Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness

Histamine has a variety of airway actions and is considered to be an important mediator in asthma. This study examined the role of endogenous histamine in allergic airway eosinophil recruitment and hyperresponsiveness using L-histidine decarboxylase gene knockout mice. Histamine levels of the airways in L-histidine decarboxylase knockout mice were largely diminished compared with wild-type mice. Inhalation challenge with ovalbumin (OVA) in OVA-sensitized wild-type mice caused eosinophil accumulation in the lung as well as airway hyperresponsiveness to methacholine 3 days after the challenge. The eosinophil recruitment was significantly reduced in the knockout mice. In the bone marrow, the proliferation of eosinophils was enhanced after OVA challenge in the wild-type mice; however, the proliferation was significantly reduced in the knockout mice. The induction of P-selectin in the lung after OVA challenge was also inhibited in the knockout mice. In contrast, airway hyperresponsiveness was not suppressed in the knockout mice. These results suggest that endogenous histamine is involved in the accumulation of eosinophils into the airways after allergic challenge, possibly acting in the bone marrow and producing P-selectin in the airways. Furthermore, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model.     

Precore and core promoter mutations,hepatitis B virus DNA levels and progressive liver injury in chronic hepatitis B

BACKGROUND/AIMS: To elucidate the viral factors responsible for progressive liver injury in chronic hepatitis B. METHODS: We analyzed 179 persistently infected patients (21 asymptomatic carriers, 126 with chronic hepatitis and 32 with cirrhosis) with genotype C hepatitis B virus (HBV). HBeAg/anti-HBe, levels of HBV DNA, mutations in the basic core promoter (BCP) region at nucleotides 1762/1764 and mutation in the precore (preC) region at nucleotide 1896 were determined. Serial samples from 18 patients also were analyzed. RESULTS: HBeAg/anti-HBe and HBV DNA levels per se were not related to liver fibrosis. The frequency of BCP mutations increased with progression of liver fibrosis. Although the preC mutation was detected more often among the LC group, the role of this mutation in progression of fibrosis seems less than that of the BCP mutations. Sequential analysis showed that (1) rapidly progressing cases were positive continuously for double mutations in the BCP with a wild-type precore sequence, and (2) asymptomatic cases with anti-HBe acquired the preC mutation during their clinical course. CONCLUSIONS: Double mutations in the BCP region at nucleotide 1762/1764 are closely related to progression of chronic liver disease. Acquisition of mutation in the preC region at nucleotide 1896 may contribute to inactivation of chronic liver disease.     

单纯疱疹病毒性食道炎—25例尸检病例分析

运用免疫组织化学及原位杂交方法，对２１７９例尸检病进行了回顾性研究，其证实单纯疱疹病毒性食道炎２５例（１．１％）。主要表现为食道中下段多发性浅表溃疡。其原发病以恶性肿瘤居多，本病并非十分少见，应引起临床工作重视。     

Intravenous dopexamine in the treatment of acute congestive heart failure: Results of a multicenter,double-blind,placebo-controlled withdrawal study

Summary Acute hemodynamic effects of intravenous infusion of dopexamine were evaluated by a placebo-controlled withdrawal study in patients with acute congestive heart failure. Twenty patients were enrolled at 10 centers in Japan. All patients had a pulmonary capillary or diastolic pressure of 15 mmHg or greater and a cardiac index of 2.5 l/min/m² or less.Phase I: Intravenous dopexamine was introduced in a single-blind, uncontrolled fashion at the rate of 0.5 µg/kg/min and was titrated up to achieve a 30% or more increase in the cardiac index. Two patients withdrew from the study due to sinus tachycardia and ventricular ectopy or exacerbation of heart failure.Phase II: The remaining 18 responders who were free of limiting side effects were randomized in double-blind fashion to continue dopexamine or to switch to placebo for an additional 60 minutes. At the end of phase II, the hemodynamic improvement obtained in phase I of the study disappeared completely after substitution of placebo but was maintained in dopexamine-treated patients. Our findings suggest that dopexamine, when given in appropriate doses to selected patients, shows balanced vasodilator action suitable for the treatment of acute congestive heart failure.See Appendix 1 for complete list of participating centers and principal investigators     

Effect of Tumor Deposits on Overall Survival in Colorectal Cancer Patients with Regional Lymph Node Metastases

