Epithelium-derived inhibitory factor in human bronchus

The potencies of histamine and methacholine were significantly increased by approximately 2- and 5-fold respectively in human non-diseased isolated bronchi on removal of the epithelium. In contrast, no increases in spasmogen potency were observed following epithelium removal in bronchi obtained from a sample of asthmatic human lung. The failure of epithelium removal to increase asthmatic bronchial sensitivity to histamine may have been due to a reduction in the release of an epithelium-derived inhibitory factor (EpDIF) resulting from disease-induced epithelial damage. A co-axial bioassay system in which endothelium-denuded rat aorta was used as the assay tissue was used to detect the release of a vasorelaxant EpDIF from human bronchial tissue. Histamine (100 microM) and methacholine (25 microM), in the presence of indomethacin (5 microM), reduced phenylephrine-induced tone in endothelium-denuded rat aorta in co-axial assemblies by 75 +/- 11 and 67 +/- 9% respectively. Removal of the bronchial epithelium abolished these responses, indicating that they were mediated by an EpDIF. It is possible that human airway smooth muscle is sensitive to this vasorelaxant EpDIF and that the absence of the source of this factor following epithelium removal caused the increases in sensitivity to spasmogens. Alternatively, the human bronchial epithelium may also release an EpDIF selective for airway smooth muscle.     

Large-scale screening of nasal swabs for Bacillus anthracis: descriptive summary and discussion of the National Institutes of Health's experience

In October 2001, a letter containing a large number of anthrax spores was sent through the Brentwood post office in Washington, D.C., to a United States Senate office on Capitol Hill, resulting in contamination in both places. Several thousand people who worked at these sites were screened for spore exposure by collecting nasal swab samples. We describe here a screening protocol which we, as a level A laboratory, used on very short notice to process a large number of specimens (3,936 swabs) in order to report preliminary results as quickly as possible. Six isolates from our screening met preliminary criteria for Bacillus anthracis identification and were referred for definitive testing. Although none of the isolates was later confirmed to be B. anthracis, we studied these isolates further to define their biochemical characteristics and 16S rRNA sequences. Four of the six isolates were identified as Bacillus megaterium, one was identified as Bacillus cereus, and one was an unidentifiable Bacillus sp. Our results suggest that large-scale nasal-swab screening for potential exposure to anthrax spores, particularly if not done immediately postexposure, may not be very effective for detecting B. anthracis but may detect a number of Bacillus spp. that are phenotypically very similar to B. anthracis.     

High-throughput genetic screening using matrix-assisted laser desorption/ionization mass spectrometry

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become a powerful and widespread analytical tool in all fields of life science. Compared with other techniques, its high accuracy and sensitivity makes it a superior method, especially for the analysis of nucleic acids. Recent problems in the analysis of nucleic acids by MALDI-TOF MS can be solved using an automated MALDI-compatible sample-preparation system. Together with the reliable minisequencing assay, high-throughput genotyping of single nucleotide polymorphisms by MALDI-TOF MS is able to become a routine method in research, clinical genetics and diagnostics.     

Analytic performance of two automated nonpretreatment digoxin immunoassays

The analytic performance of two automated nonpretreatment digoxin methods, AxSYM Digoxin II and Vitros digoxin immunoassays, was assessed. Both assays had analytic sensitivities of less than 0.2 microg/L, were linear from digoxin concentrations of 0.5 to 4.0 microg/L, and showed acceptable precision, with a maximum total coefficient of variation (CV) of 8.9% and 6.4% for the AxSYM and Vitros, respectively. Comparison of the two methods using samples from patients receiving digoxin gave the following relationship: Vitros = 0.91 x AxSYM + 0.23 (r = 0.97, Sy,x = 0.12). Digoxinlike immunoreactive factor (DLIF) crossreactivity was examined in specimens from patients who had hepatic disease, renal insufficiency, had undergone cardiac surgery, and in neonatal cord blood samples. Minimal crossreactivity was observed for most samples and the average crossreactivity for each group of samples was comparable for the two methods. The recovery of digoxin added to samples from each group of DLIF was similar, except for that from cord blood samples, for which recovery was significantly lower with the AxSYM method. Titration of a digoxin-spiked serum pool with digoxin-immune Fab showed a similar decrease in the measured digoxin concentration for both methods. Overall, the analytic performance characteristics of these two methods were comparable.     

Subtyping of intraductal papillary mucinous neoplasms – pitfalls of MUC1 immunohistochemistry

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN‐lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.     

Chirurgische Therapie pulmonaler Metastasen von Kopf-Hals-Tumoren

Pulmonary metastasectomy is an established procedure in oncological therapeutic concepts. A systematic literature search and an analysis of all studies published since 01.01.2000 should evaluate the advantage of pulmonary metastasectomy for patients with primary head and neck cancer. Lung metastases develop in 1.9–13?% of head and neck cancer patients. Following metastasectomy, patients reach a median survival of 9.5–78 months and 5-year survival rates of up to 58?% are achieved. Intrathoracic recurrence occurs in 18.4–81.8?% of patients, selected instances of which can be successfully treated by remetastasectomy. Patients with squamous cell carcinoma have the worst prognosis, but could also become long-term survivors (≥?60 months). Pulmonary metastasectomy is frequently the only potentially curative therapeutic approach and offers a better long-term survival than nonsurgical therapies. Lung metastasectomy is thus the treatment of choice in selected patients with pulmonary metastases from primary head and neck cancer.