Simvastatin increases AQP2 urinary excretion in hypercholesterolemic patients: A pleiotropic effect of interest for patients with impaired AQP2 trafficking.

We previously reported that statins improve the symptoms of X-linked nephrogenic diabetes insipidus (X-NDI) in animal models. The aim of this study was to verify whether the pleiotropic effect of statins on AQP2 trafficking and kidney-concentrating ability, observed in rodents, was attainable in humans at therapeutic doses. We enrolled 24 naïve hypercholesterolemic patients and measured urine excretion of AQP2 (uAQP2) at baseline and during 12 weeks of treatment with simvastatin 20 mg/day. Simvastatin induced a rapid and significant increase of uAQP2, reduced the 24-hour diuresis, and increased urine osmolality. These effects were also maintained in patients chronically treated with statins for at least 1 year. This study strongly suggests that statins may effectively enhance the efficacy of current pharmacological treatment of patients with urine-concentrating defects caused by defective AQP2 plasma membrane trafficking, like X-NDI.

Prevalence of dental anomalies in children with cleft lip and unilateral and bilateral cleft lip and palate.

AIM: To examine the prevalence of different types of dental anomalies in children with nonsyndromic cleft lip, unilateral cleft lip-palate, and bilateral cleft lip-palate. MATERIALS AND METHODS: A sample of 90 patients (aged 4-20 years) affected by isolated cleft lip, unilateral and bilateral cleft lip and palate was examined. Cleft patients were classified into one of three groups according to cleft type: (1) Unilateral Cleft Lip-Palate, (2) Bilateral Cleft Lip-Palate, and (3) Cleft Lip. Intraoral exams, panoramic radiographs and dental casts, were used to analyse the prevalence of the various dental anomalies included in this study. RESULTS: There were no statistically significant differences between patients with cleft lip, unilateral cleft lip and palate and bilateral cleft lip and palate. The congenital absence of the cleft-side lateral incisor was observed in 40% of the sample, and a total of 30% patients showed supernumerary teeth at the incisors region. Second premolar agenesis was found in 4.4% of patients, whereas in 18.9% of the sample there was an ectopic dental eruption. Lateral or central incisors rotation was noted in 31.1% of the sample, while shape anomaly, lateral incisor microdontia, and enamel hypoplasia were detected respectively in 25.6%, 5.6% and 18.9% of cleft patients. CONCLUSION: High prevalence of different dental anomalies in children with cleft lip and unilateral and bilateral cleft lip and palate has been confirmed. This study, in particular, shows the presence of ectopic and rotated teeth in the cleft area.

Speech outcome in unilateral complete cleft lip and palate patients: a descriptive study.

AIM: In this study, resonance and articulation disorders were examined in a group of patients surgically treated for cleft lip and palate, considering family social background, and children's ability of self monitoring their speech output while speaking. MATERIALS AND METHODS: Fifty children (32 males and 18 females) mean age 6.5 ± 1.6 years, affected by non-syndromic complete unilateral cleft of the lip and palate underwent the same surgical protocol. The speech level was evaluated using the Accordi's speech assessment protocol that focuses on intelligibility, nasality, nasal air escape, pharyngeal friction, and glottal stop. Pearson product-moment correlation analysis was used to detect significant associations between analysed parameters. RESULTS: A total of 16% (8 children) of the sample had severe to moderate degree of nasality and nasal air escape, presence of pharyngeal friction and glottal stop, which obviously compromise speech intelligibility. Ten children (10%) showed a barely acceptable phonological outcome: nasality and nasal air escape were mild to moderate, but the intelligibility remained poor. Thirty-two children (64%) had normal speech. Statistical analysis revealed a significant correlation between the severity of nasal resonance and nasal air escape (p ≤ 0.05). No statistical significant correlation was found between the final intelligibility and the patient social background, neither between the final intelligibility nor the age of the patients. CONCLUSION: The differences in speech outcome could be explained with a specific, subjective, and inborn ability, different for each child, in self-monitoring their speech output.

Anemia, inflammation and health-related quality of life in chronic kidney disease patients.

