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1.
Several reports have been published about familial polycythaemia vera (PV) but no information is available about the incidence of thrombocytosis in the same family. In our population of thrombocytosic patients, both with primary thrombocytosis (133 cases) and secondary (37 cases), we found only two family related subjects. One of them had PV and the other essential thrombocytosis (ET). Our results seem to indicate that familial thrombocytosis is a rare phenomenon, much less frequent then familial thrombocytopenia.  相似文献   

2.
Eighteen consecutive patients with advanced and/or metastatic colorectal carcinoma have been treated with intraperitoneal administration of radiolabelled (iodine-131) monoclonal antibodies raised against different antigens associated to these kinds of tumours: anti-CEA FO23C5, anti-CEA BW494/32, anti-TAG B72.3, AUA1. The doses of isotope ranged between 21 and 150 mCi (777–5550 MBq) which delivered a radiation dose to the target tumour from 768 to 4628 cGy. Thirteen patients were previously treated with conventional regimens which consisted of chemotherapy (5-fluoracil with or without other anti-neoplastic drugs) both in adjuvant or palliative setting. Three patients are considered non-evaluable owing to concomitant chemotherapy in 2 and lack of objective parameters in 1. Out of 15 evaluable patients 2 achieved complete remission and 2 partial remission with a response rate of 26.6%. Three stable and 8 with progressive disease have also been registered. The toxicity was negligible consisting of hematologic WHO grade 1 in 7 patients, grade 2 in 1 patient and grade 3 in 1 patient, as well as hepatic WHO grade 1 in 8 and grade 2 in 2 patients. The authors conclude that this innovative way of treatment for advanced colorectal carcinoma seems to offer promising therapy; from these data, therefore, a new trial is justified employing radiolabelled MoAbs in well selected patients with metastatic or locally advanced colorectal carcinoma.  相似文献   

3.
《Analytical biochemistry》1985,144(2):329-335
Theoretical calculations showed that biosynthetic radiolabeling of cells using typical concentrations of 32P (1 mCi/ml) resulted in high radiation doses (200–500 rad/h) being absorbed by the cells. Subsequent investigations with a mouse myelomonocytic leukemia cell line (WEHI-3B(D+)) showed significant loss of replicative ability during brief (less than 1 h) exposures to 1 mCi/ml of 32P. Complete loss of cell replicative ability was found with isotopic doses less than 100 rad (i.e., 100 μCi/ml for 5 h). Experiments employing a less radiosensitive pre-B-cell line (18.81) revealed that significant loss of viability occurred during incubation with 32P under identical conditions to those employed for the WEHI-3B(D+) cell line. Control experiments utilizing decayed batches of 32P and physical separation of the isotope solution from the cells confirmed that the cytotoxicity was caused by radiation emission rather than the presence of toxic components in the isotopic solution. The radiation doses absorbed by cells biosynthetically labeled with 59Fe, 33P, 35S, and 14C were calculated. Although significant levels of radiation can be absorbed 32P was considerably more radiotoxic than the other isotopes. The results of calculations indicated that the judicious choice of container geometry could reduce the absorbed radiation dose from 32P solutions. In particular the biosynthetic radiolabeling of cells in capillary tubes (diameter less than 1 mm) can reduce the absorbed rate to less than one-tenth of the dose received by cells suspended in Petri dishes or centrifuge tubes.  相似文献   

4.
From 1984 to 1990 we have treated altogether 25 children with [131I]metaiodobenzylguanidine (131I-MIBG) for a refractory, relapsed or metastasized neuroblastoma. Three children had stage III and 22 children had stage IV of the disease; at diagnosis their ages were between 4 months and 10 years. Children with stage III disease had at diagnosis a median age of 3.0 years and at treatment 3.8 years. After first-line chemotherapy 2 children had achieved a complete remission (CR), while in 1 child the tumor did not respond (NR) to the initial treatment. At the time of 131I-MIBG treatment 2 children had relapsed and in the other one no further response was achievable. The children were treated by a 13.5 +/- 12.9 mCi/kg BW per course with a mean total dose of 280.7 +/- 243.9 mCi. One child achieved CR by 131I-MIBG alone, while in 2 cases no measurable success was observed. All 3 children were treated additionally by surgery, chemotherapy and bone marrow transplantation (BMT). Two children have died but one is alive and in CR. The 22 children with stage IV disease were treated in two different study groups. In group A, 14 children were studied for side-effects and response to 131I-MIBG. All children were pretreated with standard chemotherapy. Five were treated in relapse, 5 in progression and 3 at a refractory state of the disease; only 1 child was in complete remission when being treated with 131I-MIBG. Group A patients were treated with a mean of 2.4 courses, with 10.3 mCi/kg BW for each course.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

