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At least 1,153 records · Page 64Linked to original sources
PubMed1998

Practice guidelines: a more rational approach to diagnosis and treatment and a more effective use of health care resources.

Practice guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances. The implementation of practice guidelines is justified by factors such as variations in clinical practice, malpractice and its associated costs, and the need to contain health care expenditures. In this context, practice guidelines promote a more rational approach to clinical decision making and better quality of care. Although there are several limitations to the use of guidelines in current practice, different organizations (professional societies, government agencies, licensing authorities, educational institutions) have a potential interest in their development. A working group on the development of practice guidelines endorsed by the Italian Society of Neurology has been active since 1995. The aims of this group include the development of guidelines to be accepted by the medical community and to be placed within the framework of initiatives of the Italian Ministry of Health.

Health Care Costs↗
PubMed1994

General practitioners for rational use of drugs. Examples from Sweden.

In the south west region of Stockholm a group of 125 general practitioners (GPs) at 27 health centres asked about the extent to which the drug formulary of the University Hospital was useful in their practices. To answer this question, the GPs asked their local pharmacies for prescribing data. When presented this started a process towards rational prescribing from within the group of GPs, including repeated prescribing surveys, starting with health centres as the unit of analysis and proceeding to individual prescribing analyses on request by the GPs. As the prescribing data revealed major differences between health centres, the GPs arranged two workshops on drug use in primary health care. They developed a list of 167 recommended drugs based on drug statistics and morbidity in general practice. Signs of increased cost cautiousness could be shown. There was a clear trend towards both smaller volumes and cost per prescription item for the health centres in the study area. Compared to the national prescribing pattern, prescribing practice in the study area represented a 20 per cent lower drug cost. Although the GPs decided on a drug list separate from that of the hospital, collaboration between the Drug and Therapeutic Committee at the hospital and the GPs increased as a result of their increased engagement in drug management, thereby also bridging the gap between primary health care and clinical pharmacology.

Drug Prescriptions↗
PubMed1998

Rational approaches to immune regulation.

Our studies are mainly focused on developing strategies of immune regulation. In the case of infectious and neoplastic disease, our approach is to upregulate cell-mediated immunity to viral of tumor antigens using an intracellular bacterium as a vector for targeting these antigens to the major histocompatibility complex (MHC) class I and class II pathways of antigen processing, in addition to exploiting the adjuvant properties of the vector to stimulate innate immunity. In the area of autoimmunity, we are attempting to downregulate the immune response by specific immune intervention directed against autoreactive T cells. In these studies we use murine models for multiple sclerosis. Our approach is to use both rationally designed T cell receptor (TCR) peptide analogs and recombinant viral vectors that express TCR components to regulate the disease.

Animals↗
PubMed2006

Whole genome expression analysis for biologic rational pathway modeling: application in cancer prognosis and therapy prediction.

Using semi-quantitative microarray technology, almost every one of the approximately 30 000 human genes can be analyzed simultaneously with a low rate of false-positives, a high specificity, and a high quantification accuracy. This is supported by data from comparative studies of microarrays and reverse-transcription PCR for established cancer genes including those for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2/ERBB2), estrogen receptor (ESR1), progesterone receptor (PGR), urokinase-type plasminogen activator (PLAU), and plasminogen activator inhibitor-1 (SERPINE1). As such, semi-quantitative expression data provide an almost completely comprehensive background of biological knowledge that can be applied to cancer diagnostics. In clinical terms, expression profiling may be able to provide significant information regarding (i) the identification of high-risk patients requiring aggressive chemotherapy; (ii) the pathway control of therapy predictive parameters (e.g. ESR1 and HER2); (iii) the discovery of targets for biologically rational therapeutics (e.g. capecitabine and trastuzumab); (iv) additional support for decisions about switching therapy; (v) target discovery; and (vi) the prediction of the course of new therapies in clinical trials. In conclusion, whole genome expression analysis might be able to determine important genes related to cancer progression and adjuvant chemotherapy resistance, especially in the context of new approaches involving primary systemic chemotherapy. In this review, we will survey the current progress in whole genome expression analyses for cancer prognosis and prediction. Special emphasis is given to the approach of combining biostatistical analysis of expression data with knowledge of biochemical and genetic pathways.

Cluster Analysis↗
PubMed1998

[Preoperative diagnosis of a patent foramen ovale: rational use of transthoracic and transesophageal contrast echocardiography].

