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Therapeutic Protocol (therapeutic + protocol)
Selected AbstractsREVIEW ARTICLE: Anti-phospholipid Antibodies and Other Immunological Causes of Recurrent Foetal Loss , A Review of Literature of Various Therapeutic ProtocolsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Shrimati Shetty Problem, An immune-based aetiology is one of the several accepted causes for recurrent foetal loss (RFL). However, most of the immunological theories have not fulfilled the criteria for causality. This is a review of the various immunological causes of RFL and the outcome of different treatment protocols. Method of study, Both auto- and alloimmune maternal immunological abnormalities have been proposed to account for foetal loss. Among the autoimmune factors, anti-phospholipid antibodies (APAs) have been demonstrated to be the strongest risk factors for foetal loss, the prevalence of which is as high as 40% in women with RFL. Other autoimmune antibodies implicated in RFL are anti-nuclear antibodies (ANAs), anti-thyroid antibodies and anti-endothelial cell antibodies. The alloimmune factors implicated in pregnancy loss of unknown aetiology include abnormal natural killer (NK) cell activity, alteration in T helper 1 (Th1) and T helper 2 (Th2) ratios, presence of alloimmune antibodies like anti-paternal cytotoxic antibodies, anti-idiotypic antibodies, mixed lymphocyte reaction blocking antibodies and abnormal expression of HLA-G molecules. Management of patients with RFL is mainly based on immunomodulatory (prednisolone, intravenous immunoglobulins, plasma exchange, paternal lymphocyte therapy), anti-aggregation (aspirin) or anti-coagulation (unfractionated or low molecular weight heparin) agents. Results, Low-molecular-weight heparin with low-dose aspirin has been found to be the most effective treatment for women with APAs and RFL. Differences in dosage, timing of treatment, inclusion criteria, outcome assessment parameters etc. are some of the factors which have resulted in discrepancies in various reports. Conclusion, Identification of the immunological mechanisms involved in pregnancy loss and the action of different therapeutic reagents is important so that effective therapies can be designed and investigated. [source] Etiology and Management of Chylothorax Following Pediatric Heart SurgeryJOURNAL OF CARDIAC SURGERY, Issue 4 2009Michael Milonakis M.D. The purpose of this study was to review our experience with the management of chylothorax following congenital heart surgery. Methods: Between September 1997 and August 2006, of 1341 pediatric patients undergoing correction of congenital heart disease in our institution, 18 (1.3%) developed chylothorax postoperatively. Surgical procedures included tetralogy of Fallot repair in 10 patients, ventricular septal defect closure (one), atrial septal defect with pulmonary stenosis repair (one), Fontan procedure (three), coarctation of the aorta repair (one), aortopulmonary shunt (one), and ligation of patent ductus arteriosus in one patient. All patients followed a therapeutic protocol including complete drainage of chyle collection and controlled nutrition. Somatostatin was used adjunctively in six (33.3%) patients. Surgical intervention was reserved for persistent lymph leak despite maximal therapy. Following resolution of chylothorax, a medium-chain triglyceride diet was implemented for six weeks. Results: There were no deaths. Fifteen patients (83.3%) responded to conservative therapy. Lymph leak ranged from 2.5 to 14.7 mL/kg per day for 8 to 42 days. Three patients with persistent drainage required thoracotomy with pleurodesis to achieve resolution, in two of which previously attempted chemical pleurodesis with doxycycline proved ineffective. Duration of lymph leak in this subgroup ranged from 15 to 47 days with 5.1 to 7.4 mL/kg per day output. Conclusions: Postoperative chylothorax is an infrequent complication of surgery for congenital heart disease and can occur even after median sternotomy in the absence of pathologically elevated venous pressure or Fontan circulation. Although hospitalization can be prolonged, conservative therapy is effective in most cases, while surgical pleurodesis proved successful in the refractory cases. [source] Possible Emergence of Drug-Resistant Variants of Babesia gibsoni in Clinical Cases Treated with Atovaquone and AzithromycinJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009M. Sakuma Background: There is no well-established treatment strategy for Babesia gibsoni infection. A new therapeutic protocol using atovaquone (ATV) and azithromycin (AZM) has been proposed, but there is concern about the possible induction of relapse and the emergence of ATV-resistant variants after treatment. Objective: To evaluate the clinical use of combination therapy with ATV and AZM as a first-line treatment of clinical B. gibsoni infection in dogs, and to investigate the emergence of ATV-resistant variants. Animals: Eight B. gibsoni naturally infected dogs showing signs of acute onset of disease. Methods: Retrospective case study. Eight clinical