Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

An investigation of the smoking behaviours of parents before, during and after the birth of their children in Taiwan

[[abstract]]Background: Although many studies have investigated the negative effects of parental smoking on children and Taiwan has started campaigns to promote smoke-free homes, little is known about the smoking behaviours of Taiwanese parents during the childbearing period. To help fill the gap, this study investigated Taiwanese parents' smoking behaviours before, during and after the birth of their children, particularly focusing on smoking cessation during pregnancy and relapse after childbirth. Methods: We used data from the Survey of Health Status of Women and Children, conducted by Taiwan's National Health Research Institutes in 2000. After excluding survey respondents with missing information about their smoking behaviours, our sample consisted of 3,109 women who were married at the time of interview and had at least one childbearing experience between March 1, 1995 and February 28, 1999. Data on parental smoking behaviour in the six months before pregnancy, during pregnancy, and in the first year after childbirth were extracted from the survey and analysed by descriptive statistics as well as logistic regression. Results: Four percent of the mothers and sixty percent of the fathers smoked before the conception of their first child. The educational attainment and occupation of the parents were associated with their smoking status before the first pregnancy in the family. Over 80% of smoking mothers did not quit during pregnancy, and almost all of the smoking fathers continued tobacco use while their partners were pregnant. Over two thirds of the women who stopped smoking during their pregnancies relapsed soon after childbirth. Very few smoking men stopped tobacco use while their partners were pregnant, and over a half of those who quit started to smoke again soon after their children were born. Conclusion: Among Taiwanese women who had childbearing experiences in the late 1990s, few smoked. Of those who smoked, few quit during pregnancy. Most of those who quit relapsed in the first year after childbirth. The smoking prevalence was high among the husbands of these Taiwanese women, and almost all of these smoking fathers continued tobacco use while their partners were pregnant. It is important to advocate the benefits of a smoke-free home to Taiwanese parents-to-be and parents with young children, especially the fathers. The government should take advantage of its free prenatal care and well-child care services to do this. In addition to educational campaigns through the media, the government can request physicians to promote smoke-free homes when they deliver prenatal care and well-child care. This could help reduce young children's health risks from their mothers' smoking during pregnancy and second-hand smoke at home

Healthcare costs associated with progressive diabetic retinopathy among National Health Insurance enrollees in Taiwan, 2000-2004

<p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy is one of the most common microvascular complications of diabetes and one of the major causes of adult visual impairment in national surveys in Taiwan. This study aimed to identify the healthcare costs of Taiwan's National Health Insurance program on behalf of diabetic patients with stable or progressive retinopathy.</p> <p>Methods</p> <p>A retrospective cohort study was conducted with 4,988 medication-using diabetic retinopathy subjects ≥ 40 years of age under National Health Insurance Program coverage between 2000 and 2004. Study cohort subjects were recorded as having diabetic retinopathy according to ICD-9-CM codes. States of diabetic retinopathy were strategically divided into stable and progressive categories according to subjects' conditions at follow-up in 2004. Expenditures were calculated and compared for the years 2000 and 2004.</p> <p>Results</p> <p>During the 4-year follow-up (2000 through 2004), 4,116 subjects (82.5%) of 4,988 diabetic subjects were in the stable category, and 872 (17.5%) were in the progressive category. Average costs of those in the normal category increased by US $48 from US$1921 in 2000 to US $1969 in 2004 (p = 0.594), whereas costs for those progressing from normal to non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) increased by US$1760, from US $1566 in 2000 to US$3326 in 2004 (p < 0.001). The PDR category had the highest average costs at US $3632 in 2000. The NPDR-to-PDR category experienced the greatest increase in costs at US$3482, from US $2723 in 2000 to US$6204 in 2004 (p = 0.042), and the greatest percentage of increase at 2.3% (2.2% when adjusted by comparing to normal category).</p> <p>Conclusions</p> <p>This large-scale longitudinal study provides evidence that increased healthcare costs are associated with progressive diabetic retinopathy among diabetic NHI enrollees in Taiwan.</p

Inhibition of Enterovirus 71 (EV-71) Infections by a Novel Antiviral Peptide Derived from EV-71 Capsid Protein VP1

Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC50 values ranging from 6–9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71

RASSF2, a potential tumour suppressor, is silenced by CpG island hypermethylation in gastric cancer

