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Metastatic colorectal cancer. 5-FU 200 mg m2 day as 14-day continuous iv infusion for six cycles ; plus OHP at increasing doses 25-30-35 mg m2 day, as 12 h chronomodulated iv infusion on days 1-2-3-4, every 14 days for six cycles ; were administered to reach maximum tolerated dose MTD ; . At MTD 30 mg m 2 day ; , a PK study of 5-FU and OHP in total and ultrafiltered-UF plasma ; was performed. 5-FU plasma levels were fairly stable, below that reported in similar studies and closely related to the lack of the most typical 5-FU toxicities. OHP Cmax occurred 7 h after infusion start; a progressive accumulation of free Pt and ultrafiltered Pt UFOHP ; through cycles 1-6 was noted. A marked difference between total plasma and UF Pt was seen in the elimination phase. OHP plasma clearance decrease was related to Vz volume of distribution of late elimination phase ; , whereas in UF-OHP was due to a change in Ke or conclusion, the association of 5-FU with chronomodulated OHP do not seem to influence PK parameters of either drugs. Toxicity was modest acceptable and clinical efficacy good: preliminary data showed a threshold neurotoxicity at total plasma Pt concentrations 1500 ng ml and UF plasma Pt concen trations 150 ng ml. 2003 Published by Editions scientifiques et m dicales Elsevier SAS. e 623. Cobalt chloride and low oxygen tension trigger differentiation of acute myeloid leukemic cells: Possible mediation of hypoxia-inducible factor-1 - Huang Y., Du K.-M., Xue Z.-H. et al. [Dr. G.-Q. Chen, 280 Chong-Qing South Road, Shanghai 200025, China] - LEUKEMIA 2003 17 11 ; - summ in ENGL Cellular and systemic O2 concentrations are tightly regulated to maintain delicate oxygen homeostasis. Although the roles of hypoxia in solid tumors have been widely studied, few studies were reported regarding the possible effects of hypoxia on leukemic cells. Here, we showed for the first time that low concentrations of cobalt chloride CoCl2 ; a hypoxia-mimicking agent, and 2-3% O2 triggered differentiation of various subtypes of human acute myeloid leukemic AML ; cell lines, including NB4, U937 and Kasumi-1 cells, respectively, from M3, M5 and M2b-type AML, but CoCl2 did not modulate AML subtype-specific fusion proteins promyelocytic leukema-retinoic acid receptor alpha PML-RAR ; and AML1-ETO. Treatment with CoCl2 also induced primary leukemic cells from some AML patients to undergo differentiation. Similar to what occurs in solid tumor cells, CoCl2 -mimicked hypoxia also increased the level of hypoxia-inducible factor HIF ; -1 protein and its DNA-binding activity in leukemic cells. The CoCl2 induction of HIF-1 protein and its DNA-binding activity were inhibited by 3-morpholinosydnonimine, which also blocked CoCl2 -induced cell differentiation in leukemic cells. These results provide an insight into a possible link of hypoxia or HIF-1 and leukemic cell differentiation, and are possibly of significance to explore clinical potentials of hypoxia or hypoxia-mimicking agents and novel target-based drugs for differentiation therapy of leukemia. 624. Transferrin receptor ligand-targeted toxin conjugate TfCRM107 ; therapy of malignant gliomas - Weaver M. and Laske D.W. [Dr. D.W. Laske, Department of Neurosurgery, Temple University, School of Medicine, 3401 N. Broad St., Philadelphia, PA 19140-5103, United States] - J. NEURO-ONCOL. 2003 65 1 ; - summ in ENGL The authors review the preclinical and clinical results of the ligand-targeted toxin conjugate Transferrin-CRM107 Tf-CRM107 ; , for the treatment of malignant gliomas. Tf-CRM107 is a conjugate protein of diphtheria toxin with a point mutation CRM107 ; linked by a thioester bond to human transferrin Tf ; . This conjugate exhibits potent cytotoxicity in vitro against mammalian cells expressing the transferrin receptor with activity at picomolar concentrations. Phase I clinical trial results demonstrated that Tf-CRM107, delivered via a high-flow convection method utilizing stereotactically placed catheters, produced tumor response in patients with malignant brain tumors refractory to conventional therapy without severe neurologic or systemic toxicity. The results of a Phase II study are also summarized. Tf-CRM107 treatment results in complete and partial tumor response without severe toxicity in 35% of the evaluable patients. These data warrant a Phase III study as well as continued research in the field of targeted toxin therapy. Future directions of research include optimizing Tf-CRM107 Section 30 vol 126.2.
