5' dinucleotide repeat polymorphism of NRAMP1 and susceptibility to tuberculosis among Caucasian patients in Houston, Texas.

SETTING: Houston Tuberculosis Initiative (HTI) and Baylor College of Medicine, Houston, Texas. OBJECTIVE: To further explore the association between the polymorphisms of NRAMP1 and human susceptibility/resistance to tuberculosis (TB), specifically to determine whether the reported association shown for blacks and Asians holds true for Caucasian populations. DESIGN: In a case-control study, 135 adult Caucasian TB patients and 108 adult Caucasian HIV-seronegative non-TB controls were analyzed for the association between the polymorphisms in NRAMP1 gene and clinical TB. RESULTS: Heterozygote at 5'(GT)n, a dinucleotide repeat polymorphism in the promoter of NRAMP1, was observed at significantly higher frequencies among HIV-negative patients with pulmonary TB (41.6%; OR 2.02; 95%CI 1.11-3.64), extra-pulmonary TB (66.7%; OR 4.80; 95%CI 1.34-17.15), and HIV-seropositive TB patients (50%; OR 3.77; 95%CI 1.33-10.66) in comparison with the controls (27.8%). Homozygotes (GT)(10,10) were over-represented among HIV-positive TB patients (18.2%; OR 6.86; 95%CI 1.55-30.21) compared to the controls (5.5%). CONCLUSION: These findings suggest that the 5'(GT)n polymorphism of NRAMP1 modifies TB susceptibility in this Caucasian population, and could possibly be related to the site of infection among HIV-negative individuals and HIV-coinfected TB.

Treatment of isoniazid-resistant tuberculosis in southeastern Texas.

BACKGROUND: Isoniazid-resistant tuberculosis (INHr-TB) can be treated successfully with several treatment regimens. However, the optimal regimen and duration are unclear. STUDY OBJECTIVE: To analyze the efficacy of treatment regimens used for INHr-TB in the southeastern Texas region. DESIGN: Retrospective cohort study. SETTING: Health-care facilities reporting tuberculosis (TB) patients in the Houston and Tyler areas. SUBJECTS: All patients reported to have INHr-TB from 1991 to 1998. Exclusion criteria included poor compliance, additional first-line drug-resistance (except aminoglycosides), and death before completion of 1 month of treatment. MEASUREMENTS AND RESULTS: Main treatment outcomes were treatment failure, relapse, and TB-related death. Fifty-three of 83 patients were included in the study; aminoglycoside resistance coexisted in 37.5% of isolates. Seven types of treatment regimens were identified. Eighteen patients (34%) received rifampin, pyrazinamide, and ethambutol thrice weekly for 9 months. Four patients (7.5%) had a total effective treatment duration of < 9 months. Thirty patients (56.6%) and 16 patients (30.2%) received thrice-daily and daily treatment regimens, respectively. Forty-nine patients achieved sputum conversion. Treatment failure and death occurred in one patient (1.9%). Three patients (5.7%) experienced relapses. There was a significant difference in total effective treatment time between patients with and without relapses (8.3 +/- 1.1 months vs 11.1 +/- 2.1 months; p < 0.02). Twice-weekly treatment regimens were associated with relapse (p = 0.05). CONCLUSIONS: Several treatment regimens were prescribed for INHr-TB in southeastern Texas. INHr-TB treatment durations were > 7 months, and treatment regimen efficacy was adequate. Twice-weekly treatment was associated with relapse, whereas thrice-weekly and daily treatments performed similarly. A prospective study with different treatment durations is needed to determine the optimal treatment regimen for patients with INHr-TB.

A rapid and inexpensive method for processing induced sputum for detection of Pneumocystis carinii.

The authors describe a method to process induced sputum specimens for detection of Pneumocystis carinii which is simple, rapid and inexpensive. Induced sputum and bronchoalveolar lavage (BAL) were obtained within a 24-hour period from 41 patients who were HIV-positive and had pulmonary symptoms suspicious for P carinii pneumonia. Induced sputum or BAL fluid was placed into Saccomanno's fixative, blended, and centrifuged. The sediment was stained for P carinii cysts by a modified method with Fungi-Fluor Solution A (Polysciences, Warington, PA) and the Genetic Systems Pneumocystis carinii Immunofluorescence Antibody (Genetic Systems, Seattle, WA). The Genetic Systems stain on the BAL specimen was positive in 35 patients and was the standard for comparison. With a single induced sputum, the Genetic Systems stain detected 31 (89%) positive patients, whereas the Fungi-Fluor stain detected 21 (60%). The sensitivity for detecting P carinii cysts in induced sputum was significantly greater (P < 0.05) for the Genetic Systems stain.

Lung cancer in association with human immunodeficiency virus infection.

