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Debilitating Condition (debilitating + condition)
Selected AbstractsThe science of endothelin-1 and endothelin receptor antagonists in the management of pulmonary arterial hypertension: current understanding and future studiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2009N. J. Davie Abstract Pathological vascular remodelling is a key contributor to the symptomatology of pulmonary arterial hypertension (PAH), and reversing this process may offer the best hope for improving this debilitating condition. The vascular remodelling process is believed to be due to endothelial cell dysfunction and to involve altered production of endothelial cell-derived vasoactive mediators. The observation that circulating plasma levels of the vasoactive peptide endothelin (ET)-1 are raised in patients with PAH, and that ET-1 production is increased in the pulmonary tissue of affected individuals, makes it a particularly interesting target for a therapeutic intervention in PAH. Clinical trials with ET receptor antagonists (ETRAs) show that they provide symptomatic benefit in patients with PAH, thereby proving the clinical relevance of the ET system as a therapeutic target. In this paper, we review the role of ET-1 together with the available data on the roles of the specific ET receptors and ETRAs in PAH. In particular, we discuss the possible role of ET receptor selectivity in the vascular remodelling process in PAH and whether selective ETA or nonselective ETA/ETB blockade offers the greatest potential to improve symptoms and alter the clinical course of the disease. [source] Neuromodulators for Migraine PreventionHEADACHE, Issue 4 2008Robert Kaniecki MD Migraine is a debilitating condition characterized by a cycle of painful headaches and headache-related symptoms interspersed with periods of worry, distress, and apprehension. The negative impact of migraine on patient functioning, workplace productivity, and other daily activities has been demonstrated through the use of a variety of clinician- and patient-reported assessment tools, including the Migraine-Specific Questionnaire and the Migraine Disability Assessment questionnaire. In addition to considering the frequency and severity of migraine, clinicians need to encourage more open dialogue with their patients about the impact of this disorder on daily activities and productivity. Only then can the most appropriate course of treatment be determined. Appropriately prescribed acute and preventive therapies should break the cycle of migraine and improve the daily activities of patients with this chronic condition. Divalproex sodium and topiramate are neuromodulators that are approved by the US Food and Drug Administration (FDA) for the prophylaxis (prevention) of migraine headache in adults. Non-FDA-approved neuromodulators sometimes used in the management of migraine headache include gabapentin, lamotrigine, levetiracetam, and zonisamide. All medications need to be titrated, and treatment-related adverse events need to be managed appropriately. Preventive medications should be taken for at least 2-3 months to ascertain their therapeutic effect. [source] Repeat Trigeminal Nerve Radiosurgery for Refractory Cluster Headache Fails to Provide Long-Term Pain ReliefHEADACHE, Issue 2 2007Shearwood McClelland III MD Objective/Background.,Medically refractory cluster headache (MRCH) is a debilitating condition that has proven resistant to many modalities. Previous reports have indicated that radiosurgery for MRCH provides little long-term pain relief, with moderate/significant morbidity. However, there have been no reports of repeated radiosurgery in this patient population. We present our findings from the first reports of repeat radiosurgery for MRCH. Methods.,Two patients with MRCH underwent repeat gamma knife radiosurgery at our institution. Each fulfilled clinical criteria for treatment, including complete resistance to pharmacotherapy, pain primarily localized to the ophthalmic division of the trigeminal nerve, and psychological stability. Both patients previously received gamma knife radiosurgery (75 Gy) for MRCH with no morbidity, but no long-term improvement of pain relief (Patient 1 = 5 months, Patient 2 = 10 months) after treatment. For repeat radiosurgery, each patient received 75 Gy to the 100% isodose line delivered to the root entry zone of the trigeminal nerve, and was evaluated postretreatment. Pain relief was defined as: excellent (free of MRCH with minimal/no medications), good (50% reduction of MRCH severity/frequency with medications), fair (25% reduction), or poor (less than 25% reduction). Results.,Following repeat radiosurgery, long-term pain relief was poor in both patients. Neither patient sustained any immediate morbidity following radiosurgery. Patient 2 experienced right facial numbness 4 months postretreatment, while Patient 1 experienced no morbidity. Conclusion.,Repeat radiosurgery of the trigeminal nerve fails to provide long-term pain relief for MRCH. Given the reported failures of initial and repeat radiosurgery for MRCH, trigeminal nerve radiosurgery should not be offered for MRCH. [source] Advances in understanding bone cancer painJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2005M.J. Goblirsch Abstract Experimental animal models of bone cancer pain have emerged and findings have provided a unique glimpse into unraveling the mechanism that drives this debilitating condition. Key contributors to the generation and maintenance of bone cancer pain are tumor-induced osteolysis, tumor itself, and production of nociceptive mediators in the bone-tumor microenvironment. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] A Cost Utility Analysis of Interdisciplinary Early Intervention Versus Treatment as Usual For High-Risk Acute Low Back Pain PatientsPAIN PRACTICE, Issue 5 2010Mark D. Rogerson PhD Abstract Chronic pain is a costly and debilitating condition that has proven difficult to treat, solely with medical interventions, due to the complex interplay of biological, psychological, and social factors in its onset and persistence. Many studies have demonstrated the effectiveness of interdisciplinary treatment that includes psychosocial interventions for low back pain. Nevertheless, these interventions continue to be under-utilized due to concerns of cost and applicability. The present study utilized a cost utility analysis to evaluate effectiveness and associated costs of interdisciplinary early intervention for individuals with acute low back pain that was identified as high-risk for becoming chronic. Treatment effectiveness was evaluated using a standard pain measure and quality-adjusted life years, and associated medical and employment costs were gathered for 1 year. Results indicated that subjects improved significantly from pretreatment to 1-year follow-up, and that the early intervention group reported fewer health-care visits and missed workdays than the treatment as usual group. The majority of 1,000 bootstrapped samples demonstrated the dominance of the early intervention program as being both more effective and less costly from a societal perspective. The early intervention treatment was the preferred option in over 85% of samples within an established range of acceptable costs. These results are encouraging evidence for the cost-effectiveness of interdisciplinary intervention and the benefits of targeted early treatment. [source] Anal stenosis: use of an algorithm to provide a tension-free anoplastyANZ JOURNAL OF SURGERY, Issue 5 2010Zeev Duieb Abstract Background:, Anal stenosis is a debilitating condition that often is iatrogenic in cause. Various surgical procedures to manage this problem have been described. The present study evaluates the use of different anoplasty techniques in a series of 11 patients with anal stenosis. To the best of the authors' knowledge, this is the first study to provide a stepwise algorithm for the anoplasty techniques used. Methods:, A series of 11 patients were evaluated for presenting symptoms, cause of anal stenosis, type of anoplasty used, complications and post-operative success in relieving symptoms. All operations were performed by one surgeon in three hospitals, and were followed up by the same surgeon and by a surgical registrar. Results:, The most common presenting symptoms were constipation and decreasing calibre of stool. The main causes of anal stenosis were previous surgery, neoplasia and fissure. Transverse closure, Y-V and diamond advancement flaps were used in an escalating manner to deal with increasing severity of stenosis. All 11 patients had some level of improvement in symptoms post-operatively. There were no long-term complications. Conclusion:, Anoplasty is a safe and successful option in the treatment of anal stenosis, and this stepwise algorithm takes the guesswork out of choosing the most appropriate procedure for each patient. [source] The economic consequences of introducing deep brain stimulation for the treatment of advanced Parkinson's disease in AustraliaAUSTRALASIAN JOURNAL ON AGEING, Issue 3 2003Bruce P. Hollingsworth Objectives: Parkinson's disease is a debilitating condition, which is increasing in prevalence as elderly populations increase in the developed world. As such, resource consumption will also increase. For advanced Parkinsons, where drug therapy is no longer effective, there are two surgical options - ablative surgery, a one-off procedure which destroys part of the brain, and deep brain stimulation (DBS), which uses electrodes to stimulate part of the brain. The specific question to be answered here is what the costs to the community of DBS are compared to ablative surgery (thalmotomy or pallidotomy) in potentially relieving the symptoms of advanced Parkinson's disease, and if there is any improvement in patients' quality of life. Design: A cost effectiveness study is undertaken. UK and Australian data are made use of and cost-effectiveness estimated in terms of cost per change in functional ability. Setting: Hospital, community and home care. Patients: Those with advanced Parkinson's Disease. Main outcome measures: Frenchay index of functional