5.
INTRODUCTION: The aim of this study was to compare the early outcomes between two groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or 100 mCi of (131)I for remnant ablation. MATERIAL AND METHODS: 224 DTC patients with primary tumor > 1 cm of diameter or multifocal were randomised into prospective clinical trial. Patients with extrathyroideal extension of primary tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi, and 125--100 mCi of radioiodine as the first ablative dose. RESULTS: The effectiveness of thyroid ablation was evaluated after one year, during endogenous TSH (thyroid stimulating hormone) stimulation, and after two years during Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine withdrawal and thyroglobulin serum level was assessed. Distant micrometastases were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no symptoms of persistent disease were detected. At one year follow up full remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The remaining ones, 13.3% and 11.2% respectively, received the second course of (131)I for remnant ablation. There were no statistically significant differences in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment. CONCLUSIONS: Our evaluation of early efficacy of adjuvant radioiodine treatment in low risk DTC patients shows no differences between two radioiodine activities - 60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is recommended.  相似文献   

6.
Short-term treatment with doxorubicin, cytarabine, and 6-thioguanine was given to 91 consecutive adults with acute myelogenous leukaemia. Fifty patients received high doses (regimen I) and 41 very high doses (regimen II). Where possible, six treatment cycles were given (total dose of doxorubicin 450 mg/m2) regardless of the number of cycles required to achieve complete remission. No additional treatment was given. The remission rate was significantly higher with regimen I than with regimen II (34/50 compared with 15/41, p less than 0.01), the latter, more intensive regimen being associated with a greater incidence of fatal infection (13/41 compared with 5/50, p less than 0.01). Duration of remission was, however, significantly longer with regimen II (p less than 0.05); the median has not yet been reached after a minimum follow-up of two years. Intensive short-term treatment is a feasible strategy for the treatment of acute myelogenous leukaemia.  相似文献   

7.
《Endocrine practice》2014,20(3):213-220
ObjectiveRadioactive iodine (RAI) has been associated with hematologic abnormalities. Previous research has shown that even a single dose of RAI can cause changes in the peripheral complete blood count (CBC). It is unclear if the use of dosimetry guidance would prevent the effects of high doses of RAI on bone marrow suppression.MethodsCBC at baseline was compared to a CBC obtained 1 year after the last RAI treatment in 50 thyroid cancer patients that received ≥ 250 mCi RAI during the course of their disease. Cumulative dose, number of treatments, patients’ age, and the use of external beam radiation therapy (EBRT) were considered in the analysis.ResultsWe observed a small but statistically significant decrease in hemoglobin (Hb), hematocrit (Hct), and platelet (Plt) counts at 1 year in 50 patients who had received ≥ 250 mCi RAI. We did not find a significant change in white blood cell count (WBC). Approximately 60% of patients who developed anemia had concomitant WBC and Plt abnormalities. RAI dose, number of treatments, and age at diagnosis did not confer a higher risk of bone marrow suppression.ConclusionHigh cumulative activities of RAI administered under dosimetric guidance are associated with a small but statistically significant decreases in Hb, Hct, and Plt counts. The clinical implications of these changes, if any, are unclear. The benefits obtained with high doses of RAI, when indicated, are likely to outweigh the minimal hematologic risks observed in the present study. (Endocr Pract. 2014;20:213-220)  相似文献   

