Fixed minidose versus-adjusted low-dose warfarin after total joint arthroplasty: a randomized prospective study.

Widespread use of adjusted low-dose warfarin has been limited by the inconvenience of outpatient laboratory monitoring and the perceived risk of bleeding complications. We sought to determine if the dose of warfarin could be lowered safely even further, eliminating the need for laboratory monitoring and lowering the complication rate. Two hundred forty-five Patients undergoing primary total joint arthroplasty (n = 245) were randomized prospectively to adjusted low-dose warfarin (international normalized ratio [INR], 1.4-1.8) or fixed minidose warfarin (2 mg daily, regardless of INR) before hospital discharge. Prophylaxis continued for 6 weeks, with twice-weekly laboratory monitoring. Patients were followed for bleeding, thromboembolic events, and minor reported complications of warfarin therapy. With the numbers available, the rates of thromboembolic and bleeding events were not significantly different using equivalence analysis. Of patients in the fixed group, 8% had INRs >3.1, necessitating a decrease in dosage to 1 mg. Although such a fixed-dose protocol may simplify outpatient prophylaxis, intermittent monitoring still would be required because a subset of patients achieve a moderate level of anticoagulation and would be at risk for bleeding complications.

An oscillating extracellular voltage gradient reduces the density and influences the orientation of astrocytes in injured mammalian spinal cord.

We have studied the cellular basis for recovery from acute spinal cord injury induced by applied electric fields. We have emphasized this recovery is due to the regeneration of spinal axons around and through the lesion, and have begun to evaluate the contribution of other cells to the recovery process. We have imposed a voltage gradient of about 320 microV/mm across puncture wounds to the adult rat spinal cord in order to study the accumulation and orientation of GFAP+ astrocytes within and adjacent to the lesion. This electric field was imposed by a miniaturized electronic implant designed to alternate the polarity of the field every 15 minutes. Astrocytes are known to undergo hyperplastic transformation within injured mammalian cords forming a major component of the scar that forms in response to injury. We have made three observations using a new computer based morphometry technique: First, we note a slight shift in the orientation of astrocytes parallel to the long axis of the spinal cord towards an imaginary reference perpendicular to this axis by approximately 10 degrees--but only in undamaged white matter near the lesion. Second, the relative number of astrocytes was markedly, and statistically significantly, reduced within electrically--treated spinal cords, particularly in the lesion. Third, the imposed voltage gradient statistically reduced the numbers of astrocytes possessing oriented cell processes within the injury site compared to adjacent undamaged regions of spinal cord.

Synthesis, hydrolysis kinetics and anti-platelet effects of isosorbide mononitrate derivatives of aspirin.

Two isomeric aspirin derivatives of isosorbide-5-mononitrate (ISMN) were prepared and evaluated as potential mutual prodrugs of aspirin and nitric oxide. The hydrolysis of both compounds was studied in pH 7.4 phosphate buffer solution, buffered alpha-chymotrypsin solution and 10% buffered rabbit plasma. The benzodioxin-4-one derivative was hydrolysed to salicylic acid and ISMN acetate in buffer solution (t(1/2) 32.1 h), 10% buffered rabbit plasma (t(1/2) 25.7 min) and alpha-chymotrypsin (t(1/2) 86.6 min). The carboxylic acid ester derivative ISMNA was hydrolysed via the salicylate ester in buffer solution (t(1/2) 48.5 h) but was rapidly and almost exclusively hydrolysed to aspirin and ISMN in plasma solution (t(1/2) 2.8 min). The hydrolysis appeared to be enzyme mediated as it was suppressed by co-incubation with eserine. ISMNA was evaluated for its ability to inhibit platelet aggregation in rabbit PRP in response to the following agonists: arachidonic acid (AA) (100 microM), ADP (1.2 microM), phorbol ester (0.5 microM), platelet activating factor (PAF) (5 nM) and the thromboxane mimic U46619 (1.5 microM). ISMNA suppressed platelet response to AA at 1 microM whereas 10 microM aspirin showed no inhibitory effects.

Endogenous electric current is associated with normal development of the vertebrate limb.

