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Biomedical subjects

K D Moore

Publications and source records attributed to K D Moore.

At least 19 recordsLinked to original sources

Antibodies to topical bovine thrombin correlate with access thrombosis.

Bovine thrombin is often used topically to promote hemostasis during vascular surgery, including dialysis-access placement. Patients frequently develop antibodies to bovine thrombin preparations, and some may develop antiphospholipid antibodies. We evaluated 88 hemodialysis patients for the presence of antibodies to topical bovine thrombin to determine if elevated antibody levels correlated with vascular access thrombosis. Twenty-seven patients (30.7%) had elevated antibody levels to topical bovine thrombin. More patients with elevated antibody levels had prior vascular access thrombosis than patients with normal antibody levels (13 of 27 versus 5 of 61 patients; P < 0.001). This difference was almost entirely the result of greater levels of thrombosis in patients with polytetrafluoroethylene (PTFE) grafts and elevated antibody levels. In these patients, 11 of 13 patients (84.6%) with elevated antibody levels had a previous thrombosis compared with 2 of 15 patients (13. 3%) with normal antibody levels (P < 0.001). Patients with elevated antibody levels and PTFE grafts also had more prior thromboses (1.92 +/- 1.60 versus 0.133 +/- 0.35 thromboses; P < 0.01) and a greater thrombosis rate (66.89 +/- 63.71 versus 4.65 +/- 12.05 thromboses/100 patient-years; P < 0.01) than patients with normal antibody levels. There were no differences in the frequency of myocardial infarction, coronary artery bypass, access age, presence of diabetes mellitus, platelet counts, anticardiolipin antibody, albumin, lactate dehydrogenase, or C-reactive protein levels. In conclusion, patients with PTFE grafts and elevated antibody levels to topical bovine thrombin had significantly more vascular access thrombosis.

Aged↗

The effect of weight-bearing on the radiographic measurement of the position of the femoral head after total hip arthroplasty.

BACKGROUND: In most radiographic studies of polyethylene wear, investigators have used routine annual radiographs made with the patient in the supine position in order to measure penetration by the femoral head into the polyethylene liner. However, researchers have begun to question the effect of weight-bearing on the position of the head within the acetabular cup and, consequently, the effect of weight-bearing on measurements of penetration by the head. The purpose of the current study was to determine the effect of weight-bearing on the two-dimensional radiographic position of the femoral head within the acetabular cup. METHODS: Thirty-seven patients (forty-seven hips) who had had a total hip arthroplasty had radiographs made at one of two separate institutions. A set of anteroposterior radiographs was made for each patient: one radiograph was made with the patient supine and one was made with the patient upright bearing full weight on the replaced hip. At one of the institutions, a third anteroposterior radiograph was made with the patient in the same upright position but not bearing weight on the replaced hip. All measurements of the two-dimensional position of the head were performed by a single observer with use of a previously published computerized measurement system. RESULTS: Data from both institutions revealed that measurements of the position of the head on radiographs made with the patient supine were strongly and significantly correlated with measurements of the position of the head on radiographs made with the patient bearing weight (r2>0.93, p<0.001 for both regressions). Examination of the differences between the measurements revealed no bias for one set of measurements to consistently underestimate or overestimate the values derived with use of the other method. Moreover, we found a nearly perfect relationship between the measurements of the position of the head on radiographs made with the patient standing and bearing weight and those on radiographs made with the patient standing but not bearing weight (r2 = 0.97, p<0.001, slope = 0.99, intercept = 0.02 millimeter). CONCLUSIONS: On the basis of these findings, there is no evidence that radiographs must be made with the patient bearing weight in order to accurately measure the position of the femoral head within the polyethylene liner.

Arthroplasty, Replacement, Hip↗

Inhibitory anti-factor V antibodies bind to the factor V C2 domain and are associated with hemorrhagic manifestations.

