Low-dose colestipol plus probucol for hypercholesterolemia

The hypocholesterolemic and adverse effects of colestipol, 20 g/day, and colestipol, 10 g/day combined with probucol, 1 g/day, were compared. A double-placebo, diet-controlled, crossover trial that lasted 19 months was undertaken on 22 hypercholesterolemic patients who had low-density lipoprotein (LDL) cholesterol levels greater than 180 mg/dl after 3 months of diet and placebo treatment. Uniformity of diet and physical activity were monitored throughout the study. Compared with baseline values after 3 months on diet-placebo treatment, "combined" therapy reduced LDL cholesterol by more than 20% in 15 patients, more than 25% in 9 patients and more than 45% in 2 patients. Treatment with "half-dose" colestipol and probucol resulted in the greatest mean LDL cholesterol reduction, from 239 mg/dl during diet-placebo period to 170 mg/dl; the difference was not statistically significantly different from the reduction to 180 mg/dl with 20 g of colestipol alone. Fifteen patients showed the greatest reduction in LDL cholesterol after combined therapy. Probucol produced statistically significant reductions in very low density lipoprotein and high-density lipoprotein cholesterol. The major gastrointestinal side effects of single therapy with colestipol (constipation) and probucol (diarrhea) were ameliorated or abolished by concomitant administration. Probucol-colestipol co-administration allowed a 50% reduction in the colestipol dosage, with similar efficacy and improved tolerability and reduced mean serum LDL cholesterol with a frequency and magnitude rarely seen with other hypocholesterolemic treatments. Hypercholesterolemic persons who cannot tolerate full doses of resins may receive equal benefit by half the dose if probucol is added to the regimen.     

Sensitivity and specificity of serology in determining recent acute Campylobacter infection

BACKGROUND: The measurement of serum antibodies to Campylobacter spp. has been used to investigate links between prior Campylobacter infections and the development of Guillain-Barre syndrome and its variants. Little is known of the serum antibody response to acute infections in the short- or long-term. AIMS: The aims of the present study were to investigate the normal serum response to an acute Campylobacter infection and the sensitivity and specificity of anti-Campylobacter antibodies in determining recent Campylobacter infection. METHODS: An enzyme-linked immunosorbent assay (ELISA) method was used to measure serum anti-Campylobacter immunoglobulin G (IgG), IgA and IgM antibodies. Controls consisted of 420 blood donors without recent gastroenteritis, 25 patients with other gastrointestinal infections, 24 patients with neurological conditions not affecting the peripheral nerves and 19 patients with autoimmune disorders. Three patient groups were assessed: 99 patients with acute Campylobacter infections, all of whom were tested 3 weeks post-infection; 69 of these patients tested 3-6 months later; and 74 additional patients tested >20 months post-infection. Western blot analysis was performed on controls and patients with high titre anti-Campylobacter antibodies to assess for cross-reactivity and specificity. RESULTS: Following acute infections, all antibody classes rose in the majority of but not in all patients, followed by decreasing titres that did not return to baseline levels. Sixteen per cent of enteritis cases did not demonstrate a rise in titres and 9% of cases had significant levels of antibodies >20 months post-infection. The ELISA used was shown to be highly specific for the detection of Campylobacter antibodies. CONCLUSION: The use of Campylobacter-specific antibody levels as the sole marker of prior infection is an unreliable method of determining the association between Campylobacter infection and neurological disease.     

Differential antibody recognition of FC27-like Plasmodium falciparum merozoite surface protein MSP2 antigens which lack 12 amino acid repeats

Three alleles of the FC27-type allelic family of the MSP2 gene of the malaria parasite Plasmodium falciparum have been sequenced from parasites from the field (The Gambia and Tanzania). These alleles lack the 12 amino acid repeat units which are usual in this family of MSP2 alleles. We have investigated the recognition by sera from an endemic area (The Gambia) of three recombinant MSP2 proteins that have 5, 1 and no copies of this repeat region. Antibody recognition of these recombinant proteins varied according to the number of repeats present. High titre antibody levels were seen with most sera using the recombinant protein with 5 × 12-mer repeats, whereas only low responses were measured using proteins containing 1 or no 12-mer repeats. Several sera entirely failed to recognise the protein which lacked 12-mer repeats. The data suggest that variation in the number of tandem repeat sequences could allow the parasite to avoid high avidity antibody binding and this may allow escape from immune recognition.     

