Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection

Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes.     

纤维支气管镜肺活检对肺移植术后急慢性排斥的诊断价值

目的 探讨肺移植术后常规应用纤维支气管镜肺活检(TBLB)在急慢性排斥反应中的应用.方法 54例肺移植患者共进行133例次TBLB.根据国际心肺移植协会(ISHLT)的分类及分级标准对患者的活检标本进行分级;将0～100 d作为肺移植早期,101～400d作为晚期.根据病理结果 分成早期排斥组(ER)和非早期排斥组(NO-ER);比较两组间100 d后急性排斥/淋巴细胞性支气管炎、细支气管炎(AR/LBB)的发生率.结果 肺移植早期和晚期的阳性检测率分别为32.9%、20.4%.肺移植晚期ER组和NO-ER组AR/LBB的发生率分别为20.8%和20.0%(P>0.05),81.8%的AR/LBB为A2或B2级以下,其中64.9%的AR/LBB患者没有典型的临床表现.结论 慢性排斥(BOS)是限制肺移植患者长期生存的关键因素,肺移植术后应常规做TBLB,及时发现并处理AR,以预防BOS发生.     

Complications of acute frontal sinusitis.

The bone separating the frontal sinus from the anterior cranial fossa and the orbit is often quite thin. This, plus the interrelated venous drainage system of these areas, forms the anatomic basis for serious orbital and intracranial complications that must be recognized early. These include orbital cellulitis and abscess, cavernous sinus thrombosis, subdural and brain abscess and meningitis. Early hospitalization for intravenous antibiotic therapy and, occasionally, emergency surgical drainage are required.     

Moxifloxacin in the treatment of acute maxillary sinusitis after first-line treatment failure and acute sinusitis with high risk of complications

This multicentre, prospective study evaluated the efficacy and safety of 7-day oral moxifloxacin (400 mg/day) for treatment of acute maxillary sinusitis after first-line treatment failure (group 1), and acute sinusitis with high risk of complications (group 2). Two hundred and fifty-eight patients with radiologically confirmed acute sinusitis were enrolled by 52 investigators; 216 patients (83.7%) qualified for per protocol efficacy analysis (group 1, n = 175; group 2, n = 41), and 92 for bacteriological analysis. Samples were collected from the middle meatus. The clinical success rate 7-10 days post-treatment was 92.6%. Bacteriological success rates were 95.7% after 3-4 days of treatment, and 97.2% and 95.2%, in group 1 and group 2, respectively, at 7-10 days post-treatment. Drug-related adverse events, including abdominal pain (2.4%), nausea (2.4%) and diarrhoea (1.2%), were reported in 12.2% of patients. Overall, moxifloxacin therapy resulted in rapid bacteriological eradication, with a high rate of clinical success.     

The diagnosis and management of acute and chronic sinusitis

Both acute and chronic sinusitis are common diseases associated with significant morbidity and consumption of health care dollars. Acute sinusitis is caused by an infectious process and can often be difficult to distinguish from a viral upper respiratory infection, as signs, symptoms, and even the results of most diagnostic tests overlap. In contrast, chronic sinusitis is an inflammatory disease and, contrary to common practice, long term antibiotics are likely not useful. This article reviews the diagnosis and management of both acute and chronic sinusitis and includes discussion of the prevalence of disease, our current understanding of disease pathogenesis, diagnosis, and contemporary treatment.     

Update on treatment guidelines for acute bacterial sinusitis

Acute bacterial sinusitis (ABS) is a common complication of viral upper respiratory tract infections and represents a considerable social burden both in terms of diminished quality of life for the patient and the economic implications of decreased productivity and treatment costs. Several national health authorities have developed guidelines for the management of ABS, which aim to promote rational selection of anti-bacterial therapy to optimise clinical outcomes while minimising the potential for selection of anti-bacterial resistance as a result of inappropriate anti-bacterial usage. This article provides an overview of current guidelines, with particular focus on the clinical significance of variations in treatment recommendations and new treatment options, such as the ketolide telithromycin, which was recently added to a number of national treatment guidelines.     

Pharmacokinetic and therapeutic trial of sultamicillin in acute sinusitis.

Sultamicillin, an antibiotic combining ampicillin and the beta-lactamase inhibitor sulbactam, was administered to 13 patients diagnosed as having acute sinusitis. Specimens from sinus were obtained for all 13 patients by transantral puncture. Pharmacokinetics, bacteriology, and therapeutic efficacy were assessed. Eighty-five percent (11 of 13) were cured; two treatment failures were subsequently shown to have chronic (rather than acute) sinusitis during surgical exploration. Diarrhea was frequently encountered, and Clostridium difficile-associated enteritis was documented for one patient. Beta-lactamase-producing organisms were not encountered in this study; however, this study provides impetus for further controlled clinical trials.     

