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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 145 records · Page 8Linked to original sources

Femoral deep vein thrombosis associated with central venous catheterization: results from a prospective, randomized trial.

OBJECTIVE: To determine the frequency of central venous catheter-induced deep vein thrombosis of the femoral vein. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary care center. PATIENTS: Forty-five patients in a medical-surgical intensive care unit who required central venous catheterization. INTERVENTIONS: Patients were randomized to receive central venous catheterization in either upper (subclavian or internal jugular veins) or lower (femoral vein) catheterization sites. Lower extremity duplex ultrasound examinations were performed before central venous catheter placement, after removal of the catheter, and 7 days after catheter removal. Ultrasound examinations were reported as positive, nondiagnostic, or negative for deep vein thrombosis. MEASUREMENTS AND MAIN RESULTS: Of the 21 patients randomized to upper access sites, none developed positive or nondiagnostic duplex ultrasound examinations. Six (25%) of 24 patients randomized to the femoral access site developed lower extremity deep vein thrombosis (p = .02). In addition, seven (29%) patients randomized to the lower access site sustained non-diagnostic ultrasound examinations. A total of 13 (54%) of 24 patients from the lower access group developed abnormal ultrasound examinations (p < .001). Age, duration of catheterization, coagulation profile, deep vein thrombosis prophylaxis, and Acute Physiology and Chronic Health Evaluation II scores were similar between the upper and lower access groups. CONCLUSIONS: Based on the data from this study, we concluded that femoral vein catheterization is associated with a 25% frequency of lower extremity deep vein thrombosis compared with similar patients receiving subclavian or internal jugular vein catheters. The femoral vein remains an important emergency venous access route. Physicians inserting femoral vein catheters should be aware of the risk of lower extremity deep vein thrombosis and should consider performing lower extremity duplex ultrasound examinations on removal of femoral vein catheters.

Catheterization, Central Venous↗

Outpatients revisited: subjective views and clinical decisions in the management of general surgical outpatients in south west England.

STUDY OBJECTIVE: To assess the scope for reducing unnecessary outpatient reattendances, using a benchmark an acute specialty at a site recognised to have an especially low ratio of repeat to new attendances. DESIGN: This was a survey of the re-attendance workload at general surgery outpatient clinics over a three month period. Patient re-booking and discharge rates for different grades of staff; clinicians' perception of the ability of the GP to have managed the patient; perception of the value of individual re-attendances; reason given for discharging/re-booking; and outcome of attendance for patients in relation to diagnostic category were determined. SETTING: General surgery outpatients clinics with re-attendance rates that were 50% below average, in Taunton and Somerset Hospital, a non-teaching district general hospital. PATIENTS: Altogether 454 patients who made 470 second or subsequent visits (re-attendances) within the same episode of outpatient care. MAIN RESULTS: Thirty eight percent (178/470) of visits were perceived as manageable by the GP, 45% (79, 17% of total re-attendances) of which were also thought to have been of marginal or little value. A substantial group of patients was being followed up largely for reasons of convention and traditional policy. Re-booking rates were higher among junior staff. Subjective views of the value of attendance at the hospital outpatient clinic and the ability of the GP to have seen the patient varied systematically between consultants and junior staff. Judgements varied to some extent according to the diagnostic group. CONCLUSION: The numbers of patients being followed up equivocally at most general surgical outpatient departments will be 50% more an average than those in this benchmark department. A department seeing 2000 new patients per annum will have 3600 reattendances, 25.5% (918) of which may be avoidable on the basis of these results. A variety of approaches can be used to increase the proportion of patients seen appropriately by GPs. In some cases this might be achieved without the intensive commitment required to plan and develop shared care protocols or new formal discharge guidelines, but by encouraging GPs to manage some patients, increasing of hospital clinicians' access to knowledge of local general practices, and internal clinic review of 'routine' follow up policies as shown in this study. This type of review of outpatient practice can also help prioritise conditions likely to repay the effort of developing and implementing clinical management guidelines and local protocols.

Delivery of Health Care↗

Characterization of the alloreactivity and anti-leukemia reactivity of cord blood mononuclear cells.

