in peripheral blood mononuclear cells (PBMCs) derived from patients homozygous for the JAK2 V617F mutant. These findings suggest that the JAK2 V617F has overcome normal SOCS regulation by hyperphosphorylating SOCS3, rendering it unable to inhibit the mutant kinase. Thus, JAK2 V617F may even exploit SOCS3 to potentiate its myeloproliferative capacity.
Cyclin D–Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization
Authors: Muntean Andrew G. , Pang Liyan , Poncz Mortimer , Dowdy Steven F. , Blobel Gerd A. , Crispino John D.
Published: February 2007

Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size. Although several transcription factors, including GATA-1 and RUNX-1, have been implicated in this process, the link between transcription factors and polyploidization remains undefined. Here we show that GATA-1–deficient megakaryocytes, which display reduced size and polyploidization, express nearly 10-fold less cyclin D1 and 10-fold increased levels of p16 compared with their wild-type counterparts. We further demonstrate that cyclin D1 is a direct GATA-1 target in megakaryocytes, but not erythroid cells. Restoration of cyclin D1 expression, when accompanied by ectopic overexpression of its partner Cdk4, resulted in a dramatic increase in megakaryocyte size and DNA content. However, terminal differentiation was not rescued. Of note, polyploidization was only modestly reduced in cyclin D1–deficient mice, likely due to compensation by elevated cyclin D3 expression. Finally, consistent with an additional defect conferred by increased levels of p16, inhibition of cyclin D-Cdk4 complexes with a TAT-p16 fusion peptide significantly blocked polyploidization of wild-type megakaryocytes. Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity.
Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT
Authors: Miller Jeffery S. , Cooley Sarah , Parham Peter , Farag Sherif S. , Verneris Michael R. , McQueen Karina L. , Guethlein Lisbeth A. , Trachtenberg Elizabeth A. , Haagenson Michael , Horowitz Mary M. , Klein John P. , Weisdorf Daniel J.
Published: February 2007

Natural killer (NK) cells can alter the outcome of hematopoietic cell transplantation (HCT) if donor alloreactivity targets the recipient. Since most NK cells express inhibitory killer-immunoglobulin receptors (KIRs), we hypothesized that the susceptibility of recipient cells to donor NK cell–mediated lysis is genetically predetermined by the absence of known KIR ligands. We analyzed data from 2062 patients undergoing unrelated donor HCT for acute myeloid leukemia (AML; n = 556), chronic myeloid leukemia (CML; n = 1224), and myelodysplastic syndrome (MDS; n = 282). Missing 1 or more KIR ligands versus the presence of all ligands protected against relapse in patients with early myeloid leukemia (relative risk [RR] = 0.54; n = 536, 95% confidence interval [CI] 0.30-0.95, P = .03). In the subset of CML patients that received a transplant beyond 1 year from diagnosis (n = 479), missing a KIR ligand independently predicted a greater risk of developing grade 3-4 acute graft-versus-host disease (GVHD; RR = 1.58, 95% CI 1.13-2.22; P = .008). These data support a genetically determined role for NK cells following unrelated HCT in myeloid leukemia.
Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines
Authors: Rodríguez Teresa , Méndez Rosa , Del Campo Ana , Jiménez Pilar , Aptsiauri Natalia , Garrido Federico , Ruiz-Cabello Francisco
Published: February 2007

Background

The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines.

Methods

Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan®Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells.

Results

Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway.

Conclusion

We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence of IFN-γ-mediated HLA class I expression in ESTDAB-159 cells is due to epigenetic blocking of IFN-regulatory factor 1 (IRF-1) transactivation.
A novel method for the evaluation of proximal tubule epithelial cellular necrosis in the intact rat kidney using ethidium homodimer
Authors: Edwards Joshua R , Diamantakos Evangelos A , Peuler Jacob D , Lamar Peter C , Prozialeck Walter C
Published: February 2007

Background

Ethidium homodimer is a cell-membrane impermeant nuclear fluorochrome that has been widely used to identify necrotic cells in culture. Here, we describe a novel technique for evaluating necrosis of epithelial cells in the proximal tubule that involves perfusing ethidium homodimer through the intact rat kidney. As a positive control for inducing necrosis, rats were treated with 3.5, 1.75, 0.87 and 0.43 mg/kg mercuric chloride (Hg2+, intraperitoneal), treatments which have previously been shown to rapidly cause dose-dependent necrosis of the proximal tubule. Twenty-four h after the administration of Hg2+, ethidium homodimer (5 μM) was perfused through the intact left kidney while the animal was anesthetized. The kidney was then removed, placed in embedding medium, frozen and cryosectioned at a thickness of 5 μm. Sections were permeabilized with -20°C methanol and then stained with 4',6-diamidino-2-phenylindole (DAPI) to label total nuclei. Total cell number was determined from the DAPI staining in random microscopic fields and the number of necrotic cells in the same field was determined by ethidium homodimer labeling.

