IL-10 promoter gene polymorphism associated with the occurrence of chronic GVHD and its clinical course during systemic immunosuppressive treatment for chronic GVHD after allogeneic peripheral blood stem cell transplantation

BACKGROUND: The current study attempted to evaluate the association between IL-10 promoter gene polymorphism and transplant outcomes including the occurrence of chronic graft-versus-host disease (GVHD) and its clinical course during systemic immunosuppressive treatment (IST) among 60 recipients of cytokine-mobilized peripheral blood stem cell (PBSC) from HLA-matched sibling donors. METHODS: We analyzed 3 single-nucleotide polymorphisms in proximal region of IL-10 promoter gene (-1082/-819/-592). RESULTS: In the current study, only two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]) were found. An increased occurrence of chronic GVHD was noted dependent on the IL-10 haplotypes (43% vs. 68% vs. 96% in ACC/ACC vs. ATA/ACC vs. ATA/ATA haplotype, P=0.003). In a logistic regression based on multinomial model, ATA/ATA homozygote had 7-fold increasing risk of the development of chronic GVHD compared with ACC/ACC homozygote. The incidence of chronic GVHD at 1 year was 46%+/-20%, 64%+/-10%, and 82%+/-5% in ACC/ACC, ATA/ACC and ATA/ATA group, respectively (P=0.0266). Plus, the duration of systemic IST was significantly shorter in recipients without ATA-haplotype comparing with those with ATA haplotype (339 days vs. 1,146 days, P=0.0091). CONCLUSION: IL-10 promoter gene polymorphism was found to be apparently associated with chronic GVHD after allogeneic peripheral blood stem cell transplantation from HLA-matched sibling donors.     

Hand-sewn coloanal anastomosis for distal rectal cancer: Long-term clinical outcomes

As the oncologic safety of coloanal anastomosis (CAA) has been proved by many other authors, the incidence of CAA following ultralow anterior resection has increased. The purpose of this study is to evaluate the functional outcome and complications of patients who underwent ultralow anterior resection and CAA for distal rectal cancer. Fifty-seven patients underwent CAA following ultralow anterior resection between July 1997 and November 2003. Forty-four patients, who were followed up more than 6 months after diverting ileostomy closure, were evaluated for recurrence, complications, and functional outcomes. The mean follow-up period was 36.3 +/- 22.8 months (range, 8-83 months). The complications were multiple fistula (n = 3), fistula with anal stenosis (n=1), local recurrence with anal stenosis (n = 1), and anal stenosis (n = 7). Anal incontinence (Kirwan grade III) was noted in 14 patients, and bowel movements were observed more than six times per day in 16 patients. Overall recurrence occurred in six patients (13.6%). The 5-year survival rate was 85.3%, and the disease-free 5-year survival rate was 73.3%. Although CAA in patients with rectal cancer provides excellent long-term survival, a low risk of recurrence, and tolerable function, complications and poor functional outcomes of CAA do occur. Therefore, the choice of this method should be considered carefully.     

Fentanyl Attenuates α1B-Adrenoceptor-Mediated Pulmonary Artery Contraction

Background: The authors tested the hypothesis that the intravenous anesthetic fentanyl would attenuate the pulmonary vasoconstrictor response to [alpha]1-adrenoceptor activation. They also investigated the [alpha]1-adrenoceptor subtypes that could potentially mediate this effect of fentanyl.

Methods: Endothelium-denuded canine pulmonary arterial rings were suspended for isometric tension recording. Dose-response curves for the [alpha]1-adrenoceptor agonist phenylephrine were generated in the absence and presence of fentanyl. The effects of inhibiting [alpha]2 (rauwolscine), [alpha]1 (prazosin), [alpha]1A (5-methylurapidil), [alpha]1B (chloroethylclonidine), and [alpha]1D (BMY 7378) adrenoceptors on phenylephrine contraction were also investigated. Receptor "protection" studies were performed to investigate the specific role of [alpha]1B adrenoceptors in mediating fentanyl-induced changes in phenylephrine contraction. Finally, competition binding studies were performed in rat-1 fibroblasts stably transfected with human [alpha]1-adrenoceptor complementary DNAs corresponding to the [alpha]1A-, [alpha]1B-, or [alpha]1D-adrenoceptor subtypes to directly assess whether fentanyl can compete for the [alpha]1-adrenoceptor activation pocket.

Results: Fentanyl attenuated phenylephrine contraction in a dose-dependent fashion. Rauwolscine had no effect on phenylephrine contraction. Phenylephrine contraction was inhibited by prazosin and abolished by chloroethylclonidine but was relatively resistant to inhibition by 5-methylurapidil and BMY 7378. Pretreatment with fentanyl before exposure to chloroethylclonidine increased the maximal contractile response to phenylephrine compared to chloroethylclonidine pretreatment alone. Competition binding studies revealed that fentanyl binds to all three [alpha]1-adrenoceptor subtypes, with a fivefold greater affinity for the [alpha]1B-adrenoceptor compared with the [alpha]1D-adrenoceptor subtype.     

Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.     

Obstructive uropathy

Summary A patient with primary linitis plastica of the colon has been presented. The unusually aggressive nature of this tumor is demonstrated in a young man who presented with obstructive uropathy. Extensive renal involvement is a rare complication of this disease, and obstructive uropathy is a previously undescribed presentation. If early recognition is to favorably alter prognosis, then awareness of this form of colonic malignancy is essential.     

Concurrent male gynecomastia and testicular hydrocele after imatinib mesylate treatment of a gastrointestinal stromal tumor

We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and noncommunicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST.     

Changes of smoking behavior and serum adrenocorticotropic hormone, cortisol, prolactin, and endogenous opioids levels in nicotine dependence after naltrexone treatment

This study was done to evaluate the therapeutic effects of naltrexone on smoking behaviors and to measure the changing of brain substances for elucidating the mode of action by naltrexone. Twenty-five voluntarily participated healthy male smokers were randomly assigned to naltrexone group or placebo group for 2 weeks. In this study, naltrexone group showed significant reduction in daily cigarette consumption amount, the expiratory CO levels, brief questionnaire for smoking urge (B-QSU) score, and FTQ score. However, only 2 subjects in naltrexone group quitted smoking completely at 4th week. Plasma levels of pituitary hormones (ACTH, cortisol, and prolactin) and endogenous opioids (beta-endorphin and dynorphin A) were checked weekly before and after the 'provocation and smoking coupled' stimulus once in a week for 3 weeks. In naltrexone group, pituitary hormones showed upward tendencies even though only the prolactin had statistical significance. However, beta-endorphin and dynorphin A were not significantly different between the two groups. It was suggested that naltrexone made effects on hypothalamo-pituitary-adrenocortical axis activity as well as smoking behavior. However, the meaning of these endocrinal changes by naltrexone is not conclusive, whether it is beneficial or aversive.     

Ex Vivo Experiment of Saline-Enhanced Hepatic Bipolar Radiofrequency Ablation with a Perfused Needle Electrode: Comparison with Conventional Monopolar and Simultaneous Monopolar Modes

The purpose of this study was to validate the saline-enhanced bipolar radiofrequency ablation (RFA) technique using a perfused electrode to increase RF-created coagulation necrosis, to compare that technique with monopolar RFAs and to find appropriate concentrations and volumes of perfused NaCl solution for the bipolar RFA. A total of 90 ablations were performed in explanted bovine livers. In the initial experiments to determine appropriate conditions for bipolar RFA, we created five thermal ablation zones in each condition, with instillations of varied concentrations (0.9–36%) or injection rates (30 mL/hr–120 mL/hr) of NaCl solution. After placement of one or two 16-gauge open-perfused electrodes into bovine livers, the NaCl solution was instilled into the tissue through the electrode. In the second part of the study, 10 ablation zones were created using one or two perfused electrodes for each of five groups under different conditions: a conventional monopolar mode with 0.9% NaCl solution (group A) or with 6% NaCl solution (group B), a simultaneous monopolar mode with 6% NaCl solution (group C) and a bipolar mode with 6% NaCl solution (groups D and E). RF was applied to each electrode for 20 min in groups A, B, C, and E, or for 10 min in group D. During RFA, we measured the tissue temperature 15 mm from the electrode. The temperature changes during the RFA and the dimensions of the ablation zones were compared among the groups. Bipolar RFA created larger short-axis diameters of coagulation necrosis with 6% NaCl solution (35.8 ± 15 mm) than with 0.9% NaCl solution (17 ± 9.7 mm) (P < 0.05). However, concentrations of NaCl solution above 6% did not further increase the extent of coagulation necrosis. In addition, bipolar RFA with 6% NaCl solution instillation at a rate of 1.0 mL/min (37.9 ± 5.4 mm) or 2.0 mL/min (35.6 ± 9.3 mm) produced larger diameters at the mid-point between the electrodes of the ablated lesion than did 0.5 mL/min (25.8 ± 9.3 mm) (P < 0.05). The bipolar mode showed a more rapid increase in temperature at the mid-point between the two probes, up to 60°C, than did the monopolar modes (P < 0.05). In addition, the bipolar RFA (group E) treated for 20 min showed a larger value of the short-axis diameter than did the conventional or simultaneous monopolar modes (P < 0.05), and bipolar RFA (group D) treated for 10 min, showed similar results with conventional monopolar modes treated for 20 min (P > 0.05): 31.0 ± 5.4 mm (group A); 28.8 ± 3.8 mm (group B); 25.5 ± 6.4 mm (group C); 32.6 ± 4.2 mm (group D); 49.4 ± 5.0 mm (group E). Bipolar RFA with instillation of 6% NaCl solution through an open perfusion system demonstrates better efficacy in creating a larger ablation zone than does conventional or simultaneous monopolar modes at the various times examined. Therefore, hypertonic saline-enhanced bipolar RFA seems to be a promising approach for treating larger liver tumors.