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Systemic Treatment (systemic + treatment)
Selected AbstractsFS05.1 Treatment of hand eczemaCONTACT DERMATITIS, Issue 3 2004Niels K Veien Hand eczema is a common skin disease that often becomes chronic, and treatment of the disease is often challenging. Skin protection is of great importance for the prevention of hand eczema and is a fundamental aspect of the treatment of hand eczema. Emollients have been shown to be successful in the primary prevention of hand eczema as well as in reducing eczema activity. Topical corticosteroids are still the mainstay of treatment, but randomised controlled trials of their efficacy are needed. A combination of tacrolimus and topical corticosteroids may reduce the risk of steroid-associated side-effects. UV-therapy and Grenz rays can also suppress hand eczema. Systemic treatment with immunosuppressants such as cyclosporine and methotrexate show promising results, and acitretin may suppress keratotic hand eczema. Treatment possibilities for hand eczema, indications and side effects will be discussed. [source] Treatment of erythema multiforme, Stevens,Johnson Syndrome, and toxic epidermal necrolysisDERMATOLOGIC THERAPY, Issue 4 2002Klemens Rappersberger The "erythema multiforme disease spectrum" comprises four distinct, severe, clinical subvariants: (1) bullous erythema multiforme (bullous-EM), (2) Stevens,Johnson syndrome (SJS), (3) SJS,toxic epidermal necrolysis (TEN)-overlap syndrome, and (4) TEN. These diseases are closely related to severe mucocutaneous intolerance reactions that are mostly elicited by drugs/drug metabolites and associated with a high mortality rate. Old age and area of detached skin negatively influence the course of disease, and early withdrawal of causative drugs with short half-life is a positive prognostic factor. Therapeutic management represents a multidisciplinary challenge for colleagues from various specialities including specialized nurses and usually can be performed at a dermatologic ward unless technical equipment of an intensive care unit is needed. Topical therapy with biologic and (semi-)synthetic dressings is aimed at early re-epithelialization and the prevention of scarring, synechia formation, and infection. Systemic treatment includes antibiotics, fluid and electrolyte replacement, protein preparations and blood products, etc. Various anti-inflammatory and immunosuppressive treatment regimens with corticosteroids, cyclosporine A, cyclophosphamide, plasmapheresis have been considered to halt ongoing immunologic pathomechanisms, and some of these have shown significant efficacy. However, because we lack formal clinical trials, none of these regimens can be definitively proposed as a therapy of choice in any of the severe clinical variants of the EM spectrum. [source] Sex differences in and hormonal regulation of Kv1 potassium channel gene expression in the electric organ: Molecular control of a social signalDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2007W. Preston Few Abstract Electric fish communicate with electric organ (EO) discharges (EODs) that are sexually dimorphic, hormone-sensitive, and often individually distinct. The cells of the EO (electrocytes) of the weakly electric fish Sternopygus possess delayed rectifying K+ currents that systematically vary in their activation and deactivation kinetics, and this precise variation in K+ current kinetics helps shape sex and individual differences in the EOD. Because members of the Kv1 subfamily produce delayed rectifier currents, we cloned a number of genes in the Kv1 subfamily from the EO of Sternopygus. Using our sequences and those from genome databases, we found that in teleost fish Kv1.1 and Kv1.2 exist as duplicate pairs (Kv1.1a&b, Kv1.2a&b) whereas Kv1.3 does not. Using real-time quantitative RT-PCR, we found that Kv1.1a and Kv1.2a, but not Kv1.2b, expression in the EO is higher in high EOD frequency females (which have fast EO K+ currents) than in low EOD frequency males (which have slow EO K+ currents). Systemic treatment with dihydrotestosterone decreased Kv1.1a and Kv1.2a, but not Kv1.2b, expression in the EO, whereas treatment with human chorionic gonadotropin (hCG) increased Kv1.2a but not Kv1.1a or Kv1.2b expression in the EO. Thus, systematic variation in the ratios of Kv1 channels expressed in the EO is correlated with individual differences in and sexual dimorphism of a communication signal. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [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] Thyrotrophin-Releasing Hormone Decreases Feeding and Increases Body Temperature, Activity and Oxygen Consumption in Siberian HamstersJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2007S. Schuhler Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5,50 mg/kg body weight; i.p.) and central (0.5 µg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function. [source] Changing pattern of imported cutaneous leishmaniasis in the NetherlandsCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2005J. E. Zeegelaar Summary Cutaneous leishmaniasis (CL) in western countries seems to be appearing more frequently. Our aim was to determine if there has been a shift in countries where CL is acquired and whether the incidence has changed, and to assess current diagnostic procedures and treatment modalities. In a retrospective study medical records of patients with the diagnosis of CL at the Departments of Tropical Dermatology and Tropical Medicine, Academic Medical Center, Amsterdam, the Netherlands, from 1990 to 2000 were analysed. CL was diagnosed in 78 patients. The majority was acquired in Belize, Surinam, French Guyana and Bolivia. Giemsa stains were positive for the parasite in impression smears from 43% and in biopsies from 71%. Seventy-eight per cent of cases were culture-positive and 89% were PCR-positive. Sixty-two patients were treated systemically: pentavalent antimony (32), pentamidine isetionate (11), itraconazole (19), and 13 locally, the majority with a combination of cryosurgery and intralesional pentavalent antimony. Imported CL is becoming more frequent, with South and Middle American countries being important sources of infection. Multiple tests, of which PCR is the most sensitive, are required to confirm the diagnosis. Systemic treatment was given to the majority of the patients. [source] A Simple, Pain-Free Treatment for Ingrown Toenails Complicated with Granulation TissueDERMATOLOGIC SURGERY, Issue 11 2006F. GÜLRU ERDOGAN MD BACKGROUND The treatment of ingrown toenail complicated with granulation tissue is usually partial or total nail avulsion with or without matricectomy. It costs loss of occupational power, however, because most patients cannot go to work or school for some time after surgery, and it is a costly and uncomfortable procedure for most patients. OBJECTIVE This study aimed to find an easy, painless, and inexpensive alternative. MATERIALS AND METHODS Seven patients with ingrown toenails complicated with granulation tissue are included. A small apparatus was applied on the nails, granulation tissue was chemically cauterized, and a foot bath was recommended twice daily. They were followed on a weekly basis or every other week until recovery. None of the patients received systemic treatment. RESULTS All seven patients were completely cured without requiring surgery and/or systemic treatment. The procedure did not have any effect on their daily life. The follow-up examination of the patients at 6 months revealed that they were totally cured, and there were no recurrences. CONCLUSION Patients with ingrown toenails complicated by granulation tissue might have an inexpensive and pain-free treatment alternative, although new studies with more patients are required. [source] Update on retinoid therapy of psoriasis in: an update on the use of retinoids in dermatologyDERMATOLOGIC THERAPY, Issue 5 2006Peter C. M. Van De Kerkhof ABSTRACT:, Both in the topical and systemic treatment of psoriasis, retinoids are mainstays. In this chapter the history and modes of actions of retinoids are presented. Tazarotene and acitretin are the only retinoids that are available in both topical and systemic formulations. A more extensive description of their pharmacology, modes of action, indications and contraindications, clinical results, and treatment strategies will be presented. Finally, retinoid X receptor ligands and retinoic acid metabolism blocking agents will be introduced as potential future retinoid mimetics in psoriasis. [source] Cutaneous melanoma: interferon alpha adjuvant therapy for patients at high risk for recurrent diseaseDERMATOLOGIC THERAPY, Issue 1 2006Marko Lens ABSTRACT:, Systemic adjuvant therapy in melanoma patients is the systemic treatment that is administered with the goal of eradicating micrometastatic deposits in patients who are clinically free of disease after surgical removal of the primary melanoma, but with a high risk of systemic recurrence. Interferon-alpha (IFN-,) is one of the most frequently used adjuvant therapies. Several randomized trials evaluated the efficacy of IFN-, in melanoma patients. However, results from conducted trials are controversial. Twelve randomized IFN-, trials are discussed in detail. All trials, including meta-analysis, failed to demonstrate a clear impact of IFN-, therapy on overall survival in melanoma patients. Based on currently available evidence, IFN-, therapy in the adjuvant setting should not be considered standard of care for patients who have melanoma. Results from ongoing studies are awaited. Further research for this therapy is required. [source] Adoptive transfer of an anti-MART-127,35 -specific CD8+ T,cell clone leads to immunoselection of human melanoma antigen-loss variants in SCID miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2003Francesco Lozupone Abstract The identification of appropriate mouse models could be useful in carefully evaluating the actual role of the in vivo development of antigen-loss variants during antigen-specific vaccine therapy of human tumors. In this study we investigated the level of efficacy of a MART-1/Melan-A-specific CD8+ T,cell clone against its autologous melanoma in a severe combined immunodeficiency (SCID) mouse model, in which the tumor cells expressed in vivo heterogeneous and suboptimal levels of MART-1. The subcutaneous co-injection of the MART-1/Melan-A-reactive T,cell clone A42 with MART-1/Melan-A+ autologous human melanoma cells into SCID mice caused a total inhibition of tumor growth. However, the systemic treatment with A42 clone lymphocytes resulted inonly 50,60% inhibition of tumor growth, although the T,cell clone targeted the tumors and the MART-1+ cells virtually disappeared from the tumors. This study suggests that an immunotherapybased on the expansion of an antigen-specific T,cell clone generated in vitro is highly efficient in abolishing tumor growth when the target antigen is fully expressed, but leads to in vivoimmunoselection of antigen-loss variants in the presence of suboptimal levels of antigen expression. Furthermore, this work shows that human tumors/SCID mouse models may be useful in evaluating thein vivo efficacy of adoptive immunotherapies. [source] Prognosis of dermal lymphatic invasion with or without clinical signs of inflammatory breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Guenther Gruber Abstract It is still an open debate whether tumor emboli in dermal lymphatics without inflammatory signs represent a similar bad prognosis like inflammatory breast cancer. We evaluated the prognostic role of dermal lymphatic invasion (DLI) in breast cancer with (DLI + ID) or without (DLI w/o ID) inflammatory disease (ID). From August 1988 to January 2000, 42 patients with DLI were irradiated. Twenty-five were classified as pT4, 13 out of them as pT4d (inflammatory disease); the 17 remaining patients had 1 T1c, 12 T2 and 4 T3 cancers with DLI. Axillary dissection revealed node-positive disease in 39/41 patients (median, 9 positive nodes). Thirty-eight out of 42 patients received adjuvant systemic treatment(s). After a mean follow-up of 33 months, 22/42 patients (52%) are disease-free. The actuarial 3-year disease-free survival is 50% (DLI w/o ID, 61%; DLI + ID, 31%; p < 0.03); the corresponding overall survival was 69% (DLI w/o ID, 87%; DLI + ID, 37%; p = 0.005). The presence or absence of ID was the only significant parameter for all endpoints in multivariate analyses. Dissemination occurred in 19 (45%), local relapse in 7 (n = 17%) and regional failure in 4 (10%). Nine patients (21%) had contralateral breast cancer/relapse. Despite the same histopathologic presentation, DLI w/o ID offered a significantly better disease-free survival and overall survival than ID. The finding of dermal lymphatic tumor invasion predicts a high probability for node-positive disease. © 2003 Wiley-Liss, Inc. [source] Pyoderma gangrenosum of the scalp treated with cyclosporine AINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2002Pasquale Patrone MD A 56-year-old woman presented with an ulcer, with a depth of 9 mm, on the vertex and frontal parietal regions of the scalp. The lesion had a round shape (diameter, 7 cm), with clear-cut margins and vertical borders sinking vertically to a bottom that was entirely covered with purulent fibrinous yellowish matter and greenish colored necrotic tissue. Other numerous small roundish ulcers were present next to the large ulcer. These had irregular margins with a yellowish fibrinous bottom (Fig. 1). The patient reported the appearance of two small ulcers on the left and on the right frontal parietal regions about 1 year earlier. These had been treated locally with antimicrobials and antiseptics with no result. During the 2 months prior to our evaluation, a few small round-shaped ulcers had appeared on the scalp. These had progressively increased in size and number. Figure Figure 1 . Large ulcer with clear-cut margins, covered by purulent fibrinous matter, and other small roundish ulcers The patient had been an insulin-dependent diabetic for 23 years. Hematochemical examinations showed no significant alterations, except for a rise in glycemia. Urine examination gave normal results. Carcinoembryonic antigen and lymphocytic phenotyping indices were normal. Echographic, endoscopic, and radiocontrast studies of the abdomen did not reveal the presence of lesions either in the gastrointestinal tract or in other organs. Samples of ulcerous tissue were collected from the scalp to perform histologic and microbiologic analysis in search of fungi and bacteria. This last examination revealed the presence of Staphylococcus aureus and Candida parapsylosis. Direct search for mycobacteria was negative. Histology indicated the presence of dermal granulomatous inflammation with giant multinucleate cells, associated with large zones of suppuration and colliquative necrosis. While waiting to complete the diagnostic course, topical antiseptic, antimicrobial, and fibrinolytic therapy was administered; subsequently, as this did not lead to any improvement, systemic treatment with cyclosporine A (5 mg/kg/day) was started. Rapid improvement of the clinical picture occurred. The ulcers appeared cleaner from the first 2 weeks of treatment, radial growth stopped, and the margins were slightly more superficial. The patient continued with immunomodulating therapy at home over a period of 7 months. The dose was progressively reduced until, over a period of about 3 months, complete re-epithelialization of the lesion, with subsequent partial regrowth of the hair, was obtained (Figs 2 and 3). No relapses were observed 1 year after treatment was suspended. Figure 2. Partial re-epithelialization of the lesion with partial regrowth of the hair Figure 3. Scar and hair regrowth [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] Molecular regulation of androgen action in prostate cancer,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Scott M. Dehm Abstract Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor. Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This review will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. We will also summarize several recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer. J. Cell. Biochem. 99: 333,344, 2006. © 2006 Wiley-Liss, Inc. [source] Amino-terminus domain of the androgen receptor as a molecular target to prevent the hormonal progression of prostate cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Gang Wang Abstract Prostate cancer has a propensity to metastasize to the bone. Currently the only effective systemic treatment for these patients is androgen ablation therapy. However, the tumor will invariably progress to an androgen-independent stage and the patient will succumb to his disease within approximately 2 years. The earliest indication of hormonal progression is the rising titer of serum prostate specific antigen. Current evidence implicates the androgen receptor (AR) as a key factor in maintaining the growth of prostate cancer cells in an androgen-depleted state. Under normal conditions, binding of ligand activates the receptor, allowing it to effectively bind to its respective DNA element. However, AR is also transformed in the absence of androgen (ligand-independent activation) in prostate cells via multiple protein kinase pathways and the interleukin-6 (IL-6) pathway that converge upon the N-terminal domain of the AR. This domain is the main region for phosphorylation and is also critical for normal coregulator recruitment. Here we discuss evidence supporting the role of the AR, IL-6 and other protein kinase pathways in the hormonal progression of prostate cancer to androgen independence and the mechanisms involved in activation of the AR by these pathways. Receptor-targeted therapy, especially potential drugs targeting the N-terminal domain, may effectively prevent or delay the hormonal progression of AR-dependent prostate cancer. J. Cell. Biochem. 98: 36,53, 2006. © 2006 Wiley-Liss, Inc. [source] Role of systemic and local administration of selective inhibitors of cyclo-oxygenase 1 and 2 in an experimental model of periodontal disease in ratsJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2009C. M. Queiroz-Junior Background and Objective:, Periodontal disease is an inflammatory condition of tooth-supporting tissues. Arachidonic acid metabolites have been implicated in development of periodontal disease, especially those derived from the cyclo-oxygenase (COX) pathway. This study investigated the role of inhibitors of cyclo-oxygenases (COX-1 and COX-2) in a model of periodontal disease in rats. Material and Methods:, A ligature was placed around the molar of rats. Losses of fiber attachment and of alveolar bone were measured morphometrically in histologically prepared sections. Infiltration of cells into gingival tissue surrounding the ligated tooth was also determined. Results:, Systemic and local administration of non-selective and selective COX-2 inhibitors, preventively, resulted in significant reduction of the losses of fiber attachment and alveolar bone, as well as decreased leukocyte numbers in gingival tissue. Preventive selective inhibition of COX-1 was as effective as COX-2 inhibition in reducing local fiber attachment loss and cell migration, but did not prevent alveolar bone loss. Conclusion:, Our results provide evidence for participation of COX-1 and COX-2 in early stages of periodontal disease in rats. Furthermore, local administration of COX inhibitors reduced the signs of periodontal disease to the same extent as systemic treatment. Therapeutic approaches incorporating locally delivered anti-inflammatory drugs could be of benefit for patients suffering from periodontal disease. [source] Melatonin 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] The role of surgery in breast cancer patients with isolated bone metastases at the time of diagnosisJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2009Sevim Turanli MD Abstract Background Surgery for the primary tumor in breast cancer patients with synchronous isolated bone metastasis is applied for palliation. The aim was to determine whether surgical removal of the primary tumor provides a better survival and disease progression. Methods Forty-four patients were diagnosed between the dates June 2004 and January 2007 and these patients are classified according to the removal of the primary tumor or not. Patients and tumor characteristics, removal