BACKGROUND: There is controversy regarding whether an incremental increase in hemoglobin levels is associated with improvements in health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients treated with erythropoiesis-stimulating agents (ESAs). We hypothesized that HRQOL in anemic CKD patients has a multifactorial etiology, including the effects of anemia and inflammation. METHODS: 69 non-dialysis CKD patients over 18 years of age with a mean estimated glomerular filtration rate (eGFR) of 43.7 ± 28.8 ml/min/1.73 m2 were divided into anemic and non-anemic cohorts. Kidney disease quality of life (KDQOL) was prospectively recorded using Short Form (SF)-36 components of KDQOL-SF-™ version 1.3 questionnaire. Inflammation was assessed by using a composite of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α levels in the upper two quartiles. RESULTS: Anemic patients had significantly worse SF-36 components of KDQOL-SF-™ version 1.3, including SF-12 mental component (p = 0.02), role emotional (p = 0.002) and physical function (p = 0.01) compared to patients without anemia. However, in multiple linear regression models, adjusted for GFR, age, gender and inflammatory markers including C-reactive protein (CRP), albumin, ferritin, IL-6, IL-8 and TNF-α, anemia predicted mental components of SF-36 (SF-12 mental component (p = 0.02) and role emotional (p = 0.04)) but not physical components (SF-12 physical component (p > 0.05) and physical function (p > 0.05), supporting the multifactorial nature of reduced HRQOL in anemic patients. CONCLUSIONS: Reduced HRQOL in anemic patients is likely related to both anemic and inflammatory status. Prospective studies will be needed to evaluate whether modulating the inflammatory state independent of changes in the hemoglobin concentration improves physical components of HRQOL.

Urine proteomics--prospects for future diagnostics.

This brief overview of the potential diagnostic, prognostic and pathophysiological value of studies into the urine proteome describes hypothesis-driven investigations of individual proteins and proteome-wide search for urinary biomarkers of various diseases and their progression. It is intended to illustrate the recent progress in the area of urine proteomics and proselytize for the promise of this centuries-old technique of uroscopy, yet to reveal its secrets, using modem approaches.

Aquaporin-2 excretion and renal function during the 1st week of life in preterm newborn infants.

In many preterm infants, a characteristic pattern of fluid and electrolyte homeostasis occurs during the 1st week of life, consisting of three phases: prediuretic, diuretic, and postdiuretic. In this study, we evaluated the possible role of aquaporin-2 (AQP2) in renal concentrating ability and correlated it with other markers of the renal function in healthy preterm infants. Daily urine and spot blood samples were collected from 9 healthy preterm (32 +/- 1 weeks) infants at postnatal ages 1, 3, and 7 days. Urine and serum osmolality, creatinine, electrolytes, and AQP2 excretion were measured. All infants showed a significant (about 7%) weight loss on day 3 associated with a more than threefold increase in urine output without a significant change in fluid intake (diuretic phase). The creatinine clearance increased on day 3, indicating an increase in glomerular filtration rate. Interestingly, on day 3, the level of total excreted AQP2 (pmol/h) was significantly higher when compared to day 1 and day 7, and the same tendency was observed for urine osmolality. To conclude, the observed increase in urine osmolality and creatinine clearance during the diuretic phase, paralleled by an increase in total AQP2 excretion, suggests that AQP2 can contribute to the urinary concentrating ability early in postnatal life.

Water immersion is associated with an increase in aquaporin-2 excretion in healthy volunteers.

Here, we report the alterations in renal water handling in healthy volunteers during a 6 h thermoneutral water immersion at 34 to 36 degrees C. We found that water immersion is associated with a reversible increase in total urinary AQP2 excretion.

I-131 MIBG scintigraphy of neuroectodermal tumors. Comparison between I-131 MIBG and In-111 DTPA-octreotide.

An account is given of the results observed with I-131 MIBG scintigraphy in four patients (1 bladder pheochromocytoma, 3 neuroblastomas) chosen on account of their particular clinical and diagnostic interest from a series of 41 apudoma patients examined by means of this technique. In the first patient, the unusual site of the tumor in the posterior wall of the bladder meant that its detection by I-131 MIBG was only possible after catheterization of the bladder. In the second patient, uptake in the metastasis was only evident after removal of the primary tumor. In the third patient, the scintiscan revealed several metastases (some in bone) not detected by CT. In the fourth patient (congenital neuroblastoma), enhanced uptake accompanied the appearance of high plasma catecholamine and urinary vanillylhandelic acid values, suggesting a functional switch from a nonsecreting to a secreting form. a supplementary In-111 DTPA-Octreotide (OCT) scintiscan of this patient demonstrated the presence of somatostatin receptors on the neuroblasts. Thus, this examination would seem particularly useful for the differentiation of nonsecreting neuroblastomas. Its employment in assessment of the therapeutic capacity of OCT itself is also suggested.