Results

The Hg2+-treated animals showed a dose-dependent increase in the number of ethidium labeled cells in the proximal tubule, but not in other segments of the nephron. Other results showed that a nephrotoxic dose of gentamicin also caused a significant increase in the number of ethidium labeled cells in the proximal tubule.

Conclusion

These results indicate that this simple and sensitive perfusion technique can be used to evaluate cellular necrosis in the proximal tubule with the three-dimensional cyto-architecture intact.
Negative Regulation of c-Myc Transcription by Pancreas Duodenum Homeobox-1
Authors: Chen Lei , Yan He-Xin , Chen Jing , Yang Wen , Liu Qiong , Zhai Bo , Cao Hui-Fang , Liu Shu-Qin , Wu Meng-Chao , Wang Hong-Yang
Published: February 2007

The pancreatic and duodenal homeobox factor-1 (Pdx1) is essential for pancreatic development and insulin gene transcription, whereas c-Myc has a deleterious effect on islet function. However, the relationship between c-Myc and Pdx1 is poorly concerned. Here we demonstrated that Pdx1 could suppress c-Myc promoter activity, which relied on T cell factor (Tcf) binding elements harbored in c-Myc promoter. Furthermore, the transcription activity of β-catenin/Tcf was markedly decreased on Pdx1 expression, but cotransfection of Pdx1 short hairpin RNA abrogated this effect. Pdx1 expression did not induce β-catenin degradation nor did it alter their subcellular distribution. The mutation analysis showed that the amino acids (1–209) of Pdx1 harboring an inhibitory domain, which might lead to the reduction of β-catenin/Tcf/p300 complex levels and attenuate their binding activity with c-Myc promoter sequences. Moreover, adenovirus-mediated Pdx1 interference caused cell proliferation and cytokine-induced apoptosis via the dysregulation of c-Myc transcription. These results indicated that the Pdx1 functioned as a key regulator for maintenance of β-cell function, at least in part, through controlling c-Myc expression and the loss of its regulatory function may be an alternative mechanism for β-cell neogenesis and apoptosis found in diabetes.
Disruption of Prostate Epithelial Androgen Receptor Impedes Prostate Lobe-Specific Growth and Function
Authors: Simanainen Ulla , Allan Charles M. , Lim Patrick , McPherson Stephen , Jimenez Mark , Zajac Jeffrey D. , Davey Rachel A. , Handelsman David J.
Published: February 2007

Prostate development and maturation requires stromal-epithelial interactions and androgen action via the androgen receptor (AR) within these compartments. However, the specific roles of epithelial and stromal AR in postnatal prostate differentiation are unclear. We used Cre-LoxP technology to determine the prostate phenotype in mice with epithelial-selective genetic inactivation of the AR leaving the stromal AR functionally intact. We find that prostate development abolished in mice globally lacking a functional AR can be rescued by restricting the AR knockout to the postnatal prostate epithelium. We show that, at 8 wk of age, prostate epithelial AR knockout (PEARKO) mice exhibit prostate development with normal branching morphogenesis but lobe-specific decrease in prostate weight and hindered structural and functional differentiation of the mature prostate epithelium. No change was observed in PEARKO testis weight or serum testosterone compared with littermate controls. The most striking change was increased proliferation and abnormal lesions of epithelial cells predominantly in the anterior lobe of PEARKO mice. These findings highlight the vital role of stromal AR in postnatal prostate growth and structural differentiation and emphasize the requirement of epithelial AR in maintaining functional differentiation and restraining proliferation of epithelial cells in a lobe-specific manner. This unique PEARKO mouse provides a new paradigm with which to define the molecular mechanisms of the androgen signaling in mature prostate lobes in vivo and provides insight into the identification of better targets for treatment of prostate cancer and hyperplasia.
Lack of Gnas Epigenetic Changes and Pseudohypoparathyroidism Type Ib in Mice with Targeted Disruption of Syntaxin-16
Authors: Fröhlich Leopold F. , Bastepe Murat , Ozturk Defne , Abu-Zahra Hilal , Jüppner Harald
Published: February 2007

Pseudohypoparathyroidism type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to proximal renal tubular resistance to PTH but without evidence for Albright’s hereditary osteodystrophy. The disorder is paternally imprinted and affected individuals, but not unaffected carriers, show loss of GNAS exon A/B methylation, a differentially methylated region upstream of the exons encoding Gsα. Affected individuals of numerous unrelated kindreds with an autosomal dominant form of PHP-Ib (AD-PHP-Ib) have an identical 3-kb microdeletion removing exons 4–6 of syntaxin-16 (STX16) (STX16del4–6), which is thought to disrupt a cis-acting element required for exon A/B methylation. To explore the mechanisms underlying the regulation of exon A/B methylation, we generated mice genetically altered to carry the equivalent of STX16del4–6 (Stx16Δ4–6). Although the human GNAS locus shows a similar organization as the murine Gnas ortholog and although the human and mouse STX16/Stx16 regions show no major structural differences, no phenotypic or epigenotypic abnormalities were detected in mice with Stx16Δ4–6 on one or both parental alleles. Furthermore, calcium and PTH levels in Stx16Δ4–6 mice were indistinguishable from those in wild-type animals, indicating that ablation of the murine equivalent of human STX16del4–6 does not contribute to the development of PTH resistance. The identification of a novel intragenic transcript from within the STX16/Stx16 locus in total RNA from kidneys of Stx16Δ4–6 mice and lymphoblastoid cell-derived RNA of a patient with AD-PHP-Ib raises the question whether this transcript contributes, if deleted or altered, to the development of AD-PHP-Ib in humans.
Corporate Governance Reforms in Continental Europe
Authors: Enriques Luca , Volpin Paolo
Published: February 2007

The fundamental problem of corporate governance in the United States is to alleviate the conflict of interest between dispersed small shareowners and powerful controlling managers. The fundamental corporate governance in continental Europe and in most of the rest of the world is different. There, few listed companies are widely held. Instead, the typical firm in stock exchanges around the world has a dominant shareholder, usually an individual or a family, who controls the majority of the votes. In this essay, we begin by describing the differences in the ownership structure of companies in the three main economies of continental Europe—Germany, France, and Italy—with comparisons to the United States and the United Kingdom. We next summarize the corporate governance issues that arise in firms with a dominant shareholder. We take a look at a major European corporate scandal, Parmalat, as an extreme example of investor expropriation in a family-controlled corporation. We outline the legal tools that can be used to tackle abuses by controlling shareholders. Finally, we describe the corporate governance reforms enacted by France, Germany, and Italy between 1991 and 2005 and assess the way in which investor protection in the three countries has changed.
Payday Lending
Authors: Stegman Michael A
Published: February 2007

A “payday loan” is a short-term loan made for seven to 30 days for a small amount. Fees charged on payday loans generally range from $15 to $30 on each $100 advanced. A typical example would be that in exchange for a $300 advance until the next payday, the borrower writes a post-dated check for $300 and receives $255 in cash—the lender taking a $45 fee off the top. The lender then holds on to the check until the following payday, before depositing it in its own account. When the fee for a short-term payday loan is translated into an annual percentage rate, the implied annual interest rate ranges between 400 and 1000 percent. Virtually no payday loan outlets existed 15 years ago; today, there are more payday loan and check cashing stores nationwide than there are McDonald's, Burger King, Sears, J.C. Penney, and Target stores combined. For economists, several interesting issues arise in the study of payday loans: Is this just a situation in which willing customers and firms interact in the market for ready access to high-cost, short-term credit? Or does the payday loan industry encourage habitual borrowing and the snowballing of unaffordable debt in such a way that the state has a role to play in limiting consumers from their own excesses? Would a ban or overly restrictive regulations on payday lending just revive the market for loan-sharking? And what of a similar practice by mainstream banks, who regularly allow their customers to overdraw their checking accounts if they pay a fee comparable in size to a payday loan charge?
Daron Acemoglu: 2005 John Bates Clark Medalist
Authors: Shimer Robert
Published: February 2007

Daron Acemoglu, winner of the 2005 John Bates Clark Medal, uses theoretical and empirical analysis to tackle critical issues in a variety of fields in economics, including labor economics, macroeconomics, and political economy. His unparalleled combination of originality, thoroughness, and prolificacy has propelled him to the frontier of each field that he has explored. The Clark medal committee notes that “his work is always motivated by real-world questions that arise when facts are difficult to reconcile with existing theory.” Daron focuses on a core set of questions and uses the best tools available to answer them. What determines the accumulation of human capital both during formal schooling and on the job? How do the implications of labor market frictions depend on the information available to job searchers? How do economic incentives affect the type of technological change that we observe? Why are there such enormous differences in output per worker and total factor productivity across countries?
Cheating Ourselves: The Economics of Tax Evasion
Authors: Slemrod Joel
Published: February 2007

No government can announce a tax system and then rely on taxpayers' sense of duty to remit what is owed. Some dutiful people will undoubtedly pay what they owe, but many others will not. Over time the ranks of the dutiful will shrink, as they see how they are being taken advantage of by the others. Thus, paying taxes must be made a legal responsibility of citizens, with penalties attendant on noncompliance. But even in the face of those penalties, substantial tax evasion exists. Tax evasion is widespread, always has been, and probably always will be. This essay reviews what is known about the magnitude, nature, and determinants of tax evasion, with an emphasis on the U.S. income tax. It then places this information into a conceptual context, examining various models and theories, and considers policy implications.
Taxing Consumption and Other Sins
Authors: Hines James R
Published: February 2007

