Concentration of fatty acid ethyl esters in hair of alcoholics: comparison to other biological state markers and self reported-ethanol intake

AIMS: In a variety of clinical and forensic situations long term use of alcohol must be monitored. In this project we explore the utility of fatty acid ethyl esters (FAEE) in this regard. Additionally, we propose a cut-off value of FAEE to distinguish teetotallers/moderate/social drinkers from alcoholics or individuals drinking at harmful levels. PATIENTS AND METHODS: FAEE levels from 18 alcohol-dependent patients in detoxification were contrasted with those of 10 social drinkers and 10 teetotallers. FAEE in hair were determined, using headspace solid phase microextraction and gas chromatography mass spectrometry. C(FAEE), as sum of the concentrations of four esters, was compared to a major FAEE, ethyl palmitate. PEth was measured in heparinized whole blood with a high pressure liquid chromatography (HPLC) method. Drinking validation criteria include self reports, phosphatidyl ethanol (PEth) in whole blood as well as the traditional markers of heavy drinking, gamma glutamyl transpeptidase (GGT), mean corpuscular volume (MCV) and carbohydrate deficient transferrin (CDT). RESULTS: Receiver-operating characteristic (ROC) curve analysis for C(FAEE), indicated a sensitivity of 100% and a specificity of 90% for a cut-off of 0.29 ng/mg. By using a cut-off of 0.4 ng/mg, C(FAEE) identified 94.4% correctly. C(FAEE) and ethyl palmitate were significantly associated (r = 0.945; P < 0.001) as were C(FAEE) and PEth (r = 0.527; P = 0.025). No significant correlation was found between C(FAEE) and total grams of ethanol consumed last month, blood-alcohol concentration at admission to the hospital, CDT, MCV, or GGT. Among the serum and blood markers, %CDT identified 47.1%, MCV 38.8% and GGT 72.2% of patients with chronic intake of higher amounts of ethanol correctly, whereas PEth achieved 100% accuracy. CONCLUSIONS: The data suggest that C(FAEE) is a potentially valuable marker of chronic intake of high quantities of ethanol. Furthermore, the results indicate that a reasonable and provisional FAEE cut-off to distinguish between social/moderate and heavy drinking/alcoholism in hair is 0.4 ng/mg.     

Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study

Melanoma is among the most chemotherapy-resistant malignancies. Numerous new agents have been developed that target specific molecules on cancer cells, including the monoclonal antibody trastuzumab, which targets Her2/neu and has been very beneficial in the treatment of breast cancer. There are conflicting reports in the literature about Her2/neu expression in melanoma specimens, but all of the cohorts studied have been small. We therefore examined Her2/neu expression in a very large cohort of melanoma specimens in order to determine the value of exploring trastuzumab therapy for melanoma patients. Immunohistochemical staining was performed on two tissue microarrays, together containing 600 intact specimens. Expression was evaluated semi-quantitatively and correlated with tumour stage and other clinicopathological data. Of the 600 specimens in the cohort, 31 patients (5.2%) had positive Her2/neu expression. Among the primary cutaneous specimens (n=269), 7% had positive Her2/neu staining, while 3.6% of the recurrent or metastatic specimens (n=331) had positive Her2/neu staining (P=0.06). Among the primary lesions there was no significant correlation between Her2/neu expression, Clark level and ulceration; however, Her2/neu expression was associated with lesions with a Breslow depth of < 2 mm (P=0.05). Using this very large cohort of melanoma specimens, we found only a few cases with aberrant Her2/neu expression, many of them being primary cutaneous lesions rather than recurrent or metastatic lesions. Our findings suggest that drugs that specifically target Her2/neu are not likely to be useful for the treatment of metastatic melanoma or as adjuvant therapy for melanoma patients at high risk for recurrence.     

对食管癌多重治疗疗效的预测

Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclusively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an effort to improve survival. Results from phase Ⅲ randomized trials are encouraging however, they revealed that only patients with major histopathological response will benefit from treatment. Therefore, predictive molecular markers indicating response or non-response to neoadjuvant treatment would be extremely helpful in selecting patients for current and future treatment protocols. In this paper we review the role of the molecular markers ERCC1 (excision repair cross-complementing 1 gene) and c-erbB-2 (synonym:HER2/neu) in predicting response to radiochemotherapy and outcome for patients with locally advanced resectable esophageal cancers (cT2-4, Nx, M0). The results are promising and it appears that we might expect to unequivocally identify with ERCC1 and c-erbB-2 respectively, approximately up to one third of patients who fulfil the criteria for neoadjuvant treatment for locally advanced esophageal cancer but will not benefit from our treatment protocol. Integration of such markers in the clinical setting might prevent a substantial number of patients from expensive, non-effective and potentially harmful therapies, and could lead to a more individualized type of combined multimodality treatment in the near future.     

