Clopidogrel-associated acute arthritis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to K K Chen.
Explore the source record for details and available documents.
PURPOSE: We conducted integrated analyses of the efficacy and safety of tadalafil, a potent, selective phosphodiesterase 5 inhibitor, for the treatment of erectile dysfunction. MATERIALS AND METHODS: A total of 1,112 men with a mean age of 59 years (range 22 to 82) and mild to severe erectile dysfunction of various etiologies were randomized to placebo or tadalafil, taken as needed without food or alcohol restrictions, at fixed daily doses of 2.5 mg, 5 mg, 10 mg, or 20 mg up to a maximum of once daily [DOSAGE ERROR CORRECTED] in 5 randomized, double-blind, placebo controlled trials lasting 12 weeks. The 3 co-primary outcomes were changes from baseline in the erectile function domain of the International Index of Erectile Function and the proportion of "yes" responses to questions 2 and 3 of the Sexual Encounter Profile. Additional efficacy instruments included a Global Assessment Question. RESULTS: Compared with placebo, tadalafil significantly enhanced all efficacy outcomes. Patients receiving 20 mg. tadalafil experienced a significant mean improvement of 7.9 in International Index of Erectile Function erectile function domain score from baseline (p <0.001 versus placebo), 75% of intercourse attempts (Sexual Encounter Profile question 3, a secondary efficacy outcome) were successfully completed (p <0.001 versus placebo) and 81% reported improved erections at end point compared with 35% in the control group (p <0.001). Tadalafil was consistently efficacious across disease severities and etiologies, as well as in patients of all ages. Tadalafil was well tolerated, and headache and dyspepsia were the most frequent adverse events. CONCLUSIONS: Tadalafil was effective and well tolerated in this patient population.
The objective of this study is to investigate whether the L-arginine/nitric oxide pathway is involved in the neurotransmission of paraventricular nucleus of hypothalamus (PVN) activation-induced penile erection in the rat. Male adult Sprague-Dawley rats anesthetized with pentobarbital were used. The femoral artery was cannulated to measure systemic and mean arterial pressure (SAP and MAP), and heart rate (HR). A 26-gauge needle was inserted into corpus cavernosum to measure the intracavernous pressure (ICP) simultaneously with SAP, MAP and HR on a polygraph. Four groups of study were arranged: (1) stereotaxically delivery of L-arginine (500 nmol/500 nl) into PVN; (2) administration of a mixture (1 microl) containing N(G)-Nitro-L-arginine methyl ester (L-NAME) 500 nmol and L-arginine 500 nmol into PVN; (3) microinjection of saline 500 nl into PVN as a vehicle control; and (4) intracavernous injection of L-arginine (100 nmol/50 microl). The ICP, SAP, MAP and HR were monitored for at least 2 h after each administration of the experimental agents. Upon administration of L-arginine into PVN, there was a significant increase of ICP from resting 9.6+/-2.5 mmHg to peaked at 64.4+/-9.8 mmHg after a latency of 3016.0+/-1749.7 s and with a duration of 27.6+/-15.8 min. There was no change of resting ICP after administration of the mixture of L-NAME and L-arginine into PVN. Application of saline to PVN and intracavernous injection of L-arginine failed to increase ICP. Based on elicitation of penile erection upon administration of L-arginine into PVN, and elimination of this L-arginine induced penile erection by co-administration of L-NAME with L-arginine, the results of this study suggest that L-arginine/nitric oxide pathway may be involved in the neurotransmission of PVN activation-induced penile erection in the rat.
