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Local Treatment (local + treatment)
Selected AbstractsMelatonin protects against pressure ulcer-induced oxidative injury of the skin and remote organs in ratsJOURNAL OF PINEAL RESEARCH, Issue 3 2006Göksel Abstract:, Pressure ulcers (PU) cause morphological and functional alterations in the skin and visceral organs; the damage is believed to be due to ischemia/reperfusion (I/R) injury. In this study, we examined the role of oxidative damage in PU and the beneficial effect of treatment with the antioxidant melatonin. PU were induced by applying magnets over steel plates that were implanted under the skin of rats; this compressed the skin and caused ischemia. Within a 12-hr period, rats were subjected to five cycles of I/R (2 and 0.5 hr respectively), followed by an additional 12 hr of ischemia (to simulate the period at sleep at night). This protocol was repeated for 3 days. In treatment groups, twice a day during reperfusion periods, melatonin (5 mg per rat) was either applied locally as an ointment on skin, or administered i.p. (10 mg/kg). At the end of the experimental period, blood and tissue (skin, liver, kidney, lung, stomach, and ileum) samples were taken for determination of biochemical parameters and for histological evaluation. Local treatment with melatonin inhibited the increase in malondialdehyde levels; an index of lipid peroxidation, myeloperoxidase activity; an indicator of tissue neutrophil infiltration, and the decrease in glutathione; a key antioxidant, in the skin induced by PU, but was less efficient in preventing the damage in visceral organs. However, systemic treatment prevented the damage in the visceral organs. Significant increases in creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and collagen levels in animals with PU were prevented by melatonin treatment. The light microscopic examination exhibited significant degenerative changes in dermis and epidermis in the PU rats. Tissue injury was decreased especially in the locally treated group. Findings of the present study suggest that local and/or systemic melatonin treatment may prove beneficial in the treatment of PU. [source] 4261: FNA biopsies for genomic analysis and adjuvant therapy for uveal melanomaACTA OPHTHALMOLOGICA, Issue 2010L DESJARDINS Purpose Recent changes in the management of uveal melanoma include the use of biopsies for genomic analysis and the identification of patients with a high risk of metastasis. We wish to describe our first experience with fine needle aspiration (FNA), genome profiling and adjuvant therapy protocol for high risk patients Methods we have started a multicentric adjuvant phase III trial of intravenous fotemustine (FOTEADJ) for high risk uveal melanoma patients. Patients with tumor of 15 mm or more in diameter with retinal detachment or extrascleral extension, patients with tumors of 18 mm or more in diameter and patients with loss of chromosome 3 and gain of entire 8q were considered high risk and eligible. Tumour genome profiling was achieved by array-CGH on a NimbleGen 72K microarray, after whole genome amplification (WGA) in cases of FNAs Local treatment consisted in enucleation or proton beam radiotherapy. FNA was offered to patients treated by radiotherapy for a tumor of 5 mm of thickness or more. Results Between May 2009 and May 2010, 74 patients were offered to participate. Only 16 patients were included because of various reasons: technical problems with the biopsy (13 samples evaluable out of 26 FNA), refusal of the biopsy or the protocol or non inclusion criteria. There has been some improvement in our results since the introduction of WGA for FNA specimens Conclusion Proposing fine needle aspiration biopsy and obtaining sufficient material is not always easy. Including patients in randomized protocols is always a challenge. During the first year for FOTEADJ, only 22% of the eligible patients were enrolled but this percentage is greatly improving with time and experience . [source] Local treatment of empyema in children: a systematic review of randomized controlled trialsACTA PAEDIATRICA, Issue 10 2010Katarzyna Krenke Abstract The aim of the study is to systematically evaluate data from randomized controlled trials (RCTs) on the efficacy of using intrapleural fibrinolytic agents in the treatment of complicated parapneumonic effusions or empyema in children. The Cochrane Library, MEDLINE and EMBASE databases were searched in July 2009. Four RCTs, involving 194 children, were included. In two RCTs, intrapleural fibrinolytic treatment was compared with normal saline. One of these RCTs showed a significantly reduced hospital stay in those treated with urokinase compared with those treated with normal saline. Otherwise, no fibrinolytic agent had an effect on any other outcome. Two RCTs that compared fibrinolytic treatment with video-assisted thoracoscopic surgery (VATS) revealed no benefit of VATS. Conclusion:, There is little evidence that intrapleural fibrinolysis is more effective than normal saline in the local treatment of complicated parapneumonic effusions or empyema in children. There is no evidence that VATS is more effective than fibrinolytic treatment. Only a limited number of trials were available for analysis, so some caution must be exercised in interpreting the strength of the evidence presented. [source] Psoriasiform skin lesion and supprative acrodermatitis associated with Kawasaki disease followed by the treatment with infliximab: a case reportACTA PAEDIATRICA, Issue 7 2010S Kishimoto Abstract A 4-month-old boy was diagnosed with Kawasaki disease. The ordinary treatments with intravenous gammaglobulin and metylpredonisolone were not effective. Infliximab (5 mg/kg) was administrated on 13th day of illness which led to defeverscence and improvement of clinical manifestations. On 23 days of illness, however, desquamative papules and plaques developed on both the extensor surfaces of the forearms and legs. In addition, typical subungual desquamations of fingers and toes followed crusted hyperkeratosis which resembled supprative