Upstream thrombus growth impairs downstream thrombogenesis in non-anticoagulated blood: effect of procoagulant artery subendothelium and non-procoagulant collagen

In the present experiments we have investigated the influence of wall shear rate and axial position on platelet and fibrin deposition which results when flowing human non-anticoagulated blood is exposed to either non-procoagulant fibrillar collagen (human type III) or procoagulant subendothelium (rabbit aorta). Platelet adhesion, thrombus volume and fibrin deposition were morphometrically evaluated at axial positions of 1 and 13 mm following perfusions for 5 min at shear rates of 100, 650 and 2,600 s-1. An axially-dependent decrease of platelet adhesion (34-57%, p less than 0.01-0.05) and thrombus volume (57-80%, p less than 0.05) was observed on collagen at all shear rates. On subendothelium, an axially-dependent decrease was observed for platelet adhesion only at 100 s-1 (29%; p less than 0.01) and for thrombus volume at shear rates of 650 s-1 and above (49-58%, p less than 0.01). Deposition of fibrin on subendothelium was axially decreased (16-42%, p less than 0.05) at all shear rates, while no significant axial differences were seen on collagen. However, substantially more fibrin was deposited on the subendothelium (p less than 0.05), and the upstream platelet adhesion and thrombus volume were lower than on collagen (p less than 0.05) at 100 s-1 and 650 s-1. The axially-dependent phenomena on the two surfaces are consistent with the concept of rapid-growing upstream thrombi which deplete the blood layer streaming adjacent ot the surface of platelets, leading to decreased platelet deposition further downstream.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis and bacterial mutagenicity of the cyclopenta oxides of the four cyclopenta-fused of isomers of benzanthracene

Many polycyclic aromatic hydrocarbons containing peripherallyfused cyclopenta rings are believed to be activated primarilyby epoxidation of the cyclopenta ring. The cyclopenta epoxidesof a series of four cyclopenta benzanthracene derivatives, benz[e]aceanthrylene-5,6-oxide,benz[j]ace-anthrylene-1,2-oxide, benz(l)anthrylene-1,2-oxideand benz[k]acephenaceanthrylene-4,5-oxide were synthesized fromtheir parent hydrocarbons by formation of the bromohydrin followedby dehydrobromination, and characterized by u.v. – vis,and ¹H n.m.r. spectroscopy and mass spectrometry. The mutagenicityof these compounds was investigated in the Ames plate incorporationassay with Salmonella typhimurium strain TA98. All the oxideswere active without exogenous metabolic activation (170–320His⁺ revertants per nanomole) and also toxic above 0.5 µg/plate.Addition of S9 protein did not increase, and generally decreased,the mutagenicity of the oxides, while toxicity was largely unchanged.These results are consistent with the postulated role of cyclopentaoxides as major contributors to the mutagenicity of the parentcompounds in the Ames assay.     

Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.     

Low-molecular weight heparin for deep vein thrombosis prophylaxis in hospitalized medical patients: results from a cost-effectiveness analysis.

Multiple options exist for the prevention of deep vein thrombosis (DVT) in medical inpatients. We sought to determine the cost-effectiveness of low-molecular-weight heparin (LMWH) relative to unfractionated heparin (UFH) for DVT prevention in this setting. We conducted a cost-effectiveness analysis from the perspective of a third-party payer employing a decision model and literature-based estimates for inputs. In the base-case analysis, LMWH had little impact on the rate of DVT. Despite higher acquisition costs, however, LMWHs resulted in net savings. Routine use of LMWH saves approximately US$89 per patient. The lower rate of heparin-induced thrombocytopenia (HIT) with LMWH accounted for this differential. Univariate sensitivity analysis revealed the model was moderately sensitive to the odds ratio of HIT with LMWH and the cost of HIT. Multivariate sensitivity analysis confirmed the LMWH approach dominated financially. 'Worst-case' scenario modeling, where LMWH actually increased the risk for DVT, had little effect on the rate of HIT, and was substantially more costly than UFH, still demonstrated that LMWHs were economically superior. Monte-Carlo simulation indicated the 95% confidence interval around the estimate for savings with LMWH ranged from US$7 to US$373. We conclude that, despite their higher cost, LMWHs for thromboprophylaxis in medical patients result in savings.     

Association of circulating transforming growth factor beta, tumor necrosis factor alpha and basic fibroblast growth factor with restenosis after transluminal angioplasty.

