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1.
Terbinafine is the only systemic allylamine antifungal currently available. Its mechanism of action is unique and sets it apart from other agents. Although it is primarily used for dermatophyte infections, such as onychomycosis and tinea pedis, terbinafine has broad in vitro activity against a variety of non-dermatophyte fungal pathogens, including Candida spp. and many molds. In addition, synergistic activity is noted with other antifungals, notably triazoles. Multiple case reports exist of its use for unusual and refractory fungal infections, but no systematic review is available. We review the current literature with regard to in vitro data and clinical experience with terbinafine in the treatment of rare and refractory mycoses. 相似文献
2.
M. Ba Syllac M. Gueyes A. Ndoye G. Wotto-Gaye A. Fall I. Terolbe P. D. Ndiaye A. Mensah 《Andrologie》1995,5(4):544-547
The Sarcoidosis or Besnier Boeck Schaumann's disease is a systemic granulomatous disorders. Multiple organs but specially lungs and skin may be affected. We describe an uncommon case of genital localisation in one patient with epididymal sarcoidosis, regarding on the heterogeneous clinic presentations of this affection. References show differents hypotesis about the pathogenesis: mycobacterial, viruses, imunologic or genetic factors. There are also a race predominance in black population. The patient was referred to us for testicular pain associated with a palpable epididymal node, subcutaneous thoracic and limbs, painless nodes, and rhinorrea. With the first clinic approach we attempted the diagnosis of epididymal tuberculosis, which was corrected after to sarcoidosis with the conjunction of several items on a score disease basis. The biopsy confirmed the diagnosis of sarcoidosis, so we began the medical treatment including chloroquine: 300 mg/day during 3 years (to avoid recurrences). As the usual surgical treatment, we submitted our patient to an epididymal node resection. After a 4 years follow-up, there are no evidences of disease. 相似文献
3.
Vigna-Perez M Hernández-Castro B Paredes-Saharopulos O Portales-Pérez D Baranda L Abud-Mendoza C González-Amaro R 《Arthritis research & therapy》2006,8(3):R83-9
We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an
open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according
to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5
to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition,
the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant
reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia,
no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no
clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab
therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (TREG, Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for TREG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase
in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data
obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients
with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells
and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic
lupus erythematosis deserves additional studies. 相似文献
4.
Marie Vincent Géraldine Teppaz Laurie Lajoie Véronique Solé Anne Bessard Mike Maillasson Séverine Loisel David Béchard Béatrice Clémenceau Gilles Thibault Laure Garrigue-Antar Yannick Jacques Agnès Quéméner 《MABS-AUSTIN》2014,6(4):1026-1037
Rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless, the relapsed/refractory rates are still high. One strategy to increase the clinical effectiveness of RTX is based on antibody-cytokine fusion protein (immunocytokine; ICK) vectorizing together at the tumor site the antibody effector activities and the cytokine co-signal required for the generation of cytotoxic cellular immunity. Such ICKs linking various antibody formats to interleukin (IL)-2 are currently being investigated in clinical trials and have shown promising results in cancer therapies. IL-15, a structurally-related cytokine, is now considered as having a better potential than IL-2 in antitumor immunotherapeutic strategies. We have previously engineered the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. Compared with IL-15, RLI displayed better biological activities in vitro and higher antitumor effects in vivo in murine and human cancer models. In this study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully retained both antibody effector functions (ADCC and CDC), and the cytokine potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in combination, just delayed the disease onset (100% of death at 28, 40 and 51 days respectively). These findings suggest that such ICK could improve the clinical efficacy of RTX, particularly in patients with refractory B-cell lymphoma. 相似文献
5.