of the primary tumor, and response to systemic therapy are examined as the factors that were affecting overall survival and time to progression of the disease. Results The median follow-up time was 37.5 months. Mean time to progression and overall survival was longer for the patients who received surgery than the patients who did not (20.4 vs. 18.4 months and 57.6 vs. 44.5 months, respectively), but these were not significant (P,=,0.58, P,=,0.39). In multivariate analysis, response to systemic treatment [(P,=,0.03), hazard ratio,=,0.44, 95% confidence interval,=,0.20,0.93] was independent factor associated with overall survival. Conclusion The response to systemic therapy is the major factor on survival in the breast cancer patients with isolated bone metastasis. Excision of the primary tumor has no effect on time to progression and overall survival. J. Surg. Oncol. 2009;100:95,99. © 2009 Wiley-Liss, Inc. [source] Sentinel lymph node as a new marker for therapeutic planning in breast cancer patientsJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2004Marco Gipponi MD Abstract Background and Objectives Literature review suggests that the sentinel lymph node (sN) represents a reliable predictor of axillary lymph node status in breast cancer patients; however, some important issues, such as the optimisation of the technique for the intraoperative identification of the sN, the role of intraoperative frozen section examination of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla, still require further confirmation. The authors aimed (1) to assess the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, (2) to determine the accuracy and usefulness of intraoperative frozen section examination of the sN in order to perform a one-stage surgical procedure, and (3) to define how the sN might modulate the therapeutic planning in different stages of disease. Materials and Methods From October 1997 to June 2001, 334 patients with early-stage (T1,2 N0 M0) invasive mammary carcinoma underwent sN biopsy; the average age of patients was 61.5 years (range, 39,75 years). In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed. Results In the whole group, the sN was identified in 326 of 334 patients (97.6%), and 105 of 326 patients (37.3%) had positive axillary lymph nodes (pN+). In 9 of 105 pN+ patients, the definitive histologic examination of the sN did not show metastases but these were detected in non-sN, thus giving an 8.6% false-negative rate, a negative predictive value of 94.5% (156/165), and an accuracy of 96.5% (252/261). As regards the specific contribution of the two different techniques used in the identification of the sN, the detection rate was 73.8% (113/153) with Patent Blue-V alone, 94.1% (144/153) with RGS alone, and 98.7% (151/153) with Patent Blue-V combined with RGS (P,<,0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93,95% sensitivity; 100% specificity; 95,97% negative predictive value, and 97,98% accuracy) whichever of the three procedures was adopted (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). Intraoperative frozen section examination was performed in 261 patients, who had at least one sN identified, out of 267 patients who underwent complete axillary dissection; 170 patients had histologically negative sN (i.o. sN,) and 91 patients histologically positive sN (i.o. sN+). All 91 i.o. sN+ were confirmed by definitive histology, whereas in 14 of 170 i.o. sN, patients (8.2%) metastases were detected at definitive histology. As regards the correlation between the size of sN metastasis, the primary tumour size, and the status of non-sN in the axilla, micrometastases were detected at final histology in 23 patients and macrometastases in 82 patients. When only micrometastases were detected, the sN was the exclusive site of nodal metastasis in 20 of 23 patients (86.9%) while in 3 patients with tumour size larger than 10 mm micrometastases were detected also in non-sN. Macrometastases were never detected in pT1a breast cancer patients; the sN was the exclusive site of these metastases in 30 patients (36.6%), while in 52 patients (63.4%) there were metastases both in sN and non-sN. Conclusions Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, because of the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar whichever method is used. The intraoperative frozen section examination proved to be rather accurate in predicting the actual pathologic status of the sN, with a negative predictive value of 91.8%; in 35% of patients it allowed sN biopsy and axillary dissection to be performed in a one-stage surgical procedure. Finally, specific clinical and histopathologic features of the primary tumour and sN might be used to tailor the loco-regional and systemic treatment in different clinical settings, such as in ductal carcinoma in-situ (DCIS), early-stage invasive breast cancer, and patients with large breast cancer undergoing neo-adjuvant CT for breast-saving surgery as well as elderly patients with operable breast cancer. J. Surg. Oncol. 