伽玛刀治疗对胶质母细胞瘤复发时间的影响

目的:通过比较胶质母细胞瘤手术后行伽玛刀治疗组与未行伽玛刀治疗组复发时间有无差别,以探讨伽玛刀治疗胶质母细胞瘤的疗效.方法:34例手术后病理检查证实为胶质母细胞瘤的患者,14例术后行伽玛刀治疗,20例未行其他任何治疗,34例患者均随访至复发,复发后均再次行手术治疗.统计两组复发时间,用t-检验判断两组有无区别.结果:术后行伽玛刀治疗组平均复发时间为10.57个月,术后未行伽玛刀治疗组平均复发时间为6.15个月,t＝2.260,P＝0.031＜0.05,有统计学意义,手术后未行伽玛刀治疗组早于伽玛刀治疗组复发.结论:伽玛刀治疗可以延缓胶质瘤手术后复发时间,是胶质母细胞瘤术后综合治疗的一种重要手段.     

Polymer-Based Materials in Cancer Treatment: From Therapeutic Carrier and Ultrasound Contrast Agent to Theranostic Applications

The emergence of theranostics with ultrasound technology is a promising development, as it opens pathways to providing more effective treatments for cancer. Advancements in ultrasound imaging would give a more detailed and accurate image for better diagnosis and treatment planning. Polymeric ultrasound contrast agents (UCAs) are appealing because they are stable and easily modified for active targeting. In addition, a better therapy could be achieved in conjunction with advancements in UCAs. The active targeting not only makes the precise imaging possible, but also leads to targeted delivery of active components to specific local treatment sites. A polymeric nanocarrier with surface bioconjugation is the key to prolonging the bioavailability of the encapsulated drugs or genes and the capacity to target the specific tumor site. Using ultrasound with other imaging modalities will open more precise and better ways for diagnosis and therapy and bring us a step closer to personalized medicine. This review focuses on polymer-based materials of UCAs, multimodal imaging agents and therapeutic carriers that have been currently explored for their theranostic applications involving ultrasound for cancer diagnosis and treatment.     

A novel series of phenolic temozolomide (TMZ) esters with 4 to 5-fold increased potency,compared to TMZ,against glioma cells irrespective of MGMT expression

The standard of care treatment for patients diagnosed with glioblastoma multiforme (GBM) is temozolomide (TMZ). Tumour resistance to TMZ results in significantly limited clinical effectiveness. There is therefore an inherent need for alternatives to TMZ capable of overcoming resistance associated with MGMT and MMR. In the present study, a series of ester and amide analogues of TMZ, modified at position 8 on the imidazole ring, were prepared and investigated for antiproliferative properties. It was found that phenolic ester analogues of TMZ displayed increased potency, of up to 5-fold, against specified glioblastoma cell lines. The encouraging results displayed by the phenolic TMZ esters prompted further investigations against patient-derived primary glioblastoma cultures. The primary cultures, BTNW914 and BTNW374, were MGMT positive and MGMT negative, respectively. Lead phenolic TMZ esters were found to decrease viability in primary cells at clinically relevant concentrations, irrespective of MGMT expression. Furthermore, TMZ was found to be ineffective against the same primary cells at clinically relevant concentrations. The novel phenyl ester analogues of TMZ, described in this study, could have potential chemotherapeutic properties for the treatment of GBM, overcoming the resistance associated with the expression of MGMT.

The standard of care treatment for patients diagnosed with glioblastoma multiforme (GBM) is temozolomide (TMZ).     

替莫唑胺治疗术后恶性脑胶质瘤的疗效

【目的】探讨替莫唑胺（TMZ）对术后恶性脑胶质瘤进行化疗的疗效。【方法】经手术后病理确诊的恶性脑胶质瘤病人60例,随机分成实验组和对照组（各30例）,分别服用替莫唑胺[TMZ,200rag／（m^2·d）]和洛莫司汀[CCNU,150mg／（m^2·d）],3-5个疗程。【结果】实验组有效率、控制率（46．67％、76．,67％）均明显高于对照组（20．000,46．67％）,两组差异有显著性（P〈0．05）。实验组患者1年生存率明显高于对照组,且差异均有显著性（P〈0．05）。实验组的总生存时间[（11．77±2．08）个月]明显长于对照组[（8．90±2．84）个月]（P〈0．05）。药物安全性评价显示,TMZ较CCNU更加安全。【结论】与CCNU相比,TMZ治疗恶性胶质瘤患者更安全、有效。     

