Assembly and deployment of a branched arch stent graft using the transaortic approach

Transaortic stent grafting is an alternative method for treating distal arch aneurysms. Total arch grafts are too bulky to be inserted into a sheath catheter during usual stent grafting methods. An assembling method that uses a chain stitch enables the deployment of any type of stent graft into the distal aorta without the need for a sheath catheter. We describe how to safely assemble and use a branched arch stent graft. We consider this method to be beneficial in selected cases involving extensive distal arch aneurysms or in patients with highly calcified aortas.     

Alendronate inhibits bone resorption at the bone-screw interface

In the current study, we investigated whether the systemic administration of alendronate, a third-generation bisphosphonate, suppressed the loosening of screws at the bone-screw interface. We systemically administered alendronate to rats fitted with external fixators. External fixators with two half pins were applied to the right femurs of rats, and alendronate was administrated once a week during a 5-week postoperative period. Radiographic, histologic, and immunohistochemical findings subsequently were analyzed. Treatment with alendronate reduced the width of the fibrous loosening membrane and the number of osteoclasts at the bone-screw interface. These findings indicate that systemic treatment with alendronate exerts an inhibitory effect on local bone resorption at the bone-screw interface.     

Chest wall mesenchymal hamartoma associated with a massive fetal pleural effusion: a case report

We report on an extremely rare chest wall mesenchymal hamartoma associated with a massive fetal pleural effusion. Prenatal ultrasound examination demonstrated a heterogeneous mass in the right thorax associated with a massive pleural effusion and right lung compression at 29 weeks of gestation. The patient underwent pleuroamniotic shunting at 30 weeks and was delivered at 33 weeks by cesarean delivery secondary to fetal distress. After management of the respiratory distress and evaluation of the mass, surgery was performed at day of life 8. Histological examination confirmed the diagnosis of a chest wall mesenchymal hamartoma.     

Insulin resistance contributes to obesity-related proteinuria

OBJECTIVE: Proteinuria is a recognized complication of obesity, but the pathogenesis remains unclear. We undertook the present study to clarify the factors contributing to proteinuria associated with obesity. METHODS: We studied 12 obese patients with proteinuria. Twenty-seven age-matched obese subjects without proteinuria served as controls. A glucose tolerance test and renal biopsy were performed in all patients. Fasting serum insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were regarded as reflecting insulin resistance. To delineate the relation between insulin resistance and proteinuria, troglitazone, which acts an insulin sensitizer was given to 6 of 12 patients with a regular diet for 8 weeks. The 6 others were observed without receiving troglitazone. RESULTS: The 12 patients showed the presence of a cluster of insulin resistance factors: higher blood pressure, higher body mass index, higher fasting plasma glucose, higher fasting serum insulin, and higher HOMA-IR than controls. The renal biopsy specimens exhibited no histological abnormalities in 7, focal segmental glomerulosclerosis in 3 and benign nephrosclerosis in 2. Troglitazone attenuated HOMA-IR and ameliorated proteinuria, but did not affect body weight, creatinine clearance, or blood pressure. In contrast, the parameters in the patients not given troglitazone did not change. CONCLUSION: Insulin resistance is a factor contributing to obesity-related proteinuria. The role of insulin resistance as a factor reducing proteinuria remains to be clarified.     

Incidence of heparin-PF4 complex antibody formation and heparin-induced thrombocytopenia in acute coronary syndrome

A multicenter prospective study on the rate of seroconversion of antibodies to heparin-PF4 complexes (heparin-induced thrombocytopenia [HIT] antibodies) during and after heparin treatment for 4 weeks was carried out in Japanese patients with acute coronary syndrome (ACS). A total of 254 ACS patients treated with heparin were enrolled consecutively from 12 facilities of cardiology. Two patients with preexisting HIT antibodies were excluded from the analysis. The total seroconversion rate for four weeks during and after heparin treatment was 8.7% (n=22, 95% confidence interval [CI]: 5.9–13.1), including values of 3.2% (n=8) at the end of heparin infusion and 5.5% (n=14) at 4 weeks. Among 22 seroconverted patients, four developed HIT and two of the four had the complication of thrombosis. The incidence of HIT was 1.6% (n=4, 95% CI: 0.04–3.1). The risk for thromboembolic development was higher in the seroconverted patients (odds ratio, 17.4, 95% CI: 5.2–58.4, p<0.0001) than nonconverted patients. An analysis of factors affecting the seroconversion rate was carried out. The seroconversion rate for ACS patients who underwent percutaneous coronary intervention (PCI; n=163) was 12.3%, significantly higher than the 2.3% in patients who did not undergo PCI (n=89), leading to an odds ratio of 6.1 (95% CI: 1.4–26.7, p=0.009). A significant odds ratio was obtained for each factor affecting the seroconversion: 3.5 (95% CI: 1.3–9.9, p=0.014) for more than 5 days of heparin infusion, 3.0 (95% CI: 1.2–7.6, p=0.035) for a thrombotic history and 2.7 (95% CI: 1.1–6.8, p=0.039) for hyperlipidemia. No other factor, including age or diabetes mellitus, contributed to the seroconversion. Therefore, PCI, duration of heparin treatment and thrombotic history facilitated the seroconversion in ACS patients. PCI patients treated for more than 5 days with heparin showed a maximal seroconversion rate of 18.3% (95% CI: 13.8–22.2). This high rate in PCI patients did not interact with age, type of underlying disease of unstable angina or myocardial infarction or thrombotic history.

