Risk of extrathymic cancer in patients with myasthenia gravis in Taiwan: a nationwide population-based study.

BACKGROUND AND PURPOSE: The relationship between myasthenia gravis (MG) and extrathymic malignancies has not been determined. This study aimed to explore the risk of extrathymic malignancy in patients with MG based on a nationwide population-based dataset. METHODS: We identified 2614 patients with MG from the Taiwan National Health Insurance database between 1997 and 2005 and compared the incidence rates of extrathymic malignancies with 15, 684 randomly selected age-, sex-, and comorbidity-matched subjects without MG. Both cohorts were followed until the end of 2009. Cox proportional hazard model was used to evaluate the predictors of extrathymic malignancy in the MG cohort, including age, sex, comorbidities, and prescription drugs. RESULTS: After an average follow-up of 8 years, the MG cohort had a higher risk of extrathymic cancers with an incidence rate ratio (IRR) of 1.38 (95% CI 1.12-1.68, P = 0.002) than the control cohort. Although breast cancer was the most common cancer found, no statistically significant relationship between MG and any specific malignancy was observed. Cox multivariate proportional hazards analysis showed that only age (HR = 1.05, 95% CI 1.04-1.06, P < 0.001) and liver cirrhosis (IRR = 3.85, 95% CI 1.22-12.14, P = 0.021) were predictors of extrathymic cancers in the MG cohort. CONCLUSIONS: Our study showed that patients with MG had an increased risk of extrathymic malignancy in a follow-up of 8 years, but no specific susceptibility to certain malignancies was found.

Analysis of three lupane type triterpenoids in Helicteres angustifolia by high-performance liquid chromatography.

Kang-chih-ma is the dried roots and stems of Helicteres angustifolia (Sterculiaceae) and a commonly used folk herbal drug in Taiwan. It possesses antidotal, analgesic, anti-inflammatory and anti-bacterial effects and is also known as a kind of tumor inhibitory plant. To evaluate the quality of H. angustifolia, a simple, rapid and accurate high-performance liquid chromatographic (HPLC) method was developed for the assay of three lupane type triterpenes: 3beta-acetoxy-27-benzoyloxylup-20(29)-en-28-oic acid methyl ester (methyl helicterate), 3beta-acetoxy-27-benzoyloxylup-20(29)-en-28-oic acid, and 3beta-acetoxy-27-(p-hydroxyl) benzoyloxylup-20(29)-en-28-oic acid methyl ester. The present HPLC system used an Inertsil ODS-2 column by gradient elution with acetonitrile and water as the mobile phase and detected at UV 230 nm. Regression equations revealed good linear relationships (correlation coefficients: 0.9922-0.9997). The relative standard deviations of these three constituents ranged between 1.05-3.14% (intraday) and 2.12-4.38% (interday). The contents of these three constituents of the heartwood and the bark of the roots of H. angustifolia in five different samples have also been determined.

An intervention trial to inhibit the progression of precancerous gastric lesions: compliance, serum micronutrients and S-allyl cysteine levels, and toxicity.

Gastric cancer is the second most frequent cause of death from cancer in the world and the leading cause of death from cancer in China. In September 1995, we launched a randomized multi-intervention trial to inhibit the progression of precancerous gastric lesions in Linqu County, Shandong Province, an area of China with one of the world's highest rates of gastric cancer. Treatment compliance was measured by pill counts and quarterly serum concentrations of vitamin C, vitamin E and S-allyl cysteine. In 1999, toxicity information was collected from each trial participant to evaluate treatment-related side-effects during the trial. Compliance rates were 93% and 92.9% for 39 months of treatment with the vitamins/mineral and garlic preparation, respectively. The means for serum concentrations of vitamins C and E were 7.2 microg/ml and 1695 microg/dl among subjects in the active treatment groups compared with 3.1 microg/ml and 752 microg/dl among subjects in the placebo treatment group, respectively. No significant differences in side-effects were observed between the placebo treatment group and the vitamins/mineral and garlic preparation treatment groups during the 39-month trial period.

Modifier effects on supercritical CO2 extraction efficiency of cephalotaxine from Cephalotaxus wilsoniana leaves.

The effects of modifiers such as methanol, water, diethylamine in methanol (10 v/v %), and diethylamine in water (10 v/v %) were investigated at three different concentrations (1, 5, and 10 v/v %) of the modifiers in supercritical CO2 (SC-CO2) in order to enhance the supercritical fluid extraction (SFE) efficiency of cephalotaxine from Cephalotaxus wilsoniana leaves. Among the modifiers employed, methanol basified with diethylamine was found to greatly enhance the extraction efficiency relative to any other modifiers employed. The results suggest that cephalotaxine in plant matrices may be readily changed from SC-CO2-insoluble salt to SC-CO2-soluble free base by basified modifiers. In addition, SC-CO2 modified with basified methanol could enhance the extraction efficiency of cephalotaxine more than 30% when compared to the conventional organic solvent extraction.