It has been suggested that cord blood T cells may be less able to mediate GVHD than marrow-derived T cells due to their naive status. A decreased potential for GVHD may be advantageous for allogeneic transplant, but this benefit might be counteracted by loss of the GVHD associated graft-versus-leukemia (GVL) effect. The GVL potential of cord blood could be doubly compromised since cord blood NK cell activity is also decreased. To assess these issues we have performed extensive comparative functional and immunophenotypic evaluations of cord and adult mononuclear cells. We found a somewhat reduced alloproliferative, allostimulatory and allocytolytic capacity of cord blood mononuclear cells in bulk assays but not by limiting dilution assays. Immunophenotyping revealed no significant differences in the proportion of major lymphocyte subsets with the exception of the previously recognized predominance of CD45RA+ cells in both CD4 and CD8 cord blood T cells. Cord blood T cells expressed normal percentages of the cellular adhesion molecules, CD11a, CD18 and LFA-3; however, the antigen density of each of these molecules was less than that found on adult T cells. Fewer resting cord blood T cells expressed CD54, the ligand for LFA-1. Cord blood B cells and monocytes expressed normal levels of HLA-class I and HLA class II DR, DP and DQ antigens, suggesting that the decreased expression of cellular adhesion molecules or their receptors rather than a decrease in expression of HLA might have contributed to the lower alloreactivity of cord blood. Although the percentages of NK cells and NK cell subsets in adult and cord blood were similar our data confirmed that cord blood has very low NK lytic activity. In contrast, LAK activity was much more readily induced in cord blood compared with adult PBMC, a finding which could be explained in part by a higher frequency of LAK precursors and a more rapid expansion of NK cells in response to culture with medium containing of NK cells in response to culture with medium containing IL-2. Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML and CML. The data indicate that although the alloreactive potential of cord blood cells may be somewhat decreased, it is not absent and must be considered a factor in cord blood transplants. LAKp with the potential to lyse leukemia are present in increased numbers in cord blood and might contribute to the GVL effect of a cord blood transplant.

Adult↗

Clinical information systems and quality of care in the intensive care unit.

The introduction of new medical technology needs to be associated with the assessment of the value of this technology in patient care. Traditional outcome measures of quality in health care (such as survival, cost, and "quality of life") may be of little value in assessing quality of patient care at the bedside. A model of quality in bedside patient care is presented and used in the assessment of the impact of introducing a bedside information system on patient care quality.

Australia↗

Initial clinical experience with computer-controlled conformal radiotherapy of the prostate using a 50-MeV medical microtron.

PURPOSE: We have described previously a model for delivering computer-controlled radiation treatments. We report here on the implementation and first year's clinical experience with such treatments using a 50 MeV medical microtron. METHODS AND MATERIALS: The microtron is equipped with a multileaf collimator and is capable of setting up and treating a sequence of fixed fields called segments, under computer control. An external computer derives machine parameters for the segments from a three-dimensional treatment planning system, transfers them to the microtron control computer, checks the machine settings before allowing dose delivery to begin, and records the treatment. We describe the patient treatment methodology, portal film acquisition, electronic portal imaging, and quality assurance. RESULTS: Patient treatments began in July 1992, comprising six-segment conformal treatments of the prostate. Using the recorded treatment data, the system performance has been examined and compared to other treatment machines. The average treatment time is 10 min, of which 4 min is for computer-controlled setup and irradiation; the remaining time is for patient positioning and checking of clearances. Long-term reproducibility of computer-controlled setup of the gantry and multileaf position is better than 0.5 degrees and 1 mm, respectively. Termination due to a machine fault has occurred in 5.5% of treatments, improving to 2.5% in recent months. CONCLUSION: Our initial experience indicates that computer-controlled segmental therapy can be performed reliably on a routine basis. Treatment times with the microtron are significantly shorter than with conventional linacs, and setup accuracy is consistent with that needed for conformal therapy. We believe that treatment times can be further improved through software upgrades and integration of electronic portal imaging.

Humans↗

Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity.

A diversity of high-affinity oligosaccharide ligands are identified for NKR-P1, a membrane protein on natural killer (NK) cells which contains an extracellular Ca(2+)-dependent lectin domain. Interactions of such oligosaccharides on the target cell surface with NKR-P1 on the killer cell surface are crucial both for target cell recognition and for delivery of stimulatory or inhibitory signals linked to the NK cytolytic machinery. NK-resistant tumour cells are rendered susceptible by preincubation with liposomes expressing NKR-P1 ligands, suggesting that purging of tumour or virally infected cells in vivo may be a therapeutic possibility.

Animals↗

Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice.

The requirement for a functional retinoblastoma gene, Rb-1, in murine development around days 12-15 of gestation precludes monitoring the effect of loss of Rb-1 function on later stages of development and on tumorigenesis in adult mice. Here we describe the developmental rescue of embryonic stem cells carrying two inactive Rb-1 alleles in chimeric mice. Rb-1- cells contributed substantially to most tissues in adult chimeras, including blood, liver and central nervous system, which were severely affected in pure Rb-1- embryos. The adult chimeric erythroid compartment appeared completely normal, but an increased number of nucleated red cells was observed during fetal liver erythropoiesis in highly chimeric embryos. No ostensive abnormalities were seen in the developing and adult CNS. However, the developing retina of chimeric Rb-1- embryos showed ectopic mitoses and substantial cell degeneration, while the contribution of Rb-1- cells to the adult retina was much reduced. Moreover, the formation of lens fibre cells was severely disturbed. No retinoblastomas developed in any of these mice. Instead, nearly all animals died of pituitary gland tumours which were exclusively derived from Rb-1- cells.

