Temporal profile of release of interleukin-1beta in neurotrauma.

Timing and extent of trauma-induced release of interleukin-1beta (IL-1beta) in extracellular fluid of the CNS were analyzed. In brain tissue perfusates obtained by in vivo microdialysis a marked release of IL-1beta was unexpectedly detected within less than 60 min. At such an early stage of neurotrauma, mRNA expression of IL-1beta was detected whereas immunoreactivity for the IL-1beta protein was negative. Concentrations of extracellularly secreted IL-1beta protein gradually increased, peaked at day 2 and decreased thereafter. Drugs acting on mononuclear phagocytes significantly modulated IL-1beta secretion. This so far unrecognized acuity of IL-1beta release demonstrated here, may represent a precondition for the orchestrating role of this mediator in the cascade of inflammatory host response.

The spectrum of respiratory disease associated with exposure to metal working fluids.

Occupational respiratory diseases have been reported following exposure to metal working fluids. We report a spectrum of respiratory illnesses occurring in an outbreak in 30 workers of an automobile parts engine manufacturing plant. Workers presented with respiratory complaints and, after clinical and laboratory evaluations, were classified as those having hypersensitivity pneumonitis, occupational asthma, or industrial bronchitis, or those without occupational lung disease. Hypersensitivity pneumonitis affected seven workers, with six exhibiting serum precipitins to Acinetobacter Iwoffii. Occupational asthma and industrial bronchitis affected 12 and six workers, respectively. Oil-mist exposures were below current recommendations. Gram-negative bacteria, but no fungi, Thermophiles, or Legionella, were identified. Although specific agents responsible for each individual case could not be identified, probably both specific sensitizing agents and non-specific irritants from metal working fluids, additives, or contaminants contributed to this spectrum of occupational respiratory illness.

Pulmonary artery thrombolysis and stenting after a bilateral sequential lung transplantation.

Bilateral sequential lung transplantation was complicated by pulmonary artery anastomotic stenosis and bilateral pulmonary thromboemboli. Pulmonary artery thrombus was eliminated by intrathrombotic but not by systemic administration of urokinase. The pulmonary emboli resulted in localized pulmonary infarctions, supporting the need for thrombolytic intervention to restore pulmonary perfusion in the absence of collateral bronchial blood flow after lung transplantation. Pulmonary artery stenosis was relieved by endovascular stenting, avoiding an early reoperative procedure. This case suggests that direct administration of thrombolytic agent may be superior to intravenous administration in the treatment of pulmonary thromboemboli. Pulmonary arterial anastomotic stenoses after lung transplantation can be relieved by endovascular procedures.

Chronic lung disease secondary to ammonia inhalation injury: a report on three cases.

Inhalation of highly hydrosoluble toxicants, like ammonia, can be associated with chronic lung diseases, which have been partially characterized. We present the case of three patients who were evaluated 2 years after massive exposure to ammonia in occupational settings. They presented with chronic dyspnea, and clinical pictures consistent with restrictive lung dysfunction, obstructive lung disease, and bronchial hyper-reactivity and small airways disease, respectively. The findings in 94 reported cases of inhalation injury due to massive exposure to ammonia are reviewed; in 35 cases follow-up for at least 1 year was available. The range of chronic pulmonary diseases associated with ammonia inhalation injury is reviewed, and suggestions for appropriate diagnostic evaluation are made.

A new mask filter cartridge used to determine applicator inhalation exposure to an alachlor herbicide (Lasso) during normal spraying operations.

