Metastatic yolk sac tumor of the corpus cavernosum of the penis.
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Adult↗
Biomedical subjects
M K Lai
Publications and source records attributed to M K Lai.
An ex vivo evaluation of regulatory role of biogenic amines in rat seminal vesicle after pharmacological manipulation.
We studied the neural regulation of seminal vesicles (SV) by determining the changes of intraluminal pressure of rat SV in response to an electric stimulation of the lesser splanchnic nerve (LSN). After pharmacological manipulation with neurotoxin, the contents of monoamines and their metabolites in SV were estimated. In rats receiving electric stimulation of the LSN, an increase of intraluminal pressure was obtained with a reduction of the serotonergic turnover rate in SV. An intraperitoneal injection of DSP-4 (100 mg/kg), the noradrenergic neurotoxin, into rats decreased the level of norepinephrine (NE) in SV significantly but did not influence this functional response. Also, the intraluminal pressure was lowered by an intrathecal injection of 6-OHDA (20 microg/rat) to denervate spinal monoaminergic nerves in rats although the contents of monoamines in SV were not changed. This indicates that noradrenergic neurotransmission appears unimportant in this regulation. The lowering of intraluminal pressure in rats by 6-OHDA is mainly related to an attenuation of dopaminergic neuroregulation from the decrease of turnover rate of DA. Otherwise, an intrathecal injection of 5,7-DHT (60 microg/rat) to abolish spinal serotonergic nerves did not influence the level of monoamines in SV but increased the intraluminal pressure indicating an involvement of inhibitory regulation from spinal serotonergic pathway. These results suggest that contraction by electric stimulation of the LSN in Wistar rat SV is mainly regulated by the dopaminergic nervous pathway and an inhibitory regulation of the serotonergic nervous pathway from spinal cord while the noradrenergic nervous system seems unimportant for this regulation.
5,7-Dihydroxytryptamine↗
Early achievement of target cyclosporine levels during initial post-transplant period with a novel dosing strategy.
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Adult↗
A multicenter trial of FK506 as rescue therapy for renal transplant recipients in Taiwan.
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Adult↗
The usefulness of prostate-specific antigen (PSA) density in patients with intermediate serum PSA level in a country with low incidence of prostate cancer.
OBJECTIVES: To evaluate if a calculated PSA density (PSAD) prior to biopsy could be useful to determine the need for prostate biopsies in patients with serum PSA levels of 4.1-20.0 ng/mL in a country with low incidence of prostate cancer (PCa). METHODS: A total of 185 consecutive patients aged 50-79 years who underwent prostate biopsies were evaluated by correlating the biopsy results with the results of digital rectal examination (DRE), transrectal ultrasonography (TRUS), serum PSA levels, and PSAD. Prostate volume was calculated from TRUS using prolate ellipse formula and PSAD was obtained by dividing serum PSA level by prostate volume. RESULTS: In this study population, 27 cases (14.6%) had positive biopsies. Of 158 cases with negative biopsies, 43 (23.2%) had histologically verified prostatic inflammation. The diagnostic value of DRE and TRUS was hampered by unsatisfactory sensitivity and specificity in differentiating patients with positive biopsies from those with negative biopsies. The use of PSAD alone as an indicator for biopsy was also limited by its low specificity. A PSAD cutoff value of 0.15 resulted in a sensitivity of 100% and a specificity of only 12%. Prostatic inflammation was a confounding factor for the inadequate specificity of DRE, TRUS and PSAD. Combined use of DRE and PSAD provided the best information regarding the need for biopsies. Accordingly, if the 47 patients (25.4%) who presented with both a negative DRE and a PSAD < or = 0.20 were not biopsied, the rate of positive biopsy could have increased to 19.6% (27 of 138) without missing any cancer detection. CONCLUSIONS: It is concluded from this study that for patients with serum PSA levels of 4.1-20.0 ng/mL, biopsies should only be recommended for those with abnormal DRE and/or PSAD >0.20.
Aged↗
The effect of biological dyes and contrast media on the vas deferens in Long Evans rats.