The association of lung cancer and infection by the human immunodeficiency virus (HIV) is uncommon. This report and critical review of the medical literature defines a clinical profile of 22 patients affected with this uncommon association. This clinical profile includes young age (median, 38 years), intravenous drug abuse (14 of 22 patients), preponderance of adenocarcinoma over other cell subtypes (11 of 22 patients), and advanced clinical stage at presentation (10 of 15 patients with staging data had Stage III or IV disease). This study also examines a possible increased risk for lung cancer in patients infected by HIV. Continued surveillance and reporting of lung tumors (other than lymphomas and Kaposi sarcomas) in patients infected by HIV should help to define the frequency of the association and the validity of the clinical profile.

Lung bullae with air-fluid levels.

Fourteen patients in whom air-fluid levels developed in pre-existing emphysematous bullae were prospectively identified and followed. Although two patients were asymptomatic, 12 patients presented with one or more symptoms of fever, dyspnea, cough, pleuritic chest pain, and/or purulent sputum. Three patients had focal pulmonary abnormalities on physical examination; three patients had elevated leukocyte counts. Exudative fluid with an elevated leukocyte count was aspirated from the bullae of two patients; one aspirate grew Bacteroides melaninogenicus on culture. Bronchoscopy in seven patients influenced neither the diagnosis nor therapy. Thirteen patients received either oral penicillin (11 patients) or oral tetracycline (two patients). Complete resolution of symptoms and air-fluid levels on chest roentgenography occurred in all patients over two to 32 weeks (mean, 12).

Pasteurella multocida liver abscess.

A previously healthy 61-year-old woman was seen with an abnormal chest roentgenogram and a 3-week history of fever, chills, malaise, and right upper quadrant pain. Blood cultures revealed Pasteurella multocida sensitive to penicillin. Liver spleen radioisotope scan and CT scan revealed space occupying lesions in the right lobe of the liver. The patient was a gardener with no pets or animal exposure. This case illustrates P. multocida septicemia and a liver abscess in a patient without animal exposure. In addition, the possibility of soil as another reservoir of infection is raised.

Asbestos bodies in a general hospital/clinic population.

The presence of asbestos bodies in the sputum of individuals with known occupational asbestos exposure has been well documented. However, their prevalence and clinical implications in sputum and bronchial washings from patients not clinically known to have asbestos exposure remains controversial. From 1974 to 1979, 31,353 sputum and bronchial washing specimens were processed in the course of evaluating various pulmonary complaints of approximately 11,000 patients from the outpatient clinics and hospitals of the Harris County Hospital District in Houston, Texas. Asbestos bodies were incidentally found in five patients, and, in retrospect, each of them was discovered to have had significant occupational exposure to asbestos dust. Asbestos lung disease was also subsequently proven in four of the five patients and was felt, retrospectively, to have contributed to their presenting complaints and clinical course. It is concluded that asbestos bodies in sputum and bronchial washing specimens are highly specific markers for past asbestos exposure and reflect the presence of a significant asbestos load within the lungs. Sputum cytology is both painless and inexpensive and is recommended as a supplemental procedure to document clinically significant asbestos exposure.

Antibiotic therapy of acute exacerbations of chronic bronchitis. A controlled study using tetracycline.

We conducted a double-blind, randomized, placebo-controlled trial in 40 patients to evaluate the need for antibiotics in acute exacerbations of chronic bronchitis. All patients were sufficiently ill to require hospitalization although none needed ventilatory support; the presence of pneumonia was excluded. Treatment consisted of bronchodilators, corticosteroids, and either tetracycline, 500 mg, or placebo by mouth every 6 hours for 1 week. Arterial blood gases, spirometric tests, bacteriologic evaluation of sputum, and patient and physician evaluation of the severity of illness were assessed at the beginning and end of the study. All patients improved both symptomatically and by objective measures of lung function. At the end of the study period there were no differences between those patients receiving tetracycline and those receiving placebo. We conclude that antibiotic therapy is not needed in moderately ill patients with exacerbations of chronic bronchitis.

Comparative trial of cefonicid and cefamandole in the therapy of community-acquired pneumonia.

Cefonicid (Smith Kline & French Laboratories; D-75073) is a new parenteral cephalosporin with a markedly long half-life, high serum levels, and good in vitro activity against Haemophilus influenzae. Patients with community-acquired pneumonia were randomized 2:1 to receive cefonicid, 1 g daily (21 cases) or cefamandole, 1 g every 6 h (12 cases). The two groups were similar, except that the cefonicid patients were older (mean 42 versus 31 years). Peak serum levels of cefonicid averaged 133 microgram/ml after intravenous and 83 microgram/ml after intramuscular administration compared with 55 microgram/ml with intravenous cefamandole. All 9 patients on intramuscular cefonicid and 8 or 12 patients on intravenous cefonicid had trough serum levels of greater than 2.0 microgram/ml at 24 h. Sputum levels of cefonicid were usually between 2.0 and 4.0 microgram/ml and did not correlate with serum levels. Cefonicid was well tolerated, and all cefonicid patients responded clinically. Sputum cultures for H. influenzae or Streptococcus pneumoniae became negative in 6 of 7 cefamandole patients and 13 or 15 cefonicid patients. In in vitro studies, cefonicid inhibited 90% of beta-lactamase-negative h. influenzae at 0.5 microgram/ml and beta-lactamase-positive strains at 2.0 microgram/ml. Cefonicid inhibited 50% of S. pneumoniae at 1.6 microgram/ml, but required 6.4 microgram/ml to inhibit 90%. Cefonicid once a day appears to be as safe and as effective as cefamandole four times a day for therapy of community-acquired pneumonia.

