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Biomedical subjects

D Farley

Publications and source records attributed to D Farley.

At least 19 recordsLinked to original sources
PubMed2000

Isotopic synovectomy with P-32 in paediatric patients with haemophilia.

Isotopic synovectomy is being proposed as an option in the treatment of patients with haemophilic arthropathy. We present our experience with 11 paediatric patients who underwent 17, P-32 isotopic synovectomies for chronic haemophilic arthropathy. P-32 was injected into the joint per protocol, approved by the institutional review board. All our patients were male. Nine were factor VIII and two were factor IX deficient. The following joints were treated: ankle (n=10 procedures), elbow (n=5) and knee (n=2). The first procedure was performed on December 1993. None were human immunodeficiency virus positive. Mean age at the first procedure was 10.8 years (range, 5.2-15.2 years). Mean pretreatment joint clinical scores using the World Federation of Hemophilia guidelines for the ankle was 5.5 (SD +/- 2.3), the elbow 4.2 (+/-2.5), and knee 5.5 (+/-3.5); the corresponding post-treatment scores were 2.6 (+/-2.0), 1.4 (+/-0.5) and 2.5 (+/-3.5) respectively. Presynovectomy mean radiological scores using the Pettersson method were: ankle 1.8, elbow 1.8, and knee 1.5. A scoring system used in our centre for evaluating joints using magnetic resonance imaging (MRI) gave the following mean pretreatment scores: ankle 9.5, elbow 8.4, and knee 5.0. A marked decrease (an 80-100% decrease) in bleeding was seen in 13 of 17 procedures, and a moderate decrease (51-79% decrease) in two procedures, accounting for 85% reduction in bleeding into the target joints. The procedure was well tolerated and no untoward side-effects were noted as of May 1999, with a median follow-up of 40 months (range 19-65 months). None had any clinical evidence of cancer. Three patients had their joints retreated [elbow (one), ankle (two)]. These procedures were also well tolerated. In conclusion, in our study, isotopic synovectomy using P-32 appears to be feasible, safe and efficacious in the treatment of haemophilic arthropathy in paediatric patients who have been followed for a median of 40 months. As previously shown, MRI appears to give more detailed information about joint arthropathy than plain radiographs.

Adolescent↗
PubMed2000

Methoprene tolerance in Aedes nigromaculis in Fresno County, California.

Methoprene, a juvenile hormone analogue, has been used for at least 20 years as the primary insecticide to control the pasture mosquito Aedes nigromaculis in Fresno County, California. First reports of apparent methoprene control failures were noted in a pasture west of Fresno in September 1998. Insufficient control was noted in 12 different pastures the following season from April to September 1999. In September of 1999, field trials were conducted to better ascertain the level of control. Results based on pupal counts from different methoprene formulations and rates of application indicated that in some pastures low levels of control were achieved with Altosid (Liquid Larvicide) and Altosid XR-G. Control with Altosid Pellets was reported at 52-99%.

Aedes↗
PubMed1999

Objective and subjective measures of the quality of managed care in nursing homes.

BACKGROUND: The number of nursing home (NH) residents enrolled in managed care plans (HMO) will increase, and there is concern that the quality of their medical care may be compromised by cost-containment pressures. In this study, we evaluated the medical care of residents enrolled in 3 health maintenance organizations (HMO) that developed specific long-term care programs. OBJECTIVES: To compare the medical care received by NH residents enrolled in HMO and Fee-for-Service (FFS) plans with both objective process of care and consumer perception (subjective) measures. To describe the relationship between the objective and subjective measures. MEASURES: Number of primary care visits per month; process of medical care for 2 geriatric tracer conditions (falls, fevers); family and residents' perceptions of the adequacy of sickness episode management; and the frequency of primary provider visits. DESIGN: Quasi-experimental. RESULTS: HMO residents received more timely and appropriate responses to falls and fevers than did FFS residents. HMO residents also received more frequent routine visits by a primary care provider team consisting of a physician and nurse practitioner. Consumer perceptions of quality did not differ between the HMO and FFS groups. Families within both groups were significantly more positive than were residents about the frequency of visits by both physicians and nurse practitioners. Within the HMO group, both families and residents were more positive about the frequency of nurse practitioner visits than were physician visits even when the frequency of visits by the 2 providers were similar. CONCLUSIONS: Although the medical care received by HMO residents was better on most objective process measures than that received by FFS residents, consumer perceptions of care did not detect those differences. NH residents and families have different perceptions about the adequacy of visits by physicians and nurse practitioners, and both families and residents appear to have different expectations concerning how often they want physicians to visit as compared with nurse practitioners.