OBJECTIVES: To assess prospectively the early time course of Transforming Growth Factor beta-1 (TGFbeta-1), basic Fibroblast Growth Factor (bFGF) and Tumor Necrosis Factor alpha (TNFalpha) as possible contributors to restenosis development after angioplasty. DESIGN: Prospective Study. METHODS: The levels of the soluble forms of these factors in the early response to Percutaneous Transluminal Angioplasty (PTA) in the arteries of the lower limb were prospectively assessed. 32 patients with peripheral arterial occlusive disease (PAOD), presenting with intermittent claudication (Fontaine stage IIb) were scheduled for angioplasty treatment. Serum levels of TGFbeta-1, TNFalpha and bFGF were assessed before intervention, 15 and 60 minutes after, 24 hours after as well as 2 and 4 weeks after intervention. We compared the distribution patterns between patients treated with balloon angioplasty and patients who required secondary stent implantation. Endpoint was the development of restenosis within 6 months after interventional treatment, defined as a lumen diameter reduction of more than 50% by ultrasound measurement compared to the result after PTA. RESULTS: The patients who later developed restenosis had significantly higher levels of TGFbeta-1 at 15 minutes, 24 hours and 2 weeks after PTA (p<0.05). TNFalpha and bFGF were only detected in a few patients and no significant change of serum levels was observed. CONCLUSION: The results demonstrate a possible role of TGFbeta-1 in the formation of restenosis after PTA.     

The effect of seated positioning quality on typical 6- and 7-year-old children's object manipulation skills.

OBJECTIVE: The purpose of this study was to examine the effect of optimal seated positioning in individually fitted furniture versus suboptimal seated positioning in standard classroom furniture on typical 6- and 7-year-old children's object manipulation skills as measured by the In-hand Manipulation Test (IMT). METHOD: An experimental research design was used to compare IMT performance of two groups of 20 children. One group was positioned in standard, too-large classroom furniture that did not support an optimal seated position, and one group was positioned optimally in furniture fitted to each child for tabletop activities, which allowed for hip flexion to 90 degrees, and foot placement on the floor, and the table to be at flexed elbow height. RESULTS: Independent groups' t tests indicated that children who were optimally positioned performed significantly better (t = -2.77, df = 38, p < .01) than children who were tested in the too-large standard classroom furniture. The difference between groups was greater on the more difficult object manipulation items (t = -3.29, df = 38, p = .001) than on the easier items (t = -1.38, df = 38, p = .08). Age and gender may have differentially affected the results. CONCLUSION: The study's results suggest that the fit of furniture relative to the child's size may have a significant impact on a young, typical child's object manipulation skills. Complex hand skills, such as those involving in-hand manipulation with stabilization, appear to be more affected by the quality of the child's seated position than are simpler, more well-established skills. Findings suggest that test administrators should strive to test young children in the most optimal seated position possible, particularly when the test involves complex hand skills. Further study is needed to assess the impact of the fit of furniture on hand skills in children with disabilities and on children's performance of other tasks.     

Assessment of quality of life in children with peanut allergy

Children with a peanut allergy (PA) are faced with food and social restrictions due to the potentially life-threatening nature of their disease, for which there is no cure or treatment. This inevitably impacts upon their quality of life (QoL). QoL of 20 children with PA and 20 children with insulin-dependent diabetes mellitus (IDDM) was measured using two disease-specific QoL questionnaires (higher scores correspond to a poorer QoL). One questionnaire was designed by us and the other was adapted from the Vespid Allergy QoL questionnaire. We gave subjects cameras to record how their QoL is affected over a 24-h period. Response rates for both questionnaires were 100%. Mean ages were 9.0 and 10.4 years for PA and IDDM subjects, respectively. Children with a PA reported a poorer quality of life than children with IDDM: mean scores were 54.85 for PA subjects and 46.40 for diabetics (p = 0.004) in questionnaire 1 and 54.30 and 34.50 (p≤0.001) in questionnaire 2. PA children reported more fear of an adverse event and more anxiety about eating, especially when eating away from home. Photographs fell into seven common categories: food, management, environment, away from home, physical activities, restaurant and people. Most photographs related to food and management issues and revealed difficulties for both groups regarding food restrictions. PA subjects felt more threatened by potential hazards within their environment, felt more restricted by their PA regarding physical activities, and worried more about being away from home. However, they felt safe when carrying epinephrine kits and were positive about eating at familiar restaurants. The QoL in children with PA is more impaired than in children with IDDM. Their anxiety may be considered useful in some situations, promoting better adherence to allergen avoidance advice and rescue plans.