Inhibition of phospholipase cgamma1 and cancer cell proliferation by triterpene esters from Uncaria rhynchophylla.

Investigation of the hooks of Uncaria rhynchophylla resulted in isolation of six phospholipase Cgamma1 (PLCgamma1) inhibitors (1-6). The structures of these compounds were elucidated as pentacyclic triterpene esters by spectroscopic and chemical analysis. Three of them, namely uncarinic acids C (1), D (2), and E (3), are newly reported as natural products. All the compounds showed dose-dependent inhibitory activities against PLCgamma1 in vitro with IC(50) values of 9.5-44.6 microM and inhibited the proliferation of human cancer cells with IC(50) values of 0.5-6.5 microg/mL.

Minimal toxicity to myeloid progenitor cells of weekly 24-hr infusion of high-dose 5-fluorouracil: direct evidence from colony forming unit-granulocyte and monocyte (CFU-GM) clonogenic assay.

Although very high doses of 5-fluorouracil was used in the weekly 24-h infusion, high-dose 5-fluorouracil (2600 mg/m2/week) and leucovorin (500 mg/m2/week) protocol, myelosuppression was surprisingly low. The current study was conducted to investigate the possible mechanism underlying the low myelosuppression. To mimic the clinical situation, peripheral blood progenitor cells collected from 12 patients were used for colony forming unit-granulocyte and monocyte clonogenic assay; and 2 representative modes of 5-fluorouracil exposure (30 min. versus 24 hr) were examined for cytotoxic effects on human myeloid progenitor cells. Previous pharmacokinetic studies have estimated the concentrations of 5-fluorouracil in the bone marrow to be 200-400 microM and 1-2 microM for the 30 min. infusion (600-900 mg/m2) and the 24 hr-infusion (1000-2000 mg/m2) regimens, respectively. The results of our colony-forming unit-granulocyte and monocyte clonogenic assay showed that 24-hr exposure to 5-fluorouracil (2 microM) and 30 min. exposure to 5-fluorouracil (100 microM) resulted in 27.2% and 78.2% inhibition of the colony formation, respectively. Our data provided direct evidence which may explain why myelotoxicity is significantly less in weekly 24 hr infusion of fluorouracil than in the conventional bolus regimens.

The evaluation of the therapeutic effect of tao-shang-tsao on alpha-naphthylisothiocyanate and carbon tetrachloride-induced acute liver damage in rats.

The hepatoprotective effects of Tao-shang-tsao, Ixeris laevigata Sch.-Bip. var. oldhami Kitam., were studied on cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT, 100 mg/10 ml/kg, in olive oil, i.p.) and acute hepatitis induced by carbon tetrachloride (20% CCl4/olive oil, 1.5 ml/kg, i.p.) in rats by post-treatment with the crude methanolic extracts of I. laevigata (0.3, 1.0, and 2.0 g/kg) orally in the therapeutic model. Hepatoprotective activity was monitored by estimating the serum transaminases concentrations and histopathological changes in the livers of experimental rats. It was found that the I. laevigata extract significantly decreased the acute elevation of serum transaminases by biochemical examination. According to pathohistological studies in the liver of experimental rats, the crude I. laevigata extract ameliorates the central necrosis, fatty change or proliferation of bile duct epithelium focal necrosis caused by ANIT or CCl4-induced hepatitis rats.

The possible role of c-fos protein in hypothalamus in sleep disturbance in chronic uremic rats.

