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Conventional Therapy (conventional + therapy)
Selected AbstractsA preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degenerationINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2006Christine L. Le Maitre Summary Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% of cases is caused by degeneration of the intervertebral disc (DIVD). Targeting therapies to inhibit the process of degeneration would be a potentially valuable treatment for LBP. There is increasing evidence for a role for IL-1 in DIVD. A natural inhibitor of IL-1 exists, IL-1Ra, which would be an ideal molecular target for inhibiting IL-1-mediated effects involved in DIVD and LBP. In this study, the feasibility of ex vivo gene transfer of IL-1Ra to the IVD was investigated. Monolayer and alginate cultures of normal and degenerate human intervertebral disc (IVD) cells were infected with an adenoviral vector carrying the IL-1Ra gene (Ad-IL-1Ra) and protein production measured using an enzyme-linked immunosorbent assay. The ability of these infected cells to inhibit the effects of IL-1 was also investigated. In addition, normal and degenerate IVD cells infected with Ad-IL-1Ra were injected into degenerate disc tissue explants and IL-1Ra production in these discs was assessed. This demonstrated that both nucleus pulposus and annulus fibrosus cells infected with Ad-IL-1Ra produced elevated levels of IL-1Ra for prolonged time periods, and these infected cells were resistant to IL-1. When the infected cells were injected into disc explants, IL-1Ra protein expression was increased which was maintained for 2 weeks of investigation. This in vitro study has shown that the use of ex vivo gene transfer to degenerate disc tissue is a feasible therapy for the inhibition of IL-1-mediated events during disc degeneration. [source] Narrow-band ultraviolet B phototherapy in patients with recalcitrant nodular prurigoTHE JOURNAL OF DERMATOLOGY, Issue 10 2007Risa TAMAGAWA-MINEOKA ABSTRACT Management of nodular prurigo has been less than satisfactory. Conventional therapies such as systemic antihistamines and topical steroids have not been particularly successful. The effects of narrow-band ultraviolet B (NB-UVB) phototherapy in the treatment of various inflammatory dermatoses have been proven, however, no data exist on the efficacy and the duration of remission in NB-UVB monotherapy for nodular prurigo. The aim of this study was to evaluate the effect of NB-UVB phototherapy on recalcitrant nodular prurigo. NB-UVB phototherapy was performed once a week on 10 patients with recalcitrant nodular prurigo. The initial dose was 0.4 J/cm2, and the dose was increased by 0.1 J/cm2 for each treatment. The treatment was performed until the eruption was almost clear. In each patient, a mean cumulative dose of 23.88 J/cm2 was applied over a mean of 24.3 irradiations. The mean maximum daily dose of ultraviolet B was 1.2 ± 0.4 J/cm2. NB-UVB phototherapy notably improved the eruption of nodular prurigo in all patients. Follow up at 1 year revealed that only one patient had relapsed. The remaining nine patients continued to derive long-term benefits. NB-UVB phototherapy appears to be an effective treatment for recalcitrant nodular prurigo, offering long-term benefits in the majority of those treated. [source] Gene and immune therapy for renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2001Allan J Pantuck Abstract Conventional therapy for metastatic renal cell carcinoma is associated with a poor response rate and few patients are long-term survivors. The occurrence of spontaneous regression and the prolonged latency period between primary tumor removal and the appearance of metastases in some patients suggest the existence of important host immune responses to autologous tumor cells. With the advent of molecular gene transfer techniques and increased knowledge of the basic pathways of immune activation, the field of cancer immunotherapy has finally begun to develop novel and effective approaches for harnessing the immune system as a therapeutic agent. Current immunotherapy and gene therapy strategies, including methods of cytokine delivery and tumor-cell-based vaccines, are presented. [source] Risk factors for visual impairment registration due to diabetic retinopathy in Leeds, 2002,2005PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 3 2009Diabetes & Endocrinology, H Hayat Specialist Registrar Abstract We undertook a retrospective study of case notes of those patients registered blind or partially sighted due to diabetic retinopathy in the Leeds metropolitan area in the years 2002 and 2005. Both the incidence of visual impairment due to diabetic retinopathy and the relative contribution to total registrations are similar to those observed in other local and national studies. The main risk factors for registered visual impairment were poor glycaemic control prior to ophthalmic review, no prior retinopathy screening, late presentation with symptomatic visual loss, non-compliance with planned review and laser treatment failure. Most of these risk factors are avoidable. Nearly two-thirds of patients diagnosed with diabetes mellitus were being screened for diabetic retinopathy. These figures would suggest that the National Service Framework for Diabetes' proposed coverage of 80% by 2006 and 100% by the end of 2007 is achievable. The duration of diagnosed diabetes mellitus at the time of registration was an average of 16 years in this study. This reflects the slow development of sight-threatening retinopathy and visual loss observed previously. Conventional therapy for diabetic retinopathy with laser photocoagulation reduces the risk of visual loss more effectively than it improves visual function. Despite the increased risk of early worsening of retinopathy seen with intensive glycaemic control in the Diabetes Control and Complications Trial and the UK Prospective Diabetes Study, improved control closer to the time of diagnosis of diabetes mellitus would have helped to provide a sustained reduction in the risk of retinopathy developing or progressing. Both laser treatment failure and non-attendance may limit the benefits of improved screening coverage. Copyright © 2009 John Wiley & Sons. [source] Long-Term Efficacy of Subcutaneous Sweat Gland Suction Curettage for Axillary Hyperhidrosis: A Prospective Gravimetrically Controlled StudyDERMATOLOGIC SURGERY, Issue 9 2008STEPHANIE DARABANEANU PHD BACKGROUND Subcutaneous sweat gland suction curettage (SSGSC) is gaining acceptance as a therapy for axillary hyperhidrosis. Despite its acceptance, there remains a lack of prospective data describing the efficacy and long-term outcome of SSGSC. OBJECTIVE We examined the sweat rates and patients' satisfaction of 12 months following SGSC in 28 patients with axillary hyperhidrosis. METHODS Axillary sweat rates were determined by semiquantitative gravimetry. A questionnaire was used to determine patients' satisfaction. RESULTS A 58% reduction in sweat rate under resting conditions and an 85% reduction during aerobic exercise in sweat rates was observed. A subdivision of patients into three groups based on their baseline preoperative sweat rates (<25, 25,50, and >50 mg/min) showed that patients with resting sweat rates over 25 mg/min benefited particularly from this procedure, whereas patients with less than 25 mg/min did not. CONCLUSION SSGSC produces a significant reduction in the preoperative sweat rates. A low complication rate and a high degree of patient satisfaction were observed. Long-term follow-up evaluations demonstrate a low number of relapses, making SSGSC a convenient and satisfactory method of treating axillary hyperhidrosis. It should be considered in patients refractory to conventional therapies with baseline sweat rates greater than 25 mg/min. [source] THERAPEUTIC HOTLINE: Alefacept in the treatment of hyperkeratotic palmoplantar psoriasisDERMATOLOGIC THERAPY, Issue 5 2010Sagi Lior ABSTRACT Plaque-type palmoplantar psoriasis (PPP) is associated with marked morbidity and frequently resistant to conventional therapies. Patients with long-standing plaque-type PPP failing previous treatments were included and treated with a 12-week intramuscular alefacept. The biweekly evaluation included hyperkeratosis, itching, and pain grading. In all of the seven treated patients significant to complete improvement in hyperkeratosis, pruritus and pain were observed, along with dose reduction or complete discontinuation of additional systemic treatments and without any recorded side effects. Alefacept should be considered as a therapeutic option for plaque-type PPP. [source] Does gastroesophageal reflux contribute to the development of chronic sinusitis?DISEASES OF THE ESOPHAGUS, Issue 6 2006A review of the evidence SUMMARY., Although recent studies suggest that gastroesophageal reflux disease (GERD) may contribute to a variety of ear, nose and throat and pulmonary diseases, the cause-and-effect relationship for the vast majority remains far from proven. In this article, the evidence supporting a possible causal association between GERD and chronic sinusitis has been reviewed. The evidence would suggest that: (i) a higher prevalence of GERD and a different esophagopharyngeal distribution of the gastric refluxate occurs in patients with chronic sinusitis unresponsive to conventional medical and surgical therapy compared to the general population; (ii) a biologically plausible pathogenetic mechanism exists whereby GERD may result in chronic sinusitis; and (iii) clinical manifestations of chronic sinusitis respond variably to antireflux therapy. While these findings suggest that GERD may contribute to the pathogenesis of chronic sinusitis in some patients, it is apparent that the quality of the evidence supporting each of these three lines of evidence is low and therefore does not conclusively establish a cause-and-effect relationship. A number of unresolved issues regarding prevalence, pathophysiological mechanism, diagnosis and treatment exist that deserve further investigation in order to solidify the relationship between GERD and chronic sinusitis. In conclusion, given the possible relationship between GERD and chronic sinusitis, until more convincing data are available, it may be prudent to investigate for GERD as a potential cofactor or initiating factor in patients with chronic sinusitis when no other etiology exists, or in those whose symptoms are unresponsive to conventional therapies. [source] Progress in the development of new treatments for combined Alzheimer's and Parkinson's diseasesDRUG DEVELOPMENT RESEARCH, Issue 3 2002Eliezer Masliah Abstract Misfolding of synaptic molecules such as amyloid , peptide and ,-synuclein has been proposed to play a key role in the mechanisms of neurodegeneration in Alzheimer's and Parkinson's disease, respectively. Notably, the majority of patients with Alzheimer's disease also have ,-synuclein-immunoreactive Lewy bodies, and a substantial proportion of them develop a form of parkinsonism also known as Lewy body disease, that defies conventional therapies. Thus, factors involved in the pathogenesis of Alzheimer's disease might promote the development of particularly recalcitrant forms of Lewy body disease. We have shown that the amyloid , peptide 1-42, of Alzheimer's disease, promotes the toxic conversion of ,-synuclein and accelerates ,-synuclein-dependent deficits in transgenic mice. Understanding the mechanisms promoting the toxic conversion of ,-synuclein is of critical importance for the design of rationale treatments for Lewy body disease and transgenic models hold the promise for the development of such novel therapies. In this context therapies aimed at: (1) reducing amyloid , peptide 1-42 production, (2) blocking toxic ,-synuclein oligomerization (e.g., ,-synuclein, antioxidants), (3) promoting ,-synuclein protofibril degradation, and (4) protecting neurons (e.g., anti-oxidants, neurotrophic agents) against toxic ,-synuclein aggregates might prove to be significantly useful in the treatment of Lewy body disease. We characterized ,-synuclein, the non-amyloidogenic homologue of ,-synuclein, as an inhibitor of aggregation of ,-synuclein. Our results raise the intriguing possibility that ,-synuclein might be a natural negative regulator of ,-synuclein aggregation, and that a similar class of endogenous factors might modulate the toxic conversion of other molecules involved in neurodegeneration. Such an anti-amyloidogenic property of ,-synuclein in combination with other treatments might also provide a novel strategy for the treatment of neurodegenerative disorders. Drug Dev. Res. 56:282,292, 2002. © 2002 Wiley-Liss, Inc. [source] The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapiesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Anna Porcella Abstract The search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB1) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB1 receptor agonist, WIN 55212,2, applied topically at doses of 25 or 50 µg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 ± 0.5% and 23 ± 0.9%, respectively). A maximal reduction of 20 ± 0.7% and 31 ± 0.6%, respectively, is reached in the first 60 min. These data confirm that CB1 receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB1 receptor agonists should deserve further research and clinical development. [source] Amphiregulin is a factor for resistance of glioma cells to cannabinoid-induced apoptosisGLIA, Issue 13 2009Mar Lorente Abstract Gliomas, one of the most malignant forms of cancer, exhibit high resistance to conventional therapies. Identification of the molecular mechanisms responsible for this resistance is therefore of great interest to improve the efficacy of the treatments against these tumors. ,9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the ability of these compounds to induce apoptosis of tumor cells. By analyzing the gene expression profile of two sub-clones of C6 glioma cells with different sensitivity to cannabinoid-induced apoptosis, we found a subset of genes with a marked differential expression in the two sub-clones. Furthermore, we identified the epidermal growth factor receptor ligand amphiregulin as a candidate factor to mediate the resistance of glioma cells to cannabinoid treatment. Amphiregulin was highly overexpressed in the cannabinoid-resistant cell line, both in culture and in tumor xenografts. Moreover, in vivo silencing of amphiregulin rendered the resistant tumors xenografts sensitive to cannabinoid antitumoral action. Amphiregulin expression was associated with increased extracellular signal-regulated kinase (ERK) activation, which mediated the resistance to THC by blunting the expression of p8 and TRB3,two genes involved in cannabinoid-induced apoptosis of glioma cells. Our findings therefore identify Amphirregulin as a factor for resistance of glioma cells to THC-induced apoptosis and contribute to unraveling the molecular bases underlying the emerging notion that targeted inhibition of the EGFR pathway can improve the efficacy of antitumoral therapies. © 2009 Wiley-Liss, Inc. [source] The therapeutic potential of the proteasome in leukaemia,HEMATOLOGICAL ONCOLOGY, Issue 2 2008Scott Marshall McCloskey Abstract Many cellular processes converge on the proteasome, and its key regulatory role is increasingly being recognized. Proteasome inhibition allows the manipulation of many cellular pathways including apoptotic and cell cycle mechanisms. The proteasome inhibitor bortezomib has enhanced responses in newly diagnosed patients with myeloma and provides a new line of therapy in relapsed and refractory patients. Malignant cells are more sensitive to proteasome inhibition than normal haematopoietic cells. Proteasome inhibition enhances many conventional therapies and its role in leukaemia is promising. Copyright © 2008 John Wiley & Sons, Ltd. [source] Nocturnal Home Hemodialysis: Focus on the PartnerHEMODIALYSIS INTERNATIONAL, Issue 1 2003H Vos Background. Nocturnal home hemodialysis (NHD, 6 times weekly 6,8 hours) results in a better clinical and psychosocial condition of dialysis patients. However, this intensive therapy has important consequences for partners, who bear at least some responsibilities during the treatment. Methods. Since December 2001, we included 15 patients in a Dutch NHD project (,Nocturne'). All patients are assisted by their spouses. An aim of Nocturne is to study the effects of NHD on partners and other family members with questionnaires and interviews by a social worker. Results. NHD affects daily life of partners much more than conventional therapies. Partners feel very involved with the treatment. The invasion of the treatment in bed, the noise and light produced by the machine, the daily assisting of the patient, less freedom, and co-responsibility for the treatment are felt as a burden, specially during the first months of the treatment. However, the improved clinical condition of their spouse, resulting in less fatigue, less disability, less uremic symptoms, less complications, more attention for and contribution to family life, better quality of life and better mood are considered major improvements, with important positive effects for the quality of life of all family members. Additionally, partners consider the fact that they make an important positive contribution to their spouse's health valuable. All partners judged NHD, despite some negative consequences, as a major improvement of their life. Conclusion. The positive effects of NHD are more important than the negative consequences for partners of patients. However, partners need active support by nurses or social workers, specially during the first months of the treatment. [source] Anti tumour necrosis-, therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn's diseaseIMMUNOLOGY, Issue 2 2008Ida Ricciardelli Summary Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-, shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn's disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription,polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF-,, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF-, immunotherapy can also restore mucosal homeostasis in Crohn's disease. [source] Positioning biologic agents in the treatment of Crohn's disease,INFLAMMATORY BOWEL DISEASES, Issue 10 2009Stephen B. Hanauer MD Abstract One decade after the emergence of biologic therapy for Crohn's disease (CD), our treatment algorithms are beginning to change. Once reserved for patients with refractory disease, disease unresponsive to conventional therapies, or those requiring multiple courses of corticosteroids, there is increasing evidence that early, aggressive interventions with immunosuppressants or biologic therapies targeting tumor necrosis factor-, or ,-4 integrins can alter the natural history of CD by reducing the transmural complications of structuring and fistulization and the nearly inevitable requisite for surgical resections. More recent trials are beginning to suggest that intervention with combination therapy for selected patients with a poor prognosis may modify the long-term course of CD. Selection of patients with features predicting a complex or progressive course and early, combined intervention is now possible. Future studies are still needed to best identify predictors of response to individual agents with differing mechanisms of action, as well as to optimize the risk-benefit of long-term maintenance therapy. (Inflamm Bowel Dis 2009) [source] ApoG2, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces apoptosis and suppresses tumor growth in nasopharyngeal carcinoma xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 10 2008Zhe-Yu Hu Abstract Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China. It has been reported that overexpression of antiapoptotic Bcl-2 family proteins in NPC has caused the lack of long-term efficacy of conventional therapies. Apogossypolone (ApoG2), a novel small-molecule inhibitor of antiapoptotic Bcl-2 family proteins, has been discovered as the optimized derivative of gossypol. In this study, we found that in NPC cells, ApoG2 totally blocked the antiapoptotic function of Bcl-2 family proteins without affecting the expression levels of these proteins. ApoG2 selectively inhibited proliferation of 3 NPC cell lines (C666-1, CNE-1 and CNE-2) that highly expressed the antiapoptotic Bcl-2 proteins. This inhibitory activity was associated with release of cytochrome c, activation of caspase-9 and caspase-3 and apoptosis of sensitive NPC cells. However, ApoG2 had no obvious inhibitory effect on NPC cell line HONE-1, which expressed antiapoptotic Bcl-2 and Bcl-xL at a low level. We further found that ApoG2 effectively suppressed tumor growth of NPC xenografts in nude mice and enhanced the antitumor effect of CDDP (cisplatin) on NPC cells in vitro and in vivo. Immunohistochemical results showed that the expression of CD31 decreased after ApoG2 treatment, which suggested inhibition of angiogenesis in NPC xenografts. Our findings strongly suggest that ApoG2 may serve as a novel inhibitor of Bcl-2 family proteins and, by targeting these proteins, may become a promising drug for the treatment of NPC. © 2008 Wiley-Liss, Inc. [source] Antisense oligodeoxynucleotide therapy targeting clusterin gene for prostate cancer: Vancouver experience from discovery to clinicINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2005HIDEAKI MIYAKE Abstract Background The objective of this study was to review our experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy for prostate cancer targeting antiapoptotic gene, clusterin. Methods We initially summarized our data demonstrating that clusterin could be an optimal therapeutic target for prostate cancer, then presented the process of developing AS ODN therapy using several preclinical animal models. Finally, the preliminary data of the recently completed phase I clinical trial using AS clusterin ODN as well as the future prospects of this therapy are discussed. Results Expression of clusterin was highly up-regulated after androgen withdrawal and during progression to androgen-independence, but low or absent in untreated tissues in both prostate cancer animal model systems and human clinical specimens. Introduction of the clusterin gene into human prostate cancer cells confers resistance to several therapeutic stimuli, including androgen ablation, chemotherapy and radiation. AS ODN targeting the translation initiation site of the clusterin gene markedly inhibited clusterin expression in prostate cancer cells in a dose-dependent and sequence-specific manner. Systemic treatment with AS clusterin ODN enhanced the effects of several conventional therapies through the effective induction of apoptosis in prostate cancer xenograft models. Based on these findings, a phase I clinical trial was completed using AS clusterin ODN incorporating 2,-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), showing up to 90% suppression of clusterin in prostate cancer. Conclusions The data described above identified clusterin as an antiapoptotic gene up-regulated in an adaptive cell survival manner following various cell death triggers that helps confer a phenotype resistant to therapeutic stimuli. Inhibition of clusterin expression using AS ODN technology enhances apoptosis induced by several conventional treatments, resulting in the delay of AI progression and improved survival. Clinical trials using AS ODN confirm potent suppression of clusterin expression and phase II studies will begin in early 2005. [source] Cancer stem cells: Cell culture, markers, and targets for new therapiesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2009Candace A. Gilbert Abstract A cancer stem cell (CSC) is defined as an undifferentiated cell with the ability to self-renew, differentiate to multiple lineages and initiate tumors that mimic the parent tumor. In this review, we focus on glioblastomas, describing recent progress and problems in characterizing these cells. There have been advances in CSC culture, but tumor cell heterogeneity has made purification of CSCs difficult. Indeed, it may be that CSCs significantly vary from tumor to tumor. We also discuss the proposal that CSCs are resistant to radiotherapy and chemotherapy and play a major role in repopulating tumors following treatment. To overcome their resistance to conventional therapies, we may be able to use our extensive knowledge of the signaling pathways essential for stem cells during development. These pathways have potential as targets for new glioblastoma therapies. Hence, although there is an ongoing debate on the nature of CSCs, the theory continues to suggest new ideas for both the lab and the clinic. J. Cell. Biochem. 108: 1031,1038, 2009. © 2009 Wiley-Liss, Inc. [source] The use of therapeutic plasmapheresis in the treatment of poisoned and snake bite victims: An academic emergency department's experiencesJOURNAL OF CLINICAL APHERESIS, Issue 4 2006Cuma Yildirim Abstract The objective of this study is to describe the clinical status, procedural interventions, and outcomes of critically ill patients with poisoning and snake bite injuries presenting to a tertiary-care emergency department for treatment with therapeutic plasmapheresis. Records of 20 patients who presented to our academic emergency department over a 2-year period and who underwent plasmapheresis for poisoning or snake bite were retrospectively reviewed. Plasmapheresis was performed using centrifugation technology via an intravenous antecubital venous or subclavian vein catheter access. Human albumin or fresh frozen plasma were used as replacement fluids. Data extracted from the patient record included demographic data, clinical status, and outcome measures. Sixteen patients underwent plasmapheresis because of toxicity from snake bite. Three patients were treated for drug poisoning (phenytoin, theophylline, bipyridene HCl) and one patient for mushroom poisoning. Haematologic parameters such as platelet count, PT, and INR resolved rapidly in victims of snake bite injuries after treatment with plasmapheresis. Loss of limbs did not occur in these cases. Seven patients required admission to the intensive care unit. One patient with mushroom poisoning died. Mean length of hospital stay was 14.3 days (range 3,28 days) for all cases. Plasmapheresis was a clinically effective and safe approach in the treatment of snake bite envenomation and other drug poisoning victims especially in the management of hematologic problems and in limb preservation/salvage strategies. In addition to established conventional therapies, emergency physicians should consider plasmapheresis among the therapeutic options in treatment strategies for selected toxicologic emergencies. J. Clin. Apheresis 2006. © 2006 Wiley-Liss, Inc. [source] Molecular basis of therapeutic approaches to gastric cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2009Kaichun Wu Abstract Gastric cancer is the top lethal cancer in Asia. As the majority of cases present with advanced disease, conventional therapies (surgery, chemotherapy, and radiotherapy) have limited efficacy to reduce mortality. Emerging modalities provide promise to combat this malignancy. Target-protein-based cancer therapy has become available in clinical practice. Numerous molecules have been shown potential to target specific pathways for tumor cell growth. Cyclooxygenase-2 (COX-2) is overexpressed in and correlated with gastric cancer, and knockdown of COX-2 or administration of COX-2 inhibitors suppresses tumor formation in models of gastric cancer. Induction of apoptosis, reduction of angiogenesis, and blocking of potassium ion channels may present new mechanisms of COX-2 inhibition. Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene whose deficiency is causally related to gastric cancer. RUNX3 is downregulated in metastatic gastric cancer. RUNX3 activation inhibits angiogenesis in xenograft tumors in nude mice. Tumor microenvironment modulation also provides a powerful tool to inhibit cancer development and progress; details of the potential roles of angiopoietins are discussed in this review. Osteopontin is a secreted protein involved in stress response, inflammation, wound healing, and immune response. Inhibition of osteopontin by RNA interfering technique suppressed tumorigenesis as well as angiogenesis in gastric cancer. Immunotherapy remains another important choice of adjuvant therapy for cancer. A tumor-specific antigen MG7-Ag has been identified with great potential for inducing immune response in gastric cancer. Using HLA-A-matched allogeneic gastric cancer cells to induce tumor-specific cytotoxic T lymphocytes appeared to be an alternative option of immunotherapy for gastric cancer. [source] Acupuncture for Alcohol Dependence: A Systematic ReviewALCOHOLISM, Issue 8 2009Seung-Hun Cho Background:, Acupuncture has been used in the treatment of substance-related disorders for the past 30 years. However, a systematic review to assess the effect of various types of acupuncture for alcohol dependence has not yet been performed. The present systematic review assessed the results of randomized controlled trials (RCTs). Methods:, Nineteen electronic databases, including English, Korean, Japanese, and Chinese databases, were systematically searched for RCTs of acupuncture for alcohol dependence up to June 2008 with no language restrictions. The methodological qualities of eligible studies were assessed using the criteria described in the Cochrane Handbook. Results:, Eleven studies, which comprised a total of 1,110 individual cases, were systematically reviewed. Only 2 of 11 trials reported satisfactorily all quality criteria. Four trials comparing acupuncture treatment and sham treatments reported data for alcohol craving. Three studies reported that there were no significant differences. Among 4 trials comparing acupuncture and no acupuncture with conventional therapies, 3 reported significant reductions. No differences between acupuncture and sham treatments were found for completion rates (Risk Ratio = 1.07, 95% confidence interval, CI = 0.91 to 1.25) or acupuncture and no acupuncture (Risk Ratio = 1.15, 95% CI = 0.79 to 1.67). Only 3 RCTs reported acupuncture-related adverse events, which were mostly minimal. Conclusions:, The results of the included studies were equivocal, and the poor methodological quality and the limited number of the trials do not allow any conclusion about the efficacy of acupuncture for treatment of alcohol dependence. More research and well-designed, rigorous, and large clinical trials are necessary to address these issues. [source] Current issues for nurse practitioners: HyponatremiaJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 11 2007Ruth Haskal NP-C (Adult Nurse Practitioner) Abstract Purpose: To review the assessment, diagnosis, and management of hyponatremia (serum sodium <135 mEq/L), the most common electrolyte disturbance as a result of dysregulation of water balance in hospitalized or institutionalized patients. Data sources: Comprehensive search using keywords AVP receptor antagonists, hyponatremia, SIADH, conivaptan, tolvaptan, lixivaptan, nurse practitioner, and others was carried out using the National Library of Medicine (PubMed) Web site from which full-text articles were obtained. Meeting abstracts were obtained from scientific sessions including the American Society of Nephrology Renal Week 2004 and the Endocrine Society,s 87th Annual Meeting (2005). The Vaprisol (conivaptan hydrochloride injection) package insert was referenced and obtained from FDA.gov. Conclusions: A diagnosis of hyponatremia requires thorough investigation for underlying causes and prompt treatment to prevent poor patient outcomes. In clinical trials, a new class of drugs called the arginine vasopressin (AVP) receptor antagonists or aquaretics has been shown to be safe and effective for the treatment of hyponatremia. Among this class of agents, intravenous conivaptan hydrochloride, indicated for the treatment of euvolemic hyponatremia in hospitalized patients, is the first drug in class approved for use. Implications for practice: Elderly patients, and those with certain conditions such as heart failure, tuberculosis, cirrhosis, and head injury, may be at increased risk for hyponatremia. In hospitalized patients following surgery and the use of certain medications, hyponatremia is a common condition. A thorough understanding of the physiology of water balance and the risk factors associated with hyponatremia is essential for prompt and effective intervention. Awareness of the limitations of conventional therapies and the availability of new treatment options for hyponatremia allows clinicians to optimize patient care. [source] Extracorporeal photochemotherapy in patients with cutaneous T-cell lymphoma: is clinical response predictable?JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 9 2006V Rao Abstract Background, Extracorporeal photochemotherapy (ECP) has been accepted as a standard therapy in cutaneous T-cell lymphomas (CTCL), a category of lymphomas mainly resistant to conventional therapies. Approximately one half of patients demonstrate a reduction in skin affliction by at least 50% within 12 months of therapy and are categorized as responders to ECP. Predictive criteria for selecting patients who will respond to ECP are lacking. Such criteria would however, be of great benefit. Objectives, This study compared T-cell clonality and serum levels of soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase (LD), neopterin, beta2-microglobulin (,2 -M) and granzyme B in CTCL patients in order to evaluate their potential usefulness as predictive markers. Patients/methods, Serum and T lymphocytes obtained from 16 patients with CTCL receiving ECP treatment were evaluated in an open retrospective study. Results, We found no evident correlation between detected T-cell clonality and response to ECP. The non-responding group had on average a higher level of serum sIL-2R. This difference was significant after 6 and 12 months of therapy, but not pretreatment. An individual reduction in serum