PURPOSE: The purpose of this study was to describe the various sonographic features of xanthogranulomatous pyelonephritis (XGP). METHODS: We retrospectively reviewed the CT, sonographic, and medical records of patients diagnosed with XGP from January 1981 to December 1998. Twenty-seven patients for whom XGP was histopathologically confirmed were included in the study. There were 12 men and 15 women, with an age range of 21-86 years (mean, 57 years). All patients had undergone sonography of the kidneys. The renal size, shape, and outline were recorded. The presence of perinephric fluid accumulation, of obstructive uropathy, or of internal echoes in the dilated collecting system and the echotexture of the renal parenchyma were documented. RESULTS: We categorized the XGP into 4 groups on the basis of the sonographic features: (1) diffuse hydronephrotic, 12 patients (44%); (2) diffuse parenchymal, 9 patients (33%); (3) diffuse contracted, 4 patients (15%); and (4) segmental or focal, 2 patients (7%). A localized perinephric fluid collection was present in 4 patients (15%). The preoperative sonographic diagnoses were pyonephrosis (n = 14, 52%), renal pelvic tumor with possible associated infection (n = 5, 19%), renal parenchymal mass (n = 2, 7%), hydronephrosis (n = 2, 7%), and chronic pyelonephritis with renal atrophy (n = 4, 15%). XGP was considered a possible diagnosis in only 11 patients (41%). CONCLUSIONS: XGP has no specific sonographic features but is suggested by parenchymal thinning and hydronephrosis, sonographic signs of chronic obstructive uropathy caused by stones; echoes in the dilated collecting system; and a perinephric fluid collection. CT, needle biopsy, or both are recommended to further evaluate and confirm sonographically suspected XGP.
OBJECTIVES: Chemotherapy resistance of renal cell carcinoma (RCC) has been attributed in large part to multidrug resistance (MDR). Reported MDR-modulated chemotherapy for RCC, however, has resulted in only marginal response benefits. In this study, the MDR-modulated effect of paired tamoxifen and colchicine on vinblastine and the possible additive effect of 5-fluorouracil (5-FU) were investigated in the treatment of advanced RCC. METHODS: Chemotherapy was administered every 4 weeks with biweekly vinblastine (4 mg/m(2)/day, intravenously on days 1 and 15) modulated by oral tamoxifen (100 mg/day) and colchicine (1 mg/day) from days -1 to 2 and from days 13 to 16. 5-FU (800 mg/m(2)/day from days 2 to 5) was administered after vinblastine administration as a continuous infusion. RESULTS: Of 17 eligible patients with advanced RCC available for evaluation, 1 achieved a complete response (CR) and 3 a partial response (PR), with an overall response (CR plus PR) rate of 23.5%. The median overall survival time of all patients was 10 months (95% confidence interval [CI] 3.5 to 16.5); that of our patients with poor, intermediate, and favorable risks as stratified by Motzer's model was 6 (95% CI 1.7 to 10.3), 10 (95% CI 7.9 to 12.2), and 26 (95% CI 24.4 to 27.6) months, respectively. These results are encouraging in view of the poor efficacy of chemotherapy in RCC observed previously. Additionally, the treatment toxicity was limited: toxicity of grade 3 or greater occurred in only 1 patient with leukopenia, and no treatment-related mortality was found. CONCLUSIONS: The encouraging response rates and overall survival with limited toxicity warrant further investigation of this combination therapy as an integrated part of immunochemotherapy for RCC.
OBJECTIVES: To present our unfavorable experiences using allograft fascia lata. Allograft fascia lata is an attractive sling material providing less pain, a shorter operation time, and a reported effectiveness equal to autologous fascia. METHODS: A total of 18 women (mean age 51.7 years, range 37 to 76) underwent pubovaginal sling surgery for stress urinary incontinence between March 1999 and July 1999 and were enrolled in this study. Solvent dehydrated gamma-irradiated human fascia lata with a size of 7 x 2 cm was used as the sling. The results were collected with a questionnaire survey. RESULTS: All patients were followed up for a mean of 9.2 months (range 6.9 to 11.6). Thirteen patients considered the surgery successful or to have provided improvement, with a mean of 82.5% (range 50% to 100%) subjective improvement. Five patients (27.8%) had significant failure with full recurrence of incontinence within 3 to 6 months. CONCLUSIONS: Solvent dehydrated gamma-irradiated allograft fascia is not reliable in pubovaginal sling surgery. The high failure rates within a short period prohibit its use in the operative management of stress urinary incontinence.