ability. Results: It is estimated that the incremental extra cost for a small change in ability to undertake daily tasks is at least 23,559. Conclusions: As outcomes evidence is of low quality, at this stage it is not possible to establish that Deep Brain Stimulation offers substantial improvements in quality of life. Extra costs over ablative surgery are estimated to be in the range of 17,830 to 51,385 per patient over a five year period. [source] Xerostomia: an update for cliniciansAUSTRALIAN DENTAL JOURNAL, Issue 3 2010MS Hopcraft Abstract Saliva plays an important protective role in the oral environment, and reductions in saliva quantity are known to increase the risk of oral diseases. Importantly, xerostomia or the perception of a dry mouth is now being recognized as an important risk factor for dental diseases. Furthermore, the subjective sensation of a dry mouth is a debilitating condition in itself that impacts on the quality of life of sufferers. With approximately 1 in 5 people reporting some form of dry mouth, and an increasing prevalence in the elderly, it is important for clinicians to have a thorough understanding of this problem. The aim of this paper is to review some of the literature relating to xerostomia in order to provide an evidence based update for clinicians. [source] The dental implications of bisphosphonates and bone diseaseAUSTRALIAN DENTAL JOURNAL, Issue 2005A. Cheng Abstract In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates, pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients. [source] Predictors of avascular necrosis of bone in long-term survivors of hematopoietic cell transplantationCANCER, Issue 18 2009Stephanie Campbell BA Abstract BACKGROUND: Avascular necrosis (AVN) is a debilitating condition reported after chronic steroid use. The purpose of this study was to describe the magnitude of risk in individuals who survived ,1 years after hematopoietic cell transplantation (HCT), and to investigate the role of immunosuppressive agents such as prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and cyclosporine (CSA) in the development of AVN after HCT. METHODS: Using a retrospective study design, the authors followed 1346 eligible patients for the development of AVN. Cumulative incidence was calculated taking into consideration competing risk from death and disease recurrence. Cox proportional regression techniques were used to identify associated risk factors. RESULTS: The median age at HCT was 34 years (range, 7 months-69 years), and median length of follow-up for those surviving was 8.2 years. Seventy-five patients developed AVN of 160 joints. The cumulative incidence of AVN at 10 years was 2.9% after autologous HCT, 5.4% after allogeneic matched related donor HCT, and 15% after unrelated donor HCT (P < .001 compared with autologous HCT recipients). For allogeneic transplant recipients, male sex (relative risk [RR], 2.1; 95% confidence interval [95% CI], 1.1-4.0); presence of chronic graft-versus-host disease (RR, 2.2); and exposure to CSA, FK506, prednisone, and MMF rendered patients at increased risk, especially in patients with a history of exposure to ,3 drugs (RR, 9.2; 95% CI, 2.42-35.24). CONCLUSIONS: Future studies examining the pathogenetic mechanism underlying AVN should help develop targeted interventions to prevent this chronic debilitating condition. Cancer 2009. © 2009 American Cancer Society. [source] Clinical and Histological Aspects of CNV Formation: Studies in an Animal ModelACTA OPHTHALMOLOGICA, Issue thesis2 2008Nathan Lassota MD Abstract. The purpose of the present thesis was to develop an animal model of CNV in order to study the early formation of CNV and to test the effects of an anti-angiogenic treatment. Porcine eyes were chosen as a substrate for CNV induction, since they are similar to human eyes in terms of both macroscopic and microscopic morphology. However, a major difference is that pigs lack a fovea; instead they have a visual streak, with a relatively stable and high concentration of cones. By surgical perforation of Bruch's membrane we were able to induce formation of CNV membranes. The morphology and cellular composition of these membranes varied with the surgical technique employed. When RPE cells were locally removed at the time of perforation, the resulting CNV was thinner, contained fewer blood vessels and was less prone to leak on fluorescein angiography than when RPE cells were left intact at induction. The neuroretina overlying the perforation site was not damaged by any of the surgical techniques, thus allowing the subsequent retinal damage to be ascribed to the actual process of CNV formation. Using this animal model allowed us to directly map histological findings onto fluorescein angiograms and thereby perform meaningful correlations between histopathologic and photographic features. Such correlations have been hampered in human subjects, since human eyes are not enucleated as a consequence of CNV and are therefore only available for post-mortem studies. In such studies there often is a considerable time-gap between the death of the patient