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Biomedical subjects

M Lemon

Publications and source records attributed to M Lemon.

At least 19 recordsLinked to original sources
PubMed1998

IGF-I and IGF-binding protein-1 are related to cortisol in human cord blood.

OBJECTIVE: To assess cortisol concentrations in cord blood and investigate their relationships with the IGF system. STUDY DESIGN: Fifteen newborns with birth weight appropriate for gestational age (AGA) and 30 children with intrauterine growth retardation (IUGR) were studied. Serum samples were collected from umbilical cord blood and cortisol, IGF-I and IGF-binding proteins (IGFBPs)-1 and -3 were measured. IUGR infants were followed up for 3 months with repeated measurements of weight, supine length and knee-heel length (by knemometry). RESULTS: IUGR newborns showed significantly greater concentrations of IGFBP-1 (P<0.0001) and lower concentrations of IGF-I (P< 0.0001) and IGFBP-3 (P< 0.0001) than did controls. In AGA children, cortisol correlated inversely with IGF-I (r=-0.75, P< 0.002) and directly with IGFBP-1 (r=0.52, P <0.05), whereas no correlation between cortisol and IGF system-related variables was observed in IUGR. Finally, in IUGR children an inverse correlation was found between length gain in the first trimester of life and cortisol concentrations at birth (r=-0.54, P < 0.005). CONCLUSIONS: Cortisol might be a physiological regulator of fetal growth, at least in the last part of pregnancy, by modulating IGF-I and IGFBP-1 release under conditions of fetal stress. In IUGR children, a rearrangement of this growth control mechanism seems to occur. The close inverse relationship of cortisol with linear growth, if confirmed by large-scale studies, suggests cord blood cortisol to be potentially predictive of early postnatal catch-up growth in IUGR infants.

Fetal Blood↗
PubMed1997

Evidence-based morning report: a popular new format in a large teaching hospital.

Recent innovations in postgraduate medical education place greater emphasis on evidence-based curricula and self-directed, learner-centered education. Little has been published to date about how to apply these educational innovations to morning report, traditionally an important daily teaching venue in all internal medicine training programs. We describe here the content and conduct of a new evidence-based morning report at a large teaching hospital where it has become the popular hub for residents' self-directed academic activities. Methodologic standards are needed to study, report, and evaluate outcomes of similar educational interventions.

Evidence-Based Medicine↗
PubMed1997

Presence of the T-cell activation marker OX-40 on tumor infiltrating lymphocytes and draining lymph node cells from patients with melanoma and head and neck cancers.

BACKGROUND: The OX-40 antigen is a cell surface glycoprotein in the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells. Selective target organ expression of the OX-40 receptor on autoantigen specific T cells has been found in autoimmune disease. In order to evaluate whether OX-40 is expressed on T cells from patients with nodal-draining carcinomas, OX-40 expression was assessed in tumor infiltrating lymphocytes (TILs), draining lymph node cells (DLNCs), and/or peripheral blood lymphocytes (PBLs) of 13 patients with head and neck squamous cell carcinomas and 9 patients with melanomas. METHODS: Cell phenotype was determined by fluorescence cell analysis using a monoclonal antibody to human OX-40, and CD4+ T cell lymphokine production was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Expression of the OX-40 receptor was found in as many as 31% of the TILs and as many as 28% of the DLNCs tested. Conversely, no OX-40 expression was found in PBLs. In addition, CD4+ T cells isolated from DLNCs (but not from TILs or PBLs) secreted a Th1 pattern of cytokines (IL-2, gamma interferon). Co-culture of autologous CD4+ TILs with an MHC class II+ melanoma cell line transfected with OX-40 ligand cDNA resulted in T cell proliferation and in vitro tumor regression. CONCLUSIONS: These findings suggest that OX-40+ CD4+ T cells isolated from tumors and their adjacent draining nodes may represent a tumor-specific population of activated T cells capable of mediating tumor reactivity. These cells may play an exploitable role in future trials of immunotherapy.

CD4-Positive T-Lymphocytes↗
PubMed1997

Generation of kinins in synovial fluid from patients with arthropathy.

