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Aggressive Therapy (aggressive + therapy)
Selected AbstractsEarlier Use of Aggressive Therapy Could Prevent One-third of Bladder Cancer DeathsCA: A CANCER JOURNAL FOR CLINICIANS, Issue 3 2009Mary Desmond Pinkowish News & Views Editor No abstract is available for this article. [source] Die Grippe-Pandemie 1918,20 in der medizinischen Debatte,BERICHTE ZUR WISSENSCHAFTSGESCHICHTE, Issue 1 2006Wilfried Witte Dr. med. Abstract The Influenza Pandemic of 1918,20 in medical debate. The history of the so called Spanish Influenza 1918,1920 is summarized especially in regard to the developments in medical debate. In Germany, Richard Pfeiffer, who had discovered Haemophilus influenzae after the previous pandemic 1890 / 91, managed it to defend his thesis that his "bacillus" was the causative agent of the flu, by modifying his theory moderately. The Early Virology of influenza in postwar times was still fixed to bacteriology and did not yet have the force of school-building. Aggressive therapy, e.g. with derivatives of chinine, were used in a concept of polypragmasy. The connection between influenza in animals and influenza in mankind was unknown or of no major interest till the rise of virology as an academic discipline in the 1950s. Since the outbreak of avian influenza in Asia 1997 virological archaeology is challenged to fill the historical part in the attempt to fight the threat of the highly pathogenic bird flu. In the beginning of the "short 20. century" politicians and doctors had no interest to build a "monument" of influenza. Today, virological reductionism does not have the power to (re-)construct such a monument. [source] The maximum tumour length in biopsy cores as a predictor of outcome after radical prostatectomyBJU INTERNATIONAL, Issue 2 2008Norihiro Hayashi OBJECTIVES To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate-specific antigen (PSA)-failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis. RESULTS The median (range) MTL was 4 (0.2,19) mm and correlated with adverse pathological findings, including specimen Gleason score (P = 0.003), pT3 (P < 0.001), seminal vesicle invasion (P < 0.001) and lymph node involvement (P = 0.019) in multivariate analysis. Preoperative PSA (P < 0.001), biopsy Gleason score (P = 0.002), and MTL (P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic-failure (P < 0.001) and death from prostate cancer (P = 0.004). The median (range) follow-up after surgery was 90 (17,152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer. CONCLUSIONS The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies. [source] Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseasesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2006Eugenio Cersosimo Abstract Cardiovascular disease affects approximately 60% of the adult population over the age of 65 and represents the number one cause of death in the United States. Coronary atherosclerosis is responsible for the vast majority of the cardiovascular events, and a number of cardiovascular risk factors have been identified. In recent years, it has become clear that insulin resistance and endothelial dysfunction play a central role in the pathogenesis of atherosclerosis. Much evidence supports the presence of insulin resistance as the fundamental pathophysiologic disturbance responsible for the cluster of metabolic and cardiovascular disorders, known collectively as the metabolic syndrome. Endothelial dysfunction is an important component of the metabolic or insulin resistance syndrome and this is demonstrated by inadequate vasodilation and/or paradoxical vasoconstriction in coronary and peripheral arteries in response to stimuli that release nitric oxide (NO). Deficiency of endothelial-derived NO is believed to be the primary defect that links insulin resistance and endothelial dysfunction. NO deficiency results from decreased synthesis and/or release, in combination with exaggerated consumption in tissues by high levels of reactive oxygen (ROS) and nitrogen (RNS) species, which are produced by cellular disturbances in glucose and lipid metabolism. Endothelial dysfunction contributes to impaired insulin action, by altering the transcapillary passage of insulin to target tissues. Reduced expansion of the capillary network, with attenuation of microcirculatory blood flow to metabolically active tissues, contributes to the impairment of insulin-stimulated glucose and lipid metabolism. This establishes a reverberating negative feedback cycle in which progressive endothelial dysfunction and disturbances in glucose and lipid metabolism develop secondary to the insulin resistance. Vascular damage, which results from lipid deposition and oxidative stress to the vessel wall, triggers an inflammatory reaction, and the release of chemoattractants and cytokines worsens the insulin resistance and endothelial dysfunction. From the clinical