The conventional diagnostic procedure of vasography utilizes a contrast medium to evaluate the patency of the vas deferens. With the development of microsurgical reconstruction for obstructive azoospermia in the past two decades, intraoperative vasography with saline or biological dye injection has replaced the use of radiographic contrast media. However, there are few reports on the effect of biological dyes on the healthy vas deferens. Therefore, we used experimental vasography to evaluate histological changes and functional patency of the vas deferens after infusion with a contrast medium and biological dye. Four groups of 10 Long Evans male rats were injected by vasopuncture with 1% methylene blue, 1% gentian violet and 38% Urografin or saline into the vas deferens. The animals were killed 30 days later, and the vasa deferentia were excised and examined for histological changes and for functional patency. Vasopuncture with saline injection induced minimal change both at the puncture site and in the distal vas deferens. In both the Urografin- and methylene blue-injected groups, inflammation at the puncture site was found in 20-22% of cases, and 10-11% of cases revealed functional obstruction of the vasal lumen. In the gentian violet-injected group, severe histological and obliterated changes were found in all cases. Leakage of the dye and contrast medium or the sperm reaction may be responsible for the inflammation; otherwise, methylene blue and urografin did not seem to be harmful to the vas deferens. Although gentian violet is a blue dye, as is methylene blue, it has marked destructive effects on the vas deferens. It is concluded that some biological dyes used for vasal injection can cause occlusion of the vasal lumen, while inflammatory responses can occur from placing a needle transmurally.
Animals↗
Urethral diverticulum and urethrocutaneous fistula presenting as a mass over the medical thigh.
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Adult↗
High prevalence of voiding symptoms in Taiwanese women.
OBJECTIVE: To describe the voiding symptoms of Taiwanese women using the International Prostate Symptom Score (IPSS). SUBJECTS AND METHODS: A self-administered questionnaire was used to collect information on demographic characteristics and the IPSS used to determine the voiding symptoms of 583 consecutive women undergoing a health examination. The symptom scores of different age groups were compared using a one-way analysis of variance with a posteriori comparisons made using Scheffe's test. RESULTS: The seven symptom scores could be separated by factor analysis into two factors which corresponded with obstructive (incomplete emptying, intermittency, weak stream, and hesitancy) and irritative (frequency, urgency, and nocturia) symptoms. Various degrees of frequency and nocturia were commonly reported by the respondents, whereas obstructive symptoms were infrequently reported, except in the elderly (age > or = 65 years). The irritative scores, obstructive scores and total scores increased significantly with age (all P<0.001). The total symptom scores correlated significantly with the quality-of-life score (Pearson's r = 0.70, P < 0.001). Overall, 124 (21%) of the respondents reported an IPSS of > 7, and 98 (17%) of the respondents reported being 'mostly dissatisfied' with their urination. However, only nine (1.5%) of the respondents had ever consulted a urologist about their voiding problems. CONCLUSIONS: There was an age-dependent change in voiding symptoms in these Taiwanese women. The prevalence of voiding symptoms in women is much higher than encountered in clinical practice.
Adult↗
Megestrol acetate antagonizes cisplatin cytotoxicity.
Megestrol acetate (MGA) is being widely used for the improvement of appetite and performance status in patients receiving chemotherapy, especially cisplatin-containing therapy. However, little is known about whether MGA has an effect on cisplatin cytotoxicity. We have investigated this using two transitional carcinoma cell lines, i.e. the cisplatin-sensitive parental line NTUB1 and the resistant daughter line NTUB1/P. Combined effects of MGA and cisplatin were assayed with a microculture chemosensitivity method. We explored the level changes of several cisplatin detoxification mechanisms, including metallothionein (MT), glutathione S-transferase-pi (GST-pi) and glutathione (GSH) levels in cells treated with or without MGA. After treatment with 10 microns MGA for 24 h, the cisplatin IC50s of NTUB1 and NTUB1/P increased 1.4- (p = 0.03) and 1.6- (p = 0.02) fold, respectively. By median effect analysis, the combinations of MGA and cisplatin in the two cells appeared to produce an antagonistic interaction. By Northern analysis, MT transcript levels in both cells were significantly upregulated after treatment with MGA, as compared to those without treatment. Exposure to MGA in either sensitive or resistant cells did not alter GST-pi levels as shown by immunoblotting analysis. Cellular GSH content was increased only in NTUB1/P (p = 0.0036) but remained unchanged in NTUB1 cells (p = 0.29) after MGA exposure. In conclusion, MGA may antagonize cisplatin cytotoxicity by upregulating cellular MT and GSH levels. Use of MGA in cisplatin-containing chemotherapy may impair tumor response by antagonizing cisplatin antitumor activity.
Antineoplastic Agents↗
Antiproliferative effect in human prostatic smooth muscle cells by nitric oxide donor.
