De novo deletion of 1q31.1-q32.1 in a patient with developmental delay and behavioral disorders.

We describe the case of a 6-year-old boy with a de novo deletion of the long arm of chromosome 1 encompassing band 1q31.1-q32.1, minor facial anomalies, mild developmental delay, and behavioral disorders. His postnatal karyotype was normal. Using array-comparative genomic hybridization, we identified and characterized a de novo 1q interstitial deletion of about 15.6 Mb, which partially overlaps those of other reported cases. We considered the gene content of the deleted region in an attempt to compare the clinical features of our patient with these other cases, even though they were not characterized molecularly in detail. The most remarkable difference was the absence of microcephaly. To the best of our knowledge, this is the first report of a de novo 1q31.1-q32.1 deletion. Moreover, it illustrates how molecular delineation associated with fine clinical characterization can improve the genotype-phenotype correlations of classical cytogenetic abnormalities.

Manifestaciones neurológicas de endocarditis infecciosa en niños / Neurologic manifestations of infective endocarditis in children

Introducción. La endocarditis infecciosa (EI), es una patología poco frecuente en pediatría. Según diferentes series pediátricas reportadas, 15 a 25% de los casos, presentan una complicación neurológica como forma de presentación inicial. Las manifestaciones neurológicas más frecuentes son: accidente cerebro vascular (ACV), abscesos cerebrales, meningitis, encefalopatía, convulsiones. Estas manifestaciones son atribuidas a diferentes etiologías, sin tener en cuenta a la EI como causa probable de las mismas. Material y métodos. Se revisaron las EI del 2008 al 2011, estudio retrospectivo observacional, analizándose los datos en Epi-info versión 2008. Resultados. Se registraron 7 casos; 5 reunían los criterios de Duke, 2 asumidos como endocarditis posible. Media de edad: 73 meses (R 11-162 meses); media de fiebre: 10 días (R 2-19). Dentro de las características clínicas: 3 pacientes tenían cardiopatía congénita, 2 desarrollaron insuficiencia cardiaca, 4 eran desnutridos, 2 presentaron síndrome nefrítico y 3 insuficiencia renal. Tres pacientes desarrollaron fenómenos embólicos en SNC, uno debutó con ACV, otro con aneurismas micóticos en SNC y el 3º con absceso cerebral. Estos 3 últimos pacientes tenían síndrome parameníngeo con LCR alterado y cultivo negativo. En 5 casos la vegetación se localizó en cavidades cardiacas derechas; 3 requirieron cirugía (verrugectomía y recambio valvular). Se aisló germen de hemocultivos en 6 pacientes, siendo el Staphylococcus aureus el más frecuente. Dos pacientes fallecieron. Conclusiones. Tres de los pacientes debutaron con síntomas de SNC como forma de presentación de EI. Consideramos que ante un niño con síntomas neurológicos, como hemiplejia, debemos pensar en endocarditis como probable etiología.

Manifestaciones neurológicas de endocarditis infecciosa en niños / Neurologic manifestations of infective endocarditis in children

Introducción. La endocarditis infecciosa (EI), es una patología poco frecuente en pediatría. Según diferentes series pediátricas reportadas, 15 a 25% de los casos, presentan una complicación neurológica como forma de presentación inicial. Las manifestaciones neurológicas más frecuentes son: accidente cerebro vascular (ACV), abscesos cerebrales, meningitis, encefalopatía, convulsiones. Estas manifestaciones son atribuidas a diferentes etiologías, sin tener en cuenta a la EI como causa probable de las mismas. Material y métodos. Se revisaron las EI del 2008 al 2011, estudio retrospectivo observacional, analizándose los datos en Epi-info versión 2008. Resultados. Se registraron 7 casos; 5 reunían los criterios de Duke, 2 asumidos como endocarditis posible. Media de edad: 73 meses (R 11-162 meses); media de fiebre: 10 días (R 2-19). Dentro de las características clínicas: 3 pacientes tenían cardiopatía congénita, 2 desarrollaron insuficiencia cardiaca, 4 eran desnutridos, 2 presentaron síndrome nefrítico y 3 insuficiencia renal. Tres pacientes desarrollaron fenómenos embólicos en SNC, uno debutó con ACV, otro con aneurismas micóticos en SNC y el 3º con absceso cerebral. Estos 3 últimos pacientes tenían síndrome parameníngeo con LCR alterado y cultivo negativo. En 5 casos la vegetación se localizó en cavidades cardiacas derechas; 3 requirieron cirugía (verrugectomía y recambio valvular). Se aisló germen de hemocultivos en 6 pacientes, siendo el Staphylococcus aureus el más frecuente. Dos pacientes fallecieron. Conclusiones. Tres de los pacientes debutaron con síntomas de SNC como forma de presentación de EI. Consideramos que ante un niño con síntomas neurológicos, como hemiplejia, debemos pensar en endocarditis como probable etiología.(AU)