BACKGROUND: The detection or ruling out of a patent foramen ovale (PFO) can be determined noninvasively by contrast echocardiography (CE). The transesophageal technique is superior to the transthoracic technique regarding sensitivity, whereas the specificity of both methods is equally high. This prospective study shows the rational use of transesophageal CE for the detection of a PFO, in patients without cardiovascular disorders. METHODS: 165 patients (92 female, 73 male, age 48 +/- 18 years) with planned neuro-surgery in a sitting position, underwent CE to rule out a PFO. If the CE was positive, an alternative position was selected in order to avoid a paradoxical air embolism. RESULTS: Initially, a transthoracic CE was performed in all patients resulting in 21 patients (13%) being positive and 39 patients (24%) being negative by sufficient image quality. A transesophageal CE was performed in 96 of the remaining 105 patients (63%). Here, further 25 patients showed a positive CE in the sense of a PFO. The combined use of transthoracic and transesophageal CE revealed a PFO in 46 of 165 patients (28%). CONCLUSION: The use of both, transthoracic and transesophageal CE is an efficient approach to the preoperative detection of a PFO in the sense of quality and economics. Depending upon the image quality, the use of a transesophageal examination could be avoided in one third of the cases.

Adolescent↗
PubMed2003

[Alopecia areata. Clinical aspects, pathogenesis and rational therapy of a T-cell-induced autoimmune disease].

Alopecia areata is a T-cell mediated autoimmune disease directed against an unknown auto antigen of the hair follicle. There is a genetic predisposition to develop alopecia areata, whereas environmental triggers have so far not been identified. The diagnosis can be established by characteristic clinical features of alopecia areata including its severe forms alopecia areata totalis and universalis. Nail changes may help confirm the diagnosis. On rare occasions a histopathological examination may be necessary, whereas other laboratory investigations are unnecessary. Because of the high rate of spontaneous remission, the efficacy of a rational treatment of alopecia areata has to be proven in controlled studies and it should be associated with only minor side effects. According to the rules of evidence-based medicine, treatment with a contact sensitizer is at present the most effective treatment of alopecia areata showing only mild side effects. However, it is time-consuming and in some cases ineffective, making it desirable to develop new, more specific forms of treatment.

Alopecia Areata↗
PubMed2006

[Rational symptomatic therapy for chronic pruritus].

Chronic pruritus is a difficult-to-treat problem which accompanies many dermatologic and systemic diseases. Frequently, therapy is ineffective and prolongs the pruritus. Thus significant costs arise for the health system, which are clearly lowered by a rational therapy concept. Extensive knowledge about both topical and systemic therapy of pruritus has been acquired in recent years. Currently, new therapeutic approaches are available, which intervene in different pruritogenic mechanisms. Substances can block the cutaneous pruritus induction (e.g. antihistamines, leukotriene antagonists, cannabinoid agonists) or mediate central effects such as the inhibition of pruritus transmission via the spinal cord (e.g. naltrexone, gabapentin) or the suppression of the cerebral itch perception (e.g. antidepressants, neuroleptics). Usually combining several therapeutic principles is necessary in order to suppress chronic pruritus with lasting effect. The most effective approach is to gradually combine therapies, always considering both the medical and financial impacts.

Aged↗
PubMed2006

[Rational minimally invasive treatment of pAOD: when should a conservative approach, PTA, or stent be chosen?].

In order to obtain optimal results and satisfied patients, rational therapy of pAOD should strictly follow national and international society guidelines. In particular cases an individual therapeutic concept seems justified beyond these guidelines. Based on clinical data and driven by costs, aortic and iliac lesions may be treated by PTA or selective stent placement with equal results; however, long-term data justify also primary, direct stenting. For treatment of infrainguinal and popliteal stenotic lesions primary stenting should be restricted to PTA failure (dissection, recoil, occlusion); except for treatment of extended lesions, primary stenting compared to PTA alone seems beneficial in terms of midterm patency. Endovascular procedures below the knee and at the toe should be limited to existing limb-threatening ischemia in order to save the extremity; whether PTA or stenting is advantageous has not yet determined.

Angioplasty, Balloon↗
PubMed1998

[Rational diagnosis of the bile ducts].

