Reduced use of emergency care and hospitalization in patients with post-stroke cognitive impairment treated with traditional Chinese medicine.

BACKGROUND: The effect of traditional Chinese medicine (TCM) on the outcomes of dementia remains unclear. Our purpose is to compare the use of emergency care and hospitalization in patients with post-stroke cognitive impairment (PSCI) with or without treatment of TCM. METHODS: In a stroke cohort of 67 521 patients with PSCI aged over 40 years obtained from the 23 million people in Taiwan's national health insurance between 2000 and 2007, we identified 6661 newly diagnosed PSCI patients who were treated with TCM and 6661 propensity score-matched PSCI patients who were not treated with TCM. Under the control of immortal time bias, we calculated the adjusted rate ratios (RRs) and 95% CIs of the 1-year use of emergency care and hospitalization associated with TCM. RESULTS: The means of the emergency care medical visits (0.40 ± 0.98 vs. 0.47 ± 1.01, P = 0.0001) and hospitalization (0.72 ± 1.29 vs. 0.96 ± 1.49, P < 0.0001) were lower in the PSCI patients treated with TCM than in those without the TCM treatment. The RRs of emergency care and hospitalization associated with TCM were 0.87 (95% CI = 0.82-0.92) and 0.81 (95% CI = 0.78-0.84), respectively. The PSCI patients treated with a combination of acupuncture and herbal medicine had the lowest risk of emergency care visits and hospitalization. CONCLUSIONS: Our study raises the possibility that TCM use was associated with reduced use of emergency care and hospitalization after PSCI. However, further randomized clinical trials are needed to provide solid evidence of this benefit and identify the underlying mechanism.

Effects of red yeast rice prescription (LipoCol Forte) on adverse outcomes of surgery.

BACKGROUND: The influence of red yeast rice (RYR) on perioperative outcome remains unknown. AIM: We aimed to compare the complications and mortality after surgery between patients treated with and without RYR prescription. DESIGN: In this surgical cohort study of 3.6 million surgical patients who underwent major inpatient surgeries, 2581 patients who used RYR prescription pre-operatively were compared with 25 810 non-RYR patients selected by matching for age and sex. METHODS: Patients' demographics and medical conditions were collected from the claims data of the National Health Insurance in Taiwan. Complications and mortality after major surgeries in association with RYR prescription were investigated by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) by multiple logistic regression. RESULTS: Compared with patients without RYR prescription, patients prescribed RYR had lower risks of post-operative bleeding (OR 0.36, 95% CI 0.15-0.89), pneumonia (OR 0.54, 95% CI 0.36-0.83), stroke (OR 0.66, 95% CI 0.47-0.92) and 30-day in-hospital mortality (OR 0.37, 95% CI 0.15-0.92). Decreased risk of intensive care (OR 0.64, 95% CI 0.54-0.77), shorter length of hospital stay (P < 0.001) and lower medical expenditures (P = 0.0008) during the index surgical admission were also noted for patients with RYR prescription compared to those for patients without RYR prescription. CONCLUSIONS: This study showed a potentially positive effect of RYR on outcomes after major surgeries. However, patient non-compliance for taking medication should be noted. Our findings require future prospective studies to validate RYR prescription for improving perioperative outcomes.

Risk factors and outcome for colistin-resistant Acinetobacter nosocomialis bacteraemia in patients without previous colistin exposure.