Cephalexin in the treatment of acute and chronic maxillary sinusitis

We evaluated the efficacy of cephalexin therapy in 104 patients with infectious maxillary sinusitis. Confirmation of diagnosis was made by x-ray film, antral puncture, and culture. Sixty-nine patients met all criteria for evaluation. The majority of patients received cephalexin, 1 gm/day in four divided doses for ten days, including the 48-hour period after the patient had become asymptomatic. Patients returned for observation one week and two weeks after initiating therapy. Satisfactory clinical results were obtained in 57 (83%). Results showed that cephalexin was effective in treating sinusitis and that adverse reactions were rare. Bacteriology results showed that many of the pathogens usually involved in infectious maxillary sinusitis were resistant to the recommended or frequently prescribed antibiotics. These same pathogens, however, did not show resistance to cephalexin.     

Short courses of antibiotic in acute otitis media and sinusitis infections

Poor compliance with standard antibiotic regimens of 7 - 10 days' duration used in the treatment of acute upper respiratory tract infections contributes significantly to treatment failure. Patients fail to complete the recommended course of treatment, stopping once symptoms have resolved, which is typically within 2 - 5 days. Accumulating evidence from a large number of prospective clinical studies suggests that shortened courses of treatment may be as, or more, effective than conventional regimens of longer duration. As an example, a study comparing 5 days of cefuroxime axetil therapy with either 10 days of cefuroxime axetil or amoxycillin/clavulanate showed no differences in rates of clinical cure, bacteriological eradication and recurrence in paediatric patients with either acute otitis media or sinusitis. Shortened-course therapy with agents such as cefuroxime axetil has the potential to improve patient compliance and so reduce the rate of clinical failure and the emergence of resistant strains. Other potential benefits include fewer side-effects, improved patient satisfaction and lower treatment costs.     

Patients' and physicians' views on the management of acute maxillary sinusitis

OBJECTIVES: To study the views of patients and physicians on the management of suspected acute maxillary sinusitis and on suggested changes in practice. DESIGN: Cross-sectional survey and focus group interviews of both patients and physicians. SETTING: Primary care in Finland. RESULTS: A total of 175 patients and 245 physicians replied to the survey (response rates 88% and 70%, respectively). Eight focus groups were conducted, four with patients (n = 22) and four with physicians (n = 20). Patients had less trust than physicians in the natural healing process of acute maxillary sinusitis: only 33% as opposed to 95% of physicians agreed that acute maxillary sinusitis might heal without medication. The patients emphasised the importance of careful diagnosis. Physicians experienced the diagnostic uncertainty and the demands from authorities to use fewer antibiotics as problematic. CONCLUSIONS: Most patients with suspected acute maxillary sinusitis primarily want the physician to aim at making a specific diagnosis. Physicians feel they are forced to prescribe too many antibiotics for sinusitis because of patient's expectations and lack of good diagnostic means for acute maxillary sinusitis. Better diagnostic tools, both national and local guidelines, and patient information might help to change practice towards the use of fewer antibiotics.     

Antimicrobial resistance in the nasopharyngeal flora of children with acute maxillary sinusitis and maxillary sinusitis recurring after amoxicillin therapy

OBJECTIVE: To investigate the antimicrobial susceptibility of the organisms isolated from the nasopharynx of children who present with acute maxillary sinusitis (AMS) or maxillary sinusitis that recurred (RMS) after amoxicillin therapy. METHODS: Analysis of nasopharyngeal cultures obtained from 70 patients, 42 with AMS and 28 with RMS. RESULTS: Thirty-eight potentially pathogenic organisms were recovered in 36 (86%) of the children from the AMS group, and 40 were isolated from 26 (93%) of the children from the RMS group. The organisms isolated were Streptococcus pneumoniae (21 isolates), Haemophilus influenzae non-type b (17), Moraxella catarrhalis (15), Streptococcus pyogenes (13) and Staphylococcus aureus (12). Resistance to the eight antimicrobial agents used was found in 34 instances in the AMS group compared to 93 instances in the RMS group (P < 0.005). The difference between AMS and RMS was significant with S. pneumoniae resistance to amoxicillin (P < 0.0025), to co-amoxiclav (P < 0.0025), to trimethoprim-sulfamethoxazole (P < 0.05), to cefixime (P < 0.05), and to azithromycin (P < 0.05), and for H. influenzae to amoxicillin (P < 0.025). CONCLUSIONS: These data illustrate the higher recovery rate of antimicrobial-resistant S. pneumoniae and H. influenzae from the nasopharynx of children who had maxillary sinusitis that recurred after amoxicillin therapy than those with AMS.     

Clinical evaluation of co-tetroxazine in acute purulent sinusitis and acute tonsillitis in a double-blind comparison

127 outpatients, 78 with acute purulent sinusitis and 49 with acute tonsillitis, were treated for 7 days with a benzylpyrimidine -sulphonamide combination. In this double-blind and randomized study 59 patients received co- tetroxazine (100 mg tetroxoprim and 250 mg sulphadiazine) b.i.d., whilst the reference substance, co-trimoxazole (160 mg trimethoprim and 800 mg sulphamethoxazole) was given to the remaining 68 patients b.i.d. The test criteria were the therapeutic efficacy and both subjective and objective tolerance. An improvement in clinical symptoms and signs occurred in both conditions under each therapeutic regimen. Clinical therapeutic success was rated very good or good in 96.6% treated with co- tetroxazine and in 97.1% of patients treated with co-trimoxazole. In the former group therapy failed in 1 patient with sinusitis and in 1 with acute tonsillitis . In 98.3% of patients treated with co- tetroxazine the tolerance was very good or good, whilst the respective figure for co-trimoxazole was only 91.2%. 6 patients suffered from side effects ( gastric spasm, gastralgia , nausea, vomiting, diarrhoea) which were so severe in 2 cases that treatment had to be prematurely terminated. The generally good tolerance to both preparations was confirmed by the results of the laboratory investigations.     

