Abstract (provisional)
Background
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of multiple fluid-filled cysts that destroy the kidney architecture resulting in end-stage renal failure. Mutations in genes PKD1 and PKD2 account for nearly all cases of ADPKD. Increased cell proliferation is one of the key features of the disease. Several studies indicated that polycystin-1 regulates cellular proliferation through various signaling pathways, but little is known about the role played by polycystin-2, the product of PKD2. Recently, it was reported that as with polycystin-1, polycystin-2 can act as a negative regulator of cell growth by modulating the levels of the cyclin-dependent kinase inhibitor, p21 and the activity of the cyclin-dependent kinase 2, Cdk2.
Methods
Here we utilized different kidney cell-lines expressing wild-type and mutant PKD2 as well as primary tubular epithelial cells isolated from a PKD transgenic rat to further explore the contribution of the p21/Cdk2 pathway in ADPKD proliferation.
Results
Surprisingly, over-expression of wild-type PKD2 in renal cell lines failed to inactivate Cdk2 and consequently had no effect on cell proliferation. On the other hand, expression of mutated PKD2 augmented proliferation only in the primary tubular epithelial cells of a rat model but this was independent of the STAT-1/p21 pathway. On the contrary, multiple approaches revealed unequivocally that expression of the cyclin-dependent kinase inhibitor, p57KIP2, is downregulated, while p21 remains unchanged. This p57 reduction is accompanied by an increase in Cdk2 levels.
Conclusions
Our results indicate the probable involvement of p57KIP2 on epithelial cell proliferation in ADPKD implicating a new mechanism for mutant polycystin-2 induced proliferation. Most importantly, contrary to previous studies, abnormal proliferation in cells expressing mutant polycystin-2 appears to be independent of STAT-1/p21.
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Abstract (provisional)
Background
Maternal mortality remains poorly researched in Africa, and is likely to worsen dramatically as a consequence of HIV/AIDS.
Methods
The 2001 census of South Africa included a question on deaths in the previous 12 months, and two questions on external causes and maternal mortality, defined as “pregnancy-related deaths”. A microdata sample from the census permits researchers to assess levels and differentials in maternal mortality, in a country severely affected by high death rates from HIV/AIDS and from external causes.
Results
After correcting for several minor biases, our estimate of the Maternal Mortality Ratio (MMR) in 2001 was 542 per 100,000 live births. This level is much higher than previous estimates dating from pre-HIV/AIDS times. This high level occurred despite a relatively low proportion of maternal deaths (6.4%) among deaths of women aged 15-49 years, and was due to the astonishingly high level of adult mortality, some 4.7 times higher than expected from mortality below age 15 or above age 50. The main reasons for these excessive levels were HIV/AIDS and external causes of deaths. Our regional estimates of MMR were found to be consistent with other findings in the Cape Town area, and with the Agincourt DSS. The differentials in MMR were considerable: 1 to 9.2 for population groups (race), 1 to 3.2 for provinces, and 1 to 2.4 for levels of education. Relationship with income and wealth were complex, with highest values for middle income and middle wealth index. The effect of urbanization was small, and reversed in a multivariate analysis. Higher risks in provinces were not necessarily associated with lower income, lower education or higher proportions of home delivery, but correlated primarily with the prevalence of HIV/AIDS.
Conclusions
Demographic census microdata offer the opportunity to conduct an epidemiologic analysis of maternal mortality. In the case of South Africa, the level of MMR increased dramatically over the past 10 years, most likely because of HIV/AIDS. Indirect causes of maternal deaths appear much more important than direct obstetric causes. The MMR appears no longer to be a reliable measure of the quality of obstetric care or a measure of safe motherhood.