We obtained a primary culture of prostatic cells through explantation from patients with benign prostatic hyperplasia. Structural morphology, immunohistochemical staining, and growth characteristics of these cells demonstrate that they are consistent with the population of smooth muscle cells (SMCs). We examined the influence of a nitric oxide donor, sodium nitroprusside (SNP), on the regulation of human prostatic SMC proliferation. SNP exhibited a concentration-dependent (0.1-10 microM) inhibition of fetal calf serum-induced proliferation in human prostatic SMCs. In addition, growth-inhibitory responses to 8-bromo-cGMP (1-30 muM) were observed. However, the responses to SNP were significantly diminished by the presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (3 microM; a selective guanylate cyclase inhibitor). Furthermore, SNP induced an increased concentration-dependent accumulation of intracellular cGMP in human prostatic SMCs. After 48-hr period of deprivation of serum, cells were restimulated with serum to permit cell cycle progression. The addition of SNP (10 microM) at various times after the addition of serum to serum-deprived cells showed maximal inhibition of cell proliferation even when added 6 hr after the serum. This blocking effect of cell cycle progression was lost gradually as the delay from serum to SNP application increased from 6 to 18 hr. The membrane-associated protein kinase C (PKC) activity was studied in human prostatic SMCs; results showed that fetal calf serum (10%, v/v) significantly increased membrane-associated PKC activity. SNP (10 muM), which had little effect on basal kinase activity, completely abolished serum-induced augmentation of PKC activity. Therefore, we suggest that SNP mediates its antiproliferative effect by the inhibition of PKC activity on human prostatic SMCs; furthermore, its antiproliferative effect occurs at the early G1 phase of the cell cycle.
Apoptosis↗
The impact of a clinical pathway for transurethral resection of the prostate on costs and clinical outcomes.
The purpose of this study was to evaluate the effects of implementing a clinical pathway for transurethral resection of the prostate on hospital costs and procedures, outcomes, and complications. Consecutive patients who underwent transurethral resection of the prostate for benign prostate hyperplasia in our hospital before (February-August 1996) and after (October 1996-March 1997) implementation of the clinical pathway were included. Statistical analyses included Student's t-test to test the impact of the clinical pathway on resource consumption and medical care processes, and multiple linear regression to control for patient characteristics such as age, severity of disease, and comorbidity. The major findings of this study were that implementation of the clinical pathway 1) decreased resource consumption and controlled medical care expenditure; 2) influenced physicians' patterns of practice and decreased the number of procedures performed; and 3) did not affect clinical outcomes or complication rates. In conclusion, our results support the hypothesis that the clinical pathway is an effective medical management tool to contain costs, which does not adversely affect quality of care. We suggest health policy makers promote clinical pathways in more hospitals to encourage appropriate resource consumption.
Aged↗
Penile cancer in Taiwan--20 years' experience at National Taiwan University Hospital.
To analyze the characteristics and prognostic factors of penile cancer in Taiwanese, we retrospectively reviewed the clinical data of patients with a diagnosis of penile cancer treated during a 20-year period (1977-1996) at National Taiwan University Hospital (NTUH). Of 71 patients treated for penile cancer during the study period, 17 were referred from other hospitals or clinics. Our analyses focused on the 54 previously untreated patients. Growth on the penis was the main symptom in all cases. Palpable inguinal lymph nodes were found only in 14 patients. All 54 patients with primary tumors were treated surgically. Pathologic examination showed squamous cell carcinoma (SCC) in 43 cases, extra-mammary Paget's disease in three, verrucous carcinoma in three, Bowen's disease in two, cutaneous lymphoma in two and basal cell carcinoma in one. Twenty-six (48%) patients had stage I penile cancer, 13 (24%) had stage II, seven (13%) had stage III, and eight (15%) had stage IV cancer. The five-year survival rate was 78% among patients with SCC and 84% among those with nonsquamous malignancies (p = 0.80). The five-year cumulative survival rates according to Jackson's cancer stage were 100% for patients with stage I, 88.9% for those with stage II, 66.7% for those with stage III, and 0% for those with stage IV (p < 0.001). Tumor staging (p = 0.027) and adjuvant chemotherapy (p = 0.042) were found to be the most significant prognostic factors. Penile cancer accounted for 0.254% of all malignancies among male patients at the NTUH during the study period. Our findings indicate that penile cancer is uncommon in Taiwanese and its prognosis is closely related to tumor staging and management. Early diagnosis and appropriate treatment may lead to prolonged survival.
Adult↗
Factors related to delayed treatment and posttreatment symptom severity in Taiwanese patients with benign prostatic hyperplasia.
