Percutaneous Tibial Nerve Stimulation for Treatment of Idiopathic Faecal Incontinence: Mid-term Results from a Single Center

Abstract Objective: Percutaneous tibial nerve stimulation is a recent and minimally invasive treatment for faecal incontinence (FI). The aim of this study is to evaluate the mid-term results in patients with idiopathic faecal incontinence (IFI). Methods: Fifty one patients (42 female and 9 male) were prospectively recruited. Patients were treated twice a week for 6 weeks as per study protocol. We have assessed the degree of fecal incontinence using the Cleveland Clinic faecal incontinence (CCF-FI) score at baseline, at 6 weeks, at 6 months and at 1 year. Also the anorectal manometric data (mean resting pressure (MRP), squeeze pressure (SP) and, rectal sensation) at baseline, at 6 weeks and at 6 months have been evaluated. Results: The median CCF-FI score was significantly decreased from an initial baseline value from 12 to 7 at 6 weeks, 3 at 6 months and, 3 at 1 year (respectively: 1st interquartile 4.5, 1, 0 vs 10; 3rd interquartile 9, 5, 5 vs 14.5, p = 0.0001). Anorectal manometry showed an improvement of the internal (resting pressure, MRP) and the external sphincters (squeeze pressure, SP) at 6 months compared to the baseline and 6 weeks by PTNS, while, RP and SP at 6 months was greater than at baseline and 6 weeks (p = 0.004 and p = 0.002 respectively). Conclusions: This study demonstrates that stimulation of the posterior tibial nerve could be an excellent procedure for the treatment of IFI. The stimulation of the posterior tibial nerve can improve the fecal continence (CCF-FI score) in the short term and this improvement is maintained after 1 year of follow-up without treatmen

Genomic Structure and Chromosomal Location of the Rat Gene Encoding the Zinc Finger Transcription Factor Kid-1

We have previously cloned and sequenced a novel zinc finger cDNA, Kid-1 , from the rat. Because of its developmentally regulated expression pattern and its suppression after renal injury, as well as its kindey-predominant expression, we propose that Kid-1 is likely to play an important role in renal gene regulation. Kid-1 encodes a predicted protein with 13 zinc fingers at the carboxy end and Krüppel-associated box (KRAB) A and B regions at the amino terminus. Expression of a Kid-1-GAL4 chimeric protein results in strong transcriptional repression of cotransfected constructs containing GAL4 binding sites and a chloramphenicol acetyl transferase gene driven by either a minimal promoter or a SV40 enhancer. We now report the cloning, structural organization, and chromosomal localization of the Kid-1 gene. The Kid-1 gene is composed of four exons and three introns, closely reflecting the organization of the Kid-1 protein. The KRAB A and B regions are encoded by the second and third exons, respectively. The entire zinc finger region is encoded by the fourth exon. Using a combination of linkage analysis and somatic cell hybrid analysis, Kid-1was mapped to rat chromosome (RNO) 10. Kid-1, Il3, and Sparc form a tight linkage group on RNO10. Regional sublocalization to RNO10q21.3-q22 was established by fluorescence in situ hybridization.

Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury

Kidney injury molecule-1 (KIM-1) is a specific histological biomarker for diagnosing early tubular injury on renal biopsies. In this study, KIM-1 expression was quantitated in renal transplant biopsies by immunohistochemistry and correlated with renal function. None of the 25 protocol biopsies showed detectable tubular injury on histologic examination, yet 28% had focal positive KIM-1 expression. Proximal tubule KIM-1 expression was present in all biopsies from patients with histological changes showing acute tubular damage and deterioration of kidney function. In this group, higher KIM-1 staining predicted a better outcome with improved blood urea nitrogen (BUN), serum creatinine, and estimated glomerular filtration rate (eGFR) over an ensuing 18 months. KIM-1 was expressed focally in affected tubules in 92% of kidney biopsies from patients with acute cellular rejection. By contrast, there was little positive staining for Ki-67, a cell proliferation marker, in any of the groups. KIM-1 expression significantly correlated with serum creatinine and BUN, and inversely with the eGFR on the biopsy day. Our study shows that KIM-1 staining sensitively and specifically identified proximal tubular injury and correlated with the degree of renal dysfunction. KIM-1 expression is more sensitive than histology for detecting early tubular injury, and its level of expression in transplant biopsies may indicate the potential for recovery of kidney function

Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia.

We report the isolation and characterization of a cDNA encoding the novel mammalian serine protease Omi. Omi protein consists of 458 amino acids and has homology to bacterial HtrA endoprotease, which acts as a chaperone at low temperatures and as a proteolytic enzyme that removes denatured or damaged substrates at elevated temperatures. The carboxyl terminus of Omi has extensive homology to a mammalian protein called L56 (human HtrA), but unlike L56, which is secreted, Omi is localized in the endoplasmic reticulum. Omi has several novel putative protein-protein interaction motifs, as well as a PDZ domain and a Src homology 3-binding domain. Omi mRNA is expressed ubiquitously, and the gene is localized on human chromosome 2p12. Omi interacts with Mxi2, an alternatively spliced form of the p38 stress-activated kinase. Omi protein, when made in a heterologous system, shows proteolytic activity against a nonspecific substrate beta-casein. The proteolytic activity of Omi is markedly up-regulated in the mouse kidney following ischemia/reperfusion

Barium study associated with water siphon test in gastroesophageal reflux disease and its complications.

