Double-blind trial RU 41740 vs. placebo: immunological and clinical effects in a group of patients with chronic bronchitis

A double-blind trail was performed to investigate the effects of RU 41740, a glycoprotein extract from Klebsiella pneumoniae, on host defenses and its efficacy in reducing the number of exacerbation in 29 evaluable patients with chronic bronchitis, out of 36 patients who entered the study. The drug enhanced the phagocytosis indexes of both polymorphonuclear and mononuclear phagocytes. Increased candidacidal activity of monocytes was also observed. These effects, already detectable after one course of therapy and during the entire period of treatment, were no longer detectable when tested 6 months after the end of treatment. A significantly (p less than 0.05) larger number of patients in the treated group than in the placebo group had no exacerbations during drug administration (0-3 months). Moreover, patients treated with RU 41740 had significantly fewer and shorter episodes of acute exacerbation. The positive decreases in these two parameters persisted throughout the follow-up.     

Characteristics of the phagocytic reaction of the neutrophils in healthy children and children with acute bronchitis and varying sensitivity to tuberculin

The feature of blood neutrophils to phagocyte BCG Mycobacterium and Staphylococcus in healthy children and those with acute bronchitis having both positive and negative tuberculin tests was analysed. Healthy children with an altered tuberculin response demonstrate an intensified phagocytic Myco. reaction and a relative inhibition of staphylococcal phagocytosis. In case of acute bronchitis, there is no increase in the overall absorbing capacity of neutrophils, typical of the tuberculin-negative children, and consequently, the detected feature of the phagocytosis is eliminated. The absence of variations in the total phagocytic response of the affected children is considered as a decrease of their adaptation potential. It is presumed that such an immunological status can predetermine the course of respiratory diseases and be the cause of tuberculous infection reactivation with intercurrent diseases.     

Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis

STUDY OBJECTIVES: To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB). DESIGN: Multicenter, multinational, randomized, double-blind study of two parallel treatment arms. PATIENTS: Outpatients >or= 45 years old with stable chronic bronchitis, smoking history of >or= 20 pack-years, two or more AECBs in the previous year, and FEV(1) < 85% of predicted value. Patients were enrolled when in a stable condition, and patients with exacerbations within 12 months of enrollment were randomized. INTERVENTIONS: Randomization (stratified on steroid use) between moxifloxacin (400 mg qd for 5 days) and standard therapy (amoxicillin [500 mg tid for 7 days], clarithromycin [500 mg bid for 7 days], or cefuroxime-axetil [250 mg bid for 7 days]). MEASUREMENTS: Assessment at enrollment, randomization (Anthonisen type 1 exacerbation), 7 to 10 days after treatment, and monthly until next AECB or up to 9 months. The primary efficacy variable was clinical success (sufficient improvement, no alternative antimicrobial therapy required) 7 to 10 days after therapy. Secondary predefined end points were clinical cure (return to pre-exacerbation status), further antimicrobial use, time to next AECB, and bacteriologic success. RESULTS: Three hundred fifty-four patients received moxifloxacin, and 376 patients received standard therapy. At 7 to 10 days after therapy, clinical success rates were similar in intention-to-treat (ITT) patients (95% confidence interval [CI], - 0.7 to 9.5) and per-protocol (PP) patients (95% CI, - 3.0 to 8.5). Moxifloxacin showed superior clinical cure rates over standard therapy in both ITT patients (95% CI, 1.4 to 14.9) and PP patients (95% CI, 0.3 to 15.6), and higher bacteriologic success in microbiologically valid patients (95% CI, 0.4 to 22.1). Fewer ITT patients required antimicrobials after treatment with moxifloxacin than standard therapy (p < 0.01). Time to next exacerbation was longer with moxifloxacin; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin, and 103.5 days and 118.0 days in standard therapy, respectively (p = 0.03). The occurrence of failure, new exacerbation, or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up (p = 0.03). CONCLUSIONS: Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes.     

