An unusual association of contralateral congenital small kidney, reduced renal function and hyperparathyroidism in sponge kidney patients: on the track of the molecular basis.

Of unknown pathogenesis, sponge kidney (SK) is variably associated with nephrocalcinosis, stones, nephronic tubule dysfunctions and precalyceal duct cysts. Amongst 72 unrelated renal SK patients with renal stone disease, we detected one with unilateral bifid renal pelvis and six with unilateral small kidneys (longitudinal diameter difference >15%). Secondary causes of small kidney were excluded. Of the seven cases, four had reduced renal function (67 vs 7% in the entire cohort), and three developed hyperparathyroidism during follow-up (43 vs 4%). The pathogenesis of SK ought to explain why anatomical structures of different embryological origin are involved (the precalyceal and collecting ducts and the nephron) and why there is frequent association with hyperparathyroidism. In embryogenesis, the metanephric blastema synthesizes the chemotactic glial-derived neurotrophic factor (GDNF) to prompt the ureteric bud to branch off from Wolff's mesonephric duct, and to approach and invade the blastema. The bud's tip expresses the GDNF receptor (RET). RET-GDNF binding is crucial not only for the correct formation of ureters and collecting ducts (both of Wolffian origin), but also for nephrogenesis. We advance the hypothesis that SK results from a disruption in the ureteric bud-metanephric blastema interface, possibly due to one or more mutations or polymorphisms of RET or GDNF genes. This would explain: the concurrent alterations in precalyceal ducts and the functional defects in the nephron, the occasional association with size and the functional asymmetry between the two kidneys, some degree of renal dysplasia causing the reduction in the glomerular filtration rate and (given the role of RET in parathyroid cell proliferation) the association with hyperparathyroidism.     

Adrenomedullin plasma concentrations in patients with retinitis pigmentosa

PURPOSE: To evaluate the relationship between retinitis pigmentosa (RP) and plasma adrenomedullin (ADM) levels. METHODS: Blood samples were obtained from a group of 40 consecutive patients with RP matched with 35 healthy subjects (HS) as control. We carried out a complete ophtalmological examination. The study group included 26 patients with RP and 14 patients with syndromic RP. Plasma ADM levels were determined in duplicate with a specific radioimmunoassay method. RESULTS: In the HS plasma ADM levels were 13.7 +/- 6.1 pg/mL. The mean of plasma ADM concentrations in all patients with RP (23.4 +/- 10.7 pg/mL) was significantly (P < 0.0001) higher than that of HS. Moreover, in the syndromic RP patients, plasma ADM levels (28.6 +/- 14.35 pg/ml) were higher than those of HS and RP patients (P < 0.0017). CONCLUSION: The increase of plasma ADM levels in RP patients may be a response to photoreceptor damage.     

Huge Isolated Port-Site Recurrence after Laparoscopic Partial Nephrectomy: A Case Report

A 66-yr-old man with pain and swelling in the right flank was referred to our clinic for diagnosis. In 2005, the patient underwent a laparoscopic partial nephrectomy for renal cancer of the lower pole of the right kidney. A computed tomography scan revealed a 20-cm tumor in the right abdominal wall, resulting in a suspected diagnosis of port-site metastasis from the first laparoscopic operation. The patient underwent open surgery, which confirmed the diagnosis. After the operation, the patient recovered rapidly.     

Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly

The cyclopic and laterality phenotypes in model organisms linked to disturbances in the generation or propagation of Nodal-like signals are potential examples of similar impairments resulting in birth defects in humans. However, the types of gene mutation(s) and their pathogenetic combinations in humans are poorly understood. Here we describe a mutational analysis of the human NODAL gene in a large panel of patients with phenotypes compatible with diminished NODAL ligand function. Significant reductions in the biological activity of NODAL alleles are detected among patients with congenital heart defects (CHD), laterality anomalies (e.g. left–right mis-specification phenotypes), and only rarely holoprosencephaly (HPE). While many of these NODAL variants are typical for family-specific mutations, we also report the presence of alleles with significantly reduced activity among common population variants. We propose that some of these common variants act as modifiers and contribute to the ultimate phenotypic outcome in these patients; furthermore, we draw parallels with strain-specific modifiers in model organisms to bolster this interpretation.     

External Biliary Fistula in Orthotopic Liver Transplantation

During orthotopic liver transplantation (OLT), various situations may occur in which biliary reconstruction is neither technically feasible nor recommended. One bridge to a delayed anastomosis can be an external biliary fistula (EBF). This procedure allows the surgeon to execute hemostatic maneuvers, such as abdominal packing; therefore, biliary reconstruction can be subsequently performed in a bloodless operative field without edematous tissues. EBF can be made by placing in the donor biliary tract a cannula that is fixed to the bile duct using 2-0 silk ties and secured outside the abdominal wall. The biliary anastomosis will be performed within 2 days after the OLT. The aim of this study was to examine the safety of EBF in terms of the incidence of biliary complications compared with a direct anastomosis. Among 1634 adult OLTs performed in 17 years in our center, 1322 were carried out with termino-terminal hepaticocholedochostomy (HC-TT); two with side-to-side hepaticocholedochostomy; 208 with hepaticojejunostomy (HJ); 31 with EBF and delayed HC-TT, and 71 with EBF and delayed HJ. Biliary complication rates in the EBF group were 24.5%, including 23.9% in the delayed HJ and 25.8% in the delayed HC-TT. Biliary complication incidence among all OLTs was 24.6% (P = NS). No complications related to the procedure were observed. Therefore, EBF is a safe technique without a higher biliary complication rate. It may be useful when a direct biliary anastomosis is dangerous.     

The glycobiology of uropathogenic E. coli infection: the sweet and bitter role of sugars in urinary tract immunity

Urinary tract infections (UTI) are among the most prevalent infectious diseases and the most common cause of nosocomial infections, worldwide. Uropathogenic E. coli (UPEC) are responsible for approximately 80% of all UTI, which most commonly affect the bladder. UPEC colonize the urinary tract by ascension of the urethra, followed by cell invasion, and proliferation inside and outside urothelial cells, thereby causing symptomatic infections and quiescent intracellular reservoirs that may lead to recurrence. Sugars, or glycans, are key molecules for host–pathogen interactions, and UTI are no exception. Surface glycans regulate many of the events associated with UPEC adhesion and infection, as well as induction of the host immune response. While the bacterial protein FimH binds mannose‐containing host glycoproteins to initiate infection and UPEC‐secreted polysaccharides block immune mechanisms to favour intracellular replication, host glycans on the urothelial surface and on secreted glycoproteins prevent or limit infection by inhibiting UPEC adhesion. Given the importance of glycans during UTI, here we review the glycobiology of UPEC infection to highlight fundamental sugar‐mediated processes of immunological interest for their potential clinical applications. Interdisciplinary approaches incorporating glycomics and infection biology may help to develop novel non‐antibiotic‐based therapeutic strategies for bacterial infections as the spread of antimicrobial‐resistant uropathogens is currently threatening modern healthcare systems.     

The 1.3-A resolution structure of Nitrosomonas europaea Rh50 and mechanistic implications for NH3 transport by Rhesus family proteins

The Rhesus (Rh) proteins are a family of integral membrane proteins found throughout the animal kingdom that also occur in a number of lower eukaryotes. The significance of Rh proteins derives from their presence in the human red blood cell membrane, where they constitute the second most important group of antigens used in transfusion medicine after the ABO group. Rh proteins are related to the ammonium transport (Amt) protein family and there is considerable evidence that, like Amt proteins, they function as ammonia channels. We have now solved the structure of a rare bacterial homologue (from Nitrosomonas europaea) of human Rh50 proteins at a resolution of 1.3 A. The protein is a trimer, and analysis of its subunit interface strongly argues that all Rh proteins are likely to be homotrimers and that the human erythrocyte proteins RhAG and RhCE/D are unlikely to form heterooligomers as previously proposed. When compared with structures of bacterial Amt proteins, NeRh50 shows several distinctive features of the substrate conduction pathway that support the concept that Rh proteins have much lower ammonium affinities than Amt proteins and might potentially function bidirectionally.     

MR imaging and proton spectroscopy of the breast: how to select the images useful to convey the diagnostic message

PURPOSE: The purpose of this study was to propose a short way to summarise a breast magnetic resonance (MR) examination including a precontrast and contrast-enhanced dynamic study and proton spectroscopy (1H-MRS) in order to convey the diagnostic message. MATERIALS AND METHODS: At the Department of Radiology of the Policlinico San Donato (University of Milan), breast MR is routinely performed at 1.5 T as follows: 36-slice axial 2D short-time inversion-recovery (STIR) sequence; 128-partition 3D gradient-echo coronal sequence (1-mm3 siotropic voxel) before and after rapid automatic intravenous injection of 0.1 mmol/kg of Gd-DOTA (one precontrast and four postcontrast phases). Postprocessing includes temporal subtraction (postcontrast minus precontrast), maximum intensity projections (MIPs), percent enhancement-to-time curves for small regions of interest, and axial and/or sagittal multiplanar reconstructions. Single-voxel 1H-MRS is acquired to characterise focal lesions. Applying this protocol, more than 1,200 images are generated for each examination. We select only four MIPs of an early subtracted dynamic phase: one axial similar to craniocaudal x-ray mammographic views, one coronal, and two lateral similar to lateral 90 degrees x-ray mammographic views. For each lesion described in the report, we select five items, including three images, one graph, and one table: STIR image, precontrast and subtracted postcontrast images (morphology), percent enhancement-to-time curves and a table of raw data generating the curves (dynamics). If 1H-MRS has been performed, we add other five items: two postprocessed spectra (metabolism) and three images localising the volume of interest. Only the selected items are printed on films and attached to the report. RESULTS: The selected items range usually from four (no detected lesion) to 14 (one lesion, studied also with 1H-MRS), to 44 (five lesions, one of them studied also with 1H-MRS). The percentage of items presented with the report if compared with the total number of generated images is equal to 0.33% (4/1,200), 1.17% (14/1,200), and 2.83% (34/1,200), respectively. CONCLUSIONS: Breast MR imaging and 1H-MRS can be effectively summarised presenting only a minimal fraction of all generated images.