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Biomedical subjects

K Barber

Publications and source records attributed to K Barber.

At least 19 recordsLinked to original sources

Life expectancy of adult liver allograft recipients in the UK.

BACKGROUND: Liver transplantation is a very successful therapy for those with end stage disease. Although there are numerous data on patient and graft survival after liver transplantation, life expectancy and possible loss of life (compared with a normal matched population) in those who survive remains unknown. AIMS: To assess the life expectancy and life years lost of adult liver allograft recipients, compared with an age and sex matched UK population to provide patients with more information and to improve the use of a scarce resource. METHODS: Using the National Transplant Database held by UK Transplant, on over 3600 adult liver allograft recipients transplanted between 1985 and 2003, we analysed survival of all adults who survived more than six months after transplantation and compared survival after transplantation with national age and sex matched controls to assess life years lost. RESULTS: Estimated median survival time of the analysis cohort of 2702 adult liver allograft recipients was 22.2 years (95% confidence interval 19.3-25.6), with an estimated loss of seven life years compared with an age and sex matched population. CONCLUSIONS: Overall, female recipients have a longer life expectancy and lose fewer life years than male recipients. While younger recipients have a longer life expectancy, they also lose more life years. Those transplanted for cancer, hepatitis C virus infection, and alcoholic liver disease had the greatest loss of life years.

Adolescent↗

Modular phakoemulsification training adapted for a left-handed trainee.

BACKGROUND: The increasing demand for high-volume, high-quality cataract surgery creates additional challenges for surgeons providing phakoemulsification training. We describe the modular training programme used by the Worcester Eye Department for inexperienced trainees and the adaptation of this programme to the needs of a left-handed trainee. METHODS: The intraoperative complications of a left-handed trainees' first 161 cases are reported. RESULTS: In this series, there was one case of vitreous loss (0.62%) and one case of posterior capsular tear (0.62%). Two cases developed stable anterior capsular tears (1.24%) and two cases required a single suture to ensure wound stability. CONCLUSION: We demonstrate a safe, effective and flexible method of phakoemulsification training.

Clinical Competence↗

Gamete intra-fallopian transfer or intrauterine insemination after controlled ovarian hyperstimulation for treatment of infertility due to endometriosis.

We compared the effectiveness of gamete intra-Fallopian transfer (GIFT) and intrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) in the treatment of infertility due to endometriosis. This was a retrospective study carried out at a tertiary teaching medical center. A total of 127 consecutive patients with endometriosis were treated with GIFT or IUI after COH between June 1990 and December 1998. Patients were divided into two groups. Group 1 (n = 97) included patients with stages 1 and 2 endometriosis, and group 2 (n = 30) included patients with stages 3 and 4 endometriosis. Laparoscopic conservative surgery for endometriosis was performed prior to IUI for patients in both group 1 and group 2. In group 1, 55 patients underwent 95 cycles of IUI after COH and 42 patients underwent 57 cycles of GIFT. In group 2, 14 patients underwent 16 cycles of IUI after COH, while 16 patients underwent 22 cycles of GIFT. The stimulation protocol for both GIFT and IUI was mid-luteal pituitary down-regulation with a gonadotropin releasing hormone agonist (GnRH-a) followed by gonadotropins. In group 1, the pregnancy rates (GIFT = 50.9%, IUI = 29.4%) and the delivery rates (GIFT = 28.1%, IUI = 14.7%) per cycle were significantly higher in GIFT compared to IUI (p = 0.009 and p = 0.05, respectively). There was no significant differences in the pregnancy rate (GIFT 69%, IUI 50.9%, respectively) or the delivery rate (GIFT 38.1%, IUI 25.5%) per patient. In group 2, there was no significant difference in the pregnancy rate (GIFT 54.5%, IUI 31.3%) or the delivery rate (GIFT 40.9%, IUI 12.5%) per cycle, but the difference in the pregnancy rate (GIFT 75%, IUI 35.7%) and the delivery rate (GIFT 56.3%, IUI 14.3%) per patient was significantly higher in GIFT compared to IUI (p = 0.04 and p = 0.02, respectively). We conclude that, when the same stimulation protocol is used in the early stages of endometriosis, a few cycles of IUI can achieve similar results to GIFT, and therefore should be used first. In advanced stages of endometriosis GIFT appears to be more effective.

Abortion, Spontaneous↗

Cardiac rehabilitation for community-based patients with myocardial infarction: factors predicting discharge recommendation and participation.