Sensitization to granary mites in patients with allergic diseases

As many as 71 patients selected from a group of 550 patients suffering from allergic diseases, sensitized to the house dust mites Dermatophagoides pteronyssinus were examined. A study was made of the presence of allergen-specific IgE antibodies against house dust mites, storage mites (7 species altogether) using allergenic discs and commercial kits RAST (Pharmacia, Sweden). The group under examination mostly manifested sensitization to the house dust mites: Dermatophagoides ferinae (80%), Euroglyphus maynei (55%); storage mites: Acarus siro (45%), Lepidoglyphus destructor (35%). The latter one possesses the most powerful allergenic properties as compared to the acaroid mites of other types. The elevated sensitivity to storage mites is encountered among adults and children living both in Moscow and other regions (urban and rural). The problem of sensitization to storage mites in the USSR mandates thorough studies, which will enable the treatment and diagnostic agents to be designed and introduced into practice.     

综合疗法治疗瘢痕疙瘩

目的：探讨提高瘢痕疙瘩治疗效果，降低复发率的有效方法，方法：采用综合疗法，即手术切除后放疗，局部注射去炎松，外肜疤痕贴及局部压迫，结果：治疗61例，经1－5年随访，49例治愈，12例复发，优于单独一种方法。结论：采用综合治疗法治疗瘢痕疙瘩具有较好的疗效。     

索拉非尼联合TACE治疗中晚期肝癌的临床观察

目的探讨索拉非尼联合经皮肝动脉化疗栓塞术（TACE）治疗中晚期肝癌的疗效。方法选取30例中晚期肝癌患者,给予索拉非尼联合TACE治疗（试验组）,同时选取30例中晚期肝癌患者作为对照组仅行TACE;于1-2个治疗周期后比较临床疗效及生存质量卡氏评分。结果试验组与对照组,治疗3个月后临床获益率分别为83.3%、60.0%,差异有统计学意义（P〈0.05）,而生存质量卡氏评分2组差异无统计学意义（P〉0.05）;6个月生存率分别为93.3%、86.7%,差异无统计学意义（P〉0.05）,12个月生存率分别为86.4%、60.0%,差异有统计学意义（P〈0.05）。结论采用索拉非尼联合TACE治疗中晚期肝癌,可提高患者临床获益率及1年生存率。     

A Combination Drug Treatment for Acute Common Migraine

SYNOPSIS
Thirty subjects were admitted to a double blind study comparing Migraleve with placebo for the relief of acute common migraine attacks. A flexible dose cross over design was used. Twenty four subjects completed the six month study. The results suggest that Migraleve may reduce the duration and possibly the severity of an acute common migraine attack. Although the study was not designed to test for prophylactic effects since the drug was taken only for acute attacks, the results suggest possible long term prophylactic effects. These findings merit further investigation. While depressed patients had a greater number of common migraine attacks of all kinds, depression did not influence the effect of the drug. No serious side effects were noted in the patients during treatment, and the trial drug had an acceptably low incidence of other side effects. Of the 15 patients who expressed a drug preference in comparing the two 3 month study periods blindly, 14 expressed a preference for the Migraleve over the placebo. Further systematic study of these findings is necessary.     

Pilot Study of Ampicillin-Ceftriaxone Combination for Treatment of Orthopedic Infections Due to Enterococcus faecalis

