Evaluating Lead Bioavailability Data by Means of a Physiologically Based Lead Kinetic Model

A method of bioavailability estimation is presented in whicha physiologically based kinetic model of lead kinetics is fitsimultaneously to blood and bone lead concentrations after aperiod of exposure to dietary lead. Optimization of the simultaneousfit, varying only fractional absorption, gives the best estimateof fractional bioavailability for each treatment group. Theanalysis was applied to data from three separate studies inwhich rats were fed for 30 consecutive days purified diets containinglead added as lead acetate, mine waste-contaminated test soils,or mine waste itself. Fractional absorption decreased as leadintake increased, regardless of the source of the lead; butthe magnitude of this dose dependence was lead source-dependent.There were no differences in lead absorption by male and femalerats when lead intake was expressed per unit body weight. Fractionalabsorption varied from 4 to 5%, at low exposure rates (1–2mg lead/kg/day) when lead acetate was added to the diet, to0.24% at a high exposure rate (24 mg/kg/day) when a mine waste-contaminatedtest soil was added to the diet. Comparison of the results ofthis analysis with the results of a more conventional analysis,in which the bone and blood lead concentrations were separatelycompared with bone and blood lead concentrations in rats givendaily injections of lead acetate intravenously for 29 consecutivedays, demonstrated that the standard analysis failed to revealthe dose dependence of fractional absorption.     

OVERALL LONG-TERM IMPACT OF TOTAL HIP AND KNEE JOINT REPLACEMENT SURGERY ON PATIENTS WITH OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS

All patients with OA or RA entering an orthopaedic waiting listfor total hip or knee replacement surgery over a period of 2.5yr were prospectively assessed for overall pain (Visual AnalogueScale) and disability (Health Assessment Questionnaire) priorto and following their operation at annual intervals for upto 5 yr. A total of 293 patients had 335 operations (OA, hip164; OA, knee 76; RA, hip 41; RA, knee 54). A few patients (14)showed a deterioration in pain and function 1 yr after surgery,but the remainder showed improvements which took 1 yr or moreto reach maximum and were maintained for at least 3 yr. Althoughgreater for OA hip patients, improvements occurred and weremaintained in all groups, in spite of the polyarticular natureof RA. KEY WORDS: Osteoarthritis, Rheumatoid arthritis, Surgery, Outcome, Operation     

Adhesion of platelets to surface-bound fibrinogen under flow

After platelet activation, fibrinogen mediates platelet-platelet interactions leading to platelet aggregation. In addition, fibrinogen can also function as a cell adhesion molecule, providing a substratum for adhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flow in different shear rates. Heparinized whole blood containing mepacrine-labeled platelets was perfused for two minutes at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seconds with an epifluorescent videomicroscope and digital image processing system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant increase in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s-1. The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no significant adhesion was observed on fibronectin- or vitronectin-coated surfaces. Although platelet adhesion to collagen was substantially inhibited by the platelet inhibitors prostaglandin E1 and theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen. Platelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain.