Homocysteine metabolism in renal failure

PURPOSE OF REVIEW: This review focuses on recent findings (June 2002-July 2003) on the topic of homocysteine, a sulfur amino acid associated with cardiovascular disease, and its metabolism in renal failure, a condition with a high prevalence of both hyperhomocysteinemia and cardiovascular disease. RECENT FINDINGS: A large meta-analysis of prospective studies in the general population established that hyperhomocysteinemia is a risk factor for cardiovascular disease. The results of intervention trials, once available, will also have to be tested in a meta-analysis, because of predicted problems with their statistical power. In kidney patients, intervention trials, still in the recruiting stage, target transplant patients, because of their unique characteristics related to folate responsiveness. As for the cause of hyperhomocysteinemia, new findings show that in humans, renal metabolic extraction depends on renal plasma flow in the post-absorptive state. Folate absorption or interconversion seems not to be affected. Riboflavin is a determinant of plasma homocysteine levels in uraemia. The consequences of hyperhomocysteinemia in uraemia are DNA hypomethylation and altered gene expression. SUMMARY: The causes of hyperhomocysteinemia in renal failure are still not clear. However, the possibilities include defective renal or extrarenal metabolism as a result of uraemic toxicity. Renal plasma flow is important in homocysteine renal metabolism. Among the consequences of hyperhomocysteinemia in renal failure are impaired protein and DNA methylation, with an alteration in the allelic expression of genes regulated through methylation. Intervention trials are under way to test whether hyperhomocysteinemia is causally related to cardiovascular disease in this patient population.     

Antibiotic therapy in the elderly: features and problems

Bacterial infections cause 30% of deaths in the elderly and are the most frequent cause of hospitalization in elderly patients. Diagnosis of infection can be difficult because aged patients may have neither fever nor leucocytosis; most patients present unusual symptoms such as changes in mental status. The clinician must be cognizant of the frequent noncompliance with drug regimens because lack of elderly adherence to a prescribed antibiotic therapy has the potential to result in treatment failure and to foster the emergence of drug-resistant bacteria. Elderly frequently are taking other drugs such as antiarrhythmics and antihypertensives; ignorance of potential antibiotic-drug interaction can result in ineffective treatment or enhanced toxicity. Aging is associated with changes in physiological processes; the age-related decline in renal function influences the excretion of some antibiotics (aminoglycosides, vancomycin, ofloxacin). The increased potential for toxicity of antimicrobial agents requires a careful drug selection as well as clinical and laboratory monitoring. The most frequent infections occurring in the elderly are pneumonia, urinary tract infection, intra-abdominal infection and soft tissue infection; prevalence and incidence of bacterial meningitis, bacterial endocarditis and bacteraemia are increasing with a mortality rate of 20 to 40%. These bacterial infections have different microbial causes and require different therapeutic approaches according to sites involved, elderly's salient features and overall susceptibility of the bacteria in the ecosystem. Appropriate empirical antibiotic treatment reduces mortality also in bacteraemic old patients.     

Gastric Perforation in an Obese Patient with an Intragastric Balloon,following Previous Fundoplication

Background: The Bioenterics Intragastric Balloon (BIB) has been a safe and effective method used in treatment of moderate obesity. Gastric perforation is a rare complication, and its possible sequelae are dangerous. Methods: A 52-year-old women (BMI 37 kg/m²), with hiatal hernia, moderate hypertension and dyspnea, 1 year ago underwent laparoscopic fundoplication. She now underwent positioning of a BIB^? filled with 500 cc of saline. After 8 days, 6 kg weight loss occurred and her clinical condition was satisfactory. On day 11, severe abdominal pain and vomiting occurred, which spontaneously regressed in the following 6-8 hours. Ultrasound confirmed the correct position of the BIB^?, and showed widespread abdominal meteorism. On day 18, acute abdomen with paralytic ileus occurred. On admission, CT scan documented hydropneumoperitonitis. At operation, a large perforation of the lesser curvature was found, with undigested food in the abdomen. She underwent peritoneal lavage, removal of the BIB, and suture of the gastric laceration. Results: She was discharged in good condition after 11 days. Conclusion: According to our experience, fundoplication represents an absolute contraindication to positioning of a BIB^?.     

