RBBP6 Is Abundantly Expressed in Human Cervical Carcinoma and May Be Implicated in Its Malignant Progression.

RBBP6 is a novel gene encoding splicing-associated proteins. There are 3 protein isoforms (isoforms 1-3). RBBP6 isoforms 1 has been shown to interact with both p53 and Rb. It also plays a role in the induction of apoptosis and the regulation of the cell cycle. The expression of RBBP6 has been documented in several cancers but RBBP6 expression in cervical cancer has not been well studied. The aim of this study was to establish expression levels and tissue distribution of the RBBP6 gene products at both protein and messenger RNA (mRNA) levels in cervical cancer by immunocytochemistry and in situ hybridization (ISH). A link between RBBP6 expression, apoptosis, and cervical cancer progression was also investigated. RBBP6 mRNA was expressed in the nuclei and cytoplasm of normal and tumour cervical epithelium. In general, expression was high in the cytoplasm and nuclei of moderately differentiated and invasive carcinoma. Immunolabelling results were confirmed by image analysis and ISH experiments. Apoptosis assays using TUNEL correlated with the expression of the RBBP6 gene in all examined cases. This is the first report on the abundant expression of RBBP6 in cervical cancer and its involvement in the malignant progression of cervical cancer. Because of the high expression and corresponding pro-apoptotic activity observed in cervical cancer cells in this study, we suggest that RBBP6 is involved in the malignant progression of cervical cancer. RBBP6 proteins can therefore be targeted for therapeutic interventions against cervical cancer.

Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD): Study Protocol for Establishing a Core Outcome Set in PD.

BACKGROUND: Worldwide, approximately 11% of patients on dialysis receive peritoneal dialysis (PD). Whilst PD may offer more autonomy to patients compared with hemodialysis, patient and caregiver burnout, technique failure, and peritonitis remain major challenges to the success of PD. Improvements in care and outcomes are likely to be mediated by randomized trials of innovative therapies, but will be limited if the outcomes measured and reported are not important for patients and clinicians. The aim of the Standardised Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) study is to establish a set of core outcomes for trials in patients on PD based on the shared priorities of all stakeholders, so that outcomes of most relevance for decision-making can be evaluated, and that interventions can be compared reliably. METHODS: The 5 phases in the SONG-PD project are: a systematic review to identify outcomes and outcome measures that have been reported in randomized trials involving patients on PD; focus groups using nominal group technique with patients and caregivers to identify, rank, and describe reasons for their choice of outcomes; semi-structured key informant interviews with health professionals; a 3-round international Delphi survey involving a multi-stakeholder panel; and a consensus workshop to review and endorse the proposed set of core outcome domains for PD trials. DISCUSSION: The establishment of 3 to 5 high-priority core outcomes, to be measured and reported consistently in all trials in PD, will enable patients and clinicians to make informed decisions about the relative effectiveness of interventions, based upon outcomes of common importance.

Changes in the worldwide epidemiology of peritoneal dialysis.

As the global burden of chronic kidney disease continues to increase, so does the need for a cost-effective renal replacement therapy. In many countries, patient outcomes with peritoneal dialysis are comparable to or better than those with haemodialysis, and peritoneal dialysis is also more cost-effective. These benefits have not, however, always led to increased utilization of peritoneal dialysis. Use of this therapy is increasing in some countries, including China, the USA and Thailand, but has proportionally decreased in parts of Europe and in Japan. The variable trends in peritoneal dialysis use reflect the multiple challenges in prescribing this therapy to patients. Key strategies for facilitating peritoneal dialysis utilization include implementation of policies and incentives that favour this modality, enabling the appropriate production and supply of peritoneal dialysis fluid at a low cost, and appropriate training for nephrologists to enable increased utilization of the therapy and to ensure that rates of technique failure continue to decline. Further growth in peritoneal dialysis use is required to enable this modality to become an integral part of renal replacement therapy programmes worldwide.

Nephrology training curriculum and implications for optimal kidney care in the developing world.