Successful long-term treatment of systemic lupus erythematosus with rituximab maintenance therapy

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disease that may involve multiple organ systems. Treatment consists of immunosuppression, cytotoxic treatment, plasmapheresis and immunoglobuline therapy. Treatment of patients refractory to standard treatment approaches is difficult and results are poor. We describe a 39-year old patient with SLE suffering from grand mal epilepsy due to cerebral vasculopathy with positive lupus anticoagulant, who was refractory to standard treatment modalities. The patient was treated with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 x 4, repeated at weekly intervals). Rituximab applications were delivered in October 2000, March 2001 and October 2001. Since March 2002 she has received maintenance therapy with rituximab 375 mg/m2 every three months. A second female with refractory SLE was treated successfully in April 2002 and receives maintenance therapy every three months. Both patients responded well to rituximab therapy. The first patient showed a major improvement of her clinical condition, and 30 months after the beginning of the rituximab therapy she is free of any symptoms. Inflammation parameters, ANA and lupus anticoagulant declined significantly after the treatment. The clinical condition of the second patient improved dramatically, all inflammation parameters normalized and her circulating immunocomplexes disappeared. In conclusion, rituximab maintenance treatment may be a new effective therapy in SLE.     

Development of chronic airway obstruction in patients with eosinophilic bronchitis: a prospective follow-up study

STUDY OBJECTIVES: Eosinophilic bronchitis (EB) presents as a chronic cough and sputum eosinophilia without airflow limitation or bronchial hyperreactivity. Its long-term clinical course remains unknown. This study evaluated how frequently EB recurs and whether it develops chronic airway obstruction. DESIGN: This study was a prospective analysis. METHODS: Cough severity, FEV(1), provocative concentration of methacholine causing a 20% fall in FEV(1), and sputum eosinophil percentages were serially measured in 36 subjects for up to 48 months. All subjects inhaled corticosteroids until cough subsided. RESULTS: Five of the twenty four follow-up subjects (21%) had a recurrent episode of EB 4 to 6 months after disappearance of the first episode of EB (recurrent eosinophilic bronchitis). Progressive FEV(1) reduction > 20% was observed in three of the subjects, including a subject with asthma developing at the ninth month. Nineteen subjects had no recurrence of cough (nonrecurrent eosinophilic bronchitis) and no progressive FEV(1) reduction > 20%. However, sputum eosinophilia recurred between 4 months and 24 months in 10 subjects. Mean values of FEV(1) at the ninth and 12th months of the study were significantly lower in the recurrent eosinophilic bronchitis group than in the nonrecurrent eosinophilic bronchitis group (p < 0.01). CONCLUSION: These results suggest that repeated episode of EB is associated with the development of chronic airflow obstruction, including asthma.     

Evaluation of systemic host defense mechanisms in chronic bronchitis

Seventy-six chronic bronchitis patients were studied in order to determine the possible presence of disorders in their systemic defense mechanisms. No significant difference in lymphocyte subsets, in serum immunoglobulin and complement component (C3 and C4) levels was found in chronic bronchitis patients compared to normal adult controls. Skin tests for delayed hypersensitivity revealed a high frequency (39%) of hypoergic patients (with 1-2 positive reactions) in comparison to normal subjects. Altered values of many functional properties of both neutrophils and monocytes were demonstrated. The percentage of patients with intermediate (between 1 and 2 SD below the mean of controls) and defective (lower than 1.96 SD) values of chemotaxis, phagocytosis index and Candida killing was about 50%. Phagocytosis frequency and nitroblue tetrazolium reduction frequency were less frequently impaired.     

The endocrine effects of long-term treatment with mifepristone (RU 486).