and the latest available fluorescein angiogram, thereby allowing macular pathology to evolve in the interim. Histological examination of the porcine membranes demonstrated that they were composed of RPE cells, glial cells, macrophages, endothelial cells, collagen and smooth muscle fibres, which are the same cellular and fibrillar elements that dominate human CNV membranes. The porcine model was applied to test the effects, in a randomized and masked fashion, of intravitreally injected bevacizumab. Bevacizumab, a pan VEGF A antibody, was found to reduce both the proliferation of endothelial cells in CNV membranes and the propensity to leak in fluorescein angiograms. Immunohistochemically, bevacizumab was detected in the inner limiting membrane, in retinal blood vessels and binding uniformly to the entire CNV membrane without any cellular predisposition. Based on the above findings we believe that the porcine CNV model shows a bearing to human disease and therefore might be used as a tool to obtain improved treatments for this debilitating condition. [source] Advances in the understanding and future therapy of COPDCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 4 2002L. Fabbri Summary Chronic obstructive pulmonary disease (COPD) is an enormous public health problem, which currently causes about 5% of all deaths worldwide. The main feature of COPD is a progressive loss of lung function as a result of structural changes in the airways and lung parenchyma. It is predominantly a disease of smokers, although only about 15% of smokers are thought to develop severe enough disease to be symptomatic. The reasons why some smokers are more susceptible to the disease than others are not clear, and are the subject of extensive research. Characteristically, inflammation is central to the pathophysiology of COPD, and it is clear that the inflammation of COPD differs from that seen in asthma. The most important treatment for COPD is smoking cessation, as other current treatments do not alter the course of the disease. Recent research into the cellular and molecular mechanisms underlying chronic obstructive pulmonary disease has provided potential new avenues for the development of rationally designed drugs, which may improve the outlook for patients with this debilitating condition. It is likely that different therapeutic approaches will be needed in different patients, because of the heterogeneity of the disease. [source] The Mainz Severity Score Index: a new instrument for quantifying the Anderson,Fabry disease phenotype, and the response of patients to enzyme replacement therapyCLINICAL GENETICS, Issue 4 2004C Whybra Anderson,Fabry disease (AFD) is an X-linked disorder caused by deficient activity of the lysosomal enzyme ,-galactosidase A. The availability of enzyme replacement therapy (ERT) for this debilitating condition has led to the need for a convenient and sensitive instrument to monitor clinical effects in an individual patient. This study aimed to develop a scoring system , the Mainz Severity Score Index (MSSI) , to measure the severity of AFD and to monitor the clinical course of the disease in response to ERT. Thirty-nine patients (24 males and 15 females) with AFD were assessed using the MSSI immediately before and 1 year after commencing agalsidase alfa ERT. Control data were obtained from 23 patients in whom AFD was excluded. The MSSI of patients with AFD was significantly higher than that of patients with other severe debilitating diseases. The MSSI indicated that, although more men than women had symptoms classified as severe, overall, the median total severity scores were not significantly different between male and female patients. One year of ERT with agalsidase alfa led, in all patients, to a significant (p < 0.001) reduction in MSSI score (by a median of nine points). This study has shown that the MSSI score may be a useful, specific measure for objectively assessing the severity of AFD and for monitoring ERT-related treatment effects. [source] Overcoming diabetic gastroparesis en route to kidney transplantCLINICAL TRANSPLANTATION, Issue 2 2006John De Csepel Abstract: Gastroparesis is a debilitating condition that affects a significant number of diabetic patients. Some of these patients have end-stage renal disease and are in need of kidney transplant. Symptoms of gastroparesis include: early satiety, pyrosis, epigastric pain, nausea and vomiting, which may lead to caloric and electrolyte deficiencies as well as significant weight loss. A viable option for diabetic gastroparesis patients who fail first line treatments consisting of dietary changes and gastric prokinetic medications is gastric electrical stimulator (GES) implantation. We present a 41-yr-old man and 35-yr-old woman with diabetic gastroparesis, who were initially deemed unacceptable candidates for renal transplantation because of marked malnourishment and a concern that they would not be able to tolerate immunosuppressant medications. In less than two yr following GES implantation, each patient underwent a successful kidney transplant. [source] | |||||||||||||