CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation.

We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. INTRODUCTION: This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. METHODS: Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. RESULTS: At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m2, and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP (p < 0.01) and of 5.9 ng/ml for rs10741657 (p = 0.05) compared to the homozygous for the major polymorphisms (HMPs). Conversely, for rs10766197 and rs12794714 SNPs, HMP had the highest mean 25(OH)D levels with difference of 6 ng/ml for rs10766197 (p = 0.003) and of 4.8 ng/ml (p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. CONCLUSION: This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East.

[Infectious peritonitis in peritoneal dialysis: an over-emphasized complication]. / Péritonite infectieuse en dialyse péritonéale: une complication trop redoutée?

Peritoneal dialysis is an extrarenal epuration modality which uses physiological properties of peritoneum as a dialysis membrane. Despite the improvement of peritoneal dialysis techniques in the last ten years, peritonitis remains one of the most redoubt complications. Peritonitis may sometimes lead to technical failures, which need catheter removing, but rarely lead to death. Our retrospective study at the dialysis center of CHUV has analyzed factors which can predict this kind of complication. It calculates peritonitis rate and median peritonitis free-survival for different groups of patients. It also describes causatives organisms and their sensitivity to antibiotics.

Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients.

BACKGROUND: Poor medication adherence is a frequent cause of treatment failure but is difficult to diagnose. In this study we have evaluated the impact of measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet-HCl were included. Medication adherence was measured using the "Medication Events Monitoring System" during 3 months, followed by another 3-month period without monitoring. The adherence results were monthly discussed with the patients, as well as strategies to improve them. RESULTS: During monitoring, the percentage of prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs. 57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs. 3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p = 0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12) improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/- 326 pg/ml (p = 0.04), without any change in medication. However, as drug monitoring was interrupted, all laboratory parameters worsened again. CONCLUSIONS: Assessment of drug adherence helped to document episodes of non-compliance and helped to avoid seemingly necessary dose increases.

The leptin/adiponectin ratio: potential implications for peritoneal dialysis.

Leptin and adiponectin are adipokines with respective pro-atherogenic and anti-atherogenic properties, defining the plasma leptin/adiponectin ratio as a novel marker for atherosclerosis. In non-renal patients, both hyperleptinemia and hypoadiponectinemia are associated with cardiovascular complications. In peritoneal dialysis (PD) patients, the leptin/adiponectin ratio is markedly elevated, which is consistent with their increased cardiovascular risk. As glucose metabolism regulates adipokines, we hypothesized that glucose and/or other PD fluid components may affect adipokine production balance. This review summarizes the available data arising from research in this area. In 3T3-L1 adipocytes, glucose-based PD4 1.36% significantly increased leptin secretion vs amino-acid-based (AA) and icodextrin (ICOD)-based PD fluids. In contrast, adiponectin secretion was significantly reduced by PD4 1.36% vs glucose-free dialysates. Glucose concentration in PD fluids was shown to determine leptin secretion. Preliminary data from PD patients showed that a single 6-h dwell with PD4 3.86% glucose acutely increased plasma leptin vs AA (P<0.05). The reduction in glucose load in a standard PD regimen was associated with an improvement in the plasma leptin/adiponectin ratio at 6 months. pH-neutral PD fluids increased leptin secretion in vitro vs acidic PD fluids, without effect on adiponectin. Whether this effect may have an impact on plasma leptin levels in PD patients is unknown. In conclusion, glucose-based PD fluids worsen the adipokine production balance in vitro while glucose-free solutions improve it. In PD patients, hypertonic glucose-based PD fluids may increase plasma leptin levels. Glucose-sparing PD regimens appear to improve the leptin/adiponectin ratio. However, their potential to reduce cardiovascular complications needs to be demonstrated.

[Chronic renal failure: what diet?]. / Insuffisance rénale chronique: quel régime?

A low protein diet has been traditionally advocated in patients with chronic renal failure (CRF), in order to slow its progression. However, CRF is often associated with malnutrition, aggravating its prognosis, especially in elderly patients. In severe CRF, the spontaneous reduction of appetite coupled with additional restrictions regarding sodium, potassium and phophates may further impact on nutrition status. The potential benefit of a low protein diet is therefore questionable. We only recommend a moderately restricted protein diet (0,8 g/kg/day) in selected patients with no sign of malnutrition. This strategy, if applied, must be supported by a multidisciplinary approach involving a nephrologist and a specialised dietician. Additional dietary restrictions are not justified, except in particular situations.

[Malnutrition on dialysis: the end of a fatality]. / Dénutrition en diatlyse: vers la fin d'une fatalité.

