TLC388 Induces DNA Damage and G2 Phase Cell Cycle Arrest in Human Non-Small Cell Lung Cancer Cells.

TLC388, a camptothecin-derivative targeting topoisomerase I, is a potential anticancer drug. In this study, its effect on A549 and H838 human non-small cell lung cancer (NSCLC) cells was investigated. Cell viability and proliferation were determined by thiazolyl blue tetrazolium bromide and clonogenic assays, respectively, and cell cycle analysis and detection of phosphorylated histone H3 (Ser10) were performed by flow cytometry. γ-H2AX protein; G2/M phase-associated molecules ataxia-telangiectasia mutated (ATM), CHK1, CHK2, CDC25C, CDC2, and cyclin B1; and apoptosis were assessed with immunofluorescence staining, immunoblotting, and an annexin V assay, respectively. The effect of co-treatment with CHIR124 (a checkpoint kinase 1 [CHK1] inhibitor) was also studied. TLC388 decreased the viability and proliferation of cells of both NSCLC lines in a dose-dependent manner. TLC388 inhibited the viability of NSCLC cell lines with an estimated concentration of 50% inhibition (IC50), which was 4.4 and 4.1 µM for A549 and H838 cells, respectively, after 24 hours. Moreover, it resulted in the accumulation of cells at the G2/M phase and increased γ-H2AX levels in A549 cells. Levels of the G2 phase-related molecules phosphorylated ATM, CHK1, CHK2, CDC25C, and cyclin B1 were increased in TLC388-treated cells. CHIR124 enhanced the cytotoxicity of TLC388 toward A549 and H838 cells and induced apoptosis of the former. TLC388 inhibits NSCLC cell growth by inflicting DNA damage and activating G2/M checkpoint proteins that trigger G2 phase cell cycle arrest to enable DNA repair. CHIR124 enhanced the cytotoxic effect of TLC388 and induced apoptosis.

Expression of IL-1ß, HMGB1, HO-1, and LDH in malignant and non-malignant pleural effusions.

IL-1ß, HMGB1, HO-1, and LDH in the pleural effusions (PE) of patients with transudative, infectious, and malignant etiologies were determined using ELISA and enzymatic assays. IL-1ß, HMGB1, HO-1, and LDH showed significant differences between the three etiologies. Post-hoc analysis revealed higher levels of HO-1 and HMGB1 in infectious versus transudative effusion. Higher levels of IL-1ß were found in infectious versus transudative or malignant effusion. The comparison of LDH levels showed significant differences. Positive correlations were found between IL-1ß, HMGB1, and LDH in infectious effusions. The samples were then divided into cancerous and non-cancerous groups, and logistic regression revealed that increasing IL-1ß levels were significantly associated with a decrease in cancer risk after adjusting for HMGB1, HO-1, and LDH. Our findings suggest that IL-1ß, HMGB1, HO-1, and LDH are expressed differently, with positive correlations between HMGB1, IL-1ß, and LDH in infectious effusions, and low IL-1ß expression in malignant effusions.

Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate Induces Cell Death with Coexisting Mitotic Arrest and Autophagy in Human Chronic Myelogenous Leukemia K562 Cells.

A natural compound from Wasabia japonica, 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) was investigated for its anti-leukemia activity and mechanism of action. It was found that 6-MITC inhibited the viability of human chronic myelogenous leukemia K562 cells along with extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation. The evidence of autophagy included the validation of autophagosomes with double-layered membranes under transmission electron microscopy, LC3I/II conversion, and the induction of G2/M phase arrest observed with acridine orange staining of treated cells, as well as the elevation of phosphorylated-histone H3 expression at the M phase. With regard to the expression of proteins related to mitosis, the downregulation of p-CHK1, p-CHK2, p-cdc25c, and p-cdc2, as well as the upregulation of cyclin B1, p-cdc20, cdc23, BubR1, Mad2, and p-plk-1 was observed. The knockdown of cdc20 was unable to block the effect of 6-MITC. The differentiation of k562 cells into monocytes, granulocytes, and megakaryocytes was not affected by 6-MITC. The 6-MITC-induced unique mode of cell death through the concurrent induction of mitosis and autophagy may have therapeutic potential. Further studies are required to elucidate the pathways associated with the counteracting occurrence of mitosis and autophagy.

Diagnosing the RGS11 Lung Cancer Biomarker: The Integration of Competitive Immunoassay and Isothermal Nucleic Acid Exponential Amplification Reaction.

