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Biomedical subjects

K D Moore

Publications and source records attributed to K D Moore.

At least 37 records · Page 2Linked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1992

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↗
PubMed1992

Health care reform: how hospitals, physicians should prepare.

As the momentum behind health care reform continues to build, hospitals should take specific steps to prepare for each likely scenario. The authors speculate about what form health care reform will take, discuss the strategic implications of each scenario and suggest steps hospitals should take, including an analysis of hospital/physician integration, marketing, services and efficiency.

Cost-Benefit Analysis↗
PubMed1987

Diversification offers new opportunities for health care.

In this excerpt from the book, Market-Driven Strategies in Healthcare, healthcare diversification is explored. The various reasons, survival strategies, and expectations for a new venture are outlined. Although many new ventures are struggling and profits are being generated slowly, there are many potentially successful opportunities available to the aggressive healthcare system. With careful screening and selection, diversification efforts by an organization can present promising results.

Evaluation Studies as Topic↗
PubMed1987

Employers looking for more than health care cost containment.

Now is the time to chart strategies for the future. One market which needs reevaluation is the behavior of employers toward health plans. The authors through a review of both secondary and their own research show that most of the efforts at cost containment are the interests of large firms. The article summarizes what employers are currently seeking from health plans and how they are evaluating the growing number of alternatives available to them.

Cost Control↗
PubMedDate not supplied

In vitro properties of a newly established medulloblastoma cell line, MCD-1.

Medulloblastomas are poorly differentiated brain tumors believed to arise from primitive pleuripotential stem cells, and tend to express mixed neuronal and glial properties. In the present study, we examined immunohistochemical and neurotransmitter phenotypic properties in a newly established medulloblastoma cell line, MCD-1. MCD-1 cells were immortal, not contact-inhibited, but did not grow in soft agar. Immunohistochemical studies showed positive staining for neurofilament protein (NF), neuron-specific enolase (NSE), synaptophysin, MAP 2, tau, NCAM 180, vimentin, and S-100 protein. The cells expressed specific uptake of glutamate, serotonin, and choline, but not GABA or dopamine. A significant increase in process extension was seen in response to agents that enhance intracellular cyclic AMP, especially 3-isobutyl-1-methylxanthine (IBMX). Process formation induced by IBMX was associated with a decrease in cell proliferation as evidenced by a reduction in numbers of cells incorporating 5-bromo-2-deoxyuridine (BrdU). No increase in process extension was observed following exposure to NGF or retinoic acid. MCD-1 cells were shown to produce transforming growth factor beta (TGF beta), and were immunopositive for mutant p53. Transfection assays with the PG13-Luc reporter plasmid, which contains a p53-responsive enhancer element and a luciferase reporter gene, suggested MCD-1 cells are deficient in wild-type p53 and do not activate p53 on treatment with the anticancer agent adriamycin. The MCD-1 cell line is suggested to represent an abnormally differentiated cell type, which has some properties consistent with a multipotent neuronal phenotype while retaining some properties of immature cells of a glial lineage. The MCD-1 cell line can be used to provide a model of a medulloblastoma cell line that is resistant to growth-controlling and anticancer agents.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Antibodies to prothrombin, factor V, and beta2-glycoprotein I and vascular access thrombosis.

We studied 88 hemodialysis patients for the presence of antibodies to human factor II (hFII), bovine factor V (bFV), and human beta2-glycoprotein 1 (beta2GPI). Forty-one patients had elevated anti-hFII antibodies, 17 had elevated anti-bFV antibodies, and 9 had elevated anti-beta2GPI antibodies. Fifty-two patients had elevated antibodies to one or more protein. Patients with PTFE grafts had elevated antibodies most frequently (21 [75%] vs. 20 fistulas [45%; p = 0.016 compared with PTFE] and 11 tunneled catheters [68.8%]). Twelve of 13 patients (92.3%) with PTFE grafts and thrombosis had elevated antibody levels, compared with 9 of 15 without thrombosis (60%; p = 0.049). The number of thromboses and mean thrombosis rates were significantly higher in PTFE patients with antibodies (1.24 vs. 0.14 thromboses, p < 0.01; 42.67 vs. 6.44 thromboses/100 patient years, p < 0.05). When analyzed individually, thrombotic complications occurred more frequently in patients with PTFE grafts and elevated anti-bFV antibodies (p = 0.016), but did not correlate with anti-hFII or anti-beta2GPI antibodies. Thrombotic complications did not correlate with elevated antibody levels in patients with AV fistulas or cuffed catheters. In conclusion, hemodialysis patients with PTFE grafts frequently have elevated antibodies to FII, FV, and beta2GPI, and the presence of elevated antibody levels to one or more of these proteins is associated with an increased thrombotic risk. Further studies are necessary to determine whether limiting exposure to bovine thrombin preparations will decrease the incidence of these antibodies and PTFE graft thrombosis.

Aged↗
PubMedDate not supplied

Changes in L1 antigen expression in the rat striatum after substantia nigra lesions.

L1 antigen promotes neurite outgrowth from dopaminergic neurons in tissue culture. In the present study, we examined the effects of dopaminergic deafferentation of the striatum on L1 expression. In the medial-periventricular part of the striatum, both complete and partial substantia nigra (SN) lesions decreased L1 expression. Complete lesions increased L1 expression in the dorso-medial and ventro-lateral parts of the striatum on the lesioned side when compared with that on the non-lesioned side. The decrease in the ventro-lateral area was maintained in animals examined three months after the lesioning. Animals with partial SN lesions showed a different pattern of altered L1 expression. After frontal cortex lesions, changes in L1 expression also occur preferentially in the dorso-medial and periventricular striatum. Therefore, the results indicate a complex regulation of L1 expression after damage of striatal circuitry, manifested by a preferential occurrence of changes in periventricular regions.

Animals↗