acrodermatitis. Skin biopsy from the forearm showed inflammatory dyskeratosis with marked hyperkeratosis, epithelial parakeratotsis, loss of granular layer and dominant infiltration of CD8 + T-cells. Local treatment of steroid followed improvement of skin lesions within a few weeks. Conclusion:, Although previous reports described the beneficial effects of infliximab in patients with Kawasaki disease, it is possible that the administration of infliximab modify psoriasiform skin lesion associated with Kawasaki disease. [source] Bisphosphonate-related osteonecrosis of the jaw and its associated risk factors: A belgian case seriesTHE LARYNGOSCOPE, Issue 2 2009Sven Saussez MD Abstract Objectives: Bisphosphonate-related osteonecrosis of the jaw (BROJ) is a serious oral complication of bisphosphonate (BP) treatment involving the exposure of necrotic maxillary or mandibular bone. Our purpose is to describe the clinical presentation of 34 cases of BROJ and to identify potential risk factors. Study Design: A retrospective study was performed in four Belgian institutions. Methods: Complete medical histories were recorded and analyzed. These data include age, gender, initial disease requiring BP, type and duration of BP treatment, symptomatology and location of BROJ, prior dental procedures, treatment of the BROJ and treatment outcome, and radiographic, histological, and microbiological data. Results: Bisphosphonates (BP) were used in the management of disseminated cancers in 30 patients (88.5% of total studied), while four patients received BP due to osteoporosis (11.5%). The most frequently used BP was zoledronic acid in 29 patients (83%). Microbiological data obtained in 25 patients demonstrated that 72% of these patients were infected or colonized by an actinomyces. Eight of the 14 patients (57%) who received only medical treatment were cured. Of the 20 patients who underwent surgical treatments, only four were completely cured (20%). BROJ lesions smaller than 1 cm are associated with better prognosis in terms of treatment outcomes (P = .0009). Local treatments combined with long-term antibiotics are also correlated with better prognosis (P = .02). Conclusions: Lesions smaller than 1 cm and lesions that were subject to medical treatments are associated with a better outcome. Surgical treatments appear to be non-beneficial for BROJ. Laryngoscope, 119:323,329, 2009 [source] Sensitivity to Myroxylon pereirae resin (balsam of Peru).CONTACT DERMATITIS, Issue 6 2005A study of 50 cases The Myroxylon pereirae resin (MP; balsam of Peru) is a natural resin used in the local treatment of burns and wounds. M. pereirae extracts and distillates are very often contained in a wide range of cosmetic products and causes frequently allergic contact dermatitis , to the extent of being considered an allergy marker to perfumes. We have carried out a retrospective study of 863 patients who have been submitted to patch tests from January 2002 to June 2004. A total of 50 patients were positive to MP. Thus, the prevalence was 5.79%, slightly higher in men (7.32%) than in women (4.91%). The positive patch tests were relevant in 64%. Over the last years, it appears that there is a clear increase of the prevalence of the sensitization to MP in all the studies published. We observe an increase of the prevalence especially in aged patients, where the sensitization is linked with the use of topical medications secondary to stasis dermatitis. The high frequency of allergy to MP in our area might be associated with manipulation of citrus fruits. The increasing use of cosmetic products by the male population can also be held responsible for the higher sensitization rate in this group of patients. [source] Injectable Hyaluronic Acid Implant for Malar and Mental EnhancementDERMATOLOGIC SURGERY, Issue 7 2006FRCP, NICHOLAS J. LOWE MD BACKGROUND The use of a thicker injectable implant version of one of the hyaluronic acid dermal fillers (Restylane SubQ, Q-Med, Uppsala, Sweden) is described. OBJECTIVE A group of treated patients has been studied for more than 1 year. Restylane SubQ was injected to the submuscular plane of the upper cheeks and chin to observe efficacy of augmentation and side effect profile, and further observations were made of the duration of benefit. METHODS Patient details,72 patients were treated, 68 for upper cheek augmentation, 2 for chin augmentation, and 2 for both areas. Four patients received second injections 8 weeks after the first to increase augmentation. RESULTS Patients all showed a persistence of benefit during the posttreatment observation period of up to 64 weeks. Four patients had minor side effects that resolved with local treatment and time. Four patients had second injections to complete augmentation without complications. CONCLUSIONS Restylane SubQ is a useful injectable agent to augment and lift upper cheeks and recontour chins. Further efficacy studies seem justified. [source] ENDOSCOPIC DIAGNOSIS OF INTRAEPITHELIAL SQUAMOUS NEOPLASIA IN HEAD AND NECK AND ESOPHAGEAL MUCOSAL SITESDIGESTIVE ENDOSCOPY, Issue 2006Manabu Muto In the multistep process of squamous epithelial carcinogenesis, squamous epithelial dysplasia has been considered to be a preinvasive stage of squamous cell carcinoma. If we could distinguish a dysplasia at high risk, such lesions could be targets for local treatment such as endoscopic mucosal resection to avoid the transformation to invasive carcinoma. Narrow-band imaging, a new optical technology, is useful to identify the cancerous lesion compared to conventional white light image. In addition, narrow-band imaging combined with magnifying endoscopy makes it possible to visualize the changes of microvascular architecture occurring in the epithelium. To evaluate whether these endoscopic findings are reliable to diagnose a dysplasia at high risk, a prospective study on the basis of the standards for reporting diagnostic accuracy initiative is needed. If endoscopic assessment of intraepithelial squamous neoplasia is reliable, it would be of benefit to the patients' outcome and improve cost effectiveness