Fee-for-Service Plans↗
PubMed1999

Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase.

The initiation and progression of adult-onset periodontitis has been associated with infection of the gingival sulcus by Porphyromonas gingivalis. This organism utilizes a multitude of virulence factors to evade host defenses as it establishes itself as one of the predominant pathogens in periodontal pockets. A feature common to many other oral pathogens is the production of ammonia due to its protective effect during acidic cleansing cycles in the mouth. Additionally, ammonia production by P. gingivalis has been proposed as a virulence factor due to its negative effects on neutrophil function. In this study, we describe the first purification of a peptidylarginine deiminase (PAD) from a prokaryote. PAD exhibits biochemical characteristics and properties that suggest that it may be a virulence agent. PAD deiminates the guanidino group of carboxyl-terminal arginine residues on a variety of peptides, including the vasoregulatory peptide-hormone bradykinin, to yield ammonia and a citrulline residue. The soluble protein has an apparent mass of 46 kDa, while the DNA sequence predicts a full-length protein of 61.7 kDa. PAD is optimally active at 55 degrees C, stable at low pH, and shows the greatest activity above pH 9.0. Interestingly, in the presence of stabilizing factors, PAD is resistant to limited proteolysis and retains significant activity after short-term boiling. We propose that PAD, acting in concert with arginine-specific proteinases from P. gingivalis, promotes the growth of the pathogen in the periodontal pocket, initially by enhancing its survivability and then by assisting the organism in its circumvention of host humoral defenses.

Amino Acid Sequence↗
PubMed1999

The design of Healthcare for Communities: a study of health care delivery for alcohol, drug abuse, and mental health conditions.

There is a shortage of data to inform policy debates about the quickly changing health care system. This paper describes Healthcare for Communities (HCC), a component of the Robert Wood Johnson Foundation's Health Tracking Initiative that was designed to fill this gap for alcohol, drug abuse, and mental health care. HCC bridges clinical perspectives and economic/policy research approaches, links data at market, service delivery, and individual levels, and features a household survey of nearly 9,600 individuals with an employer follow-back survey. Public use files will be available in late 1999.

Community Mental Health Services↗
PubMed1997

The osteoclast-associated protease cathepsin K is expressed in human breast carcinoma.

Human cathepsin K is a novel cysteine protease previously reported to be restricted in its expression to osteoclasts. Immunolocalization of cathepsin K in breast tumor bone metastases revealed that the invading breast cancer cells expressed this protease, albeit at a lower intensity than in osteoclasts. In situ hybridization and immunolocalization studies were subsequently conducted to demonstrate cathepsin K mRNA and protein expression in samples of primary breast carcinoma. Expression of cathepsin K mRNA was confirmed by reverse transcription PCR and Southern analysis in a number of human breast cancer cell lines and in primary human breast tumors and their metastases. As this protease is known to degrade extracellular matrix, including bone matrix proteins, it is possible that cathepsin K may contribute to the invasive potential of breast cancer cells, including those that metastasize to bone. Thus, cathepsin K may be a potential target leading to the design of novel drugs for cancer therapy.

Blotting, Southern↗
PubMed1997

All-payer severity-adjusted diagnosis-related groups: a uniform method to severity-adjust discharge data.

