[Precision and optimization of physical therapy--a task].
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Germany, East↗
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Results for “Precision therapy”
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[Spectrum of esophagitis: etiology, diagnosis, therapy].
Inflammatory changes of the oesophageal mucosa are in the vast majority due to reflux of gastric content. Caustic oesophagitis is rare, however, drug-induced oesophageal injury caused by delayed passage is of increasing importance. Infections by opportunistic saprophytes (candida, herpes virus) are common causes of oesophagitis in immunocompromised patients with dysphagia and odynophagia whereas specific inflammation (Crohn's disease, tuberculosis) is a rarity. Successful therapy demands precise differentiation of the different forms of oesophagitis.
Calcium Chloride↗
[Pathophysiology on the disorder of neuromuscular transmission defects].
Neuromuscular transmission defects are often puzzling but challenging diseases for the pediatric and adult neurologists. Some of these disorders entail severe or even life-threatening disability: Most are treatable, but effective therapy requires precise diagnosis sometimes difficult to make especially in congenital defects. The diagnosis rests on the combination of clinical data, the electromyogram and additional studies that may include microelectrode analysis of neuromuscular transmission, ultrastructural and cytochemical studies of neuromuscular junction (NMJ) and biochemical/molecular genetic studies on muscle specimens. Understandably, these studies often depend on the collaboration of several investigators. In each myasthenic disorder, an abnormality affects neuromuscular transmission directly or causes secondary derangements that eventually affects transmission. Namely, lesions of both the presynaptic and/or postsynaptic area manifest a variety of clinical findings. Here was discussed the pathophysiology on myasthenia gravis and Lambert-Eaton myasthenic syndrome of abnormal autoimmunity, congenital myasthenic syndromes of a chromosomal defect, and poisoning of organophosphorus, botulism and some other toxins.
Adult↗
Helicobacter pylori and gastrointestinal disease.
Helicobacter pylori infection is quite common. In the United States, prevalence varies considerably with race, nationality, socio-economic status and location of residence. In Western countries, the prevalence of the infection has shown a steady increase with increasing age. H. pylori has been shown to cause chronic gastritis. Most patients infected with H. pylori are asymptomatic and require no therapy. The precise role of the infection in the pathogenesis of peptic ulcer disease is unknown. However, H. pylori infection is associated with a high recurrence rate of both gastric and duodenal ulcers. Eradication of the infection reduces the recurrence rate. Once H. pylori infection is acquired, it usually persists for years, possibly for the patient's lifetime. Although a causative role in gastric cancer has not been proved, evidence suggests an association between H. pylori infection and well-differentiated gastric adenocarcinoma and gastric lymphoma.
Gastrointestinal Diseases↗
Recurrent clinical exacerbations of liver disease during the course of infection with hepatitis C virus.
Symptomatic clinical relapses during the course of chronic hepatitis C virus (HCV) infection are uncommon. Furthermore, acute liver dysfunction with elevated bilirubin during alpha-interferon therapy without other apparent coexisting diagnoses is rare. The case of a 31-yr-old man with three clinical exacerbations of HCV infection over an 18-month period is described. The third episode was characterized by rising serum aminotransferase levels on alpha-interferon therapy. The precise cause of this patient's flares is unknown. An immunologically mediated clearance of the hepatitis C virus, mutation of HCV, or infection with different HCV viral strains are the leading possibilities.
Adult↗
Precise modelling of the eye for proton therapy of intra-ocular tumours.
A new method is described that allows precise modelling of organs at risk and target volume for radiation therapy of intra-ocular tumours. The aim is to optimize the dose distribution and thus to reduce normal tissue complication probability. A geometrical 3D model based on elliptic shapes was developed that can be used for multimodal model-based segmentation of 3D patient data. The tumour volume cannot be clearly identified in CT and MR data, whereas the tumour outline can be discriminated very precisely in fundus photographs. Therefore, a multimodal 2D fundus diagram was developed, which allows us to correlate and display simultaneously information extracted from the eye model, 3D data and the fundus photograph. Thus, the connection of fundus diagram and 3D data is well-defined and the 3D volume can be calculated directly from the tumour outline drawn onto the fundus photograph and the tumour height measured by ultrasound. The method allows the calculation of a precise 3D eye model of the patient, including the different structures of the eye as well as the tumour volume. The method was developed as part of the new 3D treatment planning system OCTOPUS for proton therapy of ocular tumours within a national research project together with the Hahn-Meitner-Institut Berlin.