Objectives: The staging system of the International Union Against Cancer considers tumor deposits to be N1c in patients with no regional lymph node metastasis, but the significance of tumor deposits in patients with regional lymph node metastases is unclear. We investigated the effect of tumor deposits on overall survival in colorectal cancer patients with regional lymph node metastases.Patients and Methods: From 2000 to 2008, 551 patients underwent resections for colorectal cancer at our medical center. We excluded 87 patients who had distant metastases or had received neoadjuvant chemotherapy or radiotherapy from our study and statistically analyzed the remaining 464 patients.Results: Stepwise multivariate Cox proportional hazards analysis in patients with regional lymph node metastases showed only tumor deposits to be significant for overall survival (hazard ratio: 2.813; P = 0.0002). Recurrence was seen in 49.2% of patients with tumor deposits (30/61) compared with 14.4% of patients without them (58/403; P < 0.0001). Tumor deposits did not show the same effect on overall survival as lymph node metastases.Conclusions: Tumor deposits were significantly associated with poorer overall survival in colorectal cancer patients with regional lymph node metastases. The effect of tumor deposits on overall survival was between that of lymph node metastasis and distant metastasis.     

Comparison of efficacy and safety of low-dose-rate vs. high-dose-rate intraluminal brachytherapy boost in patients with superficial esophageal cancer

PurposeTo compare the efficacy and the incidence of complications of high-dose-rate (HDR) and low-dose-rate (LDR) intraluminal brachytherapy (IBT) boost after external beam radiation therapy in patients with superficial esophageal cancer.Methods and MaterialsFifty-four consecutive patients with Stage I thoracic esophageal squamous cell carcinoma who were treated with definitive radiotherapy using IBT between 1991 and 2007 were studied retrospectively. LDR-IBT and HDR-IBT were performed for 19 and 35 patients, respectively. After external beam radiation therapy of 56–60 Gy with a conventional fractionation, LDR-IBT (5 Gy × 2) or HDR-IBT (3 Gy × 3) was given within 2 weeks. The median follow-up was 47 months (7–151 months).ResultsOverall, the 5-year overall survival, cause-specific survival (CSS), and locoregional control (LRC) rates were 61%, 86%, and 79%, respectively. The 5-year overall survival, CCS, and LRC rates did not differ significantly between the LDR-IBT and HDR-IBT groups (68% vs. 58% (p = 0.50), 83% vs. 85% (p = 0.63), and 84% vs. 75% (p = 0.42), respectively). Salvage treatment was given in 8 locally recurrent patients, and 6 patients were rescued. The Grade ≥2 late morbidities of esophagus and heart/lung were observed in 5 patients (4 in the LDR-IBT group and 1 in the HDR-IBT group) and 2 patients (one from each group), respectively.ConclusionsIn view of the safety profile and effectiveness, our results encourage the continued adoption of HDR-IBT as radiation boost in medically inoperable or elderly superficial esophageal cancer patients undergoing definitive radiotherapy.     

Living donor liver transplantation for the patients with portal vein thrombosis: use of an interpositional venous graft passed posteriorly to the pancreatic parenchyma without using jump graft

Background

It is difficult to reconstruct the portal vein (PV) using a long interpositional venous graft in living donor liver transplant (LDLT) patients with portal vein thrombosis (PVT), which involves the confluence of the superior mesenteric vein (SMV) and splenic vein (SV). We successfully performed LDLT for three patients with PVT using an interpositional vascular conduit passing posterior to the pancreas without a jump graft.

Methods

Three of 130 patients who underwent LDLT in our hospital between March 2002 and June 2011 required this technique. After indentifying the location of the SMV, SV and gastrocolic trunk, we ligated and cut the posterior superior pancreaticoduodenal vein and other short branches from the PV. The PV was drawn inferiorly to the pancreas and transected at the confluence of SMV and SV. The external iliac vein or internal jugular vein was sacrificed as a graft for anastomosis to the cut end of the SMV using 6-0 polypropylene running sutures. Then the venous graft was drawn superiorly to the pancreas by passing it posterior to the pancreas parenchyma for anastomosis to the liver graft PV. The interpositional vein was placed posterior to the pancreas where the PV used to be.

Results

All three patients displayed favorable postoperative courses with the Doppler ultrasound demonstrating good portal flow perioperatively. The postoperative portogram demonstrated patency of the vascular graft.

Conclusion

This method is easy and helpful to treat portal vein thrombosis, by providing the shortest route between the PV of the donor and the SMV of the recipient.