Measuring severity of illness within diagnosis-related groups (DRGs) has become increasingly important because of the growing need to compare outcomes across providers. In response to these needs, the Health Care Financing Administration (HCFA) has developed a DRG-based severity system as a refinement to its current Medicare DRG structure. As a result of this recent HCFA research, all-payer severity-adjusted DRGs (APS-DRGs) have been developed to provide a uniform approach for severity classification that is also applicable to the all-payer population.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1995

FDA's Rx for better medication information.

Under a newly proposed program, by the turn of the century at least 75 percent of patients getting new prescriptions would receive easily understandable written information. The public has until Nov. 22 to comment.

Drug Information Services↗
PubMed1995

Strategic responses by hospitals to increased financial risk in the 1980s.

OBJECTIVE: This research addresses the following types of responses by hospitals to increased financial risk: (a) increases in prices to privately insured patients (testing separately the effects of risk from the effects of "cost-shifting" that depends on level of Medicare payment in relation to case mix-adjusted cost); (b) changes in service mix offered and selectivity in acceptance of patients to reduce risk; and (c) efforts to reduce variation in resource use for those patients admitted. DATA SOURCES: The database includes a national panel of over 400 hospitals providing information from patient discharge abstracts, hospital financial reports, and county level information over the period 1980-1987. STUDY DESIGN: Econometric methods suitable to panel data are implemented, with tests for pooling, hospital-specific fixed effects, and possible problems of selection bias. PRINCIPAL FINDINGS: The prices paid by private insurers to a particular hospital were affected by the changes in risk imposed by Medicare prospective payment, the generosity of Medicare payment, state rate regulation, and ability of the hospital to bear risk. The risk-weighted measure of case mix did not respond to changes in payment policy, but other variables reflecting the management of care after admission to reduce risk did change in the predicted directions. CONCLUSIONS: Some of the findings in this article are relevant to current Medicare policies that involve risk-sharing, for instance, special allowances for "outlier" patients with unusually high cost, and for sole community hospitals. The first type of allowance appears successful in preserving access to care, while the second type is not well justified by the findings. State rate regulation programs were associated not only with lower hospital prices but also with less risk reduction behavior by hospitals. The design of regulation as a sort of risk-pooling arrangement across payers and hospitals may be attractive to hospitals and help explain their support for regulation is some states.

Cost Allocation↗
PubMed1993

Cloning and sequence analysis of rat hepsin, a cell surface serine proteinase.

A cDNA coding for the rat serine proteinase hepsin was isolated and its nucleotide sequence has been determined. The cDNA was 1739 nucleotides long and contained an open reading frame encoding a protein consisting of 416 amino-acid residues. The deduced amino-acid sequence of the rat enzyme was very similar to the human hepsin sharing an amino-acid sequence identity of 88.7%. Hydropathy plots reveal the presence of a short hydrophobic region close to the N-terminus believed to be a transmembrane domain which anchors the proteinase on the cell surface. The predicted sequence contains the His, Asp and Ser residues which make up the catalytic triad common to all serine proteinases.

Amino Acid Sequence↗
PubMed1993

Finasteride: a slow-binding 5 alpha-reductase inhibitor.

A microsomal preparation of human prostatic tissue was used to study the kinetics of interaction of steroid 5 alpha-reductase with finasteride, a known 5 alpha-reductase inhibitor. This molecule has been reported to reversibly bind 5 alpha-reductase in a competitive manner to testosterone with a Ki value in the 10 nM range. The results presented in this paper show that enzyme-inhibitor complex formation does not take place instantaneously as assumed in previous studies. At neutral pH and 37 degrees C, the association of enzyme with inhibitor is governed by a rate constant, kon, of 2.7 x 10(5) M-1 s-1. This low kon value, in combination with the high energy of activation of the association reaction (150 kJ mol-1), indicates that the association process is not diffusion controlled and may proceed through intermediate steps. However, such an intermediate was not detected kinetically under the inhibitor concentrations investigated. We therefore conclude that the equilibrium dissociation constant, Ki*, for the initial binding of the enzyme to the inhibitor is higher than 1.5 x 10(7) M. Even at inhibitor concentrations as low as 1 nM, the reaction was completely displaced to the EI complex and no residual activity detected once the equilibrium was reached. Hence, the interaction between finasteride and 5 alpha-reductase can also be characterized by a very low overall equilibrium dissociation constant (Ki << 10(-9) M), at least 1 order of magnitude lower than previously reported values.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1991

Expression of rat 5 alpha-reductase in Saccharomyces cerevisiae.