Mifepristone (RU 486) is a compound with progesterone as well as cortisol-blocking activities. We investigated the endocrine effects of long-term therapy of 10 patients with meningiomas with 200 mg mifepristone daily for 1 yr. Most patients initially complained of nausea, vomiting, and/or tiredness. In four patients prednisone (7.5 mg/day) had to be given simultaneously in order to overcome these side-effects. In retrospect those patients who presented with the most severe side-effects showed the most rapidly occurring activation of the hypothalamo-pituitary-adrenal-axis, as measured by an increase of circulating cortisol levels as well as of urinary cortisol excretion. Therapy with RU 486 activated the hypothalamo-pituitary-adrenal axis, resulting in a resetting of this system at a higher level at which the diurnal rhythm and the responsiveness to CRH stimulation were maintained, whereas the sensitivity to dexamethasone had diminished. Secondarily the production of androstenedione and estradiol increased considerably. These endocrine changes were caused by the induction of partial cortisol receptor resistance during therapy with RU 486. The compensatory overproduction of androgens and consequently of estrogens during long-term RU 486 therapy might limit its use as a single treatment in the treatment of estrogen-dependent cancer.     

不同表型的COPD患者对长效b2受体激动剂/吸入型糖皮质激素的治疗应答性比较

【】目的 探讨不同表型的慢性阻塞性肺疾病(COPD)患者对长效b2受体激动剂/吸入型糖皮质激素治疗的应答性。方法 选取2014年2月至2016年10月在我院治疗的COPD患者217例,其中肺气肿型COPD患者94例,慢性支气管炎型COPD患者123例,观察两组治疗前后肺功能情况。结果 慢性支气管炎型组体重指数(BMI)为(24.13±3.72)kg/m2,明显高于肺气肿型组(p＜0.05);肺气肿型组第1秒用力呼气容积占预计值百分比(FEV1%预计值)和残气量占预计值百分比(RV%预计值)分别为(47.52±9.80)%和(138.89±52.29)%,明显低于慢性支气管炎型组(p＜0.05),而深呼气量占预计值百分比(IC%预计值)为(87.71±13.26)%,明显高于慢性支气管炎型组(p＜0.05);慢性支气管炎型组治疗前后第1秒用力呼气容积(FEV1)、肺总量(TLC)、深吸气量(IC)和残气量(RV)改善值分别为(0.35±0.09)L、(-0.53±0.12)L、(0.17±0.06)L和(-0.60±0.11)L,明显优于肺气肿型组(p＜0.05)。结论 不同表型的COPD患者对长效b2受体激动剂/吸入型糖皮质激素的治疗存在差异,其中慢性支气管炎型COPD的治疗效果较好,肺功能改善明显。     

Intraluminal airway inflammation in chronic bronchitis. Characterization and correlation with clinical parameters

In order to characterize intraluminal airway inflammation in subjects with chronic bronchitis, bronchoscopy and bronchoalveolar lavage were performed in 28 subjects with chronic bronchitis with fixed airway obstruction and, for comparison, 15 asymptomatic smokers and 25 normal nonsmoking volunteers. The chronic bronchitics had a cough productive of sputum on most days of the month for 6 months in the preceding 2 yr, had at least one exacerbation requiring medical intervention in each of the previous 2 yr, and had an FEV1 less than 76% of predicted without response to bronchodilator. During bronchoscopy the airways were assessed for visual evidence of inflammation by assigning them a score, the bronchitis index, that graded the airways according to the apparent severity of airway edema, erythema, friability, and secretions. Bronchoalveolar lavage was performed by sequentially instilling and retrieving with gentle suction five 20-ml aliquots of sterile normal saline into each of three separate lobes. The first aliquots, the "bronchial" sample, were pooled and processed separately from the final four aliquots, the "distal" sample. Cell counts, cell differentials, and albumin were determined for both the bronchial and distal samples. In order to correlate inflammation with clinical parameters, sputum was collected for 24 h prior to bronchoscopy; spirometry was performed just prior to bronchoscopy, and smoking histories were obtained. Visual inspection of the airways, as quantified by the bronchitis index, demonstrated significantly more evidence for inflammation in the chronic bronchitics than in either the asymptomatic smokers or the normal subjects. The bronchial sample lavage fluids from the chronic bronchitics tended to contain more cells (6.1 +/- 2.2 x 10(6) cells) than the bronchial sample fluids from the asymptomatic smokers (3.6 +/- 0.6 x 10(6) cells) or normal subjects (3.7 +/- 0.5 x 10(6) cells). Furthermore, the chronic bronchitics had a higher percentage of neutrophils in their bronchial lavage fluid (35.8 +/- 5.6%) than did either the asymptomatic smokers (20.7 +/- 2.6%, p = 0.0001) or the normal subjects (10.3 +/- 5.6%). The distal sample lavage fluid also recovered more neutrophils from both the chronic bronchitics (15.0 +/- 4.2%, p = 0.0012) and asymptomatic smokers (5.7 +/- 1.3%, p = 0.002) than from the normal subjects (2.8 +/- 0.4%). The chronic bronchitics were divided into two groups: those with low (less than 20%) and those with high (greater than 20%) bronchial sample neutrophils. Those with higher bronchial sample neutrophils had significantly more sputum production and lower FEV1, FEV1/FVC, and FEF25-75 than did the subjects with lower bronchial sample neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immune defense in hormone-dependent bronchial asthma

