Is bronchoscopy always justified in diagnosis of haemoptysis? Response to the letter of Solidoro and Guerrera

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Is bronchoscopy always justified in diagnosis of haemoptysis?

Introduction: Fiber-optic bronchoscopy (FOB) is commonly performed in the first line in diagnostic process of haemoptysis.However, lots of evidences suggest that in haemoptysis FOB do not always provide additional, useful information to radiologicaldiagnostics. Therefore, this study aimed to evaluate the validity of performing FOB as a method of choice in first line diagnosticsof haemoptysis. Material and methods: Data comprised consecutively collected results from patients referred for FOB assessment for clinicalpurposes were retrospectively analysed. We included all examinations, which were performed due to haemoptysis as the onlyindication, excluding any other lung-related conditions. Results: 114 patients were finally included to the study. The median age was 59 (IQR: 46–64.75). Active bleeding was visualizedduring examination of 13 (11.4%) patients. Patients with active bleeding did not differ significantly according to age: 59 (54–69)vs 59 (45–64) years; W = 532.5, p-value = 0.27, and gender: c2 = 1.68, p-value = 0.2. On the other hand, in 29 (25.44%)patients, FOB revealed no visible abnormalities. This subgroup of patients was significantly younger — 46 (34–62) years vs 60(53–67) years; W = 782, p-value = 0.003. Conclusion: Low number of visualized active bleeding sites suggest overuse of bronchoscopy in diagnosis of haemoptysis. Indicationsfor this examination should be reconsidered especially in young patients with non-massive haemoptysis

The role of bronchoscopy in diagnosis of chronic cough in adults: a retrospective single-center study

Introduction: Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional testing of samples collected during FOB in the differential diagnosis of chronic cough in adults.Material and methods: This was a single-center retrospective study. Out of 7115 conventional white light FOB examinations, we finally selected 198 with cough as the only indication.Results: In 40.9% of bronchoscopic examinations, no visible cause of cough was found. Visual signs of chronic bronchitis (CB) were detected in 57.6% of reports. Only in 3 cases (1.5%) bronchoscopy revealed a potential cause of chronic cough other than CB. Mycobacterium tuberculosis or other mycobacteria were spotted in none of the samples. In 91.1% of bronchoalveolar lavage (BAL) cytologic examinations, at least one cell count abnormality was detected, but only in case of increased percentage of eosinophils, it might be considered clinically relevant. In 53% of bacteriological culture results, at least one potentially pathogenic bacterium was isolated. Conclusions: The present study results strengthen the evidence that FOB combined with additional testing of airway specimens obtained during FOB is not a powerful tool in the differential diagnosis of chronic cough, and FOB as a diagnostic tool may be overused. The appropriate timing and decision regarding referral for FOB and additional testing of achieved material requires careful clinical consideration

Substituted Lactam and Cyclic Azahemiacetals Modulate Pseudomonas aeruginosa Quorum Sensing

Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence that is critical for establishing infection. The most common QS signaling molecule used by Gram-negative bacteria are acylhomoserine lactones. The development of non-native acylhomoserine lactone (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram-negative bacteria. In this work, we have synthesized a set of optically pure γ-lactams and their reduced cyclic azahemiacetal analogues, bearing the additional alkylthiomethyl substituent, and evaluated their effect on the AHL-dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of these ligands and the simple structural modification such as the length of the alkylthio substituent has notable effect on activity. The γ-lactam derivatives with nonylthio or dodecylthio chains acted as inhibitors of las signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent was found to strongly inhibit both las and rhl signaling at higher concentrations while the propylthio analogue strongly stimulated the las QS system at lower concentrations

Investigation of reactions postulated to occur during inhibition of ribonucleotide reductases by 2 0 -azido-2 0 -deoxynucleotides

a b s t r a c t Model 3 0 -azido-3 0 -deoxynucleosides with thiol or vicinal dithiol substituents at C2 0 or C5 0 were synthesized to study reactions postulated to occur during inhibition of ribonucleotide reductases by 2 0 -azido-2 0 -deoxynucleotides. Esterification of 5 0 -(tert-butyldiphenylsilyl)-3 0 -azido-3 0 -deoxyadenosine and 3 0 -azido-3 0 -deoxythymidine (AZT) with 2,3-S-isopropylidene-2,3-dimercaptopropanoic acid or N-Boc-Strityl-L-cysteine and deprotection gave 3 0 -azido-3 0 -deoxy-2 0 -O-(2,3-dimercaptopropanoyl or cysteinyl) adenosine and the 3 0 -azido-3 0 -deoxy-5 0 -O-(2,3-dimercaptopropanoyl or cysteinyl)thymidine analogs. Density functional calculations predicted that intramolecular reactions between generated thiyl radicals and an azido group on such model compounds would be exothermic by 33.6e41.2 kcal/mol and have low energy barriers of 10.4e13.5 kcal/mol. Reduction of the azido group occurred to give 3 0 -amino-3 0 -deoxythymidine, which was postulated to occur with thiyl radicals generated by treatment of 3 0 -azido-3 0 -deoxy-5 0 -O-(2,3-dimercaptopropanoyl)thymidine with 2,2 0 -azobis-(2-methyl-2-propionamidine) dihydrochloride. Gamma radiolysis of N 2 O-saturated aqueous solutions of AZT and cysteine produced 3 0 -amino-3 0 -deoxythymidine and thymine most likely by both radical and ionic processes

Czy bronchoskopia jest zawsze niezbędna w diagnostyce krwioplucia?