Sleep disturbance is very common in patients with chronic renal failure, but its mechanism is not clear. The activity of c-fos protein (FOS) in ventrolateral preoptic neurons (VLPO) is associated with the sleep pattern. The purpose of this study was to evaluate the relationship between sleep disturbance and the expression of FOS in VLPO of chronic uremic rats. Chronic uremia was induced by the 5/6 nephrectomized model. The movements of the rats were measured with infrared monitoring during the daytime (8.00-20.00) and nighttime (20.00-8.00). Rats were killed at 10.00 or 16.00 h for the daytime (uremic rats 7, control 8) and at 22.00 h for the nighttime (uremic rats 7, control 9). The expression of FOS in VLPO was examined with the immunohistochemical method. The number of recorded daytime movements in uremic rats was significantly higher than in control rats (458 +/- 185 vs. 222 +/- 41, p < 0.001), but the number of recorded nighttime movements in uremic rats was lower than in control rats (949 +/- 430 vs. 1,618 +/- 261, p < 0.001). In the daytime, the number of FOS immunoreactive cells in uremic rats was lower than in control rats (18.4 +/- 5.3 vs. 42.8 +/- 6.3, p < 0. 001), but there was no difference between two groups in the nighttime (10.8 +/- 8.4 vs. 12.5 +/- 5.1, p = 0.62). There was a strong negative correlation between the number of recorded movements and the number of FOS immunoreactive cells in VLPO (r = -0.700, p < 0.001). This finding suggests that sleep disturbances in chronic uremic rats might be related to the decreased expression of FOS in VLPO.

Analysis and confirmation of synthetic anorexics in adulterated traditional Chinese medicines by high-performance capillary electrophoresis.

Six synthetic anorexics, clobenzorex, diethylpropion, fenfluramine, methamphetamine, phenylpropanolamine and phentermine, which can be found as adulterants in traditional Chinese medicines were assayed simultaneously by high-performance capillary electrophoresis. The electrolyte was a buffer solution containing 120 mM phosphate buffer (NaH2PO4/H3PO4, pH 2.0) and 15% acetonitrile. Applied voltage was 16 kV and temperature was 30 degrees C. Fluoren-2,7-diammonium chloride was used as an internal standard and detector set at 200 nm. The recoveries of the synthetic anorexic adulterants in traditional Chinese medicinal formula using C8-SCX mixed solid-phase extraction were studied. Several traditional Chinese medicinal powders obtained from clinics were also studied by the above HPCE method and confirmed by GC-MS. Clobenzorex, diethylpropion and fenfluramine were found and determine in these samples.

Studies of the chemical structure of gangliosides in deer antler, Cervus nippon.

The biological activity of deer antler has been considered to originate in the gangliosides, although the structures of gangliosides have not been well elucidated. The quality of deer antler as an Asian folk medicine has often been evaluated by the amount of gangliosides contained in the crude drug. We have completed the structural determination of five gangliosides isolated from deer antler in the present study. Five ganglioside fractions were isolated and purified from deer antler, Cervus nippon, by the Folch-Suzuki partition method, DEAE-Sephadex A-25, and further by silica gel column chromatography. High field proton nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry, and fast atom bombardment-mass spectrometry studies characterized the isolated ganglioside fractions. GM3 and GD3 were present in the isolated ganglioside fractions. Samples were hydrolyzed in trifluoroacetic acid for direct compositional analysis and analyzed for sialic acid and neutral sugar without prior derivatization. Separation of the monosaccharides was achieved by HPLC on a Dionex CarboPac column eluted at a high pH. The resolved monosaccharides were identified using standard monosaccharides by pulsed amperometric detection. N-Acetyl GM3 (Neu5Ac), N-glycolyl GM3 (Neu5Gc), and N-acetyl GD3 (Neu5Ac) were present in the antler. The major ceramide moiety was composed of C16:0 or C22:0 fatty acids along with either C18 sphingosine or C20 eicosasphingosine.

Solid-phase extraction for the determination of caffeine in traditional Chinese medicinal prescriptions containing Theae folium by high performance liquid chromatography.

A high performance liquid chromatographic method in combination with C-18 reverse phase solid-phase extraction (SPE) was developed for determination of caffeine (CA) in traditional Chinese medicinal prescriptions which contain Theae folium. The frequently used prescriptions include Shin-Yi-San, Chuan-Chyong-Char-Tyau-San, Tsang-Eel-San, San-Hwang-Shyr-Gau-Tang, Tzy-Shenn-Ming-Mu-Tang and Shiang-Chyong-San. The present HPLC system uses a Merck RP-select B column by isocratic elution with methanol and 1% (v/v) acetic acid (1:4) as the mobile phase and detected at UV 270 nm. 8-Chlorotheophylline was used as an internal standard. The extracts of prescriptions were treated by Supelclean LC-18 SPE tube for eliminating interferences. Blank decoctions of each prescription were also examined as a test for interferences. The recoveries of caffeine from the Chinese medicinal prescriptions ranged from 88.5 to 92.3%. The relative standard deviations of caffeine ranged between 0.86 and 1.97% (intraday) and 1.04 and 3.90% (interday). The contents of caffeine in standard decoctions ranged from 13.98 to 19.62 mg g(-1).

High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers.

