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971.
Autoimmune thrombocytopenic purpura (AITP) is generally a chronic disorder in affected adults. Twenty-five percent of these patients will become refractory to routine therapy (corticosteroids and splenectomy), as well as most other available agents. Intravenous pulse cyclophosphamide therapy was used to treat 20 patients with severe refractory AITP who had previously failed to achieve a sustained remission with a mean of 4.8 agents (range 2 to 8). Patients received 1 to 4 doses (mean 2.0) of 1.0 to 1.5 g/m2 intravenous cyclophosphamide per course. Of the 20 patients treated with pulse cyclophosphamide therapy, 13 patients (65%) achieved a complete response (CR), four (20%) a partial response (PR), and three patients (15%) failed to respond. Of the 13 complete responders, eight have remained in remission with stable platelet counts during followup intervals of 7 months to 7 years (median 2.5 years). Five patients developed recurrent AITP 4 months to 3 years following a CR. Of these, two patients responded to subsequent courses of pulse cyclophosphamide therapy with current remissions of 1 and 4 years. Of the four patients who obtained a PR, two remain in partial remission after 10 months and 4 years; one relapsed after 18 months and, after retreatment, is still in remission at 6 months. Of the patient characteristics examined, duration of disease was most strongly associated with response to pulse cyclophosphamide. Side-effects of treatment included neutropenia (three patients, one of whom developed staphylococcal sepsis), acute deep venous thrombosis (two patients), and psoas abscess (one patient). Intravenous pulse cyclophosphamide should be strongly considered in the treatment of patients with refractory AITP. There is a relatively low incidence of side-effects, and it can be administered easily on an out- patient basis. 相似文献
972.
Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid 总被引:24,自引:1,他引:24
The recent finding that retinoic acid induces terminal granulocytic differentiation of the human promyelocytic leukemia cell line, HL-60, prompted an investigation of the sensitivity to this inducer of human myelocytic leukemia cells in primary suspension culture. Of the 21 leukemic specimens, only cells from the two patients with acute promyelocytic leukemia differentiated in response to retinoic acid. After an incubation period of 5--7 days in 1 microM retinoic acid, the cells from these two patients showed extensive morphological and functional maturation. Thus, because it appears that retinoic acid specifically induces granulocytic differentiation of leukemic promyelocytes, this compound may have therapeutic utility in the treatment of acute promyelocytic leukemia. 相似文献
973.
Biochemical and functional consequences of dissociation of the platelet membrane glycoprotein IIb-IIIa complex 总被引:10,自引:1,他引:10
The platelet membrane glycoproteins, IIb and IIIa, form a Ca2+- dependent heterodimer complex that functions as the fibrinogen receptor in activated platelets to mediate platelet aggregation. Little is known about factors that affect the IIb-IIIa complex within the platelet membrane. It has been observed that platelets incubated with ethylene glycol tetra-acetic acid (EGTA) at 37 degrees C are unable to aggregate or to bind monoclonal antibodies specific for the IIb-IIIa complex. To determine whether this is due to a dissociation of IIb from IIIa, we developed a method for quantitating the complex on nondenaturing, polyacrylamide gradient gels. Platelets were surface-labeled with 125I and then solubilized and electrophoresed in 0.2% Triton and 10 mmol/L CHAPS. Under these conditions and in the presence of 1 mmol/L Ca2+, glycoproteins IIb and IIIa migrated on the gels as a discrete band at Rf = 0.33. Protein that was eluted from this band bound to an immunoaffinity column specific for the IIb-IIIa complex. In contrast, when the IIb-IIIa complex was solubilized and then dissociated with EGTA, the discrete band at Rf = 0.33 was no longer present, and IIb and IIIa were now found in a broad band at Rf = 0.45 to 0.50. To study IIb and IIIa within the surface membrane, the 125I-labeled platelets were first incubated with 0.5 mmol/L EGTA (1 nmol/L free Ca2+) at 22 degrees C and then solubilized in the absence of EGTA. The IIb and IIIa from these platelets migrated at Rf = 0.33, indicating the presence of the intact IIb-IIIa complex. In contrast, when the platelets were incubated at 37 degrees C for one hour with the EGTA, the discrete band at Rf = 0.33 representing the IIb-IIIa complex gradually disappeared. This phenomenon could not be reversed by adding Ca2+ back to the platelets before solubilization and electrophoresis. This loss of the IIb-IIIa complex from intact platelets was accompanied by (a) a progressive and irreversible decrease in adenosine diphosphate (ADP)-induced platelet aggregation and (b) decreased binding of a complex-dependent monoclonal antibody to the platelets. These studies demonstrate that when platelets are exposed to low Ca2+ at 37 degrees C, the IIb-IIIa heterodimer complexes in their surface membranes are irreversibly disrupted. Because intact IIb-IIIa complexes are required for platelet aggregation, the loss of these complexes may account for the failure of these platelets to aggregate in response to ADP. 相似文献
974.
