Sweat test in patients with glucose-6-phosphate-1-dehydrogenase deficiency

BACKGROUND: A false-positive sweat test in patients with deficiency of glucose-6-phosphate-1-dehydrogenase (EC 1.1.1.49; G6PD) is repeatedly reported. METHODS: Sweat chloride or conductivity was measured in 11 patients with G6PD deficiency. RESULTS: Mean (SD) chloride level (n = 8, median age 9.2 years, range 1.9-48.5) was 18.8 (9.6 mmol/l) and, mean (SD) sodium level was 26.0 (10.0 mmol/l), respectively, and mean (SD) conductivity (n = 3, median age 6.6 years, range 1.9-40.5) was 34.3 (6.5 mmol/l). CONCLUSION: In sweat of 11 patients with G6PD deficiency we did not find any abnormality. The reason for alleged false-positive sweat test in patients with G6PD deficiency is not known and we were unable to identify any original reference. It appears that tables of putative false-positive sweat tests in several disease states have been directly "copied and pasted" from one paper or textbook to another without verifying the original literature, a phenomenon one can call "chain citation".

Outcome after radical cystectomy with limited or extended pelvic lymph node dissection

PURPOSE: We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000. MATERIALS AND METHODS: Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined. RESULTS: The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p <0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p <0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series. CONCLUSIONS: Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

The complement inhibitor low molecular weight dextran sulfate prevents TLR4-induced phenotypic and functional maturation of human dendritic cells

Low molecular weight dextran sulfate (DXS) has been reported to inhibit the classical, alternative pathway as well as the mannan-binding lectin pathway of the complement system. Furthermore, it acts as an endothelial cell protectant inhibiting complement-mediated endothelial cell damage. Endothelial cells are covered with a layer of heparan sulfate (HS), which is rapidly released under conditions of inflammation and tissue injury. Soluble HS induces maturation of dendritic cells (DC) via TLR4. In this study, we show the inhibitory effect of DXS on human DC maturation. DXS significantly prevents phenotypic maturation of monocyte-derived DC and peripheral myeloid DC by inhibiting the up-regulation of CD40, CD80, CD83, CD86, ICAM-1, and HLA-DR and down-regulates DC-SIGN in response to HS or exogenous TLR ligands. DXS also inhibits the functional maturation of DC as demonstrated by reduced T cell proliferation, and strongly impairs secretion of the proinflammatory mediators IL-1beta, IL-6, IL-12p70, and TNF-alpha. Exposure to DXS leads to a reduced production of the complement component C1q and a decreased phagocytic activity, whereas C3 secretion is increased. Moreover, DXS was found to inhibit phosphorylation of IkappaB-alpha and activation of NF-kappaB. These findings suggest that DXS prevents TLR-induced maturation of human DC and may therefore be a useful reagent to impede the link between innate and adaptive immunity.

Extracorporeal shock wave lithotripsy for distal ureteral calculi: what a powerful machine can achieve

PURPOSE: We assessed the efficacy of extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia) for distal ureteral calculi with the HM3 (Dornier Medical Systems, Inc.) lithotriptor. MATERIALS AND METHODS: A total of 585 consecutive patients with distal ureteral calculi were treated with ESWL using an unmodified HM3 lithotriptor. Of these patients 67 referred for treatment only for whom no followup was available were excluded from further analysis. The remaining 518 cases were followed until they were radiologically documented to be stone-free or considered treatment failures. Before ESWL additional procedures were performed in 144 patients, including stone push back, ureteral catheter or Double-J (Medical Engineering Corp., New York, New York) stent placement, percutaneous nephrostomy, ureteral endoscopic maneuvers or stone basket manipulation. A total of 374 patients needed no preliminary treatment before ESWL. RESULTS: Of the 518 patients 469 (91%) were successfully treated with 1 ESWL session, while 49 (9%) needed 2 or 3. Manipulation after ESWL was performed in 22 cases, including stent placement, percutaneous nephrostomy, ureteral endoscopic stone removal and a stone basket procedure. On day 1 after ESWL 327 patients (63%) were stone-free, 158 (30%) had less than 5 mm. fragments and 33 (7%) had more than 5 mm. fragments. At 3 months the stone-free rate increased to 97%. CONCLUSIONS: These data show that ESWL for distal ureteral calculi with the powerful unmodified HM3 lithotriptor has a high success rate with a low rate of minimally traumatic manipulations before and after intervention. Results in terms of the re-treatment and stone-free rates are superior to those of any other second or third generation lithotriptor and comparable to the results of the best ureteroscopic series.

Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program

OBJECTIVES The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. BACKGROUND The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. METHODS We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. RESULTS The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). CONCLUSIONS The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

Differentiating atrioventricular nodal reentrant tachycardia from tachycardia via concealed accessory pathway.

Studies analyzing the diagnostic value of 12-lead electrocardiographic criteria differentiating slow-fast atrioventricular nodal reentrant tachycardia (AVNRT) from atrioventricular reentrant tachycardia (AVRT) due to concealed accessory pathway have shown inconsistent results. In 97 patients (50 with AVNRT, 47 with AVRT) 12-lead electrocardiograms (ECGs) were recorded during sinus rhythm and tachycardia (QRS <120 ms). The ECGs were blinded for diagnosis and patient and analyzed independently by 2 electrophysiologists. The studied criteria differentiating AVNRT from AVRT included pseudo-r'/S, the presence of a retrograde P wave, RP interval, ST-segment depression >/=2 mm with the number and location of the affected leads, QRS amplitude, and cycle length alternans.

Regulation of mucin gene expression by CREB via a nonclassical retinoic acid signaling pathway.

Vitamin A and its metabolite retinoic acid (RA) are essential elements for normal lung development and the differentiation of lung epithelial cells. We previously showed that RA rapidly activated cyclic AMP response element-binding protein (CREB) in a nonclassical manner in normal human tracheobronchial epithelial (NHTBE) cells. In the present study, we further demonstrated that this nonclassical signaling of RA on the activation of CREB plays a critical role in regulating the expression of airway epithelial cell differentiation markers, the MUC2, MUC5AC, and MUC5B genes. We found that RA rapidly activates the protein kinase Calpha isozyme and transmits the activation signal to CREB via the Raf/MEK/extracellular signal-regulated kinase/p90 ribosomal S6 kinase (RSK) pathway. Activated RSK translocated from the cytoplasm to the nucleus, where it phosphorylates CREB. Activated CREB then binds to a cis-acting replication element motif on the promoter (at nucleotides [nt] -878 to -871) of the MUC5AC gene. The depletion of CREB using small interfering RNA abolished not only the RA-induced MUC5AC but also RA-induced MUC2 and MUC5B. Taken together, our findings demonstrate that CREB activation via this nonclassical RA signaling pathway may play an important role in regulating the expression of mucin genes and mediating the early biological effects of RA during normal mucous differentiation in NHTBE cells.

The Law of the WTO and the Communications Law of the EC : On a Path of Harmony or Discord?

This paper presents an overview of the law of the World Trade Organization (WTO) relevant to telecommunications services and correlates this body of law with the current regulatory framework for electronic communications networks and services in the European Community. The latter has been adapted to meet the challenges of technological and market developments in communications, epitomized by the processes of digitization, enhanced transport networks and convergence. The novel solutions embodied in the EC electronic communications regime, notably, a new design of the Significant Market Power mechanism, a projected withdrawal of sector specific regulation and an affirmation of the principle of technological neutrality, pose interesting questions as to the conformity of this reformed EC communications law with the WTO rules on telecommunications services and the obligations of the European Communities and their Member States. Looking beyond the WTO legal compatibility test, essential questions regarding the need for evolution of the WTO telecommunications rules are raised. The present paper contributes to the ongoing debate in that context in light of the EC experience.