The clinical characteristics of patients with colistin-resistant Acinetobacter baumannii bacteraemia have been documented, but those of patients with bacteraemia caused by other Acinetobacter species remain unknown. Previous exposure to colistin has been shown to be associated with the emergence of colistin resistance, but may be not the only predisposing factor. In the current study, we highlight the risk and outcome of patients without previous exposure to colistin who acquired colistin-resistant Acinetobacter nosocomialis (ColRAN) bacteraemia. This 11-year single-centre retrospective study analysed 58 patients with ColRAN bacteraemia and 213 patients with colistin-susceptible A. nosocomialis (ColSAN) bacteraemia. Antimicrobial susceptibilities were determined with an agar dilution method. The clonal relationship of ColRAN isolates was determined with pulsed-field gel electrophoresis. A conjugation mating-out assay was conducted to delineate the potential transfer of colistin resistance genes. Multivariable analysis was performed to evaluate the risk factors for ColRAN bacteraemia. Chronic obstructive pulmonary disease (COPD) was independently associated with ColRAN bacteraemia (OR 3.04; 95% CI 1.45-6.37; p 0.003). Patients with ColRAN bacteraemia had higher APACHE II scores, but the two groups showed no significant differences in 14-day mortality (10.3% vs. 10.3%) or 28-day mortality (15.5% vs. 15.0%). ColRAN isolates had greater resistance than ColSAN isolates to all antimicrobial agents except for ciprofloxacin (0% vs. 6.6%). There were 16 different ColRAN pulsotypes, and two major clones were found. Colistin resistance did not transfer to colistin-susceptible A. baumannii or A. nosocomialis. These results show that COPD is an independent risk factor for acquisition of ColRAN bacteraemia. The mortality rates were similar between patients with ColRAN and ColSAN bacteraemia.

Interventions for relieving pain associated with panretinal photocoagulation: a prospective randomized trial.

PURPOSE: To evaluate the efficacy of pain relief by oral diazepam, acetaminophen, mefenamic acid, intramuscular ketorolac tromethamine, and peribulbar anaesthesia in panretinal photocoagulation (PRP). METHODS: A total of 220 patients with proliferative diabetic retinopathy requiring PRP treatment were enrolled in this study. Before laser treatment, the patients were allocated randomly to one of eight groups: group 1: diazepam (n=22), group 2: acetaminophen (n=21), group 3: mefenamic acid (n=21), group 4: diazepam and acetaminophen (n=22), group 5: diazepam and mefenamic acid (n=22), group 6: peribulbar anaesthesia with lidocaine (n=23), group 7: intramuscular injection of ketorolac tromethamine (n=22), group 8: placebo (n=67). Pain after the laser treatment was assessed by a verbal descriptive scale. Blood pressure and heart rate were measured before and after laser treatment. RESULTS: Patients receiving peribulbar anaesthesia had a significantly lower pain score than the control group (P<0.0001). Additionally, the peribulbar anaesthesia-treated group had the significantly least PRP-associated rise in either systolic (P=0.043) or diastolic blood pressure rates (P=0.030). There were no significant differences in pain score using other anesthetic agents when compared with the control group. There were no significant changes in heart rate after PRP treatment. CONCLUSION: Peribulbar anaesthesia is effective in reducing pain and blood pressure increase after PRP treatment. Oral diazepam, mefenamic acid, and acetaminophen (either alone or in combination with each other) are not effective in preventing PRP treatment-associated pain. Intramuscular injection of ketorolac tromethamine is also not effective in reducing PRP-associated pain.

Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53.

p53 tumor suppressor is a transcription factor that functions, in part, through many of its downstream target genes. We have identified a p53-inducible gene by performing mRNA differential display on IW32 murine erythroleukemia cells containing a temperature-sensitive p53 mutant allele, tsp53(Val-135). Sequence analysis of the full-length cDNA revealed its identity as the mouse homologue of the human thiamine transporter 1 (THTR-1). Induction of the mouse THTR-1 (mTHTR-1) mRNA was detectable as early as 1 h at 32.5 degrees C; upon shifting back to 38.5 degrees C, mTHTR-1 transcript was rapidly degraded with a half-life of less than 2 h. Elevation of mTHTR-1 expression was found in DNA damage-induced normal mouse embryonic fibroblast cells, but not in p53(-/-) mouse embryonic fibroblast cells, suggesting that mTHTR-1 induction was p53-dependent. A region within the first intron of the mTHTR-1 gene bound to p53 and conferred the p53-mediated transactivation. Furthermore, increased thiamine transporter activities were found in cells overexpressing mTHTR-1 and under conditions of DNA damage or p53 activation. Our findings indicate that p53 may be involved in maintaining thiamine homeostasis through transactivation of THTR-1.

Induction of cytochromes P450 1A1 and 1B1 by emodin in human lung adenocarcinoma cell line CL5.

Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is an active compound of many laxative herbal drugs. The present study aimed to determine the effects of emodin on cytochrome P450 (P450)-dependent monooxygenases of human lung adenocarcinoma CL5 cells. Treatment of CL5 cells with 100 microM emodin for 24 h induced benzo[a]pyrene hydroxylation, 7-ethoxyresorufin O-deethylation, and 7-ethoxycoumarin O-deethylation activities of S9 fractions. Immunoblot analysis of CL5 S9 proteins revealed that emodin induced proteins immunorelated to P450s 1A1 and 1B1. Northern blot analysis of total cellular RNA showed that emodin induced P450s 1A1 and 1B1 mRNA levels in CL5 cells. These inductive effects on P450 monooxygenase activity, protein, and mRNA were concentration- and time-dependent. Addition of emodin to CL5 cell microM S9 inhibited its 7-ethoxycoumarin O-deethylation activity. Treatment of CL5 cells with 10 microM 3-methylcholanthrene for 24 h induced monooxygenase activity and P450s 1A1 and 1B1 proteins and mRNA levels. Treatment of the lung cells with 100 microM emodin or purpurin (1,2,4-trihydroxyanthraquinone) for 24 h produced greater induction of P450s 1A1 and 1B1 mRNA than did anthraflavic acid (2,6-dihydroxyanthraquinone) or anthraquinone. The emodin treatment induced P450s 1A1 and 1B1 mRNA in human lung carcinoma NCI-H322 and breast cancer MCF-7 cells. Emodin induced P450 1A1, but not 1B1, mRNA in human hepatoma HepG2 cells. The present study demonstrates that emodin is an inducer of P450s 1A1 and 1B1 protein and mRNA in human lung adenocarcinoma CL5 cells. Modulation of P450 by emodin may be an important factor affecting metabolism and toxicity of the hydroxyanthraquinone in humans.

Novobiocin in combination with high-dose chemotherapy for the treatment of advanced breast cancer: a phase 2 study.

We conducted the first phase 2 and pharmacologic study to evaluate the combination of novobiocin (a coumeromycin antibiotic that has been shown to augment alkylating agent cytotoxicity in experimental models) and high-dose cyclophosphamide and thiotepa followed by autologous marrow support in women with chemosensitive advanced breast cancer. Its aims were (1) to determine progression-free survival (PFS) and overall survival (OS), (2) to evaluate the pharmacokinetics of cyclophosphamide and thiotepa, and (3) to measure the ability of novobiocin to reverse alkylator drug resistance in vitro. Forty-one women with chemotherapy-responsive advanced breast cancer received cyclophosphamide (4 g/m2) for peripheral blood stem cell mobilization (treatment 1) followed by high-dose cyclophosphamide (1.5 g/m2 per day for 4 days), thiotepa (200 mg/m2 per day for 4 days), and novobiocin (4 g/day orally for 7 days) (treatment 2) and autologous marrow support. The median PFS was 10 months (range, 0.2-70.6 months) and OS, 21.5 months (range, 0.2-70.6 months). There was no statistically significant relationship between PFS or OS and area-under-the-curve values of cyclophosphamide, thiotepa, or 4-hydroxycyclophosphamide. Patient plasma samples (n = 12) obtained during novobiocin therapy were able to reverse alkylator drug resistance in an in vitro colony-forming assay. Correlative laboratory studies in an in vitro model system demonstrated that patient plasma after novobiocin treatment resulted in the magnitude of resistance reversal that had been predicted by prior preclinical experiments. Clinically, however, this activity of novobiocin did not translate into a substantial increase in PFS or OS compared with historical controls treated with high-dose alkylator therapy alone.

Chemical constituents and biological activities of the fruit of Zanthoxylum integrifoliolum.

Through continuing studies on the chemical constituents and antiplatelet aggregation principles of the fruit of the Formosan Zanthoxylum integrifoliolum, four new compounds-including two new lignans, (+)-pinoresinol-di-3,3-dimethylallyl ether (1), and (+)-pinoresinol-3,3-dimethylallyl ether (2); zanthonitrile (3), and one new flavonoid, 3,5-diacetyltambulin (4)-and 18 known compounds were isolated from the CHCl3-soluble fraction. Their structures were elucidated on the basis of spectral data and chemical evidence. Among the isolates, including the previously reported isobutylamides, 13 compounds showed strong in vitro antiplatelet aggregation activity, with only (-)-tetrahydroberberine showing weak vasorelaxing effect in high potassium- or norepinephrine-induced contraction of rat aorta.