《MABS-AUSTIN》2013,5(4):1026-1037
Rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless, the relapsed/refractory rates are still high. One strategy to increase the clinical effectiveness of RTX is based on antibody-cytokine fusion protein (immunocytokine; ICK) vectorizing together at the tumor site the antibody effector activities and the cytokine co-signal required for the generation of cytotoxic cellular immunity. Such ICKs linking various antibody formats to interleukin (IL)-2 are currently being investigated in clinical trials and have shown promising results in cancer therapies. IL-15, a structurally-related cytokine, is now considered as having a better potential than IL-2 in antitumor immunotherapeutic strategies. We have previously engineered the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. Compared with IL-15, RLI displayed better biological activities in vitro and higher antitumor effects in vivo in murine and human cancer models. In this study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully retained both antibody effector functions (ADCC and CDC), and the cytokine potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in combination, just delayed the disease onset (100% of death at 28, 40 and 51 days respectively). These findings suggest that such ICK could improve the clinical efficacy of RTX, particularly in patients with refractory B-cell lymphoma. 相似文献
6.
7.
W Kociecka E Simon M Paku?a D Fundowicz 《Polski tygodnik lekarski (Warsaw, Poland : 1960)》1992,47(36-37):805-807
Two cases of sarcoidosis with peripheral lymphatic nodes involvement and coexisting toxoplasmosis are presented. Both cases illustrate diagnostic and differentiating problems in patients with chronic lymphatic nodes enlargement and positive serological reaction to T. gondii antigen. An emphasis is on the importance of the histological examination of the lymphatic nodes for the sarcoidosis diagnosis and contribution of T. gondii to the disease. Positive serological reaction to T. gondii antigen in patients with sarcoidosis may reflect inactive toxoplasmosis; however, periodical serological tests are necessary monitoring the due immunosuppressive treatment used in patients with sarcoidosis. 相似文献
8.
Three patients were seen who had sarcoidosis associated with glomerulonephritis. Subsequent review of published reports of cases in which the two conditions occurred simultaneously showed a pattern of histological type of glomerulonephritis different from that seen in patients without associated disease. In sarcoidosis with glomerulonephritis there appeared to be a dearth of minimal-change disease and an excess of membranous glomerulonephritis compared with the prevalence that would be expected if the renal disease was merely a chance occurrence. These findings may provide evidence for an important relation between sarcoidosis and glomerulonephritis. 相似文献
9.
Benyamin Ranjbar Louise Bechmann Krogh Maria Bach Laursen Maria Nascimento Primo Sara Correia Marques Karen Dybk?r Jacob Giehm Mikkelsen 《PloS one》2016,11(4)
Diffuse large B-cell lymphoma (DLBCL) is characterized by great genetic and clinical heterogeneity which complicates prognostic prediction and influences treatment efficacy. The most common regimen, R-CHOP, consists of a combination of anthracycline- and immuno-based drugs including Rituximab. It remains elusive how and to which extent genetic variability impacts the response and potential tolerance to R-CHOP. Hence, an improved understanding of mechanisms leading to drug tolerance in B-cells is crucial, and modelling by genetic intervention directly in B-cells is fundamental in such investigations. Lentivirus-based gene vectors are widely used gene vehicles, which in B-cells are an attractive alternative to potentially toxic transfection-based methodologies. Here, we investigate the use of VSV-G-pseudotyped lentiviral vectors in B-cells for exploring the impact of microRNAs on tolerance to Rituximab. Notably, we find that robust lentiviral transduction of cancerous B-cell lines markedly and specifically enhances the resistance of transduced germinal center B-cells (GCBs) to Rituximab. Although Rituximab works partially through complement-mediated cell lysis, increased tolerance is not achieved through effects of lentiviral transduction on cell death mediated by complement. Rather, reduced levels of PARP1 and persistent high levels of CD43 in Rituximab-treated GCBs demonstrate anti-apoptotic effects of lentiviral transduction that may interfere with the outcome and interpretation of Rituximab tolerance studies. Our findings stress that caution should be exercised exploiting lentiviral vectors in studies of tolerance to therapeutics in DLBCL. Importantly, however, we demonstrate the feasibility of using the lentiviral gene delivery platform in studies addressing the impact of specific microRNAs on Rituximab responsiveness. 相似文献
10.
