Renal transplantation in developing countries

Healthcare in developing countries less funded than developed nations (0.8 to 4% vs. 10 to 15%, respectively), and must contend against approximately 1/3 of the population living below the poverty line ($1US/day), poor literacy (58% males/29% females), and less access to potable water and basic sanitation. Cultural and societal constraints combine with these economic obstacles to translate into poor transplantation activity. Donor shortage is a universal problem. Paid donation comprises 50% of all transplants in Pakistan. Post-transplant infections are a major problem in developing countries, with 15% developing tuberculosis, 30% cytomegalovirus, and nearly 50% bacterial infections. The solutions to these problems may seem simplistic: alleviate poverty, educate the general population, and expand the transplant programs in public sector hospitals where commerce is less likely to play a major role. The SIUT model of funding in a community-government partnership has increased the number of transplantations and patient and organ survival substantially. Over the last 15 years, it has operated by complete financial transparency, public audit and accountability. The scheme has proven effective and currently 110 transplants/year are performed, with free after care and immunosuppressive drugs. Confidence has been built in the community, with strong donations of money, equipment and medicines. We believe this model could be sustained in other developing nations.     

The hypomagnesaemic action of FK506: urinary excretion of magnesium and calcium and the role of parathyroid hormone

A side-effect of the immunosuppressive drug FK506 (Prograf; tacrolimus) is hypomagnesaemia. We have investigated the effects of short-term (7-day) treatment of rats with FK506, using a protocol designed to indicate whether there are modifications in the renal tubular handling of magnesium and other electrolytes, or in the tissue deposition of magnesium, which may account for the hypomagnesaemia. We have also investigated whether parathyroid hormone has a role in the observed hypomagnesaemia. Two studies have been performed; in the first we administered FK506 (0.5 mg x kg(-1) body weight x day(-1)) or vehicle by intraperitoneal injection for 7 days, and then housed the rats in metabolic cages for the 24 h collection of urine. At the end of the metabolic cage period, the animals were anaesthetized, and blood and tissue samples were taken for analysis. In the second set of experiments the dosage regime was identical, but at the end of the treatment period the animals were anaesthetized for implantation of arterial and venous cannulae, and then received a saline (plus inulin) infusion for 6 h, during which time blood and urine samples were collected. The dose of FK506 employed did not decrease the glomerular filtration rate. FK506 elicited hypomagnesaemia in both sets of experiments, accompanied by inappropriately high fractional excretion of magnesium. There was also evidence of disruption of the normal renal reabsorption of calcium, but this did not result in hypocalcaemia. Plasma parathyroid hormone activity was not significantly different between the two groups, and there was no evidence of altered tissue content of magnesium in kidney, liver, heart, skeletal muscle or bone. The study confirms that hypomagnesaemia is a significant side-effect of FK506, even at a relatively low dose which did not decrease the glomerular filtration rate. The effect is not due to a decrease in parathyroid hormone release, or to translocation of magnesium from plasma to tissues, but does reflect decreased renal tubular magnesium (and calcium) reabsorption.     

Is routine histological evaluation of pediatric hernial sac necessary?

Advocates of routine histological examination of hernial sac recommend it for surgical quality assurance, to report injuries to the vas deferens, and to detect occult malignant and benign diseases such as tuberculosis. However, the value of this routine examination is debated in this era of cost containment in health care. We conducted a retrospective study of our practice and reviewed the relevant literature to find any justification to continue this practice. Only 2.2% of hernial sacs submitted for histopathology showed unusual findings, and none of these findings were clinically important. In conclusion, the findings of our study and our review of the current literature do not support the routine histological examination of hernial sac in the pediatric age group.     

Hepatic glucagon receptor binding and glucose-lowering in vivo by peptidyl and non-peptidyl glucagon receptor antagonists

Glucagon receptor antagonists have been actively pursued as potential therapeutics for the treatment of type 2 diabetes. Peptidyl and non-peptidyl glucagon receptor antagonists have been shown to block glucagon-induced blood glucose elevation in both animals and humans. How the antagonists and the glucagon receptor interact in vivo has not been reported and is the subject of the current study. Using (125)I-labeled glucagon as a radiotracer, we developed an in vivo glucagon receptor occupancy assay in mice expressing a human glucagon receptor in place of the endogenous mouse glucagon receptor (hGCGR mice). Using this assay, we first showed that the glucagon receptor is expressed predominantly in liver, to a much lesser extent in kidney, and is below detection in several other tissues/organs in the mice. We subsequently showed that, at 2 mg/kg body weight (mg/pk) dosed intraperitoneally (i.p.), peptidyl glucagon receptor antagonist des-His-glucagon binds to approximately 78% of the hepatic glucagon receptor and blocks an exogenous glucagon-induced blood glucose elevation in the mice. Finally, we also showed that, at 10 and 30 mg/kg dosed orally (p.o.), compound A, a non-peptidyl small molecule glucagon receptor antagonist, occupied 65-70% of the hepatic glucagon receptor, and significantly diminished exogenous glucagon-induced blood glucose elevation in the mice. At 3 mg/kg, however, compound A occupied only approximately 39% of the hepatic glucagon receptor and did not affect exogenous glucagon-induced blood glucose elevation in the mice. Taken together, the results confirmed previous reports that glucagon receptors are present predominantly in the liver, and provide the first direct evidence that peptidyl and non-peptidyl glucagon receptor antagonists bind to the hepatic glucagon receptor in vivo, and that at least 60% receptor occupancy correlates with the glucose lowering efficacy by the antagonists in vivo.     

A model for effective involvement of private medical practitioners in TB care

The purpose of this paper is to propose a process to help to develop a new model for partnerships in tuberculosis (TB) control, based on experiences to date. We start by identifying the essential service components needed in order to deliver quality care. Secondly, we identify the main partners in a collaboration or partnership. We describe a generic model linking the partners and the components. This model is then used to describe and analyse successful partnerships currently in existence, identifying those features that produced a successful outcome regarding increased access, coverage and quality for TB control. Finally, we illustrate how the process and generic model has been used to develop a locally appropriate model for partnerships in TB control, taking Bangladesh as our example.     

HIV knowledge and risk behaviors among Pakistani and Afghani drug users in Quetta,Pakistan

Situated on the Pakistan-Afghan border, Quetta is home to growing numbers of Afghan refugees. We studied HIV knowledge and risk behaviors among Pakistani and Afghani drug users between July 2001 and November 2001. Of 959 drug users, all were male and the majority used heroin. Most were Pakistani (84.8%), 14.9% were Afghani, and 0.3% were Iranian. Relative to Pakistani drug users, a higher proportion of Afghanis reported no formal education, homelessness, and unemployment ( p <.001). Afghanis were more likely to have used an opiate as their first illicit drug (16% vs. 7%, p <.001), to have ever injected (18.8% vs. 12.3%, p =.04), to report needle sharing (72.2% vs. 48.2%, p =.08), or to report a drug user in their family ( p =.08). None of sexually active Afghanis had ever used a condom compared with 5.0% of the Pakistanis ( p =.01). Only 4.3% of Afghans had ever heard of HIV/AIDS compared with 18.3% of Pakistanis ( p <.001). Extremely low levels of HIV/AIDS awareness and high HIV risk behaviors were evident among drug users in Quetta, among whom Afghanis were especially vulnerable. Interventions to prevent transition to injection, needle exchange, and drug treatment are urgently required to prevent blood-borne infections.