sIL-2R, neopterin and ,2 -M during a 6-month course of ECP was well correlated to clinical remission. Conclusions, Seven out of 16 patients were classified as responders. Neither T-cell clonality nor any of the serum markers assessed pretreatment could reliably predict the response to ECP treatment. However, the individual relative changes in sIL-2R, neopterin and ,2 -M during 6 months of ECP treatment coherently displayed correlation to the clinical response, as assessed after 12 months of ECP treatment. [source] IPL technology: A reviewLASERS IN SURGERY AND MEDICINE, Issue 2 2003Christian Raulin MD Abstract Background and Objectives Intense pulsed light (IPL) systems are high-intensity light sources, which emit polychromatic light. Unlike laser systems, these flashlamps work with noncoherent light in a broad wavelength spectrum of 515,1,200 nm. These properties allow for great variability in selecting individual treatment parameters and adapting to different types of skin types and indications. The purpose of this article was to critically review international medical publications of the many indication in which IPL technology can be used, including our own evaluations and experiences. Study Design/Materials and Methods The range of therapeutic uses for high-intensity flashlamps was reviewed, ranging from benign cavernous hemangiomas, benign venous malformations, essential telangiectasias, leg telangiectasias, poikiloderma of Civatte, and port-wine stains to pigmented lesions, cosmetically undesired hypertrichosis, and facial rhydids. The relative benefits and risks were discussed in detail and compared with other laser systems. Results Because of the wide spectrum of potential combinations of wavelengths, pulse durations, pulse frequency, and fluences, a great deal of experience is required when using IPL technology. Proper patient selection and critical diagnostics serve to keep the adverse effects of the treatment to a minimum. Conclusions The distinctive technical conditions involved combine to make IPL technology an alternative and auxiliary treatment option to existing laser systems and conventional therapies. Lasers Surg. Med. 32:78,87, 2003. © 2003 Wiley-Liss, Inc. [source] Evaluation of the cost-effectiveness of Helicobacter pylori eradication triple therapy vs. conventional therapy for ulcers in JapanALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2001S. Ikeda Background: Helicobacter pylori eradication triple therapy with a combination of lansoprazole, amoxicillin and clarithromycin was approved in Japan in September 2000. Aim: To compare the cost-effectiveness of this eradication therapy with conventional histamine-2 receptor antagonist therapy in Japan. Methods: We established two Markov models for gastric and duodenal ulcers. The model design was based on the Japanese H. pylori eradication guideline and a specialist's opinions, and the model inputs were obtained from a literature review. The models predict the direct medical costs, number of disease-free days and cost per disease-free day for 5 years. Results: In the gastric ulcer model, the expected total costs of eradication and conventional therapies per patient were ¥169 719 and ¥390 921, respectively; the expected numbers of disease-free days were 1454 days and 1313 days, respectively. In the duodenal ulcer model, the expected total costs were ¥134 786 and ¥324 689, respectively; the expected numbers of disease-free days were 1503 days and 1387 days, respectively. The sensitivity analyses showed that the results of the base case analysis were robust. Conclusions: This eradication therapy is less costly and more effective than conventional therapy for the treatment of gastric and duodenal ulcers in a Japanese medical setting. [source] Oral tacrolimus long-term therapy in patients with Crohn's disease and steroid resistanceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2001E. Ierardi To report the results of a prospective, open-label, uncontrolled study in 13 patients affected by Crohn's disease with resistance to steroids. Methods: The patients were treated long-term with oral tacrolimus, aiming to both resolve acute attacks and maintain remission. Tacrolimus was administered at the dose of 0.1,0.2 mg.day/kg and adjusted in order to achieve levels of 5,10 ng/mL; only mesalazine was continued concomitantly. Steroids and total parenteral nutrition were tapered when appropriate. Results: Median treatment was 27.3 months. Only one patient dropped out due to adverse events. Crohn's disease activity index score significantly decreased after 6 months in 11 patients; for 1 year in nine of them, and 7 years in two of them. The inflammatory bowel disease life-quality questionnaire score significantly increased over the same periods. A marked drop in hospitalizations was recorded. In three out of six patients complete closure of fistulas occurred. Tacrolimus allowed total parenteral nutrition to be withdrawn in three out of five patients. Supplementation with low-dose steroids was required in five patients. Two patients underwent surgery. Conclusions: Tacrolimus therapy appears to be associated with both short- and long-term benefits, and may represent a therapeutic option in Crohn's disease when conventional therapies fail. This study encourages its use in controlled trials. [source] Review article: the clinical role of anti-TNF, antibody treatment in Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2000The recent licensing of anti-TNF, antibody treatment offers the potential to radically alter the course of severe Crohn's disease using genetically-engineered drugs directed against a specific inflammatory mediator. Controlled randomized trials have demonstrated clinical benefit associated with tissue healing in patients with active intestinal disease and fistulae, often when conventional therapies were unsuccessful. This therapy is expensive, however, and long-term efficacy and safety data are still awaited. This review considers the nature of this therapy and the current evidence for its clinical benefit and adverse effects. The treatment is also considered in the context of available immunosuppressive agents, with suggestions about its practical application. [source] Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict responseALLERGY, Issue 5 2009H.