Sarala Naicker

Loss of health professionals from sub-Saharan Africa : The pivotal role of the UK

The already inadequate health systems of sub-Saharan Africa have been badly damaged by the emigration of their health professionals, a process in which the UK has played a prominent part. In 2005, there are special opportunities for the UK to take the lead in addressing that damage, and in focusing the attention of the G8 on the wider problems of health-professional migration from poor to rich countries. We suggest some practical measures to these ends. These include action the UK could take on its own, with the African countries most affected, and with other developed countries and WHO.

Kallikrein and Kinin Receptor Expression in Inflammation and Cancer

Abstract The kallikrein family of serine proteases has been investigated in many inflammatory disorders as molecular mapping, gene characterisation and cloning of kinin receptor genes have unfolded experimentally. In the molecular events of the inflammatory response the kallikrein cascade plays a significant role, since it is considered to initiate and maintain systemic inflammatory responses and immune-modulated disorders. A primary event is the chemotactic attraction of neutrophils which deliver the kallikrein-kinin cascade to sites of cellular injury and carcinogenic transformation of cells. The present study establishes the casual involvement of the kallikrein cascade in infection, inflammatory joint disease, acute transplant rejection, renal glomerular diseases, angiogenesis and carcinoma. We provide strong evidence for new or enhanced expression of kinin B1 receptors in inflammation, and additionally the induction of kallikrein genes in angiogenesis and carcinoma. The results provide insights into possible roles of kallikrein inhibitors and kinin receptor antagonists.

Colon cancer: genomics and apoptotic events

Abstract 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 overexpression 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 PPARγ, 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.

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.

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.

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

Abstract 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.

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.

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.

Nephrology in developing countries: the ISN's story

What could you do to support medical care in developing countries? This question should be compelling to many physicians in developed regions of the world, particularly those working in nephrology—a subspecialty often associated with expensive and technologically advanced therapies. In many low-income and middle-income countries (LMICs), long-term dialysis or transplantation for end-stage kidney disease are not available, but other ways to reduce the burden of kidney disease do exist— eg, management of reversible acute kidney injury by early detection, and the use of peritoneal dialysis, which is feasible, eff ective, and aff ordable. Another example is to address non-communicable diseases—for which chronic kidney disease is a powerful risk multiplier— by use of low-cost community-based detection and treatment strategies for chronic kidney disease that are eff ective and aff ordable in most settings. However, the most important thing that can be done is to build capacity for sustainable self-suffi ciency in nephrology. Since the 1980s, the International Society of Nephrology (ISN) has used its resources for education and training and, in doing so, advanced nephrology in LMICs worldwide through a portfolio of fi ve outreach programmes. These programmes, delivered at very low cost, are a model for what can be achieved by volunteers in a specialist society or other group committed to helping patients and colleagues in developing countries. In the past 25 years, the ISN’s fellowship programme has sponsored more than 600 nephrology trainees from more than 80 LMICs, who are required to sign an agreement stipulating that they will return to their home country after training; 35% are now training within their own region of the world. Survey data show that the trainees go on to become leaders in their own hospitals and universities, showing that ISN’s strategy of selecting individuals with the greatest potential is working. The ISN also helps to establish sister renal centres in LMICs, which develop nephrological expertise through relationships with established centres in developed countries, with notable successes. A typical sister centre graduates after 6–8 years and in turn supports another emerging centre in its own country or region. This approach is a two-way process, with staff in the supporting centre often having to learn as much as those in the emerging centre. Furthermore, there is the option for experienced nephrologists to join our educational ambassador scheme and to visit a nephrology centre in an LMIC for several weeks to help to establish new programmes that will benefi t patient care. ISN has more than 100 volunteers covering every aspect of clinical nephrology who are available to travel and teach anywhere in developing regions of the world. Additionally, the clinical research and prevention programme builds research capacity in LMICs by providing seed funding for small clinical research projects, and by assigning research mentors. It supports chronic kidney disease surveillance programmes, helping LMICs to generate their own epidemiological data—crucial for infl uencing health policy. These data are generated independently, and also in partnership with WHO and the Global Burden of Diseases project.

Uniquely South African: time to consider offering HIV-positive donor kidneys to HIV-infected renal failure patients?

Kidney transplantation has been established as the most effective form of renal replacement therapy from a cost and quality of life perspective in the developed world.