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.     

Non-viral in vivo thrombomodulin gene transfer prevents early loss of thromboresistance of grafted veins.

OBJECTIVE: Immediate loss of thrombomodulin activity in the endothelium of vein grafts has been demonstrated during 90 min exposure to arterial circulation; this loss of activity is ascribed as an important cause of early thrombosis. Conventional ex vivo gene transfection after vein harvest cannot cover this acute period immediately after implantation. We have established a highly efficient non-viral gene therapy protocol utilizing modified transferrin receptor-facilitated gene transfer. Using this technique, we examined whether in vivo thrombomodulin gene therapy, directed to the endothelium of rat veins 2 days prior to grafting, may prevent thromboresistance impairment of vein grafts under simulated arterial circulation. METHODS: Abdomen of SD rat was opened and cationic liposome:transferrin:thrombomodulin gene complexes or the vector without DNAs were applied to the inferior vena cava of rats while blood flow was reduced by proximal and distal clamping. After 2 days, the transfected veins were harvested and thrombomodulin expression and thromboresistance properties determined before and after exposure to an artificial circuit. RESULTS: The trial of gene transfection using variable doses of DNAs confirmed that 7.5 microg of total DNAs was the most efficient quantity for thrombomodulin gene transfection to IVCs, although accompanying an increase of gene expression in other downstream organs. By transfection of the thrombomodulin gene in IVCs, the generation capacity of activated protein C in venous endothelium increased three-fold compared with veins treated with vector alone (P<0.01). Under simulated arterial circulation, perfusion of veins treated with vector alone decreased thrombomodulin activity to 36% of preperfused levels (P<0.01), whereas transfected grafts preserved the activity at normal vein endothelium levels even after perfusion. Consequently, the increase in endothelial thrombin activity induced by simulated arterial circulation was markedly attenuated in transfected veins (P<0.01), while immunohistochemistry confirmed the preservation of endothelial lining. CONCLUSIONS: Transferrin receptor-facilitated in vivo gene transfer to the inferior vena cava resulted in sufficient thrombomodulin gene expression immediately after graft implantation and subsequent maintenance of thromboresistance even after exposure to arterial pressure. Although further studies are needed, the present results suggest the possibility of gene therapy targeting acute phases of vein graft disease.     

Distortion and movement of the expander during skin expansion.

Distortion and movement of tissue expanders can cause expansion of the wrong area, such as the naevus or the scar that is to be resected. In 71 rectangular expanders, we examined the incidence of distortion (over 15 degrees) and movement (over 3 cm). We divided the expanders into three anatomical site groups: scalp, body, and extremities, and compared the complication rate between two study groups (distortion or movement, or not). In total, the incidence of distortion was 15/71 (21%) and that of movement 5/71 (7%). Distortion occurred mainly in the extremities (11/33,33%). The implanted expanders tended to move more often in the body part (3/15, 20%). In the extremities, the bigger the angle between the axis of the implanted expander and that of the extremity, the bigger the angle of distortion. Although the incidence of complications between the two groups was not significant, except for alteration in design of the flap, we recommend that these points should be considered when preoperative plans are being made for appropriate patients.     

Decreased VIP content in peripheral nerve from streptozocin-induced diabetic rats

After induction of diabetes with streptozocin (STZ-D) in rats, we measured vasoactive intestinal polypeptide (VIP) content in sciatic nerve and spinal cord obtained from nondiabetic, untreated STZ-D, and insulin-treated STZ-D rats. Eight weeks after the onset of diabetes, caudal nerve conduction velocity (NCV) in the untreated STZ-D rats (n = 13) was slower than in the controls (n = 11; mean +/- SE 30.9 +/- 0.6 vs. 41.4 +/- 1.8 m/s, P less than 0.001). The decrease in NCV was less marked in the insulin-treated STZ-D rats (n = 11; 36.3 +/- 0.9 m/s, P less than 0.05 vs. control). VIP content in sciatic nerve decreased in the untreated STZ-D rats (1.33 +/- 0.23 ng/g wet wt) compared with the other groups (control, 3.10 +/- 0.44, P less than 0.01; insulin-treated STZ-D, 2.44 +/- 0.55, P less than 0.05). However, in spinal cord, VIP content was not significantly different among the three groups. The VIP levels in sciatic nerve showed a positive correlation with NCV (r = 0.430, P less than 0.01). In addition, an inverse correlation between VIP levels and blood glucose levels was observed (r = -0.5624, P less than 0.001). NCV was also inversely correlated with blood glucose levels (r = -0.7662, P less than 0.001). Together with a previous morphological study, these findings suggest a possible causal relationship between reduced VIP content and diabetic neuropathy.     

Dorsal skin responses to topical application with hydrogen peroxide in Mini and Wistar rats.

Mini rats (Jcl: WistarTGN(ARGHGEN) 1Nts) (MRs) are Wistar rat (WR)-derived transgenic rats in which the expression of growth hormone (GH) gene is suppressed under the presence of antisense RNA transgene. In order to evaluate the effects of GH-deficiency on the acute injury by external stimuli, the dorsal skin responses to a single topical application with 20% hydrogen peroxide (HPO), one of the environmental oxidative stressors, were histologically compared between male MRs and WRs of 8 weeks old, whose hair cycle was under the telogen phase. As a result, formation of granulation tissues, reepithelialization and regrowth of hair follicles were delayed in MRs compared with WRs. While hair follicles of MRs of this age are under a long-lasting telogen phase after their 2nd cycle, a new hair cycle started not only in the HPO-applied area but also in the solvent-applied area with a little time lag. These findings suggest that GH-deficiency may influence the skin responses to the external chemical stimuli.     

Horseshoe anomaly of the pancreas.

A 72-year-old man with recurrent pancreatitis and a horseshoe-shaped anomaly of the pancreas is described. The diagnosis was made by endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography scan; laparotomy was confirmatory. The abnormal duct branched to the lower left from an enlarged Santorini's duct; a thin Wirsung's duct was joined at its distal portion to the junction of the abnormal duct. The anomaly was associated with a cystic dilatation of the common bile duct with stone and cholecystolithiasis. This anomaly is considered to be a variation of the dominant dorsal duct syndrome.