4G/5G Variant of Plasminogen Activator Inhibitor-1 Gene and Severe Pregnancy-Induced Hypertension: Subgroup Analyses of Variants of Angiotensinogen and Endothelial Nitric Oxide Synthase

Background

Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3).

Methods

An association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls.

Results

No significant differences were found between the cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In subgroup analyses, after adjustment for multiple comparison, a significant association with the AGT TT genotype was found among women with the PAI-1 4G/4G genotype, and an association with the NOS3 GA+AA genotype was found among women with the 5G/5G or 4G/5G genotypes.

Conclusions

Our findings suggest that there are at least 2 pathways in the pathogenesis of severe PIH. However, with respect to early prediction and prevention of severe PIH, although the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH.Key words: pregnancy-induced hypertension, plasminogen activator inhibitor-1, angiotensinogen, endothelial nitric oxide synthase, gene polymorphism     

Bladder cancer develops 6 years earlier in current smokers: Analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association

Objectives:   It is generally recognized that cigarette smoking is the most important risk factor for bladder cancer. The present study was undertaken to examine the relationships between smoking history of bladder cancer patients and the age of onset of bladder cancer and tumor characteristics.
Methods:   The present study examined the data for 5959 cases (4728 males and 1231 females) collected in the bladder cancer database of the Japanese Urological Association from 1999 to 2001. Patients were divided by smoking history into three categories as current non-smokers, current smokers and unknown smoking history. Relationship between smoking history and the age at diagnosis of bladder cancer, gender, T stage, grade, tumor size, tumor number and initial symptoms was analyzed
Results:   In both males and females the onset of bladder cancer is about 6 years (6.1 years in males and 5.9 years in females) earlier for current smokers than for current non-smokers. At the time of diagnosis, tumor stage was significantly higher in the current smokers group. The current smokers group tended to have larger tumor size.
Conclusions:   The finding of 6-year-earlier onset of bladder cancer among current smokers is of great importance to both health care and medical economics. It is essential to make people better informed concerning the need to quit smoking.     

Clinical outcome of tumor recurrence for Ta, T1 non-muscle invasive bladder cancer from the data on registered bladder cancer patients in Japan: 1999–2001 report from the Japanese Urological Association

Objective:   To characterize the clinical outcome in a large contemporary series of Japanese patients with newly diagnosed Ta, T1 non-muscle invasive bladder cancer who underwent transurethral bladder tumor resection with or without intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) therapy.
Methods:   We developed a database incorporating newly diagnosed non-muscle invasive bladder cancer data and outcomes from a Japanese bladder cancer registry between 1999 and 2001 and identified a study population of 3237 consecutive patients who had complete data based on pathological features. Median patient age was 69.9 years.
Results:   The 1-year, 3-year, and 5-year overall recurrence-free survival rates were 77.0%, 61.3%, and 52.8%, respectively. In multivariate analyses, the multiplicity of bladder tumors, tumor size greater than 3 cm, pathological stage T1, tumor grade G3, and the absence of adjuvant intravesical instillation were independent risk factors for tumor recurrence. Overall, 1710 patients (52.8%) received intravesical instillation; chemotherapy in 1314 (76.8%) and BCG treatment in 396 (23.2%). In patients treated with intravesical chemotherapy in which an anthracycline chemo-agent was used in 90.5% of the cases, multivariate analyses demonstrated that male gender, multiple bladder tumors, a tumor size greater than 3 cm, and pathological stage T1 were associated with tumor recurrence.
Conclusions:   The accumulation and analysis of data from the Japanese National Bladder Cancer Registry made it possible to determine the clinical characteristics, management trends, and survival rates for the period studied. Further study with a dataset created from longer follow-up data would be warranted to analyze tumor progression and disease survival.     

Intracorporeal esophagojejunal anastomosis after laparoscopic total gastrectomy for patients with gastric cancer

Background  To facilitate acceptance of laparoscopic total gastrectomy (LTG) for patients with upper gastric cancer, a simple, secure technique of reconstruction is necessary. The authors developed a new technique for intracorporeal esophagojejunal anastomosis that does not require hand sewing. Methods  From September 2006 to January 2008, 16 patients (11 men and 5 women) with gastric cancer underwent LTG at the authors’ institution. Laparoscopic esophagojejunal anastomosis using the following method was attempted for all patients. The esophagus was transected while being rotated by about 45° counterclockwise to make the subsequent anastomosis easier. After the Y-anastomosis was created, an endoscopic linear stapler was applied to create a side-to-side anastomosis between the left dorsal side of the esophagus and the jejunal limb. The entry hole was first closed roughly with hernia staplers. Subsequently, an endoscopic linear stapler was applied so that all hernia staplers could be removed and the closure completed. Results  Laparoscopic esophagojejunal anastomosis was successfully performed for 15 patients. Intracorporeal anastomosis failed for one patient because a nasogastric tube was caught between the jaws of an endostapler, which resulted in a conversion to open procedure. No postoperative anastomotic complications occurred. Conclusions  Using the new technique, intracorporeal linear-stapled esophagojejunal anastomosis can be performed easily and securely. This technique could become one of the standard methods for reconstruction after LTG, facilitating the acceptance of LTG as a surgical option for patients with upper gastric cancer.     

