Health financing reform in Kenya - assessing the social health insurance proposal.

Kenya has had a history of health financing policy changes since its independence in 1963. Recently, significant preparatory work was done on a new Social Health Insurance Law that, if accepted, would lead to universal health coverage in Kenya after a transition period. Questions of economic feasibility and political acceptability continue to be discussed, with stakeholders voicing concerns on design features of the new proposal submitted to the Kenyan parliament in 2004. For economic, social, political and organisational reasons a transition period will be necessary, which is likely to last more than a decade. However, important objectives such as access to health care and avoiding impoverishment due to direct health care payments should be recognised from the start so that steady progress towards effective universal coverage can be planned and achieved.     

Famotidine has no effect on cardiac performance and liver blood flow in the rat

Conflicting results have been reported on the effect of famotidine on cardiac performance and visceral hemodynamics, studied by non-invasive techniques. It is for that reason that we used the radioactive microsphere technique to study the effect of famotidine on cardiac performance in the rat. Hepatic blood flow (HBF) and portal blood flow (PBF) were measured during the same experiment. Rats were either given famotidine (2.0 mg/kg per day) or drinking water for 7 days through an orogastric tube. Administration of famotidine had no effect on cardiac output (CO), HBF, PBF, or liver blood flow (LBF), which is the sum of HBF and PBF. In both groups, LBF consisted of a similar fraction of CO, 14.5±3.9% and 15.7±4.38%, in the control and the famotidine groups, respectively. Pulse rate, systolic pressure and left ventricular contractility were not affected by famotidine. It is concluded that in the rat, administration of famotidine for 7 days has no effect on systemic, hepatic or portal hemodynamics.     

Evaluation of a new immunochromatographic test for Helicobacter pylori IgG antibodies in elderly symptomatic patients

Aim: To determine the diagnostic value of a new serum and whole blood serological IgG antibody test, FlexPack HP, for the diagnosis of Helicobacter pylori in elderly symptomatic patients. Methods: 94 consecutive symptomatic patients who underwent upper endoscopy were studied (mean age, 62.6 years). On endoscopy, the presence of H. pylori infection was examined by biopsies from gastric antrum and body for rapid urease test and histologic examination. Blood was drawn prior to endoscopy and both blood and serum were immediately analyzed for human IgG antibodies to H. pylori by a new commercially available qualitative immunochromatographic method, FlexPack HP. This test incorporates high-molecular weight cell-associated proteins (HM-CAP), which are highly specific for H. pylori IgG antibodies. Results: Overall agreement for FlexPack HP whole blood vs FlexPack HP serum was 100%, and agreement with biopsy results was 71%. The gold standard (detection of H. pylori by histology or urease test) identified H. pylori in 61 patients (65%). Complete agreement was observed between the gold standard test and the serology kit in 72% (68/94) of sera (51 positive and 17 negative). Disagreement was found in sera of 26 patients; 16 sera were negative by the gold standard and positive by FlexPack HP and 10 patients were found negative by serology. The sensitivity of FlexPack HP was 84% and the specificity 52% when compared with the gold standard. Conclusions: FlexPack HP serum and whole blood test is a simple and reliable method for the detection of H. pylori antibodies, with 100% agreement between the serum and blood results. In the elderly symptomatic patients the sensitivity of FlexPack HP was similar to that of other serologic tests, but the specificity was relatively low, limiting its use in this population. (Received Jan. 7, 1998; accepted Aug. 28, 1998)     

A transgenic mouse model expressing exclusively human hemoglobin E: indications of a mild oxidative stress

Hemoglobin (Hb) E (β26 Glu→Lys) is the most common abnormal hemoglobin (Hb) variant in the world. Homozygotes for HbE are mildly thalassemic as a result of the alternate splice mutation and present with a benign clinical picture (microcytic and mildly anemic) with rare clinical symptoms. Given that the human red blood cell (RBC) contains both HbE and excess α-chains along with minor hemoglobins, the consequence of HbE alone on RBC pathophysiology has not been elucidated. This becomes critical for the highly morbid β(E)-thalassemia disease. We have generated transgenic mice exclusively expressing human HbE (HbEKO) that exhibit the known aberrant splicing of β(E) globin mRNA, but are essentially non-thalassemic as demonstrated by RBC α/β (human) globin chain synthesis. These mice exhibit hematological characteristics similar to presentations in human EE individuals: microcytic RBC with low MCV and MCH but normal MCHC; target RBC; mild anemia with low Hb, HCT and mildly elevated reticulocyte levels and decreased osmotic fragility, indicating altered RBC surface area to volume ratio. These alterations are correlated with a mild RBC oxidative stress indicated by enhanced membrane lipid peroxidation, elevated zinc protoporphyrin levels, and by small but significant changes in cardiac function. The C57 (background) mouse and full KO mouse models expressing HbE with the presence of HbS or HbA are used as controls. In select cases, the HbA full KO mouse model is compared but found to be limited due to its RBC thalassemic characteristics. Since the HbEKO mouse RBC lacks an abundance of excess α-chains that would approximate a mouse thalassemia (or a human thalassemia), the results indicate that the observed in vivo RBC mild oxidative stress arises, at least in part, from the molecular consequences of the HbE mutation.     

