Pinocytosis by human alveolar macrophages. Comparison of smokers and nonsmokers.

Alveolar macrophages were obtained from human volunteers, smokers and nonsmokers, by bronchial lavage through a fiberoptic bronchoscope. Cells were incubated in a chemically defined medium containing [(14)C]sucrose (0.36 mM) and varying concentrations of rabbit serum. Pinocytosis was assessed by the cellular uptake of isotope over 30, 75, and 120-min periods. Pinocytic activity of smokers' cells was dependent on serum concentration but always less than the activity of nonsmokers' cells. The degree of pinocytosis by nonsmokers' cells was independent of serum concentration. It is concluded that the decreased level of pinocytic activity in smokers' alveolar macrophages as indicated by the uptake of sucrose in the presence of rabbit serum may represent a form of reticuloendothelial blockade.

Presenting characteristics as predictors of duration of treatment in sarcoidosis.

BACKGROUND: Some sarcoidosis patients never need therapy, but many still require therapy more than 2 years after initial diagnosis. AIM: To determine what features at initial presentation are associated with treatment 2 years later. METHODS: Patients with biopsy-confirmed sarcoidosis enrolled in the ACCESS (A Case Control Etiologic Study of Sarcoidosis) study were initially evaluated within 6 months of diagnosis. Pulmonary function, chest X-ray and dyspnoea score were measured, and systemic therapy for the sarcoidosis recorded. Organ involvement was assessed using a standardized instrument. A subset (n = 215) were seen 18-24 months later for follow-up, and these patients constitute our study group. RESULTS: Ten patients had only received therapy before the first visit, with no further therapy, and were excluded from analysis. Of the remaining 205, 95 were not on therapy at the initial visit and 75 (79%) of these were never treated during follow-up. Of the 110 initially on therapy, 52 (47%) remained on therapy at follow-up. Other initial features associated with continued therapy were the level of dyspnoea and predicted vital capacity. On logistic regression, only dyspnoea and therapy at initial visit remained significant. Patients on systemic therapy at initial evaluation were more likely to be on therapy at follow-up (OR 3.6, p = 0.003). Neither ethnicity nor gender independently predicted therapy at follow-up. DISCUSSION: This study group represents a sample of newly diagnosed sarcoidosis patients. However, this is a referral population, and there was no set protocol for treatment. Use of systemic therapy within the first 6 months after diagnosis appears to be strongly associated with continued use of therapy 2 years later.

Hyaluronan receptor (CD44) expression and function in human peripheral blood monocytes and alveolar macrophages.

CD44 glycoproteins are present on the surfaces of many hematopoietic cells and in some cases can bind hyaluronan, a major component of the extracellular matrix. In the present study, we have found that newly explanted human peripheral blood monocytes (PBMs) exhibit a major CD44 band of 85 kDa, whereas autologous alveolar macrophages (AM phi) express multiple isoforms ranging from 85 to 200 kDa. Within 4 h in culture, PBMs began expressing new CD44 isoforms of 120, 150, and 180 kDa. Newly explanted AM phi specifically bound [3H]hyaluronan (135 cpm/microgram protein), but newly explanted PBMs did not. However, in vitro cultured PBM progressively acquired the ability to bind [3H]hyaluronan and exhibited specific binding of hyaluronan similar to that of AM phi (113 cpm/microgram protein) after 4 days in culture. In both case, the binding of [3H]hyaluronan was specifically inhibited by the addition of monoclonal antibody directed against CD44. AM phi readily degraded [3H]hyaluronan and reached a plateau after 4 days in culture (115 cpm/microgram protein). Newly explanted PBM exhibit no hyaluronan degradation and only a small degradative activity after 4 days in culture (6 to 11 cpm/microgram protein). Thus, CD44 expression and function appear to change as PBM mature in vitro resembling more that found in AM phi.

Idiopathic pulmonary hemosiderosis: ultrastructural studies and responses to azathioprine.

Two boys are presented who fulfilled criteria for a diagnosis of idiopathic pulmonary hemosiderosis. A lung biopsy specimen from the first patient showed alveolar-capillary basement membrane abnormalities, together with abnormalities of capillary endothelial cells and hemosiderin-laden macrophages. A lung biopsy specimen from the second patient showed mainly capillary endothelial abnnormalities and interestitial fibrosis. Both patients had a noticeable improvement in symptoms and relative stabilization of their roentgenographic and pulmonary function abnormalities following azathioprine therapy.

Resin hemoperfusion: a method of removing circulating thyroid hormones.