Although there is substantial evidence that cardiac rehabilitation is beneficial for post myocardial infarction (MI) patients, such programs are currently under utilized. This study examined systematic criteria predicting physician referral to and patients' participation in cardiac rehabilitation programs. Patients discharged for MI were interviewed in-hospital and at 6-12 weeks post discharge to determine referral, participation, and completion. Stepwise logistic regression analyzed factors associated with rehabilitation. Factors associated with referral to rehab were catheterization (p < 0.001), bypass surgery (p < 0.01), cardiologist/cardiac surgeon appointment (p < 0.02), and age (p < 0.01). Participation was increased for those with bypass surgery (p < 0.001), and referral to cardiologist or cardiac surgeon (p < 0.001). Type of provider significantly influences referral to and participation in cardiac rehabilitation. This suggests that encouragement plays a strong role in attendance for rehabilitation. The same strong encouragement should be given to the broader range of MI patients who stand to benefit from cardiac rehabilitation.

Adult↗

A single-centre study of 1000 consecutive peribulbar blocks.

PURPOSE: To assess the efficacy and safety of the peribulbar block as practised by anaesthetists in a District General Hospital and also to assess the effect of using the 'painless local' subconjunctival injection on the pain of the peribulbar block. METHOD: Audit data collected from 1000 consecutive patients undergoing peribulbar blocks with 2% lignocaine were analysed. Efficacy was assessed by visual rating scores for operative pain, eye movement, intraocular pressure and reinjection rate, and safety by looking at complications. Comparison of pain of injection scores was used to assess the effect of the 'painless local' injection. Visual rating scores for pain were analysed using the Mann-Whitney U-test. RESULTS: Akinesia was achieved in 79% of blocks and operative pain scores were very low (median = 0, IQR = 0). All complications recorded were minor and there were no sight- or life-threatening events. The 'painless local' injection given to 499 patients resulted in significantly lower visual rating scores for pain of injection (p<0.05). CONCLUSION: These data suggest that the peribulbar block is a safe and effective method of providing anaesthesia for eye surgery provided that it is taught methodically and practised by experienced staff. The 'painless local' injection reduces the pain experienced during administration of this block.

Adult↗

Emergency medicine residencies: A descriptive study of program structure

The steady growth in EM residency programs reflects the desirability of EM as a specialty area for training. However, a profile of programs offered nationwide is not available. OBJECTIVE: To characterize emergency medicine (EM) programs nationwide according to program format, curriculum, and opportunities for subspecialty training. METHODS: In this descriptive study, U.S. emergency medicine residency curriculums were evaluated electronically using SAEM and FRIEDA residency information websites. Data collected included program format, hospital size and volume, rotation durations, curriculum and electives offered. RESULTS: The most common format (72%, n = 87) is PGY 1, 2, 3 and PGY 2, 3, 4 accounted for 18% (n = 22) and PGY 1, 2, 3, 4 for 10% (n = 12). The average length of training in the ED is 19 months (range 7-40). Average general pediatric training is 1.8 months (range 0-5). The average number of rotations outside the primary site is 4.9 (range 0-19) and elective rotation time and topics varied considerably. Opportunities for air medical training differed by program format (82% of PGY 1-3, 79% of PGY 1-4, 75% of PGY 2-4) (table 11-1). CONCLUSIONS: There is substantial variation in curriculum, in subspecialty exposure, and in opportunity for electives for residents depending on program format and location.

Journal Article↗

Use of physician assistants as surgery/trauma house staff at an American College of Surgeons-verified Level II trauma center.

BACKGROUND: Historically, surgical physicians staff trauma centers, which provide trauma patients with improved outcomes. Such benefits fuel the expansion of designated trauma centers. Cutbacks in residency programs of surgical specialties, however, necessitate substitutions for traditional trauma providers. METHODS: A literature and record review was conducted to examine the use of physician assistants in a large community hospital's verified trauma center. Current and historical outcomes were analyzed regarding the trauma surgeon/physician assistant model. RESULTS: Injury Severity Scores increased 19%, transfer time to the operating room decreased 43%, transfer time to the intensive care unit decreased 51%, and transfer time to the floor decreased 20%. The length of stay for admissions decreased 13%, and the length of stay for neurotrauma intensive care unit patients decreased 33%. CONCLUSION: The Hurley Medical Center trauma surgeon/physician assistant model is a viable alternative for verified trauma centers unable to maintain a surgical residency program. Consistency and quality of care indicated by shortened length of stay is a hallmark of such a model providing the highest quality of care.

Adolescent↗

CNS neuronal focal adhesion kinase forms clusters that co-localize with vinculin.

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that appears to play a central role in integrin-mediated signal transduction in non-neuronal cells, linking the extracellular matrix to the actin-based cytoskeleton at focal adhesion contacts. Biochemical analysis has revealed the presence of FAK immunoreactivity in cells of neuronal lineage (Zhang et al., 1994) and in the CNS (Burgaya et al. 1995; Grant et al., 1995). In the current work, we have examined the immunodistribution of FAK in nerve cell cultures and tissue sections from the rat CNS. Cultures of B103 CNS neuroblastoma cells and primary cultures of hippocampal neurons both showed abundant FAK immunoreactivity in nerve cell bodies. Immunoreactivity also extended into neurites and growth cones. The most striking feature of FAK distribution was the presence of short, punctate clusters of high FAK concentration. These FAK clusters were maintained in triton-extracted cell ghosts, indicating association with the cytoskeleton. Double-label confocal imaging showed that clusters of FAK coincided with clusters of vinculin, another actin-associated signal transduction molecule implicated in control of growth cone motility. Data from hippocampal sections verified the presence of FAK in adult neurons where it was enriched in somato-dendritic domains and showed a non-uniform distribution. Quantitative FAK immunoprecipitation to compare adult with embryonic brain showed a 7-fold developmental down-regulation of FAK and a 21-fold down-regulation of FAK TyrP. The data suggest that neuronal FAK may participate in signal transduction complexes relevant to neuronal morphogenesis and plasticity.

Age Factors↗

Delivery of membrane-impermeant fluorescent probes into living neural cell populations by lipotransfer.

Use of fluorescent probes to monitor f-actin in living cells typically relies on difficult microinjection procedures. The current work has developed cationic lipotransfer of membrane-impermeant probes as an alternative to microinjection. BODIPY FL-phallacidin, a fluorescent f-actin probe, was packaged into 40-50 nm cationic liposomes. Packaging, verified by gel filtration, enabled delivery of the probe into living nerve cells and provided an image of f-actin that was identical to that seen in fixed, permeabilized cells. Phallacidin alone did not enter living cells, nor was its uptake stimulated by the presence of empty liposomes. All predicted f-actin structures were fluorescent in living cells, indicating a high efficacy of delivery. Cationic lipotransfer of fluorescent probes was rapid, not disruptive to cells, and delivered a probe en masse to a large sample population. Lipotransfer appears to be a promising alternative to microinjection for introducing membrane-impermeant probes and reagents into living cells.

Actins↗

Fetal exposure to involuntary maternal smoking and childhood respiratory disease.

BACKGROUND: Several studies have now gone beyond the effects of smoking during pregnancy to examine the effects of involuntary maternal smoke exposure on fetal development. A link has also been indicated between postnatal environmental smoke exposure and long-term respiratory problems in infants. OBJECTIVE: Our study examines whether an association exists between maternal exposure to environmental tobacco smoke and childhood respiratory disorders. METHODS: A cross-sectional design was implemented utilizing a maternal questionnaire survey. The surveys were distributed throughout the county's health department and outlying clinic immunization sites. The county population is a diverse community of all racial and socioeconomic levels and includes a metropolitan population of approximately 300,000. The questionnaire comprised inquiries about the child's wheeze, acute respiratory illnesses, and maternal and paternal exposure to passive smoke and/or other environmental air pollutants. RESULTS: Chi-square and logistic regression analysis showed no statistically significant difference between passively smoke-exposed-in-utero subjects and non-smoke-exposed in-utero subjects on the outcomes of allergy and wheeze. Asthma, however, did show a statistically significant association to passive smoke exposure (chi2 = 12.4, P = .05 and Log reg = 8.7, P = .03). CONCLUSION: Passive maternal exposure to tobacco smoke during pregnancy is associated with increased incidence of asthma and supports other research findings that children born of mothers who are passively exposed to smoke during pregnancy are at risk for patterns of negative developmental outcomes.

Adult↗

Particulate forms of APP in the extracellular milieu of cultured cells.

The principle externalized forms of amyloid precursor protein (APP) are soluble and well-characterized, but some evidence has suggested the additional presence of externalized APP in a nonsoluble form. To further assess this possibility, the current study has applied high resolution microscopy protocols in addition to immunoprecipitation to characterize externalized APP in three commonly used cell culture models (SH-SY5Y human neuroblastoma cells, fetal rat brain cells, and HEK 293 human embryonic kidney cells). Confocal immunofluorescence microscopy, using an antiserum against the c-terminal domain of APP, showed typical cell-associated APP, but hot spots of APP also were evident in cell-free areas, apparently associated with the culture substrata. These hot-spots were examined for evidence of cellular deterioration by whole mount transmission electron microscopy. Neither cell debris nor disrupted cells were present. Instead, the hot spots of substratum-bound APP comprised discrete microparticles, approximately 50-100 nm across. These microparticles also could be found near cells and in some cases were attached to cell surface fibrils. Substratum-bound APP also could be found clustered within the extracellular matrix made by primary cell cultures. Occurrence of APP in extracellular microparticles was verified by centrifugation-immunoprecipitation analysis of media conditioned by APP-transfected cells. Radiolabeling data showed that particulate APP was from metabolically active cells. Metabolic labeling of particle-associated APP, as well as the absence of cellular debris near the APP-containing particles, suggests that the occurrence of nonsoluble APP in the extracellular milieu derives from a physiologically active process.

Amyloid beta-Protein Precursor↗

Alzheimer's-associated phospho-tau epitope in human neuroblastoma cell cultures: up-regulation by fibronectin and laminin.

Alzheimer's-afflicted neurons contain phosphorylated forms of tau that are not present in healthy adults. these can be recognized with great specificity by monoclonal antibodies such as paired helical filament-1 (PHF-1) [Greenberg S. G. and Davies P. (1990) Proc. natn. Acad. Sci. U.S.A. 87, 5827-5831; Greenberg S. G. et al. (1992) J. biol. Chem. 267, 564-569]. The PHF-1 phospho-tau epitope is also present in immature neurons undergoing axodendritic differentiation [Pope W. B. et al. (1993) Expl Neurol. 120, 106-113]. Analogous to its presence in immature neurons, we report here that the PHF-1 tau epitope spontaneously occurs in the human neuroblastoma cell line SHSY5Y, where its level can be regulated by differentiation and by molecules found in the extracellular matrix. Confocal immunofluorescence studies showed PHF-1 epitope to be constitutively expressed in the somatic cytoplasm as well as in short neurites typical of undifferentiated SHSY5Y cells. Induction of differentiation with retinoic acid produced cells with a neuronal morphology and a redistribution of the expression of PHF-1 tau in the long neurites. Protracted exposure to retinoic acid decreased the levels of PHF-1 immunofluorescence without a loss of neurites, similar to the developmental down-regulation seen in situ. The effects of retinoic acid on PHF-1 immunofluorescence were modifiable by fibronectin, which can be released by some neuroblastoma cell lines [Ciccarone V. et al. (1989) Cancer Res. 49, 219-225; Yoshihara T. et al. (1992) Int. J. Cancer 51, 620-626]. Exogenous human fibronectin caused a marked up-regulation of PHF-1 immunofluorescence. Quantitative analysis of 15 multicellular areas, from six different cultures, per experimental condition showed a 16-fold increase compared to untreated controls. Up-regulation by fibronectin was also evident in undifferentiated cells. Cell counts indicated no proliferative effects of the fibronectin under the conditions used. Laminin also caused an increase of PHF-1 tau in retinoic acid-treated cells. Data obtained from immunoblots verified the results observed with immunofluorescence. The data show that the PHF-1 tau epitope is spontaneously expressed by non-degenerating human neuroblastoma cells, down-regulated by cellular differentiation, induced by retinoic acid and up-regulated by the extracellular matrix components fibronectin and laminin. One explanation of the data is that fibronectin maintains a population of SHSY5Y cells in a biochemical state of differentiation in which PHF-1 tau is expressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Alzheimer Disease↗

Functional analysis of the effects of a fully humanized anti-CD4 antibody on resting and activated human T cells.

A fully humanized anti-CD4 antibody was studied for its effects on resting and activated CD4 T cells. Whereas the antibody was poorly lytic, it induced dramatic down-modulation of CD4 expression on both types of cell. In order to down-modulate CD4 on resting, normal CD4 T cells there was an absolute requirement for FcR-mediated cross-linking of the anti-CD4 antibody, and only CD4 levels were affected. When activated cloned T-cell lines were studied there was no requirement for cross-linking and several other cell surface markers were also affected. Although the total cellular CD4 was reduced in the down-modulated cells, as judged by Western blot analysis, that CD4 which remained was associated with p56lck. The results are discussed in relation to the potential use of humanized anti-CD4 antibodies in the therapy of autoimmune disease and the choice of antibody isotype for such a therapeutic antibody.