The study was undertaken to examine the clinical and immunological features of hormone-dependent bronchial asthma. Long-term corticosteroid therapy was found to have a pronounced immunodepressive effect on both lymphocytic subpopulations and opsonophagocytosis. The sequelae of immunological disorders are lower anti-infective defense, which contributes to a more severe course of the disease generally running in the presence of chronic obstructive bronchitis. The use of immunomodulators, extracorporeal techniques, which favours to reduce the adverse immunosuppressive effect of long-term therapy, is an alternative to corticosteroid dosage increment.     

Treating patients with venous thromboembolism: initial strategies and long-term secondary prevention

Therapy for venous thromboembolism (VTE) currently involves a minimum of 3 months of anticoagulation. After cessation of therapy, however, recurrent venous thrombosis occurs at rates of 6 to 9% per year. Clinical trials have demonstrated the benefits of extending anticoagulation beyond 3 months for the prevention of recurrent VTE events. Despite this, many eligible patients do not receive the required thromboprophylaxis and the incidence of recurrent VTE remains too high for a preventable condition. A reason for failure to use prophylaxis is the fear of bleeding complications with current oral anticoagulants such as warfarin. Warfarin has an unpredictable pharmacokinetic profile and a variable dose-response relationship that requires frequent coagulation monitoring and dose adjustments to maintain a target intensity that is both safe and effective. Alternative strategies for long-term prophylaxis, which may potentially provide more consistent anticoagulant responses and reduce coagulation monitoring requirements, include the use of low-molecular-weight heparin (LMWH), treatment with warfarin at a lower intensity, and the introduction of novel anticoagulants. The long-term use of LMWH has been found to be a particularly favorable treatment option for cancer patients in whom it is difficult to control the intensity of anticoagulation. In clinical trials, LMWH significantly reduced the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of the LMWHs, however, is a drawback for long-term use in the outpatient setting. A clinical trial assessing the efficacy and safety of long-term low-intensity warfarin treatment found this therapy to be better than placebo, but another study showed that conventional intensity warfarin was significantly more efficacious than low-intensity warfarin. New therapies in development that may offer improved safety-efficacy profiles are the synthetic pentasaccharides fondaparinux and idraparinux and the oral direct thrombin inhibitor ximelagatran. Parenterally administered fondaparinux has been shown to be as effective as LMWH for the acute treatment (5 to 7 days) of symptomatic deep vein thrombosis. Idraparinux, with once-weekly parenteral dosing, is currently being assessed in phase III clinical trials for the long-term secondary prevention of VTE. Ximelagatran is the first oral agent in the new class direct thrombin inhibitors. With a fast onset of action and oral administration, ximelagatran is a candidate for both acute and chronic therapy. The Thrombin Inhibitor in Venous Thromboembolism (THRIVE) clinical trial program has demonstrated that this agent has a favorable benefit-risk profile compared with standard therapy for the initial treatment (6 months) and secondary prevention (up to 18 months) of VTE. However, in a substantial proportion (6 to 13%) of patients given extended ximelagatran therapy, elevated serum transaminase enzymes developed, typically in the first 2 to 4 months of treatment. Even though these elevations usually abated without clinical sequelae whether or not treatment was continued, their clinical relevance remains unclear. In addition, locally reported coronary events occurred more frequently in ximelagatran-treated patients during the initial 6 months of treatment, the reason for which is yet unclear. The consistent anticoagulant response and fixed oral dosing without coagulation monitoring allows ximelagatran to overcome many of the limitations inherent to current treatment options for VTE treatment and secondary prevention, provided the problem of liver enzyme elevation and coronary events is resolved.     