Food groups and alcoholic beverages and the risk of stomach cancer: a case-control study in Italy

To investigate the role of a wide range of foods and beverages on the risk of stomach cancer, we analyzed data from a case-control study carried out in Italy between 1997 and 2007 on 230 subjects with incident histologically confirmed stomach cancer (143 men and 87 women, age range 22-80 yr) and 547 controls (286 men and 261 women, age range 22-80 yr) admitted to hospital for acute, non-neoplastic diseases. Odds ratios (OR) of stomach cancer and their corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models, adjusted for age, sex, energy intake, and other selected variables. A direct association with stomach cancer risk was observed for cereals (OR = 2.07, 95% CI = 1.01-4.24, for the highest compared to the lowest quintile of intake, P for trend = 0.03), soups (OR = 1.94, 95% CI = 1.10-3.42, P for trend = 0.05), and potatoes (OR = 2.04, 95% CI = 1.05-3.98, P for trend = 0.04). Conversely, inverse trends in risk were observed with vegetables (OR = 0.47, 95% CI = 0.27-0.81, P for trend = 0.01) and fruit intake (OR = 0.53, 95% CI = 0.30-0.93, P for trend = 0.08). The results of this study confirm a protective role of vegetables and fruit against stomach cancer and suggest a detrimental effect of (refined) cereals on this neoplasm.     

Medium-term effects of bisoprolol administration on renal hemodynamics and function in mild to moderate essential hypertension

Arterial hypertension is a significant cause of end-stage renal failure; effective treatment of hypertensive patients reduces the rate of progression of this disorder. β-Blockers, particularly nonselective agents, are associated with deterioration of renal function in patients with chronic renal failure. Previous studies on the interaction of the β₁-selective adrenergic antagonist bisoprolol with kidney function have been performed only acutely and over the short term. This study was designed to evaluate the antihypertensive efficacy and effects on renal hemodynamics and function of bisoprolol during medium-term (6 mo) treatment of patients with mild to moderate essential hypertension. After a 2-wk run-in period on placebo, 87 consecutive hypertensive patients (46 men, 41 women) according to ESH-ESC (European Society of Hypertension/European Society of Cardiology) guidelines, aged from 27 to 64 y (mean age, 50±11 y), without renal or cardiovascular disease, were enrolled and assigned to treatment with bisoprolol 5 mg once daily for 6 mo. At recruitment and at 6 mo after treatment, renal function was assessed and renal hemodynamics evaluated in all patients through radioisotope studies. The mediumterm effects of bisoprolol included a significant reduction in blood pressure and heart rate (P< .001) without significant adverse drug reactions. Moreover, bisoprolol produced no alteration in renal function or hemodynamics, or in cardiac output. Data presented here indicate that bisoprolol 5 mg given once daily to treat patients with mild to moderate essential hypertension is effective and safe for treatment and for preservation of renal performance when given on a medium-term basis.     

Skp2 overexpression is associated with loss of BRCA2 protein in human prostate cancer

BRCA2 (breast cancer 2, early onset) is a tumor suppressor gene that confers increased susceptibility for prostate cancer (PCa). Previous in vitro experiments demonstrated that Skp2, an E3 ubiquitin ligase aberrantly overexpressed in PCa, is involved in the proteolytic degradation of BRCA2 in PCa cells, suggesting that the BRCA2-Skp2 interaction may play a role in prostate tumorigenesis. Herein, we investigated BRCA2 and Skp2 expression during PCa development using a prostate TMA. Although luminal and basal benign prostate epithelium exhibited moderate to strong nuclear BRCA2 immunostaining, the intensity and number of positive nuclei decreased significantly in high-grade prostatic intraepithelial neoplasia and PCa. Decreased frequency and intensity of nuclear BRCA2 labeling were inversely correlated with Skp2 expression in high-grade prostatic intraepithelial neoplasia and PCa. To functionally assess the effects of BRCA2 and Skp2 expression on prostate malignant transformation, we overexpressed Skp2 in normal immortalized prostate cells. Skp2 overexpression reduced BRCA2 protein and promoted cell growth and migration. A similar phenotype was observed after reduction of BRCA2 protein levels using specific BRCA2 small-interfering RNA. Forced BRCA2 expression in Skp2-overexpressing stable transfectants inhibited the migratory and growth properties by >60%. These results show that loss of BRCA2 expression during prostate tumor development is strongly correlated with both migratory behavior and cancer growth and include Skp2 as a BRCA2 proteolytic partner in vivo.     

Variability of influenza AH1N1 infections in a neonatal unit in Spain

We describe three positive influenza AH1N1 cases in a neonatal unit during the influenza pandemic in Spain. One term baby presented with an upper respiratory tract infection, another preterm infant with an apnea episode following nosocomial infection, and thirdly, a term infant of a mother with influenza AH1N1 had severe respiratory distress and pneumothoraces needing high-frequency ventilation.     

Diabetes and endometrial cancer: effect modification by body weight, physical activity and hypertension

Among 777 endometrial cancer cases and 1550 controls from Italy and Switzerland, odds ratio was 1.7 (95% confidence interval: 1.2-2.5) for diabetes, and 5.1 for obese diabetic women as compared with non-obese non-diabetic ones. Diabetes shows a supramultiplicative effect with body mass index, but not with physical activity or hypertension.