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At least 217 records · Page 12Linked to original sources

PubMed2005

Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro.

Although aqueous mistletoe extracts are widely used in complementary cancer therapy, the precise mode of action of their main therapeutic agents, the three mistletoe lectins (MLs), is poorly understood as they act both as cytotoxic agents and as immunomodulators due to their cytokine release by mononuclear cells. Thus, this study aims to investigate both the direct and the indirect effects of MLs on the growth of human melanoma cells in vitro. Proliferation of six human melanoma cell lines under ML treatment and additionally under the influence of cytokines induced by them (TNF-alpha, IL-1, IL-6) was assessed by means of the tetrazolium derived reduction (XTT) assay. Furthermore, ML binding patterns were analysed and correlated with the biological effects. All three MLs inhibited melanoma cell proliferation in a dose-dependent manner starting at very low ML concentrations (0.001-100 ng/ml) with ML-I being the most cytotoxic lectin (significant inhibition of ultra-sensitive cell line MV3 at 1 x 10(-13) ng ML-I/ml). Even if applied in a broad concentration range (0.0001-100 ng/ml) cytokines had no influence on cell proliferation at all. For ML-I, no association between binding intensity and cytotoxicity was observed, while for ML-II and -III an association between binding and toxicity was established. In conclusion, this study emphasises the direct anti-proliferative effect of the mistletoe lectins on melanoma cells with ML-I being superior to MLs-II and -III. The observation of an ultra-sensitivity of one cell line towards ML-I toxicity may serve as an explanation for the therapeutic success in anecdotal case reports and needs further investigations.

Apoptosis↗

PubMed1999

Transpupillary thermotherapy in the management of circumscribed choroidal hemangioma.

PURPOSE: To report a case of circumscribed choroidal hemangioma effectively managed with transpupillary thermotherapy. METHOD: A 53-year-old man affected by extramacular circumscribed choroidal hemangioma had sustained a decline in visual acuity caused by subretinal fluid exudation into the macular area. Multiple attempts at treatment with scatter photocoagulation over the surface of the lesion for several years had been unsuccessful in reducing tumor-related exudation. The patient was examined on referral and underwent a single session of treatment employing transpupillary thermotherapy. The course of the lesion after treatment was documented with fundus photography and ultrasonography. RESULT: Complete atrophy of the choroidal hemangioma with resorption of subretinal fluid was documented over the 6 months after transpupillary thermotherapy, with improvement in visual acuity. CONCLUSION: Transpupillary thermotherapy is an effective alternative to conventional scatter photocoagulation or radiation therapy for precise ablation of circumscribed choroidal hemangioma.

Choroid Neoplasms↗

PubMed2000

Helical CT and ureteral colic.

The advantages of nonenhanced helical CT for the diagnosis of ureteral calculi include rapid scan time and patient throughput, safety (no contrast, less radiation), cost-effectiveness, high accuracy, minimal invasiveness, and ability to suggest of alternative diagnoses for flank pain--urologic and otherwise. Size measurement and location in the ureter, the two most important determinants of therapy, are precise with CT. It is particularly good for imaging small or radiolucent calculi, and calculi located at the ureterovesical. Secondary signs of obstruction and the soft-tissue rim sign are additional aids to the routine diagnosis of ureteral calculi. CT numbers indicate the fragility and therefore the likelihood of successful treatment of a calculus. Postprocessing options may help guide management decisions and may help plan interventions. The authors' experience after 30 months of using helical CT exclusively in the work-up of ureteral colic has been extremely favorable. Without hesitation, the authors believe that nonenhanced helical CT is the study of choice for the work-up of ureteral calculi.

Clinical Protocols↗

PubMed2003

Trends in clinical trials in surgical oncology: implications for outcomes research.