Clinical significance of FGF-23 measurement in dialysis patients.

AIMS: Considering the growing relevance of fibroblast growth factor-23 (FGF-23) in the pathogenesis of chronic kidney disease bone and mineral disorder (CKD-MBD), an analysis was performed to determine the relative importance of C-terminal (cFGF-23) and intact (iFGF-23) assays in assessing CKD-MBD status in the first place and the relationship between FGF-23 and mortality as a secondary aim. METHODS: In 77 patients (15 peritoneal dialysis and 62 hemodialysis), levels of calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin- D (25D), 1,25D, FGF-23 (C-terminal and intact molecule) were measured and their correlations were analyzed. The relationship between FGF-23 levels and patient survival was also analyzed. RESULTS: A significant correlation was found between cFGF-23 and 1,25D, PTH and 25D while iFGF-23 was significantly correlated with phosphate, 25D and PTH. PTH and 1,25D were independent predictors of cFGF-23, while for iFGF-23 independent predictors were phosphate and 25D. No significant relationship was found between FGF-23 and mortality. CONCLUSIONS: C-terminal or intact FGF-23 levels are weakly correlated and thus not clearly indicative of FGF-23 effects on PTH, P and vitamin D metabolism in dialysis patients. Assays for cFGF-23 and iFGF-23 showed a good correlation, but the intact molecule was not superior in defining interactions with CKD-MBD molecules. Measuring FGF-23 on a regular basis with the current assays in CKD and dialysis patients does not yet seem clinically useful.

Unsuccessful application of taurolidine in the treatment of fungal peritonitis in peritoneal dialysis.

Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients, determining hospitalization, technique failure, catheter loss and death. In the 2005 update, treatment recommendations for FP from the International Society of Peritoneal Dialysis (ISPD) advocate catheter removal immediately after fungi are identified by microscopy or culture. The availability of more effective medical treatments could therefore be of great importance. The aim of this report is to describe a case of a 43-year-old, diabetic, HIV positive PD patient with fluconazole resistant Candida peritonitis, who was treated with an i.p. taurolidine solution. Taurolidine is a non-antibiotic antimicrobial, with broad bactericidal and fungicidal properties. It has been used during surgery for lavage of the peritoneum in cases of peritonitis. Its mechanism of action is related to direct toxic action on micro-organisms, through a chemical reaction between active taurolidine derivatives and structures on the cell wall. Treatment failed because the patient had severe burning pain during i.p. administration of the drug, limiting its dose. PD catheter removal allowed complete recovery. It remains undetermined if, with different doses and methodology, taurolidine could be more effective in treating bacterial and/or fungal peritonitis. Currently, catheter removal remains the most effective therapy of fungal peritonitis.

Pulse wave velocity measurements are reproducible in multiple trained observers: a short report.

