Two different therapeutic regimes in patients with sequelae of hemolytic-uremic syndrome

Renal disease is the most important long-term complication of hemolytic-uremic syndrome (HUS). A comparative study of renal function was carried out in two groups of patients. Group 1 included 19 children followed for a median of 11 years, 1960–1980, with a low-sodium diet, antihypertensive drugs, and a restricted protein intake in the end stage of renal disease. Group 2 included 26 children treated for a median of 9 years, 1988–2002, on a low-sodium diet, early restriction of protein intake according to recommendations, and angiotensin converting enzyme inhibitors (ACEi). Long-term renal function was assessed by the inverse of the plasma creatinine concentration (1/[Cr]) over time. Linear regression lines were fitted to individual values of 1/[Cr] for each child. Regression coefficients of children in group 1 were all negative, ranging from –0.031 to –0.00043; 7 were significantly different from zero, indicating a linear fall in renal function over time. In contrast, children from group 2 had 11 negative slopes (only 1 significant) and 15 positive slopes, ranging from 0.17893 to –0.3899. Fishers exact test showed that group 1 had significantly more children with negative slopes than group 2. This comparatively better long-term outcome of renal function in children under contemporary treatment was probably associated with early restriction of protein and use of ACEi.     

Survival and Recurrence After a Sphincter-Saving Resection and Abdominoperineal Resection for Adenocarcinoma of the Rectum At or Below the Peritoneal Reflection: A Multivariate Analysis

Purpose. The purpose of this study was to determine whether the type of operation [sphincter-saving resection (SSR) or abdominoperineal resection (APR)] for primary adenocarcinoma of the rectum at or below the peritoneal reflection affects survival and recurrence after curative surgery. Methods. This retrospective study included 184 patients who underwent curative surgery achieved by the following two types of operation between 1989 and 1998: (1) SSR (n = 116 patients) including a low anterior resection with either double-stapling technique (n = 86) or transanal coloanal anastomosis (n = 30); (2) APR (n = 91). The outcome factors evaluated were survival and tumor recurrence. Both univariate and corrected (multivariate Coxs and logistic regression) analyses were used to evaluate the data. The median follow-up was 47.4 months for patients alive at study conclusion. Results. Disease-free and disease-specific survivals, and the frequency and location of recurrence after surgery did not differ between the two types of operations. Multivariate analyses showed that the type of operation was not a significant independent variable in predicting disease-free survival or in the development of both local and distant recurrences after surgery. In addition, tumor-related factors (stage or histologic grade) were significant predictors of the outcome after surgery. Conclusions. The type of operation (SSR or APR) did not affect the survival or recurrence after a curative resection for adenocarcinoma of the rectum at or below the peritoneal reflection.     

Salt preference of congenic strains derived from the spontaneously hypertensive rat

Previous studies using reciprocal crosses between the spontaneously hypertensive rat (SHR) and the normotensive Wistar–Kyoto (WKY) strain suggested a role for the Y chromosome in the SHR's exaggerated preference for saline solutions. We have reexamined the role of the Y chromosome in the salt preference of the SHR using a consomic strain derived from SHR and Brown Norway (BN-Lx) progenitors. We also studied congenic lines in which regions of BN-Lx chromosomes 8 and 20 had been introgressed into the SHR genome. Animals were given a choice of water and 0.9% saline to drink over a period of 7 days and their total fluid intake (TFI; water plus saline) and saline preference (proportion of the TFI taken as saline) calculated. SHR bearing the BN-Lx Y chromosome had a significantly reduced saline preference when compared to progenitor SHR. Evidence was also found for the existence of a region on chromosome 8, which influences fluid intake in the SHR. The causative genes involved in these effects however remain to be determined.     

Systemic lupus erythematosus: a combined deficiency disease

To date, the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. By critically analyzing clinical facts and laboratory data, a hypothesis is proposed: drug-induced lupus erythematosus (DILE) is linked to a deficiency in Coenzyme A (CoA) that is secondary to a deficiency in pantothenic acid. This hypothesis is used to explain the high incidence of SLE in females, the role of sex hormones in this disease and the mechanism underlying a flare. The actions of anti-malarials and steroids are also discussed. The protean clinical presentation of SLE is attributed to co-existing deficiencies of dietary factors in addition to pantothenic acid. Contributing factors to these deficiencies may include increased nutritional requirements resulting from gene mutations. Treatment is replacement therapy with doses of pantothenic acid that is hundreds of times higher than that of the Dietary Reference Intake (DRI) and other vitamins. Using this method, 12 SLE females were studied with promising results.     