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Sexual dysfunction is not an inevitable part of aging, but it is strongly related a number of factors, such as mental and physical health, demographics and lifetime experiences, many of which are interrelated, according to a new study by researchers at the University of Chicago.The study, funded by the National Institutes of Health, found that a history of sexually transmitted disease also has an impact on sexual health later in life. People who had an STD are also more likely to have had sexual experiences over their lifetimes that included more risks and multiple sex partners.”Having had an STD roughly quadruples a woman’s odds of reporting sexual pain and triples her lubrication problems,” said Edward Laumann, the George Herbert Mead Distinguished Service Professor of Sociology at the University, and lead author of the paper, “Sexual Dysfunction Among Older Adults: Prevalence and Risk Factors from a Nationally Representative U.S. Probability Sample of Men and Women 57 to 85 Years of Age,” published in the current issue of the Journal of Sexual Medicine. Men are more than five times as likely to report sex as non-pleasurable if they have previously had an STD. Laumann was joined in writing the paper by University researcher Aniruddha Das, and Linda Waite, the Lucy Flower Professor in Sociology at the University.The study showed that women may be more likely than men to experience sexual dysfunction because of health issues. The most common problem for men is erectile dysfunction, a problem that increases with age. “The results point to a need for physicians who are treating older adults experiencing sexual problems to take into account their physical health and also consider their mental health and their satisfaction with their intimate relationship in making any assessment,” Laumann said. The study is based on interviews with a national sample of 1,550 women and 1,455 men, ages 57 to 85, who were part of the 2005-2006 National Social Life, Health and Aging Project, a nationally representative survey of community-dwelling older U.S. adults. The survey collected data on social life, sexuality, health, and a broad range of biological measures. The study is a companion to a 1999 study Laumann led that looked at sexual dysfunction among men and women, ages 18 to 59. That study found that physical health was a bigger predictor of sexual problems for men than it was for women. For that younger age group, having an STD did not increase the odds of experiencing sexual dysfunction. The new study found that among older women, a common factor correlated with sexual dysfunction was urinary tract syndrome, which was associated with decreased interest in sex, as were mental health issues such as anxiety.Among men, mental health issues and relationship problems contributed to a lack of interest in sex and the inability to achieve orgasm, while being treated for urinary tract syndrome was associated with trouble maintaining and achieving an erection.Daily alcohol consumption seems to improve a woman’s sexual health, increasing her interest and pleasure in sex. Among men, there was no reported impact of alcohol consumption.Demographic characteristics and cultural factors also are related to sexual performance, the study found. Hispanic women were twice as likely to report pain during intercourse. Among men, blacks were twice as likely to report a lack of interest in sex and more likely to report climaxing too early. The National Social Life, Health, and Aging Project is supported by several components of the National Institutes of Health, including the National Institute on Aging, the Office of Research on Women’s Health, the Office of AIDS Research and the Office of Behavioral and Social Sciences Research. The National Opinion Research Center, whose staff was responsible for the data collection, also supports the project.University of Chicago
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Background
Prior studies using creatinine-based estimated glomerular filtration rate (eGFR) have found limited associations between kidney function and markers of inflammation. Using eGFR and cystatin C, a novel marker of kidney function, the authors investigated the association of kidney function with multiple biomarkers in a diverse cohort.
Methods
The Multi-Ethnic Study of Atherosclerosis consists of 6,814 participants of white, African-American, Hispanic, and Chinese descent, enrolled from 2000-2002 from six U.S. communities. Measurements at the enrollment visit included serum creatinine, cystatin C, and six inflammatory and procoagulant biomarkers. Creatinine-based eGFR was estimated using the four-variable Modification of Diet in Renal Disease equation, and chronic kidney disease was defined by an eGFR < 60 mL/min/1.73m2.
Results
Adjusted partial correlations between cystatin C and all biomarkers were statistically significant: C-reactive protein (r=0.08), interleukin-6 (r=0.16), tumor necrosis factor-alpha soluble receptor 1 (TNF-alphaR1; r=0.75), intercellular adhesion molecule-1 (r=0.21), fibrinogen (r=0.14), and factor VIII (r=0.11; two-sided p<0.01 for all). In participants without chronic kidney disease, higher creatinine-based eGFR was associated only with higher TNF-alphaR1 levels.
Conclusions
In a cohort characterized by ethnic diversity, cystatin C was directly associated with multiple procoagulant and inflammatory markers. Creatinine-based eGFR had similar associations with these biomarkers among subjects with chronic kidney disease.
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Background
The main hypothesis of this study is that Oxpentifylline administration will effectively treat erythropoietin- or darbepoietin-resistant anaemia in chronic kidney disease patients.
Methods
Inclusion criteria are adult patients with stage 4 or 5 chronic kidney disease (including dialysis patients) with significant anaemia (haemoglobin less than or equal to 110 g/L) for at least 3 months for which there is no clear identifiable cause and that is unresponsive to large doses of either erythropoietin (greater than or equal to 200 IU/kg/week) or darbepoetin (greater than or equal to 1 microgram/kg/week). Patients will be randomized 1:1 to receive either placebo (1 tablet daily) or oxpentifylline (400 mg daily) per os for a period of 4 months. During this 4 month study period, haemoglobin measurements will be performed monthly. The primary outcome measure will be the difference in haemoglobin level between the 2 groups at the end of the 4 month study period, adjusted for baseline values. Secondary outcome measures will include erythropoiesis stimulating agent dosage, Key’s index (erythropoiesis stimulating agent dosage divided by haemoglobin concentration), and blood transfusion requirement.