8.
INTRODUCTION: The aim of the study was to estimate the influence of a thyroid remnants' volume, postsurgical concentration of thyroglobulin and radioiodine dose on the early treatment efficacy of well differentiated thyroid cancer. MATERIAL AND METHODS: We retrospectively analyzed 91 patients (76 females, 15 men) with well differentiated thyroid cancer. RESULTS: Histological classification revealed 68.1% (62/91) papillary thyroid cancers, 25.3% (23/91) follicular thyroid cancers, and 6.6% (6/91) oxyphilic thyroid cancers. Among the group, 74 (81.3%) patients reached the remission criteria and the remaining 17 patients (18.7%) showed biochemical and morphological evidence of metastatic disease. The remission was obtained in 100% of patients in stage I of the disease, 68.4% - in stage II, 78.6% - in stage III and 33.3% in stage IV. The total radioiodine dose used in patients with remission, did not differ from the dose used in patients without remission. We did not observe the influence of remnant's volume on treatment efficacy, however larger remants required higher dose of radioiodine to obtain the remission. Patients with remission had lower postsurgical thyroglobulin concentration than patients without remission. (22.2 vs. 103.3 ng/ml; p = 0.00025). CONCLUSIONS: Early treatment results of well differentiated thyroid cancer depend on the clinical stage, and postoperative serum thyroglobulin level measured after endogenous TSH stimulation. Early treatment results are not dependent on age, sex, histological type of thyroid cancer, the dose of radioiodine used in brackets of 60-150 mCi and additional diseases. Total thyroidectomy is equally efficient as near total.  相似文献   

9.
In order to study a possible dose/response relationship in the tumorigenic effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), groups of hairless mice were treated topically on the back skin with different doses and treatment schedules of TPA in acetone. A group of 104 mice (56 M/48 F) received a single application of 20 nmol TPA; 80 mice (32 M/48 F) received 2 X 20 nmol TPA at 3 day intervals; 95 mice (48 M/47 F) received five applications; and 32 mice (16 M/16 F) received 50 applications of 20 nmol TPA twice weekly. Two groups of 32 mice (16 M/16 F) were painted topically on the back skin twice weekly with doses of 17 and 10 nmol TPA, respectively, in each application for 60 weeks or until the animals died. All applications were given in 0.1 ml reagent grade acetone. A control group was treated twice weekly with acetone alone for 60 weeks. Long-term application of 17 nmol TPA was toxic to the animals, and only 20% survived 10 months. Doses of 10 nmol TPA twice weekly were less toxic, and 80% of the animals survived 14 months. The other doses were fairly non-toxic. The results were assessed statistically by accepted methods for tumor rates and yields, respectively. There was a significant tumor incidence after the higher doses of TPA and a clear dose-response relationship. This further strengthens the evidence that TPA is a complete carcinogen, and not merely a promoter.  相似文献   

10.
We report the first treatment of metastatic breast cancer by systemic radioimmunotherapy. The serial therapy doses were chosen based on quantitative imaging data in a treatment planning approach. A terminally ill patient with aggressive, locally advanced breast cancer who had failed radiation treatment and chemotherapy was injected intravenously with radiolabeled I-131 chimeric L6, a human-mouse chimeric lgG1 monoclonal antibody to adenocarcinoma. Initially, an imaging 10 mCi dose of I-131 chimeric L6 (dose 1) deposited 8.8% of the injected dose in her chest wall tumor at 48 hours. Ten days later the patient was given a 150 mCi I-131 chimeric L6 dose (dose 2) followed three weeks later by a 100 mCi dose (dose 3). Tumor uptake and retention were comparable for doses 1 and 2, and decreased for dose 3. Following dose 3 the patient developed a manageable thrombocytopenia and transient Grade IV granulocytopenia. The tumor was observed to decrease in size with peak tumor regression occurring two weeks after dose 3. This partial response (PR) was achieved by radioimmunotherapy at a time when conventional therapy had been unable to impact the growth of the patient's massive and aggressive tumor.  相似文献   

