Results of a multicenter study of nebulized inhalant bronchodilator solutions.

The efficacy, persistence of bronchodilator action, and safety of the quaternary ammonium anticholinergic agent, ipratropium bromide (500 microgram), and placebo were compared when each was added in solution form to the beta-adrenergic agonist solution, metaproterenol sulfate (15 mg), and administered three times daily for 12 weeks to a total of 213 patients with chronic obstructive pulmonary disease (COPD). Subjects had a mean forced expiratory volume in 1 second (FEV1) of approximately 1 liter (37% of predicted) and were permitted to use nonanticholinergic therapy for COPD throughout the trial. The study was a randomized, double-blind, 85-day, parallel-group, eight-center study. On a 3 test days, 1, 43, and 85, mean peak responses for FEV1 and forced vital capacity and mean area under the curve were significantly higher for the iprathropium bromide-metaproterenol combination than for metaproterenol only. Duration of action was also significantly longer for the combination therapy than for the beta-agonist alone on test days 1 and 43. Neither treatment regimen produced an demonstrable effect on daily morning peak expiratory flow rates, reported respiratory symptoms, or quality of life. Both treatment regimens were similarly well tolerated with a comparable frequency of adverse events. These results suggest that the combination of iprathropium bromide and metaproterenol inhalation solutions offers a potential therapeutic advantage to patients with symptomatic COPD over nebulized metaproterenol alone without the risk of increased side effects.

Clinical and pathologic features of Mycobacterium fortuitum infections. An emerging pathogen in patients with AIDS.

The clinical and pathologic features of Mycobacterium fortuitum infection in 11 patients with AIDS were characterized. Nine patients had cervical lymphadenitis; 2 had disseminated infection. The infection occurred late in the course of AIDS, and the only laboratory abnormality seen in more than half of patients (7/11) was relative monocytosis. Absolute monocytosis also was seen in 4 of 11 patients. In both cytologic and histologic preparations, the inflammatory pattern was suppurative with necrosis or a mixed suppurative-granulomatous reaction. M fortuitum, a thin, branching bacillus, stained inconsistently in direct smear and histologic preparations. Staining was variable with Gram, auramine, Brown-Hopps, Gram-Weigert, Kinyoun, Ziehl-Neelsen, modified Kinyoun, and Fite stains. Organisms, when present, were always seen in areas of suppurative inflammation. Incorrect presumptive diagnosis, based on misinterpretation of clinical signs and symptoms or on erroneous identification of M fortuitum bacilli as Nocardia species, led to a delay in proper therapy for 7 of 11 patients. Definitive therapy after culture identification resulted in complete resolution of infection in all patients except 1.

Generalized tuberculosis in the acquired immune deficiency syndrome.

OBJECTIVE: Generalized, or hematogenously disseminated, tuberculosis (TB) in patients with the acquired immune deficiency syndrome (AIDS) has been associated with a high incidence of cases remaining undiagnosed until postmortem. To better characterize generalized TB in the setting of AIDS, this report describes the clinical, laboratory, radiologic, and pathologic features of 20 fatal cases. DESIGN: The medical records, autopsy protocols, and histologic material from patients with AIDS and concomitant TB were reviewed. All patients were autopsied at a tertiary care medical center during the years 1985-1997. RESULTS: In 50% of our 20 cases, diagnosis was not made until postmortem. Signs and symptoms were few, including the absence of fever (temperature > or = 38 degrees C) in 55% of patients. Consistent laboratory abnormalities of a nonspecific nature were limited to hyponatremia (sodium <135 mmol/L) in 60%. Both peripheral and deep (thoracic and abdominal) lymphadenopathy, unusual in adults with TB, occurred in 45% and 95% of cases, respectively. In contrast to previous reports, all of the 6 cases of tuberculous meningitis presented as acute meningitis with a predominance of neutrophils in cerebrospinal fluid. Necrotizing encephalitis with extension of the acute inflammation into the superficial cortex was seen in all cases and tuberculous brain abscesses occurred in 50% of cases, a higher frequency than previously reported. Despite lung involvement in 90% of the cases, 33% of chest radiographs were interpreted as normal and disseminated mycobacterial disease was not suggested in the radiograph report in any of the other cases. Soft tissue abscesses in uncharacteristic locations such as the neck, mediastinum, and perirectal area occurred in these patients. Histologically, 95% of organs sampled showed inflammatory foci characterized by extensive necrosis with numerous neutrophils and/or karyorrhectic debris, numerous acid-fast bacilli, few or no epithelioid histiocytes, and no Langhans giant cells. CONCLUSION: Clinically and pathologically, generalized TB in the setting of AIDS is characterized by either unusual features or a lack of the typical features described for generalized TB in patients who do not have AIDS. This absence of classic features contributes to the high incidence of cases that remain undiagnosed until postmortem examination.

