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Biomedical subjects

L Young

Publications and source records attributed to L Young.

At least 91 records · Page 5Linked to original sources
PubMed1999

Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer.

PURPOSE: BMS-182248-1 (BR96-doxorubicin immunoconjugate) is a chimeric human/mouse monoclonal antibody linked to approximately eight doxorubicin molecules. The antibody is directed against the Lewis-Y antigen, which is expressed on 75% of all breast cancers but is limited in expression on normal tissues. Preclinical xenograft models demonstrated significant antitumor activity, including cures. A randomized phase II design was chosen to estimate the activity of the BR96-doxorubicin conjugate in metastatic breast cancer in a study population with confirmed sensitivity to single-agent doxorubicin. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer and immunohistochemical evidence of Lewis-Y expression on their tumor received either BR96-doxorubicin conjugate 700 mg/m2 IV over 24 hours or doxorubicin 60 mg/m2 every 3 weeks. Patients were stratified on the basis of prior doxorubicin exposure, visceral disease, and institution. Cross-over to the opposite treatment arm was allowed with progressive or persistently stable disease. RESULTS: Twenty-three patients who had received a median of one prior chemotherapy regimen were assessable. There was one partial response (7%) in 14 patients receiving the BR96-doxorubicin conjugate and one complete response and three partial responses (44%) in nine assessable patients receiving doxorubicin. No patient experienced a clinically significant hypersensitivity reaction. The toxicities were significantly different between the two treatment groups, with the BR96-doxorubicin conjugate group having limited hematologic toxicity, whereas gastrointestinal toxicities, including marked serum amylase and lipase elevations, nausea, and vomiting with gastritis, were prominent. CONCLUSION: The BR96-doxorubicin immunoconjugate has limited clinical antitumor activity in metastatic breast cancer. The gastrointestinal toxicities likely represent binding of the agent to normal tissues expressing the target antigen and may have compromised the delivery of the immunoconjugate to the tumor sites.

Adult↗
PubMed1999

External versus internal attributions in suicide and their implications for crisis intervention and suicide prevention.

The concept of belief of locus of control is explored for its relevance in crisis intervention and suicide prevention. Although research into the association has produced inconsistent findings, the counselor has rich possibilities for intervention, especially if belief in locus of control is explored along with feelings of powerlessness and helplessness.

Crisis Intervention↗
PubMed1999

Recombinant and tissue extract thromboplastins for determination of international normalised ratio in over-anticoagulated patients.

The international normalised ratio (INR)/international sensitivity index (ISI) system is established for calibration of thromboplastins for laboratory monitoring of oral anticoagulant therapy. The calibration procedure employs patients stabilised on oral anticoagulants, and is therefore validated for patients within the therapeutic range. For practical reasons, the system is used for patients at all levels of therapy, including over-anticoagulated patients with particularly low levels of factors II, VII and X. We studied patients within and above the therapeutic range, using a thromboplastin containing recombinant human tissue factor (Innovin) and two tissue extract thromboplastins. In samples with INRs from 2.0 to 4.0, there was good agreement between results obtained with the three systems (mean INRs within 4% of each other). In patients with INRs > 4.0, results with a human placental extract reagent (Thromborel S) were similar to those obtained with a rabbit brain thromboplastin (IL PT Fib Hs Plus); mean INRs were 6.30 and 6.32 respectively (not significant). Results with Innovin (mean INR: 7.67) were significantly (P < 0.001) greater (on average by 22%) than those obtained with the other two materials. The discrepancy between results with different reagents negatively correlated with factor VII levels. Thus, the lower the factor VII level, the greater was the discrepancy between INRs. Unexpectedly, there was a positive correlation between factor V level and the difference between INRs with different reagents. Thus, the higher the factor V level, the greater was the discrepancy between INRs. The effect of these differences at higher INRs on patient management is unknown, but the recently revised UK guidelines recommend that management of these patients should be influenced by clinical factors, reducing the relative importance of discrepancies between results obtained with different systems.

Anticoagulants↗
PubMed1998

Proposed new duplex classification for threshold stenoses used in various symptomatic and asymptomatic carotid endarterectomy trials.