2004;85:102,111. © 2004 Wiley-Liss, Inc. [source] European S3-Guidelines on the systemic treatment of psoriasis vulgarisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2009Supported by the EDF/EADV/IPC [source] The use of topical calcineurin inhibitors in lupus erythematosus: an overviewJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2008U Wollina Abstract Lupus erythematosus (LE) shows a broad range of cutaneous symptoms, including acute, subacute and chronic lesions. The gold standard of established topical treatment consists of medium- to high-potency corticosteroids. Because face and neck are often involved, adverse effects of prolonged corticosteroid use are not uncommon. There is a need of steroid-free topical treatment in LE. With the development of topical calcineurin inhibitors, tacrolimus and pimecrolimus, there is an alternative available. The present study reviews the literature data on topical tacrolimus and pimecrolimus for malar rash, subacute lesions and discoid chronic lesions among others. The present data argue for an efficacy of these compounds in acute and subacute cutaneous LE manifestations with a rapid response and only minor side-effects when used as an adjunct to systemic treatment. In chronic discoid LE, hypertrophic plaques do not well respond because of limited penetration. The primary target seems to be the decrease or blocking of cytokine production by activated T lymphocytes. [source] Systemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routineJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2007D Nashan Abstract Aims, In the metastatic stage, malignant melanoma is resistant to systemic treatment and carries a poor prognosis. A critical, evidence-based analysis of standard approaches based on an extended search of published literature and from different Internet sources is presented. Material and methods, A critical, evidence-based analysis of standard approaches and their variations to systemic therapy based on an extended search of published literature and from different Internet sources is presented. Few meta-analyses are available. Therefore, assessment of therapies is mainly based on randomized multicentre studies or clinical studies achieving an evidence level grade 1 or 2. Results, Monotherapy with DTIC (dacarbazine) is the standard. Based on overall survival data, polychemotherapies cannot be recommended. Combination of polychemotherapy with the cytokines interferon-, and interleukin-2 substantially augments chemotherapy induced response rates, but a meta-analysis for survival does not support its therapeutic superiority. Biological therapies such as vaccinations have not yet delivered results on a higher evidence level. Thus, immunotherapies as well as chemo-immunotherapies will have to be evaluated in further studies. Conclusions, Although the therapeutic efficacy is very limited, dacarbazine cannot be rejected as standard therapy for disseminated melanoma, because no other therapeutic regimen exhibits a survival benefit over DTIC in an evidence-based analysis. This lack of therapeutic progress over the past 40 years clearly calls for further clinical studies, and patients should be enrolled into clinical trials whenever possible. [source] Topical class I corticosteroids in 10 patients with bullous pemphigoid: correlation of the outcome with the severity degree of the disease and review of the literatureJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2004A Stockman ABSTRACT Background, Treatment of bullous pemphigoid (BP) with systemic immunosuppressive agents, in particular with systemic corticosteroids, has many long-term side-effects. A dozen reports were published regarding the efficacy of topical corticosteroids in the treatment of bullous pemphigoid. Objective, To evaluate the efficacy of potent class I topical corticosteroids in relation to the affected body surface area (BSA) in patients with bullous pemphigoid and to review the literature. Methods, An open prospective trial with 10 patients with BP with measurement of the affected BSA. Treatment protocol consisted of three steps: potent class I topical corticosteroid treatment, systemic tetracyclines and systemic corticosteroids. Follow-up period was between 24 and 72 months. Results, Our study suggests a correlation between the success rate of topical corticosteroid treatment and the body surface area initially affected: all patients with an affected BSA of less than 20% healed with topical treatment only. The patients with more than 40% affected BSA needed systemic treatment with steroids. Conclusion, Topical class I corticosteroids seem to be effective in healing lesions of BP, especially if less than 20% of the BSA is affected. This study comprises only 10 patients, making further studies necessary to draw definite conclusions. [source] Methotrexate in psoriasis: 26 years' experience with low-dose long-term treatmentJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2000U-F. Haustein Abstract Objective,To evaluate the efficacy, safety and side-effects of methotrexate (MTX) in psoriasis. Design,A 26-year retrospective study. Setting,Department of Dermatology, Leipzig University, Leipzig, Germany. Patients,One hundred