Inhibition of experimentally-induced liver cirrhosis in rats by a nonpeptidic mimetic of the extracellualr matrix-associated Arg-Gly-Asp epitope

Aims/Methods: in the present study, we examined whether a nonpeptidic mimetic of Arg-Gly-Asp (RGD), which specifically inhibits RGD-dependent adhesion of CD4⁺ T lymphocytes or fibroblasts to fibronectin, can prevent thioacetamide-induced liver cirrhosis in rats. The nonpeptidic RGD mimetic, rather than the RGD peptide was utilized, since the peptide is rapidly degraded, and therefore, relatively ineffective for in vivo use.Results: We now report that rats treated with thioacetamide and the RGD analogue SF-6,5 for 12 weeks had lower histopathologic scores than those treated with thioacetamide alone. Further improvement in liver histology was observed after another 8 weeks of treatment with the analogue SF-6,5. Quantitative microscopic analysis by computerized imaging morphometry of liver biopsies from the three groups and controls confirmed the semi-quantitative histopathologic scores (pτ0.001). After 3 months of treatment, the spleen weights in the SF-6,5-treated rats were 30% less than those of rats and that received only thioacetamide, which indicated that the analogue-treated rats were less portal hypertensive.Conclusions: The observed inhibition of the progression of cirrhosis in rats by the nonpeptidic RGD analogue suggests that RGD mimetics may be useful therapeutically in inhibiting pathological processes that involve RGD recognition.     

Bone biopsies and serum vitamin-D levels in patients with hip fracture

To assess the correlation between osteoid and vitamin D in patients with a proximal femoral fracture, bone biopsies of the fracture site and the iliac crest were studied; and vitamin-D levels were measured in fasting blood taken on the day of admission. No osteomalacia was found at either site in any of the 95 patients investigated. In 65/95 patients, levels of 25-hydroxy-vitamui D (25-OHD) and 24, 25-dihydroxy-vitamin D(24, 25 -OH₂D) were within the normal range, whereas 30/95 patients were deficient. Because there was no correlation between the amount of osteoid and vitamin-D metabolites in our patients, we concluded that osteomalacia was not a contributory factor in the pathogenesis of the hip fracture.     

Function-specific blockage of M(1) and M(3) muscarinic acetylcholine receptors by VX and echothiophate

Certain organophosphate (OP) cholinesterase inhibitors (ChEIs) are also known to bind to the muscarinic acetylcholine receptor (mAChR). The functional consequences of such binding were investigated here using the following OP compounds: VX, echothiophate, sarin, and soman. VX (charged at physiological pH) and echothiophate (formally charged) inhibited a specific signal transduction pathway in CHO cells expressing either the M(1) or M(3) mAChR. Hence, they blocked carbamylcholine (CCh)-induced cyclic adenosine monophosphate (cAMP) synthesis (muM) and had almost no effect on CCh-induced phosphoinositide (PI) hydrolysis. These substances were inactive on forskolin-induced cAMP inhibition signaling in CHO cells expressing M(2) mAChR. In binding studies, using [(3)H]-N-methyl scopolamine ([(3)H]NMS) as the competitor ligand, the ChEIs, VX and echothiophate exhibited binding to rat cortical mAChR with K(i) values in the muM range. The non-charged compounds, sarin and soman, were inert in modulating both cAMP metabolism and PI hydrolysis in CHO cells expressing M(1), M(2), and M(3) mAChRs, and no binding was observed in presence of [(3)H]NMS. These data suggest that VX and echothiophate act as function-specific blockers via a non-classical path of antagonistic activity, implying the involvement of allosteric/ectopic-binding site in M(1) and M(3) mAChRs. The functionally selective antagonistic behavior of echothiophate and VX makes them potential tools for dissecting the interactions of the mAChR with different G proteins.     

Interleukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction

The aim of this study was to evaluate the prognostic value of interleukin-6 (IL-6) for myocardial infarction (MI) and mortality in a population with stable coronary artery disease (CAD) during a mean period of 6.3 years. IL-6 is a major proinflammatory cytokine of acute phase response; elevated levels are associated with worse prognosis in unstable angina and after acute MI. However, data regarding its long-term prognostic value in stable CAD are limited and controversial. A nested case-control study design was used. Of 3,090 patients with stable CAD, 129 with an adequate blood sample for IL-6 and who reached the end points (MI or sudden death) were randomly selected. Each case was 1:1 matched with 129 controls (alive at the end of the study and free of cardiovascular events) according to age, gender, and treatment. Of the 129 cases, 113 had a MI as the initial event, and for the other 16 the initial event was sudden death. There were 8 patients who first had a MI and later died suddenly. IL-6 was significantly higher in cases (2.34 pg/ml) than in controls (1.65 pg/ml) (p = 0.0004). IL-6 was significantly correlated with C-reactive protein (r = 0.2, p = 0.002); a borderline significance was also found for fibrinogen (r = 0.11, p = 0.07). Each increase of 1 pg/ml in IL-6 was associated with a 1.70 (range 1.23 to 2.45) increased relative odds of subsequent MI or sudden death. Events rate per 1,000 patients-years for the 5 quintiles of IL-6 were 72.26, 89.61, 79.76, 142.53, and 181.08, respectively (p <0.0001). A significantly higher risk in the upper quintile was found (odds ratio, 3.44; 95% confidence interval 1.57 to 8.13). In conclusion, elevated IL-6 levels are strongly associated with future cardiac events and mortality in a population with stable CAD during a long-term follow-up.