Serious Enterococcus faecalis infections usually require combination therapy to achieve a bactericidal effect. In orthopedic infections, the prognosis of enterococcal etiology is considered poor, and the use of aminoglycosides is questioned. The ampicillin-ceftriaxone combination has recently been accepted as alternative therapy for enterococcal endocarditis. After one of our patients with endocarditis and vertebral osteomyelitis was cured with ampicillin-ceftriaxone, we started a pilot study of orthopedic infections. Patients with infections due to E. faecalis (with two or more surgical samples or blood cultures) diagnosed during 2005 to 2008 were recruited. Polymicrobial infections with ampicillin- and ceftriaxone-resistant microorganisms were excluded. Patients received ampicillin (8 to 16 g/day)-ceftriaxone (2 to 4 g/day) and were followed up prospectively. Of 31 patients with E. faecalis infections, 10 received ampicillin-ceftriaxone. Including the first patient, 11 patients were treated with ampicillin-ceftriaxone: 3 with prosthetic joint infections, 3 with instrumented spine arthrodesis device infections, 2 with osteosynthesis device infections, 1 with foot osteomyelitis, and 2 with vertebral osteomyelitis and endocarditis. Six infections (55%) were polymicrobial. All cases except the vertebral osteomyelitis ones required surgery, with retention of foreign material in six cases. Ampicillin-ceftriaxone was given for 25 days (interquartile range, 15 to 34 days), followed by amoxicillin (amoxicilline) being given to seven patients (64%). One patient with endocarditis died within 2 weeks (hemorrhagic stroke) and was not evaluable. For one patient with prosthesis retention, the infection persisted; 9/10 patients (90%) were cured, but 1 patient was superinfected. Follow-up was for 21 months (interquartile range, 14 to 36 months). Ampicillin-ceftriaxone may be a reasonable synergistic combination to treat orthopedic infections due to E. faecalis. Our experience, though limited, shows good outcomes and tolerability and may provide a basis for further well-designed comparative studies.Enterococcus faecalis is a low-virulence microorganism that colonizes the human gastrointestinal tract (23) and produces a variety of infections, especially under antimicrobial pressure or in nosocomial settings, including urinary tract and intra- abdominal infections, bacteremia, endocarditis, meningitis, and orthopedic and foreign-body-related infections (20). In orthopedic infections, enterococci are relatively common etiologic agents (26, 27); however, it is often difficult to distinguish infection from colonization, as the bacteria may be isolated in samples of doubtful significance or in combination with other microorganisms.As is well known in clinical practice, some enterococcal infections are difficult to treat (21). Though susceptible at relatively low MICs, enterococci are characteristically resistant to the bactericidal effect of cell wall-active antibiotics (16). Most E. faecalis strains show the “paradoxical or Eagle effect,” in which penicillins are more bactericidal just above the MIC and less bactericidal as the drug concentration increases (6, 9). This phenomenon has been attributed by some authors to an intrinsic defect in the autolytic activity of the microorganism (14). As a result of these special features, in the absence of high-level aminoglycoside (AG) resistance, an ampicillin-AG combination is now the therapy of choice for deep-seated infections by E. faecalis where a bactericidal effect is desirable, such as for endocarditis or meningitis (20, 23).In orthopedic and foreign-body infections, in which biofilm formation occurs, the bactericidal effect is sought in order to eradicate infection and avoid relapses. For serious enterococcal orthopedic infections, most authors recommend a combination therapy with AG (26, 37). However, the role of AG in the treatment of orthopedic infections has often been questioned, as the local conditions in infected bone may reduce their efficacy against susceptible microorganisms (17), and they have serious side effects that may limit their use.The ampicillin-ceftriaxone (AMP-CRO) combination has recently been recommended (strength, IIbC) for endocarditis due to E. faecalis that is highly resistant to AG (2) after the studies of Gavaldà et al. (11-13). The basis for these reports was an in vitro study by Mainardi et al. which found a synergistic effect between amoxicillin (amoxicilline) and low levels of cefotaxime against several AG-susceptible and AG-resistant E. faecalis strains (18).Pyogenic vertebral osteomyelitis may present as a complication of infective endocarditis (22, 25, 32). We undertook this pilot study after one of our patients with enterococcal endocarditis and vertebral osteomyelitis was treated with AMP-CRO and cured at both infection sites. To our knowledge, this is the first study to evaluate a double β-lactam combination for the treatment of orthopedic infections caused by E. faecalis.(These data were partially reported at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008 [8a].)     

Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, verapamil SR 240 mg plus indapamide 2.5. mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg, patients with sitting diastolic blood pressures of 95--115 mm Hg were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. (Patients with diastolic BP < 95 mm Hg on this initial treatment were excluded from further study.) Efficacy assessed after 16 weeks or at the end point showed all three treatments significantly reduced sitting diastolic blood pressure from baseline levels. Compared with Group I (low-dose) verapamil SR treatment, there was a reduction in Group III combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction in Group II high-dose verapamil SR therapy of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Efficacy results were independent of age or body weight. Patients who were poor responders to lead-in verapamil SR 240 mg daily prior to randomization tended to have a greater response to combination therapy than to high-dose verapamil SR. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving high-dose verapamil (Group II), exceeding the withdrawal from the other two treatment groups (8.5% from Group II and 4% from Group I). The most frequent adverse experiences in Group II were constipation and peripheral edema; headache was most common in Groups I and III. This trial demonstrates that adding indapamide to low-dose verapamil SR enhances efficacy and is well tolerated.     

Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, combination therapy of verapamil SR 240 mg plus indapamide 2.5 mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg daily, those patients with diastolic blood pressures of <95 mm Hg were excluded from further study; 137 remaining patients with sitting diastolic blood pressure of 95--115 mm Hg, representing "incomplete" responders to verapamil SR 240 mg, were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. Efficacy was assessed after 16 weeks of double-blind therapy or at end point. All three treatments significantly reduced sitting diastolic and systolic blood pressure from baseline levels. Compared with Group I (verapamil SR 240 mg daily), there was a significant reduction (p < 0.05) in Group II combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction (p < 0.05) in Group II (verapamil SR 480 mg daily) of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Patients who had the least change in blood pressure (diastolic blood pressure decreases of <5 mm Hg) to lead-in verapamil SR 240 mg daily, prior to randomization, tended to have a greater response to combination therapy than to verapamil SR 480 mg. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving verapamil SR 480 mg daily (Group II). There was a significantly greater withdrawal from Group II than the other two treatment groups (8.5% from Group III and 4% from Group I). This trial demonstrated that adding indapamide 2.5 mg to the incomplete responders of verapamil SR 240 mg enhances efficacy and was well tolerated.     

T Cells Redirected to EphA2 for the Immunotherapy of Glioblastoma

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.     

联合治疗复发性外阴阴道假丝酵母菌病168例

采用内服斯皮仁诺胶囊、中药完带汤合止带汤加减,外用臭氧水治疗复发性外阴阴道假丝酵母菌病168例。对治疗和巩固治疗方案进行疗效观察,并对停药后1、2、3个月受试者进行回访调查分析。结果治疗组治愈率88.4%,总有效率94%;对照组治愈率56.3%,总有效率85.0%。两组比较有统计学意义(P<0.05)。停药后1个月,两组均无复发;2个月治疗组无复发,对照组5例复发;3个月治疗组2例复发,对照组12例复发。两组比较有统计学意义(P<0.05)。联合治疗对复发性外阴阴道假丝酵母菌病效果好,复发率低。     

Efficacy of Atropine Sulfate in Combination with Albuterol in the Treatment for Acute Asthma

Objective : To determine the efficacy of combination therapy using atropine sulfate and albuterol in the treatment for an acute exacerbation of asthma.
Methods : A prospective, randomized double-blind, placebo-controlled study was performed in the ED of a large, inner-city, university-affiliated teaching hospital. Participants were a convenience sample of patients presenting to the ED between September 1993 and March 1994 with acute exacerbations of their asthma. Patients judged to be in extremis were excluded. All patients received 3 nebulized treatments with 2.5 mg of albuterol at 0, 30, and 60 minutes. Patients were randomized into 1 of 3 groups with the following added to their nebulizer solutions: 1) saline placebo during all 3 treatments; 2) 2.0 mg atropine sulfate added to the first nebulizer and saline in the second and third; or 3) 2.0 mg atropine to the first and third treatments (with saline in the second). No other medication was administered during the study period. At 90 minutes, the patients were evaluated for admission or release from the ED according to predetermined criteria, and additional medications were given as necessary. Vital signs, peak expiratory flow rate (PEFR), degree of wheezing, level of distress, and side effects were measured before and after each nebulizer treatment. Results : Of the 153 patients eligible for the study, 126 completed the entire study protocol. There was no significant difference between the 3 groups on any parameter studied, including improvement of PEFR, vital signs, or level of distress. There was no difference in the admission rate between the 3 groups, nor was there a difference in the incidence of side effects among the groups.
Conclusion : In this study population, combination therapy with atropine sulfate and albuterol offered no significant benefit over the use of albuterol alone in the treatment for acute exacerbation of asthma.     

吡柔比星与阿霉素为主的方案治疗非霍奇金淋巴瘤30例疗效比较

【目的】分析比较吡柔比星（吡喃阿霉素,THP）与盐酸阿霉素（ADM）治疗非霍奇金淋巴瘤（NHL）的疗效与不良反应。【方法】将58例NHL患者随机分成两组,A组30例,选用THP联合化疗;B组28例,选用ADM联合化疗,4个疗程后比较两组疗效及不良反应。【结果】A组与B组比较,总有效率分别为76．66％和71．43％,A组高于B组,但差异无显著性（P〉0．05）。两组心脏毒性发生率分别为6．25％和17．66％,胃肠道反应分别为50％和67．66％,两者比较有显著性差异（P〈0．05）,脱发分别为37．5％和82．14％,两者比较有非常显著性差异（P〈0．01）,骨髓抑制两者比较无明显差异。【结论】THP相对于ADM联合化疗患者不良反应发生率低,尤其消化道反应、脱发率及心脏毒性较低,且程度上也较轻,故THP较适合用于NHL患者。