A steady ionic current is driven out of both developing and regenerating amphibian limbs. In the developing limbs of anurans and urodeles, focal outwardly directed current (0.5-2 microA/cm(2)) predicts the location of mesenchyme accumulations producing the early bud. Here, we report measurements of a similar outwardly directed ionic current associated with the development of the limb bud in the mouse and chick embryo by using a noninvasive, self-referencing electrode for the measurement of extracellular current. In both the mouse and chick embryo, flank currents were usually inwardly directed - the direction of Na(+) uptake by ectoderm. Outward currents associated with the mouse limb bud ranged from 0.04-10.8 microA/cm(2). Mouse limb bud and flank currents were similar to those measured in amphibian larvae, because they were reversibly collapsed and/or reversed by application of 30 microM amiloride, a Na(+) channel blocker. Unlike the amphibian embryos, flank ectoderm adjacent to the mouse limb bud in the anterior/posterior axis was usually associated with outwardly directed ionic current. This raises the possibility of a different, or changing, gradient of extracellular voltage experienced by mesenchyme cells in this plane of development than that observed in other regions of the limb bud. In the chick flank caudal to the somites, a striking reversal of the inwardly directed flank currents to very large ( approximately 100 microA/cm(2)) outwardly directed currents occurred three developmental stages before limb bud formation. We tested the relevance of this outwardly directed ionic current to limb formation in the chick embryo by reversing it by using an artificially applied "countercurrent" pulled through a microelectrode inserted just beneath the caudal ectoderm of the embryo. This application was performed for approximately 6 hr 2.5-3 developmental stages before hindlimb bud formation. This method resulted in abnormal limb formation by the tenth day of gestation in some embryos, whereas all control embryos developed normally. These data suggest an early physiological control of limb development.

The macrophage in acute neural injury: changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems.

We evaluated the timing and density of ED-1-positive macrophage accumulation (ED 1 is the primary antibody for the macrophage) and measured cytokine production by macrophages in standardized compression injuries to the spinal cord and sciatic nerves of individual rats 3, 5, 10 and 21 days post-injury. The actual site of mechanical damage to the nervous tissue, and a more distant site where Wallerian degeneration had occurred, were evaluated in both the peripheral nervous system (PNS) and the central nervous system (CNS) at these time points. The initial accumulation of activated macrophages was similar at both the central and peripheral sites of damage. Subsequently, macrophage densities at all locations studied were statistically significantly higher in the spinal cord than in the sciatic nerve at every time point but one. The peak concentrations of three cytokines, tumor necrosis factor &agr; (TNF &agr; ), interleukin-1 (IL-1) and interleukin-6 (IL-6), appeared earlier and were statistically significantly higher in injured spinal cord than in injured sciatic nerve. We discuss the meaning of these data relative to the known differences in the reparative responses of the PNS and CNS to injury.

Two- and three-dimensional computer graphic evaluation of the subacute spinal cord injury.

We have evaluated three-week-old compression lesions of the rat spinal cord using two-dimensional and three-dimensional morphometry, reconstruction, and visualization techniques. We offer a new computer assisted method to determine the number and density of macrophages within the spinal lesion using the macrophage specific monoclonal label ED1. We also provide quantitative information on pathological cyst formation and cavitation. This technique does not require: (1) subjective identification of the cell type, (2) human interaction with the data during the phase of quantification, and (3) can be applied to any sampling paradigm based on immunocytochemical labeling. Using novel algorithms based on solutions to 'correspondence' and 'branching' problems inherent in cross-sectional histological data, we provide three-dimensional reconstructions and visualizations of the macrophagic lesions and cysts imbedded within it. Our three-dimensional surface reconstructions can be interrogated to determine volumes and surface areas of structures within the data set. Using these methods we have learned that macrophage numbers approach the maximum density possible for such isodiametric cells (approximately 12 microm diameter) in the central lesion ranging from 4000-7000 cells per mm2 of lesion. At the time point studied, macrophage numbers would have peaked following the initial insult, and would not be expected to decline for several months. While the density of macrophages is highest in the region of most tissue damage, we show that the central regions of cavitated and cystic spinal parenchyma is not. We discuss how this density of cells may effect the secondary pathological responses of the spinal cord to injury.

Hydroxyapatite-coated femoral stems. A matched-pair analysis of coated and uncoated implants.

Fifty-two pairs of patients who had had a total hip arthroplasty with a porous-coated femoral implant were studied in a retrospective, matched-pair analysis. Half of the patients had received a femoral component coated with hydroxyapatite and the other half (the controls), an identical component but without hydroxyapatite. The patients were matched for age, sex, weight, diagnosis, Charnley class, operative approach, and duration of follow-up. Identical uncoated hemispherical acetabular implants were used in both groups. At the time of follow-up, at a mean of 2.2 years (range, two to 3.4 years) after the operation, the mean Charnley scores for pain, function, and motion were 5.6, 5.5, and 5.6 points, respectively, in the group that had received a hydroxyapatite-coated femoral component and 5.6, 5.6, and 5.6 points, respectively, in the group that had received a non-coated component; none of these differences were significant (p = 0.86, 0.89,, and 0.80, respectively). There were no revisions in either group. Radiographs indicated stable fixation in both groups and no differences in the radiographic parameters of loosening between the two groups. Within the relatively short time-frame of this study, there appeared to be no clinical or radiographic advantage to the use of hydroxyapatite in primary total hip arthroplasties. However, these results should be considered as preliminary. Longer follow-up may reveal unrecognized advantages or disadvantages.

Predicting quality-of-life outcomes following total joint arthroplasty. Limitations of the SF-36 Health Status Questionnaire.

