Post-operative adjuvant thoracic radiotherapy for patients with completely resected non-small cell lung cancer with nodal involvement: outcome and prognostic factors

The purpose of this study was to analyse the outcome and prognostic factors of non-small cell lung cancer (NSCLC) patients with nodal disease treated by complete tumour resection followed by radiotherapy alone. Between October 1990 and October 1999, 49 NSCLC patients with N1 or N2 stage were treated with complete resection of tumour followed by post-operative radiotherapy in our department. The radiation was delivered with 10 MV X-rays given 5 days per week at 1.8-2 Gy per fraction. Total doses ranged from 40 Gy to 64.8 Gy, with a median dose of 55.8 Gy. All patients had at least 30 months of follow-up. The 5 year overall survival rate (OS), local control rate (LC) and distant metastasis-free rate (DMF) were 34%, 52% and 29%, respectively. In multivariate analysis, stage and margin were found to influence OS. The total number of involved lymph nodes and positive margins were significant factors for LC. Only N stage was found to correlate with DMF. In conclusion, patients with multiple involved lymph nodes, advanced stage or positive surgical margins had a poor outcome even with post-operative radiotherapy. Based on these prognostic factors, new therapeutic regimens and modalities for NSCLC need to be further investigated.     

Generalized chorea associated with bilateral chronic subdural hematoma

A variety of acquired disorders cause chorea, such as hypoxia-ischemia injury, drugs, toxins, infections, autoimmune disorders, and endocrine and electrolyte abnormalities, but rarely subdural hematoma. We report the case of a 76-year-old woman who presented with sudden onset of generalized choreiform movements 1 day prior to admission. Computed tomography revealed a bilateral lateral convexity subdural effusion, which was later confirmed by magnetic resonance imaging as a chronic subdural hematoma. After surgical evacuation of the subdural hematoma, the choreoathetoid movements ceased completely. We propose that transient ischemia in the bilateral subcortical regions was from compression and distortion of the brain by the bilateral hematomas and resulted in generalized chorea.     

The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor

Objectives: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. Methods and results: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (ΔDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P VALUE=0.0076 for DBP, and P VALUE=0.0005 for ΔDBP). We further divided all patients into three groups based on the tertiles of the ΔBP distribution. Compared to subjects in the lowest tertile of ΔDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. Conclusions: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.     

Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents (berberine, coptisine and icariin) on hepatoma and leukaemia cell growth

1. The present study was conducted to evaluate the cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts and their major constituents on hepatoma and leukaemia cells in vitro. 2. Four human liver cancer cell lines, namely HepG2, Hep3B, SK-Hep1 and PLC/PRF/5, and four leukaemia cell lines, namely K562, U937, P3H1 and Raji, were used in the present study. 3. Of the two crude drugs, C. chinensis exhibited the strongest activity against SK-Hep1 (IC50 = 7 microg/mL) and Raji (IC50 = 4 microg/mL) cell lines. The IC50 values for C. chinensis on HepG2, Hep3B and PLC/PRF/5 cell lines were 20, 55 and 35 microg/mL, respectively. The IC50 values for C. chinensis on K562, U937 and P3H1 cell lines were 29, 29 and 31 microg/mL, respectively. 4. With the exception of HepG2 and Hep3B, the E. sagittatum extract inhibited the proliferation of all cell lines (SK-Hep1, PLC/PRF/5, K562, U937, P3H1 and Raji), with IC50 values of 15, 57, 74, 221, 40 and 80 microg/mL, respectively. 5. Interestingly, the two major compounds of C. chinensis, berberine and coptisine, showed a strong inhibition on the proliferation of both hepatoma and leukaemia cell lines, with IC50 values varying from 1.4 to 15.2 microg/mL and from 0.6 to 14.1 microg/mL, respectively. However, icariin (the major compound of E. sagittatum) showed no inhibition of either the hepatoma or leukaemia cell lines. 6. The results of the present study suggest that the C. chinensis extract and its major constituents berberine and coptisine possess active antihepatoma and antileukaemia activities.     

Isoliquiritigenin inhibits the proliferation and induces the apoptosis of human non-small cell lung cancer a549 cells

1. Isoliquiritigenin (ISL) is a natural pigment with the simple chalcone structure 4,2',4'-trihydroxychalcone. In the present study, we report, for the first time, ISL-induced inhibition of the proliferation of the human non-small cell lung cancer A549 cell line. 2. The results showed that ISL not only inhibited A549 cell proliferation, but also induced apoptosis and blocked cell cycle progression in the G1 phase. An ELISA assay demonstrated that ISL significantly increased the expression of p53 and p21/WAF1 protein, which caused cell cycle arrest. 3. An enhancement in Fas and its two ligands, namely membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), may be responsible for the apoptotic effect induced by ISL. 4. Taken together, the results indicate that the p53 and Fas/FasL apoptotic system may participate in the antiproliferative activity of ISL in A549 cells.     

Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells

In Madin-Darby canine kidney (MDCK) cells, the effect of maprotiline, an antidepressant, on intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured using fura-2. Maprotiline (>2.5 µM) caused a rapid rise of [Ca²⁺]_i in a concentration-dependent manner (EC₅₀ 200 µM). Maprotiline-induced [Ca²⁺]_i rise was reduced by removal of extracellular Ca²⁺ or by addition of La³⁺, but was not altered by voltage-gated Ca²⁺-channel blockers. Maprotiline-induced Mn²⁺ influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca²⁺ influx. In Ca²⁺-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺-ATPase, caused a monophasic [Ca²⁺]_i rise, after which the increasing effect of maprotiline on [Ca²⁺]_i was nearly abolished; also, pretreatment with maprotiline reduced a portion of thapsigargin-induced [Ca²⁺]_i rise. U73122, an inhibitor of phospholipase C, abolished [Ca²⁺]_i rise induced by ATP (but not by maprotiline). Overnight incubation with 1–10 µM maprotiline enhanced cell viability, but 20–50 µM maprotiline decreased it. These findings suggest that maprotiline rapidly increases [Ca²⁺]_i in renal tubular cells by stimulating both extracellular Ca²⁺ influx and intracellular Ca²⁺ release, and may modulate cell proliferation in a concentration-dependent manner.     