cases received combination therapy with ATV and AZM at Kagoshima University Veterinary Teaching Hospital during 2007,2008, and their clinical courses and clinicopathological parameters were evaluated. In addition, alterations in the cytochrome b (CYTb) gene of B. gibsoni were analyzed by polymerase chain reaction and DNA sequencing techniques. Results: All of the dogs responded well to the treatment, with rapid improvement in their clinical condition and hematological parameters. However, 5 of the 8 dogs relapsed after treatment. Analysis of the CYTb gene strongly suggested the emergence of ATV-resistant variants after treatment. Conclusions and Clinical Importance: The combination of ATV and AZM can be used as a first-line treatment for dogs with babesiosis, but relapses occur. Attention should be paid to the possible in vivo selection of drug-resistant variants. [source] The Cardio-Protective Properties of Ncx-6550, a Nitric Oxide Donating Pravastatin, in the MouseMICROCIRCULATION, Issue 6 2010CLARA DI FILIPPO Please cite this paper as: Di Filippo, Monopoli, Ongini, Perretti and D'Amico (2010). The Cardio-Protective Properties of Ncx-6550, a Nitric Oxide Donating Pravastatin, in the Mouse. Microcirculation17(6), 417,426. Abstract Objective:, Determine the cardio-protective properties of a nitric oxide-releasing pravastatin (Ncx-6550), in comparison to pravastatin. Methods:, A mouse model of myocardial infarct was used assessing tissue damage both at 2 and 24 hour post-reperfusion, administering compounds both prophylactically and therapeutically. Results:, Ncx-6550 induced a significant dose-dependent (2.24,22.4 ,mol/kg i.p.) cardioprotection in the two hour reperfusion protocol. In vehicle-treated mice, infarct size (expressed as fraction of area at risk; IS/AR) was 41.2 ± 1%, and it was reduced to 22.2 ± 0.9% and 32.6 ± 0.9% following 22.4 and 6.72 ,mol/kg Ncx-6550 (p < 0.05). 22.4 ,mol/kg Ncx-6550 also increased cardiac levels of the enzyme heme oxygenase-1. Treatment of mice with pravastatin induced significant reduction of myocardial injury only at 22.4 ,mol/kg (IS/AR value: 33.7 ± 0.9%). In a 24 hour reperfusion protocol, Ncx-6550 and pravastatin were tested only at 22.4 ,mol/kg i.p. being given either one hour prior to ischemia (prophylactic protocol) or one hour into reperfusion (therapeutic protocol). With either treatment scheme, Ncx-6550 produced higher cardioprotection compared to pravastatin, as reflected also by a reduction in the incidence of lethality as well as in circulating troponin I and interleukin-1, levels. Conclusions:, These results indicate Ncx-6550 as a novel therapeutic agent with a potential for the treatment of myocardial infarct. [source] Current diagnostic approaches to invasive candidiasis in critical care settingsMYCOSES, Issue 5 2010Javier Pemán Summary For the specialist, the management of invasive candidiasis infections, from diagnosis to selection of the therapeutic protocol, is often a challenge. Although early diagnosis and treatment are associated with a better prognosis, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, relying on many different factors, clinical and laboratory findings but there is certainly a need for the specific markers in this disease. Recently, new serodiagnostic assays as Candida albicans germ-tube antibodies or (1,3)-,- d -glucan detection and molecular techniques for the detection of fungal-specific DNA have been developed with controversial results in critical care setting. One of the main features in diagnosis is the evaluation of risk factor for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. For these reasons, an approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the new prediction rules and its application situations has been made. Currently, the combination of prediction rules and non-culture microbiological tools could be the clue for improving the diagnosis and prognosis of invasive fungal infections in critically ill patients. [source] Complete resolution of a squamous cell carcinoma of the skin using intralesional 5-aminolevulinic acid photodynamic therapy intralesional PDT for SCCPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2010Eleni Sotiriou We present an 82-year-old female patient with a 2-year history of an infiltrative squamous cell carcinoma (SCC) on her right cheek. The patient was treated with one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic acid solution. We used red light by a non-coherent light source at a light dose of 100 J/cm2 and a fluency rate of 100 mW/cm2. Complete clinical and histological response was achieved 3 months after the treatment procedure. Cosmetic outcome was evaluated as fair. The patient remains disease free with the absence of any clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed for assessment of recurrences. Optimization of the therapeutic protocol, as well as justification of our results in larger studies are needed in order to elicit safe conclusions. [source] Formatted anti,tumor necrosis factor , VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 6 2006Ken Coppieters Objective The advent