Evaluation of pre-operative 5-fluorouracil treatment of the patients with gastric cancer--alteration of the inhibition rate of thymidilate synthetase by dose difference

5-fluorouracil (5-FU) was orally administered before surgical operation to two groups of patients, one treated at 300 mg for 7 days and the other treated at 400 mg for 5 days, to examine the change of TSIR in gastric patients. Tumor tissue, lymph node and normal lesions were collected from removed specimens immediately frozen. As a result, there were no differences in FdUMP volumes of various tissues between 300 mg and 400 mg groups. TSIR tended to be higher in the order of normal tissue, lymph node and tumor lesions. TSIR was significantly higher in 400 mg group than 300 mg group. We believe that further studies on TSIR will provide a useful information as to various studies, including efficacy reinforcement by combination therapy, problems in resistance, histological efficacy and sensitivity tests.     

Association of FLT3 polymorphisms with low BMD and risk of osteoporotic fracture in postmenopausal women.

The genetic effects of FLT3 polymorphisms on BMD and fracture risk in postmenopausal women were studied. We found that FLT3+13348C>T polymorphism and haplotype 2 were significantly associated with low BMD and high risk of fracture. INTRODUCTION: FMS-related tyrosine kinase 3 (FLT3) has been shown to play a critical role in the development of myelolymphoid progenitors and in the development of osteoclasts, but any possible genetic effect of FLT3 on bone metabolism has not been studied. MATERIALS AND METHODS: To study a possible genetic effect of FLT3, we directly sequenced the FLT3 gene in 24 Korean individuals and identified 23 sequence variants. Seven polymorphisms were selected and genotyped in Korean postmenopausal women (n = 946). RESULTS: We found that FLT3+13348C>T was associated with low BMD at the lumbar spine (p = 0.04) and femoral neck (p = 0.04). Haplotype analysis revealed that FLT3-ht2 (TTCTT) containing the rare allele in the +13348 position also showed significant association with low BMD in the lumbar spine (p = 0.04) and femoral neck (p = 0.05). Consistent with these results, the FLT3+13348C>T polymorphism and FLT3-ht2 were also significantly associated with high risk of fracture in the vertebrae (OR = 1.44-1.58; p = 0.03-0.04 and OR = 1.45-1.59; p = 0.02-0.03, respectively) and in any sites (OR = 1.34-1.81; p = 0.02-0.03 and OR = 1.34-1.81; p = 0.02-0.03, respectively). CONCLUSIONS: These results suggest that FLT3 polymorphisms play a role in determination of BMD and subsequent fractures in postmenopausal women.     

A novel, simple way to insert percutaneous central venous catheters in newborn babies.

Percutaneous central venous catheters (PCVC) have become commonplace in neonatal intensive care units, There is now available a 27-gauge silicone catheter (Premicath, Vygon, Germany) that is inserted through a 24-gauge butterfly needle. We describe a simple technique that allows a PCVC to be inserted without the need for a butterfly needle or guide wire in any baby who has an indwelling peripheral intravenous cannula.     

Cell cycle: Immunolocalization of bcl-2 protein in human endometrium in the menstrual cycle and simulated early pregnancy

Cell death by apoptosis is now regarded as an important featureof normal endometrial physiology. Recent reports have suggestedthat bcl-2, a proto-oncogene responsible for the suppressionof apoptosis, is expressed in endometrium and may be involvedin the regulation of menstruation. Using standard immunohistochemicalprocedures, the immunoreactivity of bcl-2 and progesterone receptorshas been investigated in normal human endometrium throughoutthe menstrual cycle (n = 25) as well as endometrium exposedto continued oestradiol and progesterone stimulation by ‘rescue’of corpus luteum (n = 4) with exogenous human chorionic gonadotrophin(HCG) administration (pseudopregnancy). Marked immunoreactivity,consistent with previous reports, was noted in the glandularepithelium during the proliferative phase of the cycle. Immunostainingpersisted in the glandular epithelium during the secretory phase,although the percentage and intensity of staining was markedlyreduced. Staining in the stromal compartment was only notedduring the late secretory phase of the cycle. Co-localizationwith an antibody against CD56 demonstrated that this immunoactivitylargely reflected the presence of lymphocytes in the stroma.Endometrium from subjects who underwent ‘luteal rescue’displayed limited immunostaining in either glands or stroma.The absence of significant bcl-2 expression in endocrinologicallymaintained endometrium makes it highly unlikely that bcl-2 isimportant in prolonging endometrial cell survival in the lutealphase of the menstrual cycle.     

Idiopathic benign biliary stricture

A rare case of idiopathic benign biliary stricture is reported. A 50-year-old man with liver dysfunction underwent ultrasonography, which revealed dilation of the intrahepatic bile ducts, and endoscopic retrograde cholangiopancreatography, which revealed a short, ring-like stenosis at the junction of the left and right hepatic ducts. Although a benign stricture was suspected, radiologic tests alone were insufficient to make a firm diagnosis. Therefore, a cholecystectomy and resection of the extrahepatic biliary tract were performed. Microscopic examination of the resected specimen demonstrated no evidence of malignancy. The final diagnosis was mild, localized, chronic cholangitis. The patient had not had previous biliary tract surgery, choledocholithiasis, nor did he have a congenital abnormality of the biliary tract, bile duct carcinoma, or pancreatic disease. Since there was no evidence of primary sclerosing cholangitis, the stricture was considered to be idiopathic. Received for publication on May 30, 1997; accepted on April 13, 1998     

Comparison of 1-day, 2-day,and 3-day administration of antimicrobial prophylaxis in radical prostatectomy