Factor V inhibitors may develop as spontaneous autoantibodies, as alloantibodies after exposure to bovine thrombin preparations, or in factor V-deficient patients after plasma therapy. Clinical manifestations range from asymptomatic laboratory abnormalities to life-threatening hemorrhage. We have characterized the anti-factor V antibodies from 12 patients diagnosed with factor V inhibitors. In 8 patients, hemorrhagic complications (5 autoantibodies and 3 bovine thrombin-induced alloantibodies) developed, and 4 were asymptomatic (2 autoantibodies and 2 alloantibodies). The IgG fractions from all 12 patients immunoprecipitated the factor Va light chain, but only the 8 IgG fractions associated with hemorrhage inhibited factor V activity in a prothrombinase assay. Nine IgG fractions, including the 8 patients with hemorrhage, immunoprecipitated the isolated second C-type domain (C2). The 8 IgG fractions from the symptomatic patients also immunoprecipitated recombinant chimeras containing only the N-terminal third of the factor V C2 domain, and isolated recombinant C2 domain abrogated the inhibitory effect of the antibodies. Five of the inhibitory IgG fractions blocked binding of factor V to phosphatidylserine. These results suggest that inhibitory anti-factor V antibodies are associated with hemorrhagic manifestations and frequently bind to a common region within the C2 domain, whether originating spontaneously or after exposure to bovine thrombin.

Adolescent↗

Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fractures: a randomised, prospective study.

We report a prospective, randomised, blinded clinical comparison of the use of indomethacin or radiation therapy for the prevention of heterotopic ossification (HO) in 75 adults who had open reduction and internal fixation of acetabular fractures through either a Kocher-Langenbeck, a combined ilioinguinal and Kocher-Langenbeck, or an extended iliofemoral approach. Indomethacin, 25 mg, was given three times daily for six weeks. Radiation with 800 cGy was delivered within three days of operation. Plain radiographs were reviewed and given Brooker classification scores by three independent observers who were unaware of the method of prophylaxis. One patient died from unrelated causes and two were lost to follow-up, leaving 72, 33 in the radiation group and 39 in the indomethacin group, available for evaluation at a mean of 12 months (6 to 48). There was no significant difference in the two groups in terms of age, gender, injury severity score, estimated blood loss, delay to surgery, head injury, presence of femoral head dislocation, or operating time, and no complications due to either method of treatment. The final extent of HO was already present by six weeks in all patients who were followed up. Three patients in the radiation group and five who received indomethacin developed HO of Brooker grade III. Two patients in the indomethacin group developed Brooker IV changes; both had failed to receive proper doses of the drug. Cochran-Armitage analysis showed no significant difference between the two treatment groups as regards the formation of HO. Indomethacin and single-dose radiation therapy are both safe and effective for the prevention of HO after operation for acetabular fractures. Radiation therapy is, however, approximately 200 times more expensive than indomethacin therapy at our institution and has other risks.

Acetabulum↗

Total hip arthroplasty with porous-coated prostheses fixed without cement in patients who are sixty-five years of age or older.

We reviewed the results of 212 total hip arthroplasties performed without cement in 203 unselected, consecutive patients who were sixty-five years of age or older. The outcome was known for 196 hips, thirty-seven of which had been followed until the death of the patient and 159 of which had been followed for a minimum of five years. A reoperation was done in 4 percent (seven) of the 196 hips. These reoperations included one revision because of loosening of the stem and five revisions of the cup. Three of the acetabular revisions were done because of fracture due to polyethylene wear; one, because of recurrent dislocation; and one, because of polyethylene wear and a fracture due to lysis. In the seventh reoperation, a cup and stem were exchanged because of infection. The probability that a hip prosthesis would survive twelve years without a reoperation was 0.92 (95 percent confidence interval, 0.85 to 0.99). We evaluated the clinical results for 152 patients who had not had a reoperation and had been followed for at least five years (mean, 8.5 years; range, five to fourteen years). Of these patients, thirteen (9 percent) had pain that limited activity: five (3 percent) had pain in the thigh (four patients) or groin (one patient), and eight (5 percent) had trochanteric pain and tenderness. One hundred and forty-four (95 percent) of the patients noted an improvement in overall function, and 149 (98 percent) reported satisfaction with the outcome. One hundred and thirty-five hips that were not revised were followed radiographically for at least five years (mean, 8.2 years; range, five to fourteen years). In this group, osteolysis was observed in three hips (2 percent); loosening of the cup, in three (2 percent); and loosening of the stem, in one (1 percent). Stress-shielding was seen on the two-year postoperative radiographs of forty-five (26 percent) of the 174 hips that were followed for at least that duration. The prevalence of osteolysis, loosening of a component, and reoperations was no greater in this subgroup than in the overall group. These results indicate that total hip arthroplasty without cement can be successful in older patients. This study also provides a reference for comparison with the results of total hip arthroplasty performed with cement and those of so-called hybrid total hip arthroplasty (an acetabular component fixed without cement and a femoral component fixed with cement) in patients who are sixty-five years of age or older.