of tumor necrosis factor (TNF),blocking drugs has provided rheumatologists with an effective, but highly expensive, treatment for the management of established rheumatoid arthritis (RA). Our aim was to explore preclinically the application of camelid anti-TNF VHH proteins, which are single-domain antigen binding (VHH) proteins homologous to human immunoglobulin VH domains, as TNF antagonists in a mouse model of RA. Methods Llamas were immunized with human and mouse TNF, and antagonistic anti-TNF VHH proteins were isolated and cloned for bacterial production. The resulting anti-TNF VHH proteins were recombinantly linked to yield bivalent mouse and human TNF-specific molecules. To increase the serum half-life and targeting properties, an anti,serum albumin anti-TNF VHH domain was incorporated into the bivalent molecules. The TNF-neutralizing potential was analyzed in vitro. Mouse TNF-specific molecules were tested in a therapeutic protocol in murine collagen-induced arthritis (CIA). Disease progression was evaluated by clinical scoring and histologic evaluation. Targeting properties were evaluated by 99mTc labeling and gamma camera imaging. Results The bivalent molecules were up to 500 times more potent than the monovalent molecules. The antagonistic potency of the anti-human TNF VHH proteins exceeded even that of the anti-TNF antibodies infliximab and adalimumab that are used clinically in RA. Incorporation of binding affinity for albumin into the anti-TNF VHH protein significantly prolonged its serum half-life and promoted its targeting to inflamed joints in the murine CIA model of RA. This might explain the excellent therapeutic efficacy observed in vivo. Conclusion These data suggest that because of the flexibility of their format, camelid anti-TNF VHH proteins can be converted into potent therapeutic agents that can be produced and purified cost-effectively. [source] Genistein reduces glycosaminoglycan levels in a mouse model of mucopolysaccharidosis type IIBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2010A Friso Background and purpose:, Mucopolysaccharidoses (MPS) are lysosomal storage disorders resulting from a deficit of specific lysosomal enzymes catalysing glycosaminoglycan (GAG) degradation. The typical pathology involves most of the organ systems, including the brain, in its severe forms. The soy isoflavone genistein has recently attracted considerable attention as it can reduce GAG synthesis in vitro. Furthermore, genistein is able to cross the blood,brain barrier in the rat. The present study was undertaken to assess the ability of genistein to reduce urinary and tissue GAG levels in vivo. Experimental approach:, We used mice with genetic deletion of iduronate-2-sulphatase (one of the GAG catabolizing enzymes) which provide a model of MPS type II. Two doses of genistein, 5 or 25 mg·kg,1·day,1, were given, in the diet for 10 or 20 weeks. Urinary and tissue GAG content was evaluated by biochemical and histochemical procedures. Key results:, Urinary GAG levels were reduced after 10 weeks' treatment with genistein at either 5 or 25 mg·kg,1·day,1. In tissue samples from liver, spleen, kidney and heart, a reduction in GAG content was observed with both dosages, after 10 weeks' treatment. Decreased GAG deposits in brain were observed after genistein treatment in some animals. Conclusions and implications:, There was decreased GAG storage in the MPSII mouse model following genistein administration. Our results would support the use of this plant-derived isoflavone in a combined therapeutic protocol for treatment of MPS. [source] Melanoma stem cells: targets for successful therapy?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 7 2008Roland Houben Summary Increasing evidence suggests that cancer is a disease in which the persistence of the tumor relies on a small population of tumor-initiating cells, the so called tumor stem cells (TSC). Only these cells are capable of self-renewal and thereby possess the ability for unlimited proliferation. One reason for the inability of conventional tumor treatments to achieve long-term cures seems to be that TSC are resistant to many therapeutic approaches. A detailed characterization of TSC should have a substantial impact on the optimization of therapeutic protocols. While TSC in hematopoietic malignancies have been most intensively studied, subpopulations with stem cell properties have been identified in some solid tumors including breast carcinomas, gliomas and melanomas. In case of melanoma, however, a clear-cut molecular characterization is still pending. Considerable research is needed to establish standard procedures for the isolation of melanoma stem cells to facilitate determining how these cells, critical for tumor persistence and progression, can be effectively eliminated. A pressing question is if melanoma stem cells are in principle sensitive to immunotherapy. [source] HHV8 a subtype is associated with rapidly evolving classic Kaposi's sarcomaJOURNAL OF MEDICAL VIROLOGY, Issue 12 2008Roberta Mancuso Abstract The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p,=,0.006 and p,=,0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III,IV compared to stages I,II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection. J. Med. Virol. 