Adult beta-thalassemic patients with chronic hepatitis C: long-term efficacy of alpha-IFN treatment

Background: The purpose of this study was to assess the effectiveness of alpha-IFN in adult beta-thalassemic patients with chronic hepatitis C. After a long-term follow-up, we describe the special pattern of biochemical and virological response of thalassemics. Methods: Thirty-two anti-HCV-positive adult thalassemic patients (19 female and 13 male, mean age 23.4+/-5.5 years) with biopsy-proven chronic hepatitis were treated with IFN alpha2beta at a dose of 3 MU thrice weekly for 6-12 months. The patients were followed up until 45-62 months after the end of treatment. Results: A sustained response was obtained in eight patients (25%). Only two of the sustained responders (25%) normalized ALT during the first 3 months of treatment. Both early and late biochemical responders cleared HCV-RNA after 6 months of treatment. Eight patients (25%) responded with ALT normalization within 2 months of treatment but relapsed soon after stopping IFN. Sixteen patients (50%) did not respond to IFN. Conclusion: The response rate in multitransfused thalassemic patients with chronic hepatitis C treated with IFN is similar to that in non-thalassemics. The special feature of thalassemics is that early biochemical response does not predict a sustained response; on the contrary, patients who normalize ALT after 6 months of IFN treatment usually do not relapse.     

Treatment of chronic rhinosinusitis with low-dose,long-term macrolide antibiotics: An evolving paradigm

The 14-membered and 15-membered ring macrolide antibiotics express immunomodulatory effects in chronic respiratory disorders in humans that are distinct from their antimicrobial properties. These drugs downregulate the excessive immune and inflammatory responses observed in these conditions while promoting tissue repair. To this end, chronic rhinosinusitis is characterized by mucosal inflammation of nasal and sinus mucosa for more than 3 months and accounts for significant health care resource allocation due to difficulties in treatment. Clinical efficacy of macrolide antibiotics as biologic response modifiers in patients with chronic rhinosinusitis is suggested by compelling basic research and small, uncontrolled clinical studies. Hence, long-term, prospective double-blind placebo-controlled clinical studies are indicated to establish the utility of these drugs in the treatment of patients with chronic rhinosinusitis.     

Double-blind study of Biostim in the prevention of superinfection in patients with chronic bronchopathy

In a multicenter trial conducted with patients suffering from chronic bronchopathy, Biostim, an immunomodulating compound of biological origin has been studied using the double-blind placebo-controlled method for prevention of respiratory tract infections. One hundred and ten patients from 10 french pneumology health centers entered the study. The treatment was administered at random in three sequences of 8 days a month for 3 months (2 mg/day the first month, 1 mg/day the second and third months). Patients were separated into 2 groups regarding severity of the disease: group I (non complicated chronic bronchitis); group II (obstructive chronic bronchitis with or without respiratory failure). Patients were examined during 6 months with a monthly appraisal of number, duration and treatment clinically defined infectious episodes. The study of propensity to infections with respect to severity of the disease in patients given placebo showed a significantly lower number of infectious episodes in group I when compared to group II. In the group I (patients suffering from simple chronic bronchitis), no significant difference could be noted between placebo and Biostim but, at all events, the low frequency of episodes makes it difficult to evidence a protective effect in such a group. In contrast, with patients presenting a high infectious risk (group II), one can observe in Biostim treated patients compared with placebo group a significant decrease of infectious episodes and a larger number of patients standing free of episodes throughout the whole period of trial. Tolerance to Biostim has revealed itself satisfactory.     

Characteristics of bronchoalveolar lavage fluid in patients with sulfur mustard gas-induced asthma or chronic bronchitis.

