To explore the use of oscillometry as a measure of airway responsiveness, 69 asthmatic children underwent histamine and methacholine bronchoprovocation using dosimeter-MedicAid (Jaeger Co.; Germany) and DeVilbiss nebulizers (DeVilbiss, Bornemouth; England). The mean increase in R5 resistance in challenge testing measured after methacholine with the dosimeter-MedicAid nebulizer was 77.14% compared with 65.05% using histamine. Using the dosimeter-DeVilbiss nebulizer, the mean increases in R5 resistance following methacholine and histamine testing were 57.50% and 59.36%, respectively. The resistance R5 over R20 significantly correlated with forced expiratory volume in 1 second (FEV1). The MedicAid produced a more aggressive challenge than the DeVilbliss nebulizer. Oscillometry can be used to monitor the level of airway hyperresponsiveness following bronchoprovocation tests.
- MeSH
- Asthma diagnosis physiopathology MeSH
- Bronchial Hyperreactivity diagnosis physiopathology MeSH
- Bronchial Provocation Tests instrumentation MeSH
- Child MeSH
- Financing, Organized MeSH
- Histamine diagnostic use MeSH
- Humans MeSH
- Methacholine Chloride diagnostic use MeSH
- Adolescent MeSH
- Nebulizers and Vaporizers MeSH
- Oscillometry MeSH
- Spirometry MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Comparative Study MeSH
CTIVES: The current standard treatment of organophosphate poisoning consists of an administration of anticholinergic drugs and cholinesterase reactivators (oximes). Oximes can react - except their reactivating effect on cholinesterases - directly with cholinoreceptors. HI-6 is an oxime that may have an inhibitory effect on the muscarinic receptors, too. METHODS: In our work, we have investigated an influence of HI-6 on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and on the muscarinic receptors in vitro. The study was conducted using biosensor technique and on the rat bladder using in vitro test (tissue bath; methacholine as muscarinic agonist). IC50 for BChE from human serum was determined to be 1.01x10-6 M and for human erythrocytes AChE 3.31x10-6 M, respectively. CONCLUSION: We assume that the demonstrated contractile response can be attributed to the inhibition of the AChE at the lower concentration and to a predominant inhibition of muscarinic receptor at higher concentration of compound tested.
- MeSH
- Acetylcholinesterase metabolism MeSH
- Muscarinic Agonists pharmacology MeSH
- Biosensing Techniques MeSH
- Butyrylcholinesterase metabolism MeSH
- Cholinesterase Inhibitors pharmacology MeSH
- Rats MeSH
- Methacholine Chloride pharmacology MeSH
- Urinary Bladder innervation drug effects MeSH
- Oximes MeSH
- Parasympathetic Nervous System drug effects MeSH
- Pilot Projects MeSH
- Rats, Sprague-Dawley MeSH
- Pyridinium Compounds pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Allergic rhinitis and bronchial asthma can coexist and affect each other. OBJECTIVE: To investigate the relationship between the postseasonal increase in the concentration of leukotriene (LT) B4 and LTE4 in exhaled breath condensate (EBC) and bronchial responsiveness to methacholine (BRM) in patients with seasonal allergic rhinitis (SAR). METHODS: In 28 patients with SAR and 50 healthy study patients, the leukotrienes were measured in EBC during and after the pollen season by gas chromatography/mass spectrometry. The BRM was determined after the pollen season. RESULTS: In 7 patients with SAR, significantly increased concentrations of both the leukotrienes were found in EBC during and 5 months after the pollen season. The following seasonal and postseasonal median values were measured in patients with SAR in comparison with control patients: LTB4: 131 and 90 pg/mL vs 80 and 79 pg/mL, P < .001 and P = .03, respectively; LTE4: 122 and 86 pg/mL vs 76 and 74 pg/mL, P < .001 and P = .02, respectively. Five months after the pollen season, the concentrations of LTB4 and LTE4 decreased with respect to their seasonal values (90 and 86 pg/mL, respectively, P < .001, for both leukotrienes). In 7 patients with SAR and leukotriene levels exceeding the reference limits, significantly increased BRM was also found (LTB4: P = .02; LTE4: P = .002). CONCLUSIONS: The seasonal and postseasonal increases in LTB4 and LTE4 concentrations in EBC of the patients with SAR correlated significantly with the later increase in BMR. This relationship could provide a useful predictive parameter for early inflammatory processes in the lower airways of patients with allergic rhinitis.