Evaluation of peribulbar anesthesia in encircling scleral buckle surgery and its postoperative pain course.

BACKGROUND: Retrobulbar anesthesia is considered effective in ocular surgery but it can give rise to serious complications. We used peribulbar anesthesia with sub-Tenon's irrigation to perform encircling scleral buckling for retinal detachment, as it could reduce the complications caused by retrobulbar anesthesia. We also recorded the course of pain for 72 hours after surgery. METHODS: Thirty patients who were diagnosed with rhegmatogenous retinal detachment were treated with an encircling scleral buckle. The surgery was performed with peribulbar anesthesia with occasional sub-Tenon's irrigation. We evaluated the patient's pain with a visual analogue scale after surgery at 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours. RESULTS: In 24 cases (80%), the anesthesia was complete with the peribulbar block. Only 6 patients (20%) needed sub-Tenon's irrigation and four of them felt no pain after augmentation. Although all the surgical procedures proceeded without problem, two of the patients felt pain and were uncomfortable during the surgery. No serious complications occurred. The course of pain peaked 6 hours after surgery when 26 patients (86.7%) felt pain and 12 patients (40%) were uncomfortable (pain score > or = 5). Forty-eight hours after surgery, 9 patients (30%) still felt pain but no one felt uncomfortable. CONCLUSION: Peribulbar anesthesia can be used safely in encircling scleral buckling for retinal detachment. The postoperative pain is maximal 6 hours after surgery and becomes mild (pain score < or = 4) after 48 hours.

Phase I and pharmacologic study of the alkylating agent modulator novobiocin in combination with high-dose chemotherapy for the treatment of metastatic breast cancer.

PURPOSE: Resistance to alkylators may potentially be overcome by drugs that inhibits DNA repair, thus improving the efficacy of high-dose chemotherapy. This trial was performed to determine if novobiocin, an agent that inhibits DNA repair, could be given with high-dose alkylators. Study aims were to define the toxicities and maximal-tolerated dose (MTD) of novobiocin and the pharmacokinetics of novobiocin and high-dose cyclophosphamide and thiotepa. PATIENTS AND METHODS: Thirty-eight women with responsive metastatic breast cancer received high-dose cyclophosphamide (3 to 6 g/m2 over 4 days), thiotepa (400 to 800 mg/m2), and novobiocin (0.5 to 5.0 g/d x 7, orally) with autologous marrow support. Toxicity was monitored. The pharmacology of novobiocin, cyclophosphamide, and thiotepa was evaluated. RESULTS: There were no toxic deaths. The MTD of novobiocin was 4 g/d. All seven patients treated at 5 g/d developed grade III/IV mucositis and vomiting. The severity of mucositis correlated with the plasma levels of novobiocin. Other severe toxicities were not observed. Plasma novobiocin levels > or = 100 micrograms/mL, which are associated with reversal of drug resistance in animal models, were consistently seen at dose levels greater than 2 g. The dispositions of cyclophosphamide and thiotepa were not altered by novobiocin. CONCLUSION: Novobiocin may be given with high-dose alkylators in doses that produce plasma levels that augment the activity of these cytotoxics in experimental models. The pharmacology of high-dose cyclophosphamide and thiotepa is unaffected. Novobiocin 4 g/d orally for 7 days is recommended for future study.

Difference in efficacy of the Cell Saver in coronary bypass grafting surgery and cardiac valvular reoperations.