The ability of an extracorporeal hemoperfusion system employing neutral Amberlite resin to bind thyroid hormone and to decrease circulating levels of triiodothyronine (T3), thyroxine (T4), and free thyroxine (FT4) was evaluated in dogs made thyrotoxic by the intramuscular administration of thyroid hormone. Since the resin column and tubing were charged with saline, the effects of hemodilution from this source on serum T3 and T4 was assessed by control perfusion through a column which did not contain any resin. After correction for hemodilution, the mean serum T3, T4 and FT4 decreased during 2 hours of resin hemoperfusion by 39%, 35%, and 46%, respectively. Hormonal clearance rates were calculated in two experiments and the estimated net hormone removed averaged 60.4 mug of T3 and 1990 mug of T4. Hematologic indices and routine chemistries did not change significantly in these dogs during the procedure except for a decrease in mean serum albumin concentration and an increase in mean serum glucose concentration. Hemoperfusion through this resin system seems to be a safe, effective means of decreasing serum T3, T4, and FT4 in thyrotoxic dogs and warrants evaluation for the treatment of thyroid storm in man.

Antiglomerular basement membrane antibody-mediated glomerulonephritis and Goodpasture's syndrome.

The originally dismal prognosis associated with anti-GBM Ab-mediated GN and Goodpasture's syndrome may be changing as we recognize a broader spectrum of disease, improve general supportive care, and improve specific treatment. Immunosuppressive therapy, if started early in the course of disease, may prevent or allow recovery from renal failure and may also result in cessation of recurrent pulmonary hemorrhage in most patients with this form of Goodpasture's syndrome. The administration of pharmacologic doses of corticosteroids intravenously can result in cessation of and dramatic recovery from severe pulmonary hemorrhage and obviate the need for emergency bilateral nephrectomy. Plasmaspheresis may represent a useful therapeutic procedure for the immediate and long term reduction in amounts of circulating anti-GBM Ab, but the definition of its true value and role awaits completion of controlled, prospective trials. Immunosuppressive therapy, with or without plasmapheresis, can reduce quantities of anti-GBM Ab in serum to undetectable levels without nephrectomy. Thus, it is likely, but not proven, that nephrectomy can be discontinued as a routine pretransplantation procedure in patients with anti-GBM Ab mediated GN. Finally, in patients who suffer irreversible renal failure, renal transplantation can be successfully undertaken with minimal risk of recurrent disease, when circulating anti-GBM Ab becomes undetectable.

The ultrastructure of bronchial macrophages and lymphocytes in sarcoidosis.

A physical interaction between macrophages and lymphocytes was observed more frequently in bronchial lavage fluid obtained from patients with sarcoidosis than from normal volunteers, irrespective of their history of smoking. In this spontaneous interaction more than two lymphocytes were commonly seen adhering to a macrophage without evidence of cytoplasmic bridging or membrane fusion. To a greater extent than in normal volunteers, macrophages from patients with sarcoidosis were characterized by the appearance of a more highly irregular cell surface, more membrane bound inclusions, however, was positively correlated with the smoking history of the individual, and the number of surface projections (microvilli) of macrophages from smokers appeared to be reduced. Significant differences were not apparent in the nuclear or cellular diameters of macrophages from sarcoid and normal individuals.

Late bronchopleural fistula and Hemophilus influenzae empyema complicating longstanding oleothorax: report of two cases.

Bronchopleural fistula and Hemophilus influenzae empyema developed in two patients with longstanding oleothorax. The first patient died after drainage with a pleurocutaneous flap, and a seven-rib thoracoplasty failed to resolve her infection. In the second, resection of the oleothorax cavity and left upper lobe resulted in cure.

Parapneumonic empyema. A pitfall in diagnosis.

Two patients eventually shown to have empyema were encountered in which the initial thoracentesis revealed fluid compatible with either a simple or a complicated parapneumonic effusion. In both cases, the diagnosis of empyema was made by a second thoracentesis done at a close interval of time from a different site. Therefore, the physician should approach parapneumonic effusions systematically, and remember that in some cases, multiple thoracenteses may be required to make the correct diagnosis of an empyema.

Asthma: comparative bronchodilator effects of ipratropium bromide and isoproterenol.

The effect of ipratropium bromide administered at two dosage levels, 40 and 80 mug, isoproterenol, 150 mug, and placebo using a metered dose inhaler was evaluated in ten adult patients with asthma in a double-blind, crossover study. The new atropine-like drug proved to be as effective a bronchodilator as isoproterenol in this study, although it had a later peak effect. Ipratropium bromide had a longer course of action than isoproterenol (4 hours compared to 1-2 hours) and was free of significant side effects. The larger dose of the new drug produced a slightly greater and longer-acting effect than the smaller dose. Ipratropium bromide seems to have had bronchodilator effects on both large and small airways.

