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Sequential Treatment (sequential + treatment)
Selected AbstractsSequential Treatment of Severe Postmenopausal Osteoporosis After Teriparatide: Final Results of the Randomized, Controlled European Study of Forsteo (EUROFORS),,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Richard Eastell Abstract It is unclear which treatment should be given after stopping teriparatide therapy for severe osteoporosis. In a prospective, randomized, controlled, 2-yr study, we compared BMD effects and clinical safety of three follow-up treatments (anabolic with teriparatide, antiresorptive with raloxifene, or no active treatment) after 1 yr of teriparatide. Postmenopausal women with osteoporosis and a recent fragility fracture received open-label teriparatide (20 ,g/d) for 12 mo before they were randomized (3:1:1) to continue teriparatide (n = 305), switch to raloxifene 60 mg/d (n = 100), or receive no active treatment for the second year (n = 102). All patients received calcium and vitamin D supplementation. Changes in areal BMD from baseline to 24 mo were analyzed using mixed-model repeated measures. Daily teriparatide treatment for 2 yr significantly increased spine BMD by 10.7%. Patients receiving raloxifene in year 2 had no further change in spine BMD from year 1 (change from baseline, 7.9%), whereas patients receiving no active treatment had a BMD decrease of 2.5% in year 2 (change from baseline, +3.8%). At the total hip, BMD increases from baseline at 2 yr were 2.5% with teriparatide, 2.3% with raloxifene, and 0.5% with no active treatment; the respective changes at the femoral neck were 3.5%, 3.1%, and 1.3%. The study had insufficient power to assess antifracture efficacy. In conclusion, BMD increases progressively over 2 yr of teriparatide therapy in women with severe osteoporosis. After discontinuation of teriparatide, raloxifene maintains spine BMD and increases hip BMD. [source] Effect of Sequential Treatment of Warm Water Dip and Low-dose Gamma Irradiation on the Quality of Fresh-cut Green OnionsJOURNAL OF FOOD SCIENCE, Issue 3 2005Hyun Jung Kim ABSTRACT: The effect of warm water dip in combination with irradiation on quality of fresh-cut green onions was studied. Fresh-cut green onions were treated with and without warm water (50°C for 20 s) and packaged prior to irradiation at 0, 0.5, 1.0, and 1.5 kGy, then stored at 4°C for 14 d. Color, texture, decay percentage, electrolyte leakage, sensory qualities, and total aerobic count (TAC) were measured at 1,4,8, and 14 d of storage. The warm water treatment reduced the TAC by 0.9 log initially but the beneficial effect disappeared during storage. With the test conditions used in this study, the warm water treatment did not provide added benefits for quality improvements. Irradiation at all tested doses reduced TAC and the development of decay and off-odor, improved visual quality, and preserved green color. [source] Sequential treatment of angiosarcoma of the back with liposomal doxorubicin and radiotherapyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2005P Santos [source] UIII -Induced Reductive Co-Coupling of NO and CO to Form UIV Cyanate and Oxo DerivatesCHEMISTRY - A EUROPEAN JOURNAL, Issue 31 2010Alistair S. CO and NO give NCO and O! Sequential treatment of [U(,-C8H6{SiiPr3 -1,4}2)(,-Cp*)] with CO followed by NO (or vice versa) affords a mixture of the bridging cyanate complex [{U(,-C8H6{SiiPr3 -1,4}2)(,-Cp*)}2(,-OCN)2] and the bridging oxo complex [{U(,-C8H6{SiiPr3 -1,4}2)(,-Cp*)}2(,-O)], both of which have been structurally characterised (see scheme). [source] Induction of eotaxin production by interleukin-4, interleukin-13 and lipopolysaccharide by nasal fibroblastsCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2004M. Nonaka Summary Background There is growing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. Fibroblasts are a major source of eotaxin. The severity of diseases with eosinophilic inflammation like nasal polyposis, atopic dermatitis and asthma, where Th2-type cytokines (IL-4 and IL-13) and TGF-, are expressed locally, was shown to correlate with bacterial factors such as lipopolysaccharide (LPS) rather than allergen. Objective We examined eotaxin production by nasal fibroblasts stimulated with IL-4 or IL-13 alone or in combination with LPS, and the effect of TGF-,1 on it. Moreover, we compared the magnitude of eotaxin produced by nasal fibroblasts with that produced by lung or skin fibroblasts. Methods Fibroblast lines were established from human biopsy tissue. The expression of eotaxin mRNA was evaluated by RT-PCR. The amount of eotaxin in the supernatants was measured by ELISA. Results IL-4, but