A group of 114 patients undergoing total hip and knee arthroplasty were evaluated to assess the effect of total joint arthroplasty on quality of life, as measured by the SF-36 Health Status Questionnaire, and to determine the predictive relationship between preoperative and postoperative scores. A highly significant improvement was seen comparing preoperative with postoperative scores at 2 years for physical function, social function, physical role function, emotional role function, mental health, energy, and pain. Despite a significant change in health status (P < or = .001), no change was seen in the patient's health perception (P = .61). Regression analysis failed to indicate a predictive relationship between preoperative and postoperative scores for any scale. Total joint arthroplasty dramatically improves the quality of life and function of patients afflicted with arthritis; however, because of the poor ability of the SF-36 to predict postoperative improvement on an individual basis, it cannot be used alone to determine treatment selection.

Clinical and roentgenographic evaluation of hydroxyapatite-augmented and nonaugmented porous total hip arthroplasty.

Sixty osteoarthritic patients undergoing primary, uncemented total hip arthroplasty were matched for age and weight and randomized into one of four groups with respect to implant coating and postoperative, protected weight-bearing status: group 1, hydroxyapatite-augmented, 12 weeks; group 2, nonaugmented, 12 weeks; group 3, hydroxyapatite-augmented, 6 weeks; and group 4, nonaugmented, 6 weeks. Tantalum spheres were implanted periprosthetically into the femur at the time of the arthroplasty, thus providing constant references for stereoscopic radiographs. Patients were then evaluated over a 2-year period with clinical examination, plain radiography, and roentgen stereophotogrammetric analysis. Clinical evaluation using the Charnley scoring system showed no significant preoperative or postoperative intergroup differences, whereas visual analog testing noted less thigh pain with hydroxyapatite-augmented stems at the 12-week and 6-month follow-up evaluations. Plain radiographic analysis produced no significant differences, with no instability detected, and bony ingrowth was uniform in all groups. Stereographic evaluation showed migration in all groups, but there were no significant differences between the augmented and nonaugmented stems or the 6-week and 12-week partial weight-bearing protocols. Charnley, plain radiographic, and stereogrammetric evaluations all suggest that migration is unaltered by enhanced surfaces and early, unprotected weight bearing does not jeopardize implant fixation regardless of coating design. The lower incidence of visual analog thigh pain with the hydroxyapatite-augmented stems, however, may be a reflection of bony ingrowth and, as such, add some validity to the theoretic advantages of enhanced surface prostheses.

Establishing a home care protocol for early discharge of patients with hip and knee arthroplasties.

Joint arthroplasty procedures are significant in number and cost. Discharging hip and knee arthroplasty patients early from the hospital to a transitional home care program has the potential to reduce costs, while maintaining quality. A retrospective review of hospital records of hip and knee arthroplasty patients quantified patient problems during postoperative days 3 through 12 and analyzed them by age, gender, and joint type. The pilot study also allowed the development of a protocol for transitional home care after hip and knee arthroplasty.

Transitional home care after joint arthroplasty.

Two case studies allow authors to share the need to further refine a proposed protocol for transitional home care after joint arthroplasty. The case reports present the clinical consequences after early discharge from the hospital to transitional home care. In addition, the impact on physical and psychosocial outcomes, as well as cost, is addressed for the two cases.

Clinical and roentgenographic evaluation of hydroxyapatite-coated and uncoated porous total hip arthroplasty: a preliminary report.

Sixty osteoarthritic patients undergoing primary uncemented total hip arthroplasty were matched for age and weight and randomized into one of four groups with respect to implant coating and postoperative protected weight-bearing status: group 1, hydroxyapatite, 12 weeks; group 2, uncoated, 12 weeks; group 3, hydroxyapatite, 6 weeks; group 4, uncoated, 6 weeks. Tantalum spheres were implanted periprosthetically into the femur at the time of arthroplasty, thus providing constant references for stereoscopic radiographs. Patients were then evaluated over a 1-year period with clinical examination, plain radiography, and roentgen stereophotogrammetric analysis (RSA). Clinical evaluation using Charnley scoring showed no significant preoperative or postoperative intergroup differences, whereas visual analog testing noted less thigh pain with hydroxyapatite-coated stems at 12 weeks and 6 months follow-up. Plain radiographic analysis produced no significant differences, with no instability detected and bony ingrowth noted uniformly in all groups. The preliminary stereographic evaluation showed migration in all groups, but there were no significant differences between coated and uncoated stems or 6-week and 12-week partial weightbearing protocols. The Charnley, plain radiographic, and preliminary stereogrammetric evaluations all suggest that migration is unaltered by enhanced surfaces and that early unprotected weightbearing does not jeopardize implant fixation regardless of coating design. The lower incidence of visual analog thigh pain with the hydroxyapatite-coated stems, however, may be a reflection of bony ingrowth and as such add some validity to the theoretical advantages of enhanced surface prostheses.