Federal and state governments in the United States use income and payroll taxes as their primary tools to collect revenue. Relative to the United States, governments in the rest of the world rely much more heavily on taxing consumption. Heavy American reliance on income rather than consumption taxation has not served the U.S. economy well. The inefficiency associated with taxing the return to capital means that the tax system reduces investment in the United States and distorts intertemporal consumption by Americans. While the economic logic of consumption taxation is compelling even for a closed economy, it is even more powerful for an open economy exposed to the world capital market. Consumption taxes in the form of excises can be designed to help protect the environment and control other externalities. Excise taxes can also serve the function of more closely aligning tax burdens with the benefits that taxpayers receive from certain government services. Understandable concerns arise about the distributional consequences of consumption taxation, but a system that relies heavily on consumption taxes, particularly if accompanied by an income tax, can be as progressive as any income tax the United States would realistically want to adopt.
The Goals and Promise of the Sarbanes–Oxley Act
Authors: Coates John C
Published: February 2007

The primary goal of the SarbanesOxley Act was to fix auditing of U.S. public companies, consistent with its full, official name: the Public Company Accounting Reform and Investor Protection Act of 2002. By consensus, auditing had been working poorly, and increasingly so. The most important, and most promising, part of SarbanesOxley was the creation of a unique, quasi-public institution to oversee and regulate auditing, the Public Company Accounting Oversight Board (PCAOB). In controversial section 404, the law also created new disclosure-based incentives for firms to spend money on internal controls, above increases that would have occurred after the corporate scandals of the early 2000s. In exchange for these higher costs, which have already fallen substantially, SarbanesOxley promises a variety of long-term benefits. Investors will face a lower risk of losses from fraud and theft, and benefit from more reliable financial reporting, greater transparency, and accountability. Public companies will pay a lower cost of capital, and the economy will benefit because of a better allocation of resources and faster growth. SarbanesOxley remains a work in progress -- section 404 in particular was implemented too aggressively - but reformers should push for continued improvements in its implementation, by PCAOB, rather than for repeal of the legislation itself.
A plea for more research on access to sexual health services
Authors: Fairley Christopher K , Williams Hennie , Lee David M , Cummings Rosey
Published: February 2007

Access to sexual health services, by those at highest risk of sexually transmitted infections (STI) is critical to effective STI control. Access to services is determined by the systems that clinics use to prioritize clients. However, despite there being thousands of sexual health services world wide, only three published studies in the last 25 years have specifically assessed changes in the process of access to STI clinics in which a control period was used. These studies indicate that appointments booked in advance provide the least access for higher risk clients, whereas both triage systems and systems with a significant proportion of same day appointments improve access. It is likely, however, that many services have changed their practices and evaluation of these changes could provide valuable data to improve the efficiency and hence improve STI control.
Immune reconstitution sarcoidosis presenting with hypercalcaemia and renal failure in HIV infection
Authors: Ferrand R A , Cartledge J D , Connolly J , Standish R A , Miller R F
Published: February 2007

An HIV-positive white man developed hypercalcaemia and renal failure 15 months after starting highly active antiretroviral therapy. Investigations showed systemic sarcoidosis affecting parotids, skin and kidneys. This presentation was thought to be a manifestation of immune reconstitution inflammatory syndrome, and the patient was successfully treated with corticosteroid therapy.
Multi-skeletal Pneumocystis jiroveci (carinii) in an HIV-seropositive patient
Authors: Panos George Z , Karydis Ioannis , Velakoulis Stamatios E , Falagas Matthew E
Published: February 2007

We present our experience with skeletal involvement of Pneumocystis jiroveci ( ex P. carinii) infection in an HIV-seropositive patient. The objective of this study was to alert clinicians to the possibility that extrapulmonary P. jiroveci could affect the skeletal system in HIV-infected patients with extremely rapid progression. P. jiroveci infection of skeletal system has been rarely described elsewhere. A 51-year-old man complained of fever for six weeks, cough, anorexia, fatigue, and chest pain. He was found to be HIV seropositive. Repetitive (six samples) sputum and bronchoalveolar lavage fluid microbiologic tests were negative. High-resolution chest computed tomography (CT) scan revealed a small pulmonary mass. Abdominal CT scan revealed lesions in liver, spleen, kidneys, adrenal glands, lumbar vertebrae, and sacrum. Brain and skull CT scan was normal. A fine-needle biopsy of the lung mass was unrevealing. Cytological examination of sputum specimens showed findings consistent with non-small-cell lung carcinoma. Nineteen weeks post-presentation, the patient reported low-back pain. Within 24 hours after the onset of low-back pain, he developed focal neurological deficits, and a magnetic resonance imaging (MRI) of the skull and spine showed osteolytic lesions of the temporal bones bilaterally, multiple vertebral lesions, and lesions of sacrum and iliac bones. Radiotherapy of the lumbar spine and pelvis was given. Sternal aspiration was performed. Cytological examination revealed P. jiroveci. In conclusion, we describe a rare case of disseminated P. jiroveci infection in an HIV-seropositive patient, with multiple skeletal lesions, especially in the skull and in vertebrae region, and concomitant non-small-cell lung cancer, with a very poor prognosis.
Persistent sexual arousal in a woman with associated cardiac defects and raised atrial natriuretic peptide
Authors: Bell C , Richardson D , Goldmeier D , Crowley T , Kocsis A , Hill S
Published: February 2007