Lung cancer is the primary cause of cancer-associated mortality worldwide, which makes the identification of reliable lung cancer biomarkers a pressing need for early diagnosis and prognosis. RGS11, which is a regulator of G-protein signaling and also a lung cancer biomarker, plays an important role in cancer-related metastasis. However, trace levels of RGS11 (in the range of pg/mL) in serum samples make it difficult to quantify using currently available enzyme-linked immunosorbent assay (ELISA) kits and, therefore, this hinders progress in the discovery of new approaches for treating lung cancer. The aim of this study is to develop a rapid, sensitive, and reliable platform for the detection of RGS11 lung cancer biomarker based on a suspension immunoassay coupled with an isothermal exponential amplification strategy. Our study was initiated by the functionalization of magnetic beads with anti-RGS11 antibodies (Ab-MB) by EDC (1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide)/NHS ( N-hydroxysulfosuccinimide) activation. Ab-MB served as a sensing probe for the competitive immunorecognitions between known concentrations of His-tag RGS11 and unknown concentrations of target RGS11 in serum. The reporter anti-His antibodies, which were modified with primers that induced an isothermal exponential amplification reaction, were subsequently introduced to the reaction mixture that resulted in the formation of immunosandwich complexes. The exponentially amplified DNA duplex that was intercalated with SYBR Green was designated as a signal reporter for the assessment of RGS11 in an inversely proportional relationship. The sensing platform was excellent for the determination of RGS11 with an exceptional detection limit of 148 fg/mL and a linear dynamic range of 0.1-10 pg/mL using a minimal sample volume (20 µL) and with a reaction time of 1.5 h. In addition, we challenged the sensing platform with RGS11-spiked samples (in 2× diluted serum), and an acceptable recovery rate (>90%) was observed. Finally, 24 clinical samples acquired from patients with advanced lung cancer (C), inflammation (I), and heart failure (H) were analyzed by this newly developed sensing platform and a commercial ELISA kit for validation. This sensing platform has potential in biomedical applications for clinically diagnosing liquid biopsy samples for patients with lung cancer. Moreover, the universal design of our proposed system is easily adapted to detect any other protein if a His-tag recombinant protein is available.

Bidirectional association between obstructive sleep apnea and depression: A population-based longitudinal study.

An association may exist between obstructive sleep apnea (OSA) and depression. However, results regarding this association are inconsistent, and the direction of the association between OSA and depression remains unknown. Therefore, we used the Taiwan National Health Insurance Research Database to investigate the bidirectional association between OSA and depression.A total of 6427 OSA patients and 32,135 age and sex-matched control subjects were enrolled to analyze the risk of depression among patients with OSA, where 27,073 patients with depression and 135,365 control subjects were enrolled to address the risk of OSA among patients with depression. All subjects were followed to identify their outcomes of interest from January 1, 1997 to December 31, 2012.Cox proportional-hazards models, after adjusting for potential confounders, demonstrated that patients with OSA had an increased risk (adjusted hazard ratio 2.48, 95% confidence interval 2.20-2.79) of developing depression, whereas those with depression were associated with an increased risk of future OSA (adjusted hazard ratio 2.30, 95% confidence interval 2.11-2.50).Our results suggested that a strong bidirectional relationship exists between OSA and depression, with each disease influencing the development of the other. Health providers are recommended to ensure the early detection and management of depression among patients with OSA and vice versa.

Quantiferon TB-Gold conversion can predict active tuberculosis development in elderly nursing home residents.

AIM: The study was carried out on elderly nursing home residents in Taiwan. We assessed whether the serial QuantiFERON-TB Gold (QFT-G) assay and serial tuberculin skin test (TST) were reliable tools to predict or exclude the development of active tuberculosis (TB). METHODS: This prospective observational cohort study involved non-bacillus Calmette-Guérin-vaccinated 259 elderly nursing home residents free of active TB at baseline. Of these, 147 were eligible for follow up. Participants underwent serial QFT-G and TST at baseline and 2-year follow up, and were monitored for active TB over 5 years. Agreement between QFT-G and TST, incidence rate ratio, positive predictive value, and negative predictive value for progression to active TB were measured. RESULTS: During 5-year follow up, three participants developed active TB. The agreement between these two tests was 54.13% (ĸ = 0.167, P = 0.001). The incidence rate ratio was 15.8 (P = 0.016) for the QFT-G-conversion group compared with the TST-positive group at baseline. Positive predictive value for QFT-G conversion groups was 25%. Negative predictive value was 100% for the TST-negative group at baseline. CONCLUSION: In the elderly nursing home residents, QFT-G conversion is a more reliable tool to predict the development of active TB. Meanwhile, TST is a valuable tool for predicting the chance of not developing active TB.