BACKGROUND: Arterial stiffness, measured by pulse wave velocity (PWV), is highly predictive of mortality in dialysis patients. As such, PWV is frequently used in clinical research studies and may have a role in clinical practice if shown to be suitably reliable. Measurement of PWV using the SphygmoCor system is known to be an observer-dependent technique. The aim of this study was to investigate the ability of 4 observers to acquire reproducible PWV and pulse wave analysis (PWA) measurements after a 6-week training period. METHODS: Reproducibility of this technique was investigated using repeated measurements of the carotid-femoral PWV and PWA of the radial pulse by the 4 observers after a period of training. Both healthy volunteers and individuals with chronic kidney disease (CKD) were recruited for this study. Measurements were considered to have met quality control if 2 consecutive measurements were visually acceptable, within 1.5 m/s of each other and had a standard deviation of less than 10%. A fixed-effect analysis of variance was used to test the variation in measurements between the observers; the intraclass correlation coefficient (ICC) was used to assess the statistical agreement between the observers. RESULTS: A total of 20 individuals volunteered for PWV and PWA measurements (13 with CKD and 7 without); the mean age was 58 years (range 24-83). The average PWV was 9.4 +/- 3.6 m/s. There was no significant difference shown between the 4 observers' measurements (p = 0.25). Further, there was good statistical agreement between the observers (ICC = 0.95). CONCLUSIONS: After a period of training it is possible for multiple observers to have reproducible measurements of PWV and PWA. Assurance of reproducibility is important when more than one individual is collecting data in a study, particularly when assessing changes over time.

[Pathogenesis and treatment of vascular calcification in CKD]. / Invecchiamento cardiovascolare nel soggetto uremico: nuove acquisizioni.

Increased vascular calcification is a major cause of cardiovascular events in patients with chronic kidney disease (CKD). It is the result of an active ossification process counteracted by ''bone'' proteins such as osteopontin, alkaline phosphatase, osteoprotegerin, and osteocalcin. Chronic kidney disease - mineral and bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism that occurs in CKD. In addition to abnormalities in the serum calcium and phosphate profile, CKD-MBD is characterized by abnormalities of bone turnover, mineralization, volume and growth as well as vascular calcification. Considering that the presence and extent of vascular calcification in CKD portend a poor prognosis, many efforts have been made to shed light on this complicated phenomenon to prevent vascular calcium deposition and its progression. Indeed, careful control of calcium load, serum phosphate and parathyroid hormone along with the use of calcium-free phosphate binders and vitamin D receptor activators represent a new therapeutic armamentarium to improve quality of life and reduce mortality in CKD.

Early initiation of phosphate lowering dietary therapy in non-dialysis chronic kidney disease: a critical review.

Dietary management of hyperphosphatemia and hyperparathyroidism have long been important elements in the clinical management of CKD stage 4 and 5 for the prevention of mineral bone disease. The rationale for phosphate lowering has been further justified, given the accumulating data to support the association of phosphate with vascular damage, in this population who are at high risk of cardiovascular (CV) death. Phosphate is a novel CV risk factor in both CKD and in the general population, and a growing body of literature suggests that high normal serum phosphate may be a risk factor for progression of CKD. Few studies have examined hard outcomes after phosphate lowering. Nonetheless, given the balance of data both in cell, animal and human studies, the use of phosphate lowering strategies at earlier stages of CKD, perhaps even prior to serum phosphate level rising, may well be justified. This review will discuss the complications associated with higher serum phosphate, the potential benefits of early phosphate intervention, practical considerations of low phosphate diets and novel strategies for evaluating these strategies in clinical practice.

[New insights in the pathogenesis of secondary hyperparathyroidism]. / Nuove acquisizioni nella patogenesi dell'iperparatiroidismo secondario.

Parathyroid gland growth is a major cause of secondary hyperparathyroidism in renal failure. It is well known that high serum phosphate levels, low serum calcium levels and vitamin D deficiency are the three promoters of parathyroid hyperplasia in renal failure. Recent studies have investigated in depth the potential role of growth factors (transforming growth factor alpha) and their receptors (epidermal growth factor receptor) in the pathogenesis of parathyroid cell hyperplasia in chronic renal failure. The identification of molecular mechanisms involved in calcium, phosphate and vitamin D manipulations in an experimental renal failure model could help design more effective therapy for secondary hyperparathyroidism in uremic patients.

Facial changes in adult uremic patients on chronic dialysis: possible role of hyperparathyroidism.