and fifty-seven patients with extensive plaque psoriasis, erythrodermic, pustular and arthropathic forms, were treated with low-dose methotrexate (15,20 mg maximum weekly dosage [Weinstein schedule]), the majority for long-term periods. The mean cumulative dose was 3394 mg, the mean duration 237 weeks. Results,The effect of MTX treatment was good in 76%, moderate in 18% and poor in 6% of subjects; 61% experienced side-effects, most frequently due to liver function abnormalities, bone marrow suppression, nausea, gastric complaints and hair loss. In 20% of cases the subjects were forced to discontinue therapy; 9% refused therapy due to physical and psychological discomfort, 2% wanted to become pregnant, 16% were lost to follow-up, 6% died from multimorbidity and old age. Three subjects (2%) developed cancer of the lung, breast or cervix uteri, possibly in relation to long-term MTX treatment. Altogether there were no deaths or life-threatening side-effects attributable to MTX treatment, and no cases of progressive liver cirrhosis apart from two extensive skin necroses due to overdosage (misunderstanding, suicidal attempt) that were treated successfully with citrovorum factor. Conclusion,Low-dose MTX (<15,20 mg/week) is an effective therapy for extensive and severe forms of psoriasis if patients are selected carefully and monitored regularly, particularly with respect to liver and bone marrow toxicity. This helps to reduce severe side-effects even during long-term treatment. Drug interactions must be avoided. MTX therapy according to the guidelines is relatively safe and still has a place in the systemic treatment of psoriasis with 40 years of experience and an acceptable safety record. [source] Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agentsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2008M. CHAPARRO Summary Background, Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Unresectable disease patients have median survival of few months. There is a substantial need for novel treatments for patients with advanced HCC. Aim, To provide an update review of mechanism of hepatocarcinigenesis and systemic therapies for HCC and the relevant role of Sorafenib in patients with advanced disease. Methods, A Medline search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated. Results, Systemic chemotherapy for HCC has been quite ineffective. Preclinical studies demonstrated that Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway has a role in HCC. HCC tumours are highly vascularized and vascular endothelial growth factor (VEGF) augments HCC development and metastasis. Sorafenib blocks tumour cell proliferation by targeting Raf/MEK/ERK signalling and exerts an antiangiogenic effect by targeting VEGF receptors-2/3 and platelet derived growth factor receptor , tyrosine kinases. Conclusions, Currently available therapies are not effective for patients with advanced HCC. Sorafenib has demonstrated for the first time to prolong survival in patients with advanced HCC, and it is the new reference standard for systemic treatment in these patients. [source] Study to compare the efficacy and safety of fluconazole cream with flutrimazole cream in the treatment of superficial mycosis: a multicentre, randomised, double-blind, phase III trialMYCOSES, Issue 6 2010S. M. Yim Summary Fluconazole, which is a drug of the azole family, is safely used in systemic treatment of oral and intravenous injection, but it is difficult to use fluconazole as a topical application because of its large molecular weight and strong hydrophilic property. This study is a multicentre, double-blind, randomised, non-inferiority study to compare the antifungal effect and safety of fluconazole cream 0.5% and 1% with flutrimazole cream 1% in superficial mycosis. A total of 162 subjects selected to participate in this study were equally divided into three groups and assigned to be given fluconazole cream 0.5%, fluconazole cream 1%, and flutrimazole cream 1% in the ratio of 1 : 1. The primary index of drug efficacy was determined by complete mycological cure in which no fungus was detected on KOH smear test 4 weeks after application of fluconazole. The secondary index of efficacy was defined as complete mycological cure 4 weeks after the application of fluconazole, improvement of clinical symptoms and overall effectiveness assessed by the research staff. According to this study, on comparing the efficacy of cure of superficial dermatomycosis after 4 weeks of application, both fluconazole 0.5% and fluconazole 1% cream were found to be equally effective and non-inferior to flutrimazole 1% cream. Given the effectiveness and safety of the drug, both fluconazole 0.5% and 1% cream might be said to be optimal concentration in the treatment of superficial dermatomycosis. [source] Drug-induced ocular side-effects with isotretinoinOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 5 2008Jacinto Santodomingo-Rubido Abstract Whereas there are numerous reported ocular side-effects from isotretinoin medication, we present the first case report of corneal steepening after systemic treatment with isotretinoin