A reduction in anti-tuberculosis drug resistance after the implementation of the national "STOP TB" program in central Taiwan, 2003-2007.

The aim of this study was to determine the performance of the national "STOP TB" program in central Taiwan during 2003-2007 by examining trends in the combined drug resistance to first-line anti-tuberculosis (TB) drugs among clinical Mycobacterium tuberculosis isolates. Using 4,819 clinical M. tuberculosis isolates obtained from two mycobacteriology referral laboratories, the resistance to drugs was measured and analyzed along with the treatment outcomes in notified TB patients. The proportion of isolates showing total resistance and multidrug-resistant tuberculosis (MDR-TB) isolates were 17.7% and 3.67%, respectively. More number of MDR-TB isolates showed high-level resistance to isoniazid (84.18%) and streptomycin (SM) (30.51%); low-level resistance to ethambutol (EMB) (61.58%), SM (41.81%), and pyrazinamide (66.1%); and resistance to ofloxacin (30.4%). However, fewer isolates showed high-level resistance to EMB (19.77%), levofloxacin (17.9%), moxifloxacin (19.6%), kanamycin (8.9%), amikacin (8.9%), and capreomycin (8.9%). Of these MDR-TB isolates, 7.1% were extensively drug-resistant. Trends in combined drug resistance to all the first-line anti-TB drugs and the incidence of MDR-TB were stable during the 2 years (2003-2004) before the implementation of the national "STOP TB" program. After the "STOP TB" program, there were significant declines in the incidence of MDR-TB during 2005-2007 in central Taiwan as well as improved TB-treatment outcomes. Thus, the national "STOP TB" program had a significant positive impact on TB control in central Taiwan.

Rapid identification of the Mycobacterium tuberculosis complex by combining the ESAT-6/CFP-10 immunochromatographic assay and smear morphology.

Early secretory antigen 6 (ESAT-6) and cell filtrate protein 10 (CFP-10) are two antigens secreted as a complex by the replicating Mycobacterium tuberculosis complex (MTC). Recently, an immunochromatographic assay (ICA) using a monoclonal antibody against the ESAT-6/CFP-10 complex was developed for the purpose of MTC detection. In this study, the efficacy of the assay was tested with 603 BACTEC cultures that were incubated for 3 additional days after positive signals appeared in the BACTEC MGIT 960 system. Bacterial isolates were recovered from these 603 BACTEC cultures, and 332 MTC isolates, 270 nontuberculosis mycobacterial isolates, and 1 Nocardia isolate were identified by using standard biochemical assays. The ESAT-6/CFP-10 assay detected 322 MTC cultures, resulting in a sensitivity of 97% and a specificity of 97.4%. To reduce the false-negative rate and improve the sensitivity, either serpentine cording in an acid-fast bacillus stain of the cultural smear, the ESAT-6/CFP-10 assay, or a combination of both was used for MTC detection. The sensitivity was then increased to 99.1%, and the negative predictive value increased to 98.9%, but the specificity decreased to 94.8% and the positive predictive value decreased to 95.9%. However, a combination of serpentine cording in cultural smears and the positivity of the ICA resulted in the specificity and positive predictive values of 100%. Therefore, BACTEC cultures with both serpentine cording and positivity of the ESAT-6/CFP-10 assay could be reported to contain MTC directly. The ESAT-6/CFP-10 assay may be an alternative of the Capilia assay (MPB64-ICA) as a convenient and cost-effective method for identification of MTC in culture.

High efficacy of clofazimine and its synergistic effect with amikacin against rapidly growing mycobacteria.

The aim of this study was to determine whether clofazimine, dapsone and cycloserine may be suitable antimicrobial agents for the treatment of infections due to rapidly growing mycobacteria (RGM). The antimicrobial activity of the three drugs against 117 Mycobacterium abscessus isolates, 48 Mycobacterium fortuitum isolates and 20 Mycobacterium chelonae isolates was evaluated based on their broth microdilution minimal inhibitory concentrations (MICs) against the isolates. Clofazimine was highly efficacious against these RGM. The vast majority of M. abscessus, M. fortuitum and M. chelonae isolates (99.1%, 91.7% and 100%, respectively) had clofazimine MICs of

Effect of treatment by nasal continuous positive airway pressure on serum high mobility group box-1 protein in obstructive sleep apnea.