PURPOSE: To examine the pattern of immunoglobulins and cellular constituents in bronchoalveolar lavage fluid obtained from patients with sulfur mustard gas-induced asthma or chronic bronchitis as compared with healthy control subjects. SUBJECTS AND METHODS: We studied two groups of nonsmoking veterans with either bronchial asthma (n = 21) or chronic bronchitis (n = 28) believed to have been caused by sulfur mustard gas exposure and a third group of healthy, nonsmoking, non-sulfur mustard gas exposed controls (n = 17). Bronchoalveolar lavage was performed in all three groups. The cellular constituents, albumin content, and immunoglobulin concentrations were determined. RESULTS: The three groups did not differ in age or in the serum albumin and immunoglobulin concentrations. The volume of bronchoalveolar lavage fluid recovered was approximately 10% less in the patients with asthma and chronic bronchitis (P = 0.008). The proportions of lymphocytes among the bronchoalveolar lavage cells were similar in all three groups, whereas the proportion of eosinophils was greater in lavage fluid from the asthmatic subjects than in either the healthy control subjects or the patients with chronic bronchitis (P = 0.0001). Both the total number of the recovered cells per milliliter of lavage fluid and the proportion of neutrophils were significantly greater in bronchoalveolar lavage from patients with chronic bronchitis than in healthy subjects or in the patients with asthma (all P <0.001). CONCLUSION: The bronchoalveolar lavage cellular constituents of patients with sulfur mustard gas-induced asthma and chronic bronchitis are similar to those that have been observed previously in patients with asthma and chronic bronchitis from other common causes.     

Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis

The clinical effect of N-acetylcysteine (NAC) controlled-release tablets, 300 mg b.i.d., and placebo, in chronic bronchitis was investigated. The study was performed as a double-blind six month comparison between active drug and placebo in two parallel groups, with statistical evaluation after four and six months. The patients were chosen from nine centres. One hundred and sixteen out-patients were included and ninety one of them completed the six month study. The acetylcysteine-treated group had a significantly reduced number of sick-leave days caused by exacerbations of chronic bronchitis after the four winter months December-March compared with the control group (NAC 173, placebo 456). The number of exacerbation days was also very much reduced, however, not significantly (NAC 204, placebo 399). At the end of the six month trial, including also two spring months, the absolute numbers of sick-leave days and exacerbation days were still fewer in the acetylcysteine-treated group, (NAC 260, placebo 739) and (NAC 378, placebo 557) respectively. This study demonstrates a significant reduction in sick-leave days after four months of NAC-treatment. A constant tendency to reduction in the number of exacerbations and exacerbation days was also registered after four and six months. The differences in these parameters were, however, not statistically significant. This was probably due to the small number of patients participating.     

An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis.

BACKGROUND: In previous studies, itraconazole was revealed to be an effective therapy and was considered to be the gold standard treatment for mild-to-moderate acute and chronic clinical forms of paracoccidioidomycosis. A pilot study was conducted to investigate the efficacy, safety, and tolerability of voriconazole for the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as the control treatment. METHODS: A randomized, open-label study was conducted at 3 Brazilian tertiary care hospitals. Patients were randomized (at a 2 : 1 ratio) to receive oral therapy with voriconazole or itraconazole for 6 months. Patients receiving >or=1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed >or=6 months of therapy (treatment-evaluable patients) were evaluated for treatment efficacy. Satisfactory global response was assessed at the end of treatment. RESULTS: Fifty-three patients were evaluated for treatment safety (35 received voriconazole, and 18 received itraconazole). Both drugs were well tolerated. The most common treatment-related adverse events in the voriconazole group included abnormal vision, chromatopsia, rash, and headache; the most common treatment-related adverse events in the itraconazole group included bradycardia, diarrhea, and headache. Liver function test values were slightly higher in patients receiving voriconazole than in those receiving itraconazole; 2 patients in the voriconazole group were withdrawn from treatment because of increased liver function test values. In the intent-to-treat populations, the satisfactory response rate (i.e., complete or partial global response) was 88.6% among the voriconazole group and 94.4% among the itraconazole group. The response rate among treatment-evaluable patients was 100% for both treatment groups; no relapses were observed after 8 weeks of follow-up. CONCLUSIONS: This is, to our knowledge, the first study to demonstrate that voriconazole is as well tolerated and effective as itraconazole for the long-term treatment of paracoccidioidomycosis.     