Current duplex ultrasound criteria for internal carotid artery (ICA) stenosis (1%-15%, 16%-49%, 50%-69%, 70%-99%) may not be applicable to threshold stenoses used in symptomatic (North American Symptomatic Carotid Endarterectomy Trial [NASCET], Veterans' Administration [VA]) and asymptomatic (Asymptomatic Carotid Atherosclerosis Study, VA) carotid endarterectomy (CEA) trials. This, along with increasing reports advocating CEA based on duplex results alone, prompted us to identify (1) new velocity criteria consistent with threshold stenoses used by these trials, and (2) velocity criteria with a high positive predictive value (PPV) (> 95%) and accuracy for detecting > or = 60% and > or = 70% ICA stenoses. This is the first study to propose criteria which can be used for all current CEA trials. The color duplex ultrasound (CDU) and arteriogram results of 462 ICAs were analyzed in blind fashion. Angiographic stenosis was calculated as in NASCET. Three velocity criteria (peak systolic velocity [PSV] of the ICA, end diastolic velocity [EDV] of the ICA, and the ratio of the PSV of the ICA/common carotid artery) were recorded and subjected to receiver operator characteristic curves (ROC) analysis to determine optimum criteria for identifying ICA stenoses of > or = 30%, > or = 50%, > or = 60%, and > or = 70%-99%. For > or = 30% stenosis (st): PSV > or = 120 cm/sec had an overall accuracy (OA) of 87%, sensitivity (sen.) of 93%, specificity (spec.) of 67%, PPV of 90%, and negative predictive value (NPV) of 77%; for > or = 50% st: PSV > or = 140 cm/sec had an OA of 93%, sen. of 92%, spec. of 95%, PPV of 97%, and NPV of 89%; for > or = 60% st: PSV > or = 150 cm/sec and an EDV of > or = 65 had an OA of 90%, sen. of 82%, spec. of 97%, PPV of 96%, and NPV of 86%; for > or = 70%-99% st: PSV > or = 150 cm/sec and an EDV of > or = 90 had an OA of 92%, sen. of 85%, spec. of 95%, PPV of 91%, and NPV of 92%. An ICA-PSV and EDV of 150, 65, and 150, 110 had the best PPV (> or = 95%) in detecting > or = 60% and > or = 70% st, respectively. When these new criteria are used, CDU can accurately detect threshold stenoses used by various CEA trials. Selected velocities with a high PPV (> 95%) may be used as the sole preoperative imaging.

Adult↗
PubMed1998

House dust mite allergen exposure in infancy.

BACKGROUND: Infancy may be a critical time for exposure to house dust mite allergens, when exposure to high levels can increase the risk of allergic sensitization and the development of asthma in later life. OBJECTIVE: To measure house dust mite allergen (Der p 1) concentration in the infants' environment and examine lifestyle factors which may influence mite allergen exposure. METHODS: Infants aged between 4 and 12 months (n = 134) from the western region of Sydney, Australia. participated. Reservoir dust samples were collected from four sites within each home: infant's bed, second bed (adult or second child's bed), lounge floor and sheepskins (where available). Settling aeroallergen was collected for 10-14 d in Petri dishes in the infant's room. Der p 1 was measured by ELISA. A questionnaire on types of bedding, sleeping and playing patterns of the infant was completed by the parents at the time of dust collection. RESULTS: All infants were exposed to at least one site with Der p 1 concentrations greater than 10 microg/g fine dust. The mean settling aeroallergen level in the infants' room was 24 ng De p l/m2 day and this was weakly related to bed allergen levels (r=0.21, P<0.05). Mattress type had a weak effect on Der p 1 levels as measured in the whole bed (P = 0.07), while bed cover and bed type had no effect (P>0.6). The mean product of time spent at a site and its allergen concentration was highest for beds in 69% of infants. CONCLUSION: The high level of allergen exposure in the environment of this group of infants places them at an increased risk of early sensitization and development of asthma. Any strategy to reduce asthma prevalence should address these high and avoidable levels.

Animals↗
PubMed1998

Embryonic and somatic cell cloning.

Revolutionary opportunities in biology, medicine and agriculture arise from the observation that offspring are obtained after nuclear transfer if somatic donor cells are induced to become quiescent. Exploitation of many of these opportunities will depend upon optimizing procedures for nuclear transfer. This may come about through an understanding of the means by which factors in the oocyte cytoplasm act upon the DNA of the transferred nucleus to regulate gene expression. Similarly, research will extend the procedure to other species. This technology may be used for embryo production, the introduction of genetic change and the derivation of cells needed to treat human diseases. Groups of genetically identical animals will be used in research to control genetic variation and to allow transfer of cells between individuals. In agriculture, production of a small number of clones will separate genetic and environmental effects, whereas production of larger numbers of offspring will disseminate genetic improvement from nucleus herds. Precise genetic modification will be achieved by site specific recombination in the donor cells before nuclear transfer. In all mammals it will become possible to define the role of any gene product and to analyse the mechanisms that regulate gene expression. Medical uses of these techniques will include the production of proteins needed to treat disease and the supply of organs such as hearts, livers and kidneys from pigs. As genome mapping projects identify loci associated with traits of commercial importance in agriculture then gene targeting will be used to study this effect. Finally, cells capable of differentiation into any of the tissues of a patient will provide treatment for diseases reflecting damage to a specific cell population that neither repairs nor replaces itself.