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A Cancer Guideline Implementation Workshop was held on 14 October 2004 at Level 3, Medical Foundation Building. The meeting was held under the auspices of the National Institute of Clinical Studies NICS ; , NBCC and ACN. It was facilitated by Professor Dave Davis from Toronto and was positive in every respect. Apart from identifying and discussing a range of issues in a positive manner, it allowed a number of people with like interests to learn of each other's existence. It will also have impact on the matrix being developed for the ACN Guideline Implementation Steering Committee. Guideline development activities continue with progress being made in a number of important areas.
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TABLE 1 Baseline characteristics Healthy volunteers M F Smokers n ; Age years ; BMI kg m2 ; Diabetes duration years ; H b A1 Glucose mmol l ; Total cholesterol mmol l ; HDL cholesterol mmol l ; Triglycerides mmol l ; UAE mg 24 h ; Noradrenaline nmol l ; Systolic blood pressure mmHg ; Diastolic blood pressure mmHg ; MAP mmHg ; Heart rate beats min ; FBF ml 100 ml1 min1 ; Infused arm Control arm 10 2 5 ; 23.3 22.824.1 ; - - 4.3 4.24.4 ; 4.6 3.55.3 ; 1.2 1.01.3 ; 1.45 0.901.72 ; -- 0.61 0.510.81 ; 107 103122 ; 70 6274 ; 81 7585 ; 53 5159 ; 2.8 2.13.2 ; 2.3 1.83.4 ; C 8 3 ; 22.7 20.623.7 ; 13 1122 ; 8.4 6.89.0 ; 7.1 5.67.4 ; * 4.3 4.05.4 ; 1.4 1.21.6 ; 0.82 0.661.08 ; 11 516 ; 0.63 0.390.95 ; 106 98117 ; 67 6184 ; 80 7784 ; 67 5870 ; 2.5 2.24.1 ; 2.2 1.83.1 ; R + 9 ; 23.6 22.925.1 ; 19 1723 ; 8.8 8.29.0 ; 6.7 6.47.5 ; * 4.7 4.15.1 ; 1.1 0.71.4 ; 0.77 0.571.07 ; 11 516 ; 0.71 0.660.77 ; 108 100133 ; 75 6579 ; 87 8092 ; 66 6369 ; * 3.0 1.93.9 ; 2.3 1.83.2 ; MA + 10 ; 24.3 23.725.5 ; 20 1726 ; 9.6 7.810.1 ; 7.5 6.77.9 ; * 4.1 3.54.5 ; 1.0 0.91.3 ; 0.78 0.500.96 ; 150 70431 ; 0.72 0.570.81 ; 123 116140 ; 80 7286 ; 94 8899 ; 74 6483 ; * 2.8 2.35.6 ; 2.8 1.83.3.
Instruction 8 is to provide answers for that scientific development linked to the Dolly case, but we already know that the technique used to create Dolly is outdated. Therefore, our first conclusion was that Normative Instruction 8 has to be reviewed in the light of the new scientific perspectives related to the therapeutic application of stem cells. We suggest that CTNBio should be part of the conclusions of this seminar, and that Normative Instruction 8 should be reviewed, especially article 2, which prohibits any work with totipotent cells or germinative cells. We would have to make a distinction between the work with these two types of cells, maybe creating a new item in the document and establishing that the work with totipotent cells is, in fact, permitted by law. In fact, article 8, item III states that work with human germinative cells is allowed for the treatment of genetic diseases. This `exception' under the law, contained in article 8, would open a path to work with totipotent cells for therapeutic purposes. So, the group proposes that Normative Instruction 8 should be reviewed, eliminating the work with germinative cells and totipotent cells and permitting the work with totipotent cells for the treatment of human beings, according to the provisions of article 8, item III. That would be our first recommendation. The document should contain general principles so as to allow for future scientific and technological advances. The Code of Ethics for Genetic Manipulation should contemplate ethics not only in research but also in the commercialization of such products. We propose that CTNBio should review its Normative Instructions, particularly Normative Instruction 8, and maybe Normative Instruction 9 as well, in the light of new scientific advances, more specifically with regard to stem cells. We propose the liaison of CTNBio with the Veterinary Medical Council and with the Federal Medical Council for a wider discussion on the Code of Ethics, where the Code of Ethics for Genetic Manipulation would be part of a more comprehensive Code of Ethics. Maria Celeste Emerick I would like to suggest the review of article 13, as it has raised some criticism. We are regulating a Law, so we should focus on the law. Article 13 is heavily controversial from the legal point of view, so it might be important, at this moment, to review this specific article and theo-dur.
