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.     

Antibacterial properties of 4 orthodontic cements.

BACKGROUND: White spot lesions are observed in nearly 50% of patients undergoing orthodontic treatment. Long-lasting antibacterial properties of orthodontic cements can reduce this phenomenon. METHODS: The antibacterial properties of 4 orthodontic cements were evaluated by direct contact test (DCT) and agar diffusion test (ADT). With the DCT technique, octet specimens of glass ionomer (CX-Plus; Shofu, Kyoto, Japan), reinforced glass ionomer (GC Fuji ORTHO LC; GC Corporation, Tokyo, Japan), and 2 composite (Transbond XT and Transbond Plus; 3M Unitek, Monrovia, Calif) orthodontic cements were placed on the sidewalls of wells of a 96-microtiter plate. Streptococcus mutans cells (ca. 1 x 10(6) ) were placed on the surface of each specimen for 1 hour at 37 degrees C. Then, fresh media was added to each well, and bacterial growth was monitored for 16 hours with a temperature-controlled spectrophotometer. This was repeated on specimens aged in phosphate-buffered saline for 1 day, 1 week, and 1 month. The ADT was performed by placing specimens in wells punched in agar plates. RESULTS: Measurement of the halo in bacterial lawn after 48 hours showed that only the glass ionomer cement (CX-Plus) produced an inhibition zone (1.2 mm around the sample). Results at the DCT showed that only the reinforced glass ionomer cement (GC Fuji ORTHO LC) exhibited potent antibacterial activity, which lasted 1 week and diminished over the next 3 weeks. CONCLUSIONS: The reinforced glass ionomer cement possessed the most potent and long-lasting antibacterial activity.     

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.