11.
Myeloproliferative neoplasms are divided into essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Although ruxolitinib was proven to be effective in reducing symptoms, patients rarely achieve complete molecular remission. Therefore, it is relevant to identify new therapeutic targets to improve the clinical outcome of patients. Bcl‐xL protein, the long isoform encoded by alternative splicing of the Bcl‐x gene, acts as an anti‐apoptotic regulator. Our study investigated the role of Bcl‐xL as a marker of severity of MPN and the possibility to target Bcl‐xL in patients. 129 MPN patients and 21 healthy patients were enrolled in the study. We analysed Bcl‐xL expression in leucocytes and in enriched CD34+ and CD235a+ cells. Furthermore, ABT‐737, a Bcl‐xL inhibitor, was tested in HEL cells and in leucocytes from MPN patients. Bcl‐xL was found progressively over‐expressed in cells from ET, PV and PMF patients, independently by JAK2 mutational status. Moreover, our data indicated that the combination of ABT‐737 and ruxolitinib resulted in a significantly higher apoptotic rate than the individual drug. Our study suggests that Bcl‐xL plays an important role in MPN independently from JAK2 V617F mutation. Furthermore, data demonstrate that targeting simultaneously JAK2 and Bcl‐xL might represent an interesting new approach.  相似文献   

12.
Twenty-eight patients with histologically proven metastatic or invasive, unresectable pheochromocytomas, which were shown to concentrate and retain tracer doses of [131I]metaiodobenzylguanidine (131I-MIBG), were treated with therapeutic quantities of this radiopharmaceutical. Between one and six doses ranging from 97 to 301 mCi (cumulative dose 111-916 mCi) were administered. Partial response in tumor size was achieved in 8/28 patients and partial biochemical responses in 12/28 patients. No pharmacological toxicity was observed. Mild radiation sickness (nausea, vomiting, anorexia) occurred in 21/28. Minor degrees of leukopenia and thrombocytopenia were observed in 3/28. There were three cases of hypothyroidism but no significant hepatic, renal, adrenocortical or autonomic nervous dysfunction. We conclude that therapeutic 131I-MIBG can achieve significant therapeutic responses in some cases of malignant pheochromocytoma without pharmacological toxicity and only mild radiotoxicity.  相似文献   

13.
Summary During previous therapeutic trials with interferon, decreased levels of peripheral platelet counts have been observed. Taking advantage of this effect, we investigated the efficacy of recombinant interferon (rec-IFN) in the treatment of thrombocytosis in myeloproliferative diseases. A total of 15 patients with polycythemia vera, essential thrombocytosis, or chronic myeloid leukemia received rec-IFN-alfa at initial doses of 25–70×106 units/week; maintenance therapy following week 8 of treatment consisted of 20–35×106 units/week rec-IFN. Observation periods ranged from 24 to 48 weeks. Significant reductions in the number of platelets were noted in all cases; 12/15 patients achieved platelet counts below 440×109/1 and maintained those normal values for at least 4 weeks. The number of bone marrow megakaryocytes, which had been increased prior to treatment, diminished during rec-IFN therapy, while the previously shortened platelet half-life further decreased with rec-IFN treatment. During rec-IFN-induced remission, the plasma levels of platelet factors, the activity of natural killer cells, and platelet aggregation showed changes between slight improvement and normal values. Severe side effects were only observed with the highest rec-IFN doses; dosage adjustments were effective in improving or eliminating all treatment-related symptoms. Rec-IFN may prove to be a valuable therapeutic alternative to cytostatic treatment of thrombocytosis in myeloproliferative disorders.This study was supported in part by the Austrian Research Grant: P4999 and the Ludwig Boltzmann Institute for Gerontology, Vienna, Austria  相似文献   

