Mesothelial cells in tuberculous pleural effusions of HIV-infected patients.

The scarcity of mesothelial cells is a well-known characteristic of tuberculous pleural effusions. We report three HIV-infected patients with tuberculous pleural effusions, in which mesothelial cells were found in significant numbers in the pleural fluid. Clinicians should be aware that the altered immune responses that occur in HIV-infected patients may affect the cytologic profile of tuberculous pleural effusions, and they should be cautious not to exclude this diagnosis based solely on the presence of mesothelial cells in the fluid.

Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus.

Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p < 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p < 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs.

Spontaneous lymphokine activated killer (LAK) activity in bronchoalveolar lavage cells from patients with bronchogenic carcinoma.

Bronchoalveolar lavage cells (BAC) are considered to be representative of cells that are in the interstitium and in patients with lung cancer, may represent, in part, cells that infiltrate cancerous tissue. We used bronchoalveolar lavage (BAL) specimens to test the hypothesis that cells within this region might be regulated locally by factors and show activities that are dependent on these growth and activation mediators. We showed previously that Natural Killer (NK) activity and IL2 titers were proportional. As compared to normal subjects, patients with all stages of bronchogenic carcinoma consistently had very high levels of IL2 in their bronchoalveolar lavage (BAL) fluid and this titer correlated with an increase in NK activity in the BAC both in absolute level and in relative level to the blood. Now, we report results that show that spontaneous lymphokine activated killer (LAK) activity also can be measured in most patients, but not all patients, that express IL2 titers. These findings support the hypotheses that different types of nonspecific cytotoxic cells are present and active in cancerous lung specimens secondary to the secretion of lymphokines from activated T lymphocytes in that region and that LAK activity is a physiological phenomenon that may be expressed in regional rather than systemic areas of the body.

Cresyl violet: a rapid, simple, easily interpretable stain for detecting Pneumocystis carinii in sputum.

Over a three-month period at the pathology laboratory of Jackson Memorial Hospital, 110 sputum samples from 62 hospitalized patients with suspected AIDS were examined for Pneumocystis carinii. Sputum specimens were either expectorated spontaneously (most patients) or expectorated after the inhalation of small amounts of nebulized normal saline. Each sputum sample was cytocentrifuged onto two slides. One slide was stained with Gomori methenamine-silver (GMS) and the other with cresyl violet (CV). Among the 62 study patients, 18 were proven to have no histologic evidence of P carinii pneumonia. Of the remaining 44 patients, P carinii organisms were found by GMS stain in 14 (32%) and by CV stain in 18 (41%). Among those with a positive CV stain, the diagnosis was made on the first sputum specimen in 14 patients and on the second specimen in the remaining four patients. CV stain is at least as sensitive as GMS in detecting P carinii cysts in the sputum of AIDS patients with P carinii pneumonia, and its diagnostic sensitivity may exceed 40% under field conditions. Further, CV stain is much simpler to prepare than GMS and much simpler to interpret than Giemsa. It could be easily adapted for general use to expedite the diagnosis and treatment of P carinii pneumonia.

Granulomatous vasculitides of the lung: a clinicopathologic approach to diagnosis and treatment.

The granulomatous vasculitides of the lung are uncommon. Overlap of their clinical and histopathologic features may create a confusing picture for the clinician and pathologist. This confusion is of concern because therapy differs depending on the exact diagnosis, with concomitant variations in associated drug toxicity. An integrated clinical and pathologic approach must be used to arrive at a prompt and accurate diagnosis. The true granulomatous vasculitides, a group that includes Wegener's granulomatosis, allergic granulomatosis and angiitis (Churg-Strauss syndrome), and necrotizing sarcoid granulomatosis, have various degrees of systemic involvement. Therapy is mainly immunosuppressive, and prognosis is generally good. The lymphoproliferative granulomatous vasculitides, which include benign lymphocytic angiitis and granulomatosis, lymphomatoid granulomatosis, and malignant lymphoma with angioinvasion, are progressively abnormal lymphoproliferative processes. Therapy may require combination chemotherapy, and prognosis is often poor.

Lung natural killer and interleukin-2 activity in lung cancer. A pulmonary compartment of augmented natural killer activity occurs in patients with bronchogenic carcinoma.