Association between sleep duration and hemoglobin A1c level

ObjectiveThe association between sleep habits and hemoglobin A_1c (HbA_1c) level has not been sufficiently examined. In the present study of residents in a local community, the associations between sleep duration and HbA_1c level were examined.MethodsSelf-administered questionnaires were mailed to 1062 residents in a rural community in Japan, and completed questionnaires were collected. At the time of collection, the fasting plasma glucose and HbA_1c levels were measured using peripheral blood samples. For the analyses, values that were considered to represent high levels were a fasting plasma glucose level of ⩾126 mg/dl and a HbA_1c level of ⩾6.5%. Logistic regression analyses were performed to examine the associations between sleep duration and high fasting plasma glucose or high HbA_1c levels.ResultsThe prevalence of high fasting plasma glucose and high HbA_1c levels was significantly high (p < 0.01) in subjects with a short or a long sleep duration. Logistic regression analyses demonstrated a significant association between high HbA_1c level and sleep duration. The adjusted odds ratios for a high HbA_1c level showed high values with regard to both short and long sleep durations.ConclusionsHbA_1c level showed a U-shaped association with sleep duration. These results suggest that there may be an appropriate range of sleep duration in individuals with glucose tolerance disorders. It is expected that the present findings will contribute to the treatment and prevention of diabetes mellitus.     

De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis

Abstract:  Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33-yr-old woman who presented complaining of marked fatigue and jaundice four yr after living-donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome-specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.     

The rapid growth of intraluminal tumor metastases at the intestinal wall sites damaged by obstructive colitis due to sigmoid colon cancer: Report of a case

A 53-year-old woman who was traveling in Australia was admitted to a local hospital with pyrexia and diarrhea. Megacolon was diagnosed from an X-ray and an emergency operation was performed. However, the cause of megacolon was not clear, and the attempted operation ended in a simple laparotomy. Sigmoid cancer was found 3 weeks after the first operation and a colostomy was performed at the ascending colon. After the second operation, she returned to Japan and was thereafter admitted to our hospital. Total colonoscopy before the third surgery (sigmoidectomy) revealed erosive mucosa but no tumor. The damaged mucosa in the proximal colon (compatible with a diagnosis of obstructive colitis) was found during a sigmoidectomy. Watery diarrhea and melena persisted after the third operation. Colonoscopy showed disseminated tumor nodules at the proximal colon of the anastomosis at 37 days after the third surgery. Finally, a subtotal colectomy and jejunal pouch reconstruction were carried out. The exfoliated malignant cells from the sigmoid colon appeared to form micrometastases in the mucosal sites damaged by obstructive colitis. In conclusion, in a case of obstructive colitis due to cancer, we must consider the possibility that the tumor may spread to damaged mucosal sites and grow intraluminally.     

Efficacy of a continuous venous infusion of fluorouracil and daily divided dose cisplatin as adjuvant therapy in resectable colorectal cancer: A prospective randomized trial

PURPOSE: Daily divided dose cisplatin (DDD-P) is used as an efficient modulator of fluorouracil (5-FU), as is leucovorin (LV). We performed a randomized trial to compare the efficacy 5-FU plus DDD-P (DDD-FP) therapy with 5-FU alone in resected colorectal cancer as the adjuvant therapy. METHODS: One hundred and eighty-eight stage II or III colorectal cancer patients were enrolled. Patients were randomly assigned to receive DDD-FP (5-FU, 320 mg/ m(2), daily for 21 days; CDDP, 3.5 mg/m(2) daily for 21 days) followed by oral 5-FU (200 mg/body daily for 2 years) (DDD-FP arm) or oral 5-FU therapy (200 mg/ body daily for 2 years) exclusively (oral 5-FU arm). RESULTS: The 5-year disease-free survival (DFS) rates and the overall survival (OS) rates indicated no significant difference between the two arms. By stratified analysis, in the colon cancer patients, the DFS and the OS for the DDD-FP arm were significantly increased: 93.5% and 95.7% in the DDD-FP arm as compared with 76.9% and 82.2% in the oral 5-FU arm (P = 0.024 and P = 0.038). Regarding adverse effects, grade 3-4 toxicities were not significant in two arms. CONCLUSIONS: DDD-FP followed by oral 5-FU therapy suggested a feasible regimen for patients with resected colon cancer as the adjuvant therapy.     

Effects and risks of radiofrequency ablation on the pulmonary tissue and vascular system: A preliminary histological study

Purpose Radiofrequency ablation (RFA) is one of the minimally invasive therapeutic modalities for malignant tumors. However, the effects and risks associated with RFA on pulmonary tumors have not yet been well investigated. We pathologically examined the effects of RFA on the healthy pulmonary parenchyma in the inflated and deflated states of swine lungs. Methods We used two 2-year-old female pigs. Under general anesthesia, RFA was performed twice. Results The mean duration of cauterization for the inflated lungs (93.0 ± 65.4 s) was significantly shorter than that for the deflated lungs (390.3 ± 75.6 seconds) (P = 0.0062). Histologically, the dilatation and congestion of the microvessels were more marked in the lungs. However, no histopathological differences were noticed between the inflated and deflated lungs. Adventitial degeneration was seen in the small vessels, but not in the wall of the large vessels. Conclusions This study confirmed, pathologically, that RFA is effective with an acceptable degree of minimal damage to the normal lung tissue, irrespective of its conditions, i.e., inflated or deflated, and can be safely done near the pulmonary vessels. Therefore, RFA appears to be a promising therapeutic strategy to control local lesions in the field of thoracic surgery. The authors have nothing to declare regarding any conflicts of interest.