In conclusion, ACS patients demonstrating seroconversion are at risk of thromboembolic development due to the likelihood of immunomediated endothelial dysfunction. The increase in the rate of seroconversion in ACS patients would be affected by factors such as PCI with mechanical stress, longer duration of heparin treatment, thrombotic history and presence of hyperlipidemia. If PCI is undertaken with heparin anticoagulation for more than 5 days, seroconversion would easily occur, and the seroconverted patients could subsequently suffer from HIT.     

An EP4 receptor agonist prevents indomethacin-induced closure of rat ductus arteriosus in vivo

Indomethacin exerts a strong tocolytic effect by suppressing uterine contractions mediated by prostaglandins. However, indomethacin also induces in utero closure of fetal ductus arteriosus (DA), leading to serious neonatal consequences. Using rats, we tested the effect of an agonist for a subtype of prostaglandin E2 receptor (EP4), ONO-AE1-437 and its prodrug ONO-4819, as a DA dilator during indomethacin treatment. In vitro, ONO-AE1-437 exhibited a potent dilatory effect on DA against O(2)- and indomethacin-induced contractions in a concentration-dependent manner. In vivo, rat dams were given indomethacin (10 mg/kg, p.o.) alone or with ONO-4819 (0.3 micrograms/kg/h, s.c.) on d 21 of gestation and pups were delivered 4 h later through cesarean section to evaluate the ratio of diameter of DA to that of pulmonary artery. Pups from dams with no drug had DA/PA ratio of 0.9 +/- 0.05, whereas those from dams with indomethacin alone had a decreased ratio of 0.2 +/- 0.03. When ONO-4819 was co-administered to the dams, the ratio recovered significantly to 0.7 +/- 0.06. The administration of ONO-4819 to the dams did not induce any increase in the uterine activity. These results suggest that administration of an EP4 agonist in addition to indomethacin might prevent adverse reactions of indomethacin on fetal DA without restricting its tocolytic effects.     

Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: a COOPERATE-ABP substudy

BACKGROUND: In the COOPERATE trial, the combination treatment of the angiotensin-II receptor blocker losartan and the angiotensin-converting-enzyme inhibitor trandolapril significantly retarded progression of non-diabetic kidney disease compared with each monotherapy. The benefit could be greatly attributable to the potent reduction of proteinuria, because the three treatment groups showed the same reductions of office blood pressure (OBP). Ambulatory blood pressure (ABP) is reported to be better than OBP in predicting progression of kidney disease. METHODS: Ninety-two patients enrolled in the COOPERATE trial underwent 24-hour ABP monitoring at randomization and at month 6, year 1, year 2 and year 3 on randomized treatment. RESULTS: Both OBP and ABP were similarly reduced among the three groups at all measurement points (p = NS) and throughout the whole study period (p = NS). No significant correlation between the change in 24-hour ABP and the change in proteinuria was seen (p = NS). A Cox-multivariable analysis showed that covariates affecting the renal outcomes (a doubling serum-Cr level and/or end-stage renal failure) were the change in proteinuria (hazard ratio 0.49, 95% CI 0.34-0.78, p = 0.01) and treatments (0.58, 0.45-0.99, 0.03), but not 24-hour ABP (0.98, 0.89-2.01, 0.17). CONCLUSION: The better renoprotective effect of the combination treatment is attributed to BP-independent mechanisms by more complete renin-angiotensin system blockade.     

RETRACTED ARTICLE: Dual blockade of the renin-angiotensin system in chronic renal disease: <Emphasis Type="Italic">to do or not to do</Emphasis>

The renin-angiotensin-aldosterone system has an important role in the progression of both diabetic and nondiabetic nephropathy. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor blocker can effectively retard or halt this progression. However, their renoprotective effect is not enough, because approximately 20% of patients have a progressive course to endstage renal disease. There is now clear evidence that combination therapy of two agents is more antiproteinuric and, likely renoprotective, than each agent alone. However, several critical issues should be addressed before recommending it as standard treatment in chronic renal disease.