Discussion
This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their chronic kidney disease patients determine whether oxpentifylline represents a safe and effective strategy for treating erythropoiesis stimulating agent resistance in chronic kidney disease. Trial Registration: Australian Clinical Trials Registry Number ACTRN12608000199314.
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Background
We examine whether practices in areas with higher risks of CHD prescribe different levels of cardiovascular drugs and describe how they differ in GP and practice characteristics.
Methods
Propensity score matching was used to identify two groups of practices in Scotland. The cases were in areas with 5% or more of the population in South Asian ethnic groups. The controls were in areas with less than 1% of the population in South Asian ethnic groups and were matched for other population characteristics.
Results
The 39 case practices have lower prescribing rates than the matched controls for all heart disease drugs Significant different are found for six drugs (statins, ace Inhibitors, clopidogrel, thiazides, warfarin and digoxin. The differences range from 12.8% less for amlodipine to 43.9% for clopidogrel. The case practices also have lower prescribing costs than the unmatched group with the exception of ace inhibitors and aspirin. The highest prescribing costs for all drugs are found in the matched control group. The case practices are smaller than the controls, and have fewer GPs per 1,000 patients. Case practices have fewer quality markers and receive less in total resources, but have higher sums reimbursed to cover their employed staff costs.
Conclusion
Patients with higher risk of CHD tend to live in areas served by practices with lower prescribing rates and poorer structural characteristics. The scale of the differences in prescribing suggests that health care system factors rather than individual treatment decisions cause inequity in care. Identifying whether South Asian individuals are less likely to receive heart disease drugs than non South Asians requires individual-level prescribing data, which is currently not available in the UK.
Background
In 2003 CHD was second only to cancer as the major cause of mortality in Scotland. [1] Although CHD mortality has fallen in recent years death rates from CHD are amongst the highest in the world and the second highest in Western Europe. [2] There is a strong correlation between increasing incidence and mortality from CHD and deprivation. CHD is also the major cause of morbidity and mortality in the South Asian population in the United Kingdom. [3] South Asians have been found to be at increased risk compared to the rest of the population of England and Wales [4] by at least 40 percent. [5-7] Though Scotland has one of the worst incidences of heart disease in Europe [8] only one of the 19 studies identified in Bhopal’s review was based in Scotland. [4,9]
The concept of equity is a central objective of most health care systems in the developed world. While governments from across the political spectrum, both in the UK and internationally, have attempted to tackle perceived inequities in health care the concept of equity remains somewhat elusive. [10,11] A theoretical framework has been set out which examines equity through three domains: equal access to health care for people in equal need; equal treatment for people in equal need; and equal outcomes for people in equal need. [11] This simple framework has been used as a basis to examine the equity of GP prescribing rates for statins and five major CHD drug groups focused around the equal treatment in equal need domain. [12,13] These papers are amongst a growing body of work in the UK, which have focused on equity of prescribing. However, these studies have largely been confined to England and Wales. The purpose of this paper is to explore the equity of prescribing for a range of heart disease drugs in Scotland. Having established prescribing differences, the analysis then considers structural differences in GP and practice provision. Using a matching technique, we use examine the notion of equal treatment for people in equal need and how this relates to differences in equal access to health care.
Many patients do not receive the appropriate treatment for CHD. Research has found that prescribing rates of statins and lipid lowering drugs were negatively correlated with deprivation. [9,14] The Acheson report highlighted the need for studies of ethnic inequalities. [15] Several studies have highlighted ethnic variations in access to and provision of hospital interventions. [16,17] Although a more recent study found no evidence that South Asian ethnicity was associ
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User fees were introduced in public health facilities in Cambodia in 1997 in order to inject funds into the health system to enhance the quality of services. Because of inadequate health insurance, a social safety net scheme was introduced to ensure that all people were able to attend the health facilities. However, continuing high rates of hospitalization and mortality from dengue fever among infants and children reflect the difficulties that women continue to face in finding sufficient cash in cases of medical emergency, resulting in delays in diagnosis and treatment. In this article, drawing on in-depth interviews conducted with mothers of children infected with dengue in eastern Cambodia, we illustrate the profound economic consequences for households when a child is ill. The direct costs for health care and medical services, and added indirect costs, deterred poor women from presenting with sick children. Those who eventually sought care often had to finance health spending through out-of-pocket payments and loans, or sold property, goods or labour to meet the costs. Costs were often catastrophic, exacerbating the extreme poverty of those least able to afford it.
