The Effect and Safety of the Antithrombotic Therapies in Patients with Atrial Fibrillation and CHADS2 Score 1

Anticoagulation in CHADS₂ Score 1 . Background: The revised ACC/AHA/ESC 2006 guideline recommends either aspirin or warfarin for the prevention of ischemic stroke in patients with atrial fibrillation (AF) in CHADS₂ score 1. We hypothesized that warfarin is superior to aspirin therapy for the prevention of stroke without increasing bleeding complication in AF patients with CHADS₂ score 1. Methods and Results: Among 1,502 patients (mean 62.4 ± 13.8 years old, male 65.4%) who were treated for nonvalvular AF without previous stroke, the number of patients with CHADS₂ score 1 was 422 (62.9 ± 10.7 years old, male 290 [68.7%]) and their antithrombotic therapies were as follows: warfarin (n = 143), aspirin (n = 124), other antiplatelet (n = 45), and no antithrombosis (none: n = 110). We reviewed the incidences of ischemic stroke, mortality, and bleeding complications during the follow‐up period. Results were: (1) during 22.3 ± 17.8 months of follow‐up, the incidence of ischemic stroke was significantly lower in warfarin (6 patients, 4.2%, mean international normalized ratio [INR] 2.0 ± 0.5 IU) than in aspirin (16 patients, 12.9%, P = 0.008) than none (23 patients, 20.9%, P < 0.001) without differences in all‐cause mortality. (2) The incidence of major bleeding (decrease in hemoglobin ≥2 g/dL, requiring hospitalization or red blood cell transfusion ≥2 pints) was not different between warfarin (2.1%) and aspirin (0.8%, P = NS), but minor bleeding was more common in warfarin (10.5%) than in aspirin (2.4%, P = 0.007). Conclusion: In AF patients with CHADS₂ score 1, warfarin was better to prevent ischemic stroke than aspirin without increasing the incidence of major bleeding complications. However, the incidence of minor bleeding was higher in the warfarin group than the aspirin group. (J Cardiovasc Electrophysiol, Vol. 21, pp. 501‐507, May 2010)     

Bronchoscopic features and bronchoscopic intervention for endobronchial hamartoma

Background and objective: Bronchoscopic resection of endobronchial hamartomas has been reported to have a favourable outcome. This study describes the bronchoscopic features of endobronchial hamartoma and reports the clinical outcome of bronchoscopic intervention. Methods: A retrospective analysis was conducted of patients with histologically proven endobronchial hamartomas, diagnosed in the 10‐year period 1999–2009 to elucidate the clinical, radiological and bronchoscopic features of hamartoma and to describe the clinical outcomes. Results: Seventeen of the 135 patients with pulmonary hamartomas were diagnosed as having endobronchial hamartomas. CXR was abnormal in 11 of the 17 patients. On chest CT (n = 16), the median diameter of the lesion was 15.6 mm. Calcification and areas of focal fat in the lesion, the diagnostic CT findings of pulmonary hamartoma, were found in two of 16 (12.5%) patients. At bronchoscopy (n = 16), all tumours had a mass appearance and most were smooth surfaced round masses (50.0%) with 18.8% having a ‘stalk’. Bronchoscopic forceps biopsies were performed in 13 patients, which resulted in five patients (38.5%) being diagnosed with endobronchial hamartoma. Fifteen patients were treated with rigid or flexible bronchoscopic resection, one had lobectomy, and one had no intervention. No procedure‐related mortalities or late complications developed. Conclusions: Bronchoscopic intervention appears to be a safe and effective method to resect endobronchial hamartomas.     

Reactive oxygen species in rats with chronic post-ischemia pain

Background: An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw.
Methods: Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague–Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N -nitro- l -arginine methyl ester ( l -NAME, 10 mg/kg), or SOD (4000 U/kg)+ l -NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats.
Results: Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and l -NAME, which were used to investigate the roles of superoxide (O_2 ˙⁻) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks.
Conclusions: Our findings suggest that O_2 ˙⁻ and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects.     