Using a focus group to design a diabetes education program for an African American population

PURPOSE: The purpose of this project was to determine what factors need to be considered in planning a diabetes education program to better meet the needs of African Americans with diabetes in a community served by a suburban community hospital. METHODS: Two focus group sessions were conducted. The sessions were recorded, transcribed, and analyzed by members of the research team. RESULTS: Four themes emerged that had bearing on program development: (1) a sense of personal powerlessness, (2) fear related to complications, (3) recognition of knowledge deficits accompanied by an inability to link behavior to outcomes, and (4) a clear vision of what kind of educational setting would interest and benefit the group. CONCLUSIONS: There were significant differences between what was being offered for diabetes education at the facility and what was desired according to the focus group, including factors of cost and leadership. Recommendations for future program planning are given.     

Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function?

OBJECTIVES: This study sought to determine whether changes in intra-abdominal pressure (IAP) with aggressive diuretic or vasodilator therapy are associated with improvement in renal function in acute decompensated heart failure (ADHF). BACKGROUND: Elevated IAP (>or=8 mm Hg) is associated with intra-abdominal organ dysfunction. There is potential for ascites and visceral edema causing elevated IAP in patients with ADHF. METHODS: Forty consecutive patients admitted to a specialized heart failure intensive care unit for management of ADHF with intensive medical therapy were studied. The IAP was measured using a simple transvesical technique at time of admission and before removal of the pulmonary artery catheter. RESULTS: In our study cohort (mean age 59 +/- 13 years, mean left ventricular ejection fraction 19 +/- 9%, baseline serum creatinine 2.0 +/- 0.9 mg/dl), the mean baseline IAP was 8 +/- 4 mm Hg, with 24 (60%) patients having elevated IAP. Elevated IAP was associated with worse renal function (p = 0.009). Intensive medical therapy resulted in improvement in both hemodynamic measurements and IAP. A strong correlation (r = 0.77, p < 0.001) was observed between reduction in IAP and improved renal function in patients with baseline elevated IAP. However, changes in IAP or renal function did not correlate with changes in any hemodynamic variable. CONCLUSIONS: Elevated IAP is prevalent in patients with ADHF and is associated with impaired renal function. In the setting of intensive medical therapy for ADHF, changes in IAP were better correlated with changes in renal function than any hemodynamic variable.     

Prospective assessment of magnetic resonance cholangiopancreatography for noninvasive imaging of the biliary tree.

BACKGROUND: Traditionally, ERCP has been the only reliable method for imaging the biliary tree, but it is invasive and carries a risk of complications. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive method for imaging the biliary tree. The aim of this study was to prospectively assess the accuracy of MRCP in a large number of patients. METHODS: Consecutive patients referred to a teaching hospital for ERCP were eligible for study entry. MRCP was performed within 24 hours before ERCP. MRCP findings were compared with ERCP findings or, when the initial ERCP was unsuccessful, with results of repeat ERCP, percutaneous transhepatic cholangiography, or surgery. RESULTS: One hundred forty-six patients underwent 149 ERCP/MRCP procedures, of which 129 were evaluable with successful MRCP and ERCP or an ERCP-equivalent study. Diagnoses included choledocholithiasis in 46 and biliary stricture in 12 patients. The sensitivity, specificity, positive, and negative predictive values for MRCP in the diagnosis of choledocholithiasis were 97.9%, 89.0%, 83.6%, and 98.6%, respectively. All 12 strictures were diagnosed by MRCP (sensitivity 100%, specificity 99.1%). CONCLUSIONS: MRCP is an accurate, noninvasive alternative to ERCP for imaging the biliary tree. Choledocholithiasis and biliary strictures can be reliably diagnosed or excluded by MRCP. MRCP should be used increasingly in patients with suspected biliary obstruction to select those who require a therapeutic procedure.     