of care because of the avoidance of developing invasive carcinoma and the reduction of unnecessary biopsies. [source] Cutaneous head and neck squamous cell carcinoma metastatic to parotid and cervical lymph nodesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2007FRANZCR, Michael J. Veness MMed (Clin Epi) Abstract Nonmelanoma skin cancers occur at an epidemic rate in Australia and are increasing in incidence worldwide. In most patients, local treatment is curative. However, a subset of patients will be diagnosed with a high-risk cutaneous squamous cell carcinoma (SCC) and are defined as patients at increased risk of developing metastases to regional lymph nodes. Patients with high-risk SCC may be identified based on primary lesion and patient factors. Most cutaneous SCC arises on the sun-exposed head and neck. The parotid and upper cervical nodes are common sites for the development of metastases arising from ear, anterior scalp, temple/forehead, or scalp SCC. The mortality and morbidity associated with high-risk cutaneous SCC is usually a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Patients with operable nodal disease have traditionally been recommended for surgery. The efficacy of adjuvant radiotherapy has previously been questioned based on weak evidence in the early literature. Recent evidence from larger studies has, however, strengthened the case for adjuvant radiotherapy as a means to improve locoregional control and survival. Despite this, many patients still experience relapse and die. Research aimed at improving outcome such as a randomized trial incorporating the addition of chemotherapy to adjuvant radiotherapy is currently in progress in Australia and New Zealand. Ongoing research also includes the development of a proposed new staging system and investigating the role of molecular factors such as the epidermal growth factor receptor. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double-blind, phase III study in North America,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2003Dan J. Castro MD Abstract Background. The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods. Eighty-seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double-blind study. Tumors were ,20 cm3; most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. Dose: 0.25 mL CDDP/epi gel/cm3 tumor volume. Treatments: ,6 weekly intratumoral injections in an 8-week period. Primary outcomes: target tumor response and symptom relief. Results. During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p < .001). Responses occurred within a median of four treatments (range, 2,6) and were durable (median, 95 days; range, 34,168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p = .036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3,12 weeks. Renal and hematologic toxicities were rare. Conclusions. This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor-related symptoms, and is an effective local treatment for recurrent tumors. © 2003 Wiley Periodicals, Inc. Head Neck 25: 717,731, 2003 [source] Evidence-based clinical practice guidelines for renal cell carcinoma (Summary , JUA 2007 Edition)INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2009Tomoaki Fujioka Abstract: The text of these guidelines was published for general clinicians, general urologists, and patients, with the aim of providing a system of effective and efficient clinical practices for managing renal cell carcinoma based on evidence-based medicine,intended techniques. The guidelines contain the answers to a total of 21 clinical questions (CQ) that were formulated under the headings of ,risk factors and prophylaxis,',diagnosis,',surgical treatment and local treatment,' and ,systemic treatment,' along with the recommendation grades and systems/algorithms for clinical practice based on structured abstracts prepared through critical reviews of the relevant published reports; the literature search was conducted using the key words for each CQ. An abridged edition of these guidelines can be found on the web pages of the Japan Society of Clinical Oncology and the Medical Information Network Distribution Service. [source] Ultrasonographic assessment of Baker's cysts after intra-articular corticosteroid injection in knee osteoarthritisJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2006J. Carlos Acebes MD Abstract Purpose: To assess sonographic changes in Baker's cysts (BCs) of patients with knee osteoarthritis after a single intra-articular corticosteroid injection. Methods: Thirty patients with knee osteoarthritis complicated with a symptomatic BC received a single intra-articular injection of 40 mg triamcinolone acetonide. Knee pain, swelling, and range of motion were evaluated. BC area and thickness of the cyst wall were measured with sonography before and 4 weeks after local treatment. Results: A significant improvement in knee pain, swelling, and range of motion after corticosteroid injection was accompanied by a decrease in size of the BCs as well as in thickness of the cyst wall as measured by sonography. Moreover, the reduction of BC area on sagittal scans after treatment was significantly correlated with the improvement in range of motion. Conclusions: In this series of osteoarthritis patients, injection of corticosteroids inside the knee joint accounted for a reduction in BC dimensions as well as cyst wall thickness. Sonography can be used not only for the diagnosis of BCs but also to monitor response to therapy. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:113,117, 2006 [source] Reduced age-related plasticity of neurotrophin receptor expression in selected sympathetic neurons of the ratAGING CELL, Issue 1 2003T. Cowen Summary Selective vulnerability of particular groups of neurons is a characteristic of the aging nervous system. We have studied the role of neurotrophin (NT) signalling in this phenomenon using rat sympathetic (SCG) neurons projecting to cerebral blood vessels (CV) and iris which are, respectively, vulnerable to and protected from atrophic changes during old age. RT-PCR was used to examine NT expression in iris and CV in 3- and 24-month-old rats. NGF and NT3 expression in iris was substantially higher compared to CV; neither target showed any alterations with age. RT-PCR for the principal NT receptors, trkA and p75, in SCG showed increased message during early postnatal life. However, during mature adulthood and old age, trkA expression remained stable while p75 declined significantly over the same period. In situ hybridization was used to examine receptor expression in subpopulations of SCG neurons identified using retrograde tracing. Eighteen to 20 h following local treatment of iris and CV with NGF, NT3 or vehicle, expression of NT receptor protein and mRNA was higher in iris- compared with CV-projecting neurons from both young and old rats. NGF and NT3 treatment had no effect on NT receptor expression in CV-projecting neurons at either age. However, similar treatment up-regulated p75 and trkA expression in iris-projecting neurons from 3-month-old, but not 24-month-old, rats. We conclude that lifelong exposure to low levels of NTs combined with impaired plasticity of NT receptor expression are predictors of neuronal vulnerability to age-related atrophy. [source] Treatment recommendations in patients diagnosed with high-risk cutaneous squamous cell carcinomaJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 5 2005MJ Veness Summary Non-melanoma cutaneous cancers occur at an epidemic rate in Australia. With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high-risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high-risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature. [source] Involvement of nerve injury and activation of peripheral glial cells in tetanic sciatic stimulation-induced persistent pain in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2010Lingli Liang Abstract Tetanic stimulation of the sciatic nerve (TSS) produces long-lasting pain hypersensitivity in rats. Long-term potentiation (LTP) of C- and A-fiber-evoked field potentials in the spinal cord has been explored as contributing to central sensitization in pain pathways. However, the peripheral mechanism underlying TSS-induced pain hypersensitivity remains largely unknown. We investigated the effect of TSS on peripheral nerve and the expression of activating transcription factor 3 (ATF3) in dorsal root ganglion (DRG) as a marker of neuronal injury. TSS induced a mechanical allodynia for at least 35 days and induced ATF3 expression in the ipsilateral DRG. ATF3 is colocalized with NF200-labeled myelinated DRG neurons or CGRP- and IB4-labeled unmyelinated ones. Furthermore, we found that TSS induced Wallerian degeneration of sciatic nerve at the level of myelinisation by S100 protein (to label Schwann cells) immunohistochemistry, luxol fast blue staining, and electron microscopy. TSS also elicited the activation of satellite glial cells (SGCs) and enhanced the colocalization of GFAP and P2X7 receptors. Repeated local treatment with tetrodotoxin decreased GFAP expression in SGCs and behavioral allodynia induced by TSS. Furthermore, reactive microglia and astrocytes were found in the spinal dorsal horn after TSS. These results suggest that TSS-induced nerve injury and glial activation in the DRG and spinal dorsal horn may be involved in cellular mechanisms underlying the development of persistent pain after TSS and that TSS-induced nerve injury may be used as a novel neuropathic pain model. © 2010 Wiley-Liss, Inc. [source] Locally delivered rhTGF-,2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injuryJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2001Dr. Sumner The purposes of the present study were to determine if recombinant human transforming growth factor-beta-2 (rhTGF-,2) enhances bone ingrowth into porous-coated implants and bone regeneration in gaps between the implant and surrounding host bone. The implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs in the presence of a 3-mm gap. In three treatment groups of animals, the test implant was treated with hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF-,2 in buffer at a dose per implant of 1.2 ,g (n = 6), 12 ,g (n = 7), or 120 ,g (n = 7) and placed in the left humerus. In these same animals, an internal control implant treated only with HA/TCP and buffer was placed in the right humerus. In a non-TGF-, treated external control group of animals (n = 7), one implant was treated with HA/TCP while the contralateral implant was not treated with the ceramic. In vitro analyses showed that approximately 15% of the applied dose was released within 120 h with most of the release occurring in the first 24 h. The TGF-, treated implants had significantly more bone ingrowth than the controls with the greatest effect in the 12 ,g/implant group (a 2.2-fold increase over the paired internal control (P = 0.004) and a 4-fold increase over the external control (P < 0.001)). The TGF-, treated implants had significantly more bone formation in the gap than the controls with the greatest effect in the 12 and 120 ,g groups (1.8-fold increases over the paired internal controls (P = 0.003 and P = 0.012, respectively) and 2.8-fold increases over the external controls (P < 0.001 and P = 0.001, respectively)). Compared to the external controls, the internal control implants tended to have more bone ingrowth (1.9-fold increase, P = 0.066) and had significantly more bone formation in the gap (1.7-fold increase, P = 0.008). Thus, application of rhTGF-,2 to a porous-coated implant-stimulated local bone ingrowth and gap healing in a weakly dose-dependent manner and stimulated bone regeneration in the 3-mm gap surrounding the contralateral control implant, a site remote from the local treatment with the growth factor. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Inflammatory Pain Reduction In Rats By Local Treatment With oATP, A Selective Inhibitor Of P2X7 ATP ReceptorJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001G Dell'Antonio Peptide neurotransmitters, as substance P or ATP, are released during inflammatiory processes by the nerve endings of sensory fibers. ATP is also released from the cytoplasm of damaged cells at the site of inflammation. It acts at the level of many P2X subtypes of purinoreceptors. The receptor for extracellular ATP named P2Z/P2X7 is selectively blocked by the periodate oxidized ATP (oATP). We have hypothesized that P2X subunits present on peripheral sensory nerve terminals, able to initiate a nociceptive signal, could be blocked by local treatment with oATP, so inducing pain relief. Male inbred Fisher rats weighing about 250 g were used. Unilateral inflammation into rat hind paw was induced by intraplantar injection of Freund's complete adjuvant (FCA). The following signs of inflammation, from 3 to 48 h after FCA injection, were detected: increased paw volume, increased paw temperature and hyperalgesia. The latter was evaluated using an algesiometric test wich measured the paw pressure threshold (PPT, expressed in g). We treated some rats, bearing paw inflammation by 12 h, with local injection of 56 ,M oATP. We showed a significant reduction of hyperalgesia in treated rats (PPT = 190 ± 2.3 in inflamed paw of oATP treated vs. PPT = 60 ± 1.6 in inflamed paw of untreated rats, at 60 min following oATP innoculation). We showed also that treatment with oATP was more efficient than treatment with diclofenac in reducing local inflammatory pain (PPT expressed as percentage of the maximum possible effect = 60 ± 0.5, at 120 min following intraplantar administration of oATP, vs. 25 ± 1.9 at the same time following intraplantar administration of diclofenac). The use of polyclonal antibody anti P2X7 receptor to perform immunohistochemical analysis of inflamed tissue, showed a reduction of receptor expression at the level of nerve endings in sections obtained from rat paw treated with oATP with respect to sections obtained from untreated rats. Such an effect was independent on the recruitment of immunocytes in inflamed tissue. Our results demonstrate that ATP exerts a key role in the pathophysiology of peripheral inflammation and that oATP may be effective in treating inflammatory pain. [source] Preinvasive and invasive cervical cancer: an ex vivo proton magic angle spinning magnetic resonance spectroscopy studyNMR IN BIOMEDICINE, Issue 3 2004Marrita M. Mahon Abstract The aim of this study was to obtain 1H MR spectra using magic angle spinning (MAS) techniques from punch biopsies (<20,mg) of preinvasive and invasive cervical disease and to correlate the spectral profiles with sample classification on the basis of histopathology. Tissue samples were obtained at colposcopic examination, during local treatment of cervical intraepithelial neoplasia (CIN) or at hysterectomy. 1H MAS MRS was performed at 25°C while spinning the sample at 4.5,kHz. After measurement, the tissue was immersed in formalin and the pathology determined. Histological examination after 1H MAS MRS defined 27 samples with squamous cell carcinoma (SCC), 12 with CIN and 39 with only normal tissue. The standardized integrals of the lipid, choline and creatine regions of the spectra were significantly higher in SCC than in normal or CIN tissue. There was no obvious difference in the standardized integral of the region 4.15,3.5,ppm. The acyl fatty acid side-chain length was longer or less unsaturated in SCC than in normal tissue. Normal tissue from patients with SCC showed significantly higher triglycerides than normal tissue from patients with benign uterine disease but significantly lower triglycerides than SCC tissue. 1H MAS MRS of the uterine cervix ex vivo may be used to differentiate non-invasive from invasive cervical lesions, increase interpretation of in vivo MRS and provide insights into tumor biology. Copyright © 2004 John Wiley & Sons, Ltd. [source] Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2003Peter Meyer Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 µg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and ,2 -macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of ,2 -macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in ,2 -macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects. [source] Benign pineal cysts in children with bilateral retinoblastoma: A new variant of trilateral retinoblastoma?PEDIATRIC BLOOD & CANCER, Issue 7 2006Maja Beck Popovic MD Abstract Purpose Patients with hereditary retinoblastoma (Rb) develop in 4%,8% a malignant midline tumor called trilateral Rb (TRb). We report in this study on benign pineal cysts observed in patients investigated for TRb. Patients and Methods Between September 1990 and December 2001, 172 patients were screened for TRb. Ninty-five had bilateral, 77 unilateral disease. The median age at diagnosis of Rb was 7 months (range 1,26). Treatment included enucleation, local treatment with cryotherapy or photocoagulation, first-line chemotherapy (CT), thermo-chemotherapy (TCT), Ruthenium plaque, and, rarely, external beam radiation (EBR). Results TRb was found in 5/95 patients (5.3%) with bilateral disease. Interestingly, five other patients (5.3%) presented a pineal cyst on magnetic resonance imaging (MRI). No cysts were recorded in the 77 patients with unilateral disease. This difference was statistically significant (P,<,0.05). The median age at diagnosis of the pineal cyst was 26 months (range 16,80), much younger than reported in literature for healthy children. Four of five patients with TRb died of the disease, while all the patients with pineal cysts remained stable and asymptomatic during a median follow-up of 41 months (range 37,54). Conclusions This report describes benign cystic lesions of the pineal gland in patients with hereditary Rb, suggesting a benign variant of TRb. Underlying possible pathogenetic mechanisms are discussed. © 2005 Wiley-Liss, Inc. [source] The Diagnosis and Treatment of Ductal Carcinoma In Situ of the BreastTHE BREAST JOURNAL, Issue 2 2000Eleanor E. R. Harris MD Abstract: Ductal carcinoma in situ of the breast is the most favorable presentation of breast cancer; therefore appropriate local treatment is imperative. Intraductal carcinoma is being diagnosed more frequently with the increasing use