Search PubMed⌕ Search

Biomedical subjects

M L Brown

Publications and source records attributed to M L Brown.

At least 37 records · Page 2Linked to original sources
PubMed1999

Obtaining long-term disease specific costs of care: application to Medicare enrollees diagnosed with colorectal cancer.

OBJECTIVES: This study develops estimates of long-term, cancer-related treatment cost using a modeling approach and data from the SEER-Medicare linked database. The method is demonstrated for colorectal cancer. METHODS: Data on Medicare payments were obtained for colorectal cancer patients for the years 1990 to 1994 from the SEER-Medicare linked database. Claims payment data for control subjects were obtained for Medicare enrollees without cancer residing in the same areas as patients. Estimates of long-term cost (< or = 25 years following the date of diagnosis) were obtained by combining treatment/phase-specific cost estimates with estimates of long-term survival from SEER. Treatment phases were defined as initial care, terminal care, and continuing care. Cancer-related estimates for each phase were obtained by subtracting costs for control subjects from the observed costs for cancer patients, matching on age group, gender, and registry area. Estimates of long-term cost < or = 11 years obtained by this method were compared with 11-year estimates obtained by application of the Kaplan-Meier sample average (KMSA) method. RESULTS: The mean initial-phase cancer-related cost was approximately $18,000 but was higher among patients with more advanced cancer. The mean continuing-phase cancer-related cost was $1,500 per year and declined with increasing age, but was higher on an annual basis among persons with later stages of cancer and shorter survival time. The mean terminal-phase cancer-related cost was $15,000 and declined with both age at death and more advanced stage at diagnosis. After the phase-specific estimates were combined, the average long-term cancer-related cost was $33,700 ($31,300 at 3% discount rate) for colon cancer compared with $36,500 ($33,800 at 3% discount rate) for cancer of the rectum. This represented about half of the total long-term cost for Medicare enrollees diagnosed with this disease. Long-term cost was highest for Stage III cancer and lowest for in situ cancer. Eleven-year cancer-related costs estimated by the KMSA method were similar to estimates using the phase-based approach. CONCLUSIONS: This paper demonstrates that valid estimates of cancer-related long-term cost can be obtained from administrative claims data linked to incidence cancer registry data.

Age Distribution↗
PubMed1999

Survival and treatment for colorectal cancer Medicare patients in two group/staff health maintenance organizations and the fee-for-service setting.

The current study compares treatment use and long-term survival in colorectal cancer patients between Medicare beneficiaries enrolled in two large prepaid group/staff health maintenance organizations (HMOs) and the fee-for-service (FFS) setting. The study is based on 15,352 colorectal cancer cases diagnosed between 1985 and 1992 and followed through 1995. Survival differences between the HMO and FFS cases were assessed using Cox regression. Treatment differences were evaluated using logistic regression. HMO cases had a lower overall mortality than did FFS cases but not a significantly lower colorectal cancer-specific mortality. Use of surgical resection was similar between HMO and FFS cases. However, rectal cancer cases in the HMOs were more likely to receive postsurgical radiation therapy than FFS cases. Superior overall survival in the HMOs may be the result of increased colorectal cancer screening, greater use of adjuvant therapies, and selection of healthier individuals.

Aged↗
PubMed1999

Antipeptide antibodies reveal interrelationships of MBP 200 and MBP 235: unique apoB-specific receptors for triglyceride-rich lipoproteins on human monocyte-macrophages.