Since the introduction of MR cholangiography (MRC) diagnostic imaging of the biliary tract has been significantly improved. While percutaneous ultrasonography is still the primary examination, computed tomography (CT), conventional magnetic resonance imaging (MRI), as well as the direct imaging modalities of the biliary tract--i.v. cholangiography, endoscopic-retrograde-cholangiography (ERC), and percutaneous-transhepatic-cholangiography (PTC) are in use. This article discusses the clinical value of the different diagnostic techniques for the various biliary pathologies with special attention to recent developments in MRC techniques. An algorithm is presented offering a rational approach to biliary disorders. With further technical improvement shifts from ERC(P) to MRC(P) for biliary imaging could be envisioned, ERCP further concentrating on its role as a minimal invasive treatment option.

Biliary Tract Diseases↗
PubMed2000

Rational design of biologically active peptides: inhibition of T cell activation through interference with CD4 function.

In our laboratory we generated one synthetic cyclic peptide (Pep4) and tested it in human mitogen stimulation assays (MSA) and mixed lymphocytes reactions (MLR) generating dose-response curves showing a dose-dependent inhibition of MSA up to 80% and MLR up to 98%. MSA and MLR were repeated after pre incubation of the Pep4 with each separate responder cell subset and subsequent reconstitution: these experiments showed inhibition only when the peptide was present in culture. Pep4 showed species specificity since it was ineffective in inhibiting rat MLR. Combination effect analysis with Pep4 and cyclosporine showed a combination index > 1. This rationally designed peptide (Pep4) shows powerful inhibition of human T cell activation and, although the exact mechanism is still undefined, it seems to exert its major action on the T cell surface, interfering with co receptor interaction and disrupting the same activation signal pathway inhibited by cyclosporine A.

Animals↗
PubMed2002

Cellular levels of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) as predictors of therapeutic responses to cyclophosphamide-based chemotherapy of breast cancer: a retrospective study. Rational individualization of oxazaphosphorine-based cancer chemotherapeutic regimens.

PURPOSE: In preclinical models, established molecular determinants of cellular sensitivity to cyclophosphamide, long a mainstay of chemotherapeutic regimens used to treat breast cancers, include the aldehyde dehydrogenases that catalyze the detoxification of this agent, namely, ALDH1A1 and ALDH3A1. As judged by bulk quantification of relevant catalytic activities, as well as of relevant proteins (ELISAs), tissue levels of these enzymes vary widely in primary and metastatic breast malignancies. Thus, interindividual variation in the activity of either of these enzymes in breast cancers could contribute to the wide variation in clinical responses obtained when such regimens are used to treat these malignancies. Direct evidence for this notion was sought in the present investigation. METHODS: Cellular levels of ALDH1A1 and ALDH3A1 in 171 repository human breast tumor (122 primary and 49 metastatic) samples were semiquantified using immunocytochemical staining. Clinical responses were retrieved from the archived medical records of each of 48 metastatic breast cancer sample donors, 26 of whom had been treated with a cyclophosphamide-based chemotherapeutic regimen subsequent to tumor sampling and 22 of whom had not. The premise that cellular levels of ALDH1A1 and/or ALDH3A1 predict clinical responses to cyclophosphamide-based chemotherapeutic regimens was submitted to statistical analysis. RESULTS: Confirming an earlier report, ALDH1A1 and ALDH3A1 levels varied widely in both primary and metastatic breast tumor cells. When measurably present, each of the enzymes appeared to be evenly distributed throughout a given tumor cell population. Retrospective analysis indicated that cellular levels of ALDH1A1, but not those of ALDH3A1, were (1) significantly higher in metastatic tumor cells that had survived exposure to cyclophosphamide than in those that had not been exposed to this drug, and (2) significantly higher in metastatic tumors that did not respond (tumor size did not decrease or even increased) to subsequent treatment with cyclophosphamide-based chemotherapeutic regimens than in those that did respond (tumor size decreased) to such regimens. The therapeutic outcome of cyclophosphamide-based chemotherapy corresponded to cellular ALDH1A1 levels in 77% of cases. The frequencies of false-positives (cyclophosphamide-based chemotherapy not effective when a low level of ALDH1A1 predicted it would be) and false-negatives (cyclophosphamide-based chemotherapy effective when a high level of ALDH1A1 predicted it would not be) were 0.00 and 0.43, respectively. Thus, partial or complete responses to cyclophosphamide-based chemotherapy occurred 2.3 times more often when the ALDH1A1 level was low than when it was high. CONCLUSIONS: Given (1) the wide range of ALDH1A1 levels observed in malignant breast tissues, (2) that ALDH1A1 levels in primary breast tumor tissue, as well as those in normal breast tissue, directly reflect ALDH1A1 levels in metastatic breast tumor cells derived therefrom, and (3) the findings reported here, measurement of ALDH1A1 levels in primary breast malignancies and/or normal breast tissue prior to the initiation of chemotherapy is likely to be of value in predicting the therapeutic potential, or lack of potential, of cyclophosphamide and other oxazaphosphorines, e.g. ifosfamide, in the treatment of primary, as well as metastatic, breast cancer, thus providing a rational basis for the design of individualized therapeutic regimens for this disease. Failure to observe the expected inverse relationship between clinical responses to cyclophosphamide-based chemotherapeutic regimens and ALDH3A1 levels was probably because even the highest breast tumor tissue ALDH3A1 level thus far reported appears to be below the threshold level at which ALDH3A1-catalyzed detoxification of oxazaphosphorines becomes pharmacologically meaningful. However, ALDH3A1 levels in certain other malignancies, e.g. those of the alimentary tract and lung, may be of a sufficient magnitude in that regard.