- MeSH
- Anti-Asthmatic Agents therapeutic use MeSH
- Asthma drug therapy MeSH
- Bronchi drug effects MeSH
- Adult MeSH
- Financing, Organized MeSH
- Leukotriene B4 analysis MeSH
- Leukotriene E4 analysis MeSH
- Middle Aged MeSH
- Humans MeSH
- Methacholine Chloride pharmacology therapeutic use MeSH
- Young Adult MeSH
- Reference Standards MeSH
- Rhinitis, Allergic, Seasonal drug therapy MeSH
- Exhalation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
Realizácia bronchoprovokačných testov s použitím priameho alebo nepriameho stimulu pre identifikáciu bronchiálnej hyperreaktivity znižuje možnosť naddiagnostikovania a poddiagnostikovania astmy posudzovanej len podľa anamnézy a príznakov. V tomto prehľadovom článku diskutujeme o niektorých dlhodobo uznávaných tézach o bronchoprovokačných testoch z hľadiska potvrdenia alebo vylúčenia astmy a námahou navodenej bronchokonstrikcie. Nové poznatky: V skupine 240 pacientov so stanovenou diagnózou astmy bola na konci štúdie zistená vysoká prevalencia negativity metacholínového testu, pričom u mnohých pacientov bola potvrdená námahou navodená bronchokonstrikcia. Na základe toho je možné predpokladať, že negativita metacholínového testu by nemala byť považovaná za stopercentne spoľahlivú na jednoznačné vylúčenie astmy. Pozitivitu metacholínového testu samotnú je potrebné interpretovať opatrne, pretože môže odrážať skôr poškodenie dýchacích ciest ako samotnú astmu alebo námahou navodenú bronchokonstrikciu. V troch štúdiách vykazoval manitol – nepriamy stimul – podobnú prevalenciu bronchiálnej hyperreaktivity ako metacholín a identifikoval viac pacientov ako jednorazový test fyzickou záťažou. Ani manitol, ani metacholín však nedokázali identifikovať všetkých pacientov s hyperreaktivitou navodenou námahou. Manitol má vyššiu špecificitu voči lekárom stanovenej diagnóze astmy ako metacholín. Súhrn: Je pravdepodobné, že u niektorých pacientov je na jednoznačné potvrdenie alebo vylúčenie diagnózy astmy potrebné získať výsledky ako priameho, tak aj nepriameho testovania.
Performing a bronchial provocation test (BPT) using a direct or indirect stimulus to identify bronchial hyper-responsiveness (BHR) reduces the possibility of over and under-diagnosis of asthma based on history and symptoms. This review discusses some long-held beliefs of BPTs to include or exclude a diagnosis of asthma or exercise-induced bronchoconstriction (EIB). RECENT FINDINGS: A high frequency of negative methacholine tests has been reported in 240 patients given a diagnosis of asthma at the end of the study, many of whom had documented EIB. This suggests that a negative methacholine test should not be relied upon to rule out asthma. Further, a positive methacholine test alone should be interpreted with caution as it may reflect airway injury rather than asthma or EIB. Mannitol, an indirect stimulus, identified a similar prevalence of BHR to methacholine and identified more patients than a single exercise test in three studies. However, neither mannitol nor methacholine identified all patients with EIB. Mannitol has a higher specificity for a physician diagnosis of asthma than methacholine. SUMMARY: It is likely that both a direct test and an indirect test result may be required in some patients in order to confirm or exclude a diagnosis of asthma with certainty.
- MeSH
- Asthma, Exercise-Induced diagnosis physiopathology MeSH
- Asthma diagnosis physiopathology MeSH
- Bronchial Hyperreactivity diagnosis MeSH
- Bronchial Provocation Tests methods trends MeSH
- Financing, Organized MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Mannitol diagnostic use MeSH
- Inflammation Mediators physiology MeSH
- Methacholine Chloride diagnostic use MeSH
- Exercise Test MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
The purpose of this study was to assess whether during standard methacholine (Mch) challenge (concentration up to 128 mg x mL(-1)) healthy supine subjects a) develop tidal expiratory flow limitation (FL) and hyperinflation, and b) whether the onset of tidal FL is associated with dyspnoea. Eight healthy subjects were studied. Dyspnoea was assessed using the Borg scale, FL by the negative expiratory pressure (NEP) method and hyperinflation in terms of decrease in inspiratory capacity (IC). Seven patients became flow limited at Mch doses ranging 4-64 mg x mL(-1), with FL encompassing 34-84% of the control tidal volume. In six of them the onset of tidal FL was associated with little or no dyspnoea and a modest degree of hyperinflation (deltaIC <-0.4 L). In one subject, however, onset of FL was associated with a substantial reduction in IC (0.58 L) and moderately severe dyspnoea. In all of these seven subjects FL was transiently reversed after an IC manoeuvre. In conclusion, the results show that a) most healthy subjects may develop flow limitation and hyperinflation during methacholine challenge in supine position, and b) at onset of flow limitation there is little or no dyspnoea, suggesting that onset of dynamic airway compression per se does not elicit significant dyspnoea. Significant dyspnoea probably only occurs with marked dynamic hyperinflation.