80:2153,2160, 2008. © 2008 Wiley-Liss, Inc. [source] Oral pemphigus: long term behaviour and clinical response to treatment with deflazacort in sixteen casesJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2000Michele D. Mignogna Abstract: Systemic corticosteroids remain the mainstay of therapy for pemphigus. Their use has transformed what was almost invariably a fatal illness into one whose mortality is now below 10%. Unfortunately, the high doses and prolonged administration of corticosteroids that are often needed to control the disease result in numerous side effects, many of which are serious or even life-threatening. Sixteen patients affected by oral pemphigus vulgaris were retrospectively examined to illustrate the natural course of the disease and to describe the efficacy of the treatment we utilised. Deflazacort, used with azathioprine, is the steroid of first choice in our therapeutic protocols, while cyclophosphamide and methylprednisolone "pulse therapy" are reserved for cases unresponsive to high doses of oral corticosteroids. In addition, the literature on oral pemphigus vulgaris was reviewed with respect to clinical history, signs and symptoms, management, and treatment outcome. [source] Differential kinetic features by tumour topography in cutaneous small-cell neuroendocrine (Merkel cell) carcinomasJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 9 2007L Pozo Abstract Background/Objectives Merkel cell carcinomas (MCC) reveal epithelial and neuroendocrine differentiation, but its topographic cell kinetics remains unknown. This study analyses proliferation, apoptosis, and DNA ploidy by topography, features that can help planning therapeutic protocols. This study topographically analyses proliferation, apoptosis, and DNA ploidy. Methods We selected 27 small-cell MCCs (expressing one epithelial and two neural markers, with consistent ultrastructural findings) to evaluate mitotic figure counting, Ki-67 index, apoptosis index based on the in situ end labelling of fragmented DNA (using Escherichia coli DNA polymerase I, Klenow fragment), DNA ploidy, and BCL2 and TP53 immuno-expression. At least 50 high-power fields were screened per topographic compartment (superficial or papillary dermis, and deep or reticular dermis), recording average and standard deviation for each variable. Variables were statistically compared in each tumour compartment using analysis of variance and Student's t -test (significant if P < 0.05). Results MCCs revealed superficial aneuploid DNA content, and no topographic differences for proliferation markers. Apoptosis showed significantly lower values in the deep compartment (average, P = 0.0050, and standard deviation, P = 0.0074), correlating with increased BCL2 and TP53 immuno-expressions. Conclusions High homogeneously distributed proliferation and superficial aneuploid DNA content defines MCCs. Apoptosis follows proliferation in superficial compartments, being less variable and proliferation independent in deep compartments, where it is inversely correlated with BCL2/TP53 expression. [source] The critical role of type-1 innate and acquired immunity in tumor immunotherapyCANCER SCIENCE, Issue 9 2004Hiroaki Ikeda The discovery of a large array of tumor antigens has demonstrated that host lymphocytes can indeed recognize and destroy tumor cells as originally proposed in the cancer immunosurveillance hypothesis. Recent reports that led to the cancer immuno-editing concept also strongly support the immunosurveillance hypothesis, and they further indicate that the host immune system plays a critical role not only in promoting host protection against cancer but also in selecting tumors that can better escape from immune attack. Thus, it is now clear that T cells have the ability to recognize and destroy spontaneously arising tumors. However, the generation of antitumor immunity is often difficult in the tumor-bearing host because of various negative regulatory mechanisms. Here, we review our recent work on tumor immunotherapy, which utilizes the activation of type-1 innate and/or acquired immunity as a potent strategy to overcome immunosuppression in the tumor-bearing host. We have established a variety of tumor therapeutic protocols that aim to activate type-1 immunity, such as tumor-vaccine therapy with CpG encapsulated in liposomes, cell therapy using tumor-specific Th1 cells, and gene therapy using gene-engineered Th1 cells. We found that CpG encapsulated in liposomes stimulated IL-12-producing DC and induced IFN-,-producing NK cells, NKT cells, and tumor-specific CTL. Th1 cell therapy was also shown to be beneficial for acceleration of APC/Th1 cell-cell interaction in the DLN, which was critical for inducing tumor-specific CTL at the tumor site. Therefore, we conclude that the activation of type-1 innate and acquired immunity is crucial for tumor immunotherapy in order to overcome strong immunosuppression in the tumor-bearing host. [source] | ||||||||||