Dihydrotestosterone (DHT) is the principle androgen in certain tissues such as the prostate. DHT is formed from testosterone by the NADPH-dependent enzyme 5 alpha-reductase (5AR). In this paper we report the expression of catalytically active steroid 5AR from the rat in Saccharomyces cerevisiae. A full length cDNA coding for 5AR was isolated from a rat liver cDNA library and fixed in frame to the signal sequence of yeast acid phosphatase. A constitutive short promoter fragment of the acid phosphatase gene (PHO5) and the PHO5 transcriptional terminator were added and the expression cassette ligated into the yeast 2 mu vector pDP34. S. cerevisiae transformed with the 5AR expression plasmid pDP34/PHO5AR exhibited about 100-fold more activity per gram wet weight than rat prostate.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1989

The human neutrophil elastase gene. Analysis of the nucleotide sequence reveals three distinct classes of repetitive DNA.

DNA sequence analysis reveals the gene encoding human neutrophil elastase to be contained on a 6-kb EcoRI fragment. The gene contains five exons and closely resembles rat mast cell proteinase II and mouse adipsin in its exon structure and intron splice phase. Non-coding regions are very rich in repetitive DNA, containing seven Alu-like segments, three distinct clustered direct repeats with monomer lengths of 53 (six repeats), 23 (three repeats) and 41 (ten repeats) nucleotides, and a 200-nucleotide AT-rich region. Protein sequence analysis, inferred from the coding regions of the gene, indicates that neutrophil elastase may contain an unusual activation peptide similar to that found in the other major neutrophil serine proteinase, cathepsin G.

DNA↗
PubMed1988

Neutrophil elastase and cathepsin G: structure, function, and biological control.

When neutrophils invade inflamed areas of the body to remove either dead or foreign components they inadvertently release potent enzymes which can, if not properly controlled, cause severe damage to healthy tissue. This can lead to a myriad of diseases including emphysema, rheumatoid arthritis, and glomuerlopnephritis, all of which are really problems of abnormal connective tissue turnover due to uncontrolled protelysis by neutrophil elastase and cathepsin G. An important step in elucidating the functions of both elastase and cathepsin G has been made by virtue of the fact that the amino acid sequence of each has been determined. Furthermore, the crystal structure of one, neutrophil elastase, is now understood. With this knowledge in mind and with the potential for a similar understanding of the mechanism of action of cathepsin G, it should soon be possible to produce synthetic inhibitors of each enzyme which can act as adjunct inhibitors to those naturally circulating in the blood or present in other tissues. As a result there is great hope for reducing the severity of injury produced by these enzymes and, therefore, in decreasing the risk for development of the debilitating diseases associated with abnormal proteolysis by neutrophil proteinases.

Amino Acid Sequence↗
PubMed1988

Molecular cloning of human neutrophil elastase.

The human U937 cell line, a promonocyte-like leukemic line, has been shown to synthesize neutrophil elastase (Senior, R. M. et al. (1982) J. Clin. Invest. 69, 384-393). We have constructed a lambda gt11 cDNA library using RNA from this cell line and isolated a clone encoding part of the protein sequence of neutrophil elastase. Nucleotide sequencing indicates the clone encodes residues 108-243 (standard chymotrypsinogen numbering) of the enzyme, plus a hitherto unsuspected 20 residue-C-terminal extension of unusual structure. Comparison of the nucleotide and amino-acid sequence of elastase with the recently reported sequence of medullasin, a proteinase isolated from bone marrow, suggests they are identical.

Amino Acid Sequence↗