standpoint, much experimental evidence supports the concept that therapies that improve insulin resistance and endothelial dysfunction reduce cardiovascular morbidity and mortality. Moreover, interventional strategies that reduce insulin resistance ameliorate endothelial dysfunction, while interventions that improve tissue sensitivity to insulin enhance vascular endothelial function. There is general agreement that aggressive therapy aimed simultaneously at improving insulin-mediated glucose/lipid metabolism and endothelial dysfunction represents an important strategy in preventing/delaying the appearance of atherosclerosis. Interventions that 1 correct carbohydrate and lipid metabolism, 2 improve insulin resistance, 3 reduce blood pressure and restore vascular reactivity, and 4 attenuate procoagulant and inflammatory responses in adults with a high risk of developing cardiovascular disease reduce cardiovascular morbidity and mortality. Whether these benefits hold when the same prevention strategies are applied to younger, high-risk individuals remains to be determined. Copyright © 2006 John Wiley & Sons, Ltd. [source] Mineral metabolism disturbances in patients with chronic kidney diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2007B. Kestenbaum Abstract Background Kidney disease, especially chronic kidney disease (CKD), is a worldwide public health problem with serious adverse health consequences for affected individuals. Secondary hyperparathyroidism, a disorder characterized by elevated serum parathyroid hormone levels, and alteration of calcium and phosphorus homeostasis are common metabolic complications of CKD that may impact cardiovascular health. Materials and methods Here, we systematically review published reports from recent observational studies and clinical trials that examine markers of altered mineral metabolism and clinical outcomes in patients with CKD. Results Mineral metabolism disturbances begin early during the course of chronic kidney disease, and are associated with cardiovascular disease and mortality in observational studies. Vascular calcification is one plausible mechanism connecting renal-related mineral metabolism with cardiovascular risk. Individual therapies to correct mineral metabolism disturbances have been associated with clinical benefit in some observational studies; clinical trials directed at more comprehensive control of this problem are warranted. Conclusions There exists a potential to improve outcomes for patients with CKD through increased awareness of the Bone Metabolism and Disease guidelines set forth by the National Kidney Foundation,Kidney Disease Outcomes Quality Initiative. Future studies may include more aggressive therapy with a combination of agents that address vitamin D deficiency, parathyroid hormone and phosphorus excess, as well as novel agents that modulate circulating promoters and inhibitors of calcification. [source] Early intervention in CF: How to monitor the effectPEDIATRIC PULMONOLOGY, Issue 11 2007Giora Weiser MD Abstract Early and aggressive therapy already at the stage when no apparent signs of significant lung disease are detectable, may delay the development and progression of cystic fibrosis (CF). Identification of markers for early pulmonary disease in CF is crucial to monitor adherence to preventive therapy and determine its success. Currently several surrogate markers are available that are used in both the decision making and evaluation of the timing and success of early intervention namely, pulmonary function tests (PFT), microbial cultures, imaging techniques, inflammatory markers, serological markers, and several general signs such as exacerbation rate and nutritional status. This review will present the current status and discuss the significance of their application as well as their limitations for patients with CF and no apparent pulmonary disease. 2007;42:1002,1007. © 2007 Wiley-Liss, Inc. [source] Overexpression of cathepsin,B in gastric cancer identified by proteome analysisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2005Matthias P. A. Ebert Abstract We aimed to validate an analytical approach based on proteomics on gastric cancer specimens for the identification of new putative diagnostic or prognostic markers. Primary screening was performed on gastrectomy specimens obtained from ten consecutive patients with gastric cancer. Gastric epithelial cells were obtained with an epithelial cell enrichment technique, homogenized and then separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The differential protein expression pattern was verified stepwise by Western blotting and immunohistochemistry on samples from 28 and 46,cancer patients, respectively. The putative clinical applicability and prognostic use were tested by an enzyme-linked immunoabsorbent assay on serum samples obtained from 149,cancer patients. One hundred-ninety-one differentially