RASSF2, a member of the RASSF1 family, has recently been identified as a potential tumour suppressor. We examined methylation status in multiple regions which included the CpG island and spanned the transcription start site of RASSF2 in 10 gastric cancer cell lines, as well as 78 primary gastric cancers and corresponding non-neoplastic gastric epithelia. Hypermethylation of RASSF2 in at least one of the regions examined was detected in seven (70%) of the 10 cell lines; two (20%) exhibited hypermethylation in all the regions examined including the transcription start site and lost expression of RASSF2 mRNA, which could, however, be restored by 5-aza-2′ deoxycytidine treatment, while the other five (50%) cell lines exhibited hypermethylation at the 5′- and/or 3′- edge, with four of them expressing RASSF2 mRNA. In primary gastric cancers and corresponding non-neoplastic gastric epithelia, frequencies of RASSF2 methylation ranged from 29% (23 out of 78) to 79% (62 out of 78) and 3% (two out of 78) to 60% (47 out of 78), respectively, at different CpG sites examined. Methylation was frequently observed at the 5′- and 3′- edges, and became less frequent near the transcription start site in both the primary gastric cancers and corresponding non-neoplastic gastric epithelia. Hypermethylation near the transcription start site was mostly cancer-specific. We thus showed that RASSF2 is silenced by hypermethylation near the transcription start site in gastric cancer. Hypermethylation was found initially to occur at the 5′- and 3′- furthest regions of the CpG island in non-neoplastic gastric epithelia, to gradually spreads near the transcription start site to shut down RASSF2 expression, and ultimately to constitute a field-defect placing tissue increased risk for development of gastric cancer

A population study on the association between leisure time physical activity and self-rated health among diabetics in Taiwan

<p>Abstract</p> <p>Background</p> <p>There is strong evidence for the beneficial effects of physical activity in diabetes. There has been little research demonstrating a dose-response relationship between physical activity and self-rated health in diabetics. The aim of this study was to explore the dose-response association between leisure time physical activity and self-rated health among diabetics in Taiwan.</p> <p>Methods</p> <p>Data came from the 2001 Taiwan National Health Interview Survey (NHIS). Inclusion criteria were a physician confirmed diagnosis of diabetes mellitus and age 18 years and above (n = 797). Self-rated health was assessed by the question "In general, would you say that your health is excellent, very good, good, fair, or poor?" Individuals with a self perceived health status of good, very good, or excellent were considered to have positive health status.</p> <p>Results</p> <p>In the full model, the odds ratio (OR) for positive health was 2.51(95% CI = 1.53-4.13), 1.62(95% CI = 0.93-2.84), and 1.35(95% CI = 0.77-2.37), for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. Those with duration over 10 years (OR = 0.53, 95%CI = 0.30-0.94), heart disease (OR = 0.50, 95%CI = 0.30-0.85), and dyslipidemia (OR = 0.65, 95% CI = 0.43-0.98) were less likely to have positive health than their counterparts. After stratified participants by duration, those with a duration of diabetes < 6 years, the adjusted OR for positive health was 1.95(95% CI = 1.02-3.72), 1.22(95% CI = 0.59-2.52), and 1.19(95% CI = 0.58-2.41) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals. In participants with a duration of diabetes ≥ 6 years, total energy expenditure showed a gradient effect on self-perceived positive health. The adjusted OR for positive health was 3.45(95% CI = 1.53-7.79), 2.77(95% CI = 1.11-6.92), and 1.90(95% CI = 0.73-4.94) for those with a total weekly energy expenditure of ≥ 1000 kcal, between 500 and 999 kcal, and between 1 and 499 kcal, respectively, compared to inactive individuals.</p> <p>Conclusions</p> <p>Our results highlight that regular leisure activity with an energy expenditure ≧ 500 kcal per week is associated with better self-rated health for those with longstanding diabetes.</p

In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells

<p>Abstract</p> <p>Background</p> <p>Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This <it>in vitro </it>study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules.</p> <p>Methods</p> <p>The cytotoxicity, radiosensitising potential and cell cycle effect of MTA were investigated in A549 (NSCLC) and CAL-27 (SCCHN) cells. Using simultaneous or sequential exposure schedules, the cytotoxicity and radiosensitising effect of 24 h MTA combined with 1 h or 24 h dFdC were analysed.</p> <p>Results</p> <p>Including a time interval between MTA exposure and irradiation seemed favourable to MTA immediately preceding or following radiotherapy. MTA induced a significant S phase accumulation that persisted for more than 8 h after drug removal. Among different MTA/dFdC combinations tested, the highest synergistic interaction was produced by 24 h MTA followed by 1 h dFdC. Combined with irradiation, this schedule showed a clear radiosensitising effect.</p> <p>Conclusions</p> <p>Results from our <it>in vitro </it>model suggest that the sequence 24 h MTA → 1 h dFdC → RT is the most rational design and would, after confirmation in an <it>in vivo </it>setting, possibly provide the greatest benefit in the clinic.</p

Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells

CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133+) and CD133-negative cells (LC-CD133−) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133+ displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133+, unlike LC-CD133−, highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133+ to form spheres and can further facilitate LC-CD133+ to differentiate into LC-CD133−. In addition, knock-down of Oct-4 expression in LC-CD133+ can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133+ can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133+. Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133+ and malignant lung cancer

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012