The efficacy and safety of sildenafil were evaluated in a randomised, double-blind, placebo-controlled, flexible-dose study in Taiwanese men aged 26 to 80 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months' duration. A total of 236 patients were randomised at six medical centres in Taiwan to receive either sildenafil (50 mg initially increased if necessary to 100 mg or decreased to 25 mg depending on efficacy and toleration) (n=119) or matching placebo (n=117) taken on an 'as needed' basis 1 h prior to anticipated sexual activity for a period of 12 weeks. At the end of 12 weeks, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the IIEF (International Index of Erectile Function) scale, (2) the percentage of successful intercourse attempts; and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P<0.0001). Treatment-related adverse events occurred in 43.7% of patients receiving sildenafil and 18.8% receiving placebo. The most common adverse events with sildenafil were flushing, dizziness and headache (25.2, 6.7 and 5.9% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in the population of Taiwanese men appears similar to that reported in other studies in western populations.
beta-Lapachone, a novel anti-neoplastic drug, induces various cancer cells to undergo apoptosis. In a previous report, we showed that beta-lapachone-induced apoptosis of HL-60 cells is mediated by oxidative stress. However, in the present study, we found that beta-lapachone-induced apoptosis of human prostate cancer (HPC) cells may be independent of oxidative stress. In contrast to the 10-fold beta-lapachone-induced increase in H(2)O(2) production seen in HL-60 cells, only a 2- to 4-fold increase was observed in HPC cells. N-acetyl-L-cysteine (NAC), a thiol antioxidant, inhibited the apoptosis in DU145 cells after 12 h exposure to beta-lapachone. Nonetheless, NAC, along with other antioxidants, failed to exert similar effect in HPC cells subjected to beta-lapachone treatment for 24 h. Under this premise, we suggest that the oxidative stress may not play a crucial role in beta-lapachone-mediated HPC cell apoptosis. Here we demonstrate that damage to genomic DNA is the trigger for the apoptosis of HPC cells induced by beta-lapachone. According to our results, beta-lapachone stimulates DNA dependent kinase expression and poly(ADP-ribose) polymerase cleavage in advance of significant morphological changes. beta-Lapachone promotes the expression of cyclin-dependent kinase (cdk) inhibitors (p21(WAF1) and p27(Kip1)), induces bak expression, and subsequently stimulates the activation of caspase-7 but not of caspase-3 or caspase-8 during the apoptosis of HPC cells. Taken together, these results suggest that the signaling pathway involving the beta-lapachone-induced apoptosis of HPC cell may be by DNA damage, induction of cdk inhibitors (p21 and p27), and then subsequent stimulation of caspase-7 activation.
Comparative studies on resin-dentin bond strength and failure mode were performed between the conventional tensile test and the microtensile test with non-trimming small specimens, 1 x 1 mm in cross-section, for two brands of dentin bonding systems. The fracture surface of the conventional large specimen showed a catastrophic cohesive failure in dentin at its center and a lesser adhesive failure, suggesting that the whole failure was due to the development of some major cracks. The non-trimming microtensile test showed significantly larger average bond strength with markedly larger standard deviation and significantly larger fraction of adhesive failure than the conventional test. Some small specimens were extremely strong and some were weak according to the heterogeneous distribution of tight bonding and defective or deficient bonding over the whole dentin surface. These results suggest that the non-trimming microtensile test may potentially provide more realistic aspects of resin-dentin bonding than the conventional bulk specimen.
