[Compound heterozygosis with novel AQP2 gene mutation in sisters affected by autosomal congenital nephrogenic diabetes insipidus].

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder, mostly caused by antidiuretic hormone receptor type 2 (ADHR2) gene mutations, which are inherited as X-linked traits. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene, inherited in autosomal recessive or dominant manner. We report the case of two adult sisters, of 30 and 27 years of age, diagnosed in early infancy with X-linked CNDI. The patients' sex and family history did not fit in well with this diagnosis, so we sequenced the coding regions of the ADHR2 and AQP2 genes. As expected, no mutations were found in the ADHR2 gene, while we found a compound heterozygosis for two different mutations in the AQP2 gene. A missense mutation (c. 439G>A, p.Ala147Thr), an already known cause of CNDI, and a novel missense putative mutation of an adenine to cytosine at position 551 (c.551A>C), resulting in the substitution of asparagine with threonine at amino acid position 184 (p.Asn184Thr). This second mutation changes a fundamental extracellular Asn-Pro-Ala motif (NPA) of the AQP2 protein, inhibiting its function. Its pathogenicity has been confirmed by in silico predictions and is in line with comparable alterations to the intracellular NPA motif of the AQP2 protein.

Congenital diaphragmatic hernia: endotracheal fluid phospholipidic profile following tracheal occlusion in an experimental model.

OBJECTIVE: To compare endotracheal fluid (EF) and amniotic fluid (AF) phospholipidic profile changes following tracheal occlusion (TO) in the congenital diaphragmatic hernia (CDH) fetal lamb model, in order to support the efficacy of TO on lung maturity. METHODS: A diaphragmatic defect was induced at 70 days' gestation, TO was carried out at day 102 and cesarean section at 136 days' gestation. EF and AF samples, collected at delivery, were evaluated using mass spectrometry (the analysis focused on palmitoyloleoyl-phosphatidylcholine [POPC, PC(18:1/16:0)], dipalmitoyl-phosphatidylcholine [DPPC, PC(16:0/16:0)] and sphingomyelins [SMs]). RESULTS: The effects of CDH and TO were different on AF and EF. POPC levels were higher than DPPC levels in AF of healthy lambs. Following induction of the diaphragmatic malformation, an evident decrease in POPC was noted, while a substantial return to normal POPC levels and an increased DPPC peak were prompted by the TO. After CDH induction, a decrease in N-palmitoyl-D-sphingomyelin [SM(d18:1/16:0)] was revealed (P<0.01) and an increased peak in SMs in AF was prompted by the TO (P=0.05). While the most represented phosphatidylcholine (PC) species in EF of healthy lambs was DPPC, CDH induced a decrease in the DPPC peak and treatment with TO induced its partial recovery. SMs were detectable only in healthy EF samples. CONCLUSION: The phospholipid recovery profile following TO suggests the potential role of this therapy in restoring processes involved in surfactant-mediated lung maturation, even though other interactions involved in AF turnover should be considered. Moreover, these metabolites could be used as biomarkers of fetal pulmonary development.

Retrospective comparison of two different approaches for ultrasound-guided internal jugular vein cannulation in hemodialysis patients.

BACKGROUND: Prevalent hemodialysis patients with vascular access consisting of a central venous catheter (CVC) are continuously increasing over the years. Improvement in evolution and CVC placement procedures represents therefore an essential tool to enhance performance and reduce intraoperative and long-term CVC complications. Internal jugular vein (IJV) catheterization techniques are different according to ultrasound probe position in relation to vein axis and to needle direction in relation to ultrasound beam. Lateral in-plane (LIP) approach has been proposed to be advantageous compared to traditional anterior out-of-plane (AOP) technique. METHODS: In this retrospective nonrandomized study we evaluated outcomes of 337 hemodialysis CVCs positioned in our center (Dono Svizzero Hospital) between 2011 and 2016, 237 using the AOP technique and 100 using the LIP approach. RESULTS: We found no significant differences among considered outcomes (procedure success, arterial puncture, pneumothorax, first-use malfunction, kinking/pinching) between the two approaches. CONCLUSIONS: In our experience AOP and LIP approaches have shown the same outcomes. However, we believe that the LIP technique has potential benefits and it should be considered in the decision process of IJV cannulation.

Phospholipid profile of amniotic fluid in ovine model of congenital diaphragmatic hernia (CDH): the effect of fetal tracheal occlusion.

Fetal endoscopic tracheal occlusion has been proposed as a prenatal intervention to ameliorate congenital diaphragmatic hernia (CDH) prognosis. Tracheal occlusion (TO) prevents pulmonary fluid egress, leading to tissue expansion, reversal of lung hypoplasia, and potential maturation. Fetal lung maturity strongly correlates with amniotic fluid (AF) phospholipidic composition. In this preliminary study, we characterized the AF phospholipidic profile in CDH-induced, TO-treated, and healthy fetal lambs to define the prenatal treatment benefits of TO on lung maturity. CDH induction was performed at 70 days of gestation, TO was carried out at 102 days of gestation, and caesarean section was carried out at 136 days of gestation. AF samples, taken at 102-136 days of gestation, were evaluated using mass spectrometry. The analysis focused on phosphatidylcholines (PCs) and sphingomyelins (SMs). The most abundant phosphatidylcholine species retrieved in healthy AF was POPC [PC(18:1/16:0)], while the level of DPPC [PC(16:0/16:0)] was extremely low at both gestational ages. CDH induction caused a decrease in POPC and many other PCs. A substantial return of some PCs, in particular POPC, PC(34:2) and PC(18:0/16:0), to a more physiological level was prompted by TO. SMs were unaltered. The AF phospholipidic profile could provide prenatal prognostic markers of CDH and possible indices of lung maturation after fetal treatment.