Aged↗

Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat.

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels were due to chemical induction of hepatic thyroid hormone metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixture was found to significantly increase the clearance of [125I]T4 from the serum, suggesting an enhanced excretion of the hormone. In the liver, the activity of hepatic uridine glucuronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase activity trended downward with dose. Bile flow as well as the hepatic uptake and biliary excretion of [125I]T4 were increased following exposure to FOE 5043. Thyroidal function, as measured by the discharge of iodide ion in response to perchlorate, and pituitary function, as measured by the capacity of the pituitary to secrete thyrotropin in response to an exogenous challenge by hypothalamic thyrotropin releasing hormone, were both unchanged from the controlled response. These data suggest that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver.

Acetamides↗

Ambulatory care heads for the 21st century.

There is increasing market pressure to deliver ambulatory care in a most traditional manner, that is, with a high level of service and personal touch. The ambulatory care providers of the future will meet this demand. However, they will do so with approaches and support systems that are anything but traditional. Care is increasingly being delivered in large, integrated systems. Extraordinary service levels are being made feasible again--this time through a combination of new support systems, including total quality management task forces, patterns of care software, consolidated phone centers that can provide access from anywhere anytime, electronic data interfaces, and the Internet.

Ambulatory Care↗

Prevention of heterotopic bone formation after acetabular fracture fixation by single-dose radiation therapy: a preliminary report.

A common complication after acetabular fracture fixation is formation of heterotopic ossification (HO) in the soft tissues about the hip. We are reporting on the use of a single, low-dose radiation therapy regimen to prevent HO in the population of postoperative acetabular fracture patients. Thirty acetabular fracture patients who were at risk for HO after surgery were reviewed with an average follow-up of 12 months. Twenty-one of these patients received radiation therapy in the postoperative period according to a single dose protocol. Nine patients did not receive any prophylactic treatment for the prevention of HO during the same period. One patient from each of these categories was lost to follow-up. Of the 20 treated and followed patients, none developed HO higher than grade 2, and nine had no HO at all. None of the treated patients had any functional deficit due to HO, and none had any complications related to radiation treatment. Of the untreated patients, all had grade 2 HO or above. Three developed grade 4 HO and have undergone reoperation for resection of HO. Study weakness include the fact that the non-treated patients were significantly different from the treated patients in several ways; including the incidence of multiple trauma, head injury, and delay to surgery. No attempt was made to randomize patients prospectively, nor to directly compare the two groups. However, we can conclude, based on comparison with reported rates of HO formation, that single, low-dose radiation therapy is a safe and effective method for prevention of HO in the postoperative acetabular fracture patient. It is as effective as previously reported multidose regimens.

Acetabulum↗

Making integrated health care work.

This article summarizes the authors' thinking on value added in health care, and offers examples of the major strategies being implemented by integrated systems across the United States to increase their value and improve their competitive positioning. The research results are based on a review of published literature on 150 health care organizations in various stages of integration, and 20 in-depth case studies of integrating systems.

Cost Control↗

Optimizing primary care services.

One of the most recent and pervasive trends in healthcare is the restructuring of primary care. In many markets, the solo family practice physicians increasingly family practice physician is a thing of the past. Primary care physicians increasingly are aligning themselves with larger players such as multispecialty groups, hospitals, health plans, or practice management companies. This article draws on the authors' research into 20 healthcare systems in various stages of development as well as their own consulting experience to answer several questions: Why is the establishment or purchase of primary care physician practices an exploding national trend? What are the pros and cons of this approach? Is it better to purchase existing practices or establish new ones from the ground up? What are the pros and cons of virtual integration (affiliation without purchase) versus other forms of integration?

Community Networks↗

Effect of heterologous factor V heavy chain sequences on the secretion of recombinant human factor VIII.

Factor VIII and factor V share a repetitive domain structure of A1-A2-B-A3-C1-C2. To define the region(s) within the factor VIII heavy chain that result in inefficient expression of the recombinant protein, we expressed a series of factor VIII/factor V chimeras that contained heterologous sequences from the A1 and/or A2 domains. Substitution of the factor VIII A1 domain dramatically reduced secretion of factor V approximately 500-fold, whereas substitution of the factor VIII A2 domain had minimal effect on secretion. Conversely, substitution of the factor V A1 domain increased secretion of factor VIII approximately 3-fold, whereas substitution of the factor V A2 domain actually reduced secretion approximately 4-fold. Pulse chase experiments confirmed that reduced expression levels were due to decreased secretion rather than instability of secreted protein. Smaller substitutions did not further localize within the A1 domain the regions responsible for inefficient secretion.