Eye Neoplasms↗
B cell targeted therapies.
Although the precise pathogenesis of rheumatoid arthritis (RA) remains unclear, many cell populations, including monocytes, macrophages, endothelial cells, fibroblasts and B cells, participate in the inflammatory process. Ongoing research continues to evaluate the critical roles played by B cells in sustaining the chronic inflammatory process of RA. These findings have contributed to the development of targeted therapies that deplete B cells, such as rituximab, as well as inhibitors of B lymphocyte stimulation, such as belimumab. In a phase I trial, belimumab treatment significantly reduced CD20+ levels in patients with systemic lupus erythematosus. Phase I and phase II trials of rituximab found that rituximab plus methotrexate achieved significantly better American College of Rheumatology 50% responses for patients with RA than those patients receiving monotherapy with methotrexate. These clinical trial data present promising evidence for B cell targeted therapies as future therapeutic options for RA.
Antibodies, Monoclonal↗
Treatment of cancer of the pancreas by precision high dose (PHD) external photon beam and intraoperative electron beam therapy (IOEBT).
Twenty-five patients with a diagnosis of unresectable adenocarcinoma of the pancreas were explored in the Clement O. Miniger (COMROC) IOEBT operating amphitheater at the Medical College of Ohio. Seventeen were treated with IOEBT (20-30 Gy, 15 or 18 meV electrons) PHD external beam radiation therapy (40-60 Gy, 1.8 Gy per fraction) plus appropriate operative biliary and gastrointestinal bypass procedures. No intraoperative complications were observed. Two patients died of causes that may have been treatment-related. Two patients developed abdominocutaneous fistulae. Pain was ameliorated in eleven of twelve patients. Jaundice was relieved in all patients. Four of ten patients with weight loss showed a reversal of that trend. Patient survival was not significantly different from that of patients treated with high-dose precision therapy alone.
Adenocarcinoma↗
Antiplatelet therapy for secondary stroke prevention.
The precise role of antiplatelet therapy in secondary stroke prevention remains a matter of some debate. Although specific antiplatelet agents (notably aspirin, ticlopidine, dipyridamole, and clopidogrel) have been shown to be active in the prevention of secondary stroke, questions remain about the effective dose of these agents and their potential efficacy in combined therapeutic regimens. In addition, haematological and gastrointestinal side-effects of antiplatelet agents remain a significant clinical concern for patients and prescribing physicians. This review article examines research on both monotherapy and combination antiplatelet therapy for secondary stroke prevention, with an emphasis on lessons learned about dosage schedules, treatment protocols, and side-effect profiles.
Aspirin↗
[Hypertensive syndromes in pregnancy. Diagnosis and therapy].
UNLABELLED: ACHIEVE PRECISE DIAGNOSIS: Hypertensive syndromes during pregnancy secondary to placental ischemia still cause threatening matemofetal complications. A precise differential diagnosis between gestational hypertension, chronic hypertension and preeclampsia must be achieved as the management protocols are quite different. PATIENT MONITORING: Blood tests for urea, creatinine, platelet counts, coagulation, and liver enzymes are required. Fetal monitoring, urine protein and ambulatory blood pressure measurements are also helpful. Ultrasound-Duplex explorations allow an evaluation of the maternal vascular status and fetal development. THERAPEUTIC MANAGEMENT: These patients should be managed in specialized centers, limiting the minimum the number of hospitalizations. Unlike good rules of hygiene and dietetics, antihypertensive therapy has little effect on the progression of the pregnancy. An antihypertensive therapy is only warranted to avoid cardiovascular complications in the mother. In case of chronic hypertension, treatment should be tailored to the measured pressures. Prudent antihypertensive therapy may be useful for severe gestational hypertension and preeclampsia. Because of their safety profile and pharmacologic properties, antihypertension drugs with central action and alph-beta-blockers should be preferred over other drug classes. PREVENTIVE TREATMENT: Antiaggregates (aspirin 50-100 mg/d) starting at 16 weeks gestation should be reserved for high-risk pregnancies. Regular follow-up, both pre- and post-natally, is essential, especially in light of the large number of women who can be expected to progress to established hypertensive states.