An enzyme-linked immunosorbent assay method is described for the measurement of kinin formation in synovial fluid from patients with rheumatoid and osteoarthritis (RA and OA). Basal kinin concentrations were less than 6 ng/ml in synovial fluid collected in the presence of inhibitors of kinin forming (kininogenase) and kinin metabolising (kininase) enzymes. During incubation of synovial fluid in the presence of kininase inhibitors alone, kinins were produced rapidly over the first 10 min, but production ceased completely within 30 min due to inhibition of the endogenous kininogenases; the rate of kinin generation during the early rapid phase correlated well with the plateau kinin concentration. Plateau kinin levels in synovial fluid from 15 patients with OA and RA ranged from 98 to 427 ng/ml, with a median value of 148 ng/ml. This study demonstrates clearly that synovial fluid from arthritis patients has the capacity to produce kinins. Although the number of patients was small, the amount of kinin generated in vitro varied over a wide range and a relationship between intra-articular kinin formation and clinical features may become apparent in a larger group of patients. The technique could also be used to investigate other biological systems in which a role has been proposed for kinins.

Arthritis, Rheumatoid↗
PubMed1996

OX-40 antibody enhances for autoantigen specific V beta 8.2+ T cells within the spinal cord of Lewis rats with autoimmune encephalomyelitis.

The V beta 8.2 T cell receptor (TCR) component is the predominant V beta gene product associated with antigen specific CD4+ T cell response to the major encephalitogenic epitope of myelin basic protein (MBP) in Lewis rats. Lewis rats were actively immunized with MBP in complete Freund's adjuvant and the V beta 8.2 positive and negative cells were analyzed for IFN-gamma mRNA production and OX-40 cell surface expression during the onset of EAE. The V beta 8.2+ T cells isolated from the spinal cord produced the majority of mRNA for IFN-gamma and also showed a marked enhancement for OX-40 expression compared to V beta 8.2+ T cells isolated from the lymph nodes. Only a fraction of IL-2 receptor positive T cells examined ex vivo from the inflammatory compartments co-expressed the OX-40 antigen. These results suggested that OX-40 cell surface expression could be used to identify and isolate the most recently activated T cells ex vivo. OX-40+ T cells isolated from the spinal cord were highly enriched for the V beta 8.2 T cell receptor component compared to OX-40- or unsorted spinal cord lymphocytes. OX-40+ T cells isolated from the spinal cord had an enhanced response to MBP, whereas OX-40+ cells isolated from the lymph nodes responded to both MBP and purified protein derivative. These data suggest that activated T cells can be isolated and characterized with the OX-40 antibody which only respond to the antigens present at the local site. The data also imply that isolation of OX-40+ T cells will be useful in identifying V beta biases and autoantigen specific cells within inflamed tissues even when the antigen specificity is unknown.

Animals↗
PubMed1996

Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates autoimmune encephalomyelitis.

The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.

Animals↗
PubMed1995

Communication as an essential part of program and institutional development.

The Longitudinal Primary Care Program, an innovative curriculum in generalist medicine at the University of Illinois at Chicago College of Medicine, has been enhanced by a commitment to fostering good communication among all of its participants (who include more than 350 students and nearly 300 office-based generalist preceptors) and between participants and administrators. The diverse and widely scattered group of preceptors is brought together through orientation sessions and faculty development workshops that stress precepting skills and mentoring. Preceptors are regularly surveyed and the survey data are analyzed to help administrators learn how best to recruit and retain these faculty members. Students' input comes through surveys, small-group meetings, and their participation on committees. Program evaluation data and formal notes from committee meetings are promptly compiled and disseminated. Such efforts to promote good communication among preceptors, students, program administrators, and the medical college have both enhanced the generalist program and encouraged other curricular reforms in the college.

Chicago↗
PubMed1995

Identification and functional importance of plasma kallikrein in the synovial fluids of patients with rheumatoid, psoriatic, and osteoarthritis.

OBJECTIVES: To determine and identify, unequivocally, if plasma kallikrein (PK) is present in the synovial fluid of patients with rheumatoid (RA), psoriatic (PA) and osteo (OA) arthritis, and to consider its functional importance in the inflamed joint. METHODS: Therapeutically aspirated synovial fluids (pooled and individual samples, n = 66) were obtained from patients with arthritis. In addition, serum (n = 14) was collected from RA patients, and saliva (n = 10) and urine (n = 10) from normal individuals. Enzymic (amidase) and immunoreactive activities of PK and its precursor, prokallikrein (PPK), were determined. The presence of PK was assessed by incubation with soya bean trypsin inhibitor (SBTI), and by adsorption with anti-PK antibody linked to Sepharose. An enzyme-linked immunosorbant assay (ELISA) for PK was developed for quantitative measurement of total PK in biological fluids. Enhancement of the PK dose-response by RA synovial fluid made it necessary to remove RF from synovial fluids before determination of PK by ELISA. RESULTS: Amidase activity was demonstrated in synovial fluid pools and shown to be inhibited completely by SBTI, and removed by prior treatment with anti-PK Sepharose. Total PK activity (PK + PPK) from individual synovial fluid specimens did not differ significantly between patients with RA (median activity 76 mU/g protein), PA (80 mU/g protein) or OA (60 mU/g protein). Similar results were obtained when active PK alone was measured. No correlation was found between active PK or total PK values and the severity score for individual joints. Most of the measured immunoreactivity was removed by adsorption with anti-PK antibody linked to Sepharose. CONCLUSION: The results support the hypothesis that plasma kallikrein is present in synovial fluid. The enzyme may be important in the pathogenesis of inflamed joints.

