Pituitary function and glucose tolerance in a family with a PAX6 mutation.

BACKGROUND: PAX6 is a transcription factor involved in the regulation of eye and islet cell development in humans and has also been shown to be an early marker of the pituitary gland in mice. While some subjects with PAX6 mutations were found to have impaired glucose tolerance or diabetes in two previous studies, there has been no report of systematic pituitary function assessment in these patients. AIM: The objective of this report was to assess pituitary function and glucose tolerance in five related patients with a heterozygous PAX6 mutation and an unusual ocular and neurological phenotype. SUBJECTS AND METHODS: Pituitary function (static and dynamic exploration of the five ante-pituitary axes) and glucose tolerance (oral glucose tolerance test) were explored in all patients. RESULTS: Glucose tolerance was normal in all patients. We found no obvious pituitary deficiency in four of the five patients. However, borderline cortisol levels were observed in three out of these patients, with subnormal values, at baseline and/or after stimulation test. Basal and stimulated cortisol levels were both more clearly diminished in one subject. CONCLUSIONS: We report here the first complete pituitary function assessment, together with glucose tolerance evaluations, in five related patients with a PAX6 mutation. We cannot rule out subtle corticotrope deficiency induced by PAX6 mutation. The conflicting results with the literature about glucose tolerance could be explained by genotype/phenotype correlations.

Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function.

In this single-institution study, we compared outcomes in diabetic recipients of living donor (LD) kidney transplants that did vs. did not undergo a subsequent pancreas transplant. Of 307 diabetic recipients who underwent LD kidney transplants from January 1, 1995, through December 31, 2003, a total of 175 underwent a subsequent pancreas after kidney (PAK) transplant; 75 were deemed eligible (E) for, but did not receive (for personal or financial reasons), a PAK, and thus had a kidney transplant alone (KTA); and 57 deemed ineligible (I) for a PAK because of comorbidity also had just a KTA. We analyzed the three groups (PAK, KTA-E, KTA-I) for differences in patient characteristics, glycemic control, renal function, patient and kidney graft survival rates, and causes of death. Kidney graft survival rates (actuarial) were similar in the PAK vs. KTA-E groups at one, five, and 10 yr post-transplant: 98%, 82%, and 67% (PAK) vs. 100%, 84%, and 62% (KTA-E) (p = 0.9). The long-term (greater than four yr post-transplant) estimated glomerular filtration rate (GFR) was higher in the PAK than in the KTA-E group: 53 +/- 20 mL/min (PAK) vs. 43 +/- 16 mL/min (KTA-E) (p = 0.016). The patient survival rates were also similar for the PAK and KTA-E groups. We conclude that the subsequent transplant of a pancreas after an LD kidney transplant does not adversely affect patient or kidney graft survival rates; in fact, it is associated with better long-term kidney graft function.

Two types of circulating endothelial progenitor cells in patients receiving long term therapy by HMG-CoA reductase inhibitors.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used to decrease cholesterol synthesis and are well established to reduce vascular diseases. Recently, it has been proposed that statins mobilize endothelial progenitor cells from bone marrow during the first four weeks, which could help to prevent vascular diseases. However, in humans there are few data concerning the long term effects of statin treatment on these endothelial progenitor cells. We investigated whether endothelial progenitor cells can be detected and characterized in patients receiving long term statin therapy. Mononuclear cells from patients receiving or not receiving statin therapy were assessed for progenitor cell content by flow cytometry and were cultured in specific conditions to determine the number and the type of progenitors. Our results showed there were significantly more CD34(+), CD34(+)/CD144(+) circulating progenitor cells in the statin(pos) group than in the statin(neg) group. In culture two types of endothelial progenitor cells were detected. Early endothelial progenitor cells gave colonies at day 5 comprising elongated cells whereas late endothelial progenitor cells generated cobblestone-like colonies with strong proliferation capacities. The number of circulating early endothelial progenitor cells was significantly higher in the statin(neg) group, while only late endothelial progenitor cells were detected in the statin(pos) group. Moreover, cells from cobblestones clearly had an endothelial phenotype CD31(+), VEGF-R2(+), CD34(+), CD146(+) in contrast to cells from colonies from early endothelial progenitor cells, which were VEGF-R2(low), CD34(-). These results strongly suggest that long term statin treatment specifically maintains late endothelial progenitor cells in circulation with a CD34(+)/CD144(+) phenotype.

[Erectile dysfunction in renal failure patients and renal transplant recipients]. / Dysfonction érectile chez les patients insuffisants rénaux et transplantés rénaux.

The frequency of erectile dysfunction can be increased in certain populations, such as patients with renal failure in whom the incidence of erectile dysfunction is estimated to be between 50% to 70% depending on the stage of renal failure. In this population, even more than in the general population, erectile dysfunction appears to be due to multiple aetiologies, combining organic and psychological disorders. Although renal transplantation is the treatment of choice for end-stage renal failure, it appears to have very variable effects on erectile dysfunction, as it may improve erectile dysfunction in the same way as global quality of life. However, some authors have demonstrated the aggravating role of renal transplantation on quality of erection, or even de novo appearance of erectile dysfunction. Progress in the fields of dialysis and renal transplantation have considerably improved the quality of life of patients with chronic renal failure. However, this improvement of quality of life does not always concern the patient's sex life. The main causes of erectile dysfunction in haemodialysed patients are endocrine disorders, uraemic neuropathy, tissue lesions related to chronic renal failure, and drugs. These factors of erectile dysfunction are partially corrected by transplantation, but other factors can subsequently be involved, such as drugs or vascular causes. The objective of this study is therefore to conduct a review of the literature on erectile dysfunction (epidemiology, pathophysiology, treatment) in patients with end-stage renal failure (dialysis) and after renal transplantation.