Studies were performed to determine if natural killer (NK) cell and interleukin-2 (IL-2) activities are increased in lungs that harbor malignancy. The NK activity (ability to lyse 51Cr-K562 cells) in bronchoalveolar lavage mononuclear cells (BAC) and washed whole blood cells (Blood) was measured in 8 patients with bronchogenic carcinoma and 8 healthy control subjects. The mean NK activity by BAC from the patients with bronchogenic carcinoma was 2.81 lytic units, and from the control subjects it was 0.19 lytic units (p less than 0.001). When the data were expressed as a ratio of NK activity for BAC/Blood, the mean ratio was 0.98 in patients with cancer compared with 0.12 in control subjects (p less than 0.003). IL-2 activity was bioassayed in recovered bronchoalveolar lavage fluid (BAL) using 3H-thymidine uptake by IL-2-dependent T-cells. The concentration of IL-2 was expressed as units per microgram albumin and also as units multiplied by a dilution factor. The median concentration of IL-2 in BAL from the patients with bronchogenic carcinoma was 10.5 units x 10(-3)/micrograms albumin (range, 3.7 to 229), and from the healthy control subjects it was 0.37 units x 10(-3)/micrograms albumin (range 0.26 to 0.70) (p less than 0.001). When IL-2 activity was expressed as total number of IL-2 units in recovered lavage fluid times a dilution factor (volume of saline used for lavage/volume of lavage fluid recovered), the median number of IL-2 units was 4.7 for the patients with bronchogenic carcinoma and 0.085 for the control subjects (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Human T-cell lymphotropic virus-III (HTLV-III) seropositivity and related disease among 71 consecutive patients in whom tuberculosis was diagnosed. A prospective study.

The incidence of tuberculosis has recently risen in Southeast Florida. In order to determine the number and proportion of tuberculosis cases and the characteristics of tuberculosis that might be related to human T-cell lymphotrophic virus-III (HTLV-III) infection, all patients seen by the Dade County Florida Public Health Department-Tuberculosis Clinic during a 6-month period were medically evaluated and screened for HTLV-III antibody by an enzyme-linked immunosorbent assay. Of 71 consecutive patients confirmed to have tuberculosis (70 by culture) during the study period, 22 (31%) were seropositive and 49 (69%) were seronegative for HTLV-III antibody. The seropositive group had a significantly higher proportion of patients who were black, Haitian, and within the age group of 25 to 44 yr. The seropositive group also had a significantly higher rate of mild-to-moderate serum aspartate transaminase elevations (less than or equal to 5 times normal), tuberculin skin test false negativity, extrapulmonary tuberculosis (especially lymphatic), and pulmonary tuberculosis with an atypical radiographic picture. The seropositive group had a significantly lower proportion of patients with sputum cultures positive for M. tuberculosis. There was no significant difference between the groups with respect to the proportion of patients with positive sputum smears when sputum cultures were positive, serious antituberculosis drug reactions (requiring discontinuation of therapy), or percent of home contacts who were tuberculin skin tested and found to be positive. At the time of the diagnosis of tuberculosis, only 6 (27%) of the seropositive patients with tuberculosis had clinical evidence of AIDS or AIDS-related complex (unexplained thrush).(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of HTLV-III/LAV-specific IgG and antigen in bronchoalveolar lavage fluid from two patients with lymphocytic interstitial pneumonitis associated with AIDS-related complex.

Lymphocytic interstitial pneumonitis, a disorder of unknown cause, has been described in association with infection by the retrovirus human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). This report describes the isolation of HTLV-III/LAV in bronchoalveolar lavage fluid and the quantitation of antibodies directed against HTLV-III/LAV in bronchoalveolar lavage fluid and peripheral blood of two patients with lymphocytic interstitial pneumonitis associated with acquired immune deficiency syndrome-related complex. The ratio of the concentrations of HTLV-III/LAV-specific IgG to total IgG in the bronchoalveolar lavage fluid of both patients was higher than that of the peripheral blood. These findings are consistent with the hypothesis that lymphocytic interstitial pneumonitis is sometimes associated with HTLV-III/LAV infection of pulmonary tissue that evokes a specific humoral immune response locally in the lung.

Value of repeat fiberoptic bronchoscopies and significance of nondiagnostic bronchoscopic results in patients with the acquired immunodeficiency syndrome.

