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Biomedical subjects

M Hagan

Publications and source records attributed to M Hagan.

36 records · Page 2Linked to original sources
PubMed1996

Adapting a statewide patient database for comparative analysis and quality improvement.

BACKGROUND: In 1991 the Michigan Health and Hospital Association established the Michigan Patient Outcome Measures Program to support quality improvement activities among member hospitals. Data submitted by each hospital are based on the Uniform Hospital Discharge Data Set (UHDDS). REPORTING THE MEASURES: Each participating hospital is provided with tabulations for each of the 18 indicators, along with comparative data for each of five hospital peer groups. CASE STUDY 1: FACILITATING DEVELOPMENT OF A CLINICAL PATHWAY: Review of data on stroke patients indicated that patients discharged to home represented the single largest group of patients and that their length of stay was lower than for other groups of stroke patients. Hospital A used a clinical pathway to achieve reduction in length of stay of almost a day for this group. CASE STUDY 2: IMPROVING OBSTETRICS AND GYNECOLOGIC SERVICES THROUGH EDUCATION: The Department of Obstetrics and Gynecological Surgery at Hospital B achieved improvement in birth trauma, hysterectomy, cesarean section (C-section) births, and vaginal births after C-section. Program participants are considering adopting a birth trauma indicator. CASE STUDY 3: ESTABLISHING A HOSPITALWIDE QI PROGRAM: The Newborn Team at Hospital C initiated several QI initiatives aimed at reducing the newborn mortality rate, including guidelines for earlier identification of high-risk obstetric cases and for earlier intervention by the perinatalogist. CONCLUSIONS: Data that are not risk or severity adjusted have value in assessing hospital procedures and systems and can be used to educate and effect change in practice patterns.

Adult↗
PubMed1995

Altered pharmacokinetic and tumour localization properties of Fab' fragments of a murine monoclonal anti-CEA antibody by covalent modification with low molecular weight dextran.

This paper describes the modification of Fab' fragments of ZCE025, a murine monoclonal antibody recognizing carcinoembryonic antigen (CEA), with oxidized dextran of low molecular weight. This modification altered the in vitro and in vivo characteristics of the Fab'. The dextran conjugated fragments exhibited markedly reduced renal uptake and excretion and the prolonged residence time of the Fab' in the vascular compartment. The result was enhanced tumour localization of the derivative compounds compared with underivatized Fab', even though the process of chemical coordination reduced the immunoreactivity of the molecule. The isoelectric point of the molecule was much lower than the unaltered Fab' and previous research has shown this to reduce markedly its potential for inducing a human anti-mouse antibody (HAMA) response. Thus, the conjugation of Fab' fragments with low molecular weight oxidized dextrans can increase the bioavailability of these fragments for tumour localization, while simultaneously reducing their immunogenic potential and renal accumulation problems.

Adenocarcinoma↗
PubMed1995

Causes of suppurative keratitis in Ghana.

AIMS: Suppurative keratitis is a serious problem in all tropical countries, but very little information is available about the causative organisms in Africa. The objectives were to identify the causative organisms and the proportion of cases caused by fungi in southern Ghana, and to determine whether correct decisions about treatment could be made on the basis of Gram stain in the eye clinic. METHODS: Scrapings were taken from corneal ulcers of consecutive new patients presenting at Korle Bu Hospital, Accra, and inoculated on 'chocolate' and Sabouraud's agars. Further scrapings were taken for Gram staining and interpretation in the eye clinic. Duplicate slides were assessed by an experienced microbiologist in the UK. RESULTS: One or more organisms were cultured from 114 of 199 patients (57.3%), the most common being Fusarium species, Pseudomonas aeruginosa, and Staphylococcus epidermidis. Fungi, alone or in combination, were isolated from 56% of the patients who had positive cultures. In total, 122 patients (61.3%) had their treatment either determined or altered based on the results of the microbiological diagnosis; in 87 of these solely on the basis of direct microscopic examination. CONCLUSIONS: Infection by filamentous fungi accounted for more than half of the ulcers from which cultures were obtained. Both training in technique and experience in interpretation are necessary for microscopy based diagnosis by staff in the clinic to be of greatest value. Direct microscopy was particularly useful for detecting fungi.

Adolescent↗
PubMed1994

Erythroid progenitor (BFU-E, CFU-E) proliferation as inferred from 5'bromodeoxyuridine labeling.