Animals↗

High glucose and insulin decrease fetal lung insulin receptor mRNA and tyrosine kinase activity in vitro.

Specific insulin binding by the fetal lung insulin receptor is reduced in vitro by a combination of high glucose and insulin. Using 19-22 day fetal rat lung, we studied the effect of culture for 48 hours under conditions of low (10mM) and high (100mM) glucose with and without added insulin on insulin receptor tyrosine kinase activity, mRNA abundance, and glucose uptake. Culture in high glucose + insulin reduced tyrosine kinase activity to 77.2 +/- 5.2% of control values (p < .001); high glucose or insulin alone had no effect. Insulin-receptor mRNA abundance was reduced by high glucose + insulin to 37 +/- 6% of control values (p < .05). Again, no significant differences were seen with high glucose or insulin alone. Uptake of 3H-2-deoxy-glucose by explants cultured under high glucose + insulin conditions was also significantly reduced. These data indicate that down-regulation of fetal lung insulin receptors by high glucose + insulin occurs at the pre-translational level and that glucose transport is adversely affected under these conditions. Down-regulation of lung insulin receptors late in fetal life may limit the availability of glucose as substrate for surfactant synthesis in the perinatal period and may partially explain the increased incidence of respiratory distress syndrome in infants of poorly controlled diabetic mothers.

Animals↗

Measuring maternal mortality in developing Pacific island countries: experience with the sisterhood method in the Solomon Islands.

AIMS: To estimate the maternal mortality rate in the Solomon Islands, and to assist health planning and implementation of effective interventions. METHOD: The sisterhood method, an indirect technique for deriving population-based estimates of maternal mortality was used in interviews with 2580 randomly chosen women reporting on the fertility and mortality experience of their sisters. RESULTS: The maternal mortality ratio in this study was 549 per 100,000 (95% CI 431, 684). This equates to one maternal death in every 180 pregnancies. CONCLUSION: The sisterhood method was found to be easy to administer, inexpensive and quick, and is recommended as a measurement tool to other developing countries.

Adolescent↗

Sulfated blood group Lewis(a). A superior oligosaccharide ligand for human E-selectin.

In earlier studies of oligosaccharide probes (neoglycolipids) generated from an ovarian cystadenoma glycoprotein, one of the components that strongly supported binding of the endothelial adhesion molecule, E-selectin, was identified as an equimolar mixture of tetrasaccharides of blood group Le(a) and Le(x) type sulfated at position 3 of the outer galactose (C.-T. Yuen, A. M. Lawson, W. Chai, M. Larkin, M. S. Stoll, A. C. Stuart, F. X. Sullivan, T. J. Ahern, and T. Feizi (1992) Biochemistry 31, 9126-9131). In the present studies, the individual sulfated Le(a) and sulfated Le(x) oligosaccharides synthesized chemically have been investigated, first, for their ability to support E-selectin binding when converted into neoglycolipids, and second, for their ability to inhibit E-selectin binding to immobilized lipid-linked sialyl-Le(a), sialyl-Le(x), or sulfated Le(a) pentasaccharides; their activities have been compared with those of the sialyl-Le(a) and sialyl-Le(x) analogues. From these studies, the sulfated Le(a) tetra- and pentasaccharides emerge as the most potent E-selectin ligands so far. In particular, the inhibitory activity of the sulfated Le(a) pentasaccharide is substantially greater than that of the sialyl-Le(x) trisaccharide, which is currently the most widely used inhibitor of E-selectin binding: 45-, 35-, or 15-fold greater depending on whether adhesion is to sialyl-Le(a), sulfated Le(a), or sialyl-Le(x) pentasaccharides, respectively. These findings have an important bearing on design of new generations of inhibitors of E-selectin binding as antiinflammatory compounds.

Animals↗

Antibodies to pneumococcal capsular polysaccharides in children with human immunodeficiency virus infection given polyvalent pneumococcal vaccine.

Antibody to 7 common pneumococcal capsular polysaccharides was measured in 11 children with human immunodeficiency virus (HIV) infection who had been previously vaccinated with 23-valent polysaccharide pneumococcal vaccine, 11 unvaccinated children with HIV infection, and 11 healthy subjects. No differences in capsule-specific IgG levels against serotypes 4, 6B, 8, 12F, 14, 19A, and 19F were observed among the vaccinees with HIV infection compared with unvaccinated children with HIV infection and age-matched control children.