WSTĘP: Bronchofiberoskopia jest często wykonywanym badaniem we wstępnej diagnostyce krwioplucia. Wiele danych wskazuje jednak na to, że badanie to nie zawsze dostarcza dodatkowych istotnych informacji, ponad te uzyskane z badań obrazowych. Z tego powodu przeprowadzono analizę, której celem było określenie przydatności bronchofiberoskopii w pierwszoplanowej diagnostyce krwioplucia. MATERIAŁ I METODY: Przedmiotem retrospektywnej analizy były wyniki badań bronchoskopowych wykonanych u pacjentów kierowanych do pracowni bronchoskopowej. Zawarto w niej jedynie te badania, w których wyłącznym wskazaniem było krwioplucie, wyłączając inne przyczyny z zakresu układu oddechowego. WYNIKI: Do ostatecznej analizy włączono 114 pacjentów. Mediana wieku wynosiła 59 lat (IQR: 46–64,75). Aktywne krwawienie stwierdzono w badaniu u 13 pacjentów (11,4%). Nie różnili się oni od pozostałych pod względem wieku: 59 (54–69) v. 59 (45–64) lat; W = 532,5, p = 0,27, oraz płci: c2 = 1,68, p = 0,2. Natomiast u 29 pacjentów (25,44%) w bronchofiberoskopii nie ujawniono żadnych nieprawidłowości. Pacjenci należący do tej grupy byli istotnie młodsi — 46 (34–62) v. 60 (53–67) lat; W = 782, p = 0,003. WNIOSKI: Mały odsetek wyników wskazujących na aktywne krwawienie sugeruje nadużywanie bronchofiberoskopii w diagnostyce krwioplucia. Wskazania do tego badania powinny być zrewidowane, w szczególności w grupie młodych pacjentów z niemasywnym krwiopluciem.WSTĘP: Bronchofiberoskopia jest często wykonywanym badaniem we wstępnej diagnostyce krwioplucia. Wiele danych wskazuje jednak na to, że badanie to nie zawsze dostarcza dodatkowych istotnych informacji, ponad te uzyskane z badań obrazowych. Z tego powodu przeprowadzono analizę, której celem było określenie przydatności bronchofiberoskopii w pierwszoplanowej diagnostyce krwioplucia. MATERIAŁ I METODY: Przedmiotem retrospektywnej analizy były wyniki badań bronchoskopowych wykonanych u pacjentów kierowanych do pracowni bronchoskopowej. Zawarto w niej jedynie te badania, w których wyłącznym wskazaniem było krwioplucie, wyłączając inne przyczyny z zakresu układu oddechowego. WYNIKI: Do ostatecznej analizy włączono 114 pacjentów. Mediana wieku wynosiła 59 lat (IQR: 46–64,75). Aktywne krwawienie stwierdzono w badaniu u 13 pacjentów (11,4%). Nie różnili się oni od pozostałych pod względem wieku: 59 (54–69) v. 59 (45–64) lat; W = 532,5, p = 0,27, oraz płci: c2 = 1,68, p = 0,2. Natomiast u 29 pacjentów (25,44%) w bronchofiberoskopii nie ujawniono żadnych nieprawidłowości. Pacjenci należący do tej grupy byli istotnie młodsi — 46 (34–62) v. 60 (53–67) lat; W = 782, p = 0,003. WNIOSKI: Mały odsetek wyników wskazujących na aktywne krwawienie sugeruje nadużywanie bronchofiberoskopii w diagnostyce krwioplucia. Wskazania do tego badania powinny być zrewidowane, w szczególności w grupie młodych pacjentów z niemasywnym krwiopluciem

The plant apoplasm is an important recipient compartment for nematode secreted proteins

Similarly to microbial pathogens, plant-parasitic nematodes secrete into their host plants proteins that are essential to establish a functional interaction. Identifying the destination of nematode secreted proteins within plant cell compartment(s) will provide compelling clues on their molecular functions. Here the fine localization of five nematode secreted proteins was analysed throughout parasitism in Arabidopsis thaliana. An immunocytochemical method was developed that preserves both the host and the pathogen tissues, allowing the localization of nematode secreted proteins within both organisms. One secreted protein from the amphids and three secreted proteins from the subventral oesophageal glands involved in protein degradation and cell wall modification were secreted in the apoplasm during intercellular migration and to a lower extent by early sedentary stages during giant cell formation. Conversely, another protein produced by both subventral and dorsal oesophageal glands in parasitic stages accumulated profusely at the cell wall of young and mature giant cells. In addition, secretion of cell wall-modifying proteins by the vulva of adult females suggested a role in egg laying. The study shows that the plant apoplasm acts as an important destination compartment for proteins secreted during migration and during sedentary stages of the nematode

Synthesis and cytostatic evaluation of 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues

The coupling of gemcitabine with functionalized carboxylic acids (C9-C13) or reactions of 4-N-tosylgemcitabine with the corresponding alkyl amines afforded 4-N-alkanoyl and 4-N-alkyl gemcitabine derivatives. The analogues with a terminal hydroxyl group on the alkyl chain were efficiently fluorinated under conditions that are compatible with protocols for (18)F labeling. The 4-N-alkanoylgemcitabines showed potent cytostatic activities in the low nanomolar range against a panel of tumor cell lines, whereas cytotoxicity of the 4-N-alkylgemcitabines were in the low micromolar range. The cytotoxicity for the 4-N-alkanoylgemcitabine analogues was reduced approximately by 2 orders of magnitude in the 2'-deoxycytidine kinase (dCK)-deficient CEM/dCK(-) cell line, whereas cytotoxicity of the 4-N-alkylgemcitabines was only 2-5 times lower. None of the compounds acted as efficient substrates for cytosolic dCK; therefore, the 4-N-alkanoyl analogues need to be converted first to gemcitabine to display a significant cytostatic potential, whereas 4-N-alkyl derivatives attain modest activity without measurable conversion to gemcitabine.status: publishe