Locally Applied Stem Cell Exosome-Scaffold Attenuates Nerve Injury-Induced Pain in Rats.

PURPOSE: Nerve injury-induced pain is difficult to treat. In this study, we developed an alginate scaffold with human umbilical cord mesenchymal stem cell exosomes (EX-SC) to treat nerve injury-induced pain. MATERIALS AND METHODS: The scaffold was prepared and characterized for its physical traits and biocompatibility. In vitro studies of PC12 and HEK293 cells were used to evaluate the neuroprotective and neurotrophic effects of exosomes. Right L5/6 spinal nerve ligation (SNL) was performed in Sprague-Dawley rats to induce mechanical allodynia and thermal hyperalgesia, evaluated by von Frey hair and radiant heat tests. The EX-SC was wrapped around ligated L5/6 spinal nerves for treatment. Western blotting and immunofluorescence staining were used to evaluate neuron/glial activation, cytokines and neurotrophic factor of affected dorsal root ganglion (DRG). RESULTS: In cell culture assay, the exosomes induce neurite outgrowth of PC12 cells and protect PC12 and HEK293 cells against formaldehyde acid treatment. On post-ligation day 21, rats receiving EX-SC had significantly higher median (interquartile range) withdrawal threshold and latency [14.1 (13.7-15.5) g, 14.2 (13.7-15.3) s] than saline-SC-treated rats [2.1 (1.7-3.0) g, 2.0 (1.8-2.4) s, P=0.02 and 0.002]. The EX-SC also attenuated SNL-induced up-regulation of c-Fos, GFAP, Iba1, TNF-α and IL-1ß, while enhancing the level of IL-10 and GDNF, in the ipsilateral L5/6 DRG. After implantation for 21 days, the EX-SC enhanced the expression of myelin basic protein and IL-10 in injured L5/6 axons. CONCLUSION: We demonstrate the EX-SC possesses antinociceptive, anti-inflammation and pro-neurotrophic effects in the SNL pain model. It could be a promising therapeutic alternative for nerve injury-induced pain.

The risk factors and complications of forgotten double-J stents: A single-center experience.

BACKGROUND: Postoperative urology patients may require the insertion of a ureteral stent. However, the delayed removal or change of the ureteral stent may lead to serious consequences for some patients. This study primarily aimed to examine the risk factors and complications associated with forgotten double-J stents (DJSs). METHODS: In this retrospective study, postoperative patients who underwent DJS insertion were recruited. Based on the brand of DJS, the maximal stent life (MSL) was classified into 3-month, 6-month, and 12-month groups, and a forgotten DJS was defined as the one that had yet to be removed 2 weeks past its MSL. A total of 479 patients were analyzed. The reasons for the use of DJSs use and the time and method of their insertion were recorded, and the risk factors and possible complications associated with forgotten DJSs were analyzed. RESULTS: The primary reason for DJS insertion was urolithiasis (69.7%), and insertions performed using ureterorenoscopy were the most common (413/479, 86.2%). Eighteen patients (3.8%) had forgotten DJSs, with an average overdue period of 63.17 days (18-189 days). Multivariate analysis revealed that patients older than 60 years (odds ratio [OR] = 3.626, 95% confidence interval [CI] = 1.070-12.289; p = 0.039) and DJSs exchanged using fibrocystoscopy (OR = 5.437, 95% CI = 1.060-28.256; p = 0.042) were significantly associated with forgotten DJSs. Out of the 18 patients with forgotten DJS, three (16.67%) experienced symptomatic complications, with one developing acute pyelonephritis, and the remaining two experiencing stone encrustation. CONCLUSION: Patients older than 60 years were 3.6 times more likely to have forgotten DJSs than patients aged 60 and below, and DJSs exchanged using fibrocystoscopy were 5.4 times more likely to be forgotten than those inserted using ureterorenoscopy. Greater attention with regards to tracking and recalling DJSs should be paid in high-risk patients to prevent forgotten DJSs and associated complications.

Comparison of electrohydraulic and electromagnetic extracorporeal shock wave lithotriptors for upper urinary tract stones in a single center.