-W. Park Background:, Recent findings have raised new interests about the use of anticholinergics, especially tiotropium, for the treatment of asthma. This study was performed to determine whether an additional improvement in lung function is obtained when tiotropium is administrated in addition to conventional therapies in severe asthmatics, and to identify factors capable of predicting the response to tiotropium, using a pharmacogenetic approach. Methods:, A total of 138 severe asthmatics on conventional medications and with decreased lung function were randomly recruited. Tiotropium 18 ,g was added once a day and lung functions were measured every 4 weeks. Responders were defined as those with an improvement of ,15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was maintained for at least 8 successive weeks. Eleven single nucleotide polymorphisms (SNPs) in CHRM1,3 (coding muscarinic receptors one to three) which were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding ,2 adrenoreceptor) were scored in 80 of the 138 asthmatics. Results:, Forty-six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic regression analyses (controlled for age, gender, and smoking status) showed that Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07,0.59) in a minor allele,dominant model] was significantly associated with response to tiotropium. Conclusions:, As many as 30% of severe asthmatics on conventional medications with reduced lung function were found to respond to adjuvant tiotropium. The presence of Arg16Gly in ADRB2 may predict response to tiotropium. [source] Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointmentPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2p1 2010N. Doss Doss N, Kamoun M-R, Dubertret L, Cambazard F, Remitz A, Lahfa M, de Prost Y. Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointment. Pediatr Allergy Immunol 2010: 21: 321,329. © 2009 John Wiley & Sons A/S Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2,15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of ,60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was ,11.8%, exceeding the non-inferiority limit of ,15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 ± 5.0 and 8.6 ± 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep. [source] Hematopoietic stem cell transplantation in Langerhans cell histiocytosis: Case report and review of the literaturePEDIATRIC TRANSPLANTATION, Issue 3 2009Vural Kesik Abstract:, The prognosis in children with LCH who do not respond to the conventional therapies is very poor. SCT may be a new approach. However, there are limited data about the results of the transplantations. Herein we report a patient with refractory multisystem LCH who underwent allogeneic bone marrow transplantation and is disease and treatment free 54 months after transplantation. Further studies are required to establish the role of SCT in refractory LCH. [source] Interferon-alpha therapy in idiopathic thrombocytopenic purpuraPEDIATRICS INTERNATIONAL, Issue 6 2001Bunyamin Dikici AbstractBackground: Acute idiopathic thrombocytopenic purpura (ITP) represents the most frequent hemorrhagic diathesis in childhood. Up to 30% of patients with ITP are regarded as refractory to standard therapy. The rare mortality from acute ITP in childhood is almost exclusively due to intracranial hemorrhage. This complication occurs in less than 1% of ITP patients. This study was designed to evaluate the effect of ,-interferon (IFN-,) in eight patients whom did not respond to conventional therapy. Method: In spite of conventional therapies, the patient whose platelet count could not be increased to 50`109/L were accepted as refractory ITP. Eight of these patients whose platelet count lower than 20`109/L were included in the prospective cohort study. Interferon alpha 2b 5 MU/m2 was administered subcutaneously three times a week, totalling 12 times in a month. According to the platelet count on the 28th day of therapy, we grouped the patients into three categories. After 60 days, the survey was re-evaluated according to the platelet count. Results: The mean age of children was 3.5±2.5 (ranged between 3.5 and 9) years. Six of them were boys and two were girls. There was no response in one patient, partial response in one, and good response in six patients on the 28th day of therapy. The maximum rise in platelet count was observed from 7 to 14 days after the initiation of interferon. The median platelet count which was 15±5`109/L before therapy, raised to 60±12`109/L after therapy. However, on the 60th day of therapy, there were only two patients who had a platelet count over 100`109/L. Conclusion: In our study, we did not observe the long-term benefit of IFN-, therapy in refractor ITP in childhood. However, in good responding patients, platelet levels were increased in a short time. Alpha-interferon may be alternative therapy for patients whom had a platelet count below 20`109/L and not responding to standard therapy, or for patients whom immunosuppressive therapy is contraindicated. [source] | |||||||||||||||||||||||||||||||||||||||||||