Animals↗
PubMed1998

Gender, health beliefs, health behaviors, and alcohol consumption.

We conducted a study of the relationship between health beliefs, health practices, and alcohol consumption among women and men using the Health Belief Model (HBM). The study sample (N = 41,104) was drawn from the 1990 National Health Interview Survey. A 15% random sample was selected from the total data set for the purpose of selecting variables. Alcohol consumption was defined as a health-related behavior and was regressed on demographic characteristics, health beliefs, and health practices. Quantity and frequency of alcohol consumption were assessed for each gender, using the HBM. The HBM explained similar amounts of the variance in alcohol use for women and men. Quantity of alcohol consumed accounted for more variance than did frequency of consumption. We conclude that health beliefs and behaviors are related to alcohol consumption after adjustment for demographic characteristics, and that differences exist between perceived risks and behaviors for both women and men.

Adult↗
PubMed1997

Management of hypercholesterolemia: practice patterns for primary care providers and cardiologists.

This retrospective study, conducted as part of a private practice quality assurance process for patients with coronary artery disease (CAD), compares practice patterns in the LIFEHELP lipid clinic and non-lipid clinic settings at the Heart Institute of St. Petersburg. Quality assurance parameters included documentation of low-density lipoprotein (LDL) cholesterol, initiation of lipid-lowering therapy, and achievement of the Second National Cholesterol Education Program (NCEP II) goal for CAD patients of LDL cholesterol < or =100 mg/dL. A total of 934 patient charts with ICD-9 codes of 410-414 for ischemic heart disease were randomly selected and reviewed by a utilization review nurse. A higher level of documentation and treatment of elevated LDL cholesterol to NCEP II goal in CAD patients was found for those followed in the lipid clinic. Among non-lipid clinic physicians, cardiologists documented and treated elevated LDL cholesterol more frequently than primary care physicians. Women and the elderly subgroups received improved care in the lipid clinic setting. Screening activities and risk-factor management by cardiologists within a lipid clinic, therefore, demonstrated an improved standard of care that came closer to achieving national guidelines in the secondary prevention of CAD.

Age Factors↗
PubMed1997

Molecular aspects of monogamy.

Comparative studies of monogamous and nonmonogamous voles demonstrate species differences in the regional expression of oxytocin (OT) receptors in the brain. These species differences have not been observed with other neurotransmitter receptors (except vasopressin). Species differences for OT receptor distribution were also observed in other microtine and murine species selected as monogamous or promiscuous. These chemical neuroanatomic differences appear to be functionally relevant, as treatments with selective OT agonists and antagonists influence those behaviors that appear critical to pair bonding in the monogamous prairie vole. To investigate the mechanism controlling tissue-specific expression of OT receptors, we sequenced the OT receptor gene in both prairie voles and montane voles. The findings are inconclusive. Although both species differ markedly from rat and human in their regulatory (but not their coding) sequences, the species show very subtle differences from each other. Ongoing studies are investigating the consequences of these subtle differences between prairie and montane voles. At the same time, several transactivating factors that might influence OT receptor expression need to be explored. NOTE ADDED IN PROOF: The rat oxytocin receptor gene sequence, cited in FIGURES 4 and 5, was based on an error published in ref. 22. The corrected sequence has now been published (Rosen et al. 1996. Proc. Natl. Acad. Sci USA 93: 12501). The correct sequence shows greater homology with the vole oxytocin receptor gene sequences, but the remaining differences support the argument made herein for species differences in regional receptor expression.

Animals↗
PubMed1997

Southern analysis of BT-R1, the Manduca sexta gene encoding the receptor for the Cry1Ab toxin of Bacillus thuringiensis.