孟鲁司特钠治疗老年慢性喘息性支气管炎疗效观察

目的观察孟鲁司特钠治疗老年慢性喘息性支气管炎急性发作的临床效果。方法将48例老年慢性喘息性支气管炎患者随机分成对照组22例,给予低流量吸氧、抗感染、化痰止咳、解痉平喘治疗;治疗组26例在此基础上,加入孟鲁司特钠每晚10 mg口服治疗。分别于治疗后第14天评价2组临床疗效,且检测治疗前和治疗后第14天、第28天肺功能第1秒用力呼气量占预计值百分比（FEV1%）、用力肺活量（FVC）、呼气流速峰值（PEF）并进行比较。结果孟鲁司特钠治疗组总有效率（92.31%）显著高于对照组（68.18%）,具有统计学差异（P〈0.05）;治疗组肺功能FEV1%、FVC、PEF明显改善,优于对照组。结论孟鲁司特钠对老年慢性喘息性支气管炎急性发作疗效显著,而且安全、快捷。     

Prulifloxacin versus levofloxacin in the treatment of severe COPD patients with acute exacerbations of chronic bronchitis

RationaleAntimicrobial therapy of chronic bronchitis exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) is based on empiric antibiotic treatment.ObjectivesTo evaluate the efficacy of prulifloxacin versus levofloxacin therapy in severe COPD patients with exacerbations of chronic bronchitis.MethodsThis study involved a multicenter, parallel, double-blind, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers (>10 pack-years) with spirometrically confirmed severe COPD (FEV₁ ≤ 50% predicted and FEV₁/FVC ratio < 0.7) and diagnosed with an acute exacerbation of chronic bronchitis were enrolled in the study. Patients were randomized to receive prulifloxacin 600 mg once a day or levofloxacin 500 mg once a day for 7 days.Measurements and main resultsThe primary outcome measure was clinical assessment at the TOC visit (7–10 days after the end of treatment) of signs and symptoms of exacerbation, namely sputum purulence, sputum volume, dyspnoea, cough and body temperature assessed through semi-quantitative scales. The ITT population included 346 (174 prulifloxacin, 172 levofloxacin) out of 351 treated subjects. A total of 161 patients with prulifloxacin (92.5%) and 166 with levofloxacin (96.5%) were considered cured at TOC (the difference in the percentage of cured patients was ?3.98 with 95%CI of ?8.76; 0.79). At the 6-month follow-up, the rates of patients with no relapse of AECB were higher than 95% in both the prulifloxacin and levofloxacin groups.ConclusionsBoth prulifloxacin and levofloxacin showed efficacy rates higher than 90% in the treatment of severe COPD patients with exacerbations of chronic bronchitis, with no statistically significant differences between the two antibiotics. The long-term follow-up confirmed a very low incidence of relapse, endorsing the appropriateness of this therapeutic approach.EUDRACT no. 2006-004167-56.     

Cytobiologic and clinical aspects in a patient with chronic neutrophilic leukemia after thorotrast exposure

A patient with fairly typical chronic neutrophilic leukemia, as represented by some two dozen such reported cases, had been given Thorotrast more than 20 years before. Typical myeloblastic crisis developed with remarkable terminal leukocytosis. Mature blood neutrophils had normal function with respect to phagocytosis, bacterial killing, metabolic activation, and chemotactic response. The number of cells producing colonies of neutrophils and monocytes in in vitro semisolid cultures was normal in the blood and increased in marrow. Colony size was smaller than is usually observed in normal patients or in typical patients with chronic myeloid leukemia. Termination in blast crisis, also seen in a few other patients with chronic neutrophilic leukemia, indicates that this is indeed a form of leukemia and not a "leukemoid" reaction of obscure cause. The differential diagnosis of extreme neutrophilia is discussed.