PURPOSE: To compare the efficacy and outcomes of shock wave lithotripsy (SWL) for upper urinary tract stones with an electrohydraulic (EH) and an electromagnetic (EM) lithotriptor in a single center. METHODS: The medical records of 272 patients with upper urinary tract stones ≤ 2 cm in size who underwent SWL with either the Medispec E3000 EH lithotriptor (179 cases) or the Medispec EM1000 EM lithotriptor (93 cases) were reviewed. The demographic data, stone parameters, stone-free rates, and retreatment rates were analyzed. RESULTS: The EH group had a higher stone-free rate (53.6 vs. 30.1%, p < 0.001) and a lower retreatment rate (32.4 vs. 61.2%, p < 0.001) for renal and upper third ureteral stones than the EM group. The stone-free rates for renal stones < 1 cm (55.5 vs. 32.2%, p = 0.045), ureteral stones < 1 cm (64.5 vs. 42.1%, p = 0.028), and renal stones ≥ 1 cm (43.1 vs. 0%, p = 0.03) were higher in the EH group. Two patients in the EH group had a renal hematoma needing hospitalization after SWL. There were no complications in the EM group. CONCLUSIONS: The Medispec E3000 EH lithotriptor had higher stone-free rates and lower retreatment rates than the Medispec EM1000 EM lithotriptor for renal stones < 2 cm and ureteral stones < 1 cm. Complications were rare.

Zerumbone Regulates DNA Repair Responding to Ionizing Radiation and Enhances Radiosensitivity of Human Prostatic Cancer Cells.

INTRODUCTION: Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation-induced DSB in human prostate cancer cells. MATERIALS AND METHODS: The human prostate cancer PC3 and DU145 cell lines were used. A colony formation assay was performed to analyze the radiation survival of cells. DNA histogram and generation of reactive oxygen species (ROS) were examined using flow cytometry. Western blotting was used to examine the expression of regulatory molecules related to DNA damage repair. RESULTS: Pretreatment with zerumbone enhanced the radiation effect on prostate cancer cells. Zerumbone delayed the abrogation of radiation-induced expression of γ-H2AX, an indicator of DNA DSB. Zerumbone pretreatment markedly reduced ionizing radiation-induced upregulated expression of phosphorylated ATM (ataxia telangiectasia-mutated), which was partially reversed by the ATM agonist methyl methanesulfonate. Ionizing radiation augmented and zerumbone pretreatment reduced the expression of Jak2 and Stat3, which are involved in DNA damage repair signaling. No significant effect on the generation of ROS and expression of ATR was noted after zerumbone treatment. CONCLUSION: Zerumbone sensitized DU145 and PC3 prostatic cancer cells to ionizing radiation by modulating radiation-induced ATM activation during repair of DNA DSBs.

Concomitant transrectal ultrasound-guided biopsy and transurethral resection of prostate in patients with urinary retention and elevated serum prostate-specific antigen levels.

BACKGROUND: There was no consensus about the management of patients with urinary retention and elevated serum prostate-specific antigen (PSA) levels. This study aimed to determine whether concomitant transrectal ultrasound (TRUS)-guided biopsy and transurethral resection of prostate (TURP) is practical in patients with urinary retention and elevated serum PSA levels. METHODS: From March 2007 to May 2015, a total of 34 patients with urinary retention and elevated PSA (≥ 4 ng/mL) underwent concomitant TRUS-guided biopsy and TURP. The medical records were evaluated retrospectively, and data including PSA, prostate volume, TURP results, TRUS-guided biopsy results, length of hospitalization, and complications were collected. These patients were then compared with 40 patients with urinary retention who underwent TURP alone. RESULTS: The mean age of the patients was 71.6 years. The mean PSA levels were 16.9 ng/mL. Prostate cancer was detected in eight cases (23.5%): one case by TRUS-guided biopsy alone, two cases by TURP alone, and five cases by both TRUS-guided biopsy and TURP. Complications included fever in five patients (14.7%), recatheterization for urine retention in two patients (5.9%), urinary tract infection in two patients (5.9%), and de novo urge incontinence in seven patients (20.6%). The complication rate was not significantly increased compared with that of the patients who underwent TURP alone. CONCLUSION: This study showed that concomitant TRUS-guided biopsy and TURP was safe and of possible clinical significance in urinary retention patients with elevated serum PSA.

Adenocarcinoma arising from tubulovillous adenoma in a native bladder following gastrocystoplasty.