Antibodies, Bacterial↗

Characterization of the sarcoplasmic reticulum proteins in the thermogenic muscles of fish.

Marlins, sailfish, spearfishes, and swordfish have extraocular muscles that are modified into thermogenic organs beneath the brain. The modified muscle cells, called heater cells, lack organized myofibrils and are densely packed with sarcoplasmic reticulum (SR), transverse (T) tubules, and mitochondria. Thermogenesis in the modified extraocular muscle fibers is hypothesized to be associated with increased energy turnover due to Ca2+ cycling at the SR. In this study, the proteins associated with sequestering and releasing Ca2+ from the SR (ryanodine receptor, Ca2+ ATPase, calsequestrin) of striated muscle cells were characterized in the heater SR using immunoblot and immunofluorescent techniques. Immunoblot analysis with a monoclonal antibody that recognizes both isoforms of nonmammalian RYRs indicates that the fish heater cells express only the alpha RYR isoform. The calcium dependency of [3H]ryanodine binding to the RYR isoform expressed in heater indicates functional identity with the non-mammalian alpha RYR isoform. Fluorescent labeling demonstrates that the RYR is localized in an anastomosing network throughout the heater cell cytoplasm. Measurements of oxalate supported 45Ca2+ uptake, Ca2+ ATPase activity, and [32P]phosphoenzyme formation demonstrate that the SR contains a high capacity for Ca2+ uptake via an ATP dependent enzyme. Immunoblot analysis of calsequestrin revealed a significant amount of the Ca2+ binding protein in the heater cell SR. The present study provides the first direct evidence that the heater SR system contains the proteins necessary for Ca2+ release, re-uptake and sequestration, thus supporting the hypothesis that thermogenesis in the modified muscle cells is achieved via an ATP-dependent cycling of Ca2+ between the SR and cytosolic compartments.

Adenosine Triphosphate↗

Thoracoscopic drainage and decortication as definitive treatment for empyema thoracis following penetrating chest injury.

PURPOSE: The purpose of this study is to describe our experience with thoracoscopic drainage and decortication as definitive treatment for empyema thoracis following penetrating chest trauma. METHODS: Over a 9-month period, eight patients at two institutions were treated for empyema thoracis that developed following penetrating chest injury. Seven patients sustained gunshot wounds and one a stab wound. All were treated for hemothorax with a closed tube thoracostomy. Associated injuries included six spinal cord injuries, a liver and diaphragmatic injury, a subclavian injury, and a carotid injury. Each patient subsequently developed an empyema. All patients underwent one thoracoscopic drainage and decortication of the empyema. RESULTS: In all patients, complete resolution of the empyema was achieved with the thoracoscopic technique. Chest tubes were removed a median of 8.5 days after the procedure. Median blood loss was 200 mL. The average duration of the operation was 110 minutes. There were two complications, a persistent air leak and a trapped lung, both treated with thoracoscopic intervention. CONCLUSION: Thoracoscopic drainage and decortication offers an alternative to thoracotomy for definitive therapy of empyema thoracis developing after penetrating chest trauma.

Adolescent↗

The use of oral fluid for hepatitis C antibody screening.

OBJECTIVES: To assess the efficacy of oral fluid antibody testing for the detection of hepatitis C. METHODS: Paired serum and oral fluid collections were obtained from 216 subjects. A modification of the serum HCV ELISA assay was developed to improve test accuracy for an oral fluid substrate. Sensitivity was determined in 109 HCV serum ELISA-positive patients and specificity in 107 HCV serum ELISA-negative patients. RESULTS: Overall sensitivity of oral fluid collection and testing was 98.2%; specificity was 99.1%. These parameters did not seem to be altered by presence of concurrent hepatitis B infection, inflammatory state of the liver, or other factors. CONCLUSIONS: Oral fluid collection and HCV antibody testing by the modified ELISA method seems to be an effective and efficient alternatives to venipuncture and serum HCV antibody testing. Their use may facilitate epidemiological surveys and evaluation of individual patients when blood collection is not feasible.

Adult↗

Down stairs that are never your own: supporting people with developmental disabilities in their own homes.

Supported living for people with developmental disabilities challenges many common service policies, practices, and assumptions. Until recently, professionals assumed that such people who did not reside with their families needed to live in some kind of service facility. Today, a growing number of people with developmental disabilities have challenged this assumption by living, with personalized support, in their own homes. Meeting this challenge calls for new relationships among people receiving support, those who provide support, and families that are focused on assisting people with developmental disabilities to establish a sense of place, security of place, and effective personalized control over their homes and the assistance they require.

Activities of Daily Living↗