Two human monocyte-macrophage (HMM) membrane binding proteins, (MBP) 200 and 235, are receptor candidates that bind to the apolipoprotein (apo)B-48 domain in triglyceride-rich lipoproteins for uptake independent of apoE. Microsequence analysis of the purified reduced MBP 200R characterized tryptic peptides of MBP 200R. A synthetic peptide mimicking a unique, unambiguous 10-residue sequence (AEGLMVTGGR) induced antipeptide antibodies that specifically recognized MBP 200, 235 and 200R, in 1- and 2-dimensional analyses, indicating 1) the ligand binding protein was sequenced and 2) MBP 200 and 235 yielded MBP 200R upon reduction. These antibodies identified the MBPs in human blood-borne, THP-1, U937 MMs, and endothelial cells (EC) but not in human fibroblasts or Chinese hamster ovary (CHO) cells. Fluorescence activated cell sorting (FACS) analysis located the MBPs on the MM surface as necessary for receptor function. The 10-residue, unambiguous MBP 200-derived sequence is unique, with no matches in extant protein databases. Antipeptide antibodies bind to the MBPs in reticuloendothelial cells that have this receptor activity, but not to proteins in cells that lack this receptor activity. These studies provide the first direct protein sequence and immunochemical data that a new, unique apoB receptor for triglyceride-rich lipoproteins exists in human monocytes, macrophages, and endothelial cells.

Amino Acid Sequence↗
PubMed1999

Managed care, consolidation among health care providers, and health care: evidence from mammography.

We discuss the effects of managed care on the structure of the health care delivery system, focusing on managed-care-induced consolidation among health care providers. We empirically investigate the relationship between HMO market share and mammography providers. We find evidence of consolidation: increases in HMO activity are associated with reductions in the number of mammography providers and with increases in the number of services produced by remaining providers. We also find that increases in HMO market share are associated with reductions in costs for mammography and with increases in waiting times for appointments, but not with worse health outcomes.

Adult↗
PubMed1998

Apolipoprotein B-48 or its apolipoprotein B-100 equivalent mediates the binding of triglyceride-rich lipoproteins to their unique human monocyte-macrophage receptor.

Studies in animals and humans have demonstrated uptake of plasma chylomicrons (triglyceride-rich lipoprotein [TGRLP] of Sf>400) by accessible macrophages in vivo. One potential mechanism is via a unique receptor pathway we previously identified in human blood and THP-1 monocytes and macrophages for the lipoprotein lipase (LpL)- and apolipoprotein (apo) E-independent, high-affinity, specific binding of plasma chylomicrons and hypertriglyceridemic VLDL (HTG-VLDL) to cell-surface membrane-binding proteins (MBP 200, 235; apparent Mr 200, 235 kD on SDS-PAGE) that leads to lipid accumulation in vitro. Competitive binding studies reported here demonstrate that anti-apoB antibodies specifically block the high-affinity binding of TGRLP to this receptor on THP-1 cells and on ligand blots. LpL, which binds to an N-terminal domain of apoB, also inhibits TGRLP binding both to this site on THP-1s and to MBP 200, 235 by binding to apoB. Chylomicrons of Sf>1100 that contain apoB-48, but not apoB-100, bind specifically to MBP 200, 235, and this binding is blocked by anti-apoB IgG. In contrast, lactoferrin and heparin do not inhibit TGRLP binding. We conclude that the receptor-binding domain is within apoB-48 (or an equivalent in apoB-100) near the LpL-binding domain, but not a heparin-binding domain. Uptake of TGRLP by this mechanism could provide essential nutrients or, in HTG, cause excess lipid accumulation and foam cell formation.

Antibodies↗
PubMed1998

Factors associated with women's adherence to mammography screening guidelines.

OBJECTIVE: To examine individual and environmental factors associated with adherence to mammography screening guidelines. DATA SOURCES: A unique data set that combines a national probability sample (1992 National Health Interview Survey); a national probability sample of mammography facility characteristics (1992 National Survey of Mammography Facilities); county-level data on 1990 HMO market share; and county-level data on the supply of primary care providers (1991 Area Resource File). STUDY DESIGN: The design was cross-sectional. DATA EXTRACTION/ANALYSIS: Data sets were linked to create an individual-level sample of women ages 50-74 (weighted n = 2,026). We used multipart, sequential logistic regression models to examine the predictors of having ever had mammography, having had recent mammography, and adherence to guidelines. We categorized women as adherent if they reported a lifetime number of exams appropriate for their age (based on screening every two years) and they reported having had an exam in the past two years. PRINCIPAL FINDINGS: Only 27 percent of women had the age-appropriate number of screening exams (range 16 percent-37 percent), while 59 percent of women had been screened within two years. Women were significantly more likely to adhere to screening guidelines if they reported participating with their doctor in the decision to be screened; were younger; had smaller families, higher education and income, and a recent Pap smear; reported breast problems; and lived in an area with a higher percentage of mammography facilities with reminder systems, no shortage of primary care providers, higher HMO market share, and higher screening charges. CONCLUSIONS: A small percentage of women adhere to screening guidelines, suggesting that adherence needs to become a focus of clinical, programmatic, and policy efforts.