Gastrocystoplasty is a surgical form of bladder augmentation which improves bladder capacity and compliance. Patients who undergo bladder augmentation with a gastric remnant are at increased risk for malignancy. The most common types of tumors in this situation were adenocarcinoma and urothelial carcinoma. Most of the adenocarcinomas arise in the gastric remnant or anastomotic site, and adenocarcinomas arising in the residual native bladder are extremely rare. We report on a patient who received gastrocystoplasty 16 years ago. She suffered from recurrent urinary tract infections for a year and cystoscopy showed a tumor in the bladder trigone. Pathologic examination showed tubulovillous adenoma with malignant transformation to adenocarcinoma. The tumor consisted of intact adenomatous architecture from low-grade dysplastic gland to adenocarcinoma, which suggested that the pathogenesis might be related to intestinal metaplasia and dysplasia. The unique location and immunohistologic findings of the tumor suggested that it originated in the bladder mucosa.

Emphysematous pyelonephritis: patient characteristics and management approach.

INTRODUCTION: Emphysematous pyelonephritis (EPN) is an acute, severe, necrotizing infection of the renal parenchyma and perirenal tissue that requires immediate treatment. However, the ideal approach to its management remains controversial. We conducted this study to determine the appropriate treatment modalities. MATERIALS AND METHODS: A retrospective review of EPN cases revealed 10 consecutive cases from July 2003 to June 2012. Clinical and demographic data were collected from each patient. RESULTS: All patients had diabetes mellitus, 5 presented with urinary tract obstruction by urolithiasis. Seven patients had type I disease and 3 had type II disease. Six of the type I patients underwent emergent nephrectomy and 1 of these died, the remaining patient refused surgical intervention and died after receiving medical management only. The type II patients underwent percutaneous drainage, and 2 of them subsequently underwent elective nephrectomy; all 3 survived. CONCLUSION: Our results suggest that emergency nephrectomy may be considered the initial management for type I EPN, while percutaneous drainage may be an effective initial treatment option for type II EPN.

Difference in protein expression profile and chemotherapy drugs response of different progression stages of LNCaP sublines and other human prostate cancer cells.

Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, 80-90% of the patients who receive androgen ablation therapy ultimately develop recurrent tumors in 12-33 months after treatment with a median overall survival time of 1-2 years after relapse. LNCaP is a commonly used cell line established from a human lymph node metastatic lesion of prostatic adenocarcinoma. We previously established two relapsed androgen receptor (AR)-rich androgen-independent LNCaP sublines 104-R1 (androgen depleted for 12 months) and 104-R2 cells (androgen depleted for 24 months) from AR-positive androgen-dependent LNCaP 104-S cells. LNCaP 104-R1 and 104-R2 mimics the AR-positive hormone-refractory relapsed tumors in patients receiving androgen ablation therapy. Androgen treatment stimulates proliferation of 104-S cells, but causes growth inhibition and G1 cell cycle arrest in 104-R1 and 104-R2 cells. We investigated the protein expression profile difference between LNCaP 104-S vs. LNCaP 104-R1, 104-R2, PC-3, and DU-145 cells as well as examined the sensitivity of these prostate cancer cells to different chemotherapy drugs and small molecule inhibitors. Compared to 104-S cells, 104-R1 and 104-R2 cells express higher protein levels of AR, PSA, c-Myc, Skp2, BCL-2, P53, p-MDM2 S166, Rb, and p-Rb S807/811. The 104-R1 and 104-R2 cells express higher ratio of p-Akt S473/Akt, p-EGFR/EGFR, and p-Src/Src, but lower ratio of p-ERK/ERK than 104-S cells. PC-3 and DU-145 cells express higher c-Myc, Skp2, Akt, Akt1, and phospho-EGFR but less phospho-Akt and phospho-ERK. Overexpression of Skp2 increased resistance of LNCaP cells to chemotherapy drugs. Paclitaxel, androgen, and inhibitors for PI3K/Akt, EGFR, Src, or Bcl-2 seem to be potential choices for treatment of advanced prostate cancers. Our study provides rationale for targeting Akt, EGFR, Src, Bcl-2, and AR signaling as a treatment for AR-positive relapsed prostate tumors after hormone therapy.

Caffeic acid phenethyl ester as an adjuvant therapy for advanced prostate cancer.