not IL-13, synergized with LPS to produce eotaxin in a dose- and time-dependent manner. Sequential treatment of nasal fibroblasts with IL-4 and LPS did not have any effect. But when IL-4 and LPS were added together, synergy for eotaxin production was observed. Moreover, this synergy was observed in nasal and skin fibroblasts, but not in lung fibroblasts. The production of eotaxin by IL-4 and LPS was modulated by TGF-,1. Conclusion These results suggest that a co-stimulus like LPS is necessary for IL-4 to make a strong induction of eotaxin in eosinophilic inflammations such as nasal polyposis. Modulation by TGF-,1 may have important implications for the development of eosinophilic inflammation. [source] Outcome of late-life depression after 3 years of sequential treatmentACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2009R. M. Kok Objective:, To study the outcome of a sequential treatment protocol in elderly, severely depressed in-patients. Method:, All 81 patients from a 12-week double-blind randomized controlled trial (RCT) comparing venlafaxine with nortriptyline were asked to participate in a 3 year follow-up study. Thirty-two patients who did not achieve remission during the RCT, entered an open sequential treatment protocol and were treated with augmentation with lithium, switch to a monoamine oxidase inhibitor or ECT. Results:, Seventy-eight of the 81 patients (96.3%) achieved a response [,50% reduction in Montgomery Åsberg Depression Rating Scale score) and 68 patients (84%) a complete remission (final MADRS score , 10) within 3 years of treatment. Greater severity and longer duration of the depressive episode at baseline predicted poor recovery. Augmentation with lithium may be the best treatment option in treatment resistant depressed elderly. Only few patients dropped-out due to side-effects. Conclusion:, Our study demonstrates the importance of persisting with antidepressant treatment in elderly patients who do not respond to the first or second treatment. [source] Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis B virus infection for the fiscal year 2008 in JapanHEPATOLOGY RESEARCH, Issue 1 2010Hiromitsu Kumada In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older. Even for patients with chronic hepatitis who are negative for hepatitis e antigen (HBeAg), but who harbor HBV DNA in titers of 7 log copies/mL or more, a "drug-free state" is aimed for by sequential treatment with interferon (IFN) plus entecavir as the first line. For patients with chronic hepatitis B aged 35 years or older, who are HBeAg-negative and carry HBV DNA in titers of less than 7 log copies/mL, long-term IFN for 24,48 weeks is adopted anew. To HBeAg-negative patients who have either or both platelet counts of less than 150 × 103/mm3 and less than 7 log copies of HBV DNA, also, long-term IFN for 24,48 weeks is indicated. [source] Unusual products in reactions using ethyldimesitylborane, mesityllithium, and carbonyl compoundsHETEROATOM CHEMISTRY, Issue 5 2001Takayuki Kawashima Unusual carbonyl adducts, Mes2BCH=CHCHCH3CRR1OH, were obtained by sequential treatment of ethyldimesitylborane with mesityllithium (<1.0 equiv.) and carbonyl compounds instead of the normal adducts, Mes2BCHCH3CRR1OH. A mechanistic study was carried out. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:354,357, 2001 [source] Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2008Takefumi Suzuki Abstract Objective To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner. Methods In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks. Results Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9,mg; risperidone 3.14,mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5,mg; risperidone 5.50,mg). Body weight, prolactin, and total cholesterol increased significantly. Conclusions Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer- term monotherapy are warranted for refractory schizophrenia. Copyright © 2008 John Wiley & Sons, Ltd. [source] New access to thiazolo[4,5- d]pyrimidine derivativessJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2006M. Bakavoli 4-Amino-5-bromo-2-substituted-aminopyrimidines are readily obtained from the newly prepared 5-bromo-2,4-dichloro-6-methylpyrimidine by sequential treatment with ethanolic ammonia and secondary amines. These compounds were successfully reacted with various isothiocyanates in the presence of sodamide in DMF to form the new thiazolo[4,5- d] pyrimidine derivatives. [source] 5-azacitidine restores and amplifies the bicalutamide response on preclinical models of androgen receptor expressing or deficient prostate tumorsTHE PROSTATE, Issue 11 2010Giovanni Luca Gravina Abstract BACKGROUND Epigenetic