Daniel A. Decurcio Giampiero Rossi-Fedele Carlos Estrela Shaju J. Pulikkotil Venkateshbabu Nagendrababu 《Journal of endodontics》2019,45(4):387-393.e2
Introduction
This systematic review and meta-analysis aimed to assess whether machine-assisted agitation resulted in less postoperative pain (PP) compared with syringe irrigation with needle alone in adult patients undergoing root canal treatment.Methods
A literature search was performed in 3 electronic databases for articles published before August 2018. Randomized clinical trials published in English that compared PP between machine-assisted agitation and syringe irrigation with needles as part of nonsurgical root canal treatment were included. Two authors were independently involved in the article selection process, data extraction, and assessment of the quality of included studies using the revised Cochrane risk of bias tool. The pooled effect estimates of the standardized mean difference (SMD) between machine-assisted agitation and syringe irrigation with needle was calculated by a random effects–modeled meta-analysis. A subgroup meta-analysis was performed. The quality of evidence was evaluated by the Grading of Recommendations, Assessment, Development and Evaluations approach.Results
Six studies were included for systematic review. Meta-analysis was performed using 3 studies and showed that machine-assisted agitation resulted in less PP compared with syringe irrigation with needle at 24 hours (SMD = ?0.73; 95% confidence interval, ?1.04 to ?0.42; I2 = 30.6%) and 48 hours (SMD = ?0.60; 95% CI, ?0.85 to ?0.35; I2 = 0%). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations for the PP outcomes (24 hours and 48 hours) was graded as “moderate” quality.Conclusions
Machine-assisted agitation reduced PP compared with syringe irrigation with needles in nonsurgical root canal treatment. Future clinical trials are needed to support the result of this review. 相似文献975.
Venkateshbabu Nagendrababu Shaju Jacob Pulikkotil Sajesh K. Veettil Peerawat Jinatongthai James L. Gutmann 《Journal of Evidence》2019,19(1):17-27
Objectives
Pulpotomy is the favored treatment for pulp exposure in carious primary teeth. This review aimed to compare the success rates of biodentine (BD) and mineral trioxide aggregate (MTA) pulpotomies in primary molars using meta-analysis (MA) and trial sequential analysis (TSA) and also to assess the quality of the results by Grading of Recommendations, Assessment, Development and Evaluation (GRADE).Methods
PubMed, EBSCOhost, and Scopus databases were searched. Additional searching was performed in clinical trial registry, reference lists of systematic reviews, and textbooks. Randomized clinical trials (RCTs) published in the English language through October 2017 comparing the success of pulpotomies in vital primary molars with a follow-up of at least 6 months were selected. Study selection, data extraction, and risk of bias assessment were performed. MA by random effects model, TSA, and GRADE were performed.Results
Eight RCTs (n = 474) were included. Two RCTs had low risk of bias. No significant difference was observed between MTA and BD in clinical success at 6 months (risk ratio [RR], 1.00; 95% confidence interval [95% CI], 0.97-1.02; I2 = 0%), 12 months (RR, 1.00; 95% CI, 0.96-1.05; I2 = 0%), and 18 months (RR, 1.00; 95% CI, 0.93-1.08; I2 = 0%). No difference was observed in radiographic success at follow-up of 6 months (RR, 0.99; 95% CI, 0.96-1.02; I2 = 0%), 12 months (RR, 1.02; 95% CI, 0.47-2.21; I2 = 0%), and 18 months (RR, 1.02; 95% CI, 0.91-1.15; I2 = 0%). TSA indicated lack of firm evidence for the results of the meta-analytic outcomes on clinical and radiographic success. GRADE assessed the evidence from the MA comparing the effect of MTA and BD in pulpotomy to be of low quality.Conclusion
BD and MTA have similar clinical and radiographic success rates based on limited and low-quality evidence. Future high-quality RCTs between MTA and BD is required to confirm the evidence. 相似文献976.
背景和目的:对于单用吸入糖皮质激素控制不佳的成人支气管哮喘(简称哮喘)患者,加用长效β-受体激动剂(LABA)可有效改善患者的症状及肺功能.但是最近对LABA长期治疗的安全性受到了美国食品药品管理局(FDA)及部分哮喘专家的质疑.另外,鉴于每个哮喘患者对治疗的反应不尽相同,因此寻求未控制哮喘患者的其他治疗方法是必要的. 相似文献
977.
978.
