ABSTRACT
A cluster of occupational asthma (OA) cases associated with occupational exposure to 3-amino-5-mercapto-1,2,4-triazole (AMT) and N-(2,6-difluorophenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide (DE498) in a herbicide producing plant was previously reported by the National Institute for Occupational Safety and Health. Due to the limited toxicological data available for these chemicals, murine studies were undertaken to evaluate the toxicity and sensitization potential of these two agents. No signs of systemic toxicity as evaluated by body and selected organ weights or irritancy were observed following dermal exposure to concentrations up to 25% (w/v) AMT in BALB/c mice. DE498 tested negative for sensitization potential in both the TOPKAT QSAR model and in vivo in the Local Lymph Node Assay (LLNA), while AMT tested positive in both TOPKAT QSAR and the LLNA. Evaluation of the potential for AMT to induce contact hypersensitivity using the MEST yielded negative results. Cytokine evaluation and phenotypic analysis of draining lymph node (DLN) cells demonstrated an increase in IL-4 and IgE+B220+ cells 4 and 10 days post initial exposure, respectively. Following dermal exposure 7 days a week for 35 days, animals exposed to up to 25% AMT demonstrated a dose-dependent elevation in total serum IgE and an increase in airway hyperreactivity upon methacholine challenge. Following intratracheal challenge with AMT, pulmonary histopathology revealed a dose-dependent suppurative and histiocytic alveolitis in these animals. These studies indicate that DE498 does not induce sensitization following dermal exposure; however, AMT was identified as a sensitizer with the potential to induce airway hyperreactivity.
Subject(s)
Respiratory Hypersensitivity/chemically induced , Triazoles/toxicity , Administration, Cutaneous , Animals , Cytokines/metabolism , Dose-Response Relationship, Drug , Female , Immunoglobulin E/blood , Interleukin-4/biosynthesis , Interleukin-4/genetics , Lung/drug effects , Lung/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred CBA , Models, Biological , Occupational Exposure , Phenotype , Pyrimidines/administration & dosage , Pyrimidines/toxicity , Quantitative Structure-Activity Relationship , RNA, Messenger/biosynthesis , Respiratory Hypersensitivity/metabolism , Sulfonamides/administration & dosage , Sulfonamides/toxicity , Time Factors , Triazoles/administration & dosageABSTRACT
1. In patients with chronic cor pulmonale there is a regression dependence between the amount of exercise-induced increase in pulmonary arterial pressure and the level of resting value. 2. Hemodynamics during exercise are influenced by the patient's position in a certain degree. 3. The exercise-induced increase in pulmonary arterial pressure in chronic cor pulmonale is not influenced by the patient's age. 4. The time course of pressure fall during recovery depends on the amount of pressure increase during exercise, it depends less evidently on the level of the resting values. 5. Tachycardia is not a compulsory symptom of chronic cor pulmonale.
Subject(s)
Hemodynamics , Pulmonary Heart Disease/physiopathology , Blood Pressure , Chronic Disease , Humans , Physical Exertion , Posture , Pulmonary Artery/physiopathology , RestABSTRACT
11 laboratories of the working group "Pathophysiology of Breathing" cooperated with standardized methods to obtain generally admitted practical criterions for the definition of respiratory insufficiency. Function parameters of 2800 examined persons in different diagnostic groups were tested by manual statistical analysis and computed by data processing system. which were assessed with regard to their usefulness as criterions for respiratory insufficiency. The arterial O2-partial pressure proved to be the most crucial criterion of respiratory insufficiency permitting objective evidence of a manifest respiratory insufficiency by hypoxeamia under standard efforts with a bicycle-ergometer. The screening parameters of ventilation such as vital capacity and forced exspiratory volume are suitable as subjective rapid methods for a quantitative estimation of one type of respiratory insufficiency: the ventilation disturbance. Investigations, which were carried out with a higher apparatus expense like the estimation of residual volume, the functional residual capacity, and the arterial CO2-partial pressure permit the further differentiation of causes of the respiratory insufficiency and the separation between respiratory partial- and global insufficiency. The parameters of gas exchange: O2-consumption, respiratory quotient, and the screening parameter of cardiocirculation heart rate are not or only limited useful as criterions of respiratory insufficiency alone.
Subject(s)
Respiratory Insufficiency/physiopathology , Hemodynamics , Humans , Oxygen Consumption , Pulmonary Ventilation , Respiratory Function Tests/methods , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Tuberculosis, Pulmonary/complications , Ventilation-Perfusion Ratio , Vital CapacityABSTRACT
Parameters of pulmonary mechanics were measured at rest and during physical effort in patients with silicosis and normal subjects. Between normal subjects and patients with silicosis of stage I a significant difference could not be found. However, a decrease of dynamic compliance and an increase of elastic work of breathing were found in patients with silicosis III during exercise. The PT/VT-quotient is already high at rest. These results are not in agreement with the subjective symptom "dyspnea". The feeling of dyspnea appears when the PT/VT-quotient is enhanced signifcantly during exercise in comparison with the value at rest. Therefore, only the PT/VT-quotient is a suitable parameter indicating dyspnea.
Subject(s)
Lung/physiopathology , Silicosis/physiopathology , Dyspnea/physiopathology , Humans , Lung Compliance , Physical Exertion , RespirationABSTRACT
The effect of inhalation of Novodrin (beta-receptor-stimulus), Phenylephrine (alpha-receptor-stimulus) and of a mixture of both was tested in patients with chronic nonspecific respiratory syndrome. There was no significant difference of pulmonary arterial mean-pressure. Forced expiratory volume and vital capacity rose both after inhalation of Novdrin and after inhalation of the mixture. Nevertheless inhalation of the mixture can not be recommended because of a significant decrease of arterial oxygen-tension.
Subject(s)
Lung Diseases/drug therapy , Lung/physiopathology , Sympathomimetics/therapeutic use , Aerosols , Blood Pressure/drug effects , Bronchodilator Agents/therapeutic use , Drug Combinations , Drug Evaluation , Forced Expiratory Volume , Humans , Oxygen/blood , Partial Pressure , Phenylephrine/therapeutic use , Pulmonary Artery/drug effects , Respiratory Therapy , Vital CapacityABSTRACT
In patients with mitral valvular defects as well as with chronic cor pulmonale there exists an ascertained relation between the pulmonary-arterial pressure in rest and the increase of blood pressure under easy physical load. Patients with high initial value or strong increase of blood pressure reveal a retarded return of the blood pressure of the pulmonary artery to the initial value.
Subject(s)
Heart Valve Diseases/physiopathology , Mitral Valve , Pulmonary Heart Disease/physiopathology , Adult , Blood Pressure , Cardiac Catheterization , Female , Heart Function Tests , Humans , Male , Middle Aged , Physical Exertion , Pulmonary ArteryABSTRACT
Mechanics of breathing as studied in patients with different stages of silicosis in rest and during exercise show the following: dynamic compliance and work against elastic and viscous resistances could not be found to be decisive indices of exertion dyspnea. Evidence of exertion dyspnea could only be achieved by means of the ration VT/PT (VT equals tidal volume, PT equals tidal esophageal pressure). Exertion dyspnea was observed at less than 0,081 VT per cm H20 PT. In accordance with Campbell and Howell, dyspnea is seen as an inappropriateness between ventilation and pressure needed.
