Since 1982, when the World Federation of Hemophilia first published a document on the state of the art of hemophilia diagnosis and care, there have been lights and shadows in this field. Although the widespread infection of hemophiliacs with the human immunodeficiency virus (HIV) contaminating clotting factor concentrates is still a threatening and formidable shadow, the gloomy picture brought about by the AIDS epidemic is partially lightened by spectacular improvements in therapy and diagnosis. Carrier detection and first-trimester prenatal diagnosis can now be performed accurately in most kindreds by analysis of DNA of the factor VIII or IX genes. An important step forward towards the elimination of the risk of blood-borne infections transmitted by plasma products was recently made through the application of virucidal methods to clotting factor concentrates. Since HIV appears more vulnerable to such methods than the hepatitis viruses, currently available concentrates can be considered substantially free from the risk of transmitting HIV infection. Even though transmission of hepatitis is much reduced but not totally abolished, virucidal methods are continuously being improved, so that it can be foreseen that concentrates will become safer and safer. Finally, factor VIII produced by recombinant DNA technology is undergoing the first clinical trials in hemophiliacs. Hopefully, it will free from the risk of transmitting infections and will be available in sufficiently large amounts to meet the need of hemophiliacs worldwide. In 1982, the World Federation of Hemophilia published a message on the status of diagnosis and treatment of hemophilia. Since then, hemophilia care has been complicated by widespread infection of hemophiliacs with human immunodeficiency virus (HIV).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors. 相似文献
We reviewed 86 consecutive patients undergoing elective carotid endarterectomy to determine whether preoperative clinical and angiographic data could be used to predict the risk of intraoperative cerebral ischemia during carotid occlusion. Electroencephalographic (EEG) monitoring with on-line Berg-Fourier transformation was carried out in all patients. A total of 32 patients (37.2%) underwent intraoperative shunting. Of these, 13 had no EEG changes but underwent shunting because of the surgeon's preference, while 19 patients underwent shunting because of EEG changes consistent with cerebral ischemia. There was one permanent (1.2%) and one transient (1.2%) neurologic deficit. Angiographic findings, clinical histories, and intraoperative EEGs were retrospectively reviewed to determine which risk factors best predicted the occurrence of intraoperative cerebral ischemia. Stroke within six weeks increased the risk of intraoperative cerebral ischemia 20-fold. Intracranial disease and contralateral carotid stenosis increased the risk of ischemia 17-fold and 16-fold, respectively. Statistical summation of all risk factors yielded a probability equation for EEG change that accurately quantitated pre-operative risk. Prospective application of this probability equation may simplify operative decision making if EEG monitoring is not available. 相似文献
Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone-binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 microg/dL compared with 78.8 microg/dL for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (P(trend) = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (P(trend) < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research. 相似文献
Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.
Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.
Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. 相似文献