Prostate cancer is the second most frequently diagnosed cancer of men. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, the majority of prostate cancer patients receiving the androgen ablation therapy will ultimately develop recurrent castration-resistant tumors within 3 years. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. Combined treatments of CAPE with chemotherapeutic drugs exhibit synergistic suppression effects. Pharmacokinetic studies suggest that intraperitoneal injection of CAPE at concentration of 10mg/kg is not toxic. CAPE treatment sensitizes cancer cells to chemotherapy and radiation treatments. In addition, CAPE treatment protects therapy-associated toxicities in animal models. We therefore propose that administration of CAPE is a potential adjuvant therapy for patients with castration-resistant prostate cancer.

Severe acute pancreatitis with abscess after extracorporeal shock wave lithotripsy: a rare complication.

Extracorporeal shock wave lithotripsy (ESWL) is a widely accepted procedure for urolithiasis. However, the shock waves do not pass through the body without damage. Here, we reported a 57-year-old man who underwent ESWL four times before, and immediately developed acute pancreatitis and peritoneal abscess after ESWL for a right renal stone. Although the possibility of post-ESWL acute pancreatitis is extremely low, urologists must be aware of this vital complication.

Caffeic Acid phenethyl ester as a potential treatment for advanced prostate cancer targeting akt signaling.

Prostate cancer is the fifth most common cancer overall in the world. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, most prostate cancer patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant tumors within 1-3 years after treatment. The median overall survival time is 1-2 years after tumor relapse. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling, indicating that inhibition of PI3K/Akt might be a potential therapy for advanced prostate tumors. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. CAPE is a well-known NF-κB inhibitor. CAPE has been used in folk medicine as a potent anti-inflammatory agent. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. We discuss the potential of using CAPE as a treatment for patients with advanced prostate cancer targeting Akt signaling pathway in this review article.

Molecular profiling of prostatic acinar morphogenesis identifies PDCD4 and KLF6 as tissue architecture-specific prognostic markers in prostate cancer.

Histopathological classification of human prostate cancer (PCA) relies on the morphological assessment of tissue specimens but has limited prognostic value. To address this deficiency, we performed comparative transcriptome analysis of human prostatic acini generated in a three-dimensional basement membrane that recapitulates the differentiated morphological characteristics and gene expression profile of a human prostate glandular epithelial tissue. We then applied an acinar morphogenesis-specific gene profile to two independent cohorts of patients with PCA (total n = 79) and found that those with tumors expressing this profile, which we designated acini-like tumors, had a significantly lower risk of postoperative relapse compared with those tumors with a lower correlation (hazard ratio, 0.078; log-rank test P = 0.009). Multivariate analyses showed superior prognostic prediction performance using this classification system compared with clinical criteria and Gleason scores. We prioritized the genes in this profile and identified programmed cell death protein 4 (PDCD4) and Kruppel-like factor 6 (KLF6) as critical regulators and surrogate markers of prostatic tissue architectures, which form a gene signature that robustly predicts clinical prognosis with a remarkable accuracy in several large series of PCA tumors (total n = 161; concordance index, 0.913 to 0.951). Thus, by exploiting the genomic program associated with prostate glandular differentiation, we identified acini-like PCA and related molecular markers that significantly enhance prognostic prediction of human PCA.

Evaluation of computerized physician order entry system-a satisfaction survey in Taiwan.

In the rapidly developing world of information technology, computers have been used in various settings for clinical medicine application. Studies have focused on computerized physician order entry (CPOE) system interface design and functional development to achieve a successful technology adoption process. Therefore, the purpose of this study was to evaluate physician satisfaction with the CPOE system. This survey included user attitude toward interface design, operation functions/usage effectiveness, interface usability, and user satisfaction. We used questionnaires for data collection from June to August 2008, and 225 valid questionnaires were returned with a response rate of 84.5 %. Canonical correlation was applied to explore the relationship of personal attributes and usability with user satisfaction. The results of the data analysis revealed that certain demographic groups showed higher acceptance and satisfaction levels, especially residents, those with less pressure when using computers or those with less experience with the CPOE systems. Additionally, computer use pressure and usability were the best predictors of user satisfaction. Based on the study results, it is suggested that future CPOE development should focus on interface design and content links, as well as providing educational training programs for the new users; since a learning curve period should be considered as an indespensible factor for CPOE adoption.

Common variants at 8q24 are associated with prostate cancer risk in Taiwanese men.