BACKGROUND: Uremic patients on regular dialytic treatment (RDT) are often affected by a complex metabolic syndrome leading to osteodystrophy. Bone changes are primarily due to high bone turnover, often combined with a mineralization defect leading to increased bone fractures and bone deformities. Although rarely considered, the craniofacial skeleton represents one of the peculiar targets of this complex metabolic disease whose more dramatic pattern is a form of leontiasis ossea. This complication, although described, has never been evaluated in depth nor quantitatively assessed. In order to assess facial deformities in uremic conditions and to understand the possible relation with hyperparathyroidism, we undertook a quantitative evaluation of soft facial structures in a cohort of uremic patients undergoing RDT. METHODS: The three-dimensional coordinates of 50 soft-tissue facial landmarks were obtained by an electromagnetic digitizer in 10 male and 10 female patients with chronic renal insufficiency aged 53-81 years, and in 34 healthy individuals of the same age, ethnicity and sex. Uremic patients were enrolled according to hyperparathyroid status (PTH < 300 pg/mL and PTH > 500 pg/mL). From the landmarks, facial distances, angles and volumes were calculated according to a geometrical face model. RESULTS: Overall, the uremic patients had significantly larger facial volumes than the reference subjects. The effect was particularly evident in the facial middle third (maxilla), leading to an inversion of the mandibular-maxillary ratio. Facial dimensions were increased in all three spatial directions: width (skull base, mandible, nose), length (nose, mandible), and depth (mid face, mandible). The larger maxilla was accompanied by a tendency to more prominent lips (reduced interlabial angle). Some of the facial modifications (nose, lips, mandible) were significantly related to the clinical characteristics of the patients (age, duration of renal insufficiency and PTH levels). CONCLUSIONS: This report, the first in the literature, shows that facial structures of uremic patients are enlarged in comparison with matched normal subjects and that increased bone turnover could be responsible--at least in part--for facial bone changes.

Salvage insertion of tunneled central venous catheters in the internal jugular vein after accidental catheter removal.

PURPOSE: Tunneled catheters are widely used for intermediate to long-term hemodialysis (HD) access, but are prone to several complications that can require catheter replacement. Replacing malfunctioning catheters with a new line, placed in a different access site, can lead to problems with multiple vein occlusions. This has led many nephrologists to continue using the same vein as long as possible by guidewire catheter exchanges, to preserve other veins for future use. We describe a guidewire exchange technique for the Ash-Split catheter in the internal jugular vein. METHODS: In three patients, the exchange was performed because of partial catheter removal, as evidenced by the outward dislocation of the Dacron cuff. In these patients, the guidewire was inserted through the catheter. In two additional patients, the catheter had been completely removed by accident: the replacement of the dislodged tunneled venous catheters was attempted 5 hr and 1 day after accidental removal. In these patients, the guidewire was inserted through the previous tunnel. After guidewire placement, a skin incision was made in the supraclavicular region. The metal guidewire was easily located inside the fibrous structure that had previously surrounded the catheter. The guidewire was then extracted from the subcutaneous tunnel and used to insert a new catheter safely and easily after creating a new tunnel. Patients were routinely given antibiotic prophylaxis (1 g of cefazolin) immediately before the procedure. A strict aseptic technique was used, including several sterile glove changes. RESULTS: No infections developed following this procedure, which has the potential for bacterial contamination. All procedures were successful. Only in one patient did we have to convert to a different catheter: it was not possible to replace the old Ash-Split catheter with the same dual-lumen catheter because of difficulties in inserting the peel away introducer-catheter complex. In this patient, rather than forcing it with larger dilators or trying to disrupt the fibrin sheath with balloon dilatation, a single lumen Tesio catheter was successfully placed. In both patients who completely lost the previous catheter, the guidewire was readily reinserted through the subcutaneous tunnel into the vein. Catheter function was excellent in all patients, with a test blood flow rate on the 1st catheter use >350 ml/min. CONCLUSIONS: We described a new method for catheter exchange, which allows the easy insertion of a new catheter and the creation of a new and safer subcutaneous tunnel. In addition, we demonstrated that in cases of complete catheter removal, it is possible to reinsert a catheter in the same vein through a guidewire, even when reinsertion was attempted up to 1 day later.

Growth hormone secretion and bone histomorphometric study in thalassaemic patients with acquired skeletal dysplasia secondary to desferrioxamine.