The use of quantitative sterile brush culture and gram stain analysis in the diagnosis of lower respiratory tract infection.

We prospectively evaluated 55 patients (58 studies) who presented for diagnostic fiberoptic bronchoscopy for the presence of lower respiratory tract infection. A sheathed, nonplugged, sterile brush passed transbronchoscopically under fluoroscopic control was used to retrieve bronchial secretions. These were evaluated using Gram stains, Wright-Giemsa stains, and quantitative bacterial cultures. In 18 studies of patients with known or suspected infection, polymorphonuclear leukocytes and bacterial were easily identifiable on Gram stain, and potential lower respiratory pathogens were recovered in concentrations greater than or equal to 10(6) colony-forming units (cfu)/ml. In 15 control studies of patients with noninfectious lung disease and in 17 studies of patients with suspected lung infection (nine with prior antibiotic therapy), organisms were not seen on Gram stain and in 28/32 studies bacteria were present in concentrations of less than or equal to 10(4) cfu/ml. The remaining eight studies were in patients proved to have active granulomatous disease. These studies establish the ability of a fiberoptic bronchoscopic technique to diagnose bacterial infection in a group of patients presenting difficult diagnostic problems.

Unusual radiographic findings in adult pulmonary tuberculosis.

To determine the frequency of unusual chest radiographic findings in adults (older than 15 years) with pulmonary tuberculosis, charts and radiographs of 270 consecutive cases seen in a 12 month period were reviewed. Radiographic findings not typical of primary or postprimary disease (reinfection) were arbitrarily classified as unusual. The incidence of such findings (8%) was considerably lower than in several recent reports (25%, 29%). Likewise, the incidence of lower lobe tuberculosis in diabetics in this population (8.3%) was lower than in a report by Weaver (20%), and the finding of air-fluid levels in patients with cavitary disease (9%) was lower than a report by Cohen (22%). Possible explanations for these discrepancies were reviewed, including: (1) demographic characteristics, (2) the patient selection process, (3) the arbitrary nature of any system of classification of "unusual" findings, and (4) the change in the epidemiology of the disease as a result of chemotherapy and organized eradication programs. Of these, the patient selection process is probably the most significant factor in the discrepancy between the incidence of unusual findings in this series compared with those reported by others.

Carcinomatous lung abscess. Diagnosis by bronchoscopy and cytopathology.

We compared the roentgenographic, bronchoscopic, and cytopathologic findings from 26 patients with carcinomatous lung abscesses (23 of which were within the tumor) with findings from 31 patients with simple lung abscesses. Despite well-described roentgenographic characteristics of the carcinomatous abscess, differentiation from a simple abscess was frequently not possible. Direct visual findings at the time of bronchoscopy were not helpful in the absence of an endobronchial lesion. Using sputums and cytological specimens from a single fiberoptic bronchoscopy, a diagnosis was made by cytopathology on initial hospitalization in 22 (88%) of 25 patients with carcinoma. No false-positive cytological studies were reported in the nonmalignant group despite the frequent presence of inflammation and infection.

Left ventricular function during respiratory failure.

Indirect measures of left ventricular function were studied in seven patients with respiratory failure secondary to chronic obstructive pulmonary disease to determine if there were a relationship between left ventricular function and treatment of the pulmonary disease. All patients were studied during acute episodes while in respiratory failure having arterial Pco2 (Paco2) values greater than 49 torr with no clinical evidence of left ventricular failure. Indirect methods to evaluate left ventricular function included the use of the Swan-Ganz catheter for pulmonary capillary wedge pressure measurement, systolic time intervals, and cardiac output. There was improvement in left ventricular function with treatment of the respiratory failure manifested by decreases in the wedge pressure and pre-ejection period/left ventricular ejection time ratio, and an increase in the dp/dt/pulmonary capillary wedge pressure with treatment of the chronic obstructive pulmonary disease. The improvement in left ventricular function suggests that there is a depression of left ventricular function in respiratory failure. The depressed function improved with therapy of the lung disease without additional medication directed at cardiac function.

Acute tuberculous pneumonia.

A case of acute tuberculous pneumonia diagnosed by transbronchial biopsy is presented. We postulate that the unusually rapid progression was due to an exudative hypersensitivity reaction to aspirated tuberculoprotein.