Lifespan and reproduction in Drosophila: New insights from nutritional geometry

Modest dietary restriction (DR) prolongs life in a wide range of organisms, spanning single-celled yeast to mammals. Here, we report the use of recent techniques in nutrition research to quantify the detailed relationship between diet, nutrient intake, lifespan, and reproduction in Drosophila melanogaster. Caloric restriction (CR) was not responsible for extending lifespan in our experimental flies. Response surfaces for lifespan and fecundity were maximized at different protein-carbohydrate intakes, with longevity highest at a protein-to-carbohydrate ratio of 1:16 and egg-laying rate maximized at 1:2. Lifetime egg production, the measure closest to fitness, was maximized at an intermediate P:C ratio of 1:4. Flies offered a choice of complementary foods regulated intake to maximize lifetime egg production. The results indicate a role for both direct costs of reproduction and other deleterious consequences of ingesting high levels of protein. We unite a body of apparently conflicting work within a common framework and provide a platform for studying aging in all organisms.     

Drug therapy of chronic heart failure

Chronic heart failure is an irremediable terminal syndrome. The inability of the heart to pump sufficient blood to meet the demands of metabolically active tissues is aggravated by reflex increases in peripheral vasoconstriction induced by the sympathoadrenal and renin-angiotensin-aldosterone systems. Vasoconstriction is partially attenuated by atrial natriuretic hormone, prostaglandin, and bradykinin. The aim of therapy is to improve the pumping performance of the heart and reduce arterial and venous constriction in the hope that this will reduce symtoms and improve the quality of life. Many drugs achieve such benefits, at least initially. Inotropic drugs increase cardiac pumping activity, and drugs acting directly on arteries and veins improve cardiac function by reducing afterload and preload. ACE inhibitors suppress angiotensin II formation, reducing its vasoconstrictive action, its ability to increase aldosterone secretion and the consequent salt retention and expansion of plasma volume. Since the proportionate role played by various hemodynamic factors in individual patients in unknown, it is likely that most benefit will be achieved by a combined therapeutic approach.     

Renin messenger RNA localization in congenital mesoblastic nephroma using in situ hybridization

Renin messenger (m) RNA distribution was studied in congenital mesoblastic nephroma, a usually benign renal tumour of early infancy which may be associated with excess renin production and hypertension. Using in situ hybridization with synthetic radiolabelled oligonucleotide probes combined with immunohistochemical studies, renin expression was found in areas of tumours containing recognizable cortical structures including glomeruli and tubules. Renin mRNA was also detected in vessels and larger vascular spaces within the tumour not associated with cortical structures. Cells in the tumour vessel walls and sinusoids which expressed renin also stained positively for vascular smooth muscle-specific alpha actin.     

Lipid abnormalities and renal disease: is dyslipidemia a predictor of progression of renal disease?

Dyslipidemia is a cardiovascular disease (CVD) risk factor that is associated with enhanced atherosclerosis and plaque instability. Renal insufficiency is associated with abnormalities in lipoprotein metabolism in both the early and the advanced stages of chronic renal failure. These include alterations in apolipoprotein A (apo A)- and B- containing lipoproteins, high-density lipoproteins, and triglycerides. In animal models, these alterations in lipid metabolism and action lead to macrophage activation and infiltration in the kidney with resultant tubulointerstitial and endothelial cell injury. Limited data in humans suggest that, in addition to contributing to CVD, dyslipidemia may be a risk factor for the progression of renal disease. The effects of dyslipidemia on the kidney are mainly observed in those with other risk factors for renal disease progression such as hypertension, diabetes, and proteinuria. Renal disease is a strong risk factor for CVD and African Americans have high rates of renal disease. Therefore, examining the effects of dyslipidemia on the development or progression or renal disease will be an important question for the Jackson Heart Study and is the topic of this review.