A filter cartridge with a low air-flow resistance was designed for use on a modified half-face respirator worn during the application of alachlor (Lasso) herbicide. The filter trapped large concentrations of alachlor while retaining the ability to trap small respirable droplets. Moreover, alachlor could be recovered from the disassembled cartridge and analyzed by conventional methods. The test cartridges were used in combination with conventional personal air samplers to determine whether the filters trapped more alachlor when compared with personal samplers and to determine accurately the amount of alachlor reaching the breathing zone. Farmers sprayed alachlor in the form of alachlor (N = 7) or alachlor mixed with other herbicides or surfactant (N = 15). An average of 4 x 10(-2) mg or 2 x 10(-4) mg/kg of applied alachlor reached the respirator filters. This concentration was 10-fold higher than the alachlor recovered from the personal samplers. The new filter cartridge is better for determining the amount of alachlor reaching the breathing zone, and there is a low potential for significant inhalation exposure to alachlor during normal spraying operations.

Screening for occupational asthma: a word of caution.

The diagnosis of occupational asthma may be difficult due to the complex mechanisms inducing the disorder. Identification of the offending agent after historical documentation may be difficult without bronchial challenge. The hallmark of asthma is bronchial hyperreactivity as detected by methacholine challenge, and this test could be considered as a screening test for asthma in the workplace. Four cases are presented that document changes in methacholine airway reactivity dependent on temporal association with exposure to the workplace or the specific offending agent. This indicates a need for a careful evaluation of symptoms relative to exposure in patients suspected for workplace asthma as well as serial determinations of methacholine response to detect potential variability in the airway reactivity.

Environmental challenge.

A variety of organic dusts and chemicals encountered in our environment are capable of provoking a response in the lung. Frequently, they produce transient or reversible physiologic changes that may obscure the diagnosis. The patient may fail to recognize a causal relationship with a specific exposure with late-onset reactions and the development of symptoms remote from the exposure. A thorough evaluation of the individual's total environment and symptoms, with particular reference to their time course, is essential in making the diagnosis. Removal of the worker from a suspected environment, with serial clinical and physiologic monitoring to demonstrate improvement, or return to the workplace with similar studies, can be helpful in establishing a causal relationship. When a specific agent can be identified, a controlled inhalation challenge in the laboratory is the procedure of choice. Once a causal relationship has been established, the individual should be removed from exposure or the implicated agent eliminated.

Bronchial hyperreactivity and cough due to angiotensin-converting enzyme inhibitors.

Seventeen patients using angiotensin-converting enzyme (ACE) inhibitors for hypertension were evaluated with baseline spirometry followed by determination of bronchial reactivity by challenge with methacholine. There were nine coughers and eight noncoughers in the study. Among the nine coughers, eight demonstrated bronchial hyperreactivity. Conversely, none of the noncoughers disclosed bronchial hyperreactivity. Eight of the nine coughers were rechallenged two to six months following cessation of ACE inhibitor therapy. Six of these eight showed persistent bronchial hyperreactivity. We conclude that cough is associated with the use of ACE inhibitors in patients with underlying bronchial hyperreactivity. The findings indicate caution in administration of ACE inhibitors in asthmatic patients and those with known bronchial hyperreactivity.

Welders' pneumoconiosis: tissue elemental microanalysis by energy dispersive x ray analysis.

Histological examination on lung tissue obtained from 10 symptomatic welders was performed by two certified pathologists without the knowledge of the patients' clinical condition. In all cases, there was some degree of interstitial fibrosis; in five the degree of fibrosis was considered to be moderate to pronounced. The tissue was also analysed by energy dispersive x ray analysis and elemental contents were compared with age matched controls. There was a large amount of iron in the lungs of welders but the silicon content did not differ from the control subjects. No specific foreign element was detected. It is concluded that (1) interstitial pulmonary fibrosis is seen in some welders and (2) the cause of fibrosis does not appear to be coexisting silicosis.

Passive transfer of methacholine sensitivity from man to monkey.

A model of human allergic disease, in which nonhuman primates were infused with serum from allergic humans and challenged with appropriate antigen, was used to determine whether the animals also develop hyperreactive airways characteristic of asthma. Anesthetized monkeys were insufflated with increasing concentrations of methacholine aerosol, and changes in pulmonary function were measured. Airway reactivity as assessed by the dose of methacholine aerosol culminating in apnea was determined after infusion of serum from allergic or nonallergic humans or with heated allergic serum. A comparison of the results indicated that only infusion of unheated serum from allergic humans resulted in an increase in airway reactivity to aerosolized methacholine. These results suggest that a factor in the serum of allergic humans may play a role in the hyperreactivity of airways characteristic of asthma.