- MeSH
- Bronchoconstrictor Agents * diagnostic use MeSH
- Bronchial Provocation Tests MeSH
- Adult MeSH
- Dyspnea * diagnosis physiopathology MeSH
- Humans MeSH
- Lung Volume Measurements MeSH
- Methacholine Chloride * diagnostic use MeSH
- Statistics, Nonparametric MeSH
- Reference Values MeSH
- Regression Analysis MeSH
- Airway Resistance physiology drug effects MeSH
- Sensitivity and Specificity MeSH
- Spirometry MeSH
- Supine Position MeSH
- Forced Expiratory Volume MeSH
- Peak Expiratory Flow Rate MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Controlled Clinical Trial MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
Nitric oxide (NO) has pivotal roles in cyclophosphamide- (CYP-) induced cystitis during which mucosal nitric oxide synthase (NOS) and muscarinic M5 receptor expressions are upregulated. In cystitis, urothelial muscarinic NO-linked effects hamper contractility. Therefore we wondered if a blockade of this axis also affects the induction of cystitis in the rat. Rats were pretreated with saline, the muscarinic receptor antagonist 4-DAMP (1 mg/kg ip), or the NOS inhibitor L-NAME (30 mg/kg ip) for five days. 60 h before the experiments the rats were treated with saline or CYP. Methacholine-, ATP-, and adenosine-evoked responses were smaller in preparations from CYP-treated rats than from saline-treated ones. Pretreatment with 4-DAMP did not change this relation, while pretreatment with L-NAME normalized the responses in the CYP-treated animals. The functional results were strengthened by the morphological observations; 4-DAMP pretreatment did not affect the parameters studied, namely, expression of muscarinic M5 receptors, P1A1 purinoceptors, mast cell distribution, or bladder wall enlargement. However, pretreatment with L-NAME attenuated the differences. Thus, the current study provides new insights into the complex mechanisms behind CYP-induced cystitis. The NO effects coupled to urothelial muscarinic receptors have a minor role in the development of cystitis. Inhibition of NOS may prevent the progression of cystitis.
- MeSH
- Adenosine pharmacology MeSH
- Adenosine Triphosphate pharmacology MeSH
- Cyclophosphamide MeSH
- Cystitis drug therapy pathology physiopathology MeSH
- Immunohistochemistry MeSH
- Enzyme Inhibitors pharmacology therapeutic use MeSH
- Mast Cells drug effects pathology MeSH
- Methacholine Chloride pharmacology MeSH
- Urinary Bladder drug effects pathology physiopathology MeSH
- Rats, Sprague-Dawley MeSH
- Receptors, Purinergic metabolism MeSH
- Receptors, Muscarinic metabolism MeSH
- Muscle Contraction drug effects MeSH
- Nitric Oxide Synthase antagonists & inhibitors metabolism MeSH
- In Vitro Techniques MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Obidoxime, a weak acetylcholine-esterase (AChE) inhibitor, exerts muscarinic receptor antagonism with a significant muscarinic M2 receptor selective profile. The current examinations aimed to determine the functional significance of muscarinic M2 receptors in the state of AChE inhibition, elucidating muscarinic M2 and M3 receptor interaction. In the in vitro examinations, methacholine evoked concentration-dependent bladder contractile and atrial frequency inhibitory responses. Although atropine abolished both, methoctramine (1 μmol/L) only affected the cholinergic response in the atrial preparations. However, in the presence of methoctramine, physostigmine, an AChE inhibitor, increased the basal tension of the bladder strip preparations (+68%), as well as the contractile responses to low concentrations of methacholine (< 5 μmol/L; +90-290%). In contrast to physostigmine, obidoxime alone raised the basal tension (+58%) and the responses to low concentrations of methacholine (< 5 μmol/L; +80-450%). Physostigmine concentration-dependently increased methacholine-evoked responses, similarly to obidoxime at low concentrations. However, at large concentrations (> 5 μmol/L), obidoxime, because of its unselective muscarinic receptor antagonism, inhibited the methacholine bladder responses. In conclusion, the current results show that muscarinic M2 receptors inhibit muscarinic M3 receptor-evoked contractile responses to low concentrations of acetylcholine in the synaptic cleft. The muscarinic M2 and M3 receptor crosstalk could be a counteracting mechanism in the treatment of AChE inhibition when using reactivators, such as obidoxime.