ME Bradley ME Bond J Manini Z Brown SJ Charlton 《British journal of pharmacology》2009,158(1):328-338
Background and purpose:
In several previous studies, the C-X-C chemokine receptor (CXCR)2 antagonist 1-(2-bromo-phenyl)-3-(7-cyano-3H-benzotriazol-4-yl)-urea (SB265610) has been described as binding competitively with the endogenous agonist. This is in contrast to many other chemokine receptor antagonists, where the mechanism of antagonism has been described as allosteric.Experimental approach:
To determine whether it displays a unique mechanism among the chemokine receptor antagonists, the mode of action of SB265610 was investigated at the CXCR2 receptor using radioligand and [35S]-GTPγS binding approaches in addition to chemotaxis of human neutrophils.Key results:
In equilibrium saturation binding studies, SB265610 depressed the maximal binding of [125I]-interleukin-8 ([125I]-IL-8) without affecting the Kd. In contrast, IL-8 was unable to prevent binding of [3H]-SB265610. Kinetic binding experiments demonstrated that this was not an artefact of irreversible or slowly reversible binding. In functional experiments, SB265610 caused a rightward shift of the concentration-response curves to IL-8 and growth-related oncogene α, but also a reduction in maximal response elicited by each agonist. Fitting these data to an operational allosteric ternary complex model suggested that, once bound, SB265610 completely blocks receptor activation. SB265610 also inhibited basal [35S]-GTPγS binding in this preparation.Conclusions and implications:
Taken together, these data suggest that SB265610 behaves as an allosteric inverse agonist at the CXCR2 receptor, binding at a region distinct from the agonist binding site to prevent receptor activation, possibly by interfering with G protein coupling. 相似文献979.
Silber SJ; Nagy Z; Devroey P; Camus M; Van Steirteghem AC 《Human reproduction (Oxford, England)》1997,12(12):2693-2700
Factors other than spermatozoa could be the major determinant of the
success of assisted reproduction treatment in cases of male infertility.
Our aim was to evaluate the effect of the wife's age and ovarian reserve on
assisted reproduction success rates in the most severe type of male
infertility, i.e. azoospermia. A total of 249 consecutive couples suffering
from male infertility caused by azoospermia underwent microsurgical
epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE)
with intracytoplasmic sperm injection (ICSI). Of these men, 186 had
irreparable obstructive azoospermia, and 63 had non-obstructive azoospermia
due to testicular failure. Neither the pathology, the source, the quantity,
nor the quality of spermatozoa had any effect on fertilization or pregnancy
rates. Maternal age and ovarian reserve (number of eggs) had no effect on
fertilization or embryo cleavage, but did dramatically affect the embryo
implantation, pregnancy and delivery rates. Wives of azoospermic men who
were in their 20s had a 46% live delivery rate per cycle, wives aged 30-36
years had a 34% live delivery rate per cycle, wives aged 37- 39 years had a
13% live delivery rate per cycle, and wives > or = 40 years had only a
4% live delivery rate per cycle. The number of eggs retrieved also affected
pregnancy and delivery rate, but to a lesser extent than age. In virtually
all cases of obstructive azoospermia, and in 62% of cases with
non-obstructive azoospermia caused by germinal failure, sufficient
spermatozoa could be retrieved to perform ICSI, with normal fertilization
and embryo cleavage. However, the pregnancy rate and the live delivery rate
were dependent strictly on the age of the wife, and on her ovarian reserve.
Unfortunately, exaggerated claims of high pregnancy rates can thus easily
be made by manipulating, in a very simple way, selection for female
factors.
相似文献
980.
EM Varga MR Jacobson SJ Till K Masuyama F O''Brien SR Durham S Rak V Lund GK Scadding QA Hamid 《Allergy》1999,54(4):338-345
BACKGROUND: Allergen challenge in allergic rhinitis patients leads to local eosinophilia and Th2-type cytokine expression. Natural exposure to grass pollen is additionally characterized by epithelial mast-cell infiltration. We hypothesized that perennial allergic rhinitis is also associated with T-cell and eosinophil infiltration of the nasal mucosa, local Th2-type cytokine expression, and increased numbers of nasal epithelial mast cells. METHODS: Nasal biopsies from perennial allergic rhinitis patients and controls were analysed by immunocytochemistry for different cell populations and in situ hybridization for cytokine mRNA-expressing cells. RESULTS: Perennial allergic rhinitis was associated with increased numbers of submucosal CD3+ T cells (P=0.05), EG2+ activated eosinophils (P=0.01), and CD68+ macrophages (P=0.01) compared to controls. Epithelial, but not submucosal, tryptase-positive mast cells were also elevated in rhinitics compared to controls (P=0.01). The numbers of cells expressing interleukin (IL)-5 were higher (P=0.01) and the numbers of cells expressing IL-2 were lower (P=0.04) in rhinitic patients than controls. There were no significant differences for either IL-4 or interferon-gamma between the groups. CONCLUSIONS: Perennial allergic rhinitis is characterized by mast-cell migration into the epithelium; submucosal infiltration by T cells, eosinophils, and macrophages; and an imbalance in local T-cell cytokine production in favour of enhanced IL-5 and reduced IL-2 expression. 相似文献