Female↗
Novel insights into retinoblastoma: From oncogenic circuitry to precision diagnosis and eye-preserving therapies.
Retinoblastoma (RB) represents the most common primary intraocular malignancy in childhood and stands as a paradigm for translating molecular oncology into precision clinical management. This review synthesizes the comprehensive evolution in the understanding and treatment of RB. First, we deconstruct the intricate oncogenic circuitry that extends far beyond Knudson's classic "two-hit" RB1 inactivation model, describing non-classical MYCN-driven pathogenesis, multi-layered epigenetic reprogramming (including chromatin, RNA and histone changes), and distinct histological subtypes with defined clinical correlates, such as the favorable-prognosis cavitary RB. Single-cell genomics has elucidated the cellular origin from cone precursor cells and intratumoral heterogeneity. Risk stratification has been refined through well-defined classification systems, from the therapy-guiding International Intraocular Retinoblastoma Classification (IIRC) to the comprehensive American Joint Committee on Cancer Tumor-Node-metastasis (AJCC TNM) staging. Furthermore, the diagnostic paradigm has advanced from conventional anatomical imaging to liquid biopsies, enabling non-invasive molecular staging and monitoring via tumor-derived cell-free DNA analysis. Concurrently, the therapeutic landscape has undergone a radical shift, moving from enucleation and external-beam radiotherapy to an era dominated by local sight-preserving strategies. We provide a critical synthesis of the evidence for intravenous chemotherapy and the transformative role of super-selective intra-arterial chemotherapy (IAC), and describe essential randomized controlled trials, technical innovations, and optimized drug regimens. Finally, we explore emerging targeted molecular therapies and future directions. By integrating cutting-edge molecular insights with robust, high-level clinical evidence, this review offers the framework for achieving patient and eye survival as well as vision preservation in children with Retinoblastoma.
Intra-arterial chemotherapy↗
Pleiotropic effects of statins.
The advent of statin therapy has revolutionized the ability of the clinician to manage patients at risk for the development of an ischemic event due to dyslipidemia. Large-scale clinical trials involving thousands of patients in both primary and secondary prevention have clearly demonstrated that statin therapy will reduce cardiovascular mortality across a broad spectrum of patient subgroups. Additionally, in adequately powered trials, total mortality has been successfully decreased by the use of statin therapy. However, the precise mechanism underlying the benefit of statin therapy has been controversial due to the multiplicity of potential benefits that statins have demonstrated in addition to pure lipid lowering. The causal theory of pharmacologic benefit reiterates the lipid hypothesis, which states that dyslipidemia is central to the process of atherosclerosis and the clinical benefit which accrues from statin therapy is a function of the degree of lipid lowering. The noncausal theory supports the premise that clinical benefits are related primarily to pleiotropic effects of statins (endothelial function, inflammation, coagulation and plaque vulnerability) as being the major modulators of clinical benefit. This review will focus on the potential beneficial effects of statin therapy on a number of the pleiotropic effects of statins and the potential role that these activities play in the reduction of risk for ischemic events.
Cardiovascular Physiological Phenomena↗
Superficial bladder tumors and increased reactivity against mycobacterial antigens before bacillus Calmette-Guerin therapy.