of screening mammography. A number of pathologic features have been identified which are useful for classification and for prognostic information. In addition, the molecular pathology and its relationship to tumor behavior and prognosis is becoming more well understood. The role of axillary dissection has been examined in a number of series and is generally agreed to be unnecessary for this presentation of breast cancer, allowing many women to avoid the sequela of axillary surgery. This review discusses the use of breast conservation treatment and the evolving indications for excision alone in the treatment of ductal carcinoma in situ. The outcomes for breast conservation therapy from both randomized trials and institutional series have confirmed excellent survival rates. Salvage therapy for local recurrence is frequently successful, resulting in nearly equivalent survivals in women undergoing breast conservation therapy compared to mastectomy. In addition, intriguing but preliminary results from both breast cancer prevention studies and trials looking at the use of tamoxifen for intraductal cancer suggest a local control benefit in women using the drug. [source] Conjunctival Melanoma: The Role of Conservative Surgery and Radiotherapy in Regional Metastatic DiseaseTHE LARYNGOSCOPE, Issue 5 2005Taran Tatla MRCS Abstract Objective: To evaluate prognostic factors and determine the role of conservative surgery and radiotherapy in managing metastatic conjunctival malignant melanoma (MM) involving preauricular/submandibular lymph nodes. Method: A retrospective analysis (1990,2003) of clinical and histopathologic data from 12 patients presenting with regional metastases after failed local treatment for conjunctival MM. Patients received a common, multispecialty, conservative management approach: wide local excision, topical cryotherapy or radiotherapy to conjunctival MM (orbital exenteration for more advanced local disease), lumpectomy, and adjuvant "ring" radiotherapy of regional metastases, with chemotherapy for distant metastases. Results: Median age at primary diagnosis was 51 (range 28,86) years with equal sex predilection. Six of the 12 patients had primary tumors of the bulbar conjunctiva; the remainder arose in the palpebral conjunctiva, the caruncle, or the fornix. Of 11 originating in primary acquired melanosis (PAM), 2 were amelanotic. Epithelioid tumor cells were noted histologically in seven of eight specimens in which cell type could be determined. Eight tumors metastasised to preauricular nodes, three to submandibular and one to both, with a median interval of 23 (range 12,108) months after primary diagnosis. After conservative surgery and "ring irradiation," 7 of 12 patients remained free of regional nodal relapse at median interval of 16 (range 3,126) months. Five patients developed regional nodal recurrence at median interval of 11 (range 6,13) months, 3 of whom were within radiotherapy portals. Eight patients developed distant metastasis at median interval of 44 (range 22,138) months. Eleven patients had tumor-related death. The mean Kaplan-Meier adjusted survival time after primary diagnosis was 76 months with death ensuing postregional metastasis within a median 18 (range 4,127) months. The sole survivor's follow-up duration was 56 months. Conclusion: Locoregional metastasis after treatment for conjunctival MM is associated with a poor prognosis. Both epithelioid tumor cells and PAM are associated with disseminating disease and poorer outcome. Literature review has failed to demonstrate advantages of mutilating radical surgery over a conservative approach in this rare disease. [source] Making use of the primary tumourBIOESSAYS, Issue 1 2003Arnold Baars Surgical resection of a primary tumour is often not sufficient to cure a patient. Even when no residual cancer can be detected at time of surgery, metastases may appear in the following years, which indicates that the primary tumour had apparently spread before surgery. Following surgery, systemic chemotherapy may be used to eradicate micro-metastatic disease. Here we present two unconventional strategies that implement new insights into tumour biology and tumour immunology in the treatment of patients with cancer. Both experimental strategies use the individual characteristics of the patient's primary tumour to optimise the control of life-threatening micro-metastases. We aim to modulate the patient's adaptive immune system, targeting it towards the patient's own tumour cells to eradicate residual disease following local treatment. In one approach, this is done by autologous tumour cell vaccinations as adjuvant treatment for colon cancer patients and, in a second approach, by giving chemo-imunotherapy before local treatment to women with locally advanced breast cancer. BioEssays 25:79,86, 2003. © 2002 Wiley Periodicals, Inc. [source] Successful treatment of multiple actinic keratoses in organ transplant patients with topical 5% imiquimod: a report of six casesBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2006C. Ulrich Summary Background, Nonmelanoma skin cancer represents a significant cause of morbidity in organ transplant recipients (OTRs). Cutaneous malignancies, mainly invasive squamous cell carcinoma and its precursor actinic keratosis (AK), appear approximately 5,10 years after organ transplantation. Impaired wound healing and high recurrence rates in immunocompromised patients treated with destructive therapies such as cryosurgery or topical 5-fluorouracil represent frequently known complications. Objectives, To evaluate the safety and efficacy of imiqimod 5% in the treatment of AKs in OTRs. Methods, Six OTRs (two kidney, two heart, one lung and one liver) with extensive AKs were treated with imiquimod 5% cream two to three times weekly in an open-label uncontrolled, nonrandomized pilot study. Results, In five of six patients treated with imiquimod 5% cream all AK lesions were cleared after 12,16 weeks. One patient showed partial response. Local adverse events at the site of application included erythema, oedema and mild erosion. No wound