The efficacy of the Cell Saver in reducing transfusion requirements in patients who underwent either coronary artery bypass grafting (CABG) or reoperation for valvular replacement (Redo) were prospectively studied in 112 patients. In 41 patients, the Cell Saver was used from the beginning of the surgery (group 1), and in the other patients, no blood conservation techniques were undertaken (group 2). Perioperative hematological profile, postoperative chest tube drainage and transfusion requirements were examined in all patients. More red cells could be retrieved from the Redo patients than from the CABG patients (p < 0.05) during operation. The use of the Cell Saver in CABG patients reduced the total amount of blood transfusion required (p < 0.001). However, in the Redo patients, the use of the Cell Saver did not reduce the transfusion requirements during hospitalization. Furthermore, the amount of platelet concentrates transfused in the group 1 Redo patients was greater than the group 2 Redo patients. The use of the Cell Saver did not increase the postoperative chest tube drainage in either the CABG or the Redo patients. We conclude that the Cell Saver is useful in CABG patients, as far as the reduction of transfusion requirements is concerned; however, its efficacy in reducing transfusion requirements for Redo patients is questionable.

1,25-Dihydroxyvitamin D3 interaction with dexamethasone and retinoic acid: effects on procollagen messenger ribonucleic acid levels in rat osteoblast-like cells.

We previously have reported that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], dexamethasone, and retinoic acid inhibit collagen synthesis in rat osteoblast-like cell primary cultures. We also have found that dexamethasone increases 1,25-(OH)2D3 receptor levels in these cells. Furthermore, this increase in 1,25-(OH)2D3 receptor level is paralleled by an enhanced inhibition of collagen synthesis when dexamethasone and 1,25-(OH)2D3 are used in combination. In contrast, retinoic acid at high doses decreases 1,25-(OH)2D3 receptor level in rat osteoblast-like cells and attenuates 1,25-(OH)2D3 inhibition of collagen synthesis. In the present study, we have used a [32P]cDNA probe for rat pro alpha 1 (I) to determine if these osteotropic agents act by modulating steady state procollagen mRNA levels. Hybridization with a [32P]cDNA probe for human actin was used as a control. We find that the steady state levels of procollagen mRNA are decreased in all cases, while there are negligible changes in actin mRNA levels. Dexamethasone, at the low dose of 13 nM, acts synergistically with 1,25-(OH)2D3 in decreasing procollagen mRNA levels. The effects of retinoic acid and 1,25-(OH)2D3 are additive at low doses (13 and 130 nM); however, at a high dose of retinoic acid (1.3 microM), combined treatment with 1,25-(OH)2D3 does not reduce procollagen mRNA levels beyond the decrease due to retinoic acid alone. The reduction in procollagen mRNA level after each of these treatments falls in the same range as inhibition of collagen synthesis measured at the protein level. These data suggest that the synthesis of collagen under these treatments is controlled primarily through modulation of steady state procollagen mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitotic progression in stamen hair cells of Tradescantia is accelerated by treatment with ruthenium red and Bay K-8644.

The normally predictable duration of metaphase in stamen hair cells from the spiderwort, Tradescantia virginiana, is shortened significantly by treatment during prometaphase with either ruthenium red or Bay K-8644. Ruthenium red is an inhibitor of Ca2+ translocation and Bay K-8644 is a Ca2+-channel agonist. Their action on mitotic progression appears to involve a rise in the cytosolic Ca2+ level that in turn has a pronounced effect on the duration of metaphase. The timing of addition of ruthenium red for accelerated progression through metaphase is less critical than that for Bay K-8644 which will promote metaphase progression only if added 0 to 12 min after nuclear envelope breakdown. In contrast, ruthenium red can be added at any time from approximately 10 min prior to nuclear envelope breakdown up to 25 min afterward. A reduction of extracellular Ca2+ is sufficient by itself to prolong the duration of metaphase in stamen hair cells, but the duration of metaphase by ruthenium red or Bay K-8644 is significantly shortened in identical solutions with Ca2+ buffered at levels greater than 1 microM. Metaphase progression rates with either agent are independent of changes in extracellular Mg2+ levels. Correlated with the precocious entry into anaphase was rapid formation of the spindle and a marked reduction in spindle rotation during metaphase. Interestingly, we observed a modest increase in the rate of anaphase chromosome separation, but the appearance of cell plate vesicles at the site of incipient cell plate formation occurred normally approximately 19 min after anaphase onset. Similarly, the initial appearance of cell plate vesicles in Bay K-8644 was normal, approximately 19 min after the onset of anaphase. These results further implicate shifts in cytosolic Ca2+ in the regulation of mitotic events.