modifications play a key role in the in prostate cancer (Pca) progression to a hormone refractory state (HRPC) and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. In this regard, 5-Azacitine (5-Aza) represents a promising epigenetic modulator. This study tested the hypothesis that 5-Aza may restore and enhance the responsiveness of HRPC cells to anti-hormonal therapy on Androgen receptor (AR) expressing (22rv1) and AR-deficient (PC3) cells. METHODS The effects were studied in vitro and in vivo models. This sequential treatment induced in vitro cell cycle arrest and apoptosis both in 22rv1 and PC3 tumor cell lines. RESULTS This combined treatment up-regulated the expression of FasL, phospho-FADD, p16INKA, Bax, Bak, and p21WAF1, and inhibited FLIP, Bcl-2, and Bcl-XL expression. The re-activation of hormonal response of AR-negative PC3 cell line was partially due to the AR re-expression mediated by 5-Aza treatment. In contrast, the increase in the response to anti-androgenic therapy in 22rv1 did not correlate with AR expression levels. Furthermore, xenograft studies revealed that the combined treatment of 5-Aza with AR-antagonist Bicalutamide had additive/synergistic effects in repressing tumor growth in vivo and the underlying mechanisms responsible for these effects seem to be in part mediated by induction of apoptosis. CONCLUSIONS So, this study strongly suggests a therapeutic potential of 5-Aza in combination with anti-androgen therapy in patients with in AR expressing and AR-deficient HRPC. Prostate 70: 1166,1178, 2010. © 2010 Wiley-Liss, Inc. [source] Overcoming immunological tolerance to melanoma: Targeting CTLA-4ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2010F Stephen HODI Abstract The use of immunotherapeutics in melanoma has received much attention, and recent advances to further characterize the regulatory components of the immune system and the importance of co-stimulatory molecules have opened a new area for clinical investigation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) serves as a negative regulator of immunity. Recent trials administering fully human anti-CTLA-4 monoclonal antibodies to melanoma patients have demonstrated clinically meaningful responses. Treatment with CTLA-4 blocking antibodies, however, is not without potential toxicities. Autoimmune side-effects, the most common being colitis-associated diarrhea, are frequently associated with clinical responses. In efforts to build upon prior vaccination efforts as well as attempt to offer patients clinically meaningful immune responses with a CTLA-4 blockade but without significant toxicities, we conducted a clinical trial in patients who previously received autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GVAX; Cell Genesys, South San Francisco, CA, USA) with periodic infusions of CTLA-4 blocking antibodies. This sequential treatment resulted in clinically significant anti-tumor immunity without grade 3 or 4 toxicity in most patients. Pathological analyses following treatment of pre-existing tumors revealed a linear correlation between tumor necrosis and the ratio of intra-tumoral CD8+ effector cells to FoxP3+ regulatory cells (Tregs). Effective anti-tumor immunity and serious autoimmunity can be disassociated. Further targeting of anti-tumor Tregsin combinatorial therapy approaches may be a rich avenue of future investigation. [source] Phosphoinositide 3-kinase/Akt inhibition increases arsenic trioxide-induced apoptosis of acute promyelocytic and T-cell leukaemiasBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Giovanna Tabellini Summary Recent studies suggest that the prosurvival signal transduction pathway involving phosphoinositide 3-kinase (PI3K)/Akt can confer an aggressive, apoptosis-resistant phenotype to acute leukaemia cells. We have investigated the effect of modulating this signalling pathway on the sensitivity of leukaemic cell lines (NB-4, CEM, Jurkat, MOLT-4) and acute promyelocytic primary blasts to apoptosis induced by 1 ,mol/l As2O3. Whereas parental NB-4 cells did not display any phosphorylated (active) Akt, CEM, Jurkat and MOLT-4 cells exhibited high levels of Akt activation. Consistently, treatment of NB-4 cells with pharmacological inhibitors of the PI3K/Akt pathway (LY294002, wortmannin) did not increase sensitivity of these cells to arsenic trioxide (As2O3), whereas siRNA knock-down of Akt enhanced As2O3 -induced apoptosis of CEM, Jurkat and MOLT-4 cells. Overexpression of a constitutively active Akt cDNA rendered NB-4 cells less susceptible to As2O3. Upon prolonged exposure to As2O3, we isolated a NB-4 cell clone that was resistant to As2O3 and displayed high levels of active Akt. LY294002 