Intravesical hyaluronic acid and chondroitin sulphate for bladder pain syndrome/interstitial cystitis: long-term treatment results

Introduction and hypothesis

Reconstruction of the glycosaminoglycan layer plays a role in the successful treatment of bladder pain syndrome/interstitial cystitis (BPS/IC). Intravesical instillations of hyaluronic acid (HA) and chondroitin sulphate (CS) have given results in the short term. We hypothesise that these benefits continue in the longer term.

Methods

With the aim of evaluating this therapy over a longer period we treated 12 BPS/IC patients refractory to other treatments with a combination of HA 1.6?% and CS 2.0?% over a period of 3?years assessing symptoms and quality of life using a visual analogue scale, 3-day voiding diaries and validated questionnaires.

Results

Improvements in bladder function were sustained for 3?years (mean number of daily voids decreased from 17.8 at baseline to 15.5 at 9?months and 11.9 at 3?years, and mean volume per void from 136.8?ml at baseline to 143.9?ml at 9?months and 180.9?ml at 3?years). Quality of life assessments confirmed these improvements.

Conclusions

Intravesical instillations of HA and CS produced a sustained improvement of the symptomatology, up to 3?years, in patients with BPS/IC refractory to previous treatments. Further confirmation would be expected from larger controlled trials.     

Plasma bradykinin and prostaglandin metabolism and exercise testing in patients with silent myocardial ischemia compared with patients with painful myocardial ischemia

Bradykinin, alone or in combination with prostaglandin, is thought to produce pain in patients with coronary heart disease. To elucidate this further, we have investigated and compared serum bradykinin, TXB2 and 6 KPGF1 alpha levels in patients with silent myocardial ischemia (SMI, n = 18), painful myocardial ischemia (PMI, n = 8) and normal subjects (NL, n = 18). In addition, SMI and PMI subjects were given exercise testing and the results then compared. After Holter monitoring for 48 hours, exercise testing was performed. Blood was sampled in the morning between the Holter and exercise regimen. Maximal heart rate, systolic blood pressure and the double products were not significantly different between the SMI and PMI groups. The duration of exercise for the SMI group was 7.08 +/- 2.1 min vs 5.9 +/- 1.9 in the PMI group (p less than 0.10). Plasma bradykinin was 14 +/- 3 pg/ml in the SMI group and 15 +/- 3 in the PMI group (N.S), whereas it was 7 +/- 4 in the NL (p less than 0.05). The TXB2/6KPGF1 alpha for the SMI group was 1.3 +/- 0.3, which was significantly higher than that for the NL group (0.8 +/- 0.3, p less than 0.01), though this did not greatly differ from the PMI group (1.2 +/- 0.3). These results suggest that SMI patients under Holter monitoring who manifest no symptoms but show significant ST segment depressions must receive the same careful attention given to PMI patients. In both group of patients bradykinin and prostaglandin metabolism is similarly changed, as was demonstrated by exercise stress testing.     

Suppressor of cytokine signaling 1 protects mice against concanavalin A-induced hepatitis by inhibiting apoptosis

Iron overload exacerbates various liver diseases. In hepatocytes, a portion of non-heme iron is sequestered in lysosomes and endosomes. The precise mechanisms by which lysosomal iron participates in hepatocellular injury remain uncertain. Here, our aim was to determine the role of intracellular movement of chelatable iron in oxidative stress-induced killing to cultured hepatocytes from C3Heb mice and Sprague-Dawley rats. Mitochondrial polarization and chelatable iron were visualized by confocal microscopy of tetramethylrhodamine methylester (TMRM) and quenching of calcein, respectively. Cell viability and hydroperoxide formation (a measure of lipid peroxidation) were measured fluorometrically using propidium iodide and chloromethyl dihydrodichlorofluorescein, respectively. After collapse of lysosomal/endosomal acidic pH gradients with bafilomycin (50 nM), an inhibitor of the vacuolar proton-pumping adenosine triphosphatase, cytosolic calcein fluorescence became quenched. Deferoxamine mesylate and starch-deferoxamine (1 mM) prevented bafilomycin-induced calcein quenching, indicating that bafilomycin induced release of chelatable iron from lysosomes/endosomes. Bafilomycin also quenched calcein fluorescence in mitochondria, which was blocked by 20 microM Ru360, an inhibitor of the mitochondrial calcium uniporter, consistent with mitochondrial iron uptake by the uniporter. Bafilomycin alone was not sufficient to induce mitochondrial depolarization and cell killing, but in the presence of low-dose tert-butylhydroperoxide (25 microM), bafilomycin enhanced hydroperoxide generation, leading to mitochondrial depolarization and subsequent cell death. CONCLUSION: Taken together, the results are consistent with the conclusion that bafilomycin induces release of chelatable iron from lysosomes/endosomes, which is taken up by mitochondria. Oxidative stress and chelatable iron thus act as two "hits" synergistically promoting toxic radical formation, mitochondrial dysfunction, and cell death. This pathway of intracellular iron translocation is a potential therapeutic target against oxidative stress-mediated hepatotoxicity.     