The persistent sexual arousal syndrome (PSAS) is a newly described entity where the woman becomes involuntarily genitally aroused for extended periods of time in the absence of sexual desire and is distressed by this situation. The cause of this sexual problem is not well understood. We describe such a case where the subjective feelings were confirmed by observing genital engorgement. In her case, PSAS came on after initiation of fludrocortisone given for hypotension and bradycardia that was associated with an atrial septal defect (ASD). We argue that the combined effect of the ASD and fludrocortisone may be associated with an increase in her levels of atrial natriuretic peptide (ANP). ANP causes profound vasodilation and vascular leakage. We postulate that the high serum levels of ANP in her case may be contributory to her PSAS.
Three men, a paint brush and a coronavirus
Authors: MacConnachie A A , Collins T C , Seaton R A , Kennedy D H
Published: February 2007

Coronaviruses cause respiratory tract infection and a coryzal syndrome. Although described as a cause of gastroenteritis in HIV patients, with the exception of the severe acute respiratory syndrome (SARS), there is little in the literature about respiratory infection in HIV patients. We describe two patients with HIV, exacerbations of chronic obstructive pulmonary disease and proven coronavirus infection. A third patient presented with an upper respiratory tract infection but coronavirus was not isolated. All three men had spent a day decorating the first patient's flat four days prior to presentation. This is the first description of respiratory tract infection with coronavirus in HIV patients. Both patients with coronavirus required prolonged admission to hospital and extensive investigations because they were HIV infected. Coronavirus is often associated with less severe upper respiratory tract infection but can cause more severe disease and should be considered in patients with HIV and respiratory tract infection.
Do beliefs about HIV treatments affect peer norms and risky sexual behaviour among African-American men who have sex with men?
Authors: Bakeman Roger , Peterson John L ,   The Community Intervention Trial for Youth Study Team
Published: February 2007

We examined the association between perceptions about condom use among one's peers, beliefs about new HIV treatments, and HIV sexual risk behaviour among 849 young African-American men who have sex with men (MSM). Participants were randomly recruited from and anonymously interviewed in community venues in Atlanta, Georgia, USA, in cross-sectional samples between 1999 and 2002.

Data analyses indicated that 30% of the sample reported unprotected anal intercourse in the past three months; stronger peer condom norms predicted less-frequent risky sexual behaviour. However, the belief in less threat of HIV because of HIV treatments was not associated with either risky sexual behaviour or peer norms, and peer norms did not mediate the association between HIV treatment beliefs and unprotected anal intercourse.

These findings suggest that changing peer norms for condom use may reduce HIV risky sex in African-American MSM, regardless of their beliefs about HIV drug treatments.
Genital examination, microscopy and high vaginal swabs: are these valuable components of a sexually transmitted infection screen in asymptomatic women?
Authors: Green Pippa , Lacey Helen , Kasperowicz Regina
Published: February 2007

Improving access to genitourinary (GU) medicine services in the face of increasing demand and escalating rates of sexually transmitted infections (STIs) necessitates a review of current practice and modernization of service provision. At a time when GU medicine resources are limited and technology is available to perform non-invasive screening tests for chlamydia and gonorrhoea, we question the cost-effectiveness of routine genital examination, microscopy and culture of a high vaginal swab (HVS) in the management of asymptomatic women attending a GU medicine clinic. We conducted a case-note review of 206 consecutive asymptomatic female GU medicine clinic attendees who requested 'a check up'. We conclude that routine on-site microscopy of samples from the cervix, urethra and vagina, and laboratory culture of a HVS did not influence the outcome of patient care. No clinically significant genital tract pathology was identified on examination, with the possible exception of one woman in whom HSV1 was diagnosed opportunistically. The results of this study have significant implications for service provision and patient management.
Chlamydia screening in a rural population: access, outcomes and health-care planning
Authors: Bendall Richard P , Keane Frances E A , Barlow Maggie J , Paynter Stuart J
Published: February 2007

