Loss of Anticoagulant Effect of Heparin During Circulation of Human Blood In Vitro

Device-induced thrombogenesis was studied in an in vitro model using human blood circulated through an artificial ventricle. A new constant pressure filtration technique was used to detect circulating microemboli, the activated partial thromboplastin time (APTT) test was used to monitor the blood for the presence of anticoagulant activity of heparin, and hemolysis was quantified by measuring the plasma free hemoglobin level. Circulation of blood through a 20-ml stroke volume pneumatically driven ventricle for 6-9 h resulted in a significant reduction of APTT, indicating the loss of the anticoagulant effect of heparin. Microemboli concentration was minimal until the APTT decreased below 125 s, at which time the microemboli concentration increased rapidly. This was presumed to be due to the formation of thrombi following a decrease in heparin activity. A significant increase in hemolysis was also noted when blood was pumped. None of these changes was noted in the nonpumped control blood. Spontaneous loss of heparin activity in blood circulated by a pneumatically driven pump may have clinical implications and may help understanding of the problems associated with device-induced thrombogenesis.     

Pharmacology of histamine H2 receptor antagonists in the human gastric cancer cell line HGT-1. Structure-activity relationship of isocytosine-furan and imidazole derivatives related to cimetidine

Imidazole and isocytosine-furan derivatives inhibited H2 receptor activity in HGT-1 cells, in accordance with the following relative potencies (IC50 = 2.3 microM cimetidine as reference): SKF 93479 = cimetidine = 100 greater than metiamide = 62 greater than SKF 92408 = 2 greater than SKF 91581 = 0.07). The Schild plot for cimetidine was linear (slope = 0.97) with a pA2 value of 6.72 +/- 0.12 (Ki = 0.18 microM cimetidine), suggesting competitive inhibition. Preincubation of HGT-1 cells for 10 min with H2 antagonists at 2 microM concentration resulted in 90-100% inactivation (SKF 93479 and oxmetidine) and 65% inactivation (ranitidine) which persisted for 30 min, even after a washout period. Accordingly, the kinetics of 2 microM [3H] SKF 93479 binding to HGT-1 cells revealed a half-time for association of 10 min and a dissociation half-time of 120 min. There was a good correlation between the kinetics and relative potencies of cimetidine and SKF 93479 in inhibiting H2 receptor activity in purified plasma membranes (40 nM) as well as in intact HGT-1 cells preincubated for 2 hr with SKF 93479 before histamine addition (45 nM). Chronic treatment of HGT-1 cells for 6 days with 2 microM SKF 93479 specifically blocked H2 receptor activity since cyclic AMP generation induced by other hormones and agents such as VIP, glucagon, GIP and sodium fluoride was unaltered. In contrast, short term and chronic treatment by cimetidine was readily reversible. The isocytosine-furan derivative SKF 93479 differs from the imidazole analogue cimetidine by its apparent irreversible action, due to the slow onset of association from HGT-1 cells. The isocytosine ring in SKF 93479 and oxmetidine seems to play a preponderant role in their apparent long-lasting, irreversible actions.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH/IVH) in preterm neonates

Background Germinal matrix and intraventricular hemorrhage (GMH/IVH) is a known complication occurring in the first week of life in preterm neonates. However, the precise time of its occurrence and the ideal time to perform diagnostic imaging studies remain controversial. The purpose of this paper is to address these two issues in our patient population to allocate our resources to those at highest risk.Materials and methods This study included 282 premature newborns (under 37 weeks of gestation) that were admitted to our neonate ICU in a year’s time and screened for GMH/IVH. They were grouped in four categories according to their weight at birth, and according to their gestational age. All patients had a daily cranial ultrasound during the first week. It was then repeated once in the second week and once in the third.Results We found that the incidence of GMH/IVH among preterm neonates was 44.68%. It was inversely related to the weight and the age of the newborn. The onset of bleeding coordinated with the occurrence of hypoxia and respiratory distress requiring mechanical ventilation. The majorities occurred in the first 7 days of life; they were mostly grade I and II according to the Papule classification and silent for the most part. Complications were present in 41% of the survivors.     

A methodological approach to the classification of dermoscopy images.

In this paper a methodological approach to the classification of pigmented skin lesions in dermoscopy images is presented. First, automatic border detection is performed to separate the lesion from the background skin. Shape features are then extracted from this border. For the extraction of color and texture related features, the image is divided into various clinically significant regions using the Euclidean distance transform. This feature data is fed into an optimization framework, which ranks the features using various feature selection algorithms and determines the optimal feature subset size according to the area under the ROC curve measure obtained from support vector machine classification. The issue of class imbalance is addressed using various sampling strategies, and the classifier generalization error is estimated using Monte Carlo cross validation. Experiments on a set of 564 images yielded a specificity of 92.34% and a sensitivity of 93.33%.