Various subspecies of the gram-positive bacterium Bacillus thuringiensis are known to produce a wide array of insecticidal crystal proteins (ICPs) upon sporulation. These ICPs act primarily on the brush border of midgut epithelial cells of susceptible larvae. Recently, a protein of 210 kDa, isolated from the midgut of Manduca sexta, has been demonstrated to bind the Cry1Ab toxin produced by B. thuringiensis subsp, berliner and is therefore postulated to be involved in mediating the toxicity of Cry1Ab. The cDNA encoding the 210 kDa protein, termed BT-R1 (Bacillus thuringiensis receptor-1), was recently cloned, and shows limited homology to the cadherin superfamily of proteins. Quite naturally, there is a great deal of interest in the characterization of BT-R1, the gene encoding the 210 kDa Cry1Ab binding protein. The studies presented here involve the use of various restriction fragments prepared from the cDNA encoding BT-R1 as probes of Southern blots bearing M. sexta genomic DNA cleaved with a variety of restriction endonucleases. These Southern blot data reveal that there are two discrete regions within the M. sexta genome which encode sequences homologous to BT-R1. On the basis of the signal intensities seen on Southern blots, it appears that only one of these genes encodes BT-R1, whereas the other is a closely related homologue.

Animals↗
PubMed1997

Amniotic fluid index in twin gestation.

This study was performed to describe a methodology for a two-pocket amniotic fluid index (AFI) for each fetus of a twin gestation. Data included 216 pairs of measurements that were analyzed to yield regressions (curves) for all observations, as well as for the larger and smaller AFI of each observation on a particular set of twins. The twin AFI increased non-linearly until week 27. From week 27 to week 36, decreasing linear trends were found. Measures of intrasonographer, intersonographer, within-mother and between-mothers variation are reported. The estimates of variation were used to plot confidence limits for all three curves.

Adult↗
PubMed1997

Enhanced alveolar type II cell growth on a pulmonary extracellular matrix over fibroblasts.

The growth of alveolar type II cells was studied when these cells were maintained for 2 days on a pulmonary endothelium-derived extracellular matrix (ECM) on a filter with or without lung fibroblasts in the lower chambers of culture wells. Type II cell proliferation was enhanced by the ECM compared with other substrates but was significantly higher with fibroblasts beneath. This was determined by thymidine uptake and cell numbers. The diffusing factor from fibroblasts appeared to be keratinocyte growth factor (KGF), because this cytokine increased type II cell growth in culture and the neutralizing antibody to KGF blocked the observed fibroblast-induced growth increase. None of the antibodies to various cytokines had any effect on the ECM-induced proliferation. Although the type II cells were shown to produce degradative activity for the ECM, there was little secreted enzyme activity in supernatants and there was no demonstrated autocrine-regulated growth effect. The results suggest that type II cell growth may be stimulated by both 1) a matrix-bound factor that acts through a cell contact-mediated process, and 2) a fibroblast-secreted factor that appears to be KGF.

Animals↗
PubMed1997

Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats.

An early phase of proliferation by mesothelial cells and fibroblasts occurs in the lung after asbestos deposition, but the source and identity of the cytokine(s) involved is not clear. In the present study, rats received crocidolite asbestos intratracheally and were killed at 1 and 6 wk later, animals received tritiated thymidine 1 h before death. An increase in inflammatory cells was found in bronchoalveolar and pleural lavage fluids at both times, and after 6 wk the lungs showed fibrosis which was confirmed biochemically. Asbestos fibers were found in alveolar and interstitial macrophages but not in pleural macrophages. In autoradiographs, both mesothelial cells and fibroblasts showed increased DNA synthesis at 1 wk, but only fibroblast labeling was increased at 6 wk. Lavaged macrophages from the lung (alveolar macrophages; AM) and the pleura (pleural macrophages; PLM) were cultured and supernatants tested on rat lung mesothelial cells and fibroblasts in vitro; concentrated lavaged fluids were also tested. At 1 wk, macrophages secreted growth factors for both cell types but the effect was more pronounced using lavage fluids, particularly from the pleura. The increase in fibroblast growth was reduced by an antibody to platelet-derived growth factor, but this had no effect on mesothelial cells. The growth stimulation of these cells was blocked by an antibody to keratinocyte growth factor (KGF). Using cell supernatants and lavage fluids from rats 6 wk after asbestos, growth stimulation was only observed in fibroblasts. The results suggest at least 2 cytokine effects in the lung and pleural space after asbestos exposure; one responsible for fibroblast stimulation is seen up to 6 wk later, while the other, probably involving KGF, stimulates mesothelial cell proliferation in the early response phase after a single exposure to crocidolite.

Animals↗