BACKGROUND: Recently, independent genome-wide scans have found multiple genetic variants at 8q24 to be associated with prostate cancer risk. This study was performed to determine whether two of the variants more strongly associated with prostate cancer risk in European and American populations, specifically rs16901979 and rs6983561, were also associated with prostate cancer risk in Taiwanese men. METHODS: We conducted a case-control study comprising of 340 prostate patients and 336 healthy controls. Genotyping was performed for rs16901979 and rs6983561. Their association with disease stage, tumor grade, PSA level and disease aggressiveness was also determined. RESULTS: The risk allele A of rs16901979 was associated with a 1.28-fold increase in prostate cancer risk (P = 0.046), and the risk allele C of rs6983561 was associated with a 1.40-fold increase in prostate cancer risk (P = 0.006). When compared with controls, the risk allele of rs6983561 was more frequent in patients with more aggressive disease. Analysis of the cumulative risk of rs1447295, a confirmed risk variant, and one of these markers showed that compared to men who do not have any of these risk variants, men who carry any combination of 1 or 2 risk genotypes have a gradually increased prostate cancer risk (P for trend <0.001). CONCLUSION: The variants rs16901979 and rs6983561 at 8q24 are associated with prostate cancer risk in Taiwanese men.

Renal cell carcinoma presenting as a huge simple renal cyst.

Simple renal cysts are the most common renal masses, accounting for roughly 65-70% of cases. Transformation of a simple renal cyst into a renal cell carcinoma (RCC), however, is extremely rare. We reported a 48-year-old man with a right huge simple renal cyst from which about 800 ml of dark yellowish fluid with elevated protein and lactic dehydrogenase (LDH) levels was aspirated. Cytological examination disclosed negative for malignant cells. Nephrectomy was performed because of intractable flank pain 3 months after aspiration. The pathology examination confirmed RCC. While this is an extremely unusual finding, one must not exclude the possibility of malignancy in an apparently simple cyst.

CYP19 TCT tri-nucleotide Del/Del genotype is a susceptibility marker for prostate cancer in a Taiwanese population.

OBJECTIVES: The CYP19 gene encodes aromatase--a key enzyme involved in the conversion of androstenedione/testosterone to estrone/estradiol. In this study, we analyzed the association between the TCT insertion (Ins)/deletion (Del) and TTTA repeat polymorphisms of CYP19 and prostate cancer (PCa). METHODS: Automated sequencer with GeneScan software was used to determine the CYP19 gene polymorphisms in peripheral blood mononuclear cell DNA from 244 patients with PCa and 261 age-matched healthy male controls. The distribution of Stage I to IV was 3.4%, 23.8%, 19.6%, and 53.2%, respectively. The Gleason score was 2 to 5 in 22.9%, 6 to 7 in 53.2%, and 8 to 10 in 23.8%. RESULTS: The frequency of the TCT Del/Del genotype in the Taiwanese patients with PCa (12.3%) was significantly greater than that in the controls (5.4%; P = 0.015, odds ratio [OR] 2.43, 95% confidence interval [CI] 1.23 to 4.80). Individuals with a homozygous A1 (seven TTTA repeats) genotype had a significantly greater risk of developing PCa (OR 1.59, 95% CI 1.04 to 2.44, P = 0.044). The frequency of the Ins-A6 (12 TTTA repeats) haplotype was significantly greater in the control group than in the patient group (9.8% versus 6.1%, OR 0.61, 95% CI 0.38 to 0.97). The OR of developing PCa for men with the homozygous Del-A1 diplotype was 2.31 (95% CI 1.10 to 4.83). CONCLUSIONS: The results of our study have shown that the CYP19 TCT Del/Del genotype might be a susceptibility marker for PCa. Men with the Ins-A6 haplotype had a lower risk of developing PCa.

Anti-proliferative effects of evodiamine on human prostate cancer cell lines DU145 and PC3.