- MeSH
- Muscarinic Antagonists pharmacology MeSH
- Atropine pharmacology MeSH
- Cholinesterase Inhibitors pharmacology MeSH
- Diamines pharmacology MeSH
- Physostigmine pharmacology MeSH
- Receptor Cross-Talk MeSH
- Rats MeSH
- Methacholine Chloride pharmacology MeSH
- Urinary Bladder drug effects enzymology metabolism MeSH
- Obidoxime Chloride pharmacology MeSH
- Receptor, Muscarinic M2 antagonists & inhibitors MeSH
- Receptor, Muscarinic M3 antagonists & inhibitors MeSH
- Heart Atria drug effects enzymology metabolism MeSH
- Muscle Contraction drug effects MeSH
- In Vitro Techniques MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Diagnostika bronchiálního astmatu se dnes opírá kromě anamnestického rozboru a vyšetření klidové spirometrie také o hodnocení bronchiální hyperreaktivity a stanovení koncentrace vydechovaného oxidu dusnatého. V článku jsou uvedeny recentní poznatky a doporučení ve vyšetřování těchto pomocných, ale důležitých ukazatelů. V textu je též zmíněn nový pohled na mikrobiální osídlení bronchiální sliznice.
Diagnostics of asthma is based on analysing individual case history, spirometric measurements and also on evaluating bronchial hyperreactivity and measuring exhaled nitric oxide. This article focuses on recent recommendations regarding using these supplementary but important diagnostic methods in practice.
- Keywords
- astma, vydechovaný oxid dusnatý,
- MeSH
- Medical History Taking MeSH
- Asthma diagnosis etiology microbiology MeSH
- Bronchial Hyperreactivity diagnosis etiology MeSH
- Diagnostic Techniques and Procedures trends utilization MeSH
- Adult MeSH
- Eosinophils immunology MeSH
- Histamine diagnostic use MeSH
- Humans MeSH
- Mast Cells immunology MeSH
- Evidence-Based Medicine trends MeSH
- Methacholine Chloride diagnostic use MeSH
- Nitric Oxide analysis MeSH
- Respiratory Mucosa microbiology MeSH
- Practice Guidelines as Topic MeSH
- Spirometry methods utilization MeSH
- Tumor Necrosis Factor-alpha diagnostic use immunology MeSH
- Exercise Test utilization MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
Zobrazování metodami nukleární medicíny je k dispozici urologům již několik desetiletí. Vedle dávno etablované scintigrafie se stává stále dostupnější pozitronová emisní tomografie (PET) v kombinaci s výpočetní tomografií (CT). V odborné literatuře je popisováno využití celé řady různých radiofarmak, z nichž některá jsou dostupná i v České republice. Klinikům se tak otevírají nové diagnostické možnosti. Cílem tohoto stručného přehledu je poskytnout základní orientaci v moderních nukleárně medicínských metodách pro zobrazování karcinomu prostaty. Zmíněny jsou vlastnosti radioaktivních derivátů cholinu a glukózy a také osteotropních radiofarmak. S ohledem na biologickou heterogenitu karcinomu prostaty nelze jednoduše upřednostnit jedno radiofarmakum před druhým. Využití radionuklidových zobrazovacích metod lze spatřovat především při odhalování kryptogenních metastáz u jinak klinicky lokalizovaného onemocnění a pak také při časné lokalizaci zdroje PSA u biochemické recidivy neboť v obou těchto případech se nabízí změna dalšího terapeutického postupu.
Nuclear medicine imaging has been at the disposal of urologists for a number of decades. Alongside scintigraphy, positron emission tomography combined with computed tomography (PET/CT) is becoming widely available for clinical use. A range of radiopharmaceuticals has been reported in recent scientific literature, some of which are now available in the Czech Republic. The significance of this trend is that new and more effective diagnostic modalities have become available for use by practitioners. The aim of this brief communication is to provide a basic review of modern nuclear medicine techniques for imaging prostate cancer. The properties of radioactive glucose and choline derivatives as well as osteotropic radiopharmaceuticals are described. Due to the biological heterogeneity of prostate cancer no particular radiopharmaceutical agent is universally superior. The benefits of nuclear medicine imaging techniques can be seen in the detection of metastases in an otherwise cryptogenic localised disease, and in the timely localisation of biochemical recurrences. In both of these cases early disease detection might change the applicable therapeutic process.
- Keywords
- novotvary prostaty, methylcholin, pozitronová emisní tomografie a výpočetní tomografie, fluoromethylcholin,
- MeSH
- Choline analogs & derivatives diagnostic use MeSH
- Diagnostic Imaging MeSH
- Sodium Fluoride diagnostic use MeSH
- Fluorodeoxyglucose F18 diagnostic use MeSH
- Bone and Bones MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Multimodal Imaging MeSH
- Bone Neoplasms secondary MeSH
- Prostatic Neoplasms * pathology MeSH
- Positron-Emission Tomography * MeSH
- Prostate MeSH
- Radiopharmaceuticals diagnostic use MeSH
- Radionuclide Imaging * MeSH
- Fluorine Radioisotopes diagnostic use MeSH
- Carbon Radioisotopes diagnostic use MeSH
- Sensitivity and Specificity MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Review MeSH