A Novel Nonsense Mutation in RSPO4 Gene Underlies Autosomal Recessive Congenital Anonychia in a Pakistani Family

Abstract: Congenital anonychia is an inherited autosomal recessive disorder characterized by complete absence of fingernails or toenails, or both. In the present study, we have described a consanguineous Pakistani family having a family member affected with congenital anonychia. Genotyping using polymorphic microsatellite markers showed linkage of the family to gene RSPO4 encoding R‐spondin and mapped on human chromosome 20p13. Deoxyribonucleic acid sequence analysis of the gene identified a novel nonsense mutation (c.18C>A; p.Cys6X) in the affected family member.     

Hazards after the storm: Floodwater drainage pump stations and exposure to hydrogen sulfide

A hurricane can present unique hazards that exist long after the strong winds and heavy rains have subsided. These hazards may not only be physical, but chemical as well. Hydrogen sulfide (H₂S) represents an important and potentially overlooked hazard that can be naturally produced in floodwaters following a hurricane. In August of 2012, in the wake of Hurricane Isaac, Plaquemines Parish, Louisiana was submerged under a blanket of floodwater. To remove floodwaters that had breached the levee system designed to keep water out, temporary drainage pump stations were installed at strategic locations. The transfer of floodwaters at these drainage stations resulted in the generation of elevated concentrations of airborne H₂S at the pumping stations. The generation of H₂S at these pumping stations represented a potential inhalation hazard for workers; thus, awareness for possible H₂S exposure at these installments is crucial.     

Diagnosing Chronic Pancreatitis

Diagnosing CP can range from routine in those with severe disease and obvious calcifications on CT imaging to elusive in those patients with early changes in CP. The workup of suspected CP should follow a progressively noninvasive to more invasive STEP-wise approach in a patient with a suspicious clinical presentation and risk factors that raise their pretest probability of disease. After a thorough history and physical examination, basic laboratories should be obtained such as lipase, amylase, metabolic panel, and indirect PFTs (fecal elastase-1, serum trypsin). Computed tomography remains the best initial imaging modality to obtain as it has good sensitivity for severe CP and may obviate the need for other diagnostic tests. When equivocal, an MRCP should be obtained for a more detailed evaluation of the both the pancreatic parenchyma and ducts. If the diagnosis remains in doubt, EUS should be performed with or without pancreas function testing. ERCP remains a last-line diagnostic test and seldom should be used outside of therapeutic purposes. Future advances should target optimizing current diagnostic tools to more accurately diagnose early CP, as it is in this population where the benefits of delaying progression of CP may have the most profound effect. Likely the best way at establishing a diagnosis in these patients is via pancreatic function testing in the setting of indeterminate EUS results. Biomarker studies of pancreas fluid may supplement diagnosis.     

Long-Term Function After Restorative Proctocolectomy

PURPOSE Early functional outcome after restorative proctocolectomy and formation of an ileoanal pouch is known to be good, but there are minimal data on the long-term function of the pouch. The aim of this study was to look at the long-term functional outcome in patients who had undergone restorative proctocolectomy and formation of an ileoanal pouch.METHODS A total of 151 consecutive patients (96 males, 55 females) who underwent ileoanal pouch surgery between April 1983 and May 1993 were identified. Functional outcomes from the previous 12 months were appraised by a standardized questionnaire.RESULTS The median age at surgery was 31 years (range, 6–63 years), with a median follow-up of 142 months (range, 100–221 months). Eighteen patients have had their pouches excised, with another patient being defunctioned. Therefore 19 patients (13 percent) had suffered pouch failure. Altogether, 115 patients were available for follow-up, and 98 patients (85 percent) returned questionnaires. The median pouch-emptying frequency was five times (range, 1–17) during the day and one time (range, 0–6) at night. A total of 74 percent of patients had perfect continence during the day. Most of the patients had no life-style restrictions related to the pouch, and 98 percent of patients would recommend a pouch to others.CONCLUSIONS Long-term functional outcome after ileoanal pouch surgery is good in most patients. For patients requiring proctocolectomy, ileoanal pouch surgery can now be recommended as an excellent long-term option.Presented at the Association of Coloproctology of Great Britain and Ireland, Manchester, United Kingdom, July 2 to 5, 2002 Reprints are not available.     

Managing abnormal blood lipids: a collaborative approach

Current data and guidelines recommend treating abnormal blood lipids (ABL) to goal. This is a complex process and requires involvement from various healthcare professionals with a wide range of expertise. The model of a multidisciplinary case management approach for patients with ABL is well documented and described. This collaborative approach encompasses primary and secondary prevention across the lifespan, incorporates nutritional and exercise management as a significant component, defines the importance and indications for pharmacological therapy, and emphasizes the importance of adherence. Use of this collaborative approach for the treatment of ABL ultimately will improve cardiovascular and cerebrovascular morbidity and mortality.     

Urinary Nucleic Acid TSPAN13-to-S100A9 Ratio as a Diagnostic Marker in Prostate Cancer

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.     

Human Urine-derived Stem Cells Seeded Surface Modified Composite Scaffold Grafts for Bladder Reconstruction in a Rat Model

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCs-scaffold^heparin-bFGF group showed significant functional improvement (2.34 ± 0.25 mL and 55.09 ± 11.81 µL/cm H₂O) compared to the other groups (2.60 ± 0.23 mL and 56.14 ± 9.00 µL/cm H₂O for the control group, 1.46 ± 0.18 mL and 34.27 ± 4.42 µL/cm H₂O for the partial cystectomy group, 1.76 ± 0.22 mL and 35.62 ± 6.69 µL/cm H₂O for the scaffold group, and 1.92 ± 0.29 mL and 40.74 ± 7.88 µL/cm H₂O for the scaffold^heparin-bFGF group, respectively). In histological and immunohistochemical analysis, the USC-scaffold^heparin-bFGF group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold^heparin-bFGF exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.