Association of ocular dominance and anisometropic myopia

PURPOSE: To determine the association between ocular dominance and degree of myopia in patients with anisometropia. METHODS: Fifty-five subjects with anisometropic myopia were recruited. None of them had amblyopia. Refractive error and axial length were measured in each subject. Ocular dominance was determined using the hole-in-the-card test and convergence near-point test. RESULTS: There was a threshold level of anisometropia (1.75 D) beyond which the dominant eye was always more myopic than the nondominant eye. Of the 33 subjects with anisometropia of < or =1.75 D, the dominant eye was more myopic in 17 (51.5%) subjects. Dominant eyes, determined by the hole-in-the-card test, had a significantly greater myopic spherical equivalent (-5.27 +/- 2.45 D) than nondominant eyes (-3.94 +/- 3.10 D; P < 0.001). Dominant eyes also had a longer axial length than nondominant eyes (25.15 +/- 0.96 mm vs. 24.69 +/- 1.17 mm, respectively; P < 0.001). The difference was more evident in those subjects with higher anisometropia (>1.75 D), but was not significant in those with lower anisometropia (< or =1.75 D). Similar results were obtained using the convergence near-point test. CONCLUSIONS: The present study shows that the dominant eye has a greater degree of myopia than the nondominant eye in subjects with anisometropic myopia. Taking ocular dominance into account in the design of randomized clinical trails to assess the efficacy of myopia interventions may provide useful information.     

Prevalence and causes of visual impairment in an elderly Chinese population in Taiwan: the Shihpai Eye Study

OBJECTIVE: Few population-based data on the prevalence and causes of visual impairment are available from East Asia. The purpose of this study was to determine the prevalence and causes of visual impairment in an elderly Chinese population in Taiwan. DESIGN: Population-based cross-sectional study. PARTICIPANTS: The Shihpai Eye Study was a survey of vision and ocular disease among an elderly Chinese population 65 years of age or older residing in Shihpai, Taiwan. A random sample of 2045 elderly residents was identified and selected from the household registration databank. Among them, 1361 (66.6%) underwent a detailed ophthalmic examination. METHODS: The ophthalmic examination included best-corrected visual acuity measurements using standardized protocols. Visual acuity was assessed with a Snellen E chart. The major cause of visual loss was identified for all participants who were visually impaired. MAIN OUTCOME MEASURES: Low vision and blindness were defined as a best-corrected visual acuity in the eye with better vision worse than 20/60 to a lower limit of 20/400 and worse than 20/400, respectively, according to World Health Organization categories of visual impairment. RESULTS: The mean age of the participants was 72.2 (range, 65-91) years old. A total of 40 participants met the World Health Organization criteria of low vision, and 8 were diagnosed as blind. The rate of blindness and low vision was estimated to be 0.59% (95% confidence interval, 0.25%, 1.16%) and 2.94% (95% confidence interval, 2.11%, 3.99%), respectively. There was a significant increase in the rate of low vision (P<0.001) from 0.83% at 65 to 69 years of age to 8.33% at age 80 years or older. There was no gender difference in the prevalence of blindness or low vision. The leading cause of visual impairment was cataract (41.7%), followed by myopic macular degeneration (12.5%) and age-related macular degeneration (10.4%). CONCLUSIONS: The rate of blindness and low vision is close to that reported for other developed countries. The high frequency of myopic macular degeneration as a major cause of visual loss, however, is not observed in European-derived populations. Specific prevention or low-vision rehabilitation programs should be developed for the elderly Chinese population.     

Retinal temperature increase during transpupillary thermotherapy: effects of pigmentation, subretinal blood, and choroidal blood flow

PURPOSE: To study the risk of adverse events in transpupillary thermotherapy (TTT) for age-related macular degeneration by measuring how laser-induced retinal temperature increase is affected experimentally by subretinal blood, choroidal blood flow, and chorioretinal pigmentation. METHODS: An ultrafine thermocouple technique was developed to measure retinal temperature increase during TTT in albino and pigmented rabbit eyes. TTT was performed with 60-second, 0.78-mm spot size, 810-nm infrared diode laser exposures with power settings ranging from 50 to 950 mW. Intraretinal and subretinal temperature increases were measured in pigmented and albino rabbits, with or without subretinal blood and choroidal blood flow. RESULTS: Threshold power settings for visible lesions in albino and pigmented rabbits were 950 and 90 mW, respectively, corresponding to retinal temperature increases of 11.8 degrees C and 5.28 degrees C, respectively. Power settings required to produce threshold lesions in albino rabbits caused retinal temperature increases in pigmented rabbits that were five times higher than in the albino rabbits. Temperature increases in albino rabbits were 1.5 times higher with subretinal blood than without it. Choroidal blood flow generally did not affect measured retinal temperature increases. CONCLUSIONS: The results confirm prior theoretical recommendations that clinicians should consider decreasing TTT power settings in darkly pigmented eyes and proceed with caution in those with subretinal hemorrhage or pigment clumping.