Clinical manifestations of carcinoma of the lung.

In 1991 lung cancer will account for 30% of all cancer deaths in this country, or more than 140,000 deaths. One reason for this high mortality rate is our inability to diagnose carcinoma of the lung at an early stage. Carcinoma of the lung is associated with numerous systemic effects. Because many of these are subtle in their clinical presentation, they may be overlooked until more obvious signs of malignancy are present. By this time, the tumor may be no longer amenable to surgical resection, and the chance for cure is lost. The article reviews the clinical manifestations of carcinoma of the lung that may alert the clinician to its presence and perhaps allow earlier diagnosis and prolonged survival.

The microbiology, chemotherapy, and surgical treatment of tuberculosis.

Tuberculosis is a disease that has plagued humankind for centuries. The "white plague" is not only treatable and curable but also preventable. Initially, tuberculosis fell in the province of the general physician. With the advent of technologic advances in thoracic surgery, surgical management of tuberculosis was brought to the forefront. Effective bactericidal drug therapy became available by 1954 after the development of streptomycin in 1945 and isoniazid in 1952. Additional effective antituberculous drugs have relegated surgical therapy for tuberculosis to a relatively minor role.

Clinical manifestations of pulmonary fungal infections.

Coccidioidomycosis, histoplasmosis, cryptococcosis, and blastomycosis are the most common deep pulmonary fungal infections encountered by the clinician. Each has a particular environmental habitat. As world travel increases, exposure to these infections becomes increasingly more common. The article reviews the microbiology, natural history, and clinical and laboratory findings of these diseases. Treatment options for these infections also are discussed.

COPD in the ambulatory elderly: management update.

Chronic obstructive pulmonary disease (COPD) is made up of at least three entities: asthma, chronic bronchitis, and emphysema. Each has its own unique physiology, pathology, and natural history. These are reviewed, and current therapeutic options are presented, including the first-line therapy of beta 2 agonists, theophylline, and the newer anticholinergic inhalers. The role of steroids, both acute and chronic, the proper use of antibiotics and vaccinations, and the use of home oxygen therapy, pulmonary rehabilitation, and anxiolytics are discussed.

Sensitivity of basophils to histamine releasing factor(s) of various origin: dependency on allergic phenotype of the donor and surface-bound IgE.

Certain species of histamine-releasing factor (HRF) have been demonstrated to distinguish a select group of allergic patients from healthy subjects. An IgE-dependent mechanism of action has been suggested. The donor and IgE dependency of HRF produced by peripheral blood mononuclear cells (PBMCs) has not been clearly demonstrated. In this study, we have compared the response of basophils from normal subjects versus allergic patients with and without asthma. In addition, we have addressed the IgE dependency of HRF recovered from cultures of PBMCs, T cells, B cells, macrophages, and bronchoalveolar lavage fluid. We have demonstrated that basophils from allergic as well as normal subjects respond to PBMC-HRF. The response of basophils from allergic patients with asthma is significantly increased. This heightened response to HRF does not correlate with the severity of disease as assessed by baseline spirometry, medication, and skin test scores. Stripping of the membrane-bound IgE by incubating basophils with lactic acid causes a significant loss of sensitivity to HRF generated by PBMCs, T cells, B cells, and macrophages, as well as to HRF recovered from bronchoalveolar fluid. The loss of response can be restored by sera from patients with asthma but not from normal subjects or by myeloma IgE. In addition, poorly responsive basophils from normal subjects can be rendered sensitive by incubating with sera from patients with asthma. The capacity of a given serum from a patient with asthma to restore the response to HRF is not correlated with the total concentration of IgE in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)