Survival patterns of burst-forming unit-erythroid (BFU-E) and cluster-forming unit-erythroid (CFU-E) were studied in B6D2F1 mice after 5'bromodeoxycytidine (BrdCyd) infusion and near-ultraviolet (near-UV) light treatment. Comparison of the kinetics of BrdCyd sensitization of these colony formers with the kinetics of granulocyte-monocyte colony-forming cells (GM-CFC) and colony-forming unit-spleen (CFU-S) demonstrated a similar, but distinguishable, pattern of labeling between BFU-E and CFU-S. BFU-E and CFU-S each contain a subpopulation of unlabeled cells that diminishes with a half-life of 35 to 40 hours. Subsequent comparisons of this close association of BFU-E and CFU-S in Sl/Sld mice, again, showed similar patterns of BrdCyd labeling without evidence of an unlabeled or G0 subpopulation. These results are discussed with respect to the likelihood of a precursor relationship between these two cell types.

Animals↗
PubMed1993

Causes of childhood blindness: results from west Africa, south India and Chile.

Using World Health Organization definitions of visual loss and a standardised methodology, 905 children were examined in Chile, West Africa and South India. Of these 806 (89%) suffered from blindness (BL) or severe visual impairment (SVI). Causes of SVI and BL were classified anatomically and aetiologically, and avoidable causes identified. In W. Africa (n = 284) the major anatomical cause of SVI/BL was corneal scar/phthisis bulbi (35.9%). Retinal disease accounted for 20.4%, cataract 15.5% and glaucoma 13.0%. Aetiologically 33.8% of SVI/BL was due to childhood factors and 21.1% to hereditary disease. In S. India (n = 305) the major anatomical cause of SVI/BL was corneal scar/phthisis bulbi (38.4%). Retinal disease accounted for 22.6%, cataract 7.4% and glaucoma 3%. Aetiologically 37.0% of SVI/BL was due to childhood factors and 29.8% to hereditary disease. In Chile (n = 217) the major anatomical cause of SVI/BL was retinal disease (47.0%). Cataract accounted for 9.2%, glaucoma 8.3% and 6.9% was due to corneal pathology. Aetiologically 30.4% of SVI/BL was due to hereditary factors, and 20.8% to perinatal factors of which four-fifths (16.6%) was due to retinopathy of prematurity. Avoidable conditions accounted for 70%, 47% and 54% of cases in W. Africa, S. India and Chile respectively.

Adolescent↗
PubMed1988

2H1--a novel antigen involved in T lymphocyte triggering.

A mAb anti-2H1, was produced against PHA-activated T cells from a lower primate, Aotus trivirgatus. Anti-2H1 reacted with 90% of peripheral T cells but was found to react with only 10% of thymocytes and some, but not all, leukemic T cell lines. 2H1 expression was dramatically increased when thymic cells were activated by Con A plus PMA. In contrast, anti-2H1 did not react with B cells, macrophages, null cells, or hematopoietic stem cell lines. More importantly, anti-2H1 antibody can induce T cell activation and proliferation in synergy with PMA or anti-T11(3). SDS-PAGE analysis of polypeptides immunoprecipitated with anti-2H1 showed two major polypeptides of 140 and 105 kDa. Thus, the 2H1 Ag can be distinguished from T3, T11, and 9.3 Ag. These results indicate that the 2H1 Ag appears to be involved in the activation of T lymphocytes.

Animals↗
PubMed1987

Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. Analysis with anti-2H4 monoclonal antibody.

The T4+ lymphocyte population includes a subset that induces suppressor T lymphocytes (T8+ cells) and can be distinguished by dual-color fluorescence analysis with anti-2H4 and anti-T4 monoclonal antibodies. To investigate the possible role of these cells in multiple sclerosis, we used anti-2H4 antibody to characterize peripheral-blood lymphocyte subsets in 63 patients with multiple sclerosis that was progressive, stable, or acute (relapsing-remitting). Twenty-three of 37 patients with progressive multiple sclerosis had a selective decrease in the number and percentage of peripheral-blood T cells that induce suppressor cells (T4+2H4+ cells), whereas only 3 of 16 patients with stable disease and 2 of 10 patients in the midst of an acute attack had a significant decrease. These selective decreases of circulating T4+2H4+ cells occurred in only 1 of 34 patient controls with other neurologic diseases and in 2 of 50 healthy controls (P less than 0.0001 by Fisher's exact test). The absolute number of T4+2H4+ cells and the percentage of reactivity in the populations studied were 187 +/- 28 per cubic millimeter and 8.3 +/- 1 percent in patients with progressive multiple sclerosis; 353 +/- 60 per cubic millimeter and 14.5 +/- 2 percent in patients with stable disease; 368 +/- 72 and 14.6 +/- 2.1 percent in patients with acute disease; 402 +/- 64 and 15.6 +/- 2 percent in controls with other neurologic diseases; and 519 +/- 44 and 19.7 +/- 1 percent in healthy controls. Functional studies using a pokeweed mitogen-driven IgG assay demonstrated a correlation between decreased numbers of T4+2H4+ cells and increased production of IgG in vitro. Family studies showed that the 2H4 antigen was not part of an inherited polymorphic antigenic determinant. Our results suggest that in progressive multiple sclerosis decreases in inducers of suppressor T cells may permit the activation of cells reactive with elements of the central nervous system.