BACKGROUND: Serum levels of high mobility group box-1 protein (HMGB1) are increased in a variety of inflammatory disorders. Obstructive sleep apnea syndrome (OSAS) is associated with inflammation secondary to chronic intermittent hypoxia, but HMGB1 levels in treated and untreated OSAS have not been evaluated. METHODS: Twenty healthy subjects and 30 subjects with moderately severe or severe OSAS who desired nasal continuous positive airway pressure (CPAP) treatment were enrolled. Serum levels of HMGB1 and nitric oxide derivative (NO(x)) from peripheral blood samples were measured, and all subjects underwent a sleep study. These studies were repeated 2 months after nasal CPAP treatment in the patients with OSAS. RESULTS: In OSAS before nasal CPAP treatment, the serum level of HMGB1 was higher but that of NO(x) was lower than those levels of normal subjects. The HMGB1 levels correlated negatively with NO(x) levels in subjects with OSAS. After nasal CPAP treatment, the HMGB1 and NO(x) returned to normal levels. CONCLUSION: Elevated HMGB1 levels and reduced NO(x) levels in patients with OSAS normalized after nasal CPAP treatment.

Effect of uvulopalatopharyngoplasty on endothelial function in obstructive sleep apnea.

OBJECTIVES: This study evaluates the effects of uvulopalatopharyngoplasty (UPPP) on serum levels of nitric oxide derivatives (NO(x)) and endothelial function by endothelium dependent flow-mediated dilation (FMD) in obstructive sleep apnea syndrome (OSAS). STUDY DESIGN: Prospective study. SUBJECTS AND METHODS: Fifteen healthy subjects and 30 subjects with moderately severe to severe OSAS who desired UPPP were prospectively enrolled. FMD was measured by high-resolution B-mode ultrasonography; serum level of NO(x) from peripheral blood samples was also measured. All subjects participated in sleep studies. These studies were repeated 3 months after UPPP in OSAS patients. RESULTS: For healthy patients, there was no difference in serum level of NO(x) and FMD between baseline and 3 months later. The serum levels of NO(x) in 14 of 30 patients with OSAS - designated surgical responders - increased from 13.9 +/- 5.5 microM preoperation to 28.9 +/- 8.2 microM postoperatively. FMD increased from 5.2 +/- 5.0 preoperatively to 10.0 +/- 4.7 postoperatively. For the 16 unresponsive patients, serum NOx and FMD remained impaired after UPPP. CONCLUSION: Successful treatment of OSAS with UPPP leads to restoration of FMD and normal serum levels of NO(x).

Effect of erythromycin on bronchial hyperreactivity and inflammation in ovalbumin-sensitized brown Norway rats.

To evaluate the effect of erythromycin on bronchial hyperreactivity, inflammation, and T-cell related cytokine mRNA expression in rats sensitized to ovalbumin, three experimental groups of 10 brown Norway rats each were sensitized by breathing aerosolized ovalbumin. From day 1 to day 15, one group was given oral erythromycin 80 mg/kg/day, another group oral erythromycin 20mg/kg/day, and the third group oral saline only. A fourth control group of 10 rats breathed aerosolized saline. After sensitization, the three experimental groups were provoked by breathing ovalbumin, with the controls again breathing saline. The rats were then anesthetized and paralyzed, and pulmonary function tests were performed at baseline and after varying doses of acetylcholine. Bronchoalveolar lavage (BAL) fluid and lung tissues were examined for expression of mRNA for T-cell cytokines. Our results showed that erythromycin had no beneficial effects on pulmonary function and lung inflammation in the two erythromycin-treated experimental groups compared with the saline experimental group. Th2-related cytokines and their mRNA expression in the three experimental groups were higher than in controls but did not differ among the experimental groups. In conclusion, erythromycin does not prevent bronchial hyperreactivity or an inflammatory response in ovalbumin-sensitized rats.

In Vitro activities of isepamicin, other aminoglycosides, and capreomycin against clinical isolates of rapidly growing mycobacteria in Taiwan.

The in vitro activities of isepamicin against 117 Mycobacteria abscessus, 48 Mycobacterium fortuitum, and 20 Mycobacterium chelonae isolates were evaluated by a microdilution test. Isepamicin MIC(90)s were < or =16 microg/ml for the three species. Isepamicin was as active as amikacin and kanamycin and more active than tobramycin, capreomycin, gentamicin, and streptomycin.

