Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical research evidence on outcomes of using epoetin (EPO) to treat or prevent anemia in oncology has recently been systematically synthesized to provide a scientific foundation for developing and implementing clinical practice guidelines. Two groups have distinguished themselves by their meticulous research methods, the Blue Cross and Blue Shield Association Technology Evaluation Center (BCBSA TEC) and the Cochrane Review Group (CRG), and have summarized existing research evidence on the role of EPO in anemia associated with cancer treatment. An ASH/ASCO (American Society of Hematology/American Society of Clinical Oncology) panel has used the BCBSA TEC review to develop practice guidelines on the use of EPO in patients with cancer. The ASH/ASCO guideline panel identified eight important clinical circumstances for which use of EPO in oncology might be considered and used the BCBSA TEC evidence review to formulate evidence-based guidelines that support use of EPO. Both BCBSA TEC and CRG found solid evidence exists to show that EPO improves hemoglobin levels and reduce the risk for transfusion. The ASH/ASCO panel concluded that best empirical evidence exists to support the use of EPO to correct anemia due to chemotherapy if Hgb</=10g/dl. In other clinical circumstances the ASH/ASCO panel made recommendations either by extrapolating evidence from similar settings or relied on expert opinion since sufficient evidence was lacking. Both BCBSA TEC and CRG also concluded that limited evidence exists that EPO improves symptoms, fatigue, or quality of life, particularly when anemia is less severe. The finding from these systematic reviews are also reflected in the opinion of the ASH/ASCO guidelines panel, which also concluded that better evidence is needed to support use of EPO in oncology under these circumstances. In this paper, the findings from the guidelines set by ASH/ASCO that were culled from systematic reviews by BCBSA TEC and the Cochrane Review are compared and contrasted.
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PMID:Erythropoietin use in oncology: a summary of the evidence and practice guidelines comparing efforts of the Cochrane Review group and Blue Cross/Blue Shield to set up the ASCO/ASH guidelines. 1579 20

The study aim was to assess reliability of repeated laboratory sprint tests in well-trained endurance cyclists. Eleven male cyclists (mean +/- standard deviation: 27 +/- 6 yr, 1.79 +/- 0.04 m, 70.1 +/- 3.3 kg) performed a maximal 30-second sprint test on four separate occasions using their own bicycle fitted with an SRM powermeter on a Kingcycle air-braked ergometer. Peak power output (W (peak)), mean power (W (mean)) and an index of fatigue (FI) were calculated. Three minutes post sprint, capillarised blood lactate measurements were taken and analysed. No significant differences (p > 0.05) were found between trials for W (peak), W (mean), FI and blood lactate concentration. Repeatability of W (peak), W (mean), and fatigue index improved across trials 2 and 3 when compared to trials 1 and 2. The highest CV for these variables was recorded between trials 3 and 4. The CV for W (peak) was 4.5 +/- 1.6 %, W (mean) 2.4 +/- 1.2 %, and FI 17.2 +/- 7.1 %. Intraclass reliability coefficients were 0.93 (95 % CI 0.84 - 0.98), 0.94 (95 % CI 0.86 - 0.98) and 0.89 (95 % CI 0.69 - 0.95) respectively. Blood lactate concentration ranged between 5.35 and 14.52 mmol.l(-1), with a mean CV of 12.1 +/- 4.2 %. The CV for trials 2 and 3 revealed the highest CV for blood lactate concentration (15.1 %). The lowest CV for this variable (10.2 %) was recorded between trials 3 and 4. The intraclass reliability coefficient for blood lactate concentration was 0.79 (95 % CI 0.58 - 0.93). The results of this study indicate that there is no improvement in the reliability of sprint test indices when assessing well-trained, experienced cyclists, riding on their own cycle equipment.
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PMID:Reliability of sprint test indices in well-trained cyclists. 1589 22

The present phase II study aimed to define the application of a novel regimen incorporating methotrexate, paclitaxel, epirubicin, and carboplatin (M-TEC) in advanced bladder cancer, essentially as an M-VAC-like regimen, by substitution of cisplatin by carboplatin, doxorubicin by epirubicin and vinblastine by paclitaxel. Forty patients with advanced bladder cancer entered the study; 34 males/6 females, median age: 68 (range, 59-76), median PS (Karnovsky): 80, without receiving prior chemotherapy. Disease extention was as follows; 11/40 had local recurrence, 6/40 liver metastases, 14/40 lung metastases, bone and lymph node 8/40, bones-lymph node-lung metastases 4, lymph node and liver 4/40, lymph node-liver and lung metastases 2/40. Drug schedule and doses were as follows: paclitaxel 180 mg/m2, carboplatin AUC = 5 (according to creatinine clearance, based on Calvert's formula), and epirubicin 40 mg/m2 were administered during day 1, whereas methotrexate 30 mg/m2 and epirubicin 40 mg/m2 were administered on day 14. All patients were evaluable for response with 24/40 responding [response rate (RR) 60%]; 10/40 (25%) CR, 14/40 (35%) PR, 9/40 (22.5%) SD, and 7/40 (17.5%) PD. Symptomatic improvement was observed in 50% of patients. The median duration of response was 22 (14-32) weeks, median time-to-progression (TTP) 33 (12-44) weeks, and median survival was 56 (20-84) weeks. Toxicity was well accepted and was mainly neutropenia > grade 3: 17%, anemia >grade 3: 16%, thrombocytopenia > grade 2: 6%, nausea & vomiting mainly > grade 2: 31%, according to the administered chemotherapy cycles, whereas fatigue grade 2-3: 19%, neurotoxicity grade 1-2 13% of patients, and alopecia grade 2 was observed in all patients. The present pilot study indicates the feasibility of the M-TEC combination for bladder cancer with acceptable toxicity.
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PMID:Methotrexate-paclitaxel-epirubicin-carboplatin (M-TEC) combination chemotherapy in patients with advanced bladder cancer: an open label phase II study. 1616 25