for seven and a half weeks. The case was associated with a significant drop in visual acuity which could not be explained from the refractive error change. All signs and symptoms were absent seven and a half weeks after the medication was withdrawn. The case indicates that eye care professionals need to be vigilant about the possibility of adverse ocular manifestations associated with the use of systemic medications. [source] Guidelines for the Management of Tinea Capitis in ChildrenPEDIATRIC DERMATOLOGY, Issue 3 2010Talia Kakourou M.D. Tinea capitis always requires systemic treatment because topical antifungal agents do not penetrate the hair follicle. Topical treatment is only used as adjuvant therapy to systemic antifungals. The newer oral antifungal agents including terbinafine, itraconazole, and fluconazole appear to have efficacy rates and potential adverse effects similar to those of griseofulvin in children with TC caused by Trichophyton species, while requiring a much shorter duration of treatment. They may be, however, more expensive (Grading of recommendation A; strength of evidence 1a). Griseofulvin is still the treatment of choice for cases caused by Microsporum species. Its efficacy is superior to that of terbinafine (Grading of recommendation A; strength of evidence 1b), and although its efficacy and treatment duration is matched by fluconazole (Grading of recommendation A; strength of evidence 1b) and itraconazole (Grading of recommendation A; strength of evidence 1b), griseofulvin is cheaper. It must be noted, however, that griseofulvin is nowadays not available in certain European countries (e.g., Belgium, Greece, Portugal, and Turkey). [source] Illusions in advanced cancer: The effect of belief systems and attitudes on quality of lifePSYCHO-ONCOLOGY, Issue 1 2004G.F. Beadle Patients with advanced cancer frequently express positive attitudes and can be unduly optimistic about the potential benefits of treatment. In order to evaluate an illusory domain in the context of advanced cancer, we developed a scale of will to live and characterized the beliefs that patients held about the curability of their cancer, and how committed they were to using alternative treatments. A measure of quality of life was used as the dependent variable in order to assess the association between these attributes. After a preliminary exploration confirmed the presence of an illusory domain, these concepts were prospectively tested in 149 ambulant patients with advanced cancer who attended for palliative systemic treatment, radiation treatment or supportive care. The scale of global quality of life was reliable (Cronbach's alpha coefficient 0.72). The distribution of the scores of will to live was skewed, with no respondent scoring poorly, and the scale was reliable (Cronbach's alpha coefficient 0.82). The scale of belief in curability showed diverse beliefs. In some cases, there was a discrepancy between respondents' beliefs in curability and what they believed to be the report by their doctors. There was also an association between a committed use of alternative treatments and a belief in the curability of the cancer (p<0.001). In a multiple regression analysis, both will to live and performance status remained associated with better quality of life scores after adjustment for other relevant variables (p<0.05 and <0.001, respectively). These results suggest that positive illusory beliefs can be measured and are an important component of adaption for some patients with advanced cancer. Furthermore, this illusory domain may influence the perception and measurement of quality of life. Copyright © 2003 John Wiley & Sons, Ltd. [source] Gene therapy for rheumatoid arthritisTHE JOURNAL OF GENE MEDICINE, Issue 6 2002Natacha Bessis Abstract Rheumatoid arthritis (RA) is a severe autoimmune systemic disease. Chronic synovial inflammation results in destruction of the joints. No conventional treatment is efficient in RA. Gene therapy of RA targets mainly the players of inflammation or articular destruction: TNF-, or IL-1 blocking agents (such as anti-TNF-, monoclonal antibodies, soluble TNF-, receptor, type II soluble receptor of IL-1, IL-1 receptor antagonist), antiinflammatory cytokines (such as IL-4, IL-10, IL-1), and growth factors. In this polyarticular disease, the vector expressing the therapeutic protein can be administered as a local (intra-articular injection) or a systemic treatment (extra-articular injection). All the main vectors have been used in experimental models, including the more recent lentivirus and adeno-associated virus. Ex vivo gene transfer was performed with synovial cells, fibroblasts, T cells, dendritic cells, and different cells from xenogeneic origin. In vivo gene therapy is simpler, although a less controlled method. Clinical trials in human RA have started with ex vivo retrovirus-expressing IL-1 receptor antagonists and have demonstrated the feasibility of the strategy of gene therapy. The best target remains to be determined and extensive research has to be conducted in preclinical studies. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||