Out of 286 patients with the acquired immunodeficiency syndrome (AIDS) who had fiberoptic bronchoscopies performed for the diagnosis of pulmonary disease, 21 (7.3%) patients (Group I) had repeat procedures after 1 to 30 days (mean, 14.8 days) because of persistent pulmonary infiltrates despite therapy, and 46 (15.9%) patients (Group II) had repeat procedures after 2 to 32 months (mean, 7.5 months) because of recurrent pulmonary infiltrates after initial clinical and radiographic improvement. Pneumocystis carinii pneumonia was the most common diagnosis in both groups on initial evaluation, being found in 55% of the patients. Repeat bronchoscopy yielded a new treatable diagnosis in 1 (5%) of 21 patients in Group I and in 27 (59%) of 46 patients in group II. Sixty-two percent of patients in Group I died within 1 month. It appears that in patients with AIDS who have persistent or worsening pulmonary infiltrates despite therapy, repeat bronchoscopy after a short interval (i.e., less than 1 month) is unlikely to have therapeutic implications. In contrast, those patients whose pulmonary involvement resolves initially may benefit from an aggressive diagnostic approach if new pulmonary infiltrates appear. In both groups, nondiagnostic bronchoscopies were common (29% overall). The most commonly missed bronchoscopic diagnoses (proved by open lung biopsy) were cytomegalovirus pneumonia and Kaposi's sarcoma, and neither had much therapeutic implication. Further, 12 patients in Group II with nondiagnostic bronchoscopies improved both radiographically and clinically even though no treatment was given.

Cancer among Haitians in Florida.

Data on cancer rates from West Indian populations are scarce, and to the authors' knowledge there are no published data on cancer rates and distributions among Haitians. Proportional distributions of cancers among three groups of patients living in Florida were compared: Haitian born blacks, United States born blacks, and non-Haitian Caribbean born blacks. The incidence rate of cancer of the cervix among the Haitian and United States born black groups was also compared. Increased rates of certain malignancies associated with viral infection or immunodeficiency were found in the Haitian group. These tumors were hepatocellular carcinoma, nasopharyngeal carcinoma, reticulum cell sarcoma, Kaposi's sarcoma, and carcinoma of the uterine cervix. The age-adjusted incidence rate of carcinoma of the cervix was especially high among Haitian women even with a liberal estimate of the female Haitian population from whom the cases were drawn. Except for cancer of the cervix, the numbers of cancers of interest were small, and age-adjusted incidence rates were not calculated. Continued epidemiological study of larger numbers of patients is needed to evaluate these findings further.

Pulmonary nocardiosis in the acquired immunodeficiency syndrome. Diagnosis with bronchoalveolar lavage and treatment with non-sulphur containing drugs.

A patient with the acquired immunodeficiency syndrome (AIDS) presented with Pneumocystis carinii pneumonia and pulmonary nocardiosis. The nocardial lesions appeared small and localized on chest radiograph. On two separate occasions, nocardial organisms were absent in transbronchial lung biopsy specimens, but were identified in bronchoalveolar lavage fluid probably because the latter specimen sampled a larger area of lung. The patient was initially treated with trimethoprim-sulfamethoxazole (TMP/SMX) for both infections. When TMP/SMX was discontinued because of an adverse reaction, the nocardiosis promptly exacerbated but was then easily controlled with minocycline and amikacin followed by minocycline and cycloserine. Among patients with AIDS who have sulfamethoxazole hypersensitivity during treatment for nocardiosis, alternative drugs may be efficacious and may be particularly important in this setting because they have a lower incidence of toxicity.

ICU survival of patients with the acquired immunodeficiency syndrome.

The ICU records of 31 patients with the acquired immunodeficiency syndrome were reviewed. Of 23 (74%) patients admitted for respiratory failure requiring intubation and mechanical ventilation, 20 (87%) patients had Pneumocystis carinii and/or cytomegalovirus pneumonia. Of the eight patients admitted without respiratory failure, five (63%) were monitored after brain biopsy. Respiratory failure patients remained in the ICU for 10 +/- 1 days, compared to 5 +/- 1 days for those without respiratory failure (p less than .05). Overall mortality was 24 patients (77%); 21 (91%) of 23 respiratory failure patients died, compared to three (38%) of the eight without respiratory failure (p less than .01). All seven ICU survivors lived to hospital discharge.