Sarcoidosis is a chronic, systemic granulomatous reticulosis of unknown origin, characterized by formation of hard tubercles and noncaseatinggranulomas. Since other infectious diseases such as berylliosis, mycobacterium and fungal infections may present with a noncaseating granulomas, histological diagnosis of sarcoidosis is made using the elimination method. Central nervous system manifestations of sarcoidosis may be present in 5-10% of the cases involving cranial nerves, leptomeninges and third ventricle respectively. Any part of the central nervous system can be affected. Involvement of spinal cord in sarcoidosis is extremely rare and presents with only 0.3-0.4% in patients with systemic sarcoidosis. Intramedullary sarcoidosis is a rare first manifestation of the disease and it can mimic an intramedullary tumor, which is often manifested with symptoms that initiate from spinal cord compression, resulting in paraparesis, sensory disorders and sphincter dysfunction. We present a case of intramedullary sarcoidosis that mimics a tumor of the thoracic spinal cord. Clinical features, neuroradiological, pathohistological findings, laboratory analysis and surgical treatment of such a rare entity are being discussed. 相似文献
11.
《Endocrine practice》2007,13(2):159-163
ObjectiveTo report a case of Graves’ disease with concomitant sarcoidosis involving the thyroid gland.MethodsWe present the clinical, laboratory, imaging, and pathologic findings and describe the clinical course of a patient with Graves’ disease and sarcoidosis, who was unresponsive to propylthiouracil and radioiodine treatment.ResultsA 23-year-old woman presented with thyrotoxicosis and a large goiter. Laboratory studies and findings on thyroid uptake and scan were consistent with Graves’ disease. She was also found to have hilar lymph-adenopathy and hepatosplenomegaly. Despite treatment with antithyroid drugs and radioiodine therapy, her hyperthyroidism persisted. Surgical resection of the thyroid gland and 2 lymph nodes disclosed noncaseating granulomas, consistent with sarcoid.ConclusionAutoimmune endocrinopathies and, less commonly, thyroid autoimmune disease have been reported in patients with sarcoidosis. Similarities exist in the pathogenesis of these two conditions. Concomitant sarcoidosis in the thyroid gland in patients with Graves’ disease may contribute to the resistance to antithyroid drugs and radioiodine therapy. (Endocr Pract. 2007;13:159-163) 相似文献
12.
Clinically suspected hypomagnesaemia was confirmed in 21 patients over 12 months; all patients had been exposed to either short-term vigorous diuretic treatment or moderate-dosage long-term treatment. Magnesium depletion was compounded by a hospital diet surprisingly low in magnesium, a local soft water supply, and, in some patients, high alcohol intake. Common presenting symptoms included depression, muscle weakness, refractory hypokalaemia, and atrial fibrillation refractory to digoxin treatment. The administration of magnesium supplements resulted in prompt improvement of all symptoms particularly in the case of refractory atrial fibrillation. Chronic low-grade magnesium deficiency from diuretic treatment is more common than published reports suggest. Older patients are at risk, particularly those who have excessive alcohol intake, a diet low in magnesium, or a soft water supply. 相似文献
13.