During the first year of a screening programme in Cornwall, a rural area of southwest England, 5024 young people were screened for genital Chlamydia trachomatis infection. We used mapping software to assess the prevalence of genital chlamydial infection and access to genitourinary medicine services among 16–25 year olds. Using this data, we calculated that attendance at genitourinary medicine clinics in Cornwall varies between 20/1000 and 83/1000 in this age group. Similarly, the rate of positive results varies between 2.9 and 27.4%, depending on place of residence and testing site. The highest rates of infection were noted in two areas with poor access to existing genitourinary medicine clinics. This information can be used to better plan sexual health services.
Thrombotic thrombocytopaenic purpura occurring in consecutive pregnancies in an HIV-infected patient
Authors: Robertson C , Wiselka M J
Published: February 2007

We present an HIV-infected patient who presented with thrombotic thrombocytopaenic purpura (TTP) during two consecutive pregnancies. To our knowledge, relapse of TTP during successive pregnancies in HIV infection has never been reported. This case reiterates that TTP should be considered in HIV-infected patients presenting with pregnancy-related complications.
Correlates of gonorrhoea among African Americans in North Carolina
Authors: Doherty Irene A , Adimora Adaora A , Schoenbach Victor J , Aral Sevgi O
Published: February 2007

Rates of gonorrhoea (GC) infections are highest among African Americans in the USA, but risk factors for GC in this population have not been well defined. The purpose of this study was to study these risk factors. We used secondary analysis of cross-sectional data from a population-based case-control study of African Americans, aged 18–59 years, in rural North Carolina, USA. A history of past infection was 2.4 times (95% confidence interval [CI]: 1.3, 4.4) as likely among men (35%) than women (18%). Among men, a history of gonorrhoea was associated with earlier age at first intercourse (adjusted Odds Ratio [aOR] = 2.0 95% CI [1.2, 3.4]), substance use (aOR = 4.4 95% CI [1.1, 17.9]), and having a partner who had been incarcerated (aOR = 18.1 [2.8, 118.0]). Among women, factors associated with GC included diagnosis of another STD (aOR = 5.9 [1.9, 16.9]), lifetime number of sex partners (aOR = 1.9 [1.1, 3.4]), and a sex partner who used drugs (aOR = 4.1 (1.3, 12.9)). In conclusion, African Americans with a history of GC are likely to have traditional STD risk factors, including partners at high risk for sexually transmitted disease (STD). STD screening is warranted upon entry to treatment facilities for substance abuse or correctional facilities.
Methamphetamine use and sexual risk behaviours among men who have sex with men diagnosed with early syphilis in Los Angeles County
Authors: Taylor Melanie M , Aynalem Getahun , Smith Lisa V , Montoya Jorge , Kerndt Peter
Published: February 2007

Methamphetamine use has been associated with risky sexual behaviour and sexually transmitted disease (STD)/HIV transmission among men who have sex with men (MSM). Field interview records for MSM early syphilis (ES) patients were reviewed for factors associated with methamphetamine use during January 2001 through December 2004. There were a total of 2915 ES cases reported during the study period. Of these, 1904 (65%) were MSM. Of these MSM, 167 reported methamphetamine use. Methamphetamine use was associated with having multiple sex partners (prevalence ratios [PR] 1.8, 95% confidence interval [CI] 1.4–2.4), not using condoms (PR 2.0, 95% CI 1.3–2.5), having anonymous sex partners (PR 1.1 95% CI 1.03–1.2), history of recent incarceration (PR 5.4, 95% CI 3.3–8.7), and meeting sex partners via the Internet (PR 1.6, 95% CI 1.3–2.1), at bathhouses (PR 1.6, 95% CI 1.2–2.0) and on the streets (PR 2.6, 95% CI 1.7–4.0). In multivariate analysis having multiple sex partners, not using condoms, recent incarceration and meeting sex partners at bathhouses were significantly associated with methamphetamine use. In conclusion, effective STD risk reduction interventions targeting MSM methamphetamine users are needed to curb risky sexual behaviour.
Audit of cervical cytology in HIV-positive women
Authors: Morris E J , Bates S
Published: February 2007

The National Health Service (NHS) cervical-screening programme has recently produced guidelines specifically for HIV-positive women. This includes annual cervical cytology screening and colposcopy to follow national guidelines. The case notes of all women attending Sheffield genitourinary clinic were audited. Of the 46 notes available, there was no documentation that annual screening has been offered in 26, and 10% of women did not have appropriate management of an abnormal smear. Information on the cytology form could result in a breach in confidentiality in cases where general practitioners are not aware of a patient's HIV status.
A case of successful management of recurrent bacterial vaginosis of neovagina after male to female gender reassignment surgery
Authors: Jain A , Bradbeer C
Published: February 2007

