CD8alpha+ dendritic cells enhance the antigen-specific CD4+ T-cell response and accelerate development of collagen-induced arthritis

To investigate the role of CD8alpha(+) DCs in the development of collagen-induced arthritis (CIA). The immunogenic properties of CD8alpha(+) and CD8alpha(-) DC subsets were investigated by mixed-lymphocyte reaction and cytokine enzyme-linked immunoassay. CII-pulsed CD8alpha(+) DCs or CD8alpha(-) DCs with CD4(+) T cells from CIA mice were adoptively transferred onto the hind footpad of DBA mice. The onset of arthritis and the arthritis index were examined for 14 weeks after adoptive transfer. Expression of MHC-II and CD80 but not CD86 and CD40 was higher in CD8alpha(+) DCs than in CD8alpha(-) DCs from the spleens of CIA mice. Culturing CD8alpha(+) DCs with CD4(+) T cells significantly increased the proliferative response of CD4(+) T cells in the presence of CII. The production of interleukin (IL)-12p70, IL-17, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha was slightly increased in CD8alpha(+) DCs than in CD8alpha(-) DCs. DBA/1 mice that were adoptively transferred with CII-pulsed CD8alpha(+) DCs and CD4(+) T cells into the footpads showed accelerated onset of CIA compared to control group. By contrast, CD8alpha(-) DCs showed a partial inhibitory effect on CIA. These findings show that CD8alpha(+) DCs accelerated the onset of CIA when aoptively transferred with CD4(+) T cells and that CD8alpha(+) DCs provoke the development of CIA probably by stimulating the immune responses of CII-reactive CD4(+) T cells and by increasing the production of inflammatory cytokines.     

Risk factors influencing the occurrence of injuries in koreans requiring hospitalization

PURPOSE: This study focused on local communities and the factors influencing injuries requiring hospital admission that affect the quality of life for Koreans. MATERIALS AND METHODS: This study used data collected from 4,400 households during the 2001 Korea National Health and Nutrition Examination Survey (KNHANES). A stratified multistage probability sampling method was applied and the final sample included 7,924 subjects over 20 years old who had completed the questionnaire regarding factors influencing injuries requiring hospital admission. Multiple logistic regression analysis was used to estimate the risk factors influencing injuries. RESULTS: The incidence of injuries requiring hospital admission in Koreans was higher in men than in women at 2.3% (95% CI: 1.8-2.8) and 1.7% (95% CI: 1.3-2.1), respectively. Statistically significant factors affecting the occurrence of injuries requiring hospital admission were marital status (OR: 2.60, 95% CI: 2.22- 5.56), state of health (OR: 0.63, 95% CI: 0.43-0.92), frequency of heavy drinking (OR: 1.96, 95% CI: 1.01-3.79), normal physical activities (OR: 1.68, 95% CI: 1.07-2.65), and sleep (OR: 1.54, 95% CI: 1.01-2.35). CONCLUSION: The results of this study can be used to develop measures to prevent fatal injuries and be used as basic data for community health programs.     

A prospective, multicenter, open-label trial of zoledronic acid in patients with hormone refractory prostate cancer

PURPOSE: The short-term safety and efficacy of zoledronic acid for the treatment of skeletal metastasis was evaluated in patients with hormone-refractory prostate cancer. PATIENTS AND METHODS: A total of 19 hormone-refractory prostate cancer patients with bone metastases were enrolled. All patients received up to six infusions of zoledronic acid (4 mg, given intravenously over 15 minutes, every 3-4 weeks). Safety was assessed by monitoring adverse events and serum creatinine levels. Efficacy was assessed by monitoring skeletal-related events, brief pain inventory score, quality of life score, type of pain medication, and analgesic score. Mean age of patients was 67.3 years (46-86 years), mean time from diagnosis of bone metastases was 27.6 months (0-117 months), and mean time from diagnosis of hormone-refractory disease was 7.5 months (0-26 months). RESULTS: There was no clinically significant change in serum creatinine levels. Eleven adverse events (musculoskeletal disorders and systemic disorders) in 8 patients were classed as having a possible relationship to study drug. Fifteen patients completed six courses of zoledronic acid infusion. There were no significant changes in the brief pain inventory composite scores, quality of life questionnaire scores or analgesic score. No new skeletal-related events developed during the treatment period. CONCLUSION: Zoledronic acid administered in this study as a 15-minute infusion demonstrated an acceptable and well-known safety profile in patients with refractory prostate cancer with bone metastases. However, prospective placebo- controlled clinical trials are required to elucidate the efficacy of zoledronic acid.     

Docetaxel-induced onycholysis: the role of subungual hemorrhage and suppuration

Nail changes are common side effects of taxane chemotherapeutic agents. Docetaxel (Taxotere) is known to cause a great incidence of nail change. Various types of nail changes have previously been reported as a result of treatment with taxanes. We describe 2 cases of severe nail changes induced by docetaxel. The patients had previously been diagnosed with breast cancer and advanced gastric cancer, respectively. During the course of treatment with docetaxel, nail changes became apparent in both patients. Initially, they complained of nail bed purpura. Subungual hematomas with hemopurulent discharge were later observed in several fingers. Drainage of the hemopurulent material occurred spontaneously in our cases, leading to onycholysis. Following drainage, the pain in the nail with subungual hemoprulent material was relieved immediately and spontaneous healing of the patients' nails was noticed after few months. Subungual hemorrhage and suppuration therefore are considered causes of onycholysis and the pain in these patients. Although systemic or topical antibiotics were not used to treat these patients, antibiotics may be also worthwhile to hasten the drainage of the subungual hematomas and suppuration in patients for quick relief of pain.     

Beneficial effects of thiazolidinediones on diabetic nephropathy in OLETF rats

PURPOSE: Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF. MATERIALS AND METHODS: 23 Otsuka- Long-Evans-Tokushima-Fatty (OLETF) rats and eight control Long-Evans-Tokushima-Otsuka (LETO) rats were divided into the following four groups: LETO group, control OLETF group, pioglitazone treated group (10mg/ kg/day), and rosiglitazone treated group (3mg/kg/day). RESULTS: A progressive increase in urinary protein excretion was observed in the diabetic rats. Glomerular VEGF expression in the control OLETF rats was significantly higher than in the control LETO rats. However, there was a significant reduction in both the glomerular VEGF expression and the VEGF mRNA levels after treatment with pioglitazone and rosiglitazone. The twenty-four hour urine protein levels were significantly decreased in both groups of the treated OLETF rats. CONCLUSION: These results suggest that TZD may have beneficial effects on diabetic nephropathy by reducing the VEGF expression.     

Percutaneous treatment of renal cysts with OK-432 sclerosis

PURPOSE: The aim of this study was to demonstrate OK- 432 sclerotherapy efficacy for treatment of simple renal cysts. MATERIALS AND METHODS: Twenty patients with 25 symptomatic or large simple cysts were treated by ultrasonography (US)-guided percutaneous aspiration and injection of OK-432 (8 men and 12 women, mean age 63.6 years, SD 9.5). Six patients presented with flank pain, 14 presented with renal mass; renal cyst location was right, left, or bilateral sided in 9, 8, and 8 kidneys, respectively. Patients were evaluated by clinical assessment, US, or CT scan 3 months following the procedure. Complete and partial success was defined as symptom resolution with either total cyst ablation or greater than 70% reduction, respectively. Failure was defined as 30% of cyst size recurrence and/or persistent symptoms. RESULTS: Average reduction was 93.0%. Complete and partial resolution occurred in 11 (44.0%) and 13 (52.0%) cysts, respectively. One case was defined as failure, with a 64.2% size reduction from 10.9cm to 3.9cm (volume reduction rate 95.4%). Renal pain improved in all patients, regardless of complete or partial resolution. Minor complications occurred in 3 patients, 2 developed leukocytosis and 1 had mild fever (< 38.5 degrees C) following aspiration and sclerotherapy. Successful treatment was achieved with conservative measures and NSAID therapy. CONCLUSION: Percutaneous treatment of simple renal cysts with OK-432 sclerotherapy was found to be a safe, effective and minimally invasive procedure.     