14.
目的:探究检测血清肿瘤标志物对预测晚期非小细胞肺癌靶向治疗预后的影响。方法:选取2010年4月至2012年12我院收治的晚期非小细胞肺癌患者70例,均予以吉非替尼进行治疗,检测治疗前及治疗后2个月肿瘤标志物癌胚抗原CEA、角蛋白19的可溶性片段(CYFRA21—1)、癌抗原125(CA125)的表达水平,观察其表达水平与患者疗效之间的关系。结果:治疗后,患者完全缓解1例,部分缓解37例,疾病稳定19例,疾病进展13例,有效率为54.3%。治疗后,治疗有效的患者CEA、CA125明显比治疗前降低,结果具有统计学意义(P〈0.05);而疾病稳定、疾病进展的患者治疗后CEA、CA125与治疗前比却无明显差异(P〉0.05)。治疗有效与疾病稳定的患者治疗后CYFRA21.1有明显降低,但与治疗前比却无明显差异(P〉0.05);而疾病进展患者的CYFRA21—1却明显升高,与治疗前比有显著差异(P〈0.05)。而治疗前,治疗有效的患者血清中CEA、CA125比疾病稳定、疾病进展的患者明显较高,结果具有统计学意义(P〈0.05);疾病稳定患者的CEA、CA125与疾病进展患者的相比,治疗有效的患者CYFRA21-1与疾病稳定、疾病进展的相比,结果均不具有统计学意义(P〉0.05)。结论:治疗前CEA、CA125浓度较高则治疗效果不错.治疗后效果较好则CEA、CA125浓度较低,效果不好则CYFRA21-1浓度较高。利用血清肿瘤标志物可显著反映肿瘤靶向药物治疗的预后情况,为临床判断其治疗效果提供依据。  相似文献   

15.
C Mueller-Eckhardt  V Kiefel 《Blut》1988,57(4):163-167
Therapy for post-transfusion purpura (PTP) is controversial. We have evaluated the effect of high-dose IgG (HDIgG) in 11 PTP cases investigated in our institution and summarized the clinical data of 8 additional cases reported in the literature. Two of these 19 cases had to be eliminated from the analysis (1 patient received a total dose of less than 30 g of IgG; 1 patient died 2 days after starting HDIgG therapy from congestive heart failure). Out of a total of 17 cases, 16 had good or excellent response reaching normal platelet values within few days; only one failure was observed. Five patients relapsed, but attained complete remission after a second course (dose) of IgG. Total doses per course ranged between 52 and 180 g of IgG. Five different IgG preparations were used and seemed similarly effective. No adverse reactions were observed. We conclude that HDIgG is the treatment of choice for PTP.  相似文献   

16.
Recombinant interferon-gamma with a starting dose of 0.5 mg 3x/week subcutaneously, was administered to 6 patients with essential thrombocythemia (median platelet count 1172 X 10(9)/l, range 602-1564). Four of the patients had received alkylating agents previously. Hematological remission, defined as a decrease in platelet counts to less than or equal to 350 X 10(9)/l, was observed in none of these patients. Subsequently 4 of these 6 patients, supplemented by 2 others were treated with interferon-alpha 2c at a dose of 5 X 10(6) U daily subcutaneously. Five patients showed hematological remission. In case of hematological remission the interferon-alpha doses was reduced to 5 X an thereafter to 3 X weekly 5 X 10(6) U. During an observation period ranging from 12-41 weeks platelet counts remained normal in all patients. Side-effects were mild and consisted of fever, myalgias, malaise and itching occurring mainly during the first month of treatment. No dose adaptation was required. The patients treated previously with interferon-gamma experienced the side effects from this drug less tolerably than those from the alpha-compound. These observations suggest that recombinant interferon-alpha may be an effective drug in treating essential thrombocythemia resulting in a sustained response.  相似文献   

17.
We refer to 48 adult patients suffering from acute myeloblastic leukemia, whose leukemic cells showed a typical cytochemical pattern: i.e. weak staining for peroxydase and with sudanblack B and lacking or only weak staining for nonspecific esterase. In 8 patients the leukemic myeloblasts additionally showed distinct granular staining for polysaccharides using the PAS-reaction. The therapeutic response, the remission rate and the survival time of these 8 cases have been compared to those of 40 patients, whose leukemic myeloblasts differed exclusively in the absence of granular PAS-positive materials. Out of the latter PAS-negative cases 7 patients (18%) went into a complete remission (M1, P1), 5 patients achieved partial remission (M2, P1-2), the 50%-survival time was 4.9 months. Out of the 8 granular PAS-positive cases 4 patients (50%) went into complete (M1, P1), and 1 reached partial remission (M2, P1-2). The 50%-survival time of the cases now lasts 10.1 months and three patients are still alive and in persisting complete remission 19, 12.5 and 12 months after diagnosis. These results suggest a better prognosis and an improved therapeutic response in those myeloblastic leukemias which additionally contain cytoplasmic granular PAS-positive materials.  相似文献   