Outcomes analysis is emerging as a crucial tool in understanding and improving health care. To this end, outcomes research is focused on methodologies for assessing the impact and quality of clinical services and the penetration of new findings. Clinical trials are an important mechanism for generating data to support outcomes research activities. In clinical trials in surgical oncology, there has been a general broadening of the spectrum of end points that are more focused on the needs of providing data to outcomes researchers. For example, in addition to traditional "mechanical" end points reflecting the physical dimensions of disability, awareness of the importance of end points related to quality of life has increased. Moreover, a variety of innovative study designs and methodologies have found more widespread use, including noninferiority trials, preresection staging designed to direct therapy more precisely, planned early reports of conditional results, prognostic studies, assessment of an event status at a point in time, and large simple trials. The goal of this article is to summarize and assess some of the trends in clinical trials in surgical oncology. Examples of ongoing studies or of trials in development from the American College of Surgeons Oncology Group are discussed.

Clinical Trials as Topic↗

PubMed1991

Stagewise, adaptive dose allocation for quantal response dose-response studies.

A principal design objective of many dose-response studies is to estimate extreme percentiles of a dose-response distribution, e.g., the ED95 dose for a particular drug therapy, as precisely as feasible using the smallest number of experimental subjects possible. Such a design requirement necessitates that allocation of subjects to drug doses be carried out in a stagewise fashion to maximize the information obtained from each subsequent experimental observation in light of what has previously been determined. This paper describes and illustrates specialized methods and associated computer programs to evaluate, on a stagewise basis, the anticipated relative sensitivities of alternative experimental plans in the case of dichotomous responses. Following each stage of experimentation, the current estimates of the dose-response distribution parameters, as well as the uncertainties in these estimates, are updated and are used to assign subjects to experimental dose levels for the next stage of testing. Competing dose allocations are compared with respect to anticipated improvement in estimation precision. The adoption of such a stagewise dose allocation strategy is illustrated by example.

Animals↗

PubMed2002

High-dose, high-precision treatment options for boosting cancer of the nasopharynx.

PURPOSE: The aim of the study is to define the role and type of high-dose, high-precision radiation therapy for boosting early staged T1,2a, but in particular locally advanced, T2b-4, nasopharyngeal cancer (NPC). MATERIALS AND METHODS: Ninety-one patients with primary stage I-IVB NPC, were treated between 1991 and 2000 with 60-70Gy external beam radiation therapy (ERT) followed by 11-18Gy endocavitary brachytherapy (ECBT) boost. In 1996, for stage III-IVB disease, cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per protocol. Patients were analyzed for local control and overall survival. For a subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was obtained. After matching with pre-treatment computed tomogram, patients (response) were graded into four categories; i.e. LD (T1,2a, with limited disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual disease), ERD (T2b, with extensive residual disease), or patients initially diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3, Nucletron) were compared to parallel-opposed three-dimensional conformal radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan, Radionics v. 2.02). RESULTS: For stage T1,2N0,1 tumors, at 2 years local control of 96% and overall survival of 80% were observed. For the poorest subset of patients, well/moderate/poorly differentiated T3,4 tumors, local control and overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal target coverage and optimal sparing can be obtained with brachytherapy. For T2b-ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or IMRT. CONCLUSIONS: The dosimetric findings, ease of application of the brachytherapy procedure, and the clinical results in early staged NPC, necessitates ERT combined with brachytherapy boost to be the therapy of preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting the primary tumor.

Brachytherapy↗

PubMed1999

Measurement of heart rate variability: a clinical tool or a research toy?