Aged↗
PubMed1997

Effects of log P and phenyl ring conformation on the binding of 5-phenylhydantoins to the voltage-dependent sodium channel.

Binding to the neuronal voltage-dependent sodium channel (NVSC) was evaluated for 12 5-phenylhydantoins which systematically varied either log P and/or 5-phenyl ring orientation. The linear correlation of log P with in vitro sodium channel binding activity (log IC50) for hydantoins 1-12 and diphenylhydantoin (DPH) (r2 = 0.638) suggested that simple partitioning into the lipid phase is important but not sufficient to account for the effects of hydantoins on the NVSC. Comparisons among different hydantoins with the same log P but different low-energy phenyl ring orientations revealed that, in addition to log P, the correct 5-phenyl orientation is important for efficient binding.

Animals↗
PubMed1997

Crystallization and preliminary crystallographic analysis of recombinant human P38 MAP kinase.

The recombinant human p38 MAP kinase has been expressed and purified from both Escherichia coli and SF9 cells, and has been crystallized in two forms by the hanging drop vapor diffusion method using PEG as precipitant. Both crystal forms belong to space group P2(1)2(1)2(1). The cell parameters for crystal form 1 are a = 65.2 A, b = 74.6 A and c = 78.1 A. Those for crystal form 2 are a = 58.3 A, b = 68.3 A and c = 87.9 A. Diffraction data to 2.0 A resolution have been collected on both forms.

Animals↗
PubMed1997

Induction of cyclooxygenase 1 and 2 in the rat stomach during endotoxemia: role in resistance to damage.

BACKGROUND & AIMS: Prostaglandins and nitric oxide are key mediators of gastric mucosal defense. Endotoxemia alters gastric resistance to damage, but little is known of the effects of chronic endotoxemia on the expression of prostaglandin and nitric oxide synthases (NOSs). The effects of short- vs. long-term administration of endotoxin on gastric resistance to damage and on expression of NOS and prostaglandin synthesis were compared. METHODS: Rats were treated with short- or long-term bacterial endotoxin, after which susceptibility to ethanol-induced damage was assessed. The effects of various inhibitors of prostaglandin and NOS were examined. Expression of gastric NOS and cyclooxygenase (COX) messenger RNA (mRNA) were examined. RESULTS: Repeated administration of endotoxin increased gastric resistance to ethanol- but not indomethacin-induced injury. Indomethacin, but not a highly selective COX-2 inhibitor or an inducible NOS inhibitor, abolished long-term endotoxin-induced gastric resistance to injury. Expression of mRNA for both COX-1 and -2, but not for endothelial or inducible NOS, were significantly increased after long-term endotoxin administration. CONCLUSIONS: Repeated exposure to endotoxin resulted in increased resistance of the gastric mucosa to injury through a prostaglandin-dependent pathway. These prostaglandins were produced via COX-1, which like COX-2, is induced by endotoxin administration.

Animals↗
PubMed1997

Concise parathyroidectomy: the impact of preoperative SPECT 99mTc sestamibi scanning and intraoperative quick parathormone assay.