infection or scarring was observed in any of these patients. All graft-related laboratory parameters were stable during and after treatment. Immunosuppressive therapy remained unchanged throughout the treatment. Conclusions, These results suggest that imiquimod 5% cream may be useful for the local treatment of precancerous AK lesions in OTRs. [source] Interstitial laser coagulation with temporary hepatic artery occlusion for patients with cirrhosis and irresectable hepatomaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2003C. Verhoef Background: The aim was to determine the degree of local control of hepatocellular carcinoma (HCC) in patients with cirrhotic liver disease when treated with ultrasonographically guided interstitial laser coagulation (ILC) with temporary hepatic artery occlusion. Methods: Sixteen patients with 24 HCC tumours were treated. Follow-up was by computed tomography or magnetic resonance imaging every 3 months. Results: Nineteen of 24 tumours showed complete necrosis immediately after treatment, and there was no tumour recurrence during follow-up (mean 14 months, median 12 months). No effect on liver function was observed after 1 week and there was no death. In 13 of the 16 patients, new HCC foci developed at other sites. Conclusion: Percutaneous ILC combined with temporary hepatic artery occlusion during a single session is an effective local treatment for HCC nodules smaller than 5 cm. However, new HCC lesions develop in the majority of patients, which underscores the need for adjuvant therapy or repeated treatment in these patients. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Adjuvant and neoadjuvant chemotherapy for Ewing sarcoma family tumors in patients aged between 40 and 60,CANCER, Issue 4 2007Report of 35 cases, comparison of results with 586 younger patients treated with the same protocols in the same years Abstract BACKGROUND. The clinical and pathologic features of 46 patients 40 to 60 years old with Ewing sarcoma family tumor (ESFT) diagnosed at the authors' institute between 1972 and 2000 were reviewed. METHODS. Ten patients with metastatic tumors at presentation went elsewhere for treatment; 35 of 36 remaining cases with localized disease were treated at the authors' institution according to different chemotherapy protocols activated in successive years. In patients with nonmetastatic tumors local treatment was surgery in 9 patients, radiotherapy in 16, and surgery followed by radiotherapy in 10. RESULTS. At follow-up times ranging from 6 and 34 years (mean, 17.8 years), 15 patients (42.9%) remained continuously disease-free, 19 experienced recurrence, and 1 died of chemotherapy-related toxicity. The 5- and 10-year event-free survivals were 42.9% and 35.2%, respectively, and the 5- and 10-year overall survivals were 46.1% and 42.8%, respectively. Comparing this group of patients with 586 cases of younger patients seen in the same period at Rizzoli, the only difference between the 2 groups was a significantly higher rate of tumors located in the soft tissues with a larger volume in the older group. The results achieved were comparable in the 2 groups, although the older group had a lower chemotherapy dose-intensity and a higher rate of WHO grade 4 hematologic toxicity. CONCLUSIONS. For patients with localized disease treated with adjuvant and neoadjuvant chemotherapy the results were essentially comparable in the 2 groups. It is concluded that patients 40 years or older with ESFT should be treated in the same way as younger patients and included in treatment trials for these tumors. Cancer 2007. © 2007 American Cancer Society. [source] Phase II study of induction chemotherapy with paclitaxel, ifosfamide, and carboplatin (TIC) for patients with locally advanced squamous cell carcinoma of the head and neckCANCER, Issue 2 2002Dong M. Shin M.D. Abstract BACKGROUND This Phase II trial was conducted to determine the response rate, particularly of the primary sites, tolerability, and toxicity of induction chemotherapy of paclitaxel, ifosfamide, and carboplatin for patients with previously untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN). We also hypothesized that improved complete response (CR) rates with the induction chemotherapy may render better survival rates with subsequently delivered definitive local treatment. METHODS All eligible patients with locally advanced SCCHN received two courses of induction chemotherapy and underwent repeated head and neck examination and computed tomography or magnetic resonance imaging scans. If the patients achieved responses (CR or partial [PR]), they received two more courses of chemotherapy before undergoing definitive local treatment. Induction chemotherapy consisted of paclitaxel (T; 175 mg/m2 in a 3-hour infusion) on Day 1, ifosfamide (I; 1000 mg/m2 in a 2-hour infusion) on Days 1,3 with intravenous mesna (200 mg/m2 before and 400 mg/m2 after ifosfamide), and carboplatin (C) using the Calvert formula for the area under the plasma concentration-versus-time curve of 6 on Day 1, repeated every 3,4 weeks. Prophylactic hematopoietic growth factors or antibiotics were not used in this study. Definitive local treatment was given based on the investigators' preference. RESULTS Fifty-four patients were registered and 52 patients were assessable for response to induction chemotherapy; 2 were not evaluable. After four courses of induction chemotherapy, the CR rates of the primary and lymph node sites were 60%, and 41%, respectively. For both primary and lymph node sites, there were 31% CRs and 50% PRs with an overall response rate of 81%. Five (9%) patients developed neutropenic fever, all of whom recovered with antibiotic therapy. Two (4%) patients had infection without neutropenia and recovered without any complication. Grade 3/4 thrombocytopenia and anemia occurred in three (6%) and four (7%) patients, respectively. Grade 3/4 fatigue developed in four (7%), arthralgia/myalgia in two (4%), peripheral neuropathy in two (4%), and orthostatic hypotension in two (4%) patients. One patient died of severe anaphylaxis although a maximized