Anal canal carcinoma: experience from a single Korean institution

PURPOSE: The clinical features, treatment modality approaches in clinical practice, and prognostic factors for anal canal carcinoma patients were retrospectively analyzed. MATERIALS AND METHODS: Between October 1994 and December 2005, 50 patients with anal canal cancer were treated at Samsung Medical Center, Seoul, Korea. RESULTS: After a median follow up of 37.8 months (range, 6.6-136.1 months), the 5-year and 10-year survival rates for the 38 patients with early and locally advanced squamous and cloacogenic carcinoma (squamous cell carcinoma and cloacogenic carcinoma) were 74.8% and 66.5%, respectively. The 5-year survival and disease-free survival rates (DFS) of the 31 patients who received chemoradiation therapy (CRT) were 83.6% and 74.3%, respectively. The overall and DFS could not be determined for the adenocarcinoma group due to the small number of cases (n=8). Univariate analysis showed that tumor size (p=0.04) and inguinal node status (p=0.04) significantly influenced patient survival in patients with squamous cell and cloacogenic carcinomas. Furthermore, univariate analysis also showed that, inguinal node status influenced patient survival in the adenocarcinoma group. Multivariate analysis showed that inguinal node metastasis is a single independent prognostic variable for survival (p=0.04) in patients with squamous cell and cloacogenic carcinomas. CONCLUSION: Combined CRT has been adopted as standard treatment with outcomes that are comparable to those reported in randomized clinical trials. Due to the rarity and complexity of anal canal carcinoma, interdepartmental cooperation is required for disease treatment. Thus, proper treatment of patients should incorporate a team-approach and should be available to as many patients as possible.     

Gasless endoscopic thyroidectomy via an anterior chest wall approach using a flap-lifting system

PURPOSE: Endoscopic thyroidectomy (ET) requires a proper working space for adequate visualization of anatomical structures and proper instrument manipulation. The purpose of this prospective study was to estimate the feasibility and safety of ET using an anterior chest wall approach without gas insufflation. MATERIALS AND METHODS: The working space was created under a direct and endoscopic view through a 3-cm incision on the anterior chest wall. A retracting device was then inserted to establish the working space, and subsequent procedures were performed endoscopically. All data were reviewed using a prospective database. RESULTS: We performed 30 ETs in patients with benign thyroid tumors from December 2003 to December 2005. The procedures were completed successfully in 29 patients (mean operative time: 160.6 min; range: 90-345 min). One patient with ET was converted to open thyroidectomy secondary to substernal extension of the tumor. None of the patients developed permanent postoperative hypocalcemia or recurrent laryngeal nerve paralysis. Three patients exhibited some degree of transient recurrent laryngeal nerve palsy. CONCLUSION: These data suggest that gasless ET using an anterior chest wall approach is safe and feasible in selected patients for treating benign thyroid tumors. This technique may offer good operative working space when performed by surgeons with relatively low-volume ET practices.     

Combined activities of secretory phospholipases and eosinophil lysophospholipases induce pulmonary surfactant dysfunction by phospholipid hydrolysis

BACKGROUND: Surfactant dysfunction is implicated in small airway closure in asthma. Increased activity of secretory phospholipase A(2) (sPLA(2)) in the airways is associated with asthma exacerbations. Phosphatidylcholine, the principal component of pulmonary surfactant that maintains small airway patency, is hydrolyzed by sPLA(2). The lysophosphatidylcholine product is the substrate for eosinophil lysophospholipases. OBJECTIVE: To determine whether surfactant phospholipid hydrolysis by the combined activities of sPLA(2)s and eosinophil lysophospholipases induces surfactant dysfunction. METHODS: The effect of these enzymes on surfactant function was determined by capillary surfactometry. Thin layer chromatography was used to correlate enzyme-induced changes in surfactant phospholipid composition and function. Phosphatidylcholine and its hydrolytic products were measured by using mass spectrometry. RESULTS: Eosinophils express a 25-kd lysophospholipase and group IIA sPLA(2). Phospholipase A(2) alone induced only a small decrease in surfactant function, and 25-kd lysophospholipase alone degraded lysophosphatidylcholine but had no effect on surfactant function. The combined actions of sPLA(2) and lysophospholipase produced dose-dependent and time-dependent losses of surfactant function, concomitant with hydrolysis of phosphatidylcholine and lysophosphatidylcholine. Lysates of AML14.3D10 eosinophils induced surfactant dysfunction, indicating these cells express all the necessary lipolytic activities. In contrast, lysates of blood eosinophils required exogenous phospholipase A(2) to induce maximal surfactant dysfunction. CONCLUSION: The combined activities of sPLA(2)s and eosinophil lysophospholipases are necessary to degrade surfactant phospholipids sufficiently to induce functional losses in surfactant activity as reported in asthma. CLINICAL IMPLICATIONS: The phospholipases and lysophospholipases expressed by eosinophils or other airway cells may represent novel therapeutic targets for blocking surfactant degradation, dysfunction, and peripheral airway closure in asthma.