expressed protein spots were found by 2-D PAGE and identified by mass spectrometry, including cathepsin,B, which was over-expressed in six (60%) patients. Western blotting confirmed that the active form of cathepsin,B is over-expressed, while immunohistochemistry showed strong cytoplasmic staining in cancer tissues of 45 (98%) patients. The serum level of cathepsin,B was increased in patients with gastric cancer compared to healthy controls (P,=,0.0026) and correlated with T-category and the presence of distant metastases (P,<,0.05). Serum levels above 129,pmol·L,1 were associated with a reduced survival rate (P,=,0.0297). Proteome analysis is a valuable tool for the identification of prognostic markers in gastric cancer: Increased cathepsin,B serum levels are associated with advanced tumor stages and progressive disease, which enables the classification of some gastric cancer patients into a subgroup that should undergo aggressive therapy. [source] T1N0 Triple Negative Breast Cancer: Risk of Recurrence and Adjuvant ChemotherapyTHE BREAST JOURNAL, Issue 5 2009Henry G. Kaplan MD Abstract:, Adjuvant treatment of T1N0 breast cancer (BC) has evolved in recent years with chemotherapy options dependent on tumor size and cellular characteristics. Our goal is to describe the difference in outcome between T1N0 triple negative (TriNeg) and estrogen/progesterone receptor positive/her2/neu-negative BC. From our institute's registry, we identified primary BC patients diagnosed from 1998 to 2005, estrogen/progesterone receptor negative (ER,/PR,)/her-2/neu negative (her2,) (TriNeg = 110) and ER+/PR+/her2, (HR+/her2, = 919). Clinical diagnosis and treatment variables were chart abstracted. Vital and disease status were updated annually. Pearson chi-squared tests were used for bivariate analysis. Hazard ratios were calculated using the Cox proportional hazards model. Average patient age was 59 years, range 23,93 years and average length of follow-up was 4.22 years. T-stage distribution for HR+/her2, patients was 9% T1a (>0.1, ,0.5 cm), 34% T1b (>0.5 cm, ,1 cm), 57% T1c (>1 cm, ,2 cm) and for TriNeg, 6% T1a, 21% T1b, and 73% T1c. Sixty-five per cent of T1b and 73% T1c TriNeg patients received chemotherapy versus 7% of T1b and 32% of T1c HR+/her2, patients with TriNeg patients more likely to receive doxorubicin/cyclophosphamide/paclitaxel combined therapy. Recurrence rates were the following, T1b: 8.7%, TriNeg (2/23) versus 0%, HR+/her2, (0/315) and T1c: 8.8%, TriNeg (7/80) versus 2.1%, HR+/her2, (11/523). Five year relapse-free survival was 98% in the HR+/her2, group and 89% in the TriNeg group (log rank test = 27.77, p < 0.001). The hazard ratio for recurrence in the TriNeg group was 6.57 (95% CI = 2.34, 18.49) adjusted for age, tumor size, and adjuvant chemotherapy. Triple negative T1N0 patients have greater recurrence risk in spite of more aggressive therapy by both number treated and adjuvant chemotherapy type even in a low-risk category. New treatment modalities specific for triple negative disease are urgently needed. [source] Molecular targeted therapies for diffuse large B-cell lymphoma based on apoptosis profiles,THE JOURNAL OF PATHOLOGY, Issue 5 2010Saskia AGM Cillessen Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult non-Hodgkin lymphoma and is treated with chemotherapy in combination with rituximab. Despite this aggressive therapy, the disease is fatal in 30,40% of patients. Inhibition of the apoptosis signalling pathways is strongly related to response to chemotherapy and eventual clinical outcome. In order to survive, lymphoma cells depend on disruption of the apoptosis pathway by mutations in apoptosis inducing genes or by continuous expression of anti-apoptotic proteins. The development of molecules targeting these apoptosis inhibitors provides a very promising opportunity to specifically target tumour cells without toxicity to non-malignant cells in DLBCL patients. Sensitivity for most of these antagonists can be predicted based on biological markers, suggesting the possibility of pre-defining patients who will most likely benefit from these targeted therapies. Experimental therapies aimed at restoring the upstream apoptosis pathway or targeting apoptosis inhibitors are currently being tested in clinical trials and are expected to be effective particularly in chemotherapy-refractory DLBCL, providing hope for patients who are refractory to current therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Complete and sustained remission of juvenile dermatomyositis resulting from aggressive treatmentARTHRITIS & RHEUMATISM, Issue 6 2009Susan Kim Objective To assess the time needed to achieve sustained, medication-free remission in a cohort of patients with juvenile dermatomyositis (DM) receiving a stepwise, aggressive treatment protocol. Methods Between 1994 and 2004, a cohort of 49 children with juvenile DM who were followed up at a single tertiary care