High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg subcutaneous injection. There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (> or = 50,000/microL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.

Factorial trial of three interventions to reduce the progression of precancerous gastric lesions in Shandong, China: design issues and initial data.

In the fall of 1995, 3411 subjects in 13 rural villages in Linqu County, Shandong Province, China, began participating in a blinded, randomized 23 factorial trial to determine whether interventions can reduce the prevalence of dysplasia and other precancerous gastric lesions. One intervention is treatment for infection by Helicobacter pylori with amoxicillin and omeprazole. A second is dietary supplementation with capsules containing vitamin C, vitamin E, and selenium. A third is dietary supplementation with capsules containing steam-distilled garlic oil and Kyolic aged garlic extract. Investigators will evaluate histopathologic endpoints after gastroscopies with biopsies from seven standard sites in 1999. Initial data from pill counts and sampled blood levels of vitamin E, vitamin C, and S-allylcysteine indicate excellent compliance. Subjects have tolerated all interventions well, although 3.1% of those assigned to amoxicillin and omeprazole developed rashes, compared to 0.3% to those in the control group. Preliminary breath tests demonstrate substantial reductions in gastric urease activity, an indication of infection by Helicobacter pylori, among those assigned to amoxicillin and omeprazole.

Three new flavonoids and antiallergic, anti-inflammatory constituents from the heartwood of Dalbergia odorifera.

Three new flavonoids, (3R)-4'-methoxy-2',3,7-trihydroxyisoflavanone (11), 7-methoxy-3,3',4',6-tetrahydroxyflavone (18), and 2',7-dihydroxy-4',5'-dimethoxyisoflavone (22), were isolated from the heartwood of Dalbergia odorifera T. Chen. (Leguminosae), together with twenty-two known compounds, (S)-4-methoxydalbergione (1), cearoin (2), medicarpin (3), formononetin (4), sativanone (5), 3-hydroxy-9-methoxy-coumestan (6), meliotocarpan A (7), isoliquiritigenin (8), stevein (9), liquiritigenin (10), 3',4',7-trihydroxyflavanone (12), butein (13), 3'-hydroxymelanettin (14), koparin (15), bowdichione (16), fisetin (17), melanettin (19), sulfuretin (20), 3'-hydroxydaidzein (21), 3'-O-methylviolanone (23), xenognosin B (24), and dalbergin (25). These flavonoids were evaluated in antiallergic and anti-inflammatory tests. The results showed that (S)-4-methoxydalbergione (1) and cearoin (2) exhibited antiallergic activity while (S)-4-methoxydalbergione (1), cearoin (2), butein (13), koparin (15), bowdichione (16), 3'-O-methylviolanone (23), and xenognosin B (24) showed significant anti-inflammatory activity.

Helicobacter pylori infection, garlic intake and precancerous lesions in a Chinese population at low risk of gastric cancer.

BACKGROUND: Cangshan County of Shandong Province has one of the lowest rates of gastric cancer (GC) in China. While intestinal metaplasia (IM) and dysplasia (DYS) are less common in Cangshan than in areas of Shandong at high risk of GC, these precursor lesions nevertheless affect about 20% of adults age > or = 55. SUBJECTS AND SETTING: In order to evaluate determinants of IM and DYS in Cangshan County, a low risk area of GC a survey was conducted among 214 adults who participated in a gastroscopic screening survey in Cangshan County in 1994. METHOD: A dietary interview and measurement of serum Helicobacter pylori antibodies were performed. RESULTS: The prevalence of H. pylori was lowest (19%) among those with normal gastric mucosa, rising steadily to 35% for superficial gastritis (SG), 56% for chronic atrophic gastritis (CAG), 80% for IM, and 100% for DYS. The prevalence odds of precancerous lesions were compared with the odds of normal histology or SG. The odds ratio (OR) or CAG associated with H. pylori positivity was 4.2 (95% confidence interval [CI] : 1.7-10.0), while the OR of IM/DYS associated with H. pylori positivity was 31.5 (95% CI: 5.2-187). After adjusting for H. pylori infection, drinking alcohol was a risk factor for CAG (OR = 3.2, 95% CI: 1.1-9.2) and IM/DYS (OR = 7.8, 95% CI: 1.3-47.7). On the other hand, consumption of garlic showed non-significant protective effects and an inverse association with H. pylori infection. CONCLUSIONS: The findings of this study suggest that infection with H. pylori is a risk factor and garlic may be protective, in the development and progression of advanced precancerous gastric lesions in an area of China at relatively low risk of GC.

Supercritical carbon dioxide extraction of podophyllotoxin from Dysosma pleiantha roots.