Defining organ involvement in sarcoidosis: the ACCESS proposed instrument. ACCESS Research Group. A Case Control Etiologic Study of Sarcoidosis.

BACKGROUND: Sarcoidosis is a multiorgan granulomatous disease of unknown cause. Lack of an objective system for assessment of sarcoidosis to evaluate disease course and effectiveness of therapy is a major problem. METHODS: The sarcoidosis assessment instrument was developed by the Steering Committee of A Case Control Etiologic Study of Sarcoidosis (ACCESS) which included investigators at the ten ACCESS Clinical Centers, the Clinical Coordinating Center, and representatives of the National Heart, Blood, and Lung Institute. This system was developed to assess sarcoidosis organ involvement in ACCESS patients who would be followed over a two-year period. The system represents a consensus of opinions of members of the Steering Committee based on review of their experience and the medical literature. RESULTS: Criteria for involvement in patients with biopsy-confirmed sarcoidosis are presented for organs and systems that are commonly involved (lung, skin, eyes, liver, calcium metabolism), unusual but clinically important (nervous system, kidney, heart) and other sites (non-thoracic lymph nodes, bone marrow, spleen, bone/joint, ear/nose/throat, parotid/salivary glands, muscles). CONCLUSION: The proposed instrument is partially subjective in that it depends upon the clinician's diligence in pursuing evidence for sarcoidosis involvement of various organs. It is hoped that this instrument will lead to increased standardization in the definition of sarcoidosis organ involvement to help clinicians and researchers better characterize patients with sarcoidosis.

Human alveolar macrophage mediated vasodilation and the role of arginine compounds.

To determine whether human alveolar macrophages (AM) generate a compound similar to the endothelium-derived relaxing factor, we studied the effect of AM on the isometric response of the pre-contracted rat aorta preparation in the presence and absence of L-arginine or N-substituted L-arginine compounds. Addition of AM to the pre-contracted aorta preparation was ineffective even in the presence of millimolar concentrations of L-arginine. But, AM in the presence of the substituted L-arginine, N alpha-benzoyl L-arginine ethyl ester, significantly increased vasodilation. The enhanced relaxation was associated with an increase in vascular cyclic guanosine 3,5'-monophosphate formation. Hemoglobin and N omega-nitro L-arginine methyl ester are inhibitors of the endothelium-dependent relaxation, and both attenuated the vasodilation elicited by AM. Human AM were found to metabolize N alpha-benzoyl L-arginine ethyl ester to a citrulline derivative. No such metabolism was observed with L-arginine. A specific, high-pressure liquid chromatographic assay for guanidines revealed that the lack of effect of external L-arginine is not due to the presence of an excess amount of endogenous L-arginine in AM. These results demonstrate that nonactivated human AM, unlike rodent macrophages, possess an enzyme system(s) that metabolize(s) arginine derivatives but not L-arginine to a vasodilator, and this vasodilator has properties similar to that of endothelium-derived relaxing factor. This human AM-derived vasodilator may have an important role in regulating airway smooth muscle function.

Pulmonary sarcoidosis: comparison of patients at a university and a municipal hospital.

Charts and radiographs of sarcoidosis patients seen at a private university hospital and at a municipal hospital were reviewed to determine whether there was a difference in the severity of disease retrospectively. A standardized abstract form was used to identify and abstract information on new and continuing sarcoidosis patients seen at either Georgetown University Medical Center (GUMC) or District of Columbia General Hospital (DCGH) during a 2-year period. Because there were too few white sarcoidosis patients for comparison, analysis was done for African-American patients only. African-American patients at GUMC were slightly older, with a higher percentage of women. For GUMC patients, 76% had private insurance and 21% had public insurance, and for DCGH patients, one-half had public insurance and 29% had no insurance. Significantly fewer GUMC patients (7% versus 36%) reported moderate to severe dyspnea. Chest radiographs showed a larger percentage of patients with stage 1 disease at GUMC and more patients with stage 4 disease at DCGH. Spirometry showed more impairment of forced expired volume in one second (FEV1) in GUMC patients, but diffusing capacity of the lung for carbon monoxide (DLCO) values were significantly lower among DCGH patients. Less than 8% of GUMC patients showed disease progression compared with almost one-third of DCGH patients. These results demonstrate that substantially less severe pulmonary sarcoidosis was seen in African-American patients treated at a private, nonprofit university hospital compared with a municipal hospital. Factors that determine the use of municipal hospitals, such as limited financial access to care and sources of patients, may have played a major role in the differences seen.