The objectives of this review are to discuss the diversity of mechanisms that may explain the association between heart rate (HR) variability and mortality, to appraise the clinical applicability of traditional and new measures of HR variability and to propose future directions in this field of research. There is a large body of data demonstrating that abnormal HR variability measured over a 24-h period provides information on the risk of subsequent death in subjects with and without structural heart disease. However, the mechanisms responsible for this association are not completely established. Therefore, no specific therapy is currently available to improve the prognosis for patients with abnormal HR variability. Reduced HR variability has been most commonly associated with a risk of arrhythmic death, but recent data suggest that abnormal variability also predicts vascular causes of death, progression of coronary atherosclerosis and death due to heart failure. A consensus is also lacking on the best HR variability measure for clinical purposes. Time and frequency domain measures of HR variability have been most commonly used, but recent studies show that new analysis methods based on nonlinear dynamics may be more powerful in terms of risk stratification. Before the measurement of HR variability can be applied to clinical practice and used to direct therapy, more precise insight into the pathophysiological link between HR variability and mortality are needed. Further studies should also address the issue of which of the HR variability indexes, including the new nonlinear measures, is best for clinical purposes in various patient populations.

Animals↗

PubMed1996

Patient-Assisted Laparoscopy in the Diagnosis and Management of Endometriosis

Traditionally, surgeons had to diagnose endometriosis and determine themselves which lesions were painful, since the patients were anesthetized. Performing laparoscopy under local anesthesia allows the woman to assist the physician in deciding which lesions are painful and require therapy, and lets the patient determine the results of therapy. Patients reported that black lesions were not painful or were the least painful, followed by white scarred areas. The vascular lesions around the outer edge of the white lesions were significantly more painful, especially the hypervascular areas and endometriotic windows. After a 6-month course of danazol, at second-look laparoscopy, patients reported that the treated areas were no longer painful. Having the patient assist the physician during laparoscopy under local anesthesia leads to a more accurate assessment of endometriosis and outlines the boundaries of therapy more precisely.

Journal Article↗

PubMed2001

Cholangiocarcinoma.

Despite overall advances in the ability to diagnose and treat patients with cholangiocarcinoma, the prognosis for patients with this malignancy remains poor. Further improvements in the survival of patients with cholangiocarcinoma will come with the early diagnosis of these lesions. New molecular techniques should improve the ability to screen high-risk patients, such as those with primary sclerosing cholangitis, hepatolithiasis, choledochal cysts, and ulcerative colitis. Improvements in imaging will continue, and spiral CT scanning, duplex ultrasonography, MR imaging and, perhaps, PET scans will improve the ability to stage patients with cholangiocarcinoma noninvasively. Complete surgical resection remains the only curative treatment for malignancies of the biliary tract. Aggressive surgical approaches are likely to continue, and the challenge remains in being able to perform these procedures safely in jaundiced and sometimes septic patients. For patients with unresectable lesions, the optimal form of palliation, whether surgical or nonsurgical, remains to be defined. Finally, multicenter, prospective, randomized trials of chemoradiation need to be performed to delineate an effective adjuvant therapy more precisely, and to improve the overall prognosis of patients with cholangiocarcinoma.

Bile Duct Neoplasms↗

PubMed1999

Progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, is an inherited disorder of childhood in which cholestasis of hepatocellular origin often presents in the neonatal period and leads to death from liver failure before adolescence. The pattern of appearance of affected children within families is consistent with autosomal recessive inheritance. Several studies have provided support for the heterogeneity of this clinical entity suggesting the existence of different types due to different disorders affecting the hepatocyte and related to defects of bile acid secretion or bile acid metabolism. Recent molecular and genetic studies have identified genes responsible for three types of PFIC and have shown that PFIC was related to mutations in hepatocellular transport system genes involved in bile formation. These findings now provide specific diagnostic tools for the investigation of children with PFIC and should allow prenatal diagnosis in the future. Genotype-phenotype correlations performed in patients treated with ursodeoxycholic acid or biliary diversion should allow those PFIC patients who could benefit from these therapies to be precisely identified. In the future, other therapies, such as cell and gene therapies, might be considered and could also represent an alternative to liver transplantation.

ATP Binding Cassette Transporter, Subfamily B↗

PubMedDate not supplied

[Nerve lesions after hip prosthesis implantation--fate or treatment error?].