Yvette Cozier Edward Ruiz-Narvaez Craig McKinnon Jeffrey Berman Lynn Rosenberg Julie Palmer 《Human genetics》2013,132(7):803-810
In the United States, incidence and mortality from sarcoidosis, a chronic, granulomatous disease, are increased in black women. In data from the Black Women’s Health Study, a follow-up of US black women, we assessed two SNPs (rs2076530 and rs9268480) previously identified in the BTNL2 gene (chromosome 6p21), of which rs4424066 and rs3817963 are perfect proxies, to determine if they represent independent signals of disease risk. We also assessed whether local ancestry in four genomic regions previously identified through admixture mapping was associated with sarcoidosis. Finally, we assessed the relation of global percent African ancestry to risk. We conducted a nested case–control study of 486 sarcoidosis cases and 943 age- and geography-matched controls. Both BTNL2 SNPs were associated with risk of sarcoidosis in separate models, but in a combined analysis the increased risk was due to the A-allele of the rs3817963 SNP; each copy of the A-allele was associated with a 40 % increase in risk of sarcoidosis (p = 0.02) and was confirmed by our haplotypic analysis. Local African ancestry around the rs30533 ancestry informative marker at chromosome 5q31 was associated with a 29 % risk reduction (p = 0.01). Therefore, we adjusted our analysis of global African ancestry for number of copies of African alleles in rs30533. Subjects in the highest quintile of percent African ancestry had a 54 % increased risk of sarcoidosis. The present results from a population of African-American women support the role of the BTNL2 gene and the 5q31 locus in the etiology of sarcoidosis, and also demonstrate that percent African ancestry is associated with disease risk. 相似文献
14.
Fine needle aspiration cytology of parotid sarcoidosis 总被引:1,自引:0,他引:1
Granulomatous lesions of the salivary gland are rare; as such, there have been few reports of the cytologic features of granulomatous sialadenitis in general, and salivary gland sarcoidosis in particular. A case of systemic sarcoidosis involving both parotid glands, diagnosed initially by fine needle aspiration (FNA) cytology, is presented. The specific cytologic features included histiocytes of both epithelioid and giant multinucleated types, without background necrosis. The FNA cytologic differential diagnosis of bilateral parotitis is discussed. 相似文献
15.
16.
M. P. Huitema J. C. Grutters B. J. W. M. Rensing H. J. Reesink M. C. Post 《Netherlands heart journal》2016,24(6):390-399
Pulmonary hypertension (PH) is a severe complication of sarcoidosis, with an unknown prevalence. The aetiology is multifactorial, and the exact mechanism of PH in the individual patient is often difficult to establish. The diagnostic work-up and treatment of PH in sarcoidosis is complex, and should therefore be determined by a multidisciplinary expert team in a specialised centre. It is still a major challenge to identify sarcoidosis patients at risk for developing PH. There is no validated algorithm when to refer a patient suspected for PH, and PH analysis itself is difficult. Until present, there is no established therapy for PH in sarcoidosis. Besides optimal treatment for sarcoidosis, case series evaluating new therapeutic options involving PH-targeted therapy are arising for a subgroup of patients. This review summarises the current knowledge regarding the aetiology, diagnosis and possible treatment options for PH in sarcoidosis. 相似文献
17.
Alilović M Peros-Golubicić T Tekavec-Trkanjec J Ivicević A 《Collegium antropologicum》2004,28(1):423-428
The aim of this study was to investigate the prevalence of hospitalized patients of sarcoidosis in the Republic of Croatia, its distribution in relation to sex and age as well as its geographical distribution. The data on sarcoidosis patients hospitalized in Croatia in the last six years, from 1997 to 2002, were analyzed retrospectively. The prevalence of sarcoidosis patients hospitalised in the Republic of Croatia is 4.1/100,000. The prevalence among women is 4.7 and among men 3.5 per 100,000 persons, with a ratio of 1.4:1. The disease more frequently occurs in the regions with a continental climate than in the Mediterranean zone. The ratio of sarcoidosis patients in the continental zone to the Mediterranean zone is 1.5:1. It occurs predominantly among the adults. Over the investigated period, in our country we have not registered any case of sarcoidosis among children. It occurs more frequently at a younger age and therefore 44.5% of the patients with sarcoidosis were between 20 and 39 years of age, 40.1% were between 40 and 59 years of age and 15.3% were more than 60 years old. 相似文献
18.