Insulinoma with low circulating insulin levels: the diagnostic value of proinsulin measurements.

Hypoglycemia coexisting with very low plasma immunoreactive insulin concentrations was found in a 78-year-old woman with an insulinoma. However, the absolute proinsulin levels during hypoglycemia were elevated (0.9 to 1.4 ng/ml), accounting for 66.5% of the total circulating immunoreactive insulinlike material. The raised serum proinsulin concentrations together with an abnormal proinsulin:insulin ratio proved to be of critical importance in establishing the diagnosis of an islet-cell tumor in this patient.     

Incidence and mechanism of dislocated fast pathway in various forms of atrioventricular nodal reentrant tachycardia.

BACKGROUND: The incidence and mechanism of the dislocated antegrade fast pathway (A-FP) were examined in various forms of atrioventricular nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: To localize the A-FP, 5 atrial sites comprising the inferior coronary sinus ostium (CSOS), apex of the triangle of Koch (A-TOK), and 3 equidistant sites on the atrioventricular junction extending from A-TOK to CSOS (site S, M, and I) were pace mapped at 100 beats/min in 71 patients with slow-fast (n=49), fast-slow (n=7) and slow-intermediate (n=15) forms of AVNRT. The site with the shortest interval between the stimulus and His potential recorded at the A-TOK (shortest St-H) was defined as the A-FP site. The A-FP was located at A-TOK in 31 patients (nondislocated group), and inferior to A-TOK in 40 patients (site S in 26, M in 13, and I in one patient; dislocated group). There was no significant difference in the location of the A-FP among the 3 forms of AVNRT. Although the shortest St-H did not differ between groups, the St-H at A-TOK in the dislocated group was significantly longer than that in the nondislocated group. Additionally, the His potential preceding that of the A-TOK was observed more frequently inferior to the A-TOK in the dislocated group than in the nondislocated group, suggesting that the A-FP dislocation was accompanied by displacement of the His bundle. CONCLUSIONS: Dislocated A-FP was frequently and uniformly observed among various forms of AVNRT, and is probably caused by inferior displacement of the entire atrioventricular node - His bundle apparatus.     

Brief report: a retrospective study of the performance of video laryngoscopy in an obstetric unit

We evaluated the performance of tracheal intubation using video laryngoscopy in an obstetric unit. We analyzed airway management details during a 3-year period, and observed 180 intubations. All cases were managed with direct or video laryngoscopy. Direct laryngoscopy resulted in 157 out of 163 (95% confidence interval [CI], 92%-99%) first attempt successful intubations and failed once. Video laryngoscopy resulted in 18 of 18 (95% CI, 81%-100%) successful intubations on first attempt. The failed direct laryngoscopy was rescued with video laryngoscopy. The patients managed with video laryngoscopy frequently required urgent or emergency surgery and had predictors of difficult direct laryngoscopy in 16 of 18 cases. Video laryngoscopy may be a useful adjunct for obstetric airway management, and its role in this difficult airway scenario should be further studied.     

Experience of DMAT rescue activity by doctor-helicopter in Tohoku Area after the earthquake

We operated rescue activities in Tohoku area after the earthquake of March 11th, 2011. From our hospital, a doctor-helicopter flew to the staging care unit at Hanamaki airport with two members of the disaster medical assistance team (DMAT), one of whom was an anesthesiologist. The helicopter carried ten patients by nine flight missions, who were the victims of tsunami after the earthquake. There were seven doctor-helicopters from all over Japan and did the missions based at Hanamaki airport. The missions was quite different from our usual job as an anesthesiologist, but we could transfer the patients safely by using some knowledge of stabilizing the unstable patients as flight doctors. We report the details of our activities by our doctor-helicopters in Tohoku area.