An auxological and endocrinological study was performed in 21 thalassaemic patients with growth retardation and skeletal dysplasia secondary to desferrioxamine. Bone metaphyseal proximal tibial or iliac crest biopsy was performed in six patients with severe genu valgum or non-traumatic vertebral compression. GH insufficiency/deficiency (GH deficiency: peak after stimulation test below 6 ng/ml) was found in 72% of our thalassaemic patients with skeletal dysplasia, but in only 41% of patients without skeletal dysplasia. Bone histology showed abnormal chondrocytes, alteration of staining pattern of cartilage, irregular columnar cartilage and lacunae in the cartilaginous tissue. The behaviour of bone tissue was unpredictable (presence of thick or thin osteoid layer). Bone microfractures were sometimes present. The bone microstructure showed scarce mineralization, which was evenly or irregularly distributed. The bone tissue apatitic phase was quantitatively reduced. The hardness of bone tissue was remarkably lower than that of normal bone in three out of six patients. In conclusion, iron chelation therapy in patients with acquired skeletal dysplasia seems to interfere with GH secretion. The early identification of clinical and radiological abnormalities of skeletal dysplasia is of paramount importance in preventing severe bone destruction.

Use of testosterone to prevent cyclophosphamide-induced azoospermia.

BACKGROUND: Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations. OBJECTIVE: To study the possible protective effect of testosterone used to inhibit germinal cell activity in men who are receiving cyclophosphamide. DESIGN: Randomized, clinical trial. SETTING: University medical center. PATIENTS: 15 patients with the nephrotic syndrome who were treated with cyclophosphamide for 6 to 8 months. INTERVENTION: Five patients received daily oral cyclophosphamide, five received cyclophosphamide in monthly bolus injections, and five received monthly intravenous boluses of cyclophosphamide plus testosterone (100 mg intramuscularly every 15 days). MEASUREMENTS: Sperm counts, serum follicle-stimulating hormone levels, and serum luteinizing hormone levels were measured before, during, and after treatment with cyclophosphamide alone or cyclophosphamide plus testosterone. RESULTS: The 10 patients who did not receive testosterone became azoospermic during cyclophosphamide therapy. In only 1 of the 10 patients did the sperm count return to normal 6 months after discontinuation of therapy. Follicle-stimulating hormone levels were elevated in these patients (mean +/- SE, 19.20 +/- 1.28 IU/L in patients receiving oral cyclophosphamide and 16.04 +/- 2.22 IU/L in patients receiving intravenous cyclophosphamide alone). All 5 patients who received testosterone became azoospermic or severely oligospermic during treatment but had a normal sperm count 6 months after the discontinuation of therapy. In these patients, the mean sperm count was 45.78 +/- 3.89 x 10(6)/mL and follicle-stimulating hormone levels were normal (5.08 +/- 0.56 IU/L). CONCLUSION: Testosterone given to men before and during an 8-month cycle of cyclophosphamide therapy for the nephrotic syndrome may preserve fertility.

[Role of beta-carotene in the prevention of genotoxic damage in patients undergoing radiotherapy. Monitoring by the micronucleus test in exfoliative cells of the oral cavity]. / Ruolo del beta-carotene nella prevenzione dei danni genotossici in pazienti sottoposti a radioterapia. Monitoraggio mediante test del micronucleo in cellule esfoliate del cavo orale.

Radiotherapic treatment of patients with carcinoma usually causes genotoxis damage. This has been studied recently using the test of micronuclei in esfoliated cells. This test presents methodologic advantages in compared with the classic citogenetic analysis and as it is carried out on esfolieted cells from the oral cavity it faithfully reflects the genotoxic damage undergone by the cells of the basal layer of the epitelium. The preliminary result obtained so far have confirmed the anticlastogenic activity of beta-carotene in fact, the frequence of micronuclei in esfolieted cells from the oral cavity in patients undergoing radiotherapy or undergoing treatment with beta-carotene is inferior to that of patients undergoing treatment with beta-carotene is inferior to that of patients undergoing radiotherapy without the subministration of carotenoids. Treatment with carotenoids does not influence the therapeutic efficiency of radiotherapy treatment. Therefore, the results seem to confirm that indirect ossidaction processes are involved in the mechanism of the clastogenic action of radiotherapia. The carotenoids seem to be able to contrast validly this undesirable effect without interfering with the desirable therapeutic effect.