An effective workforce is essential for delivery of high-quality chronic disease care. Low-income nations are challenged by a dearth and/or maldistribution of an essential workforce required for all chronic disease care including chronic kidney disease (CKD). Nephrology education and training in developed countries have grown at pace with the technological advancement in the practice of medicine in order to meet the standards required of kidney health professionals towards high-quality, patient-centered medical care. The standards designed by institutions and/or professional societies, such as Royal Colleges and Medical Councils in high-income nations with well-developed health systems and infrastructures, are often not easily translatable to issues critical to nephrology practice in low-income nations. Little or no guidance is provided on common nephrological issues of regional nature or pertaining to ethnic minorities and disadvantaged groups living in those countries. There is an emergent need for a training curriculum that meets the needs and peculiarities of the developing nations, and this needs to leverage on the existing and well-validated systems of training across the globe. We evaluated nephrology training programs across 25 upper-middle and high-income nations to identify best practices and opportunities for adoption in low-income nations. We reviewed training guidelines from major professional societies on content and process of training. There are similarities and differences in structure, content, and process of training programs across countries, and there are clearly adoptable concepts/frameworks for application in low-income nations. We provide recommendations and a strategic plan for the future focus of nephrology training in the developing world to align with current trends in technological advancement and development as well as the need for emphasis on prevention of CKD. The essential competencies (patient- and population--based) required of a nephrologist in a developing world setting are outlined with practical measures and an action plan for adoption.

Expression analysis and association of RBBP6 with apoptosis in colon cancers.

Apoptosis is normally kept under strict control by a range of regulators and inhibitors, and loss of this regulation strongly directs tumour progression. The novel RBBP6 gene has been implicated in apoptosis due to its ability to bind both p53 and Rb, as well as its structural and functional affiliation to ubiquitin and E3 ligases. RBBP6 has already been implicated as an important marker for cancer diagnosis and many studies have investigated its suitability as a potential genetic target for cancer treatment. This study endeavoured to assess the transcription and expression patterns and levels of the three isoforms of RBBP6 in colon cancer and to evaluate its potential role in apoptosis. Colorimetric and fluorescent in situ hybridisation was used to localise the mRNA and the different RBBP6 mRNA transcripts in normal and cancerous colon tissue. Immunohistochemistry was used to localise different RBBP6 isoforms in normal and cancerous tissues. All the RBBP6 transcripts were found to be up-regulated in cancerous tissues, and the expression levels of the RBBP6-1 and RBBP6-3 (DWNN) proteins were also found to be increased in cancerous structures. Higher levels of apoptosis were detected in the same regions as those that showed increased expression of RBBP6-3 transcript and protein, whereas Bcl-2 was down-regulated in these areas. In contrast we observed an increase in Bcl-2 levels in areas where RBBP6-3 was down-regulated. These results suggest that the RBBP6-3 isoform may be involved in promoting apoptosis in cancerous cells.

An effective approach to chronic kidney disease in South Africa.

Very few patients with end-stage kidney disease in South Africa receive renal replacement treatment (RRT), despite the rapidly growing demand, because of resource constraints. Nephrologists who agonise daily about who to treat and who not to, and have been doing so since the inception of dialysis in this country, welcomed the opportunity to interact with the National Department of Health at a recent summit of stakeholders. The major challenges were identified and recommendations for short- to long-term solutions were made. While the renal community can still improve efficiencies, it is clear that much of the responsibility for improving access to RRT and reducing inequities must be borne by the national government. The summit marks the first step in a process that we hope will ultimately culminate in universal access to RRT for all South Africans.

The association of RBBP6 variant 3 expressions with apoptosis in human immunodeficiency virus-associated nephropathy (HIVAN).

South Africa has one of the highest HIV infection rates in the world. One of the complications of HIV infection is the development of HIV-associated nephropathy (HIVAN), which is characterized by deregulation in tubular epithelial apoptosis. The pathways that HIV-1 promotes in the pathogenesis of HIVAN remain less understood. There are many genes that have not been characterized in the pathogenesis of HIVAN. On the other hand, RBBP6 has been shown to play a role in both promoting and inhibiting apoptosis in human cancers. This study was aimed at determining an association between RBBP6 isoform 3 expression and the levels of apoptosis in HIVAN cases. HIVAN biopsy tissues from Johannesburg patients in South Africa were used in this study. These tissues were stained for RBBP6 expression and apoptosis levels using immunohistochemistry staining and TUNEL method respectively. Image analysis was used for quantitative analysis and GraphPad Version 4 was used for statistical analysis. High expression levels of RBBP6 were found in HIVAN cases (n=30) relative to the normal tissues (n=10). High apoptosis levels were also obtained in the HIVAN tissues. This direct association between RBBP6 expression and apoptosis levels suggests that RBBP6 may play a role in HIVAN pathogenesis. RBBP6 may then be targeted for both diagnostic and therapeutic strategies in HIVAN.

How to advocate for the inclusion of chronic kidney disease in a national noncommunicable chronic disease program.