Effect of therapy on the mental health of the elderly. Effectiveness of interventions to prevent delirium in hospitalized patients. NEW Effectivness of treatments of depression in older ambulatory patients. Effects of memory training on the subjective memory functioning and mental health of older adults: a meta-analysis Effects of respite care on patients with dementia and their caregivers Efficacy and safety of neuroleptics in behavioural disorders associated with dementia Electronic communication with patients: evaluation of distance medicine technology. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. Evaluation of medication management interventions for the elderly NEW How useful are cholinesterase inhibitors in the treatment of Alzheimer's disease. NEW Is music therapy an effective intervention for dementia; a meta-analytic review of literature, for example, aviane.
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Contrary to popular belief, not all teens smoke pot. Only about one in five 10th graders report they used marijuana within the past month. Fewer than one in four high school seniors is a current marijuana user. Marijuana--pot, grass, reefer, ganja, smoke, bud, blunts, and bhang--is one of the most widely used illicit drugs in the United States and very few young people use other illegal drugs without first trying marijuana. Just because it is common though does not mean it is safe. Marijuana today is far stronger than it was two or three decades ago, and far more dangerous.
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Pharmacists should be advocators of immunizations and educators for primary caregivers. They can help ascertain that children with SCD are indeed up to date with their immunizations by reviewing their immunization records or interviewing the primary caregiver. Ideally, an accurate immunization history is maintained with the patient's medication history. Any missing vaccines should be recommended to the pediatrician for administration. Prompt initiation and good adherence to vaccine schedules and prophylactic antibiotic regimens are key to optimizing patient outcomes.
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A.NCTdrugs.lsh.12Dec04Final.doc Lim, S. H., V. Anantharaman, et al. 1998 ; . "Comparison of treatment of supraventricular tachycardia by Valsalva maneuver and carotid sinus massage." Ann Emerg Med 31 1 ; : 30-5. ABS STUDY OBJECTIVE: To compare the efficacy of the Valsalva maneuver with that of carotid sinus massage CSM ; in terminating paroxysmal supraventricular tachycardia SVT ; in the ED. METHODS: This prospective, randomized case study was performed in the ED of a tertiary care institution. Patients were at least 10 years of age with regular narrow complex tachycardia and had an ECG diagnosis of SVT. Patients with regular narrow complex tachycardia were randomly assigned to undergo either the Valsalva maneuver or CSM. If the tachycardia was not terminated by the method chosen by randomization, then the alternative method of vagal maneuver was used. If the tachycardia was not converted by both methods of vagal stimulation, patients would undergo either synchronized electrical cardioversion or a pharmacologic method of conversion at the discretion of the treating physician, depending on the patient's hemodynamic status. RESULTS: One hundred forty-eight instances of SVT were studied Sixty-two patients underwent Valsalva maneuver first with conversion in 12 success rate of 19.4% ; . Eighty-six underwent CSM first with conversion in 9 success rate 10.5% ; . Carotid sinus massage was used in the 50 cases of SVT in which conversion was not achieved with the Valsalva maneuver. Conversion occurred in 7 cases success rate 14.0% ; . For the 77 cases of SVT in which initial CSM did not achieve conversion, conversion occurred in 13 with the Valsalva maneuver success rate 16.9% ; . The Valsalva maneuver and CSM achieved conversion in a total of 41 instances of SVT success rate 27.7% ; . CONCLUSION: Vagal maneuvers are efficacious in terminating about one quarter of spontaneous SVT cases. There is no detectable difference in efficacy between the Valsalva maneuver and CSM and ocuflox.
These activities include, but may not be limited to, the following: - conducting quality assessment and improvement activities, case management, disease management and care coordination, contacting of health care providers and patients with information about treatment alternatives and related functions that do not include treatment.
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