Femoral components of hip replacements are commonly anchored in the femur with bone cement or poly(methyl methacrylate) (PMMA). Wear or fracture of bone cement can lead to loosening of the femoral component, which drastically affects the success and longevity of hip replacements. Self-reinforced composite PMMA (SRC-PMMA) has been previously developed for potential use, as a precoat material for hip replacements. The composite consists of high strength fibers that have been shown to have greatly improved mechanical properties over bulk PMMA. The goal of this work was to examine SRC-PMMA for improved wear properties, as a function of processing temperature. Pin-on-disc tests were used to characterize and rank the wear rates of SRC-PMMA and PMMA. Composites made with higher processing temperatures had significantly lower wear rates than do PMMA at a significance level of p < or = 0.05. The lowest wear rate was 8.2 microg/m, at a processing temperature of 136 degrees C, compared to a wear rate for PMMA of 13.3 microg/m. At the lowest processing temperature (105 degrees C), a wear rate higher than PMMA was found, and failure was dominated by fiber delamination. In the more completely processed samples (122 degrees C < or = T < or = 150 degrees C), wear rates were equivalent to or better than PMMA, and smoother and more homogenous wear was noted in wear tracks. Fatigue cracks were prominent at higher processing temperatures or when the wear pin was riding orthogonal to fibers. Wear particles were collected and examined. Wear particle diameter and aspect ratio showed no correlation to processing temperature, but were similar to particles retrieved from human tissue samples.
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PMID:Pin-on-disc evaluation of self-reinforced composite poly(methyl methacrylate) for total joint replacements. 1654 4

The development of body weight gain and lipodystrophy due to antiretroviral therapy may lead to disturbances in sleep, particularly the obstructive sleep apnoea (OSA) syndrome. A retrospective review of the medical records of consecutively identified HIV-infected subjects who were diagnosed with OSA by overnight polysomnography between January 1, 2003 and December 31, 2004 was performed. Twelve HIV-infected subjects with OSA confirmed by polysomnography (total apnoea/hypopnoea index > or = 5) were identified. Daytime somnolence, fatigue, and snoring were the most common symptoms identified. Eleven (92%) subjects were overweight/obese, and seven (58%) had lipodystrophy. Eleven (92%) had a neck size > or =40.0 cm. Increased neck circumference, overweight or obese body mass index, and lipodystrophy are therefore potential risk factors for OSA among HIV patients. Clinicians caring for HIV patients with these characteristics should inquire about daytime somnolence, fatigue, and snoring and consider evaluation for a sleep-related disorder such as OSA. Overnight polysomnography can aid in the diagnosis of sleep disturbances.
Int J STD AIDS 2006 Sep
PMID:Obstructive sleep apnoea among HIV patients. 1694 53

This article presents a theoretical design of an FES controller to be used for stimulation of multiple mono and biarticulate muscles to restore multiple degree-of-freedom (DOF) motion in paralyzed individuals. The overall control strategy is based on multiple DOF musculo-skeletal model, nonlinear sliding mode control design, constrained optimization techniques to determine the needed muscle activations, and an additional inversion of the neuro-muscular stimulation relationship in order to obtain the needed controller output (electrical current amplitude/pulse-width). The combination of these methods leads to a controller that guarantees asymptotically stable tracking of reference position trajectories while assuring minimal (optimal) muscle activation and fatigue.
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PMID:Design of multiple degree-of-freedom sliding mode FES controller for concurrent stimulation of multiple mono and biarticulate muscles. 1727 39