Ipratropium bromide in asthma. A review of the literature.

In comparative studies of asthma, ipratropium bromide has been shown to have a slower onset of bronchodilator action but a longer duration of effect than beta agonists. An additive effect of ipratropium and beta agonists has been demonstrated, in addition to prolongation of the bronchodilator response. Most studies do not show a definite difference in responsiveness of atopic versus nonatopic asthmatic patients; there are, however, reports indicating a greater responsiveness to anticholinergic agents than to beta agonists in patients with chronic bronchitis and emphysema. Ipratropium has been shown not to affect mucociliary clearance, sputum volume, or viscosity. It effectively inhibits the bronchial response to methacholine and, to a lesser degree, to histamine, serotonin, bradykinin, and antigen. Protection against exercise-induced asthma with this drug has been variable, but ipratropium has been found particularly useful in psychogenic asthma. Its role in occupational asthma remains to be determined.

The pathophysiologic and roentgenologic effects of chest irradiation in breast carcinoma.

We studied the effects of radiation therapy on lung function in 21 patients who underwent modified radical mastectomy and radiotherapy for breast carcinoma. The patients had pulmonary function studies and chest X rays prior to radiation therapy and at six weeks, and three, six, and twelve months following radiation therapy. All pulmonary function studies showed a small but statistically significant decline within the first three months following radiation therapy. Changes in the moderate and large airways continued to occur after three months. None of the changes in pulmonary function were reversible. Radiographic changes occurred in 12 patients. These changes occurred later than the lung function changes (median time for the changes was twelve months) and were unrelated to changes in lung function.

Antigen-induced enhancement of bronchial reactivity.

Bronchial hyperreactivity as determined by the airway response to methacholine was evaluated pre- and post-antigen challenge in three patients with specific antigen sensitivity. No significant change in pulmonary function was noticed after inhalation of antigen alone. However, transient but significant increase in methacholine responsiveness followed the antigen challenge. The studies indicate a need for a nonspecific inhalation challenge following a negative antigen challenge when clinically indicated.

Immunoregulation in hypersensitivity pneumonitis: phenotypic and functional studies of bronchoalveolar lavage lymphocytes.

We examined the immunologic phenotype and function of bronchoalveolar lymphocytes isolated from 4 pigeon breeders who developed symptoms of hypersensitivity pneumonitis on exposure to pigeons, and 6 asymptomatic but equally exposed individuals. Similar numbers of bronchoalveolar lymphocytes were found in symptomatic breeders compared with the asymptomatic, and the percent of T11, T4, and T8 bearing cells as well as the T4/T8 ratios were similar in both groups. Despite these similarities, the groups had significantly different functional activity. Bronchoalveolar lymphocytes from symptomatic breeders demonstrated a marked (p less than 0.001) increase in blastogenic activity to both phytohemagglutinin and pigeon serum stimulation when compared with asymptomatic breeders. In addition, enriched bronchoalveolar T-cells suppressed the response of autologous preincubated peripheral blood lymphocytes to both phytohemagglutinin and pigeon serum in the asymptomatic compared with the symptomatic breeders. These studies suggest a discrepancy between the phenotype and function of immunoregulatory T-cell subsets in bronchoalveolar lavage lymphocytes in pigeon breeder's disease, and support a role for functional immunoregulatory imbalances in the pathogenesis of hypersensitivity pneumonitis.

Pneumoconiosis in workers exposed to silicon carbide.