Prostate carcinoma is one of the most common malignant tumors and has become a more common cancer in men. Previous studies demonstrated that evodiamine (EVO) exhibited anti-tumor activities on several cancers, but its effects on androgen-independent prostate cancer are unclear. In the present study, the action mechanisms of EVO on the growth of androgen-independent prostate cancer cells (DU145 and PC3 cells) were explored. EVO dramatically inhibited the growth and elevated cytotoxicity of DU145 and PC3 cells. The flow cytometric analysis of EVO-treated cells indicated a block of G2/M phase and an elevated level of DNA fragmentation. The G2/M arrest was accompanied by elevated Cdc2 kinase activity, an increase in expression of cyclin B1 and phosphorylated Cdc2 (Thr 161), and a decrease in expression of phosphorylated Cdc2 (Tyr 15), Myt-1, and interphase Cdc25C. TUNEL examination showed that EVO-induced apoptosis was observed at 72 h. EVO elevated the activities of caspase 3, 8, and 9 in DU145 cells, while in PC3 cells only the activities of caspase 3 and 9 were elevated. EVO also triggered the processing of caspase 3 and 9 in both DU145 and PC3 cells. We demonstrate that roscovitine treatment result in the reversion of G2/M arrest in response to EVO in both DU145 and PC3. However, inhibitory effect of roscovitine on EVO-induced apoptosis could only be observed in DU145 rather than PC3. In DU145, G2/M arrest might be a signal for initiation of EVO-triggered apoptosis. Whereas EVO-triggered PC3 apoptosis might be independent of G2/M arrest. These results suggested that EVO inhibited the growth of prostate cancer cell lines, DU145 and PC3, through an accumulation at G2/M phase and an induction of apoptosis.

Mechanisms of digoxin and digitoxin on the production of corticosterone in zona fasciculata-reticularis cells of ovariectomized rats.

Previous studies have indicated that digoxin (DG) inhibits testosterone production by rat testicular interstitial cells through both in vivo and in vitro experiments. DG and digitoxin (DT), but not ouabain, inhibit the progesterone, pregnenolone, and corticosterone secretion by rat granulosa cells, luteal cells, and zona fasciculata-reticularis (ZFR) cells, respectively. However, the effect of DG and DT on the enzyme kinetics of cytochrome P450 side chain cleavage enzyme (P450scc), the protein expression of P450scc and steroidogenic acute regulatory protein (StAR), and mRNA expression of StAR are unclear. ZFR cells were prepared from adrenocortical tissues of ovariectomized rats, and then challenged with adrenocorticotropin (ACTH), 8-Br-cAMP, forskolin, A23187, cyclopiazonic acid (CPA), nicotinic acid adenine dinucleotide phosphate (NAADP), trilostane, 25-OH-Cholesterol, progesterone, or deoxycorticosterone in the presence of DG, DT, or ouabain for 1 h. Enzyme kinetics of P450scc, protein expression of acute regulatory protein (StAR) and P450scc, and mRNA expression of StAR were investigated. DG and DT but not ouabain suppressed basal and other evoked-corticosterone release significantly. DG and DT also inhibited pregnenolone production. The Vmax of the DG and DT group was the same as the control group, but the Km was higher in DG- and DT-treated group than in control group. DT and ouabain significant suppressed mRNA expression of StAR. DG and DT had no effect on the P450scc and StAR protein expression at basal state, but diminished ACTH-induced StAR protein expression to basal level. These results indicated that DG and DT have an inhibitory effect on corticosterone production via a Na+, K+-ATPase-independent mechanism by diminishing actions on cAMP-, Ca2+-pathway, competitive inhibition of P450scc enzyme and reduction of StAR mRNA expression.

Is Fournier's gangrene severity index useful for predicting outcome of Fournier's gangrene?

OBJECTIVES: Fournier's gangrene (FG) is a rare but life-threatening disease. Although antibiotics and aggressive debridement have been broadly accepted as the standard treatment, the mortality rate remains high. We conducted a retrospective study to analyze the outcome and identify the risk factors and prognostic indicators. METHODS: We retrospectively reviewed the medical records of 25 patients diagnosed with FG between July 1993 and August 2003. Data collected included age, predisposing factors, treatment modalities, length of hospital stay, surgical debridement times, and outcome. The FG severity index was used to predict outcome. Univariate analysis of the different prognostic factors was performed using t test and Fisher's exact probability test. RESULTS: All patients were male, 60% were diabetic, and the mean age was 55.8 years. The mean hospital stay was 20 days and the mortality rate was 32%. The mean age of 53.8+/-18.3 (SD) years in the survival group (n=17) was significantly lower than the 59.9+/-10.2 years (n=8) of the non-survival group (p<0.05). Non-survival group patients had lower serum hematocrit (mean 28.9, p=0.019) and albumin (mean 1.93, p=0.024) levels. In our series, the mean FG severity index for survivors was 4.41+/-2.45 (range 2-9) compared to 12.75+/-2.82 (range 9-18) for those who died (t test, p<0.0001). CONCLUSION: The survival rate of younger patients with FG was higher. We agree that a FG severity index cutoff value of 9 is an excellent predictor of outcome.