PURPOSE: The aim of this study was to evaluate the role of digital cineradiography associated with the water siphon test (WST) in the diagnosis of gastroesophageal reflux and to compare the results with oesophageal motility study, pH monitoring and endoscopy associated with biopsy and histology. MATERIALS AND METHODS: One hundred and sixty consecutive patients underwent digital cineradiography with WST, motility study, pH monitoring and endoscopy with biopsy. The presence of gastroesophageal reflux, oesophagitis, Barrett''s oesophagus and intestinal metaplasia was evaluated. RESULTS: WST vs. pH monitoring showed sensitivity of 71%, specificity of 31%, positive predictive value (PPV) of 53% and negative predictive value (NPV) of 50%; when middle-proximal refluxes only were considered, sensitivity decreased to 45% and specificity increased to 55%. Furthermore, the association between reflux and oesophagitis demonstrated by the chi-square (chi(2)) test proved to be statistically significant both for WST and pH monitoring, whereas the association between reflux and Barrett''s oesophagus was not significant for either WST or for pH monitoring. With regard to intestinal metaplasia, WST (middle-proximal refluxes) showed higher sensitivity (64% vs. 58%) and specificity (63% vs. 51%) than pH monitoring, whereas the statistical association between reflux and metaplasia proved to be significant for WST but not for pH monitoring. CONCLUSIONS: WST is a simple, inexpensive and reliable test that might be useful in the diagnosis of gastroesophageal reflux disease (GERD). A positive WST might be an additional indication for endoscopy with biopsy

Arachidonate Metabolism and the Signaling Pathway of Induction of Apoptosis by Oxidized LDL/Oxysterol

Owing at least in part to oxysterol components that can induce apoptosis, oxidized LDL (oxLDL) is cytotoxic to mammalian cells with receptors that can internalize it. Vascular cells possess such receptors, and it appears that the apoptotic response of vascular cells to the oxysterols borne by oxLDL is an important part of the atherogenic effects of oxLDL. Thus, an analysis of the signaling pathway of apoptotic induction by oxysterols is of value in understanding the development of atherosclerotic plaque. In a prior study, we demonstrated an induction of calcium ion flux into cells treated with 25-hydroxycholesterol (25-OHC) and showed that this response is essential for 25-OHC-induced apoptosis. One possible signal transduction pathway initiated by calcium ion fluxes is the activation of cytosolic phospholipase A2 (cPLA2). In the current study, we demonstrate that activation of cPLA2 does occur in both macrophages and fibroblasts treated with 25-OHC or oxLDL. Activation is evidenced by 25-OHC-induced relocalization of cPLA2 to the nuclear envelope and arachidonic acid release. Loss of cPLA2 activity, either through genetic knockout in mice, or by treatment with a cPLA2 inhibitor, results in an attenuation of arachidonic acid release as well as of the apoptotic response to oxLDL in peritoneal macrophages or to 25-OHC in cultured fibroblast and macrophage cell lines

The Daily Consumption of Cola Can Determine Hypocalcemia: A Case Report of Postsurgical Hypoparathyroidism-Related Hypocalcemia Refractory to Supplemental Therapy with High Doses of Oral Calcium

The consumption of soft drinks is a crucial factor in determining persistent hypocalcemia. The aim of the study is to evaluate the biochemical mechanisms inducing hypocalcemia in a female patient with usual high consumption of cola drink and persistent hypocalcemia, who failed to respond to high doses of calcium and calcitriol supplementation. At baseline and after pentagastrin injection, gastric secretion (Gs) and duodenal secretion (Ds) samples were collected and calcium and total phosphorus (Ptot) concentrations were evaluated. At the same time, blood calcium, Ptot, sodium, potassium, chloride, magnesium concentrations, and vitamin D were sampled. After intake of cola (1 L) over 180 min, Gs and Ds and blood were collected and characterized in order to analyze the amount of calcium and Ptot or sodium, potassium, magnesium, and chloride ions, respectively. A strong pH decrease was observed after cola intake with an increase in phosphorus concentration. Consequently, a decrease in calcium concentration in Gs and Ds was observed. A decrease in calcium concentration was also observed in blood. In conclusion, we confirm that in patients with postsurgical hypoparathyroidism, the intake of large amounts of cola containing high amounts of phosphoric acid reduces calcium absorption efficiency despite the high doses of calcium therapy

Targeted Proximal Tubule Injury Triggers Interstitial Fibrosis and Glomerulosclerosis

Chronic kidney disease (CKD) remains one of the leading causes of death in the developed world and acute kidney injury (AKI) is now recognized as a major risk factor in its development. Understanding the factors leading to CKD after acute injury are limited by current animal models of AKI which concurrently target various kidney cell types such as epithelial, endothelial and inflammatory cells. Here we developed a mouse model of kidney injury using the Six2-Cre-LoxP technology to selectively activate expression of the simian diphtheria toxin receptor in renal epithelia derived from the metanephric mesenchyme. By adjusting the timing and dose of diphtheria toxin a highly selective model of tubular injury was created to define the acute and chronic consequences of isolated epithelial injury. The diphtheria toxin-induced sublethal tubular epithelial injury was confined to the S1 and S2 segments of the proximal tubule rather than being widespread in the metanephric mesenchyme derived epithelial lineage. Acute injury was promptly followed by inflammatory cell infiltration and robust tubular cell proliferation leading to complete recovery after a single toxin insult. In striking contrast, three insults to renal epithelial cells at one week intervals resulted in maladaptive repair with interstitial capillary loss, fibrosis and glomerulosclerosis which was highly correlated with the degree of interstitial fibrosis. Thus, selective epithelial injury can drive the formation of interstitial fibrosis, capillary rarefaction and potentially glomerulosclerosis, substantiating a direct role for damaged tubule epithelium in the pathogenesis of CKD