Intrathoracic tracheal obstruction caused by a carotid mycotic aneurysm in a patient with deep neck infection--a case report.

Upper airway obstruction secondary to a carotid mycotic aneurysm has not been previously reported. We describe a patient with a mycotic aneurysm associated with a deep neck infection and presenting with acute tracheal obstruction. Recognition of this condition is important to avoid inadvertent rupture of the aneurysm in the course of diagnostic aspiration or surgical drainage. Physical findings, including a pulsating mass and an arterial bruit, in addition to appropriate imaging studies, may be helpful in suggesting the diagnosis. In particular, both neck and chest contrast-enhanced computed tomography scans may give important clues to the presence of a vascular lesion. In a patient with an infected neck mass and tracheal compression, a common carotid mycotic aneurysm should be considered in the differential diagnosis.

The self-care strategies of girls with primary dysmenorrhea: a focus group study in Taiwan.

Dysmenorrhea is the most common gynaecological complaint and the leading cause of recurrent short-term school absenteeism among adolescent girls. To explore adolescent girls' self-care strategies for dysmenorrhea, we conducted four focus groups in Kaohsiung, Taiwan, with 23 female adolescents with primary dysmenorrhea. Thematic content analysis was used to explore and organize the data. The self-care strategies for dysmenorrhea reported by participants included reducing physical activity, modifying diet using herbal remedies or medication, applying complementary therapies, paying attention to symptom clusters of discomforts, and expressing emotions. This is the first study to describe the self-care strategies adopted by adolescent girls with dysmenorrhea in Asia. Data were analyzed in cultural contexts. Knowledge of beneficial food-related or herbal health practices can enable professionals to counsel this population more effectively.

Effect of laser-assisted uvulopalatoplasty on oral airway resistance during wakefulness in obstructive sleep apnea syndrome.

The aim of the study was to evaluate the effects of successful laser-assisted uvulopalatoplasty (LAUP) on oral airway resistance (R(OA)) during wakefulness in patients with OSAS. Fifteen healthy subjects (group I) and 25 subjects (group II) with moderately severe or severe obstructive sleep apnea syndrome (OSAS) proven by an overnight sleep study and who desired LAUP were enrolled. All underwent an overnight sleep study, pulmonary function testing and measurement of oral airway resistance [R(OA) (including impedance (Zrs), resistance (R) and reactance (X)] measurement by Impulse Oscillometry (IOS) (MasterScreen IOS, VIASYS Healthcare GmbH, Germany) in the upright (seated) position and then in the supine position while awake. Group II subjects had these measurements twice, both before and 3 months after LAUP. Based on the assessment of their sleep study after LAUP, they were divided into two groups: responders (group IIa) and nonresponders (group IIb). Zrs was normal in the sitting position both before and after LAUP in both groups IIa and IIb and comparable to that of group I controls. There was an increase in Zrs in the supine position in both groups IIa and IIb subjects before LAUP. After LAUP, the Zrs in group IIb subjects remained elevated, while that in group IIa subjects returned to levels comparable to those in the normal controls. OSAS patients before LAUP have abnormal R(OA) in the supine position as reflected by a high Zrs. The Zrs is improved after LAUP that successfully ameliorates OSAS.

Effect of treatment by laser-assisted uvulopalatoplasty on cardiopulmonary exercise test in obstructive sleep apnea syndrome.

OBJECTIVES: To evaluate the effects of successful laser-assisted uvulopalatoplasty (LAUP) on cardiopulmonary exercise testing (CPET) in patients with obstructive sleep apnea syndrome (OSAS). STUDY DESIGN AND SETTING: Twenty-five subjects with moderately severe or severe OSAS who desired LAUP were enrolled. All patients had an overnight sleep study and CPET before and 3 months after LAUP. Patients were divided into 2 groups based on the success (group I) or failure (group II) of LAUP to improve their sleep apnea. RESULTS: Successful LAUP in group I was followed by improvement in right ventricular ejection fraction, maximal work rate (WRmax), VO2max/kg, anaerobic threshold, oxygen pulse, and a lower breathing reserve. CPET results were unchanged after LAUP in group II subjects. CONCLUSION: Patients with OSAS before LAUP had abnormal CPET as reflected by low VO2peak/kg, WRmax, anaerobic threshold, and oxygen pulse. All of these variables improved after LAUP that successfully ameliorated OSAS.