children's hospital using disease activity measures according to a specific protocol received standardized therapy with steroids and methotrexate. If a patient's strength or muscle enzyme levels did not normalize with this initial therapy, additional medications were added in rapid succession to the treatment regimen. The primary outcome measure was time to complete remission. Additional outcome measures were onset of calcinosis, effect of treatment on height, and complications resulting from medications. Results Forty-nine patients were followed up for a mean ± SD of 48 ± 30 months. All but 1 patient received 2 or more medications simultaneously. Transient localized calcifications occurred in 4 patients (8%), and 2 additional patients (4%) had persistent calcinosis. Despite the aggressive therapy, complications associated with treatment were mild and were primarily attributable to steroids. No persistent effect on longitudinal growth was observed. A complete, medication-free remission was achieved in 28 patients; the median time to achievement of complete remission was 38 months (95% confidence interval 32,44 months). None of these patients experienced a disease flare that required resumption of medications during the subsequent period of observation (mean ± SD 36 ± 19.7 months). Conclusion Our findings suggest that aggressive treatment of juvenile DM aimed at achieving rapid, complete control of muscle weakness and inflammation improves outcomes and reduces disease-related complications. In more than one-half of the children whose disease was treated in this manner (28 of 49), a prolonged, medication-free remission was attained within a median of 38 months from the time of diagnosis. [source] Late follow-up of a randomized trial of surgery plus tamoxifen versus tamoxifen alone in women aged over 70 years with operable breast cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 6 2004M. Fennessy Background: Breast cancer has been considered a more indolent disease in the elderly, who are less tolerant of aggressive therapy. This trial tested the hypothesis that tamoxifen without surgery would provide adequate control of breast cancer for the remainder of life in elderly women, thereby sparing them surgery. Method: Women aged over 70 years with operable, invasive breast cancer were randomized to receive either tamoxifen alone or surgery plus tamoxifen. Time to treatment failure (TTF), indicating initial primary treatment failure, was the primary endpoint. Overall mortality, and death from breast cancer were also compared between the two groups. Results: Between 1984 and 1991, 455 patients were included in the trial. The analysis was based on a median follow-up of 12·7 years. The TTF was significantly shorter in the tamoxifen alone group: hazard ratio (HR) 4·41 (95 per cent confidence interval (c.i.) 3·31 to 5·88). Ninety-three (40·4 per cent) of 230 patients randomized to tamoxifen alone underwent surgery for the management of their disease. Both overall mortality and mortality from breast cancer were significantly increased in the tamoxifen alone group, although the survival curves did not diverge for the first 3 three years: HR 1·29 (95 per cent c.i. 1·04 to 1·59) and 1·68 (95 per cent c.i. 1·15 to 2·47) respectively. Conclusion: Omission of primary surgery in unselected elderly women with operable breast cancer who were fit for the procedure resulted in an increased rate of progression, therapeutic intervention and mortality. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Treatment outcome after radiotherapy alone for patients with Stage I,II nasopharyngeal carcinomaCANCER, Issue 1 2003Daniel T. T. Chua M.B.Ch.B. Abstract BACKGROUND The objective of this study was to review the long-term treatment outcome of patients with American Joint Committee on Cancer (AJCC) 1997 Stage I,II nasopharyngeal carcinoma (NPC) who were treated with radiotherapy alone. METHODS One hundred forty-one patients with NPC had AJCC 1997 Stage I,II disease (Stage I NPC, 50 patients; Stage II NPC, 91 patients) after restaging and were treated with radiotherapy alone between September 1989 and August 1991. Fifty-seven patients had lymph node disease, and the median greatest lymph node dimension was 3 cm. The median dose to the nasopharynx was 65 grays. The median follow-up was 82 months (range, 4,141 months). RESULTS Patients who had Stage I disease had an excellent outcome after radiotherapy. The 10-year disease specific survival, recurrence free survival (RFS), local RFS, lymph node RFS, and distant metastasis free survival rates were 98%, 94%, 96%, 98%, and 98%, respectively. Patients who had Stage II disease had a worse outcome compared with patients who had Stage I disease: The corresponding 10-year survival rates were 60%, 51%, 78%, 93%, and 64%. The differences all were significant except for lymph node control. Among patients who had Stage II disease, those with