18.
R. E. Alison  D. M. Whitelaw 《CMAJ》1970,102(3):278-280
In a crossover study the effectiveness of intermittent maintenance doses of nitrogen mustard was compared to that of vinblastine sulfate in the treatment of 61 patients with advanced Hodgkin''s disease. Forty-five of the patients had had previous radiation therapy. Nine of 29 patients who received nitrogen mustard as the first drug had a complete response and five had a partial response. The comparative results in 32 patients receiving vinblastine sulfate first were nine complete responses and 13 partial responses. The median duration of the complete responses to each drug was 43 weeks. The partial responses were of shorter duration. When the second drug was given in adequate doses, almost as many patients responded with a similar median duration of response.It is concluded that nitrogen mustard and vinblastine sulfate are equally effective single agents in the treatment of patients with advanced Hodgkin''s disease and that patient preference would favour vinblastine sulfate because of its negligible side effects.  相似文献   

19.
Bhol KC  Rojas AI  Khan IU  Ahmed AR 《Cytokine》2000,12(7):1076-1083
Interleukin 10 (IL-10) is an immunoregulatory cytokine produced by T lymphocytes and macrophages. Recently, it has been suggested that IL-10 may be involved in the pathogenesis of various inflammatory and autoimmune diseases. Using an ELISA we investigated the presence of IL-10 in the serum and blister fluid of pemphigus vulgaris (PV) patients with active disease and those in prolonged clinical remission compared with normal controls. Sera from patients with bullous pemphigoid (BP), ocular cicatricial pemphigoid (OCP), oral pemphigoid (OP) and blister fluid from five patients with BP were also studied. Increased levels of IL-10 were detected in the sera of 87.5% of patients with active PV and were statistically significant (P=0.0003) when compared with levels in normal human serum. Lower levels of IL-10 were detected in 12.5% PV patients in remission and were statistically significant (P=0.0001) when compared with levels in patients with active disease. Levels of IL-10 were detected in sera of 4.6% (1 of 24) of the normal controls. The levels of IL-10 were approximately four times higher in blister fluids than levels in the serum in the same PV patients. This difference was highly statistically significant (P=0.0008). A correlation was observed between serum levels of IL-10 and titres of pemphigus autoantibodies and with disease severity. Elevated level of IL-10 was detected in the blister fluid from five BP patients. Levels of IL-10 in the sera of patients with BP, OCP and OP were not significantly increased. These preliminary data suggest that IL-10 in concert with other cytokines may play an important role in the pathogenesis of PV and BP.  相似文献   

20.
The humoral response of mice and rabbits to the injection of whole-cell pertussis vaccine (PV) and acellular pertussis vaccine (APV), developed at the Mechnikov Research Institute for Vaccines and Sera (Russian Acad. Med. Sci.) in Moscow, was studied. In the sera of immunized animals antibodies to the antigenic complex were determined in the direct hemagglutination (DHA) test, specific antibodies to filamentous hemagglutinin (FHA) and pertussis toxin (PT)--in the enzyme immunoassay (EIA) and antibodies neutralizing PT in a cytopathogenic dose (CPD)--in neutralization test on Chinese hamster ovary (CHO) cells. In mice and rabbits immunized with APV the antibody titers determined in the DHA test were higher than those in the animals immunized with PV. Specific antibodies titers to FHA and PT in the sera of rabbits immunized with APV were also higher than those in the sera of rabbits immunized with PV. High dilutions of sera taken from the animals immunized with APC neutralized 4-16 doses of PT in the neutralization test on CHO cells. The most important result of this study was the detection of a more pronounced immune response in the animals immunized with APV in comparison with that induced by PV according to the results obtained in EIA and in the test of PT CPD neutralization on CHO cells.  相似文献   

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