INTRODUCTION: Nerve lesions after hip arthroplasty are common complications which may imply the reproach of a treatment mistake. Thus, the decisive question to the expert runs: fate or treatment mistake? METHODS: Retrospective analysis of all cases dealt with at the medical expert commission of the General Medical Council Nordrhein during 1977-1997 in respect of the damage mechanisms and expert judgments. RESULTS: As long as diagnosis and therapy were set on time, nerve lesions after hip arthroplasty due to extension, pressure or placement of the leg were evaluated as fateful (81%). Delayed treatment as well as incorrect operation technique, -indication, or inadequate documentation were judged as a treatment mistake (19%). CONCLUSION: Nerve lesions after hip arthroplasty cannot always be avoided and thus do not directly imply a treatment mistake. Immediate therapy and precise documentation are important to minimize the damage.

Arthroplasty, Replacement, Hip↗

PubMed1991

Fidelity of targeted recombination in human fibroblasts and murine embryonic stem cells.

Targeted recombination in murine embryonic stem cells promises to be a powerful tool for introducing specific mutations into target genes to study development in mice and to create animal models of human disease. Gene targeting also holds potential for correcting genetic defects as an approach to human gene therapy. To precisely modify target genes, homologous recombination must proceed with high fidelity. However, several results have suggested that targeted recombination may be highly mutagenic. To test the accuracy of gene targeting we analyzed 44 independent targeted recombinants at the hypoxanthine phosphoribosyltransferase (HPRT) locus in a human fibroblast cell line and in mouse embryonic stem cells. We surveyed 80 kilobases around the sites of recombination by using chemical cleavage of mismatches. Only two mutations were found: a T----G transversion and a thymidine deletion. Thus, gene targeting in mammalian cells can be extremely accurate. These results demonstrate the feasibility of generating precise modifications of mammalian genomes by gene targeting.

Animals↗

PubMed1989

Chronic depression. Issues in long-term management.

Patients with protracted depression respond well to long-term maintenance antidepressant therapy. A precise diagnosis is a prerequisite to therapeutic decisions. Diagnosis may be missed and treatment inadequate if symptoms are attributed solely to aging or to life's circumstances. Proper dosage is determined by the patient's age and metabolic capabilities, and patient education increases compliance. Although the patient may deny the need for psychotherapy, continued support and a life review help the patient acquire insights and adjust to changes. The patient can sustain progress by keeping active, pursuing interests, and socializing. The aim of long-term antidepressant pharmacotherapy is to reduce morbidity, restore productive and optimal functioning, and enhance the quality of life. The attainment of previous levels of function is the gauge of success.

Aged↗

PubMed2024

Stroke genetics and how it Informs novel drug discovery.

INTRODUCTION: Stroke is one of the main causes of death and disability worldwide. Nevertheless, despite the global burden of this disease, our understanding is limited and there is still a lack of highly efficient etiopathology-based treatment. It is partly due to the complexity and heterogenicity of the disease. It is estimated that around one-third of ischemic stroke is heritable, emphasizing the importance of genetic factors identification and targeting for therapeutic purposes. AREAS COVERED: In this review, the authors provide an overview of the current knowledge of stroke genetics and its value in diagnostics, personalized treatment, and prognostication. EXPERT OPINION: As the scale of genetic testing increases and the cost decreases, integration of genetic data into clinical practice is inevitable, enabling assessing individual risk, providing personalized prognostic models and identifying new therapeutic targets and biomarkers. Although expanding stroke genetics data provides different diagnostics and treatment perspectives, there are some limitations and challenges to face. One of them is the threat of health disparities as non-European populations are underrepresented in genetic datasets. Finally, a deeper understanding of underlying mechanisms of potential targets is still lacking, delaying the application of novel therapies into routine clinical practice.

Humans↗

PubMed2004

Intensity modulated radiation therapy (IMRT) in the management of prostate cancer.