Adult↗
PubMed2005

Medication for older people--aspects of rational therapy from the general practitioner's point of view.

This paper discusses GP perspectives on the principles underlying rational pharmacotherapy for older people. The rising use of prescription medicine forces the GP to balance the benefit of evidence group-based appropriate drug use against the problems arising when medication is given to older people and to consider different approaches when evaluating evidence of risk and benefit for the individual. Old people are facing a considerable risk of adverse drug reactions and recent initiatives, including the Continuous Medical Educational Efforts Programme, address issues of inappropriate prescribing practices. The authors recommend and present tools enabling the GP to focus on 'the core prescribing situation'. The logistics to optimise medication including compliance, the use of modern IT and better collaboration and communication between primary and secondary care are discussed. The authors state that a number of pharmacological regimens for older people are outperformed by non-pharmacological treatment alternatives involving competent individualised counselling and public provision of easy (transportation) possibilities for joining centres offering staff and equipment for physical and social activity (including basal aids for hearing and sight).

Aged↗
PubMed2000

The prediction of EEG signals using a feedback-structured adaptive rational function filter.

In this article, we present a feedback-structured adaptive rational function filter based on a recursive modified Gram-Schmidt algorithm and apply it to the prediction of an EEG signal that has nonlinear and nonstationary characteristics. For the evaluation of the prediction performance, the proposed filter is compared with other methods, where a single-step prediction and a multi-step prediction are considered for a short-term prediction, and the prediction performance is assessed in normalized mean square error. The experimental results show that the proposed filter shows better performance than other methods considered for the short-term prediction of EEG signals.

Algorithms↗
PubMed2006

Rationalizing molecular analysis of field-collected roots for assessing diversity of arbuscular mycorrhizal fungi: to pool, or not to pool, that is the question.

For rationalizing molecular analysis of field-collected roots in diversity studies on arbuscular mycorrhiza, we compared three different approaches. After DNA extraction from 50 root samples of Plantago lanceolata grown on monoculture plots at a former arable field site, (1) DNAs were amplified separately by nested PCR and each amplicon was cloned separately; (2) DNAs were amplified separately by nested PCR, 1 mul of each amplicon was pooled, and a single cloning was made from the resulting amplicons mix; and (3) DNAs were pooled and the single amplicon derived from the nested PCR was cloned. Based on these three different methods, 109 nuclear ribosomal internal transcribed spacer sequences were obtained. Methods 1 and 2 enabled the detection of almost similar levels of arbuscular mycorrhizal fungal diversity. However, method 1 was expensive and time-consuming as much more cloning had to be done. Method 3 was completely biased by preferential amplification of nontarget organisms, which were only detected in low frequencies by the other methods.

Biodiversity↗
PubMed1999

Is there a rational basis for post-surgical lifting restrictions? 1. Current understanding.

Lifting restrictions postoperatively are quite common, but there appears to be little scientific basis for them. Lifting restrictions are inhibitory in terms of return to work and may be a factor in chronicity. The mean functional spinal motion unit stiffness changes with in vitro or computer-simulated discectomies, facetectomies and laminectomies were reviewed from the literature. We modified the NIOSH lifting equation to include another multiplier related to stiffness change post surgery. The new recommended lifts were computed for different lifting conditions seen in industry. The reduction of rotational stiffness ranged from 21% to 41% for a discectomy, 1% to 59% for a facetectomy and 4% to 16% for a partial laminectomy. The recommended lifts based on our modified equation were adjusted accordingly. There is no rational basis for current lifting restrictions. The risk to the spine is a function of many other variables as well as weight (i.e., distance of weight from body). The adjusted NIOSH guidelines provide a reasonable way to estimate weight restrictions and accommodations such as lifting aids. Such restrictions should be as liberal as possible so as to facilitate, not prevent, return to work. Patients need more advice regarding lifting activities and clinicians should be more knowledgeable about the working conditions and constraints of a given workplace to effectively match the solution to the patient's condition.