Association between central venous pressure and blood loss during hepatic resection in 984 living donors

Background: Although low central venous pressure (CVP) anesthesia has been used to minimize blood loss during hepatectomy, the efficacy of this technique remains controversial. We therefore assessed the association between blood loss and CVP during hepatic resection, and examined significant determinants associated with intraoperative hemorrhage during hepatectomy in living donors.
Methods: Between April 2004 and April 2008, 984 living donors who underwent a hepatic resection were assessed retrospectively. Univariate and multivariate analyses were performed to explore the relationships between intraoperative blood loss and several variables including CVP.
Results: The mean intraoperative blood loss was 691.3 ± 365.5 ml. Only four donors required packed red blood cell transfusions (mean, 1.5 U). The mean duration of hepatic resection was 92.1 ± 26.3 min. The mean, maximum, and minimum values of CVP measured during hepatectomy were 4.6 ± 1.7, 5.3 ± 1.8, and 4.0 ± 1.8 mmHg, respectively, and were not significantly correlated with intraoperative blood loss. On multivariate analysis, predictors of hemorrhage were liver fatty change, gender, and body weight, but none of the mean CVP, surgeons, anesthesiologists, anesthesia duration, resected liver volume, hepatectomy type, systolic blood pressure, heart rate, or body temperature were significant.
Conclusions: CVP during hepatic resection was not associated with intraoperative blood loss in living liver donors, suggesting that CVP may not be an important factor in predicting blood loss during hepatectomy in healthy subjects.     

Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers

Park SW, Chung NG, Hur SY, Kim HS, Yoo NJ, Lee SH. Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers. APMIS 2009; 117: 880–5. Hypoxia is a general feature of solid cancer tissues. Hypoxia upregulates hypoxia‐inducible factor 1α (HIF1α) that transactivates downstream genes and contributes to cancer pathogenesis. HIF1α is upregulated not only by hypoxia but also by genetic alterations in HIF1α‐related genes, including VHL. Cullin 2 (CUL2) interacts with the trimeric VHL‐elongin B‐elongin C complex and plays an essential role in the ubiquitinated degradation of HIF1α. The aim of this study was to explore whether HIF1α and CUL2 genes are somatically mutated, and contribute to HIF1α activation in common human cancers. For this, we have analyzed the coding region of oxygen‐dependent degradation domain of HIF1α in 47 colon, 47 gastric, 47 breast, 47 lung, and 47 hepatocellular carcinomas, and 47 acute leukemias by a single‐strand conformation polymorphism assay. In addition, we analyzed mononucleotide repeat sequences (A8) in CUL2 in 55 colorectal and 45 gastric carcinomas with microsatellite instability (MSI). We found one HIF1α mutation (p.Ala593Pro) in the hepatocellular carcinomas (1/47; 2.1%), but none in other cancers. We found two CUL2 frameshift mutations in colon cancers (p.Asn292MetfsX20), which were exclusively detected in high MSI cancers (4.9%; 2/41). Our data indicate that somatic mutation of HIF1α is rare in common cancers, and somatic mutation of CUL2 occurs in a fraction of colorectal cancers (colorectal cancers with high MSI). The data suggest that neither HIF1α nor CUL2 mutation may play a central role in HIF1α activation in gastric, colorectal, breast, lung and hepatocellular carcinomas, and acute leukemias.     

