Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant.

Complement factor H-related protein 5 (CFHR5) nephropathy is a familial renal disease endemic in Cyprus. It is characterized by persistent microscopic hematuria, synpharyngitic macroscopic hematuria and progressive renal impairment. Isolated glomerular accumulation of complement component 3 (C3) is typical with variable degrees of glomerular inflammation. Affected individuals have a heterozygous internal duplication in the CFHR5 gene, although the mechanism through which this mutation results in renal disease is not understood. Notably, the risk of progressive renal failure in this condition is higher in males than females. We report the first documented case of recurrence of CFHR5 nephropathy in a renal transplant in a 53-year-old Cypriot male. Strikingly, histological changes of CFHR5 nephropathy were evident in the donor kidney 46 days post-transplantation. This unique case demonstrates that renal-derived CFHR5 protein cannot prevent the development of CFHR5 nephropathy.

"I don't know when it might pop up": understanding repeat HIV testing and perceptions of HIV among drug users.

PURPOSE: The study sought to understand the HIV testing patterns of low-income drug users. METHODS: Sixty-seven low-income drug users were recruited from street outreach venues in three San Francisco Bay Area counties. Participants were interviewed using an open-ended questionnaire eliciting information on HIV testing histories, sexual behavior, and drug use. Transcripts from interviews were coded and analyzed using methods consistent with the grounded theory approach of qualitative research. RESULTS: Participants identified four themes related to HIV testing: (1) anticipating positive results, (2) belief in a 10-year window period during which the virus is undetectable, (3) regular HIV testing as part of self-care, and (4) the HIV test as a means of control. These themes did not relate to personal risk behavior but rather to the community experience of HIV in small, dense populations of low-income drug users with high rates of HIV infection. IMPLICATIONS: Participants used HIV testing like regular mammograms or blood pressure checks, as if it were a screening procedure for a chronic illness. This is a reasonable response given the context of HIV within their communities. HIV testing in this population should not be limited.

This is my story: a descriptive analysis of a peer education HIV/STD risk reduction program for women living in housing developments.

Descriptive, qualitative data was collected from 30 women who participated in the Centers for Disease Control and Prevention-funded Perinatal HIV Reduction and Education Demonstration Activities (PHREDA) Project. Women were primarily heterosexual, welfare-dependent, African-American mothers. Staff trained women to conduct HIV/STD education as peer volunteers. The theory-based educational components consisted of role model stories developed by women about their experiences with HIV/STDs and discussion groups to build behavioral and communication skills. Women were given role-model stories and safer sex supplies to initiate conversations about women's health and sexual safety in their communities. PHREDA groups allowed women to identify their risk reduction, sexual, and family issues. Role model stories provided a validating medium through which high-risk women explored reproductive health risk and planned steps toward behavioral change. Descriptive data from peer volunteers can provide an important perspective on small group, peer-based community HIV/STD reduction interventions.

Managing HIV among serodiscordant heterosexual couples: serostatus, stigma and sex.

A qualitative study was conducted with 28 men and women in HIV-serodiscordant couples to explore the management of HIV in their relationship. Content analysis of the interviews revealed the role of serostatus and stigma in shaping partners' experience of HIV, sex and risk. Partners' differing serostatus often created feelings of alienation within the relationship. Compounding this interpersonal dynamic, the HIV service community was experienced as segregating because they were not funded or prepared to work with seronegative partners. Thus many, particularly seronegative women, felt invisible both within and outside of the relationship. Yet, the uninfected partners shared the burden of a stigmatizing illness because of the serodiscordant relationship. Stigma hindered communication about HIV and sex, disclosure to others and access to services. Many experienced HIV as a loss of their sexuality. Seronegative partners spoke about 'keeping sex alive' and often had to push to continue having sex. Couples used multiple strategies to manage HIV, including developing strict behavioural guidelines, connecting with other couples, accessing scientific information and becoming educators and activists. These altruistic activities, which also included participation in research, helped to transcend external and internalized stigma. Implications for developing interventions for HIV-serodiscordant couples are discussed.

The development of A-ring modified analogues of oestrone-3-O-sulphamate as potent steroid sulphatase inhibitors with reduced oestrogenicity.

Steroid sulphatases regulate the formation of oestrogenic steroids which can support the growth of endocrine-dependent breast tumours. The development of potent steroid sulphatase inhibitors could therefore have considerable therapeutic potential. Several such inhibitors have now been developed of which the most potent to date is oestrone-3-O-sulphamate (EMATE). Unexpectedly, this inhibitor proved to be a potent oestrogen. In an attempt to reduce the oestrogenicity, whilst retaining the potent sulphatase inhibitory properties associated with this type of molecule, a number of A-ring modified derivatives were designed and synthesized. A-ring modified compounds included the 2-methoxy, 2/4-nitro, 2/4-n-propyl and 2/4-allyl EMATE analogues. The ability of these derivatives to inhibit oestrone sulphatase activity was examined using placental microsomes. The allyl-substituted EMATE derivatives were more potent inhibitors than the propyl analogues but were all considerably less potent than EMATE. In contrast, the 2-methoxy and 2/4-nitro analogues were potent sulphatase inhibitors with 4-nitro EMATE being 5 times more active than EMATE. The 4-nitro, 2-methoxy, 4-n-propyl and 4-allyl derivatives were also tested in vivo for their oestrogenicity and ability to inhibit sulphatase activity. While both 4-nitro and 2-methoxy EMATE were potent inhibitors in vivo, 2-methoxy EMATE had no stimulatory effect on uterine growth in ovariectomized rats. The identification of a potent steroid sulphatase inhibitor lacking any oestrogenicity, such as 2-methoxy EMATE, should be of considerable value in evaluating the potential of steroid sulphatase inhibition for breast cancer therapy.