P. De Paoli E. Vaccher R. Tedeschi C. Caffau S. Zanussi M. T. Bortolin C. Crepaldi M. Spina U. Tirelli 《Cancer immunology, immunotherapy : CII》2001,50(3):157-162
The anti-CD20 monoclonal antibody Rituximab is a novel antitumor agent used in association with chemotherapy (CT) for the
treatment of high-grade/intermediate non-Hodgkin's lymphomas (NHL) in HIV-negative populations. This therapeutic combination
is currently also being explored in HIV-positive patients with NHL (HIV-NHL). The objective of our study was to determine
CD4 and CD8T cell counts, HIV plasma viremia and proviral load in patients with CD20-positive HIV-NHL treated with Rituximab
plus CT and highly active antiretroviral therapy (HAART). We studied eight patients with HIV-NHL treated by anti-CD20 and
CT before, after three, and after six cycles of therapy; CD4, CD8 and CD19 lymphocyte subsets were measured by monoclonal
antibodies and flow cytometry. HIV plasma viremia was determined by the b-DNA assay, and proviral load by a quantitative competitive
PCR. CD4T cell counts remained stable after three cycles of therapy, while a significant reduction of this subset was present
at the end of therapy. HIV plasma viremia was significantly reduced after the third cycle, but returned to pretreatment levels
at the end of therapy; we also observed individual fluctuations of proviral load during therapy, this marker being increased
in two out of three patients at the end of therapy. These observations suggest that Rituximab plus CT accelerated the rate
of CD4 depletion and of HIV replication in the peripheral blood of HIV-NHL patients and that HAART may be able to delay these
effects.
Received: 1 December 2000 / Accepted: 8 February 2001 相似文献
19.
Serena M. Bagnasco Srinivas Gottipati Edward Kraus Nada Alachkar Robert A. Montgomery Lorraine C. Racusen Lois J. Arend 《PloS one》2014,9(10)
Renal involvement by sarcoidosis in native and transplanted kidneys classically presents as non caseating granulomatous interstitial nephritis. However, the incidence of sarcoidosis in native and transplant kidney biopsies, its frequency as a cause of end stage renal disease and its recurrence in renal allograft are not well defined, which prompted this study. The electronic medical records and the pathology findings in native and transplant kidney biopsies reviewed at the Johns Hopkins Hospital from 1/1/2000 to 6/30/2011 were searched. A total of 51 patients with a diagnosis of sarcoidosis and renal abnormalities requiring a native kidney biopsy were identified. Granulomatous interstitial nephritis, consistent with renal sarcoidosis was identified in kidney biopsies from 19 of these subjects (37%). This is equivalent to a frequency of 0.18% of this diagnosis in a total of 10,023 biopsies from native kidney reviewed at our institution. Follow-up information was available in 10 patients with biopsy-proven renal sarcoidosis: 6 responded to treatment with prednisone, one progressed to end stage renal disease. Renal sarcoidosis was the primary cause of end stage renal disease in only 2 out of 2,331 transplants performed. Only one biopsy-proven recurrence of sarcoidosis granulomatous interstitial nephritis was identified.
Conclusions
Renal involvement by sarcoidosis in the form of granulomatous interstitial nephritis was a rare finding in biopsies from native kidneys reviewed at our center, and was found to be a rare cause of end stage renal disease. However, our observations indicate that recurrence of sarcoid granulomatous inflammation may occur in the transplanted kidney of patients with sarcoidosis as the original kidney disease. 相似文献20.
We report the case of a patient with a case of cytomegalovirus (CMV) colitis, which presented as a flare-up of her ulcerative colitis. Standard treatment for the flare-up, which included intravenous corticosteroids, bowel rest, topical salicylates and ultimately colectomy were not effective. The patient did not improve until therapy with intravenous ganciclovir was initiated. There have been 26 previous reports of CMV colitis complicating inflammatory bowel disease (IBD). The diagnosis is not frequently entertained and, if not made, leads to a high rate of colectomy (67 percent) and mortality (33 percent). Appropriate antiviral therapy appears to eliminate these complications, thus a high index of suspicion for CMV superinfection in cases of IBD refractory to traditional therapy is warranted. 相似文献