Treatment of Allergic Bronchopulmonary Aspergillosis with Fluconazole and Itraconazole

Treatment of allergic bronchopulmonary aspergillosis (ABPA) has remained both problematic as well as controversial. Although the sheet anchor in treatment of ABPA still remains steroids, various workers have tried oral antifungals (fluconazole and itraconazole) with encouraging results. This study evaluates the effect of fluconazole or itraconazole in the treatment of ABPA patients and compares them with the patients who had received palliative therapy other than antifungals. Case records of 44 proven cases of ABPA treated at our referral service hospital during February 1998 to April 2001 were analyzed. In addition to oral and inhaled bronchodilators, 16 patients received fluconazole 150 mg OD and 13 patients itraconazole 200 mg OD for six months. Response to therapy was assessed clinically, radiologically and by spirometry every 3 months. Patients who did not receive antifungals had chronic course characterized by airway obstruction, recurrent pulmonary consolidation and obstructive defect on pulmonary function test (PFT). Patients treated with itraconazole had better control of asthma symptoms, less requirement of reliever inhalers, steroids and lesser exacerbations of asthma during follow-up even after stopping antifungal. Fluconazole group had better control of symptoms but improvement in other parameters was not statistically significant. From this study it was evident that itraconazole improved the symptoms of airway obstruction, pulmonary functions, pulmonary opacities and decreased exacerbations during follow up.Key Words: Allergic bronchopulmonary aspergillosis, Fluconazole, Itraconazole     

The expression and prognostic significance of HER-2 in colorectal cancer and its relationship with clinicopathological parameters

The prognostic role of HER-2 has been established in breast cancer but remains controversial in colorectal cancer. In this study, 170 archival specimens of Dukes' B and C colorectal cancer were analysed immunohisto-chemically, using an anti-HER-2 monoclonal antibody HM64.13. Immunostaining was classified as cytoplasmic or membranous, and the intensity of the immunostaining was graded negative, weak or strong. The association between these scores and survival was estimated using Cox survival analyses. Overall, 87% of cases showed cytoplasmic HER-2 staining, with 54% exhibiting strong intensity cytoplasmic immunostaining. Membranous HER-2 was seen in 41% of cases, with most of these being of strong intensity. No correlation with clinical outcome was seen with membranous HER-2. Positive cytoplasmic immunostaining was found to be associated with a significantly better overall survival (HR 0.46, CI95 0.24-0.87) in the Dukes C cancers, but no survival benefit was seen in the Dukes' B cancers. Tumour grade, depth of tumour invasion and positive apical node were also found to be independent prognostic factors in Dukes' C cancers. We conclude that HER-2 over-expression occurs in a significant number of colorectal cancers. Since cytoplasmic HER-2 is incapable of transmitting the strong mitogenic signal via heterodimerization with other members of the Epidermal Growth Factor Receptor (EGFR) family, this may partly explain the correlation between cytoplasmic HER-2 over-expression and a better prognosis in the Dukes' C colorectal cancers. In addition, high levels of membraneous HER-2 in colorectal cancer could make HER-2 a good target for monoclonal antibody-based immunotherapy.     

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

Pulmonary histiocytosis X: comparison of radiographic and CT findings

The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.     

Immunoglobulin G subclass responses to cytomegalovirus in seropositive patients after transfusion

The immunoglobulin G subclass responses to cytomegalovirus (CMV) after red cell (RBC) transfusion were studied in 26 seropositive surgery patients and 34 transfused seropositive oncology patients. Also included as controls were 18 surgical patients who received no RBCs during surgery. None of the 78 patients studied had IgG2 to CMV before or after transfusion. The absence of a total IgG response to CMV after transfusion could not be attributed to preexisting deficiencies in one or more subclasses, because all 78 patients had similar levels of IgG1, IgG3, and IgG4 to CMV before transfusion. Discriminant analysis was used for statistical evaluation of the combined CMV subclass responses in each patient and the individual subclass responses. Individual patients responded to CMV antigens with an increase in concentration in any of the three subclasses or any combination of the subclasses, excluding IgG2. IgG subclass analysis showed that 10 of 27 patients who did not respond with at least a fourfold total IgG titer rise had a significant increase in IgG subclass antibodies to CMV. Three of 33 patients with at least a fourfold total IgG titer rise lacked a subclass response. These results suggest that the measurement of IgG subclasses may be a sensitive indicator of immune response to CMV.     

Causes, management and morbidity of acute hypoglycaemia in adults requiring hospital admission

In the community, acute hypoglycaemia is commonly caused by therapies for diabetes mellitus or the excessive consumption of alcohol. Although most episodes do not require admission to hospital, little information is available on the causes and outcome of those that do. We retrospectively surveyed adult patients admitted to a large urban teaching hospital with acute hypoglycaemia in a 12-month period, identifying 56 admissions of 51 patients. Forty-one had diabetes mellitus, 33 (80%) of whom were receiving treatment with insulin. The others had hypoglycaemia induced by excessive consumption of alcohol or by deliberate self-poisoning with insulin. A history of psychiatric illness and/or chronic alcoholism was common. Neurological manifestations of hypoglycaemia were the principal reason for admission, observed on 50 occasions (89%), and 11 events (20%) had precipitated convulsions. Although many patients (59%) had received treatment for hypoglycaemia before admission, hypoglycaemia recurred in 16% of patients in hospital. Four patients (7%) died following admission, but in only one case was this the direct result of hypoglycaemia. However, within 15 months of the index hypoglycaemia event, a further six patients (11%) had died, mostly of causes unrelated to hypoglycaemia. Patients who require hospital admission for treatment of hypoglycaemia have a high incidence of neurological manifestations, a high rate of mental illness and other medical disorders, and may represent a high-risk subgroup with a poor long-term prognosis.      

Direct identification of Yersinia enterocolitica in blood by polymerase chain reaction amplification

Primers based on the nucleotide sequence of the virF gene in the pYV plasmid and the chromosomal ail gene were used in polymerase chain reaction (PCR) amplifications to directly identify Yersinia enterocolitica in blood. Approximately 500 bacteria seeded into 100 microL of blood can be extracted and amplified by PCR to yield positive results. PCR analyses of seven Y. enterocolitica isolates previously implicated in blood contaminations showed that only one isolate harbored the plasmid-borne virF gene; however, all seven isolates were identified effectively by the PCR product amplified from the chromosomal gene. The PCR assay has the potential for use in the identification of Y. enterocolitica contamination in stored units of blood or in the rapid diagnosis of transfusion-related bacteremia caused by Y.