Correlation of serum HCV RNA and alanine aminotransferase levels in chronic hepatitis C patients during treatment with ribavirin

to evaluate the effect of ribavirin on serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels, 22 patients with chronic HCV infection were treated with oral ribavirin 1200 mg daily in three divided doses for 4 weeks. At the end of 4 weeks treatment, the serum ALT decreased in all but one patient and became normal in three individuals. The mean pretreatment serum ALT was reduced significantly from 193 ± 45 i.u./L to 95 ± 16 i.u./L after 4 weeks therapy (P= 0.009). However, 8 weeks after cessation of treatment, the serum ALT rose to a mean value of 154 ± 21 i.u./L. The mean pretreatment serum HCV RNA was not significantly decreased at the end of 4 weeks treatment (7.0 × 10⁵vs 4.1 × 10⁵ copies/mL, P > 0.05). However, serum HCV RNA levels were decreased in 12 and increased in 10 patients at the end of 4 weeks therapy. Eight weeks after cessation of therapy, the serum HCV RNA of 22 patients rose to a mean value of 4.9 ± 10⁵ copies/mL. Six patients who continued to have elevated serum ALT and positive HCV RNA after the initial 4 weeks treatment received oral ribavirin at the same dosage for an additional 24 weeks. The serum ALT again decreased in all six patients during therapy, but rose to pretreatment values by 8 weeks after cessation of the treatment. In addition, no significant changes were noted in the mean serum HCV RNA levels during and after 24 weeks of ribavirin therapy. Our results indicate that oral ribavirin only transiently lowered serum ALT values and did not efficiently suppress HCV synthesis in patients with chronic hepatitits C infection.     

Laparoscopic radical cystectomy with extracorporeal urinary diversion: Preliminary experience

AIM: We present our experience with the fi rst eight patients who underwent laparoscopic radical cystectomy with bilateral pelvic lymphadenectomy and extracorporeal urinary diversion. Patients, operative data and the surgical techniques are presented. METHODS: Between June 2003 and April 2004, seven men and one woman with organ-con fi ned muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with urinary diversion. The age range was 41-73 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using fi ve ports by a transperitoneal approach. An ileal conduit diversion or ileal W-neobladder was constructed through the site of specimen retrieval. RESULTS: We performed eight radical cystectomies with ileal conduits (six cases) or orthotopic ileal W-neobladders (two cases). Conversion to open surgery was necessary in one due to technical dif fi culty in urethroneobladder anastomosis. Mean operating time was 560 min (range 455-680). Mean estimated blood loss was 675 mL (range 400-1050). Two of the eight patients needed blood transfusion (800 mL each). Mean days to oral intake and ambulation was 4.4 (range 2-6) and 4.1 (range 3-5), respectively. Mean hospital stay was 12.8 days (range 7-28). Mean follow up was 6.1 months (range 4-14). Histopathological examination of the specimens revealed stage T2N0M0 in fi ve cases, T3aN0M0 in one, T3aN1M0 in one and T3bN1M0 in one. No metastases have been detected and all are alive and free of disease. CONCLUSION: Laparoscopic radical cystectomy is feasible, although dif fi cult and technically demanding, and our results are promising. With more experience and improvement of the surgical technique, laparoscopic radical cystectomy with urinary diversion may become an alternative surgical method for treating the selected patients with localized muscle invasive bladder cancer.     

Ureteral cancer associated with dermatomyositis

Dermatomyositis is a rare inflammatory myopathy that has characteristic cutaneous lesions. Although many malignancies are associated with dermatomyositis, urogenital malignancies have rarely been reported to be associated with dermatomyositis. We report here on the first case of ureteral cancer associated with dermatomyositis. A 42-year-old man presented to us with a skin rash. A clinical diagnosis of dermatomyositis was made due to the skin lesions, muscle weakness, arthralgia, the increased erythrocyte sedimentation rate and the increased creatine kinase level. The patient revealed microscopic hematuria and abnormal urine cytology during the investigation for the underlying malignancy. Retrograde pyelography demonstrated a suspicious lesion in the right mid-ureter, and the ureteroscopic biopsy revealed the urothelial carcinoma. Although an operation was recommended, the patient died of pneumonia associated with his interstitial lung disease, which is one of the poor prognostic indicators of dermatomyositis.