Many countries are developing or refining national strategies for noncommunicable chronic disease (NCD) prevention and control. Chronic kidney disease (CKD) is a cause and consequence of other NCDs; CKD acts as a risk multiplier for all four key NCDs as specified by the World Health Organization; CKD is associated with high health-care costs; CKD is readily identifiable; and treatment of CKD is cost-effective and improves outcomes. These observations argue in favor of including CKD in national NCD programs. The purpose of this article is to outline key steps in advocating for the inclusion of CKD in national NCD strategies.

Africa and nephrology: the forgotten continent.

Chronic kidney disease (CKD) is not a priority on the health agenda in Africa and it remains a 'forgotten condition'. Most people in Africa do not have access to dialysis or transplantation, if they develop end-stage renal disease. Cardiovascular disease (CVD) and HIV/AIDS enjoy a more prominent profile as a serious cause of morbidity and mortality, but despite the clear links of CVD and HIV with CKD, there has been a failure to highlight the link between chronic illnesses like diabetes, hypertension and HIV/AIDS and both CKD and CVD. Management of chronic illnesses requires a functioning public health system and good links between primary and specialist care. Despite calls to establish CKD prevention programs, there are very few in Africa and they have not been integrated into existing primary healthcare systems. This is aggravated by shortages of both financial and human resources and failure to strengthen health systems managing chronic diseases. The result is that very few people in Africa with CKD are managed early or receive dialysis or transplantation. This article investigates some of the issues impacting on the recognition of CKD as a public health issue, and will also consider some factors which could make CKD a more prominent chronic disease in Africa.

Managing type 2 diabetes in Soweto-The South African Chronic Disease Outreach Program experience.

Diabetes (DM) and its resultant complications are a problem worldwide, and especially in developing countries like South Africa (SA). Risk factors associated with DM are potentially modifiable, but DM control is poor. Problems in SA include high prevalence of morbidity from DM and hypertension (HTN), lack of recognition of the importance of chronic kidney disease (CKD), late presentation to health care services, lack of education of health providers and patients, and poor quality of care in primary health care settings (PHC). In response, there has been growing advocacy for prevention strategies and improved support and education for primary health care nurses (PHCNs). A Chronic Disease Outreach Program (CDOP), based on the chronic care model was used to follow patients with DM and HTN, support PHCN, and improve health systems for management in Soweto. A group of 257 DM patients and 186 PHCN were followed over 2 years, with the study including the evaluation of 'functional' and clinical outcomes, diary recordings outlining program challenges, and a questionnaire assessing PHCNs' knowledge and education support, and the value of CDOP. CDOP was successful in supporting PHCNs, detecting patients with advanced disease, and ensuring early referral to a specialist center. It improved early detection and referral of high risk, poorly controlled patients and had an impact on PHCNs' knowledge. Its weaknesses include poor follow up due to poor existing health systems and the programs' inability to integrate into existing chronic disease services. The study also revealed an overworked, poorly supported, poorly educated and frustrated primary health care team.

Guideline for the management of nosocomial infections in South Africa.

OBJECTIVE: To write a guideline for the management and prevention of nosocomial infections in South Africa in view of the following: Nosocomial infections are a common and increasing problem globally, including South Africa. Widely varying standards of prevention and management of these important infections. Increasing and emerging antimicrobial resistance among commonly isolated pathogens. The significant economic burden of these infections on the health care system as well as their impact on patient morbidity and mortality. The main aims of the guideline are to provide recommendations for the initial choice of antimicrobial agents and the appropriate management of these infections encompassing the following conditions: (i) nosocomial pneumonia, health care-associated pneumonia and ventilator-associated pneumonia; (ii) nosocomial bloodstream infections; (iii) nosocomial intravascular infections; (iv) nosocomial urinary tract infections; (v) nosocomial intra-abdominal infections; and (vi) nosocomial surgical skin and soft-tissue infections. EVIDENCE: Working group of clinicians from relevant disciplines, following detailed literature review. RECOMMENDATIONS: These include details of the likely pathogens, an appropriate diagnostic approach, antibiotic treatment options and appropriate preventive strategies. ENDORSEMENT: The guideline document was endorsed by the South African Thoracic Society, the Critical Care Society of Southern Africa and the Federation of Infectious Diseases Societies of Southern Africa.

Prevention of chronic kidney and vascular disease: toward global health equity--the Bellagio 2004 Declaration.

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment.

Guidelines for the treatment and management of new-onset diabetes after transplantation.

