Effects of oral continuous 17beta-estradiol plus norethisterone acetate replacement therapy on abdominal subcutaneous fat, serum leptin levels and body composition.

AIM: To evaluate the effects of oral continuous 17beta-estradiol plus norethisterone acetate (E2/NETA) replacement therapy on abdominal subcutaneous fat, serum leptin level (SLL) and body composition in postmenopausal women. MATERIALS AND METHODS: A 6-month, prospective, randomized, double-blind and placebo-controlled study was conducted. Forty-three healthy naturally postmenopausal women aged 43-65 years were randomly assigned to receive E2/NETA (2 mg E2 plus 1 mg NETA, n = 22) or placebo (n = 21). Fasting SLL by enzyme-linked immunosorbent assay, subcutaneous abdominal fat thickness (STh) by ultrasound and the anthropometric indices of body weight (BW), body mass index (BMI), waist and hip circumference (WC, HC) and waist-to-hip ratio (WHR) were recorded at the beginning and the end of the study. RESULTS: After 6 months of therapy, BW and SLL increased in the placebo group (p = 0.043 and 0.033, respectively). WC, HC and STh decreased significantly in the E2/NETA group (p = 0.002, 0.006 and 0.000, respectively) and they were also significantly lower in women receiving E2/NETA than in women taking placebo (p = 0.000, 0.034 and 0.000, respectively). At baseline, SLL and STh were positively correlated with all anthropometric indices except WHR. CONCLUSION: Oral continuous combined regimen of E2/NETA significantly reduced central fat accumulation as assessed by WC and STh, and attenuated the increase in SLL. The observed changes in SLL were highly and positively related to changes in STh. The oral continuous combined E2/NETA regimen appears to have protective effects on cardiovascular function and probably on metabolic diseases by its slimming effect upon WC in postmenopausal women.     

Arsenic trioxide–loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line

The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer.     

Sequential study on the treatment of moderate-to-severe chronic plaque psoriasis with mycophenolate mofetil and cyclosporin

BACKGROUND: There are numerous studies that individually evaluate the efficacy/effectiveness and toxicity of drugs in the systemic treatment of psoriasis. On the contrary, we can hardly find studies that compare each other. OBJECTIVE: To evaluate and compare the effectiveness and toxicity of mycophenolate mofetil and cyclosporin in chronic plaque psoriasis through a prospective, sequential, cross-over, non-randomized, two-phase, open-label study. PATIENTS/METHODS: Eight patients (five women and three men; mean age 57, range 35-78) with moderate-to-severe chronic plaque psoriasis were included in the study. They were treated with oral mycophenolate mofetil (30 mg/kg/day) over a period of 16 weeks. Following a variable washout period and after a new outbreak of the disease, oral cyclosporin was introduced at a dose of 4 mg/kg/day. During both treatment regimens, follow-up visits were performed at 3, 8 and 16 weeks. RESULTS: In both groups, the PASI started to decrease once treatment was begun. Cyclosporin was faster and statistically a lot more effective than mycophenolate mofetil, reaching a higher number of complete remissions and better percentages of PASI improvement from baseline (45.7%, 60.2% and 60.5% at 3, 8 and 16 weeks respectively for mycophenolate mofetil, and 89.7%, 95.3% and 95.3% respectively at the same intervals for cyclosporin). Cyclosporin was also more predictable in its action as the percentage of improvement along the follow-up visits had a much wider range for mycophenolate mofetil. Overall, the tolerability of both drugs was good. None of the patients had to discontinue treatment because of an adverse event. Two patients treated with cyclosporin showed increased plasma levels of creatinine. CONCLUSIONS: Cyclosporin is more effective, fast, and predictable in its effect than mycophenolate mofetil to control moderate-to-severe chronic plaque psoriasis. Both drugs are well tolerated in short courses of treatment.     

去除白细胞输血的临床意义

目的:评估去除白细胞输血的临床应用价值。方法:251例患者接受了去除白细胞红细胞悬液761U,(每人1￣8U不等),对其中200U红细胞悬液滤除白细胞前、后分别进行白细胞计数和血红蛋白测定,并对其输血反应进行了观察。结果:发现应用白细胞滤器后,其白细胞数比过滤前显著减低,过滤前、后白细胞数分别为(6.16±1.44)×109/L与(0.12±0.10)×109/L(P<0.01),血红蛋白过滤前、后无显著性差异,分别为:(161.58±23.31)g/L与(157.84±22.35)g/L,P>0.05。251例接受去白细胞受血者均未出现输血反应。结论:白细胞滤器能有效去除白细胞,去除白细胞能减少非溶血性输血反应。     

Transmission of Syphilis by Solid Organ Transplantation

Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.     

The pH of Exhaled Breath Condensate of Patients with Allograft Rejection After Lung Transplantation

Endogenous airway acidification, as assessed by the condensate pH, has been implicated in the pathophysiology of inflammatory airway diseases such as cystic fibrosis and asthma. The aim of this study was to investigate the pH of condensate in patients after lung transplantation (LTX). From the cohort of transplanted patients at our center, 83 patients (9 heart-lung transplantation, 48 double-lung transplantation, 26 single-lung transplantation) were recruited and analyzed in a cross-sectional manner: 26 patients were diagnosed with chronic rejection or bronchiolitis obliterans syndrome (BOS), 7 patients were diagnosed with acute rejection (AR) while 50 patients had no evidence of rejection according to the International Society for Heart and Lung Transplantation criteria. The condensate pH was significantly reduced in patients with BOS and AR when compared to patients without rejection and control subjects (5.8 +/- 0.5 and 6.2 +/- 0.4 versus 6.6 +/- 0.4 and 6.5 +/- 0 .4, respectively; p < 0.05). Moreover, there was a significant correlation between condensate pH levels and the BOS grade (r =-0.62; p < 0.01), the FEV(1) (r = 0.39; p < 0.01) and the total cell and neutrophil count in bronchoalveolar lavage fluid (r =-0.39 and r =-0.56, respectively; p < 0.01). Airway acidification occurs in BOS and may directly or indirectly reflect airway inflammation in patients with allograft rejection after LTX. Measuring condensate pH might thus be a new tool for the evaluation of rejection in lung transplant patients.     

Survivin在食管癌中的表达及其与bcl-2表达关系的相关研究

目的 探讨Survivin在食管癌组织中的表达及其与bc1-2蛋白表达的相关性。方法应用免疫组织化学SP法，检测Survivin、bc1-2蛋白在68例食管癌组织和20例正常食管组织中的表达。结果 Survivin蛋白在正常食管组织中低表达或不表达，68例食管癌组织中，49例表达阳性，占72．1％。Survivin蛋白表达与分化程度、淋巴结转移密切相关（P〈0．05）。食管癌组织bc1-2蛋白表达阳性、阴性组中，Survivin蛋白阳性表达率分别为94．7％（36／38）和43．3％（13／30），两者比较．差异有统计学意义（P〈0．05）。Survivin蛋白表达与bc1-2蛋白表达密切相关。结论 Survivin在食管癌组织中表达上调，通过抑制细胞凋亡，在食管癌的发生中起到重要作用；凋亡相关基因bc1-2的上调与Survivin的表达可能在食管癌变中起协同作用。     

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans.

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO). Methacholine and adenosine 5'-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n = 28). These results were compared with those of asthmatic (n = 30) and control children (n = 25). Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) of <16 mg x mL(-1), but only six (21.4%) were hyperreactive to AMP with a PC20 of <200 mg x mL(-1). All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges. Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 5'-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects.     

p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking.

The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption.