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Biomedical subjects

E Walker

Publications and source records attributed to E Walker.

At least 19 recordsLinked to original sources
PubMed2006

Recombinant human erythropoietin is associated with increased overall survival in patients with multiple myeloma.

BACKGROUND: Recombinant human erythropoietin (rhEPO) is effective for the treatment of anemia associated with multiple myeloma. Data from animal studies and case reports suggest that rhEPO has antineoplastic properties. METHODS: Two hundred and ninety-two patients enrolled on different chemotherapy clinical trials at the Cleveland Clinic Myeloma Program between 1997 and 2003 were the subjects of this study. Information on erythropoietin use as well as baseline prognostic variables were collected retrospectively. RESULTS: The population consisted of 257 patients with multiple myeloma treated at the Cleveland Clinic Foundation from 1997 to 2003 and followed for at least 1 month. Thirty-five patients were excluded from this analysis because information on erythropoietin use was not available. One hundred and twenty-seven patients received rhEPO for at least 1 month and the rest did not received rhEPO. On average, patients who received rhEPO were older, had a higher Southwest Oncology Group (SWOG) stage, higher serum creatinine, lower serum hemoglobin, higher beta2-microglobulin, lower platelet counts, and a longer time from diagnosis to enrollment at the myeloma program (p < 0.001 for all). After adjusting for age, months from diagnosis to enrollment, serum creatinine, hemoglobin, platelet count, and beta2-microglobulin, the use of rhEPO was associated with improved overall survival (hazard ratio = 0.6; 95% CI = 0.38-0.94) in patients with SWOG stages II, III and IV but not in patients with SWOG stage I. CONCLUSION: rhEPO was associated with improved overall survival in this population of anemic multiple myeloma patients with SWOG stages of II, III and IV. A prospective randomized trial is warranted to corroborate this finding.

Aged↗
PubMed2006

Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy.

BACKGROUND: Lenalidomide is active and well tolerated in relapsed and refractory multiple myeloma. We conducted a phase I/II trial of the combination of lenalidomide and chemotherapy to evaluate the safety and efficacy of the combination. METHODS: The 62 patients enrolled received liposomal doxorubicin 40 mg/m(2) i.v. and vincristine 2 mg i.v. on day 1, dexamethasone 40 mg p.o. on days 1-4 (DVd), and lenalidomide on days 1-21 in 28-day cycles. Primary end points were maximum tolerated dose (MTD) of lenalidomide with DVd chemotherapy and overall response rate (ORR) by Southwest Oncology Group criteria of the combination. FINDINGS: The median age was 62 years, 70% of patients were males and 65% had refractory multiple myeloma. The MTD of lenalidomide with DVd chemotherapy was 10 mg and the dose-limiting toxicity was non-neutropenic sepsis. After 7.5 months of median follow-up, the ORR of the combination was 75%, with 29% of patients achieving a complete or near complete remission. The median progression-free survival was 12 months, while the median overall survival has not yet been reached. INTERPRETATION: The combination of lenalidomide and DVd chemotherapy was well tolerated and resulted in high response rates in this mostly refractory patient population. Evaluation of this combination in newly diagnosed patients is warranted.

Aged↗
PubMed2006

Targeted disruption of the mouse ing1 locus results in reduced body size, hypersensitivity to radiation and elevated incidence of lymphomas.

Ing1 belongs to the family of evolutionary conserved genes encoding nuclear PHD finger-containing proteins implicated in a variety of processes, including tumorigenesis, replicative senescence, excision repair and response to genotoxic stress. We have generated mice deficient in all the isoforms of Ing1 by targeted disruption of the exon that is common for all ing1 transcripts. Embryonic fibroblasts from ing1-knockout mice were similar to the wild-type cells in their growth characteristics, replicative lifespan in culture, p53 induction and sensitivity to various cytotoxic treatments with minor alterations in cell cycle distribution in response to genotoxic stress. ing1-deficient animals are characterized by reduced size with no obvious morphological, physiological or behavioral abnormalities, indicating that ing1 function is dispensable for the viability of mice under normal physiological conditions. Loss of ing1 was associated with earlier onset and higher incidence of lymphomas. Consistent with the possible involvement of Ing1 in DNA repair, ing1-deficient mice were more sensitive to total body gamma radiation. Our observations are well in line with the suggested role of ing1 as a candidate tumor suppressor gene involved in control of DNA damage response.

Abnormalities, Multiple↗
PubMed2006

Spatiotemporal patterns of host-seeking Ixodes scapularis nymphs (Acari: Ixodidae) in the United States.

The risk of Lyme disease for humans in the eastern United States is dependent on the density of host-seeking Ixodes scapularis Say nymphal stage ticks infected with Borrelia burgdorferi. Although many local and regional studies have estimated Lyme disease risk using these parameters, this is the first large-scale study using a standardized methodology. Density of host-seeking I. scapularis nymphs was measured by drag sampling of closed canopy deciduous forest habitats in 95 locations spaced among 2 degrees quadrants covering the entire United States east of the 100th meridian. Sampling was done in five standardized transects at each site and repeated three to six times during the summer of 2004. The total number of adults and nymphs of the seven tick species collected was 17,972, with 1,405 nymphal I. scapularis collected in 31 of the 95 sites. Peak global spatial autocorrelation values were found at the smallest lag distance (300 km) and decreased significantly after 1,000 km. Local auto-correlation statistics identified two significant high-density clusters around endemic areas in the northeast and upper Midwest and a low-density cluster in sites south of the 39th parallel, where only 21 nymphs were collected. Peak nymphal host-seeking density occurred earlier in the southern than in the most northern sites. Spatiotemporal density patterns will be combined with Borrelia prevalence data as part of a 4-yr survey to generate a nationwide spatial risk model for I. scapularis-borne Borrelia, which will improve targeting of disease prevention efforts.

Animals↗
PubMed2006

Horizontal transfer of Shiga toxin and antibiotic resistance genes among Escherichia coli strains in house fly (Diptera: Muscidae) gut.

Whether the house fly, Musca domestica L., gut is a permissive environment for horizontal transfer of antibiotic resistance and virulence genes between strains of Escherichia coli is not known. House flies were immobilized and force fed suspensions of defined, donor strains of E. coli containing chloramphenicol resistance genes on a plasmid, or lysogenic, bacteriophage-born Shiga toxin gene stx1 (bacteriophage H-19B::Ap1). Recipient strains were E. coli lacking these mobile elements and genes but having rifampicin as a selectable marker. Plasmid transfer occurred at rates of 10(-2) per donor cell in the fly midgut and 10(-3) in the fly crop after 1 h of incubation postfeeding. Bacteriophage transfer rate was approximately 10(-6) per donor cell without induction, but induction with mitomycin C increased rates of transfer to 10(-2) per donor cell. These findings show that genes encoding antibiotic resistance or toxins will transfer horizontally among bacteria in the house fly gut via plasmid transfer or phage transduction. The house fly gut may provide a favorable environment for the evolution and emergence of pathogenic bacterial strains through acquisition of antibiotic resistance genes or virulence factors.

Animals↗
PubMed2006

Incremental risk of obstructive sleep apnea on cardiac surgical outcomes.

AIM: Obstructive sleep apnea (OSA) is not generally acknowledged as a perioperative risk factor. High incidence of Sleep disordered breathing has been noticed in patients with cardiovascular disease. The Sleep Heart Health Research Study Group found Apnea-Hypopnea indices (AHI) as modest as 1-10 to be associated with cardiovascular disease manifestations. Given the lack of data we chose to study the incremental risk of OSA in patients undergoing cardiac surgery. METHODS: We looked at 25 587 patients who underwent cardiac surgery at the Cleveland Clinic. Of these, 37 patients were also identified on the Cleveland Clinic Sleep center database as having OSA. Each of these 37 cases were propensity matched for multiple covariates with 5 controls within a distance of 0.001 units. An assumption was made that if the surgery was performed within two years of the diagnosis of OSA, the patient had OSA at the time of the surgery. RESULTS: Higher incidence of encephalopathy (p=0.008), postoperative infection (0.028) and increased ICU length of stay (p=0.031) were noted in the group with OSA after cardiac surgery. The difference in the rates of infection was mostly accounted for by the presence of mediastinitis (8.1% vs 1.6%). Differences in the rates of reintubation, tube time, and overall postoperative morbidity were not statistically significant. CONCLUSIONS: | Increased risk for postoperative complications is suggested in patients with OSA undergoing cardiac surgery. This risk is underestimated on account of lack of awareness about the incidence of OSA in the general population and the cardiovascular population in particular, difficulties in clinical suspicion and diagnosis and limited use of polysomnography.

Aged↗
PubMed2005

Obstetric recovery practice: a survey of UK obstetric anaesthetists.

BACKGROUND: The 1998 guidelines for obstetric anaesthesia services state: "postoperative care of the obstetric patient should be in accordance with that of any postoperative patient". We sought to discover whether this standard of care was provided. METHOD: A questionnaire designed to investigate recovery room practice was sent to 251 UK obstetric units. The survey took place between January and June 2003. RESULTS: The response rate was 78%. A total of 123 units (63%) had a dedicated obstetric recovery area. Midwives were exclusively responsible for postoperative parturient care in 113 units (58%) between 0900 and 1700 h and in 124 units (64%) after 1700 h. Dedicated recovery nurses were available in 59 units (30%) during the day, in contrast to 36 units (19%) after 1700 h. The level of background training ranged from no training (39%) to locally organised courses (32%), rotation through surgical areas (21%) and nationally organised English National Board courses (8%). CONCLUSION: The survey demonstrates that current obstetric recovery room practice does not always adhere to the recommended Association of Anaesthetists of Great Britain and Ireland guidelines. The provision of dedicated recovery staff or a cohort of specifically trained midwives may help to improve existing standards.

Adult↗
PubMed2004

Anaesthetic management of aortic coarctation in pregnancy.

We report two cases of aortic coarctation in pregnancy. The first was a 20-year-old nulliparous woman who underwent an aortic coarctation repair when she was 23 weeks old and subsequently developed an aneurysm at the site of initial repair. The second was a 20-year-old nulliparous woman with a severe uncorrected congenital aortic coarctation and upper body hypertension, who became pregnant whilst awaiting transcatheter dilatation of the coarctation. Antenatal care involved a multidisciplinary approach with obstetric, anaesthetic and cardiology input. Both parturients were delivered by elective caesarean section. A cautious, incremental regional anaesthetic technique was used, with no associated maternal or neonatal morbidity. Perioperative management focused on minimising haemodynamic disturbances. The management is discussed, together with the potential maternal and fetal complications of aortic coarctation in pregnancy.

Adult↗
PubMed2004

Manipulating the host response to autologous tumour vaccines.

From our way of thinking the problem facing vaccine strategies for cancer is not that we do not have "enough" tumour antigens. The problem is we cannot induce an immune response that is sufficient to mediate tumour regression. The normal "checks and balances" found in the body prevent the sustained expansion and subsequent persistence of immune killer cells. If vaccine strategies are going to become effective treatments for cancer patients, they will need to overcome this substantial roadblock. Recent developments in immunology have provided insights into the mechanisms that regulate the expansion and persistence of T cells. This has allowed investigators to reinterpret decades-old observations suggesting that chemotherapy administered before vaccination often led to a stronger immune response. This manuscript will review experiments that offer an explanation for these observations and present pre-clinical data from our laboratory that describes an innovative new approach to combining chemotherapy and vaccination. This approach is readily translatable to the clinic and is broadly applicable to any vaccine strategy for advanced cancer.

Antigens, Neoplasm↗
PubMed2004

Socio-demographic and clinical characteristics of Jamaican adolescents with HIV/AIDS.

BACKGROUND: Clinical symptomatology and socio-demographic factors have not been characterized in Jamaican adolescents with HIV/AIDS. METHODS: We studied these factors in 25 HIV-positive Jamaican adolescents, 10-19 years of age, who were seen at the Centre for HIV/AIDS Research, Education, and Services (CHARES) between the years 1996 and 2002. Data were collected between June 2003 and August 2003 from CHARES social work files and The University Hospital of the West Indies (UHWI) medical records. Microsoft Excel was used to compile descriptive statistics for the data. RESULTS: The mean age of HIV diagnosis was 15.6 (+/-3.09) years, and the mean age of enrollment at CHARES was 16.3 (+/- 2.9) years. Consensual sexual intercourse was the most prominent mode of transmission (56%), followed by vertical transmission (16%), unknown (16%), forced sexual intercourse (8%), and blood transfusion (4%). The predominant clinical presentations among these adolescent patients were generalized dermatitis (77.2%) and lymphadenopathy (50%). Of the patients for whom clinical status could be determined, 70% were "Severely Symptomatic ". Of these patients only 14% were recommended for antiretroviral treatment. CONCLUSIONS: These findings reinforce the need to globally incorporate the goal of the 2002 Joint United Nations Programme on HIV/AIDS (UNAIDS) "to provide reproductive health services, including low-cost or free condoms, voluntary counselling and testing, diagnosis and treatment of sexually transmitted diseases and infections for adolescents in order to effectively prevent HIV infection " (1).

Acquired Immunodeficiency Syndrome↗
PubMed2003

Moraxella catarrhalis induces mast cell activation and nuclear factor kappa B-dependent cytokine synthesis.

Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-kappaB) nuclear binding activity. In some experiments, NF-kappaB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-kappaB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-kappaB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.

Cell Line, Tumor↗
PubMed2003

Rapid habituation of hippocampal serotonin and norepinephrine release and anxiety-related behaviors, but not plasma corticosterone levels, to repeated footshock stress in rats.

Prior stress exposure is known to alter the activation response to a subsequent stressor. In the present study, we examined neurochemical, neuroendocrinological, and behavioral correlates of short-term adaptation to homotypic stressors administered 60 min apart. An initial electric footshock significantly induced extracellular levels of both serotonin (5-HT) and norepinephrine (NE) in the rat hippocampus (650% and 200% above baseline, respectively), as measured by in vivo microdialysis. A rapid habituation in this response was evident in the inability of a second footshock to evoke similar increases. In contrast, the hypothalamic-pituitary-adrenal (HPA) response was augmented further after the second shock session: plasma corticosterone (CORT) levels were 18.1, 316.5, and 441.6 mg/ml in nonstressed, one-footshock-, or two-footshock-treated rats, respectively. In a social interaction paradigm, rats subjected to a single footshock showed several fear- and anxiety-related behaviors such as increases in freezing and decreases in rearing and active approach for social interaction. Exposure to a second footshock completely blocked the freezing response and restored rearing behavior without affecting the disruption in social interactions. Taken together, these data raise the possibility that neurochemical and neuroendocrine adaptations to short-term homotypic stressors differentially contribute to expression of different fear and anxiety-like responses in the rat.

Animals↗
PubMed2003

Behavioural factors associated with symptom outcomes in a primary care-based depression prevention intervention trial.

BACKGROUND: A randomized trial of a primary care-based intervention to prevent depression relapse resulted in improved adherence to long-term antidepressant medication and depression outcomes. We evaluated the effects of this intervention on behavioural processes and identified process predictors of improved depressive symptoms. METHOD: Patients at high risk for depression recurrence or relapse following successful acute phase treatment (N=386) were randomly assigned to receive a low intensity 12-month intervention or continued usual care. The intervention combined education about depression, shared decision-making regarding use of maintenance pharmacotherapy and cognitive-behavioural strategies to promote self-management. Baseline, 3, 6, 9 and 12-month interviews assessed patients' self-care practices, self-efficacy for managing depression and depressive symptoms. RESULTS: Intervention patients had significantly greater self-efficacy for managing depression (P<0.01) and were more likely to keep track of depressive symptoms (P<0.0001), monitor early warning signs (P<0.0001), and plan for coping with high risk situations (P<0.0001) at all time points compared to usual care control patients. Self-efficacy for managing depression (P<0.0001), keeping track of depressive symptoms (P=0.05), monitoring for early warning signs (P=0.01), engaging in pleasant activities (P<0.0001) and engaging in social activities (P<0.0001) positively predicted improvements in depression symptom scores. CONCLUSIONS: A brief intervention designed to target cognitive-behavioural factors and promote adherence to pharmacotherapy in order to prevent depression relapse was highly successful in changing several behaviours related to controlling depression. Improvements in self-efficacy and several self-management behaviours that were targets of the intervention were significantly related to improvements in depression outcome.

Antidepressive Agents↗
PubMed2003

A comparison of travel related ID admissions in Glasgow: (1985; 1998/99).

A comparative study was made of patients admitted over 12 months to the principal infectious diseases unit for Glasgow in 1985 and in 1998/99. During this interval UK travel statistics show a 135% growth in visits abroad and a 5% rise to 17% in destinations with a risk of malaria. Travel associated admissions rose by 96% to a total of 108. Patients of Asian/Oriental ethnicity declined from 55% to 18%, whilst Caucasians increased from 38% to 81%. Travellers aged 20-39 years formed the modal age groups (51% and 50%). Gastro-intestinal problems accounted for the largest single diagnostic category in both study periods, 38% and 40% respectively. In-patients diagnosed with malaria fell by 20%; these figures are cause for encouragement to those involved in the teaching and dissemination of advice on malaria prophylaxis. The findings re-enforce the need for the continuation and expansion of travel health education for both healthcare professionals and the public.

Adolescent↗
PubMed2002

Observation of an unconventional metal-insulator transition in overdoped CuO2 compounds.

The electron dynamics in the normal state of Bi(2)Sr(2)CaCu(2)O(8+delta) is studied by inelastic light scattering over a wide range of doping. A strong anisotropy of the electron relaxation is found which cannot be explained by single-particle properties alone. The results strongly indicate the presence of an unconventional quantum-critical metal-insulator transition where "hot" (antinodal) quasiparticles become insulating while "cold" (nodal) quasiparticles remain metallic. A phenomenology is developed which allows a quantitative understanding of the Raman results and provides a scenario which links single- and many-particle properties.

Journal Article↗