OBJECTIVES: To investigate the existence and functional significance of the enhanced lipid peroxidation in bladder overdistension injury and to explore the effect of mannitol, a free radical scavenger. METHODS: Overdistension of rabbit bladders was induced and maintained for 3 hours by infusing normal saline into the bladder while keeping the intravesical pressure at 30 cm H(2)O. The bladders were then emptied and decompressed. Intravenous 20% mannitol was initiated 5 minutes before decompressing the overdistension. Detrusor tissue was obtained from the following groups: control, at the end of the overdistension period, and 30 minutes, 2 hours, and 7 days after decompressing the bladder. The tissue level of adenosine triphosphate (ATP) and phosphocreatine (PCr) and the lipid peroxidation product malondialdehyde (MDA) was assayed. Detrusor contractility was assessed by the response of the detrusor strips to KCl and bethanechol. RESULTS: Decompressing the overdistended bladder led to a period of enhanced lipid peroxidation with an increase of MDA content from 225 to 384 pmol/mg protein 30 minutes after the decompression. Two hours later, the MDA content had recovered to the normal level. Mannitol abolished this period of enhanced lipid peroxidation. Overdistension impaired detrusor contractility and reduced the content of PCr (from 24.1 to 10.8 nmol/mg protein) and ATP (from 9.6 to 4.6 nmol/mg protein). Both detrusor contractility and the content of PCr and ATP further decreased 30 minutes after the decompression (PCr 5.4 nmol/mg, ATP 2.8 nmol/mg). They had recovered, but not fully, 7 days later. Mannitol prevented the further decrease in detrusor contractility and in the content of PCr and ATP during the initial decompression period (30 minutes after the decompression). In addition, the mannitol-treated group had quicker recovery in PCr and ATP levels, which returned to normal 7 days later. CONCLUSIONS: Decompressing an overdistended bladder leads to enhanced lipid peroxidation, which is associated with an additionally decreased energetic metabolism and a more impaired contractile function. Mannitol effectively prevents enhanced lipid peroxidation and facilitates functional recovery. These results show that reactive oxygen species play a significant role in bladder overdistension injury.
OBJECTIVES: To investigate mitochondrial DNA (mtDNA) mutations in human detrusor after partial bladder outlet obstruction (BOO) and correlate the findings with the results of urodynamic studies. METHODS: Sixty-two male patients with and without BOO were recruited and assessed by the International Prostate Symptom Score, a quality-of-life assessment index, and sonography. The severity of partial BOO was determined by pressure-flow study with an International Continence Society (ICS) nomogram. Random detrusor biopsies obtained cystoscopically were analyzed by polymerase chain reaction (PCR) techniques to detect possible mtDNA deletions. Primer-shift PCR and DNA sequencing were then performed to characterize specific mtDNA deletions. A semiquantitative PCR method was used to determine the proportion of the deleted mtDNA in detrusor. Finally, the mtDNA deletion and the urodynamic results were compared statistically. RESULTS: A 4977-bp mtDNA deletion was identified in the human detrusor. Its incidence and proportion were found to increase after partial BOO (P = 0.005 and 0.012, respectively). The incidence of the mtDNA deletion was 4.2% (1 of 24) in the unobstructed group, 27.8% (5 of 18) in the equivocal group, and 40% (8 of 20) in the obstructed group. The mean proportion of the 4977-bp deleted mtDNA was 23.7 and 12.7 times higher in the obstructed and equivocal groups, respectively, compared with that of the unobstructed group. CONCLUSIONS: We found mtDNA with the 4977-bp deletion in human detrusor and an increase of this deletion after partial BOO. This molecular change might account for the previous observations of mitochondrial functional impairment and voiding dysfunction after partial BOO.
Explore the source record for details and available documents.
BACKGROUND: Cisplatin-based chemotherapy is the mainstay of the treatment for advanced urothelial cancer, but patients with renal insufficiency before therapy are usually contraindicated to receiving platinum-based chemotherapy. Paclitaxel is one of the most promising agents against advanced urothelial carcinoma in recent trials and it can be easily tolerated even in patients with compromised renal function. We conducted a study in order to evaluate the efficacy and safety of paclitaxel as a first-line therapy in advanced urothelial carcinoma patients. METHODS: Thirteen advanced chemo-naive urothelial carcinoma patients with a median age of 71 years were studied, seven of them demonstrating renal insufficiency (pretreatment serum creatinine > or = 1.5 mg/dl). All 13 patients received a minimum of two cycles of paclitaxel 175 mg/m2, delivered by intravenous infusion for 3 h every 3 weeks. RESULTS: Four of the 13 patients responded to treatment, a response rate of 30.8%, with two of these achieving complete remission and two showing partial responses. The median overall survival period of all 13 patients was nine months (95% Cl: 6.51-11.49) and our study revealed a statistical tendency in the difference of median overall survival time between responders and non-responders (13 months versus 7.5 months, log-rank p = 0.038), although the number of cases was limited. The differences in response rate and median overall survival time, comparing patients with renal insufficiency and those with normal renal function, were not significant. Treatment-related toxicity was mild, with only two (15.4%) patients suffering from grade 3-4 leukopenia. No treatment-related mortality was noted. CONCLUSIONS: Single-agent paclitaxel can be used as a first-line therapy in advanced urothelial carcinoma patients, and is especially suitable for those with pretreatment renal insufficiency, since the antitumor activity is significant while toxicity is well tolerated.