Diskectomy↗
PubMed1999

Is there a rational basis for post-surgical lifting restrictions? 2. Possible scientific approach.

Lifting restrictions postoperatively are quite common but there appears to be little scientific basis for them. Lifting restricitions are inhibitory in terms of return to work and may be a factor in chronicity. The mean changes in functional spinal motion unit (FSU) stiffness with in vitro or computer-simulated discectomies, facetectomies and laminectomies were reviewed from the literature. We modified the NIOSH lifting equation to include another multiplier related to stiffness change post surgery. The new recommended lifts were computed for different lifting conditions seen in industry. The reduction of rotational stiffness ranged from 21% to 41% for a discectomy, 1% to 59% for a facetectomy and 4% to 16% for a partial laminectomy. The recommended lifts based on our modified equation were adjusted accordingly. There is no rational basis for current lifting resctrictions. The risk to the spine is a function of many other variables as well as weight (i.e., distance of weight from body). The adjusted NIOSH guidelines provide a reasonable way to estimate weight restrictions and accomodations such as lifting aids. Such resitrictions should be as liberal as possible so as to facilitate, not prevent, return to work. Patients need more advice regarding lifting activities and clinicians should be more knowledgeable about the working conditions and constraints of a given workplace to effectively match the solution to the patient's condition.

Diskectomy↗
PubMed2006

Combination analgesia in 2005 - a rational approach: focus on paracetamol-tramadol.

A multimodal (or balanced) approach to anaesthesia is a familiar concept that offers important benefits in the management of both acute and chronic pain. Rational combinations of analgesic agents with different mechanisms of action can achieve improved efficacy and/or tolerability and safety compared with equianalgesic doses of the individual drugs. Combining different agents also enhances efficacy in complex pain states that involve multiple causes. Combinations of paracetamol plus a weak opioid agent are widely used. One such combination, paracetamol plus tramadol, exploits the well-established complementary pharmacokinetics and mechanisms of action of these two drugs. This combination has demonstrated genuine synergy in animal studies and also combines paracetamol's rapid onset of efficacy with tramadol's prolonged analgesic effect. Numerous studies have confirmed the efficacy and tolerability of paracetamol plus tramadol in both acute and chronic pain. As a single-dose treatment for acute post-operative pain, this combination delivers rapid and sustained pain relief that is greater than either agent alone. There is also extensive evidence for efficacy in the long-term management of chronic pain conditions, including osteoarthritis, low back pain and fibromyalgia. In the setting of chronic pain, paracetamol plus tramadol has shown sustained efficacy, safety and tolerability for up to 2 years without the development of tolerance. The efficacy of this combination has been demonstrated as well in respect to reduction of pain intensity and, more importantly, with regard to improvement of function and quality of life and the reduction of disability. Comparative trials have shown that paracetamol plus tramadol has comparable efficacy to paracetamol plus codeine, but with reduced somnolence and constipation compared with the codeine combination. The paracetamol plus tramadol combination is also free of organ toxicity associated with selective and non-selective non-steroidal anti-inflammatory drugs. Hence, paracetamol plus tramadol offers an effective and well-tolerated alternative to anti-inflammatory drugs or other paracetamol plus weak opioid combinations.

Acetaminophen↗
PubMed2006

Proceedings of the 1st International Symposium on Cancer Metastasis and Lymphovascular System: Basis for Rational Therapy, April 28-30, 2005, San Francisco, California, USA.

The first international symposium on Cancer Metastasis and Lymphovascular System: Basis for Rational Therapy was held in San Francisco from April 20-30, 2005. There were a total of seven sessions and three lunch mini-symposia. The symposium was to address the critical issues of cancer metastasis and the lymphovascular system. It brought the basis scientists and clinicians together to interchange ideas so that laboratory findings can be applied to explain clinical dilemmas and clinical problems can be targeted for research in the laboratory. This symposium resulted in ten major manuscripts with each session or mini-symposium being formulated as the basis for each manuscript.

Animals↗