Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study

The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m², the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m² were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m² were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m² revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m², with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.     

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.     

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.     

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.     

The Comparative Experiences of Women in Control: Diabetes Self-Management Education in a Virtual World

The purpose was to characterize participants’ experiences of a diabetes self-management (DSM) education program delivered via a virtual world (VW) versus a face-to-face (F2F) format. Participants included a randomly selected sample of participants who completed the Women in Control study. Four focus groups were conducted with 32 participants. Four researchers coded the data and conducted a qualitative thematic analysis. Four overarching themes were identified. Three domains apply to both VW and F2F formats, including (1) the value of DSM knowledge gained, (2) cultivating DSM attitudes and skills, and (3) the value of peer-derived social support. The fourth domain is labeled positive technological development for DSM (VW condition only). VW and F2F groups both reported mastery of DSM knowledge, attitudes, and skills, and there were no differences in peer-derived social support between groups. The technological aspects of VW participation afforded VW participants a unique sense of personal agency and diabetes self-efficacy not reported by F2F participants. DSM education in a VW is feasible and educational outcomes are similar to a F2F classroom experience. Furthermore, learning DSM skills in a VW offers unique advantages in supporting personal agency for health behavior change. Further research is warranted.     

Successful treatment of hemochromatosis with renal tubular dysgenesis in a preterm infant

We report the first surviving case of neonatal hemochromatosis with renal tubular dysgenesis. Renal failure was treated with peritoneal dialysis. Although hepatic failure from neonatal hemochromatosis was progressive, repeated exchange transfusions improved jaundice and coagulopathy. The patient gained weight and received a liver transplantation from her father.