PURPOSE: The precise mechanism of action of bacillus Calmette-Guerin (BCG) in bladder cancer treatment remains poorly understood. Whether bladder tumor cells are destroyed by nonspecific mechanisms or targeted by specifically activated lymphocytes recognizing cognate antigens is unclear. To investigate a possible cross-reactivity between BCG and bladder cell tumors, we tested before BCG treatment the lymphoproliferation of peripheral blood lymphocytes against several mycobacterial antigens, including the secreted fibronectin binding antigen 85 complex from BCG (AG 85) in patients with superficial bladder tumors compared to control matched patients. MATERIALS AND METHODS: Using a whole blood assay, T cell response against purified protein derivative, BCG extract, whole BCG, purified AG 85, and the nonspecific mitogens pokeweed and phytohemagglutinin was investigated in 79 patients with superficial bladder tumors before BCG and in 39 control subjects without malignancy matched for age and sex. Neither group had a history of tuberculosis. Lymphoproliferation was measured with a tritiated thymidine uptake assay on day 7 of culture. RESULTS: Of the 79 patients with superficial transitional cell carcinoma, a significant lymphoproliferative response before BCG against PPD, BCG extract, whole BCG and AG 85 was observed in 65 (82.2%), 67 (84.81%), 30 (37.97%) and 49 (62.02%) patients, respectively. Of the 39 controls only 26 (64.1%), 23 (58.9%), 3 (7.7%) and 3 (7.7%) patients, respectively, had a significant lymphoproliferation against PPD, BCG extract, BCG and AG 85 (p >0.05, p = 0.004, p = 0.00001 and p = 0.00001, respectively). In terms of lymphoproliferative levels, patients with superficial transitional cell carcinoma also showed a significantly higher response against PPD (p = 0.000012), BCG extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001) and pokeweed (p = 0.01) than controls but not against phytohemagglutinin. CONCLUSIONS: Patients with superficial transitional cell carcinoma demonstrate an increased lymphoproliferation against mycobacterial antigens before BCG compared to control subjects. Although a nonspecific activation of the immune system cannot be excluded at this stage, our data may suggest the possible existence of bladder cancer antigens cross-reactive with mycobacterial antigens responsible for boosting precursor cells witnessing previous contacts with mycobacteria. The implication of these findings in the antitumoral mechanism of action of BCG are under investigation.
Adhesins, Bacterial↗
Radiation-force technique to monitor lesions during ultrasonic therapy.
This report describes a monitoring technique for high-intensity focused ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs) and those made for noninvasive cardiac therapy and tumor treatment in the eye, liver and other organs. Designed to sense the increased stiffness of a HIFU lesion, this technique uniquely utilizes the radiation force of the therapeutic US beam as an elastographic push to detect relative stiffness changes. Feasibility was demonstrated with computer simulations (treating acoustically induced displacements, concomitant heating, and US displacement-estimation algorithms) and pilot in vitro experimental studies, which agree qualitatively in differentiating HIFU lesions from normal tissue. Detectable motion can be induced by a single 5 ms push with temperatures well below those needed to form a lesion. Conversely, because the characteristic heat diffusion time is much longer than the characteristic relaxation time following a push, properly timed multiple therapy pulses will form lesions while providing precise control during therapy.
Animals↗
Managing geometric uncertainty in conformal intensity-modulated radiation therapy.
The geometric precision of radiotherapy treatments must increase if the objectives of dose escalation and increased disease control are to be achieved. There are multiple strategies for increasing the geometric precision of a radiotherapy treatment system, including immobilization and setup aids for reducing random and systematic components of setup errors and organ motion alike. Alternatively, more complex strategies can be implemented based on additional information acquired over the course of treatment. Generally, these strategies can be divided into two categories: off-line and on-line. The strategies that are implemented in the clinic must consider the required geometric precision for a given treatment. From this specification, it is possible to select the appropriate strategies and approaches. The cost associated with each approach must also be considered. Once a system for delivery has been designed, the residual uncertainties must still be considered in the planning process. Parallel to the development of strategies for reducing uncertainty, progress is being made in better relating these residual uncertainties to margins for use in treatment planning. This article reviews advances in reducing uncertainty.
Cost-Benefit Analysis↗
Current knowledge in pharmacogenomics and precision medicine: perspectives of the PGRN global PGx committee on improving drug therapies in underrepresented ethnic populations.
