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Biomedical subjects

M K Lai

Publications and source records attributed to M K Lai.

At least 55 records · Page 3Linked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Ouabain-induced increases in resting tone of human hyperplastic prostate following repeated noradrenaline and electrical field stimulation.

1. The effect of ouabain on contractions to repeated noradrenaline stimulation and electrical field stimulation of human hyperplastic prostate was examined. Ouabain (1 microM) did not induce contractile response per se but progressively increased the resting tone (i.e., the tone between one noradrenaline stimulation, or electrical field stimulation, and the following) of human hyperplastic prostate. 2. The increased tone by ouabain following repeated noradrenaline stimulations or electrical field stimulation was fully relaxed by the removal of external calcium, and recovered following restoration of calcium. 3. The effect of noradrenaline on NA+ uptake was measured. Noradrenaline (10 microM) significantly increased the rate of Na+ accumulation in the presence of ouabain (1 microM); this stimulatory effect was almost completely blocked by prazosin (0.1 microM) and ethylisopropylamiloride (100 microM). In contrast, tetrodotoxin (1 microM) had no effect on noradrenaline-stimulated Na+ transport in human hyperplastic prostate. 4. Intracellular Na+ loading by noradrenaline (10 microM) in the presence of ouabain (1 microM) significantly increased the transmembrane Ca2+ uptake as compared with the absence of ouabain; however, nifedipine (1 microM) was ineffective on Ca2+ uptake under this condition. 5. Transmembrane CA2+ efflux was stimulated by noradrenaline (10 microM) in human hyperplastic prostate; this effect was significantly decreased in the presence of ouabain (1 microM). 6. It is suggested that the increased tone of human hyperplastic prostate following repeated excitation in the presence of ouabain is due to increased Ca2+ entry and reduced efflux of Ca2+ through the Na+/Ca+ exchange system as a consequence of Na+ pump inhibition by ouabain.

Adrenergic alpha-Agonists↗
PubMed1996

Expression of MDR-1 gene in transitional cell carcinoma and its correlation with chemotherapy response.

PURPOSE: Expression of the mdr-1 gene has been correlated with the chemoresistance mechanisms of some cancer models. In the present study, we tried to evaluate mdr-1 gene expression in transitional cell carcinoma (TCC) in both cultured cells and clinical tumors. The expression status of mdr-1 was further correlated with the response to chemotherapy in both systemic and intravesical models. MATERIALS AND METHODS: We evaluated mdr-1 expression levels by reverse transcription polymerase chain reaction and Southern blotting (RT-PCR-SB) and the activity of P-glycoprotein (P-gp) by flow cytometric rhodamine-123 retention and efflux study in 10 TCC cell lines, 2 doxorubicin-resistant sublines (RLs), T24/A and NTUB1/A, and 2 cisplatin-RLs, T24/P and NTUB1/P. Eighty-eight clinical tumors with their benign counterparts were also assayed by RT-PCR-SB to determine mdr-1 expression status. Of the 88 TCC cases, 28 were treated with systemic and 60 with intravesical chemotherapy. Response to chemotherapy in either form was correlated with mdr-1 expression status. RESULTS: By RT-PCR-SB, mdr-1 expression signals were observed in only 2 of the 10 TCC cell lines; only 1 of these had a strong signal and active P-gp function. The other, bearing a weak signal, was negative for active P-gp function. All of the 4 RLs studied showed elevated mdr-1 transcript levels as compared with their mdr-1 negative parental cell lines. Doxorubicin-RLs showed much stronger expression signals than cisplatin-RLs. Active P-gp functions were observed in the 2 doxorubicin-RLs but not in the 2 cisplatin-RLs. The efflux of rhodamine-123 in cells with active P-gp function can be significantly inhibited by 10 microM. verapamil. Of the 88 clinical tumors, 62 (70.5%) were positive and 26 (29.5%) were negative for mdr-1 expression by RT-PCR-SB. All benign counterparts of the 88 tumors were positive for mdr-1 expression. However, no differences in chemotherapy responses were found between the positive and negative mdr-1 expression groups in either systemic chemotherapy (p = 0.32, one-tailed Fisher's exact test) or intravesical chemotherapy (p = 0.52, Cox-Mantel log rank test). CONCLUSIONS: Expression of mdr-1 was not commonly seen in TCC cell lines but can be significantly induced by chronic exposure to doxorubicin. Benign transitional cell epithelia seemed to universally express the mdr-1 gene. However, clinical TCCs lost mdr-1 transcript expressions in about 30% of cases. Most important, it appeared that mdr-1 expression status did not correlate with the response to chemotherapy in either systemic or intravesical models.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Simple nephrectomy by retroperitoneoscope.

Retroperitoneoscopic simple nephrectomy was successfully performed in 10 of 12 patients with nonfunctioning kidneys. The other two patients underwent traditional open surgery. The surgical procedures, technical pitfalls, surgical results and perisurgical complications of this simple retroperitoneoscopic approach are described. Retroperitoneoscopic nephrectomy is a viable alternative for simple nephrectomy and has the benefits of minimal invasiveness, more rapid convalescence and better quality of life for patients.

Aged↗
PubMed1996

Treating benign prostatic hyperplasia with finasteride in Chinese men: one-year experience.

To evaluate the long-term efficacy and safety of finasteride in the treatment of symptomatic benign prostatic hyperplasia (BPH), 50 patients with symptomatic BPH were initially evaluated in a double blind, placebo-controlled study for 6 months. The patients were then treated with finasteride in an open extension study in which all received the same dose of finasteride (5 mg/day) for another 6 months. Among the patients (n = 23) who completed the extension study, prostate volume was significantly reduced from baseline by 15%, maximum urine flow rate improved by 1.9 mL/second, symptom scores improved by 37% and serum prostatic specific antigen (PSA) level decreased by 1.34 ng/mL. Other than serum PSA level, these data differed insignificantly from data at the end of the first 6 months. The adverse events observed at the end of the first 6 months (two patients with decreased sexual libido and two with impotency) persisted throughout the study extension period. At the end of the 12 months study, one more patient reported decreased libido. The sustained clinical efficacy and low incidence of side-effects of daily treatment with finasteride 5 mg for 1 year indicate that finasteride is safe and effective for managing symptomatic BPH in Chinese men.

Aged↗