Two men who had been exposed only to silicon carbide for many years in a factory manufacturing refractory bricks developed bilateral reticulonodular densities, as shown on chest radiograms, and complained of dyspnea. An open lung biopsy of one of them showed a large amount of black material in the fibrosed alveolar septums. Studies by X-ray diffraction revealed that the silicon carbide to which they were exposed did not contain quartz; X-ray powder diffraction analysis of the lung tissue revealed at least 6 different silicon carbides, traces of tungsten carbide, and an insignificant amount of quartz. Line-width analysis of the pattern suggested that the lung contained foreign material, with a significant number of particles smaller than 0.1 micron. The etiologic role of silicon carbide for tissue fibrosis is discussed.

Value of in situ elemental microanalysis in the histologic diagnosis of silicosis.

Pulmonary specimens obtained from ten normal subjects and 53 patients with various pulmonary diseases were studied with energy-dispersive x-ray analysis. The amount of silicon in the pulmonary tissue was determined and expressed as a silicon/sulfur (Si/S) ratio. This Si/S ratio was below 0.2 in the ten normal subjects and in 14 patients who had various interstitial pulmonary diseases but had no previous history of exposure to silica or other dusts known to cause pulmonary fibrosis. The Si/S ratio was greater than 0.3 in 19 of 22 patients who had a history of exposure to silica dust and had clear-cut histologic evidence of silicosis. The Si/S ratio was less than 0.2 in 12 and between 0.2 and 0.3 in two of the 14 patients who had a history of exposure to silica dusts but no clinical or histologic evidence of silicosis. We conclude that the determination of the silicon content of tissue by energy-dispersive x-ray analysis is useful in separating the fibrosis due to silicosis from the other causes of pulmonary fibrosis.

Indolent diffuse histiocytic lymphoma with sclerosis and chylous effusions.

A case of diffuse histiocytic lymphoma with sclerosis and chylous pleural and peritoneal effusions spanning four years from onset to diagnosis is presented. Treatment with combination chemotherapy and consolidative radiotherapy resulted in clinical improvement and the patient remains free of disease 14 months after stopping treatment. The problems of chylous effusions and the subgroup of diffuse histiocytic lymphoma with sclerosis are discussed.

Streptomyces albus: a new cause of hypersensitivity pneumonitis.

Hypersensitivity pneumonitis is an immunologic lung disease known to be induced by the inhalation of either organic or inorganic antigens, and it may thus be associated with a variety of occupations and microorganisms. To identify an inciting allergen, environmental, bacteriologic, immunologic, and bronchial challenge studies must be employed. These techniques were used to demonstrate that a bacterium uniformly present in processed dirt, Streptomyces albus, was responsible for a biopsy-proven case of hypersensitivity pneumonitis.

Spectrum of clinical disease in pulmonary infection with Mycobacterium avium-intracellulare.

Cases of infection with Mycobacterium avium-intracellulare reported in Milwaukee, Wisconsin, have become more common in recent years, and their incidence--50 cases per year--is now similar to that of tuberculosis. Cases usually occur in middle-aged men with underlying lung diseases, but variations in age, sex, presentation, and severity of disease are wide. Several cases that illustrate pathogenesis and spectrum of disease, from primary, to chronic-active, to healing stages, are presented. The disease tends to run an indolent course in most cases, but extensive disease and unfavorable early course indicate poor prognosis. At a 10-year review, mortality had reached sizable numbers in this aging population with frequent serious underlying problems. Only a small number of these deaths can be attributed directly to mycobacterial disease.

Immunoglobulin levels in bronchoalveolar lavage fluid from pigeon breeders.

Analysis of serum and BAL fluid immunoglobulin levels in individuals with PBD and in asymptomatic but similarly exposed pigeon breeders was carried out by immunofluorometric assays. The results indicate that the group with PBD have significantly higher levels of IgG and IgA in their BAL fluids but that IgM levels were not significantly different in the two groups. These differences were not reflected in the serum immunoglobulin levels of the two groups. The elevated BAL fluid IgG levels in individuals with PBD is associated with an increase in IgG4 subclass levels as determined PHA inhibition. These studies suggest a role for this subclass in the pathogenesis of the disease.