Determinants and characteristics of help provision for elderly people living at home and in relation to quality of life

The aim of this study was to investigate determinants of help from informal or formal caregivers or a combination of both among people aged 75 or more and living at home, and the characteristics of the recipients, the help they received and their quality of life (QoL). The sample for this study was 448 elderly people, 75-99 years of age, living at home and receiving help with activities for daily living, instrumental or both instrumental and personal. Regression analysis showed high QoL not to be significantly related to who was providing the help, whilst it was related to higher age, living with someone, lower number of complaints and managing to be alone at home. Multinomial regression analysis showed age, number of children, number of complaints, the ability to stay alone at home and living alone to predict receiving help from different kinds of caregivers. Recipients receiving help from informal caregivers were younger, more often married and living together with someone, whilst those receiving help from both informal and formal caregivers had more help with instrumental and personal activities for daily living and were not able to stay alone at home as much as those receiving help from other kinds of caregivers. Those receiving help from formal caregivers had fewer children, were single and were living alone more often than the other recipients. Thus the responsibility for help for elderly people rests heavily on informal caregivers, whom it seems essential to support. As public service at home is preferably given to those living alone or able to stay alone at home, those without relatives may not be able to remain at home when their need of help increases.     

What can intervention studies tell us about the relationship between fruit and vegetable consumption and weight management?

Given the recent surge in obesity, effective dietary strategies for weight management are required. Because fruits and vegetables are high in water and fiber, incorporating them in the diet can reduce energy density, promote satiety, and decrease energy intake. Although few interventions have specifically addressed fruit and vegetable consumption, evidence suggests that coupling advice to increase intake of these foods with advice to decrease energy intake is a particularly effective strategy for weight management. This approach may facilitate weight loss because it emphasizes positive messages rather than negative, restrictive messages.     

Evidence that unsaturated fatty acids are potent inhibitors of renal UDP-glucuronosyltransferases (UGT): kinetic studies using human kidney cortical microsomes and recombinant UGT1A9 and UGT2B7

Renal ischaemia is associated with accumulation of fatty acids (FA) and mobilisation of arachidonic acid (AA). Given the capacity of UDP-glucuronosyltransferase (UGT) isoforms to metabolise both drugs and FA, we hypothesised that FA would inhibit renal drug glucuronidation. The effect of FA (C2:0-C20:5) on 4-methylumbelliferone (4-MU) glucuronidation was investigated using human kidney cortical microsomes (HKCM) and recombinant UGT1A9 and UGT2B7 as the enzyme sources. 4-MU glucuronidation exhibited Michaelis-Menten kinetics with HKCM (apparent K(m) (K(m)(app)) 20.3 microM), weak substrate inhibition with UGT1A9 (K(m)(app) 10.2 microM, K(si) 289.6 microM), and sigmoid kinetics with UGT2B7 (S(50)(app)440.6 microM) Similarly, biphasic UDP-glucuronic acid (UDPGA) kinetics were observed with HKCM (S(50) 354.3 microM) and UGT1A9 (S(50) 88.2 microM). In contrast, the Michaelis-Menten kinetics for UDPGA observed with UGT2B7 (K(m)(app) 493.2 microM) suggested that kinetic interactions with UGTs were specific to the xenobiotic substrate and the co-substrate (UDPGA). FA (C16:1-C20:5) significantly inhibited (25-93%) HKCM, UGT1A9 or UGT2B7 catalysed 4-MU glucuronidation. Although linoleic acid (LA) and AA were both competitive inhibitors of 4-MU glucuronidation by HKCM (K(i)(app) 6.34 and 0.15 microM, respectively), only LA was a competitive inhibitor of UGT1A9 (K(i)(app) 4.06 microM). In contrast, inhibition of UGT1A9 by AA exhibited atypical kinetics. These data indicate that LA and AA are potent inhibitors of 4-MU glucuronidation catalysed by human kidney UGTs and recombinant UGT1A9 and UGT2B7. It is conceivable therefore that during periods of renal ischaemia FA may impair renal drug glucuronidation thus compromising the protective capacity of the kidney against drug-induced nephrotoxicity.     

Comparative effects of the antipsychotics sulpiride and risperidone in female rats on energy balance, body composition, fat morphology and macronutrient selection

Previous studies showed that the antipsychotic drugs (APDs) sulpiride (SUL) and risperidone (RIS) induced body weight gain (BWG), hyperphagia, and increased serum levels of leptin, prolactin and corticosterone in female rats. Neither SUL nor RIS increased BWG or food intake (FI) in male rats. To further develop the animal model of APD-induced obesity, SUL (20 mg/kg/sc), RIS (0.5 mg/kg/sc) or vehicle (1 cm³/kg/sc) were administered to female Wistar rats for 10 or 12 days. Body composition, fat tissue morphology, energy expenditure and food efficiency were assessed in animals fed a high-fat diet. In another experiment, macronutrient selection was evaluated in animals fed with pure diets. SUL and RIS significantly increased BWG and FI, with a stronger effect of SUL. Both drugs increased fat gain and food efficiency, and did not modify energy expenditure. Obesity was due to adipocyte hyperplasia. SUL-treated rats significantly decreased fat intake (p=0.039), showed a tendency to increase protein intake and did not modify carbohydrate consumption. No differences were observed between the RIS and the vehicle group. The macronutrient selection pattern differs from that observed in obese people undergoing APD treatment and in most animal models of obesity. Those findings suggest that SUL administration does not properly model APD treatment in humans. Results on macronutient selection in RIS-treated rats must be considered as preliminary, since in this experiment the animals did not gain weight significantly. Other diet protocols and lower APD doses must be tested to further characterize the RIS model.