Although graft and patient survival after solid organ transplantation have improved markedly in recent years, transplant recipients continue to experience an increased prevalence of cardiovascular disease (CVD) compared with the general population. A number of factors are known to impact on the increased risk of CVD in this population, including hypertension, dyslipidemia and diabetes mellitus. Of these factors, new-onset diabetes after transplantation has been identified as one of the most important, being associated with reduced graft function and patient survival, and increased risk of graft loss. In 2003, International Consensus Guidelines on New-onset Diabetes after Transplantation were published, which aimed to establish a precise definition and diagnosis of the condition and recommend management strategies to reduce its occurrence and impact. These updated 2004 guidelines, developed in consultation with the International Diabetes Federation (IDF), extend the recommendations of the previous guidelines and encompass new-onset diabetes after kidney, liver and heart transplantation. It is hoped that adoption of these management approaches pre- and post-transplant will reduce individuals' risk of developing new-onset diabetes after transplantation as well as ameliorating the long-term impact of this serious complication.

Demographic and epidemiologic transition in the developing world: role of albuminuria in the early diagnosis and prevention of renal and cardiovascular disease.

The developing world is facing a real pandemic of renal and cardiovascular disease. With the decrease of infectious disease morbidity and mortality, and the exposure to more westernized life style, signs of increasing renal and cardiovascular disease is particularly shown in the tremendous rise in type 2 diabetes and its sequelae. A group of doctors and scientists from all over the world have convened in Bellagio to halt this dramatic disease change and burden to the developing countries. They came to the conclusion that screening and treatment should clearly focus on cost-beneficial strategies, among which blood pressure and urinary albumin measurement, as well as effective and affordable treatment strategies to lower blood pressure and albuminuria, are essential.

Molecular genetics of human cervical cancer: role of papillomavirus and the apoptotic cascade.

Cervical cancer is rated the second most common malignant tumour globally, and is aetiologically linked to human papillomavirus (HPV) infection. Here the cellular pathology under consideration of stem/progenitor cell carcinogenesis is reviewed. Of the three causative molecular mechanisms of cervical cancer, two are associated with HPV: firstly, the effect of the viral oncogenes, E6 and E7; and secondly, integration of the viral DNA into chromosomal regions of tumour phenotype. The third process involved is the repetitive loss of heterozygosity in some chromosomal regions. HPV can be classified into high- and low-risk types; the high-risk types encode two oncoproteins, E6 and E7, which interact with tumour suppressor proteins. The association results in the inactivation of tumour suppressor proteins and the abrogation of apoptosis. Apoptosis is referred to as programmed cell death, whereby a cell deliberately commits suicide, and thus regulates cell numbers during development and maintenance of cellular homeostasis. This review attempts to elucidate the role of apoptotic genes, and considers external factors that interact with HPV in the development and progression of cervical cancer. Therefore, an in-depth understanding of the apoptotic genes that control molecular mechanisms in cervical cancer are of critical importance. Useful targets for therapeutic strategies would be those that alter apoptotic pathways in a manner where the escape of HPV from surveillance by the host immune system is prevented. Such an approach directed at the apoptotic genes maybe useful in the treatment of cervical cancer.

Colon cancer: genomics and apoptotic events.

Colon cancer is the third most common cancer globally. The risk of developing colon cancer is influenced by a number of factors that include age and diet, but is primarily a genetic disease, resulting from oncogene over-expression and tumour suppressor gene inactivation. The induction and progression of the disease is briefly outlined, as are the cellular changes that occur in its progression. While colon cancer is uniformly amenable to surgery if detected at the early stages, advanced carcinomas are usually lethal, with metastases to the liver being the most common cause of death. Oncogenes and genetic mutations that occur in colon cancer are featured. The molecules and signals that act to eradicate or initiate the apoptosis cascade in cancer cells, are elucidated, and these include caspases, Fas, Bax, Bid, APC, antisense hTERT, PUMA, 15-LOX-1, ceramide, butyrate, tributyrin and PPARgamma, whereas the molecules which promote colon cancer cell survival are p53 mutants, Bcl-2, Neu3 and COX-2. Cancer therapies aimed at controlling colon cancer are reviewed briefly.

Secondary glomerulonephritides.

This review of the secondary glomerulonephritides outlines presentation clues to assist the primary healthcare worker in making the diagnosis. Glomerulonephritis (GN) due to the following disorders will be described: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), sickle cell disease (SCD), and systemic lupus erythematosis (SLE).