Background
Resource-poor countries have long struggled to control infectious disease, reduce mortality and severe morbidity, and improve childhood survival rates with inadequate resources that are echoed in delayed diagnosis and poor service delivery at local levels. From the 1980s, various financing systems have been introduced to supplement government budgetary allocations, loans and bilateral aid, to deter the unnecessary use of health services, and from 1988, to improve access to and quality of services. The Bamako Initiative in particular emphasised the introduction of user fees, specifically to supplement the budgets of local health facilities, meeting salary and supply shortfalls, and so improve access and quality.
In an review published a decade ago, still apposite, Gilson notes the lack of attention to the ability of poor households to pay fees, and the effects of user fees on health seeking and treatment [1]. Subsequent studies in low and middle-income countries on the relationship between user fees and the utilization of public health services support claims that direct costs discourage presentation by poor people [2-5]. In Ghana, user fees have been shown to discourage presentation for antenatal and midwifery care, and consequently contribute to continued high maternal and neonatal mortality [6]. In Tanzania, despite general willingness to pay when quality of care at lower-level health facilities was improved, the very poor, women and elderly were negatively affected [7]; in Niger, user fees also resulted in declining patients’ attendance and variable cost recovery [8]. The current view therefore is that minimally, there need to be effective safety nets for poor and vulnerable households, with alternative approaches to user fees such as micro-health insurance and/or exemptions and waivers from cost sharing [7,9,10].
These studies, like those cited by Gilson [1,11], have largely been conducted in Africa. Yet despite the local impact of the Bamako Initiative (1988), health financing reforms to supplement government funds have been introduced far more extensively. One study in Laos produced similar results to the African studies, drawing attention to the negative impact of user fees on the very poor [12], but relatively little research has been conducted in Asia on user fees and health seeking behaviour. This is particularly important when early diagnosis and treatment is critical for individual outcomes and where prompt medical care is a cornerstone of control. This is the case for various infections, including acute respiratory infection, tuberculosis, malaria, and dengue fever, which predominate in resource-poor settings.
Appropriate funding mechanisms are necessary to ensure equitable access to health care. The costs of health care to consumers, and the sources from which money is derived to pay for health care, are therefore important from a policy perspective, because the health care system in Cambodia is heavily based on fees. In Cambodia, user fees were introduced in 1997 as a component of a broader suite of health care reforms introduced to generate cash to supplement the basic low salaries of health staff, so to motivate staff and discourage them from seeking unofficial payments from patients or undertaking extra jobs during official working time. Cash generated from user fees was also expected to contribute to the operational costs of health facilities, so improving the quality of health care. To ensure that the reforms would not prevent poor people from using government health facilities, the Ministry of Health
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Objective
Prior to 2007, forced sex with male children in South Africa did not count as rape but as “indecent assault”, a much less serious offence. This study sought to document prevalence of male sexual violence among school-going youth.
Design
A facilitated self-administered questionnaire in nine of the 11 official languages in a stratified (province/metro/urban/ rural) last stage random national sample. Setting: Teams visited 5162 classes in 1191 schools, in October and November 2002. Participants: A total of 269,705 learners aged 10-19 years in grades 6-11. Of these, 126,696 were male. Main outcome measures: Schoolchildren answered questions about exposure in the last year to insults, beating, unwanted touching and forced sex. They indicated the sex of the perpetrator, and whether this was a family member, a fellow schoolchild, a teacher or another adult. Respondents also gave the age when they first suffered forced sex and when they first had consensual sex.
Results
Some 9% (weighted value based on 13915/127097) of male respondents aged 11-19 years reported forced sex in the last year. Of those aged 18 years at the time of the survey, 44% (weighted value of 5385/11450) said they had been forced to have sex in their lives and 50% reported consensual sex. Perpetrators were most frequently an adult not from their own family, followed closely in frequency by other schoolchildren. Some 32% said the perpetrator was male, 41% said she was female and 27% said they had been forced to have sex by both male and female perpetrators. Male abuse of schoolboys was more common in rural areas while female perpetration was more an urban phenomenon.
Conclusions
This study uncovers endemic sexual abuse of male children that was suspected but hitherto only poorly documented. Legal recognition of the criminality of rape of male children is a first step. The next steps include serious investment in supporting male victims of abuse, and in prevention of all childhood sexual abuse.
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