A precision medicine strategy is likely to be more impactful, when pharmacogenomics (PGx) guided selection of drugs and dosage wherever applicable is implemented across the globe. In regions where resources are disproportionately distributed, PGx implementation in routine clinical care can play a critical role in ensuring the optimal use of limited healthcare infrastructure. At present, PGx data from the majority of the distinct ethnic populations across Asia, Africa, and South America is limited. While international consortia, working groups, and scientific bodies have made significant contributions toward evaluating the evidence for PGx implementation, the majority of existing guidelines and recommendations are derived primarily from studies conducted in a limited number of ethnic groups. Precision Medicine Initiatives in countries like Korea, Taiwan, and Malaysia and PGx organizations like the African Institute of Biomedical Science and Technology (AiBST), Consortium for Genomics & Therapeutics in Africa (CGTA), implementation of pharmacogenetic testing for the effective care and treatment in Africa, Greater Middle East (GME) whole exome sequencing program, Ibero-American Network of Pharmacogenetics and Pharmacogenomics (RIBEF), Latin American Society of Pharmacogenomics and Personalized Medicine (SOLFAGEM), Latin American Network for Validation and Implementation of Pharmacogenomic Clinical Guidelines (RELIVAF), IndiGen initiative, Southeast Asian Pharmacogenomics Research Network (SEAPharm), are working toward consolidating the PGx presence in these regions.
Precision Medicine↗
A precision cranial immobilization system for conformal stereotactic fractionated radiation therapy.
PURPOSE: Conformal radiotherapy has been shown to benefit from precision alignment of patient target to therapy beam (1, 6, 13). This work describes an optimized immobilization system for the fractionated treatment of intracranial targets. A study of patient motion demonstrates the high degree of immobilization which is available. METHODS AND MATERIALS: A system using dental fixation and a thermoplastic mask that relocates on a rigid frame is described. The design permits scanning studies using computed tomography (CT) and magnetic resonance imaging (MR), conventional photon radiotherapy, and high precision stereotactic proton radiotherapy to be performed with minimal repositioning variation. Studies of both intratreatment motion and daily setup reliability are performed on patients under treatment for paranasal sinus carcinoma. Multiple radiographs taken during single treatments provide the basis for a three-dimensional (3D) motion analysis. Additionally, studies of orthogonal radiographs used to setup for proton treatments and verification port films from photon treatments are used to establish day to day patient position variation in routine use. RESULTS: Net 3D patient motion during any treatment is measured to be 0.9 +/- 0.4 mm [mean +/- standard deviation (SD)] and rotation about any body axis is 0.14 +/- 0.67 degrees (mean +/- SD). Day-to-day setup accuracy to laser marks is limited to 2.3 mm (mean) systematic error and 1.6 mm (mean) random error. CONCLUSION: We conclude that the most stringent immobilization requirements of 3D conformal radiotherapy adjacent to critical normal structures can be met with a high precision system such as the one described here. Without the use of pretreatment verification, additional developments in machine and couch design are needed to assure that patient repositioning accuracy is comparable to the best level of patient immobility achievable.
Brain Neoplasms↗
Assessing the effects of clinic-based psychotherapy with children and adolescents.
Recent meta-analyses suggest that psychotherapy is quite effective with children and adolescents. However, most research in those analyses involved controlled laboratory interventions that may not represent typical therapy in clinics. We studied more representative treatment as it routinely occurs, in 9 clinics. We compared 93 youngsters who completed a course of therapy with 60 who dropped out after intake. At intake, the groups did not differ on demographic, family, or clinical measures, including Child Behavior Checklist (CBCL) scores. Six months later (when therapy had ended for 98% of the treated children) and again 1 year later, the 2 groups were compared on CBCL scores, parent ratings of each child's major referral problem, and (for a subsample) teacher reports. No comparison showed significant main effects of therapy. The findings (a) raise questions about the generalizability of findings from research-oriented therapy and (b) suggest that the control and precision of research therapy may be needed in clinical practice.
Adolescent↗