Supercritical fluid extraction (SFE) was utilized to extract podophyllotoxin from the roots of Dysosma pleiantha. The extraction was carried out in the temperature range of 40-80 degrees C and the pressure range of 13.6-34.0 MPa with supercritical carbon dioxide. However, podophyllotoxin was not sufficiently extracted by pure supercritical carbon dioxide. Methanol was used as modifier to enhance the extraction yield of podophyllotoxin. As a result, SFE produced a higher recovery of podophyllotoxin than conventional 95% ethanol extraction.

Synthetic osteochondral replacement of the femoral articular surface.

We have studied damage to the tibial articular surface after replacement of the femoral surface in dogs. We inserted pairs of implants made of alumina, titanium and polyvinyl alcohol (PVA) hydrogel on titanium fibre mesh into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. We discuss the clinical implications of the possible use of this material in articular resurfacing and joint replacement.

Effects of Gastrodia elata and its active constituents on scopolamine-induced amnesia in rats.

The effects of the rhizome of Gastrodia elata Blume (Orchidaceae) (abbreviated as GE) and its active constituents on learning and memory by using the one-trial passive avoidance task were studied in rats. At the 1.0 g/kg dose administered for one week, the methanol extract of GE significantly prolonged the shortened step-through latency induced by scopolamine in the passive avoidance task. Furthermore, at the 50.0 mg/kg dose administered for one week, the ethyl acetate and n-butanol fractions of the methanol extract prolonged the shortened step-through latency induced by scopolamine in rats. Gastrodin, isolated from the n-butanol fraction of the methanol extract, and p-hydroxybenzyl alcohol, isolated from the ethyl acetate fraction of the methanol extract, also significantly prolonged the shortened step-through latency induced by scopolamine on the passive avoidance task. These results suggested that gastrodin and p-hydroxybenzyl alcohol may be the active constituents of GE.

Bone remodeling around implanted ceramics.

Bone formation and remodeling around implanted materials is influenced by the kind of material, its surface properties, and the anatomical site of implantation. In this study, differences in bone formation around three kinds of ceramics and the importance of the implant location in the tibia were investigated. In the first experiment, we placed three kinds of ceramics--alumina, zirconia and hydroxyapatite (HA)--into the medullary cavity of rabbit tibiae and examined histologically the time-dependent formation of bone around the materials for up to 24 weeks postoperatively. We found that bone formation depends on whether or not the materials are in direct contact with the endosteum. In the second experiment, the same three ceramic materials were implanted transcortically into rabbit tibiae. The bone formed around the implants was most abundant in regions adjacent to the periosteum, followed by the endosteum and the marrow cavity in the approximate ratios of 70%, 40%, and 10%, respectively. In these two experiments, the difference between bioactive and bioinert ceramics could be seen in the interface between the implanted material and the bone. It can be concluded that bone formation around these materials is related to the osteoconductivity of the materials and to the osteogenic capacity of the tissues.

Inhibition on platelet activation by shikonin derivatives isolated from Arnebia euchroma.

Acetylshikonin, teracrylshikonin, beta,beta-dimethylacrylshikonin and shikonin, isolated from Arnebia euchroma, inhibited collagen (10 micrograms/ml)-induced aggregation of washed rabbit platelets in a concentration-dependent manner with IC50 values of 2.1 +/- 0.2, 2.8 +/- 0.3, 4.2 +/- 0.5 and 10.7 +/- 0.7 microM, respectively. Acetylshikonin also inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA, 100 microM), U46619 (1 microM), platelet-activating factor (PAF, 3.6 nM) and thrombin (0.1 U/ml) in a concentration-dependent manner. The IC50 values of acetylshikonin on the inhibition of these four agonists-induced platelet aggregation were 3.1 +/- 0.4, 2.2 +/- 0.2, 8.0 +/- 0.6 and 12.7 +/- 1.0 microM, respectively. The thromboxane B2 formation caused by collagen, PAF and thrombin was inhibited by acetylshikonin, while formations of thromboxane B2 and prostaglandin D2 caused by AA were not inhibited. Acetylshikonin did not inhibit cyclooxygenase activity since it did not attenuate prostaglandin E2 formation after incubation of sheep vesicular gland microsomes with AA. Acetylshikonin suppressed both the rise of intracellular Ca2+ concentration and the generation of [3H]inositol monophosphate caused by these five aggregation inducers. Platelet cyclic AMP level was unaffected by acetylshikonin. These data indicate that acetylshikonin inhibits platelet activation by suppression of phosphoinositide breakdown.