心脏移植术后急性排斥反应的监测

笔者总结3例心脏移植术后急性排斥反应的监测与护理。监测临床症状和体征、12导联心电图、超声心动图、外周血T淋巴细胞、X线影像．心内膜心肌活枪(EMB)等指标，发现1a级排斥反应3次．2级排斥反应1次。认为EMB是目前诊断心脏移植急性排斥反应最为可靠的敏感指标：超声心动图为诊断急性排斥反应的重要手段，可及时无创地监测排斥反应，为调整免疫抑制剂的剂量、适时合理地行EMB提供重要的参考依据：其它指标有助于全面了解患者情况：仔细观察、综合分析病情，能有效地减少有创性心肌活检的次数。     

TNF-alpha in acute cardiac transplant rejection.

Acute cardiac allograft rejection is an immune-mediated response, hallmarked by cellular infiltration and myocyte damage in the transplanted heart. Cardiac biopsy sampling has been the 'gold' standard for routinely monitoring episodes of acute rejection. As cardiac biopsy is invasive, attention has focused on other non-invasive methods, such as serum analysis, for monitoring purposes. Tumour necrosis factor alpha (TNF-alpha) is a lymphocyte- and macrophage-derived cytokine that is pleiotropic in its actions. Its proinflammatory functions suggest that it may play an important role in initiating and orchestrating the rejection response. Studies demonstrating a correlation in the expression of TNF-alpha with the severity of the rejection episode have placed TNF-alpha as a prime candidate marker of rejection, and have prompted further study to elucidate these findings. This review discusses the limitations of the methodologies used to identify TNF-alpha, and how intragraft expression of TNF-alpha is not reflected in the serum. Furthermore, we describe how other stimuli besides the rejection response can affect TNF-alpha production, arguing against its use as a 'rejection-specific' marker. Nevertheless, genetic studies suggest that TNF-alpha may influence transplant outcome, and offer a new tool for studying the role of TNF-alpha in acute transplant rejection     

免疫抑制剂在肾移植急性排斥反应中的作用

目的:介绍免疫抑制剂分类及免疫抑制剂在肾移植急性排斥反应中的作用和安全性。资料来源:应用计算机检索中国期刊全文数据库2003-01/2006-03与免疫抑制剂在肾移植急性排斥反应中应用相关的文章,检索词为“免疫抑制剂,急性排斥反应,肾移植”,并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与免疫抑制剂预防、治疗肾移植术后急性排斥反应的研究相关;以近3年且发表在较权威杂志者优先。排除标准:重复研究或Meta分析类文章。资料提炼:有53篇文献检索到全文,选用其中的31篇作为本文参考文献:16篇涉及免疫抑制剂预防肾移植术后排斥反应;9篇涉及免疫抑制剂治疗肾移植术后排斥反应;6篇涉及免疫抑制剂和肾移植急性排斥反应的相关研究。资料综合:①分类:免疫抑制剂根据合成方法可分为微生物酵解产物、完全有机合成物、半合成化合物和生物制剂;根据其发展状况可分为第1～4代免疫抑制剂。②目前在肾移植中常用的免疫抑制剂有环孢菌素、他克莫司、雷帕霉素、霉酚酸酯、咪唑立宾和一些生物制剂,同时详细介绍了这些药物的药理作用和毒副作用。结论:免疫抑制剂能够通过细胞免疫和体液免疫影响受者的免疫功能,预防和治疗肾移植急性排斥反应;随着移植免疫学、分子生物学的不断深入研究,药物安全性不断提高。     

移植肾急性排斥的新认识

肾移植急性排斥、慢性移植物肾病(chronic allograft nephropathy,CAN)和移植肾带功死亡是导致远期移植物失功的主要原因。器官资源共享网络(UNOS)数据库资料显示,1997年以来移植肾长期     

肝移植后急性排斥反应的诊断及防治

肝移植后急性排斥反应的诊断指标众多,有肝脏功能指标、D 二聚体、血清中趋化因子 IP10 和外周血淋巴细胞CXCR3,HSP70 等。肝移植术后急性排斥反应的防治措施除了经典的免疫抑制治疗外,大黄素、雷公藤多甙、受体骨髓间质干细胞等都有可能是有前途的治疗药物或方法。肝移植术后急性排斥反应常见,早期诊断、综合防治是降低其危害的有效手段。了解肝移植术后急性排斥反应的诊断指标和方法,分析肝移植患者手术后预防治疗急性排斥反应的方法对肝移植术后的恢复起到至关重要的作用。