Amino Acid Sequence↗

Extrathyroidally mediated changes in circulating thyroid hormone concentrations in the male rat following administration of an experimental oxyacetamide (FOE 5043).

Evidence of increased hepatic metabolizing capacity coupled with reductions in serum thyroxine (T4) levels were noted in the rat during preliminary toxicity studies with FOE 5043, an oxyacetamide with herbicidal properties. These findings were consistent with reports in the literature suggesting that declines in T4 as a result of exposure to various classes of chemicals may be mediated extrathyroidally, such as through chemical induction of hepatic thyroid hormone metabolism. To examine this question with respect to FOE 5043, male rats were surgically thyroidectomized and provided thyroid hormone replacement therapy via implanted osmotic minipumps capable of maintaining a T4/triiodothyronine (T3) serum concentration for approximately 4 weeks at a level comparable to that of euthyroid controls. Seven days after minipump implantation, thyroidectomized + T4/T3 (TX + T4/T3) and nonthyroidectomized intact rats (NTX) were fed diets containing 0, 25, 1000, or 3000 ppm FOE 5043 for up to 3 weeks. Dose-related and equivalent declines in total and free serum T4 levels in both TX + T4/T3 and NTX rats were measured at Weeks 1, 2, and 3. Alterations in thyrotropin, total, free, and reverse serum T3 levels were also noted in both TX and NTX animals; however, a compound-related trend was difficult to discern and, when compared to the T4 response, the changes were markedly less consistent with respect to both time and dose. Additionally, dose-related increases in absolute and relative liver weights were measured in both TX + T4/T3 and NTX animals. As the only source of thyroid hormone in the TX + T4/T3 animals was that provided by the pump, these data suggest that FOE 5043-induced alterations in serum thyroid hormone levels, most notably T4, are being mediated indirectly, possibly as a result of increased hepatic metabolism, rather than through a direct effect on the thyroid gland.

Acetamides↗

Fostering common vision among network players.

In summary, a common vision requires two elements: a similar view of the external environment and where it is headed, and agreement on how to position the organization--physicians, hospitals, and others--to be successful over the long haul. Developing and embracing a common vision is critically important in moving toward integration or committing to other strategies for surviving and prospering in the future.

Hospital-Physician Joint Ventures↗

Costs and benefits of integrated healthcare systems.

Although forming an integrated healthcare system can be extremely expensive, many hospitals and physician groups are discovering that by doing so, they can reap significant benefits, including increased market share, more secure physician income, and better physician "quality of life," a financially stronger organization, and an enhanced ability to adapt to the changing healthcare environment. In most cases, the return on the investment required to reorganize the physician, hospital, and healthcare plan relationship is likely to be substantial.

Capital Financing↗

Structure of the gene for human coagulation factor V.

Activated factor V (Va) serves as an essential protein cofactor for the conversion of prothrombin to thrombin by factor Xa. Analysis of the factor V cDNA indicates that the protein contains several types of internal repeats with the following domain structure: A1-A2-B-A3-C1-C2. In this report we describe the isolation and characterization of genomic DNA coding for human factor V. The factor V gene contains 25 exons which range in size from 72 to 2820 bp. The structure of the gene for factor V is similar to the previously characterized gene for factor VIII. Based on the aligned amino acid sequences of the two proteins, 21 of the 24 intron-exon boundaries in the factor V gene occur at the same location as in the factor VIII gene. In both genes, the junctions of the A1-A2 and A2-A3 domains are each encoded by a single exon. In contrast, the boundaries between domains A3-C1 and C1-C2 occur at intron-exon boundaries, which is consistent with evolution through domain duplication and exon shuffling. The connecting region or B domain of factor V is encoded by a single large exon of 2820 bp. The corresponding exon of the factor VIII gene contains 3106 bp. The 5' and 3' ends of both of these exons encode sequences homologous to the carboxyl-terminal end of domain A2 and the amino-terminal end of domain A3 in ceruloplasmin. There is otherwise no homology between the B domain exons.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