We present our experience with skeletal involvement of Pneumocystis jiroveci (ex P. carinii) infection in an HIV-seropositive patient. The objective of this study was to alert clinicians to the possibility that extrapulmonary P. jiroveci could affect the skeletal system in HIV-infected patients with extremely rapid progression. P. jiroveci infection of skeletal system has been rarely described elsewhere. A 51-year-old man complained of fever for six weeks, cough, anorexia, fatigue, and chest pain. He was found to be HIV seropositive. Repetitive (six samples) sputum and bronchoalveolar lavage fluid microbiologic tests were negative. High-resolution chest computed tomography (CT) scan revealed a small pulmonary mass. Abdominal CT scan revealed lesions in liver, spleen, kidneys, adrenal glands, lumbar vertebrae, and sacrum. Brain and skull CT scan was normal. A fine-needle biopsy of the lung mass was unrevealing. Cytological examination of sputum specimens showed findings consistent with non-small-cell lung carcinoma. Nineteen weeks post-presentation, the patient reported low-back pain. Within 24 hours after the onset of low-back pain, he developed focal neurological deficits, and a magnetic resonance imaging (MRI) of the skull and spine showed osteolytic lesions of the temporal bones bilaterally, multiple vertebral lesions, and lesions of sacrum and iliac bones. Radiotherapy of the lumbar spine and pelvis was given. Sternal aspiration was performed. Cytological examination revealed P. jiroveci. In conclusion, we describe a rare case of disseminated P. jiroveci infection in an HIV-seropositive patient, with multiple skeletal lesions, especially in the skull and in vertebrae region, and concomitant non-small-cell lung cancer, with a very poor prognosis.
Int J STD AIDS 2007 Feb
PMID:Multi-skeletal Pneumocystis jiroveci (carinii) in an HIV-seropositive patient. 1733 Dec 92

Zoledronic acid inhibits the prenylation of ras-related proteins downstream of bcr-abl and preclinical studies have shown augmentation of the inhibitory effects of imatinib in BCR-ABL expressing cells. A Phase I/II study was designed to assess the safety and efficacy of the addition of zoledronic acid to imatinib in patients with chronic myeloid leukaemia (CML) with a suboptimal response to imatinib alone. Ten patients with CML who had been treated with imatinib for at least 2 years and had achieved and maintained a complete haematological response were included. Zoledronic acid was administered intravenously on one occasion every 28 d. The initial dose of 4 mg was given for three consecutive months; in the absence of significant toxicity and/or response the dose was escalated to 8 mg for an additional 3 months. Efficacy was assessed by serial monitoring of blood levels of BCR-ABL transcripts and bone marrow cytogenetics. Addition of zoledronic acid to imatinib caused no haematological toxicity. There were no grade III or IV non-haematological adverse effects. Grade I fatigue, hypocalcaemia and fever were common side effects. No responses were demonstrated after 6 months on the combination.
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PMID:Dual inhibition of ras and bcr-abl signalling pathways in chronic myeloid leukaemia: a phase I/II study in patients in complete haematological remission. 1742 38

fickle is a P-element mutation identified from a screen for defects in courtship behavior and disrupts the fly homolog of Bruton's tyrosine kinase (Btk) gene (Baba et al., 1999). Here, we show that habituation of the olfactory jump reflex also is defective in fickle. Unlike, the prototypical memory mutants, rutabaga and dunce, which habituate more slowly than normal, fickle flies habituate faster than normal. fickle's faster-than-normal response decrement did not appear to be due to sensorimotor fatigue, and dishabituation of the jump response was normal. Based on a long-standing "two opponent process" theory of habituation, these data suggested that behavioral sensitization might be defective in fickle. To test this hypothesis, we designed a olfactory sensitization procedure, using the same stimuli to habituate (odor) and dishabituate (vortexing) flies. Mutant flies failed to show any sensitization with this procedure. Our study reveals a "genetic dissection" of sensitization and dishabituation and, for the first time, provides a biological confirmation of the two opponent process theory of habituation.
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PMID:The fickle mutation of a cytoplasmic tyrosine kinase effects sensitization but not dishabituation in Drosophila melanogaster. 1746 98

Patients with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF) have limited therapeutic options. The farnesyltransferase-inhibitor tipifarnib inhibits in vitro proliferation of myeloid progenitors from such patients. In the current phase II clinical trial, single-agent oral tipifarnib (300 mg twice daily x 21 of 28 days) was given to 34 symptomatic patients with either PMF (n=28) or post-PV/ET MF (n=6). Median time to discontinuation of protocol therapy was 4.6 months; reasons for early termination (n=19; 56%) included disease progression (21%) and adverse drug effects (18%). Toxicities (>/=grade 3) included myelosuppression (n=16), neuropathy (n=2), fatigue (n=1), rash (n=1) and hyponatremia (n=1). Response rate was 33% for hepatosplenomegaly and 38% for transfusion-requiring anemia. No favorable changes occurred in bone marrow fibrosis, angiogenesis or cytogenetic status. Pre- and post-treatment patient sample analysis for in vitro myeloid colony growth revealed substantial reduction in the latter. Clinical response did not correlate with either degree of colony growth, measurable decrease in quantitative JAK2(V617F) levels or tipifarnib IC(50) values (median 11.8 nM) seen in pretreatment samples. The current study indicates both in vitro and in vivo tipifarnib activity in PMF and post-PV/ET MF.
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PMID:A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. 1758 8


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