Oral airway resistance during wakefulness in eucapnic and hypercapnic sleep apnea syndrome.

The purpose of this study was to evaluate whether there was an abnormal increase of upper airway resistance in the sitting and supine positions in hypercapnic obstructive sleep apnea syndrome (OSAS) patients compared with eucapnic OSAS or normal controls as measured by impulse oscillometry (IOS) while awake. Twenty subjects without OSAS served as controls (group I), and 20 patients with moderate or severe eucapnic OSAS (group II) and another eight hypercapnic severe OSAS patients (group III) were studied. Group II was further divided into two subgroups. Group IIa consisted of 14 subjects whose BMI was less than 35 and group IIb of six subjects whose BMI was greater than 35. All subjects also had an overnight sleep study. Oral airway resistance (AR) (including impedance (Zrs), resistance (R) and reactance (X)) was measured by impulse oscillometry (IOS) (MasterScreen IOS, VIASYS Healthcare GmbH, Germany) in the upright (seated) position and then in the supine position while awake. The results demonstrated that in both group I and group II, Zrs was normal in the sitting position. However, there was a high Zrs in the supine position for group II patients. In contrast, in group III patients, there was a high Zrs in both the sitting and supine positions. In conclusion, upper airway resistance was increased both sitting and supine in the hypercapnic OSAS patients; this would presumably increase the work of breathing and might explain why these subjects were hypercapnic while awake, while eucapnic OSAS patients and normal controls were not. Secondly, the increased upper airway resistance in the supine position in the eucapnic OSAS patients may contribute to their OSAS.

Effect of treatment by nasal CPAP on cardiopulmonary exercise test in obstructive sleep apnea syndrome.

This study was done to evaluate whether cardiac dysfunction or abnormal measurements on cardiopulmonary exercise testing (CPET) can be improved after 2 months of nasal CPAP treatment. Twenty patients with moderate or severe OSAS received nasal CPAP treatment. All subjects also underwent blood pressure, simple spirometric, and arterial blood gas (ABG) measurements; cardiac evaluation by radionuclide scanning and CPET; and an overnight polysomnography sleep study before and after nasal CPAP treatment. No difference in left ventricular ejection fraction (LVEF) was found after 2 months of nasal CPAP treatment, but higher right ventricular ejection fraction (RVEF), VO2peak, VO2peak/kg and workpeak were observed. After 2 months of nasal CPAP treatment, these patients had a lower breathing reserve and a greater increase in anaerobic threshold and oxygen pulse. Moderate to severe OSAS patients before nasal CPAP treatment had abnormal CPET as reflected by lower RVEF, VO2peak/kg, workpeak, anaerobic threshold and oxygen pulse. These abnormalities can be improved after 2 months of nasal CPAP treatment.

The evaluation of cervical cancer screening by combining speculoscopy with Papanicolaou smear examination in Taiwan.

BACKGROUND: Cervical cancer is the most common malignancy in women in Taiwan. In order to improve the detection of cervical lesions using the Papanicolaou (Pap) smear in screening, a number of adjunctive tests have been developed. The purpose of this study is to evaluate the utility of a magnified chemiluminescent screening examination (speculoscopy) combined with the Pap smear (PapSure) in detecting cervical cancer. METHODS: A total number of 572 women underwent routine cervical cancer screening by receiving a Pap smear and speculoscopy examination. When either the Pap smear or speculoscopy result was positive, colposcopy was performed. Targeted biopsies were taken from any suspicious lesions that were found by positive colposcopies and the data analyzed using McNemar's test. RESULTS: Eighty-two women had a positive on either screening test. Of the 62 biopsy specimens obtained, 3 women showed high-grade squamous intraepithelial lesions (HGSIL), and 13 women showed low-grade squamous intraepithelial lesions (LGSIL). The histopathological findings were correlated at different levels with the results of the Pap smear alone and speculoscopy alone and both combined. The Pap smear alone detected 1.0% (6 of 572) of significant pathology, while speculoscopy alone detected 2.3% (13 of 572) of significant pathology. The use of the PapSure showed enhanced detection (16 of 572) compared with either the Pap smear alone or speculoscopy alone. CONCLUSIONS: Speculoscopy can be combined with the Pap smear (PapSure) as a cervical cancer screening test to yield a higher detection rate of biopsy-confirmed cervical pathology in women than the use of the Pap smear or speculoscopy alone.