Antibody-Dependent Cell Cytotoxicity↗

Beta/A4-evoked degeneration of differentiated SH-SY5Y human neuroblastoma cells.

beta/A4 peptides are known to induce neurodegeneration in cultures of rat brain cells and rat neural cell lines (Yankner et al: Science 250:279-282, 1990; Behl et al: Biochem Biophys Res Commun 186:944-950, 1992). The current data show that these peptides induce similar neurodegeneration in SH-SY5Y neuroblastoma cells, extending characterization of beta/A4 toxicity to a human nerve cell line. Human SH-SY5Y cells respond to aggregated beta/A4 with changes in cell shape, membrane blebbing, antigenic modification, loss of attachment to the substrate, and cell death. beta/A4 peptides require aggregation for maximum toxic effects, as cellular degeneration is evoked by aggregated beta/A4 1-42 and 4-41 cysteine but not by monomeric beta/A4 1-40. Aged (pre-aggregated) beta/A4 1-40 also evoked neurodegeneration. Antigenic changes comprise upregulation of Alzheimer's-type tau epitopes, recognized by the PHF-1 and Alz-50 monoclonals. These particular changes in tau support the connectivity between this in vitro model and mechanisms leading to neurodegeneration in Alzheimer's disease. A significant feature of the SH-SY5Y response is that cells must be differentiated before they become sensitive to the degeneration evoked by beta/A4. Signaling pathways leading to beta/A4-evoked neurodegeneration thus are under experimental control, becoming complete only when proliferating cells withdraw from the cell cycle and develop a postmitotic phenotype.

Alzheimer Disease↗

Focal adhesion kinase expressed by nerve cell lines shows increased tyrosine phosphorylation in response to Alzheimer's A beta peptide.

A beta is a 39-43-amino acid peptide that accumulates as extracellular aggregates in Alzheimer's disease-afflicted brain tissue. Contact between these aggregates and neurons is potentially pathogenic, although little is known about the cellular transduction mechanisms. We have investigated the impact of A beta aggregates on the neuronal control of protein tyrosine phosphorylation, which underlies signal transduction for multiple families of growth factor and adhesion receptors. Added to cultures of rat and human nerve cell lines, A beta aggregates evoked a non-desensitizing increase (1.3-3.6-fold) in tyrosine phosphorylation in a band at 118 kDa. The 118-kDa protein was determined by immunoprecipitation to be pp125FAK, not previously documented in cells of neuronal lineage. Immunoblots with anti-focal adhesion kinase (FAK) showed that A beta aggregates had no effect on FAK protein levels. The increase in FAK tyrosine phosphorylation occurred at doses of A beta aggregates that evoked lactate dehydrogenase release; evoked tyrosine phosphorylation preceded the first detectable lactate dehydrogenase release by 4 h. Like degeneration, the FAK response was dependent on A beta aggregation and neuronal differentiation. Since tyrosine phosphorylation of FAK is essential to its activity as a transduction component of integrin-, peptide-, and lysophosphatidic acid-mediated signaling, the data establish a link between A beta aggregates and signal transduction pathways implicated in diverse cell functions including neurite outgrowth, control of the cell cycle, and apoptosis.

Amino Acid Sequence↗

Issues of domestic violence unique to rural areas.

Domestic violence against women occurs within and across all socioeconomic, demographic, and geographic regions of the United States. Many of the dynamics related to domestic violence, and which trap women in violent relationships, also cross these boundaries. These dynamics include societal and community attitudes toward violence, isolation, fear of exposure, lack of resources to facilitate leaving a violent relationship, and lack of sufficient accessible services for victims of violence. This paper highlights that these and other issues of domestic violence are intensified in rural settings. As such, physicians working in rural areas may face unique challenges in helping battered women. Such challenges will require solutions based on knowledge of specific rural location. A number of rural-based solutions for physician interventions with rural battered women are discussed.

Causality↗

Analysis of interferon-alpha 2 sequences in human genomic DNA.

We have analyzed the genomic DNA sequence corresponding to the human interferon-alpha 2 (IFN-alpha 2) gene locus. In human lymphoblastoid Namalwa cells, we have detected sequences corresponding to IFN-alpha 2b and -2c, while in human KG-1 cells both IFN-alpha 2a and -2b were present. However, in 100 independent IFN-alpha 2 clones derived from 20 unrelated Caucasian volunteers, we found only sequences corresponding to IFN-alpha 2b. Statistical analysis of this result suggests that the sequences corresponding to IFN-alpha 2a and -2c are either rare allelic variants of this gene, occurring in only a minority of the Caucasian population, or are restricted to transformed cell lines.

Amino Acid Sequence↗