As sex reassignment surgeries become common and advanced, doctors are more likely to encounter cases with 'different' anatomy. Due to variations in examination and management as compared with non-transsexual patients, these cases generally prove challenging to the physicians. We present a case of recurrent bacterial vaginosis (BV) of neovagina in a transsexual patient successfully managed by using metronidazole gel and occasional douching. This case illustrates the difference in the microscopy of vaginal flora and management of BV in transsexual as compared with non-transsexual women.
Heterogeneity of risk among African-American men who have sex with men
Authors: Rothenberg Richard , Peterson John , Brown Mark , Kraft Joan Marie , Trotter Robert , Beeker Carolyn
Published: February 2007

The objective of this study was to examine the social mixing and sexual risk taking of African-American men who have sex with men (AAMSM). The design was a cross-sectional survey with targeted, ethnographically informed recruitment of respondents ( n = 95), and subsequent recruitment of their network partners ( n = 63). We ascertained current demographics, occupation, peer norms for sexual activity, community involvement, and information about members of their social and sexual network. Risk level was categorized by the frequency of anal sex and the consistency of condom use for anal sex. Twenty-nine of 158 (18.4%) persons were classified as being at high risk (any anal intercourse in the past three months with less than 100% condom use); 79 of 158 (50%) were at medium risk (any anal intercourse in the past three months with 100% condom use reported), and 50 (31.7%) were at low risk (no reported anal intercourse). The risk groups were similar with regard to perception of behavioural and community norms. White-collar workers associated predominantly with each other and other groups mixing preferentially with white-collar workers. Clustering within contact networks (the extent to which partners to a respondent know each other) was high for all risk groups (∼0.4–0.5), indicating dense, interactive networks. In conclusion, this study group demonstrates a greater degree of social mixing and heterogeneity than is commonly assumed for AAMSM. At least some portion of AAMSM has internalized public health messages about safer sexual activity. Intervention programmes should avoid the pitfalls of assumed homogeneity.
Developing sexually transmitted disease guidelines in the USA and the UK
Authors: FitzGerald Mark , Workowski Kimberly
Published: February 2007

Management guidelines for sexually transmitted diseases are reviewed and updated every four years at a workshop of experts convened by the US Centers for Disease Control and Prevention. They are disseminated in paper and electronic formats, and are widely accessed. Their recommendations are graded according to quality of evidence, benefits versus harms, and applicability. In the UK, guidelines are commissioned by the Clinical Effectiveness Group, following a specific methodology, then modified after consultation within the specialty of genitourinary medicine. Some issues are problematic for both guidelines, notably areas where the evidence is weak, where diagnostics and treatments are changing rapidly, and in knowing the extent to which guidelines actually influence practice.
Flexible booking systems to improve genitourinary medicine access and increase patient choice
Authors: Kellock D J , Bingwa E , Carlin E M
Published: February 2007

Access to genitourinary (GU) medicine services is crucial for the effective control of infection and it is well recognized that improved access to GU medicine will be required in order to meet a 48-hour access target. The object of this study was to evaluate whether access to our GU medicine service would be improved and the observed default rates decreased by the introduction of a partial closed booking system for new patients. The system was run in parallel to our standard appointment service and triage system. Data were collected for the first six months that the new system was operational, with additional data collection over the corresponding calendar periods of the subsequent two years. Approximately 26% of new patient appointments were booked through the partial closed booking system in the time periods specified. New patient appointment default rates fell from 26.8–30.5% in the standard appointment system to 7.5–9.5% in the partial closed booking system ( P < 0.0001). This study supports the importance of clinics adapting and providing a range of appointment system strategies as this may improve their clients' access to GU medicine services.
HIV infection and subfertility
Authors: Waters Laura , Gilling-Smith Carole , Boag Fiona
Published: February 2007

With the improvements in life expectancy and quality of life for HIV-infected individuals in the developed world, and the increasing rates of HIV transmission among heterosexuals, reproductive issues are becoming increasingly important. We discuss the management of conception and pregnancy in HIV-infected couples. Couples where one or both partners are HIV infected may also experience subfertility and in this article we review the methods available to treat subfertility in this population and the current guidelines for the use of these techniques. HIV-infected couples can enjoy normal, healthy lives and should have access to the same investigation and treatment as their HIV-negative counterparts. Current inequities in the treatment available must be addressed.
High prevalence of blood-borne virus infections and high-risk behaviour among injecting drug users in Tallinn, Estonia
Authors: Uusküla Anneli , McNutt Louise Anne , Dehovitz Jack , Fischer Krista , Heimer Robert
Published: February 2007