We evaluated the sociodemographic and clinical factors of delayed treatment and posttreatment symptom severity in outpatients with benign prostatic hyperplasia (BPH). The study included 146 BPH patients treated at the National Taiwan University Hospital in early 1997. All patients were treated with alpha-adrenergic antagonists or finasteride for at least 2 weeks. A questionnaire based on Andersen's Health Behavior Model was used to assess various sociodemographic features, while the pre- and posttreatment symptoms severity was rated according to the International Prostate Symptom Score (IPSS). Multiple logistic regression was used to assess the associations of these factors with delayed treatment and posttreatment symptom severity. Subjects who had recently quit smoking or were blue-collar workers tended to delay treatment, while those who chose a medical center as the care provider for chronic diseases tended to be less likely to delay treatment. However, none of these associations were statistically significant. No enabling factors (income, insurance) or need factors (symptom scores) evaluated were associated with delayed treatment. Predisposing factors associated with higher posttreatment symptom severity were delayed treatment (over 12 months) (adjusted odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.16-6.16), quitting smoking (adjusted OR: 4.47, 95% CI: 1.34-14.94), and having never smoked (adjusted OR: 3.73, 95% CI: 1.15-12.11). Subjects with severe pretreatment symptoms were far more likely than subjects with mild pretreatment symptoms to have severe symptoms after treatment (adjusted OR: 52.69, 95% CI: 54.46-621.90). Our findings, though based on a limited number of subjects, suggest sociodemographic factors rather than objective clinical attributes (prostate specific antigen level, prostate volume, and urodynamic results) are associated with delayed treatment in Taiwanese men with BPH. Both pretreatment symptom severity and sociodemographic factors are related to posttreatment symptom severity.
Adult↗
Viral hepatitis and kidney transplantation.
Many etiologic factors can cause hepatic dysfunction in renal transplant recipients. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the major causes of hepatitis in such patients. Taiwan is an endemic area for HBV infection, and HCV infection is also quite common among Taiwanese patients with end-stage renal disease. Whether renal transplantation can be safely performed in these patients is controversial. Advances in understanding of the natural course and improved treatment results in viral hepatitis patients in recent years have gradually improved the outlook for renal transplantation in such patients. Because of the severe shortage of organ donors worldwide, research efforts have also been directed at studying the safety and feasibility of using kidneys from donors infected with HBV or HCV. Short-term results are good for renal transplantation in HBV- or HCV- infected recipients, as well as for recipients who receive HBV- or HCV- infected kidneys. Long-term results show that these patients are at greater risk for hepatic disorders and have poorer outcomes than cohorts without infection, although their survival is better than that of patients with HBV or HCV infection who remain on dialysis. To plan effective treatment strategies, renal transplant physicians should be alert to the occurrence of hepatitis among these patients and realize its impact on renal transplant recipients in terms of increased morbidity/mortality and altered pharmacokinetics of immunosuppressive drugs. Hepatitis in renal transplant recipients is a great challenge for both transplant physicians and hepatologists. Many unresolved issues need further investigation.
Hepatitis B↗
Secular trend and age-period-cohort analysis of prostate cancer mortality in Taiwan.
PURPOSE: We evaluated the secular mortality trend of prostate cancer in Taiwan from 1964 through 1994. MATERIALS AND METHODS: Analyses were based on vital statistics. Relative risks associated with each of the age, period and cohort effects on secular mortality were estimated from a log-linear Poisson model. RESULTS: Age adjusted mortality rates increased more than 2-fold during the last 30 years in Taiwan. Age-period-cohort analysis showed that the age effect was the strongest. CONCLUSIONS: Factors related to aging are the main reason for the increase in prostate cancer mortality in Taiwan during the least 3 decades.
Adult↗
Inhibition by tamsulosin of tension responses of human hyperplastic prostate to electrical field stimulation.
Tamsulosin (10(-10)-10(-9) M) or prazosin (10(-9)-10(-8) M) concentration dependently blocked the tension responses to electrical field stimulation (0.3 ms duration, 80 V and 20 Hz) in human hyperplastic prostate with lC50 values of (1.93 +/- 0.26) x 10(-10) M and (2.11 +/- 0.21) x 10(-9) M, respectively. The relative potency of tamsulosin with reference to prazosin was 10.96. The pA2 values for tamsulosin and prazosin against phenylephrine-induced contractions were 10.05 +/- 0.16 and 9.25 +/- 0.07, respectively. The relative potency of tamsulosin with reference to prazosin was 6.31. In the presence of prazosin to block alpha 1-adrenoceptor-mediated responses, nifedipine (10(-5) M), but not tamsulosin (10(-9) M), significantly blocked the tension responses in human hyperplastic prostate induced by increasing [Ca2+]o concentrations (10(-4) to 3 x 10(-3) M) in a Ca(2+)-free environment pre-depolarized with 60 mM K+. Additionally, the effects of prazosin and tamsulosin on electrical field stimulation-evoked [3H]noradrenaline release were studied on the S3/S2 ratios. It appeared that both drugs had little effect on this release reaction, with S3/S2 ratios of 0.96 +/- 0.02 and 0.90 +/- 0.02, respectively. These results indicate that tamsulosin is a potent antagonist against endogenous sympathetic stimulation in human hyperplastic prostate.