OBJECTIVES: To compare the performance of laparoscopic skill assisted by a traditional two-dimensional (2D) and a three-dimensional (3D) endoscopic video system in a pelvic trainer. MATERIALS AND METHODS: The 3D imaging system (DeepVision((R)), Automated Medical Products Corp.) consists of a traditional single lens optic laparoscope, a light source, an endoscopic camera (Stryker), a DeepVision processor and a DeepVision monitor. The 2D images could be obtained with the same system without turning on the DeepVision processor. Thirty-four medical personnel with no laparoscopic surgical experience were enrolled to perform two skill tests, the object-pick-up and spatial orientation test in a trainer box. They were randomly divided into two groups, one group performed the test under 2D conditions first and 3D later, and another group performed the test under 3D conditions first and 2D later. The duration needed to complete the skill tests was recorded and the differences on performance time under 2D and 3D conditions were calculated for each participant. Two-way ANOVA was used to analyze the statistic difference on the performance time in two conditions. RESULTS: The duration needed to complete the initial skill tests was similar among 2D and 3D conditions. For both tests, the average performance time decreased significantly for the second attempt regardless of 2D or 3D conditions. Statistic analysis disclosed significant difference for learning factor (p < 0.001 for object-pick-up test and p < 0.01 for spatial orientation test), but no significant difference between 2D and 3D conditions (p = 0.276 for object-pick-up test and p = 0.327 for spatial orientation test). CONCLUSION: A significant decrease of the performance time at the second attempt reflected the importance of a learning process in laparoscopic surgery. It appears that no significant benefits were obtained by this 3D operating system for surgeons without laparoscopic surgical experience.
PURPOSE: We correlated ultrastructural changes in mitochondria in the human detrusor with the severity of partial bladder outlet obstruction on urodynamics. MATERIALS AND METHODS: We recruited into the study 52 men with and without bladder outlet obstruction symptoms. The severity of partial bladder outlet obstruction was determined by pressure flow study. Random detrusor biopsy specimens obtained by cystoscopy were fixed immediately and processed for transmission electron microscopic observation. Random areas were photographed for further morphological and morphometric analysis using mitochondrial damage score and stereological principles. RESULTS: Mitochondrial damage score and mean mitochondrial volume strongly correlated with the urodynamic severity of partial bladder outlet obstruction, while mitochondrial volume density, surface density of the mitochondrial outer membrane and number of mitochondria per unit of cytoplasm area did not significantly correlate with severity. CONCLUSIONS: Detrusor mitochondrial swelling and structural destruction increased with the severity of partial bladder outlet obstruction. These changes may be associated with impaired mitochondrial function and oxidative metabolism after partial bladder outlet obstruction. Detrusor mitochondrial damage may explain voiding dysfunction after partial bladder outlet obstruction develops.