Adult↗
PubMed1994

Training generalist physicians: structural elements of the curriculum.

To train more generalist physicians, structural changes must be made along the continuum of medical education. Future generalists require in-depth exposure to primary care practice, with substantive experience in the longitudinal management of patient panels and the opportunity to work with successful generalist role models. Clinical training and course work must incorporate a wide range of skills and disciplines, including areas now under-emphasized, such as epidemiology, health services, and psychosocial medicine. Recommendations for structural changes to increase the generalist focus of medical education include: 1) the development within institutions of central authorities, involving departments of internal medicine, family medicine, and pediatrics, in joint efforts to foster all aspects of generalist training, including recruitment, curriculum development, community linkages, innovative approaches to training, and recognition and support for successful generalist teachers; 2) commitment of a minimum of 50% of clinical training to ambulatory care settings at both medical school and residency levels; 3) required longitudinal care experiences for all medical students and a 20% or greater time commitment to longitudinal care for internal medicine, pediatrics, and family medicine residents; and 4) increased numbers of generalist faculty and enhanced teaching skills among faculty in the outpatient environment, to guarantee increased exposure of medical students and residents to generalist role models.

Adult↗
PubMed1994

Implementation issues in generalist education.

Devising a strategy for the implementation of a generalist medical educational program can be aided by grouping the many issues to be addressed into developmental stages. In this way, problems can be anticipated and resources marshalled. Initially, leadership and institutional support for the program must be developed. Next, detailed financial, curricular, and site planning must be undertaken. Implementation of the program must contend with faculty, site, and trainee concerns while consolidating financial and institutional support. Finally, in institutionalizing the program, financing must be secured and ongoing evaluation should provide information necessary to regularly reassess the program and renew its goals.

Adult↗
PubMed1989

Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity.

Anti-digoxin antibody fragments (ADAF, 80 mg) were infused intravenously to successfully treat severe digoxin toxicity in an 82 year old woman. During treatment, total and free digoxin were determined using an Abbot TDX analyser and an ultrafiltration technique. ADAF were measured by an enzyme-linked immunosorbent assay. By 1 h after ADAF, total serum digoxin concentrations had risen 12-fold from a pretreatment level of 15.4 nmol l-1 but free digoxin fell from 10 to 0.1 nmol l-1, indicating greater than 99.9% digoxin binding to ADAF. However, the low free levels had rebounded to 7.7 nmol l-1 by 12 h, but despite this rise the patient's condition had improved. A serum ADAF/digoxin molar ratio of around five was associated with the low concentration of free digoxin at 1 h, while at later times with ratios roughly between 3 and 4, the free digoxin concentrations ranged between 2.0 and 7.7 nmol l-1. ADAF were mainly confined to the plasma during the first hour, but subsequently distributed into an apparent volume of 193 ml kg-1. The elimination half-lives of ADAF and total digoxin were 96 and 55 h, respectively. More than 50% of the estimated digoxin load had been excreted in the urine by 5 days; for ADAF the equivalent figure was only about 3%. Renal and/or bacterial degradation may have contributed to the low detection of urinary ADAF.

Aged↗
PubMed1989

Distractibility in schizophrenia: state and trait aspects.

This report compared the selective attention of 19 schizophrenic in-patients, 10 recently discharged schizophrenic out-patients, 21 schizophrenic out-patients in stable clinical remission, 33 first-degree relatives of schizophrenics from 15 families, 25 students who scored deviantly on questionnaire measures of magical ideation, perceptual aberrations, and physical anhedonia, and 20 normal controls. Results indicated that distractors only disrupted the performance of schizophrenic in-patients, suggesting that differential deficits in selective attention are a marker of episodes of schizophrenia. A propensity to interject phonemes from the distracting message was found not only in patients in or just emerging from a psychotic episode, but also in the remaining vulnerable but non-psychotic groups, suggesting that intrusion errors might be a mediating vulnerability marker. The findings suggest both state and possibly trait aspects to distractibility in schizophrenia.

Adult↗