Bowel injury in gynecologic laparoscopy

STUDY OBJECTIVE: To review surveys of the last decade on bowel injuries to evaluate the prevalence, causes, management, and outcomes of these events occurring during or as a result of laparoscopy. DESIGN: Retrospective evaluation (Canadian Task Force classification II-2). SETTING: Surveys and databases. PATIENTS: None. INTERVENTION: Data analysis. MEASUREMENTS AND MAIN RESULTS: Combined data show that diagnostic and minor operative laparoscopy are associated with a 0.08% risk of bowel injury, and in major operative laparoscopy the risk increases to 0.33%. Injuries occurring during access and operative procedure decrease significantly with experience, but even in experienced hands injury during access cannot be avoided. Delayed diagnosis remains a major problem. Up to 15% of these injuries are not diagnosed during laparoscopy, and one of five cases of delayed diagnosis results in death. Perioperative diagnosis and immediate repair by laparoscopy or laparotomy reduce the likelihood of severe complications and consequently medicolegal actions. CONCLUSIONS: Several surveys on complications of gynecologic laparoscopy tend to underestimate the risk of bowel injury. Prevention starts by awareness that such injury is an inherent risk of the technique, even in hands of experienced surgeons.     

Neutralizing antibodies against conserved domains of p15E of porcine endogenous retroviruses: basis for a vaccine for xenotransplantation?

Porcine xenotransplants may offer a potential solution to the problem posed by the limited supply of allotransplants. However, xenotransplantation may be associated with the risk of transmission of microorganisms, in particular of porcine endogenous retroviruses (PERVs) that are an integral part of the porcine genome and able to infect human cells in vitro. Possible strategies to prevent virus transmission include the development of PERV knockout animals or of effective vaccines. When antisera prepared against the main structural proteins of PERV were screened, a goat antiserum against the recombinant ectodomain of the transmembrane envelope protein p15E was found to neutralize PERV infectivity. Epitope mapping using overlapping peptides revealed two epitopes, E1 (GPQQLEK) and E2 (FEGWFN). These sequences are identical for all PERVs and are highly conserved among all gammaretroviruses. Interestingly, antibodies isolated from AIDS patients and specific for sequences of HIV-1 partially homologous with E2 (Mab4E10, LWNWFN) or located in close proximity to E2 (Mab2F5, ELDKWA) are known to neutralize several strains of HIV-1. It is the first report showing epitope mapping of gammaretrovirus-specific neutralizing antibodies and demonstrating similarity to corresponding epitopes in HIV. These domains of the transmembrane proteins of different retroviruses are an effective target for neutralizing antibodies and may be a useful antigen to create an antiretroviral vaccine.     

Evaluation of quantitative ultrasound tissue characterization of the cervix and cervical length in the prediction of premature delivery for patients with spontaneous preterm labor

OBJECTIVE: This study was to evaluate the predictive value of the uterine cervix tissue with the use of quantitative ultrasound gray level analysis for preterm delivery. STUDY DESIGN: Sixty-eight patients with preterm labor between 20 and 35 weeks of gestation were included. When two-dimensional transvaginal ultrasound measurement of cervical length was completed, a region of interest of constant size was defined in the midsection of the posterior wall, and the tissue-specific gray scale was determined. Preterm delivery of <37 weeks of gestation was sought. RESULTS: Twenty-eight patients (41.2%) were delivered preterm. The risk for preterm delivery was increased significantly in patients with cervical length of /=4 (odds ratio, 3.44; 95% CI, 1.21-9.75), and with decreased mean gray scale value (odds ratio, 12.13; 95% CI, 3.69-39.88). Parity and uterine contractions were not significant as predictors for preterm delivery, although the risk for preterm delivery increased with higher parity (odds ratio, 1.8; 95% CI, 0.68-4.79). The risk for preterm delivery remained nearly the same by uterine contractions (odds ratio, 0.92; 95% CI, 0.28-3.01). A mean scale value of 相似文献   

Language skills in children with velocardiofacial syndrome (deletion 22q11.2)

OBJECTIVE: To further define the language profile of children with velocardiofacial syndrome (VCFS) and explore the influence of parental origin of the deletion on language. STUDY DESIGN: Children and adolescents with VCFS (n = 27) were group-matched for sex, age, and IQ with 27 children and adolescents with idiopathic developmental delay. Fifty-four typically developing control subjects were also included in the analyses investigating word association abilities. RESULTS: Children with VCFS had significantly lower receptive than expressive language skills, a unique finding when compared with IQ-matched control subjects. However, no significant differences in word association were detected. Children with a deletion of paternal origin score significantly higher on receptive language when compared with children with a deletion of maternal origin. CONCLUSIONS: The Clinical Evaluation of Language Fundamentals-III results suggest that children with VCFS show more severe deficits in receptive than expressive language abilities. Language skills of children with VCFS could be influenced by parental origin of the deletion and thus related to neuroanatomic alterations at the deletion site.