Protein-energy malnutrition in patients treated with haemodialysis (HD) is a complex, multifactorial and prevalent problem, starting well ahead of the dialysis program. It is associated with an increased morbidity and mortality. Uraemic patients are relatively resistant to nutrients because of metabolism abnormalities. Prevention of malnutrition is therefore more efficient than treatment per se. Classical supplementation including oral nutritional supplements, intradialytic parenteral nutrition and enteral nutrition remain efficient, if applied for a sufficient time. A global approach coupling supplementation and strategies designed to optimise metabolism abnormalities should increase treatment efficacy and improve the outcome and quality of life of these patients.

[Unusual location of a parathyroid adenoma: the carotid sheath]. / Localisation atypique d'un adénome parathyroïdien: la gaine carotidienne.

We report the imaging features of an occult parathyroid adenoma with unusual location in the carotid sheath. Our patient presented with primary hyperparathyroidism. Following negative neck ultrasound and scintigraphy, exploratory neck dissection with partial thyroidectomy was performed twice over a 2 day period without biological response. Cervical and mediastinal CT and MRI were performed with no result. Digital angiography showed a tumoral blush supplied by the left inferior thyroid artery and located in close contact with the carotid artery. Venous sampling of the neck confirmed the left location of the adenoma and a third surgical intervention found the adenoma embedded in the left carotid sheath. This is an unusual case of parathyroid adenoma that necessitated the use of several imaging techniques.

[IgA nephropathy: what you have need to know in 2005]. / Maladie de Berger: que faut-il savoir en 2005?

Although considered as a benign glomerulopathy, IgA nephropathy (IgAN) is now a well-known cause of end-stage renal disease (ESRD). Fifty percent of people suffering from IgAN developp renal insufficiency and 20 to 30% may reach ESRD after 20 to 25 years of evolution. ACEI is indicated to obtain a thigh control of blood pressure and to reduce proteinuria. Corticosteroids alone or in association with immunosuppressants are indicated for agressive, proliferative form of the disease or when there is an unfavorable outcome despite symptomatic treatment.

[Angioplasty with stenting for buttock claudication]. / Angioplastie avec mise en place d'un stent pour occlusion fessière.

We report the case of a patient presenting severe buttock claudication with normal neurologic and osteoarticular exams. He underwent a guidewire recanalization of his occluded superior gluteal artery followed by a percutaneous angioplasty with stenting, resulting in total relief of symptoms. This observation represents the first publication describing the use of a stent with recanalization of the gluteal artery. The technique seems promising for buttock pathology.

The DD genotype of the ACE gene polymorphism is associated with diabetic nephropathy in the type-1 diabetics.

Genetic factors are involved in the development of diabetic nephropathy in type-1 diabetes. We are examining the association of the angiotensin-converting enzyme (ACE), insertion/deletion (I/D) polymorphism with the presence of diabetic nephropathy in type-1 diabetic patients. 52 type-1 diabetic patients with diabetic nephropathy (30 with either microalbuminuria or macroalbuminuria and 22 with end stage renal disease on dialysis) were compared with 10 type-1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years and 27 non-diabetic healthy subjects. We found that the D-allele frequency was higher in patients with nephropathy than in the healthy and normoalbuminuric controls. There was an association in the DD polymorphism of the ACE gene with patients with diabetic nephropathy and not with the control subjects. We conclude that the DD genotype of ACE gene polymorphism is associated with diabetic nephropathy in patients with type-1 diabetes mellitus.

[Living donors in kidney and liver transplantation]. / Le donneur vivant: transplantation de rein et de foie.

The shortage of organs available for transplantation has rekindled the interest for the kidney living donor, and has recently induced the use of living donors for liver transplantation too. Both methods raise many medical and ethical interrogations. The aim of this paper is to analyse this type of organ harvesting, and to report our experience and results with kidney and liver living donors.

[Laparoscopic nephrectomy in the liver donor: introduction of the method and preliminary results]. / Néphrectomie par laparoscopie chez le donneur vivant: introduction de la méthode et résultats préliminaires.

INTRODUCTION: The shortage of organs available for renal transplantation has focussed attention on the use of live donors. Techniques for laparoscopic nephrectomy have recently been described, which have limited morbidity, duration of hospitalization and the period off work. However, these surgical procedures are difficult, and may be risky for the organ to be transplanted. METHOD: The laparoscopic live donor nephrectomy was introduced in stages, including the use of a videoconference from a reference center. In this article, the prospective analysis of the present authors' preliminary results has been presented. RESULTS: Ten kidneys were removed by laparoscopy, i.e., three from the left and seven from the right side. No conversion of this technique to laparotomy was necessary. The mean warm ischemic time was five minutes, and in the last six operations it did not exceed three minutes. The patients were able to leave hospital between four and eight days following surgery. After a mean follow-up of 10.5 months, organ survival was 100%, and in all grafts excellent function was observed. CONCLUSION: The quality of these preliminary results which may act as a reference and the careful introduction of a live donor laparoscopic program could provide an incentive to potential donors, and thereby increase the pool of organs available for transplantation.

Detection of low level benzene exposure in supermarket wrappers by urinary muconic acid.

Women who use the 'hot wire' and 'cool rod' machines to wrap meat in supermarkets are potentially exposed to low levels of benzene and polycyclic aromatic hydrocarbons present in fumes emitted during the thermal decomposition of the plastic used to wrap meat. In order to evaluate whether the benzene metabolite trans, trans-muconic acid (MA) can be used to monitor these low levels, we collected urine samples from supermarket workers, and assayed the urine for MA. Geometric mean after-shift MA levels were highest for subjects who used the 'hot wire' machine, i.e. > 300 ng mg-1 creatinine (Cr). The corresponding levels for subjects who used the 'cool rod' machine were similar to those for subjects who did not use either type of machine, and were much lower. These results indicate that urinary muconic acid has some potential for use in monitoring benzene exposures of less than 1 part per million (ppm). The study detected very high background MA levels (exceeding 2000 ng mg-1 Cr) in some subjects, suggesting that individuals in the general population without occupational exposure to benzene may have urinary MA levels equivalent to exposure to up to 2 ppm benzene in ambient air. However, since non-benzene sources of the metabolite cannot be completely ruled out as partially responsible for these high levels, the public health significance of this finding is not known at the moment.

Influence of antigen presentation and exogenous cytokine activity during in vitro primary immunizations employed for the generation of monoclonal antibodies.

Hybridomas secreting monoclonal antibodies (MAbs) against African horse sickness virus (AHSV) were generated using different AHSV antigen preparations (inactivated AHSV, semi-purified virus, and a preparation of nonstructural viral proteins) in one of three different in vitro primary immunization systems: (i) the Cel-prime kit, a method using immunization of splenocytes aided by antigen-primed support cells; (ii) a system based on a cytokine soup derived from a mixed lymphocyte reaction plus stimulated EL4-IL-2 cells; (iii) a system based on a cytokine soup derived from splenocytes stimulated by pokeweed mitogen in order to obtain a mixture of cytokines enriched for Th2 lymphokines. The viability of immunized BALB/c mouse splenocytes, immunoglobulin production by the subsequently generated hybridomas, and the specificity of the MAbs were compared. The most efficient in vitro primary immunization system was the Cel-prime system employing semi-purified antigen. This efficiency was manifest in terms of a greater viability of the splenocytes in the immunization, as well as a higher number of specific antibody-secreting hybridomas. It seems probable that the support cells of the Cel-prime system have an accessory function such as that attributed to antigen-presenting cells. Such a function would result in impairment of apoptosis, and thus increase the viability of the splenocytes in the in vitro primary immunization system, as well as enhancing stimulation of the immune response against the antigen used. The presence of cytokines at the beginning of the in vitro primary immunization did have an influence, but this was secondary to what appeared to be the major event of cellular interaction associated with the accessory cell function of the support cells.

Expression of early and late activation markers on peripheral blood T lymphocytes does not reliably reflect immune events in transplanted hearts.

Monoclonal antibodies directed against early (receptors for interleukin-2 and transferrin [IL-2R, TfR]) and late (PTA1, alpha 1 integrin VLA-1) activation antigens were used as probes to monitor cardiac transplant patients for episodes of acute graft rejection. Age- and sex-matched patient control groups consisting of 11 patients awaiting cardiac transplantation and 13 kidney transplant recipients with long-term grafts, respectively, were used to define an upper limit for normal activation antigen expression (mean + 3 SD) in patients. Expression of all cell markers was significantly higher in both patient control groups than in healthy control individuals. Therefore, the level of activation marker expression in heart patients awaiting transplantation was used as comparison for the patient population under study. Sequential monitoring of 24 heart transplant recipients failed to demonstrate a significant correlation of increased activation marker expression with clinical events of immune activation. Subsequently 62 consecutive endomyocardial biopsy scores in 36 patients were compared with the expression of IL-2R, TfR and VLA-1 on peripheral blood T cells. Neither increased cellular infiltration of the endocardium, nor of the myocardium, was associated with increasing proportions of IL-2R, TfR, or VLA-1 positive T cells. Elevated T-cell expression of the three markers combined indicated acute graft rejection with a sensitivity, specificity, and overall accuracy of 38%, 52%, and 43%, respectively. Acute graft rejection in biopsies with associated myofiber damage (biopsy rejection scores 2 and 3A,B) was not associated with a change in the proportion of activated T cells in circulation within the first 6 months after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)