Adult↗
PubMed1987

A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody.

The cell surface phenotype of peripheral blood lymphocytes (PBL) of systemic lupus erythematosus (SLE) patients was characterized with the anti-2H4 monoclonal antibody that defines the human suppressor inducer subset. The T4+2H4+ population of cells has been shown to be critical for the activation of T8+ suppressor cells. Patients with SLE has a markedly decreased percentage of T4+2H4+ cells (13 +/- 2%) in their PBL compared with normal controls (21 +/- 1%) (P less than 0.001). This reduction was greatest in patients with active SLE, especially those with renal disease. Serial analysis of patients with SLE and renal disease showed a correlation between percent positive circulating T4+2H4+ cells and disease activity. Moreover, there was a significant correlation between a low percentage of T4+2H4+ cells and decreased suppressor-inducer function in autologous mixed lymphocyte reaction-activated T4+ cells from SLE patients. Thus, a deficiency exists in SLE patients with active renal disease in the T4+2H4+ suppressor-inducer T cell subset.

Adolescent↗
PubMed1986

The role of the 2H4 molecule in the generation of suppressor function in Con A-activated T cells.

The molecular basis for the suppression generated in a concanavalin A (Con A)-activated T cell culture remains unknown. In this study, we have attempted to determine whether the 2H4 and 4B4 molecules on Con A-activated T cells play some role in the generation of suppression by such cells. We have shown that Con A-activated suppressor cells belong to the 2H4+ subset of T cells but not the 4B4+ (2H4-) subset. Con A-activated T cells exerted their optimal suppressor function on day 2 in culture, a time at which the expression of 2H4 on such cells was maximal and 4B4 was minimal. Furthermore, the stimulation of T cells with the higher concentration of Con A generated the stronger suppressor function. At the same time, both 2H4 expression and density were increased and 4B4 expression and density were decreased on such Con A-activated T cells. More importantly, the treatment of Con A-activated T cells with anti-2H4 antibody but not with anti-4B4, anti-TQ1, or anti-T4 antibodies can block the suppressor function of such cells. Taken together, the above results strongly suggest that the 2H4 molecule itself may be involved in the generation of suppressor function in Con A-activated T cells. The 2H4 antigen on such cells was shown to be comprised of 220,000 and 200,000 m.w. glycoproteins. Thus this study indicates that the 220,000 and 200,000 m.w. structure of the 2H4 molecule may itself play a crucial role in the generation of suppressor signals of Con A-activated cells.

Antibodies, Monoclonal↗
PubMed1986

Role of cell replication in regulation of Na-coupled hexose transport in LLC-PK1 epithelial cells.

The glucose concentration in growth medium has been shown to regulate the number of sodium-coupled glucose transporters in LLC-PK1 epithelial cells. Epithelia grown in high concentrations of glucose express fewer transporters than epithelia grown in low concentrations of glucose. In the present work, the effect of a dose of ionizing radiation sufficient to block the incorporation of thymidine was examined in order to gauge the importance of cell replication in the hexose transport regulatory process. The low rate of thymidine incorporation in the plateau phase was completely eliminated by ionizing radiation. Under conditions of irradiation that completely blocked thymidine incorporation, down-regulation, namely the loss of alpha-methylglucoside-concentrating capacity, brought about by switching the epithelium from low to high glucose-containing medium, is independent of the irradiation and therefore most likely is also independent of cell replication. In contrast, the up-regulatory phenomenon is strongly impaired by radiation. This impairment may be due to specific radiation impairment of gene expression necessary for the up-regulatory process. It is apparent from the dose-response data that up-regulation is not inhibited by irradiation in a simple manner and is not inhibited at the same radiation dose as cell replication.

Animals↗
PubMed1986

Effect of radiation on the regulation of sodium-dependent glucose transport in LLC-PK1 epithelial cell line: possible model for gene expression.

