Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease.

AIM: Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. METHODS: In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. RESULTS: There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up. CONCLUSIONS: Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.

Association of Peutz-Jeghers-like mucocutaneous pigmentation with breast and gynecologic carcinomas in women.

Most reports describe an increased risk of malignancy in Peutz-Jeghers syndrome (PJS). We identified individuals with PJS-like pigmentation but no polyposis, designated as isolated mucocutaneous melanotic pigmentation (IMMP), and 1) characterized their clinical features, 2) assessed them for cancer events, and 3) screened a sample of these subjects for mutations in LKB1, a gene responsible for a portion of PJS cases. Review of Mayo Clinic records from 1945 to 1996 identified 26 patients with IMMP. All were then interviewed or their medical records reviewed to determine if cancer had developed. Conformation-sensitive gel electrophoresis (CSGE) screening for LKB1 mutations was followed by direct sequencing. Ten of these 26 individuals (38%) developed 12 malignancies that arose in the cervix (n = 3), endometrium (n = 3), breast (n = 1), kidney (n = 1), lung (n = 2), colon (n = 1), and lymphatic tissue (n = 1). In females with IMMP, the relative risk for cancer was 3.2 (95% CI, 1.2-6.9), while that for males was not increased. The relative risk for breast and gynecologic cancers was 7.8 (95% CI, 2.5-18.1) in affected females. Of 9 individuals tested, no LKB1 mutations were detected. Classical PJS is associated with an increased cancer risk. Our results indicate that IMMP is another lentiginosis with cancer predisposition. In particular, the relative risk for cancer in females with IMMP was significantly increased, as is true in females with PJS. However, LKB1 mutations did not contribute to the development of IMMP in the patients tested.

p73 mutations are not detected in sporadic and hereditary breast cancer.

Recently, a novel tumor suppressor gene, p73, was isolated and mapped to chromosome 1p36, a region commonly associated with loss of heterozygosity in neuroblastoma and other human malignancies, including breast cancer. The p73 gene shares considerable homology with the common tumor suppressor gene p53, both in composition and function. This study examines the potential participation of p73 in the pathogenesis of sporadic and hereditary breast cancers. Mutation analysis of 29 hereditary breast cancer cases revealed five independent silent mutations in the hereditary cases that are unlikely to play a role in tumor development. Mutation analysis of 48 sporadic breast tumors did not identify any unique variants. Eleven common polymorphisms scattered throughout the gene were also detected. Thus, mutations in the p73 gene appear to play little if any role in hereditary or sporadic breast cancer.