BACKGROUND: Results of initial operation for sporadic primary hyperparathyroidism are generally excellent, yet today there is pressure to improve outcome and resource utilization. METHODS: We designed a prospective longitudinal cohort study comparing two approaches to concise parathyroidectomy. Strategy A was defined as the palpation method for selective unilateral exploration. Strategy B was defined as the routine use of both preoperative 99mTc sestamibi single photon emission computed tomography (SPECT) imaging and intraoperative quick parathormone assay. With either strategy the study period was 19 months and patients explored unilaterally were candidates for same-day discharge. We compared surgical outcome for 128 consecutive consenting patients each with 6 months or more of follow-up (mean 12 +/- 7.6 months). RESULTS: Demographic, biochemical and pathologic findings did not differ between groups. SPECT imaging precisely localized hyperfunctioning parathyroid tissue. Compared with Strategy A (n = 61), the 67 patients treated by use of Strategy B experienced a higher rate of unilateral exploration (41.0% versus 62.7%, p < 0.00001) and a shorter length of stay (1.07 versus 1.90 days, p < 0.00001) and tended to have shorter operative times, fewer operative failures, and less morbidity. Total perioperative costs did not differ between groups. CONCLUSIONS: Routine use of intraoperative quick parathormone measurement and preoperative 99mTc sestamibi SPECT is as safe, effective, and cost-effective as conventional approaches to parathyroidectomy. Use of this strategy is associated with significant reductions in extent of surgery and length of hospital stay.

Adult↗
PubMed1997

A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket.

The crystal structure of human p38 mitogen-activated protein (MAP) kinase in complex with a potent and highly specific pyridinyl-imidazole inhibitor has been determined at 2.0 A resolution. The structure of the kinase, which is in its unphosphorylated state, is similar to that of the closely-related ERK2. The inhibitor molecule is bound in the ATP pocket. A hydrogen bond is made between the pyridyl nitrogen of the inhibitor and the main chain amido nitrogen of residue 109, analogous to the interaction from the N1 atom of ATP. The crystal structure provides possible explanations for the specificity of this class of inhibitors. Other protein kinase inhibitors may achieve their specificity through a similar mechanism. The structure also reveals a possible second binding site for this inhibitor, with currently unknown function.

Adenosine Triphosphate↗
PubMed1997

Evaluation of laminin peptide fragments labeled with indium-111 for the potential imaging of malignant tumors.

The laminin peptide fragments GYIGSR-NH2 and CDPGYIGSR-NH2 are known to bind to a 67-kDa laminin receptor. This receptors is understood to be expressed at higher than normal levels in malignant tumor cells, particularly those of breast and colon carcinomas. Peptides DTPA-GYIGSR-NH2 (1), DTPA-(GYIGSR-NH2)2 (2), DTPA-CDPGYIGSR-NH2 (3), DTPA-(CDPGYIGSR-NH2)2 (4), and negative control DTPA-GAGAGA-NH2 (5) were prepared by solid-phase peptide synthesis. All five DTPA-conjugated peptides were subsequently radiolabeled with 111In and their tissue distribution evaluated in mice bearing C3H tumors. 111In-3 and 111In-4 showed the highest specific tumor localization. These preliminary data support further study of radiolabeled petide fragments for the potential detection of malignant tumors of the breast and other organs.

Amino Acid Sequence↗
PubMed1997

Cost of care for cancer in a health maintenance organization.

The direct costs of medical care for cancer are examined at Kaiser Permanente (KP) in Northern California. Use data from July 1987 through June 1991 were obtained from KP automated files for all 21,977 KP patients in the Bay Area SEER registry with cancer at one of seven cancer sites. Medical charts were reviewed for a stratified sample of 886 patients. Costs were estimated for initial, continuing, and terminal care, and for all person time within 15 years of diagnosis, by stage at diagnosis. From diagnosis until death or 15 years, long-term costs attributable to cancer were as follows: breast, $35,000; colon, $42,000; rectum, $51,000; lung, $33,000; ovarian, $64,000; prostate, $29,000; and Non-Hodgkin's Lymphoma (NHL), $48,000. The utilization and cost results reported here may be useful in assessing the cost-effectiveness of cancer prevention and control programs, in adjusting capitation rates and budgets, and in estimating the aggregate medical care costs attributable to cancer.

Ambulatory Care↗