Low concentrations of glucose induce cultured kidney epithelial cells (LLC-PK1) to produce hexose transport proteins. We have investigated the effects of ionizing radiation on this induction process in plateau-phase cultures. The induced production of hexose transporters, requiring approximately 6 to 9 days for complete expression, can be inhibited by irradiation during the first 4 days. After the fourth postinduction day, radiation sensitivity decreases with almost no radiation effect on the induction of hexose transport apparent by the sixth day of the induction period. The D0 value associated with the induction block is approximately 25 Gy, a value which is considerably greater than that necessary to inhibit cell replication. Hexose transport, itself resistant to ionizing radiation at doses in excess of 100 Gy, is sensitive to cycloheximide throughout the induction period. The sensitivity to cycloheximide decreases during the last 2 days of the induction period, approximately 1 day after the reduction in radiosensitivity. Based on these properties hexose transport may be a convenient model for the study of radiation effects upon gene expression in this cell line.

Animals↗
PubMed1985

Delayed phase of hematoporphyrin-induced phototoxicity: modulation by complement, leukocytes, and antihistamines.

We have investigated the role of complement, leukocytes, and histamine in the delayed phase of hematoporphyrin-induced phototoxicity in guinea pigs. The phototoxic response was quantified by the accumulation of intravenously injected [125I]bovine serum albumin in the skin. There was a greater than 6-fold increase in the vascular response at the completion of irradiation, which subsided partially to reach a plateau of twice the preirradiation level between 0.5 h and 12 h. At 18 h, the vascular responsiveness returned to the baseline value. The 7 h timepoint was selected in this study to evaluate the modulation of the delayed phase. In complement-depleted guinea pigs, as well as in leukopenic animals, the enhancement in the vascular response was significantly suppressed (p vs control, less than 0.0001 and 0.0022, respectively). Cimetidine, when administered prior to irradiation, significantly suppressed the phototoxic response (p vs control, 0.0365). The combination of diphenhydramine and cimetidine, administered 6 h after the induction of phototoxicity, also suppressed the vascular response (p vs control, less than 0.0001). These data indicate that the expression of the delayed phase of hematoporphyrin-induced phototoxicity, similar to the early phase, requires the presence of an intact complement system, leukocytes, and histamine.

Animals↗
PubMed1985

The isolation and characterization of the human helper inducer T cell subset.

Monoclonal antibody anti-4B4 was produced by fusing NS1 myeloma with spleen cells of a mouse immunized with Saguinus oedipus lymphocyte. This anti-4B4 antibody defines a 135-KD cell surface protein that is widely distributed throughout the hematopoietic system. More importantly, anti-4B4 is reactive with functionally unique human T cell subsets. Anti-4B4 antibody was reactive with approximately 41% of unfractionated T cells, 41% of T4+ inducer cells, and approximately 43% of T8+ cytotoxic/suppressor population. This antibody subdivided peripheral blood T4+ cells into two functionally distinct populations. The T4+4B4+ subset proliferates relatively poorly upon stimulation with Con A and autologous cell antigens (AMLR) but well on exposure to soluble antigens, and it provides a good helper signal for PWM-induced Ig synthesis. The T4+4B4- subset, in contrast, proliferates well to Con A stimulation and autologous cell antigen (AMLR) but relatively poorly to soluble antigen stimulation, and provides little help to B cells for PWM-induced Ig synthesis. The T4+4B4- subset is largely 2H4+ and functions as the inducer of the T8+ suppressor cells. Thus, the present results suggest that one can divide the human T4 population into two major subsets that are phenotypically and functionally distinct, the human helper inducer subset (T4+4B4+/H.I.) and its reciprocal population defined by anti-2H4, the suppressor inducer subset (T4+2H4+/S.I.).

Animals↗
PubMedDate not supplied

Use of anesthesia selection in controlling surgery costs in an HMO hospital.

The cost of induction and maintenance of anesthesia is analyzed in this article from the perspective of a health maintenance organization's (HMO) chief financial officer. While earlier economic studies tended to focus on the raw cost of anesthesia drugs, our model also includes the cost of the clinical labor involved in administering the drug as well as the fixed costs associated with the facility. Such a model is consistent with the goal of an HMO, which is to provide high-quality health care services to its membership while containing costs. Our model disaggregated the costs associated with anesthesia into cost centers. The costs associated with two anesthesia regimens, propofol and thiopental/isoflurane, were calculated and analyzed via cost-minimization methods. Our data were acquired from a prospective economic trial conducted in university, community, and HMO hospitals. Because institutional pricing policies differ greatly, only the findings at the HMO hospital are presented in this report. Our results suggest that intra-abdominal surgical procedures with a duration of less than 4 hours that use propofol for induction and maintenance of anesthesia reduce the total cost of surgery by $202.71, compared with the costs of using thiopental/isoflurane. Sensitivity analysis maintains the robustness of the conclusions with regard to all major parameters.

Accounting↗