T1,T2N1 NPC appeared to have a worse outcome compared with patients who had T2N0 NPC. No significant differences in survival rates were found with respect to lymph node size or status for patients with T1,T2N1 disease. CONCLUSIONS When patients with NPC had their disease staged according to the AJCC 1997 classification system, patients with Stage I disease had an excellent outcome after they were treated with radiotherapy alone. Patients with Stage II disease, especially those with T1,T2N1 disease, had a relatively worse outcome, and more aggressive therapy, such as combined-modality treatment, may be indicated for those patients. Cancer 2003;98:74,80. © 2003 American Cancer Society. DOI 10.1002/cncr.11485 [source] Pleuropulmonary complications of PVL-positive Staphylococcus aureus infection in childrenACTA PAEDIATRICA, Issue 8 2009Biju Thomas Abstract It is increasingly recognized world-wide that Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus (PVL-SA) is associated with a highly aggressive and often fatal form of community-acquired pneumonia. We report four children who presented with severe pleuropulmonary complications due to infection by community-acquired methicillin-sensitive S. aureus (CA-MSSA), producing PVL toxin. The complications included bilateral multilobular infiltrates, pneumatocoeles, recurrent pneumothoraces, pleural effusion, empyema, lung abscess and diaphragmatic paralysis. This case series highlights the diverse pleuropulmonary manifestations of this potentially lethal infection and the importance of heightened awareness, early recognition and aggressive therapy. Conclusion:, Complicated pneumonia in a previously fit young patient with a history of preceding ,flu-like' illness or skin/soft tissue infection should raise the suspicion of infection by PVL-positive Staphylococcus aureus (PVL-SA). Severe pleuropulmonary complications are a feature of this disease. [source] Elevated Serum Cardiac Troponin in Non-acute Coronary SyndromeCLINICAL CARDIOLOGY, Issue 1 2009Yeshitila Agzew MD Abstract Cardiac troponins (CTn) are the most sensitive and specific biochemical markers of myocardial injury and risk stratification. The assay for troponin T (cTnI) is standardized, and results obtained from different institutions are comparable. This is not the case with troponin I (cTnT), and clinicians should be aware that each institution must analyze and standardize its own results. Elevated cTn levels indicate cardiac injury, but do not define the mechanical injury. The differentiation of cTn elevation caused by coronary events from those not related to an acute coronary syndrome (ACS) is tiresome, at times vexing, and often costly. Elevation of cTn in non-ACS is a marker of increased cardiac and all-cause morbidity and mortality. The cause of these elevations may involve serious medical conditions that require meticulous diagnostic evaluation and aggressive therapy. At present, there are no guidelines to treat patients with elevated troponin levels and no coronary disease. The current strategy of treatment of patients with elevated troponin and non-ACS involves treating the underlying causes. Copyright © 2009 Wiley Periodicals, Inc. [source] Risks and benefits of continued aggressive statin therapyCLINICAL CARDIOLOGY, Issue S3 2003Antonio M. Gotto Jr. M.D., D.PHIL Abstract The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are a well-tolerated, effective class of medications for the reduction of low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels. Extensive data from clinical trials demonstrate that these agents reduce fatal and nonfatal cardiovascular risk in primary and secondary prevention patients, including women and the elderly. A threshold value for LDL-C reduction below which there is no further clinical benefit has not yet been identified. In the Heart Protection Study (HPS), significant relative risk reduction occurred even among patients with LDL-C levels < 2.6 mmol/l (100 mg/dl). Statin therapy also produced reductions in cardiovascular disease in a wide range of high-risk patients regardless of baseline cholesterol levels. Rhabdomyolysis, typically defined as muscle pain or weakness associated with creatine kinase levels higher than 10 times the upper limit of normal and the presence of myoglobulinuria, is a rare but potentially serious complication of statins. Although dose-dependent transaminase elevations occur in 0.5 to 2% of cases, it has not been determined whether these elevations qualify as true drug-related hepatotoxicity. Management of myopathy and elevated transaminases is addressed in a joint publication from the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI). Because statins have significant potential benefits and a low risk for serious adverse effects, aggressive therapy should be considered in patients at high risk for coronary heart disease. 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