BACKGROUND: The clinical characteristics of renal abscess caused by Klebsiella pneumoniae have not been previously reported in case-series studies. The purpose of this study is to demonstrate the clinical characteristics of K pneumoniae renal abscess for early diagnosis and to identify the clinical risk factors associating with poor prognosis. METHODS: We retrospectively reviewed the medical records of 24 patients with K pneumoniae renal abscess, from April, 1982 through February, 1998. The clinical presentations, including the demographic characteristics, predisposing disorders, initial signs and symptoms, laboratory test results, diagnostic radiology studies, therapeutic modalities and risk factors associated with mortality were studied. RESULTS: The mean age was 58.7 years and the male to female ratio was 10:14. The most common predisposing factors were diabetes mellitus (58%), urolithiasis (25%) and immunosuppression (17%). Fever, chills and flank pain were the most common symptoms and signs, whereas pyuria, elevation of leukocyte count, glucose, blood urea nitrogen and creatinine were the common laboratory features. The distinct complications of K pneumoniae renal abscess were bacteremia in 13 (54%), emphysematous pyelonephritis in five (21%), and metastatic septic infection in three (12.5%). The cure rate was 52% (11/21) in patients treated with a combination of antibiotics and percutaneous drainage; however, six (35%) patients who survived required another surgical procedure for complete recovery. The overall mortality rate was 25%. The clinical factors of elderly age (>65 years) at presentation, lethargy, elevation of serum blood urea nitrogen and pulmonary complications were associated with poor prognoses. CONCLUSIONS: Focusing on the early diagnosis of K pneumoniae renal abscess and recognition of the prognostic factors for a poor prognosis, we highlight the specific clinical characteristics that include elderly age, lethargy, impairment of renal function, metastatic septic lesions and pulmonary complications. All patients with K pneumoniae renal abscesses should receive empiric antibiotics and percutaneous drainage or aspiration, and surgical intervention as necessary for patients with intractable disease.
BACKGROUND: Persistent postchemotherapy retroperitoneal residual mass with normalization of alpha-fetoprotein (AFP) in infantile yolk sac tumor is rare. METHODS/RESULTS: A 38-month-old boy with recurrent yolk sac tumor was treated with cisplatin-based combination chemotherapy. After chemotherapy, the retroperitoneal lymph node metastasis, 7 x 6 cm in size, decreased to 2 x 2 cm. Serum AFP levels returned to normal. The retroperitoneal residual mass was resected and histologically showed complete necrosis without viable cancer cells. CONCLUSION: The patient has remained free of disease for 36 months after operation.
PURPOSE: To investigate whether the paraventricular nucleus of hypothalamus (PVN) is involved in the central regulation of apomorphine-induced penile erection in the rat, and to decipher dopamine receptor subtypes in the PVN that are involved in apomorphine-induced penile erection. MATERIALS AND METHODS: Male adult Sprague-Dawley rats (200 to 300 gm.) anesthetized with pentobarbital sodium were used. The intracavernous pressure (ICP), recorded along with systemic and mean arterial pressure (SAP, MAP) as well as heart rate (HR), was measured via a 26-gauge needle inserted into one corpus cavernosum. The PVN was activated by stereotaxically delivered apomorphine hydrochloride (0.1 nmol./100 nl.). Injection of saline into PVN served as a vehicle control. To investigate the participation of dopamine receptor subtypes in the PVN on apomorphine-induced penile erection, D1 or D2 receptor antagonist, SCH-23390 (100 pmol./100 nl.) or sulpiride (100 pmol./100 nl.) respectively, was administered into the PVN prior to subcutaneous application of apomorphine (80 microg./kg.). The effects on ICP of microinjection of D1, D2 or D3 receptor agonist, SKF-38393 (200 pmol./100 nl.), lisuride (200 pmol./100 nl.) or 7-hydroxy-DPAT (200 pmol./100 nl.) respectively, into the PVN were also evaluated. RESULTS: The mean resting ICP was 5.2+/-0.4 mm. Hg. Upon administration of apomorphine into the PVN, there was a significant increase in ICP that peaked at 50.7+/-5.3 mm. Hg and persisted for 45.2+/-18.0 minutes after an onset latency of 677.7+/-311.6 seconds. Yawning and teeth gnashing were also observed in most of animals during the period of ICP increase. There was no significant change in SAP, MAP or HR. In addition, there was no elevation in ICP after administration of saline to the PVN or direct injection of apomorphine into the cavernous tissue. Microinjection of D1 or D2 receptor antagonist into the PVN blocked the increase in ICP after subcutaneous administration ofapomorphine. Direct application of D2, but not D1 or D3 receptor agonist into the PVN, on the other hand, increased the ICP. CONCLUSIONS: Our results demonstrate that application of apomorphine to the paraventricular nucleus of hypothalamus elicited penile erection in the rat. Such an increase in ICP to apomorphine was due mainly to activation of the D2 receptor subtype in the PVN. These observations indicate that PVN may be involved in the central regulation of apomorphine-induced penile erection in the rat.