The HIV epidemic in Estonia is rapidly expanding, and injection drug users (IDUs) are the major risk group contributing to the expansion. A convenience sample of 159 IDUs visiting syringe-exchange programmes (SEPs) was selected to quantify the association of HIV-risk behaviours and blood-borne infections. A high prevalence of HIV, hepatitis B core antibody (HBVcore), hepatitis B surface antigen (HbsAg) and hepatitis C virus antibodies (56, 85.1, 21.3, and 96.2%, respectively) was associated with high-risk injections, unsafe sexual behaviour and alcohol abuse. These findings emphasize the importance of evidence-based secondary prevention among the HIV-infected, especially given the uncertain sustainability of antiretroviral and substance abuse treatments.
Treatment of vulvar intraepithelial neoplasia using topical imiquimod 5% cream in a genitourinary medicine clinic setting
Authors: McQuillan O , Morgan E
Published: February 2007

In the last five years, options for the treatment of vulvar intraepithelial neoplasia (VIN) have come to include the use of the immune response modifier imiquimod, following case reports of its efficacy in the USA and Europe. Despite topical imiquimod 5% cream being frequently prescribed for the treatment of ano-genital warts, there are no reports of it being used for the treatment of VIN in a genitourinary medicine setting. In this case report self-administered topical imiquimod 5% cream proved an effective treatment for undifferentiated VIN2/3 and should be considered as an alternative therapy in a genitourinary medicine setting.
Syphilis outbreak in Walsall, UK: lessons for control and prevention
Authors: Arumainayagam J , Pallan M J , Buckley E , Pugh R N , White D G , Morrall I A , Morris C , Chandramani S
Published: February 2007

An assessment of risk-taking behaviour among men who have sex with men (MSM) attending a sauna venue was undertaken, using a standardized questionnaire, after which outreach screening was introduced targeting MSM. The epidemiology of the continuing outbreak of syphilis was reviewed to determine the factors driving the outbreak and assess the benefit of continuing outreach screening. Findings among the 163 respondents at the sauna included a high rate of casual sex and a tendency not to disclose HIV status. Over 12 months, 51 cases of early syphilis were recorded. Our review showed a decline in incidence in MSM after outreach screening, but an increase in heterosexual spread. Given the frequent anonymous nature of syphilis transmission, traditional contact tracing is ineffective. Outreach screening is required at gay venues and other community settings to target at-risk populations.
Social science ethics: the changing context for research
Authors: Webster Andrew
Published: February 2007

This article looks at recent developments that have had an impact upon the way in which the ethical content of research is judged. It then goes on to look in some detail at the guidance offered to social science researchers in the Economic and Social Science Research Council's new Research Ethics Framework.
The challenge of lay membership of clinical ethics committees
Authors: Updale Eleanor
Published: February 2007

Most clinical ethics committees (CECs) have lay members. Why are they there, how are they chosen, and what do they do? Can their presence make health professionals less prone to jargon and hospital politicking, and can the lay members ever hope to represent the broad sweep of patients when many of them are white, middle class females? As hospital managers embrace CECs and even boast about them, will their informality be lost, with consequent exposure of professional and lay members to public scrutiny and criticism? Will brave, open discussion be stifled, and the purpose of the committees ultimately be lost?
Eugenics, embryo selection, and the Equal Value Principle
Authors: Wilkinson Stephen
Published: February 2007

Preimplantation genetic diagnosis and some prenatal screening programmes have been criticized for being 'eugenic'. This paper aims to analyse this criticism and to evaluate one of the main ethical arguments lying behind it. It starts with a discussion of the meaning of the term 'eugenics' and of some relevant distinctions: for example, that between objections to eugenic ends and objections to certain means of achieving them. Next, a particular argument against using preimplantation genetic diagnosis to 'screen out' disability is considered, one based on the Equal Value Principle, which says that we should value disability and non-disability equally. It is argued that present practice and policy probably do violate the Equal Value Principle, but that this principle is itself unsound.
Desmond's non-NICE choice: dilemmas from drug-eluting stents in the affordability gap
Authors: Mohindra Raj K , Hall Jim A
Published: February 2007

For medical interventions there is a gap between what clinical scientific research has established as likely to carry clinical benefit and what the National Institute for Clinical Excellence (NICE) has judged as cost-effective. This gap is the affordability gap. It is created by a value judgement made by NICE and affirmed by the Secretary of State for Health. This value judgement operates to affect other value judgements made in actual clinical situations where at least one choice of treatment falls into the affordability gap. This paper considers how the creation of this affordability gap impacts upon actual clinical decisions. It explores these issues in the context of the choice between a drug-eluting stent and a bare metal stent for elective coronary angioplasty. It also argues that the option of an NHS procedure with a top-up fee to cover the cost of the affordability gap is a genuine one; that this option could improve clinical outcomes; that it is morally acceptable; and that the rules that prevent the utilization of this option should be relaxed.