Catalyst activity or stability: the dilemma in Pd-catalyzed polyketone synthesis.

A series of Pd-complexes containing nonsymmetrical bis(aryl-imino)acenaphthene (Ar-BIAN) ligands, characterized by substituents on the meta positions of the aryl rings, have been synthesized, characterized and applied in CO/vinyl arene copolymerization reactions. Crystal structures of two neutral Pd-complexes have been solved allowing comparison of the bonding properties of the ligand. Kinetic and mechanistic investigations on these complexes have been performed. The kinetic investigations indicate that in general ligands with electron-withdrawing substituents give more active, but less stable, catalytic systems, although steric effects also play a role. The good performance observed with nonsymmetrical ligands is at least in part due to a compromise between catalyst activity and lifetime, leading to a higher overall productivity with respect to catalysts based on their symmetrical counterparts. Additionally, careful analysis of the reaction profiles provided information on the catalyst deactivation pathway. The latter begins with the reduction of a Pd(II) Ar-BIAN complex to the corresponding Pd(0) species, a reaction that can be reverted by the action of benzoquinone. Then the ligand is lost, a process that appears to be facilitated by the contemporary coordination of an olefin or a CO molecule. The so formed Pd(0) complex immediately reacts with another molecule of the initial Pd(II) complex to give a Pd(I) dimeric species that irreversibly evolves to metallic palladium. Mechanistic investigations performed on the complex with a nonsymmetrical Ar-BIAN probe evidence that the detected intermediates are characterized by the Pd-C bond trans to the Pd-N bond of the aryl ring bearing electron-withdrawing substituents. In addition, the intermediate resulting from the insertion of 4-methylstyrene into the Pd-acyl bond is a five-member palladacycle and not the open-chain η(3)-allylic species observed for complexes with Ar-BIANs substituted in ortho position.

[Peritoneal dialysis in adult patients with prune belly syndrome: an impossible challenge?]. / Dialisi peritoneale nel paziente adulto con sindrome di prune belly: sfida possibile?

Prune belly syndrome (PBS) is a rare congenital syndrome characterized by hypoplasia of the abdominal muscles, urinary tract malformations, and cryptorchidism in males. The estimated incidence is 1 in 35,000 to 50,000 live births. Chronic renal failure and end-stage renal disease (ESRD), due both to different degrees of renal hypoplasia or dysplasia and infectious complications, develops in 20-30% of patients who survive the neonatal period. No data are available on progression time to ESRD, owing to the variability of the phenotypic features of nephropathy. Nevertheless, PBS is primarily a pathology of pediatric interest as demonstrated, for example, by the reported average age at transplantation which usually does not exceed fifteen years of age. Therefore the need for renal replacement therapy (RRT) in adult patients with PBS is unusual. It is reasonable to suppose that the abdominal muscular defects may represent a limit for peritoneal dialysis (PD) utilization in PBS adult patients in many Kidney Units where, conversely, treatment with hemodialysis would be probably the easier choice. Here we describe the case of a 44 -year- old man with PBS who, at the age of 41, required RRT and was faced with the challenge of accepting PD. After more than three years of nocturnal automated peritoneal dialysis treatment we can safely say, as the following case illustrates, that PD is a feasible option in PBS adult patients.

[Acute heart failure secondary to takotsubo cardiomyopathy in a patient on peritoneal dialysis with residual renal function loss]. / Insufficienza cardiaca acuta secondaria a cardiomiopatia Takotsubo in paziente in dialisi peritoneale con perdita della funzione renale residua.

Takotsubo cardiomyopathy (TTC) is characterized by clinical and electrocardio-graphic signs that mimic myocardial ischemia, typical left ventricular kinesis abnormalities, and no evidence of obstructive coronary disease. It is associated with emotional or physical stress usually in postmenopausal women. A major pathogenetic role is played by excessive sympathetic stimulation of the left ventricle. Only two cases of TTC have been described in patients on hemodialysis and one case has been described in a patient on peritoneal dialysis associated with peritonitis. We observed a case of TTC in a patient on nocturnal intermittent peritoneal dialysis with a transplanted kidney and loss of residual renal function. We found that she had suffered significant emotional stress immediately before the symptoms arose. The clinical features were typical ischemic chest pain and acute heart failure. Beta-blockers were the principal pharmacological treatment. The necessary ultrafiltration was obtained with peritoneal dialysis in automated modality, reducing the abdominal filling volumes according to the patient's compliance and modifying the glucose concentration according to her hemodynamic condition. The obtained ultrafiltration was appropriate and in accordance with the few experiences reported in the literature. The symptoms resolved within a week and the left ventricular kinesis and ejection fraction normalized in almost three weeks. This clinical case suggests that peritoneal dialysis, also in automated mode, can be as effective as extracorporeal ultrafiltration in the treatment of acute heart failure.