Intensity modulated radiation therapy (IMRT) is gaining widespread use in the radiation therapy community. Prostate cancer is the ideal target for IMRT due to the growing body of literature supporting dose escalation and normal tissue limitations. The need for dose escalation and the limits of conventional radiation therapy necessitate precise patient and prostate localization as well as advanced treatment delivery. The treatment of prostate cancer has been dramatically altered by the introduction of technology that can focus on the target while avoiding normal tissue. IMRT is evolving as the treatment of the future for prostate cancer.

Dose-Response Relationship, Radiation↗

PubMed2004

Online compensation for target motion with scanned particle beams: simulation environment.

Target motion is one of the major limitations of each high precision radiation therapy. Using advanced active beam delivery techniques, such as the magnetic raster scanning system for particle irradiation, the interplay between time-dependent beam and target position heavily distorts the applied dose distribution. This paper presents a simulation environment in which the time-dependent effect of target motion on heavy-ion irradiation can be calculated with dynamically scanned ion beams. In an extension of the existing treatment planning software for ion irradiation of static targets (TRiP) at GSI, the expected dose distribution is calculated as the sum of several sub-distributions for single target motion states. To investigate active compensation for target motion by adapting the position of the therapeutic beam during irradiation, the planned beam positions can be altered during the calculation. Applying realistic parameters to the planned motion-compensation methods at GSI, the effect of target motion on the expected dose uniformity can be simulated for different target configurations and motion conditions. For the dynamic dose calculation, experimentally measured profiles of the beam extraction in time were used. Initial simulations show the feasibility and consistency of an active motion compensation with the magnetic scanning system and reveal some strategies to improve the dose homogeneity inside the moving target. The simulation environment presented here provides an effective means for evaluating the dose distribution for a moving target volume with and without motion compensation. It contributes a substantial basis for the experimental research on the irradiation of moving target volumes with scanned ion beams at GSI which will be presented in upcoming papers.

Computer Simulation↗

PubMed1988

Coombs'-negative spherocytic hemolytic anemia and severe necrotizing renal vasculitis.

Vasculitis may be complicated by either hypoproliferative or hemolytic anemias. We have described a patient with a Coombs'-negative spherocytic hemolytic anemia and severe necrotizing renal vasculitis, two disorders not having been previously linked. The disorders were temporally related and both responded to immunosuppressive therapy. The precise cause of the hemolytic anemia remains unknown.

Aged↗

PubMed1993

Serum and urine IL-6 and TNF-alpha in renal transplant recipients with graft dysfunction.

The object of the study presented here was to test whether measurement of blood or urine IL-6 or TNF-alpha could discriminate between the most common causes of renal allograft dysfunction, thus avoiding a biopsy. We present data here in which serum and urine IL-6 and TNF-alpha levels were measured at the same time as a diagnostic renal biopsy was performed. TNF-alpha and IL-6 were measured by sandwich ELISA. Thirty patients had acute cellular rejection, 18 had acute tubular necrosis/CsA toxicity, and 9 had chronic vascular rejection. There was no difference in the levels of IL-6 measured in serum and urine among the three categories of graft dysfunction (t < 1.31; P > 0.20). A similar result with considerable overlap between the groups was seen with TNF-alpha (t < 0.78; P > 0.44). Stratifying the results according to the precise immunosuppressive therapy, CsA dose, body weight, CsA level, body temperature, serum creatinine, the number of previous rejection episodes, original cause of renal failure, or the time elapsed since the transplant did not alter the results. The ratio of serum IL-6 divided by trough CsA level was compared among the three groups and there was no significant difference among them (t < 1.79; P > 0.09). In the light of our results, we therefore suggest that previously published reports of the clinical value of serum and or urine IL-6 and or TNF-alpha in relatively small numbers of patients, not all of whom had been biopsied and in whom rigorous clinical and statistical criteria had not been met, should be viewed with caution.

Antibodies, Monoclonal↗