Sputum examination for the diagnosis of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

The diagnostic utility of sputum examination in patients with Pneumocystis carinii pneumonia secondary to the acquired immunodeficiency syndrome (AIDS) has so far not been determined. Sputum was induced in 43 patients with AIDS or suspected AIDS just prior to fiberoptic bronchoscopy, scheduled because of an unexplained pulmonary infiltrate on a chest radiograph. Pneumocystis carinii pneumonia was diagnosed by sputum examination and/or by a bronchoscopic procedure in 20 patients. Of these, sputum samples were positive for Pneumocystis organisms in 11 (55%) of 20 patients tested, bronchial washings were positive in 11 (79%) of 14 patients tested, brush biopsies were positive in 9 (53%) of 17 patients tested, and transbronchial lung biopsies were positive in 18 (90%) of 20 patients tested. The presence of P. carinii cysts in sputum did not correlate with the presence of alveolar macrophages in sputum nor with the volume of sputum. Sputum examination for P. carinii organisms, employed as a first diagnostic step in patients with AIDS with pulmonary infiltrates, may frequently obviate the need for bronchoscopy.

Evaluation of patients with the acquired immunodeficiency syndrome (AIDS) by fiberoptic bronchoscopy.

Hospital records were reviewed on 78 consecutive patients (33 homosexuals, 37 Haitians and 8 IV drug abusers) who had AIDS and who underwent fiberoptic bronchoscopy over a two year period. Pneumocystis carinii pneumonia (PCP) was the most common bronchoscopic finding (53.8% of patients) followed by tuberculosis (14.1%), cytomegalovirus infection (12.8%) and atypical mycobacteriosis (3.8%). In 15.4% of patients multiple organisms were found. Twenty-seven percent of patients had non-diagnostic bronchoscopies. In 8 patients with non-diagnostic bronchoscopies, open-lung biopsy or autopsy revealed PCP (2 patients), Kaposi's sarcoma (3 patients) and non-specific lymphocytic-plasmacytic infiltrates (3 patients). Histologic studies of transbronchial biopsy specimens were more sensitive for the diagnosis of PCP than touch imprints. PCP was diagnosed in 15 patients who had received trimethoprim-sulfamethoxazole for up to 4 days. Mean duration of respiratory symptoms prior to bronchoscopy was 4.2 weeks in patients with PCP and was not significantly different in patients with other bronchoscopic diagnoses. Historical, laboratory and chest radiographic parameters were not helpful in establishing a diagnosis or assessing prognosis in these AIDS patients with pulmonary infiltrates. Fiberoptic bronchoscopy with transbronchial biopsy is safe (only one of the patients had a self limited hemorrhagic episode) and sensitive for the diagnosis of pulmonary infiltrates in patients with AIDS.

Bronchocentric granulomatosis with glomerulonephritis.

Bronchocentric granulomatosis is a chronic pulmonary disease treated with short-term therapy with corticosteroids, and the disease has an excellent prognosis. We describe a patient, and review an additional case from the literature, in whom bronchocentric granulomatosis was accompanied by glomerulonephritis. A misdiagnosis of Wegener's granulomatosis was made, and therapy with cyclophosphamide was either considered or given in each of these cases. We emphasize the need for careful histopathologic evaluation of open lung biopsies in patients suspected of having Wegener's granulomatosis in order to rule out the possibility of bronchocentric granulomatosis with concurrent renal disease, and thus avoid the unnecessary use of cytotoxic agents.

The radiographic appearance of tuberculosis in patients with the acquired immune deficiency syndrome (AIDS) and pre-AIDS.

We reviewed the medical records and chest radiographs of 23 adult patients with culture-proved tuberculosis and verified acquired immune deficiency syndrome. Seventeen patients, including 8 with disseminated tuberculosis, had positive sputum or bronchial washing cultures for Mycobacterium tuberculosis. Their initial pretreatment radiographs revealed hilar and/or mediastinal adenopathy in 10 patients (59%), localized pulmonary infiltrates limited to the middle or lower lung fields in 5 patients (29%), localized pulmonary infiltrates involving an upper lobe in 3 patients (18%), diffuse miliary or interstitial infiltrates in 3 patients (18%), no pulmonary infiltrates in 6 patients (35%), and no abnormalities in 2 patients (12%). Pulmonary cavitation was not seen. Only 1 patient (6%) had a chest radiograph typical of adult onset reactivation tuberculosis (i.e., localized pulmonary infiltrate involving the upper lung fields without hilar or mediastinal adenopathy). Six patients (35%) had pulmonary infiltrates that may have been caused by concomitant nontuberculous infection. Six patients had positive cultures for M. tuberculosis from extrapulmonary sites only. Three (50%) of these patients had hilar and/or mediastinal adenopathy. None of them had pulmonary infiltrates on their initial chest radiograph.