Adrenergic alpha-Agonists↗
An experimental model to evaluate the in vivo response of rat seminal vesicle to electrical stimulation.
This investigation demonstrated a good model to record the pressure change of rat seminal vesicle (SV) in response to electrical stimulation (ES) of lesser splanchnic nerve (LSN) in vivo. LSN was easily identified and isolated grossly. Antegrade catheterization via the SV tail to the main lumen was performed similar to the technique of i.v. catheterization, and the pressure recording was quite satisfactory. The vesicle response to ES was frequency-dependent and reproducible. Under the conditions of 10 V and 1 ms, the maximal vesicle pressure was 81.7 +/- 2.8 mmHg with 80 Hz of ES. The inhibitory response of SV to ES by clomipramine was concentration-dependent. Clomipramine (3 mg/kg) could inhibit 53% of control responses (n = 7). This experimental model is relevant to neurophysiologic and neuropharmacologic studies of SV.
Animals↗
Combined cytotoxic effects of tamoxifen and chemotherapeutic agents on bladder cancer cells: a potential use in intravesical chemotherapy.
OBJECTIVE: To evaluate whether tamoxifen enhances the cytotoxicity of chemotherapeutic agents on bladder cancer cells, and the possible mechanism(s) of action. MATERIALS AND METHODS: The in vitro inhibition of cell growth was examined in a model simulating intravesical chemotherapy using two bladder cancer cell lines (TSGH-8301, HTB9) and three commonly used intravesical cytotoxic agents (doxorubicin, mitomycin C, and thiotepa) in the presence or absence of tamoxifen or verapamil as modulators. The expression of the multi-drug resistance-related gene mdr-1 was evaluated by reverse-transcription polymerase chain reaction and Southern blotting (RT-PCR-SB) to determine its transcript level, by flow cytometric analysis of the P-glycoprotein (P-gp) product level with C-219 monoclonal antibody and by the rhodamine-123 retention and efflux assay for P-gp activity. Transforming growth factor beta-1 (TGF beta-1) levels in tamoxifen-conditioned culture medium were determined with enzyme-linked immunosorbant assay (ELISA). RESULTS: Tamoxifen at concentrations > or = 30 microM significantly enhanced the cytotoxicity of the three chemotherapeutic agents to both cell lines, as shown by a marked reduction in the drug concentration which inhibited growth by 50% (IC50). The enhancement of cytotoxicity was significantly dependent on the concentration of tamoxifen. However, tamoxifen alone caused significant toxic effects to TSGH-8301 at > or = 40 microM and to HTB9 at > or = 30 microM. Median-effect analysis showed additive or less-than-additive combination effects between tamoxifen and chemotherapeutic agents and only a minimal synergism in a narrow range of maximal cytotoxicity (fraction affected > 0.9). Thus, the reduction of IC50s by tamoxifen was mostly because it was cytotoxic to the bladder cancer cells used. No enhancement of cytotoxicity was observed in verapamil-modulated cells. Transcripts of mdr-1 could not be detected by RT-PCR-SB, nor was P-gp detected by flow cytometric analysis in the two cell lines. Furthermore, no active P-gp function was detected by the rhodamine-123 retention and efflux study, indicating that the primary chemoresistance mechanisms of the two cell lines were not mediated by mdr-1, nor could tamoxifen or verapamil act through modulation of the mdr-1 pathway in the two cell lines. Tamoxifen at 3 and 10 microM down-regulated the secretion of TGF beta-1 from TSGH-8301 in a concentration-dependent manner, in contrast to the findings that tamoxifen was cytotoxic to the bladder cancer cells used and that tamoxifen up-regulated TGF beta-1 in a breast cancer model, suggesting that there may be a different mechanism of response to TGF beta-1 in these bladder cancer cells. CONCLUSION: Tamoxifen enhanced the cytotoxicity of chemotherapeutic agents largely through its toxic effects on the bladder cancer cells. The mode of action of tamoxifen was not through the regulation of TGF beta-1 or the function of mdr-1. Although cytotoxic levels of tamoxifen (> 50 microM) can be achieved easily in the intravesical model, further study is necessary before tamoxifen can be used clinically in intravesical chemotherapy.
ATP Binding Cassette Transporter, Subfamily B, Mem↗