resuscitation effort was made. With a median follow-up of 22 months, the organ preservation rate was about 81% (42 of 52 patients). Although survival rates were not primary end points in this study, with a median follow-up of 22 months, 43 (83%) patients are still alive. Overall 1 and 2-year survival rates were 88% and 82%, respectively. Disease-free 1 and 2-year survival rates were 88% and 77% respectively. CONCLUSIONS TIC induction chemotherapy is associated with a high CR rate at the primary sites and with excellent survival and organ preservations rates with subsequently delivered definitive local therapy. The regimen was also well tolerated in the majority of patients. The TIC regimen should be developed further in the context of induction chemotherapy followed by concomitant chemoradiotherapy or with specific molecular targeted agents. Cancer 2002;95:322,30. © 2002 American Cancer Society. DOI 10.1002/cncr.10661 [source] 3465: Medical cancer therapy of lacrimal gland tumoursACTA OPHTHALMOLOGICA, Issue 2010C LE TOURNEAU Purpose The most common malignant epithelial cancer of the lacrimal gland is the adenoid cystic carcinoma (ACC). Despite a slow growth, ACCs are ultimately associated with a poor outcome. Methods Given the rarity of this disease, there are actually no conclusive recommendations for optimal therapy of this tumor. Results Surgery and postoperative radiation therapy is commonly used in the initial local treatment of ACC of the lacrimal gland. In high-risk recurrence patients, concomitant platinum-based chemoradiation should be discussed in an attempt to enhance radiosensitivity. While encouraging responses were reported with intraarterial neoadjuvant chemotherapy, this strategy was associated with substantial toxicity and should not be recommended outside of clinical trials. In the metastatic setting, systemic therapy is the only available option if no surgery and/or radiation is feasible. Although some tumour shrinkage has been reported with intravenous chemotherapy, only dismal objective response rates were achieved. Most active drugs remain anthracyclines and platinum compounds. Drug combinations do not seem to add much efficacy. More recently, non-cytotoxic molecularly targeted agents have emerged and demonstrated significant efficacy in several tumour types. These agents modulate specific targets thought to be essential for tumour proliferation and/or angiogenesis. c-KIT, PDGFR,, EGFR, and VEGFR are transmembrane receptors with oncogenic tyrosine kinase activity that are commonly overexpressed in ACC. The use of drugs triggering these targets has been disappointing so far. Conclusion The recent identification of a hallmark gene fusion transcript thought to activate critical targets involved in apoptosis, cell cycle control, cell growth and angiogenesis, heralds new treatment promise. [source] 4264: Regression of choroidal melanoma after primary chemotherapyACTA OPHTHALMOLOGICA, Issue 2010NE BECHRAKIS Purpose To describe the local regression of an intraocular choroidal melanoma after primary chemotherapy with fotemustine. Methods A 30 y.o. young man presented with drop of visual acuity in his lest eye to 0,8. The right eye was unremarkable with VA 1,2. On the same time he developed upper abdominal pain. On ophthalmic examination a circumpapillary choroidal melanoma was detected with possible optic nerve infiltration on his left eye. Ultrasound and MRI scan of the upper abdomen revealed a diffuse metastatic liver disease. Results In consultation with the department of oncology it was decided to prescribe systemic chemotherapy with fotemustine. After 4 cycles of chemotherapy, there was impressive local regression of the choroidal tumour and the liver metastases. Unfortunately after the initial response and the stable intraocular situation, there was tumour progression in other sites such as subcutaneous and lung metastases. After administration of some cycles of cisplatin as an alternative regime, the patient succumbed to the metastatic disease. Conclusion This case demonstrates that intravenous fotemustine can be effective for a limited time period as a primary treatment option in a case of choroidal melanoma, without other local treatment. [source] Clinical presentation, pathological features and natural course of metastatic uveal melanoma (MUM) as an orphan and commonly fatal diseaseACTA OPHTHALMOLOGICA, Issue 2009R VAN GINDERDEUREN Purpose Uveal melanoma (UM) is a rare disease characterized by an unpredictable course and variable outcome ranging from cure by local treatment to the occurrence of untreatable metastasis. The current project is focused on the characteristics of the metastatic phenotype of the disease Methods We performed data collection from 76 pts with MUM treated in Leuven between 1957-2008. Statistical analysis involved nonparametric technics, Kaplan Meyer and log rank test Results The median age at diagnosis of UM was 58 yrs (range 30-94). Common initial treatments were surgery (71%), brachytherapy (20%) and external beam RT (7%). Synchronous metastasis was found in only 9% of cases, all others had metachronous disease after a median interval of 40 mo (range, 7-420). Metastasis in >1 organ, was seen in 47% of cases. The most frequent metastatic site was the liver (96%), followed by lung, subcutaneous, bone and brain lesions. The median OS from diagnosis of UM was 46 months (range, 2-182), and only 4,5 months in pts with MUM (range, 1-128). 65% of MUM pts qualified for further treatment, The most common drugs given were DTIC, cisplatin, tamoxifen or phase I agents. Patient benefit (PR+SD) was seen in 16/45 pts (36%), including 2 PR Conclusion In this orphan disease with female predominance metastasis occurs late, is mainly found to the liver, and is associated with high morbidity, as >1/3 of pts do not qualify for further therapy. Advances in MUM can only be achieved by networking of sites interested in this tumour type with systematic collection of data and tissue to improve our understanding of the molecular biology of the disease [source] | ||||||||||||||||||||||||||||||||||