treatment of acute promyelocytic primary blasts with elevated Akt phosphorylation levels resulted in an increased sensitivity to As2O3. These results may provide a rationale for the development of combined or sequential treatment with PI3K/Akt inhibitors to improve the efficacy of As2O3 on acute leukaemias and also to overcome As2O3 resistance. [source] Combining endocrine agents with chemotherapy: Which patients and what sequence?,CANCER, Issue S3 2008Kathleen I. Pritchard MD Abstract In metastatic breast cancer, attempts to improve response to therapy by combining hormones and chemotherapy began in the 1970s. Since then, several randomized trials comparing single-agent hormone therapy or chemotherapy versus sequential combinations of these agents have been performed. In the majority of those studies, an increased response rate or an increased time to progression was observed when chemotherapy was added to hormone therapy or when hormone therapy was added to chemotherapy. However, in few of those trials was the increased response rate statistically significant or the response duration significantly prolonged, and no studies reported an improvement in overall survival. Furthermore, the studies did not make the correct comparisons of 1) hormone therapy alone followed by chemotherapy alone versus hormone therapy and chemotherapy given concurrently or 2) chemotherapy alone followed by hormone therapy versus concurrent chemotherapy and hormone therapy. To truly be advantageous, concurrent treatment should provide an increased response rate and response duration compared with the added or overall response rate and response duration of the same agents used sequentially. In the adjuvant setting, the timing and sequencing of hormone therapy and chemotherapy also has not been studied well. However, it has been accepted widely that adjuvant chemotherapy should be completed before beginning tamoxifen. No trials examining concurrent versus sequential treatment have been performed with hormone therapy and chemotherapy in the premenopausal setting or with aromatase inhibitors and chemotherapy in postmenopausal women. Considering the demonstrated importance of the timing of chemotherapy and tamoxifen in the postmenopausal setting, these questions should be explored further. Cancer 2008. © 2007 American Cancer Society. [source] Successful Treatment of a Cosmetic Tattoo Using a Combination of LasersDERMATOLOGIC SURGERY, Issue 1 2004Karen Rebecca Suchin MD Background. Cosmetic tattoos are becoming more popular and are often composed of several colors. Tattoo pigments containing ferric oxide and titanium dioxide can change to a blue-black color after exposure to Q-switched lasers that can be permanent. Objective. Using a patient who presented with rouge tattoos on the cheeks as an example, we describe a useful approach to laser treatment of cosmetic tattoos. Methods. Test areas were done with the Q-switched Nd:YAG at both 532 and 1064 nm and with the pulsed-dye laser at 595 nm. Results. Although an immediate blue-black color change occurred after treatment with the Nd:YAG at 532 and 1064 nm, sequential treatments at 1064 nm produced a near complete clearance of the tattoos. The pulsed-dye laser was used to remove subtle pink tones. Conclusion. Performing small test areas before complete treatment and using several laser wavelengths throughout the course of therapy are essential to the successful treatment of cosmetic tattoos. [source] Estimation of the Causal Effects on Survival of Two-Stage Nonrandomized Treatment Sequences for Recurrent DiseasesBIOMETRICS, Issue 3 2006Xuelin Huang Summary In the treatment of cancer, patients commonly receive a variety of sequential treatments. The initial treatments administered following diagnosis can vary, as well as subsequent salvage regimens given after disease recurrence. This article considers the situation where neither initial treatments nor salvage treatments are randomized. Assuming there are no unmeasured confounders, we estimate the joint causal effects on survival of initial and salvage treatments, that is, the effects of two-stage treatment sequences. For each individual treatment sequence, we estimate the survival distribution function and the mean restricted survival time. Different treatment sequences are then compared using these estimates and their corresponding covariances. Simulation studies were conducted to evaluate the performance of the methods, including their sensitivity to the violation of the assumption of no unmeasured confounders. The methods are illustrated by a retrospective study of patients with soft tissue sarcoma, which motivated this research. [source] | ||||||||||||||||||||||