An adequate protocol for antimicrobial prophylaxis (AMP) in radical prostatectomy has not been established. We retrospectively compared the incidence and severity of infectious complications after radical prostatectomy with three different protocols for AMP. The study cohort consisted of 67 patients with prostate cancer who underwent radical prostatectomy at Hakodate Goryoukaku Hospital between January 2003 and December 2005. As a prophylactic antimicrobial agent, one of the cephalosporins or penicillins was administered intravenously to all patients. The analyzed protocols were for: (1) a 3-day group: administration of AMP until the second postoperative day (POD 2), (2) a 2-day group: administration of AMP until POD 1, and (3) a 1-day group: administration of AMP only on the operative day. The incidence and severity of infectious complications were retrospectively investigated. Three patients in the 3-day group (9.4%), 2 patients in the 2-day group (12.5%), and 2 patients in the 1-day group (10.5%) developed some infectious complications. The incidence of infectious complications was not significantly different among the three groups. No patients developed severe infectious complications such as sepsis. We conclude that single-day AMP is sufficient in patients with radical prostatectomy.     

A 6-year review of surgical morbidity and oncological outcome after high anterior resection for colorectal malignancy with and without splenic flexure mobilization

Objective High anterior resection (HAR) for colorectal cancer is traditionally performed with routine mobilization of the splenic flexure. This is a retrospective review of mortality and morbidity following HAR in which the splenic flexure has been preserved. Method From a prospective database, all patients who had undergone elective HAR for colorectal cancer between 1999 and 2005 were identified. Morbidity, mortality, pathology and survival data for patients having HAR with and without splenic flexure mobilization were analysed. Results A total of 707 patients were identified. Five hundred and thirty‐one had HAR with preservation of the splenic flexure. In these patients outcome was: anastomotic leak (0.4%), wound infection (3.6%), anastomotic stricture (0.4%) and 30‐day mortality (0.9%). No statistical significant difference was found for postoperative morbidity (P = 0.1926), 30‐day mortality (P =0.3285), lymph node harvest (P = 0.2127) or survival (P = 0.1457) compared with patients in whom the splenic flexure was mobilized. Longitudinal resection margins were greater following HAR with splenic flexure mobilization (P < 0.0001). Conclusion No morbidity, oncological or survival disadvantage in performing splenic flexure preserving HAR was found.     

Oxidative injury triggers autophagy in astrocytes: The role of endogenous zinc

We have recently demonstrated that the accumulation of labile zinc in lysosomes during oxidative stress causes lysosomal membrane permeabilization (LMP) in cultured hippocampal neurons. Since autophagy involves fusion of autophagic vacuoles (AVs) with lysosomes, zinc accumulation may start in AVs. In the present study, we examined the role of endogenous zinc in H₂O₂‐induced autophagy and cell death in mouse astrocyte cultures. Live‐cell confocal imaging of astrocytes transfected with GFP‐LC3 revealed that the number of AVs positive for LC3 (microtubule‐associated protein 1 light chain 3) increased following exposure to H₂O₂ or ferrous chloride (FeCl₂). Staining of RFP‐LC3‐transfected astrocytes with FluoZin‐3 indicated that the levels of labile zinc increased in AVs as well as in the cytosol and nuclei. The majority of AVs were double‐stained with LysoTracker, indicating that they were fused with lysosomes. Chelation of zinc with tetrakis [2‐pyridylmethyl]ethylenediamine (TPEN) decreased the number of AVs in H₂O₂‐treated astrocytes, whereas exposure to zinc increased their number, suggesting that dysregulation of zinc homeostasis is mechanistically linked to autophagy. Unexpectedly, inhibition of autophagy blocked the rise in labile zinc levels. Astrocytic death induced by H₂O₂ was accompanied by LMP. Autophagy inhibitors (3‐methyladenine, bafilomycin‐1) or TPEN attenuated LMP and cell death in astrocytes. These results support the possibility that endogenous zinc plays a key role in autophagy under oxidative stress in astrocytes, and suggest that autophagy is a necessary preceding event for LMP and cell death in oxidative injury. © 2009 Wiley‐Liss, Inc.     

Arterial stiffness, metabolic syndrome and inflammation amongst Asian ischaemic stroke patients

Background and purpose:  Arterial stiffness and metabolic syndrome (MetS) are risk factors for ischaemic stroke. We studied the association of arterial stiffness, measured by carotid–femoral pulse wave velocity (PWV) and MetS amongst ischaemic stroke patients. We also investigated the role of inflammation measured by serum erythrocyte sedimentation rate (ESR) in the metabolic syndrome–arterial stiffness relationship.
Methods:  Amongst the 229 prospectively recruited acute ischaemic stroke patients, we measured carotid–femoral PWV using applanation tonometry and the inflammatory marker serum ESR.
Results:  Carotid–femoral PWV was significantly higher amongst patients with MetS ( P  = 0.002), increased waist circumference ( P  = 0.010), raised blood pressure ( P  < 0.001) and abnormal glycemia ( P  = 0.002); and increased with the number of MetS components ( P  = 0.002). In a sub-group of 199 patients, carotid–femoral PWV was significantly correlated with serum ESR ( P  < 0.001). In multivariate regression analysis including serum ESR and MetS as variables, carotid–femoral PWV was independently associated with higher ESR ( P  = 0.002) but not with MetS ( P  = 0.139).
Conclusions:  Arterial stiffness is significantly associated with MetS amongst ischaemic stroke patients, and inflammation appears to be involved in this relationship.