Assessment of Lymph Node Tuberculosis in Northern Germany* A Clinical Review Henning Geldmacher, MD; Christian Taube, MD; Clemens Kroeger, MD; Helgo Magnussen, MD; and Detlef K. Kirsten, MD, FCCP
Aim of study: To evaluate patient profiles, diagnostic approaches, and treatment strategies in patients with lymph node tuberculosis. Methods: Demographic data, diagnostic findings, and therapies were retrospectively analyzed in 60 patients with lymph node tuberculosis who were hospitalized between 1992 and 1999. Results: Thirty percent (n ⴝ 18) of patients were natives, and 70% were immigrants (n ⴝ 42). The cervical lymph nodes were most frequently involved (63.3%), followed by the mediastinal lymph nodes (26.7%) and the axillary lymph nodes (8.3%). All patients (except one patient who was HIV-positive) showed a positive response to tuberculin skin testing. Lymph node excision and fine-needle aspiration (FNA) were similarly effective in obtaining sufficient material for histologic and microbiological analysis. Mycobacterium tuberculosis was identified in 43.3% of patients by microbiological testing, and culture methods showed the highest sensitivity. Despite standard treatment, the initial enlargement of the lymph nodes occurred in 20% of patients and local complications occurred in 10%. Conclusion: Lymph node tuberculosis is still an important issue in developed countries and has to be considered in differential diagnosis. The best approach appears to be a combination of skin testing and FNA. Negative results in the identification of M tuberculosis do not exclude the diagnosis of lymph node tuberculosis. (CHEST 2002; 121:1177–1182) Key words: diagnostic findings; epidemiology; lymph node tuberculosis; treatment Abbreviations: FNA ⫽ fine-needle aspiration; PCR ⫽ polymerase chain reaction; TU ⫽ tuberculin units
is still one of the most frequently T uberculosis occurring infectious diseases worldwide. According to the World Health Organization, approximately one third of the world population is infected with tubercle bacilli, while 8 million new cases of active disease develop each year and 3 million patients die.1 As a consequence of the availability of antituberculosis medication, as well as of higher standards of living and nutrition, Western European countries show a rather low frequency of tuberculosis infection. For example, the Central Bureau of Statistics in Germany reported2 the incidence rate of tuberculosis to be 13.6 per 100,000 population in 1997. Since the disintegration of the former Soviet Union, there has been a collapse of the medical *From the Krankenhaus Grosshansdorf, Zentrum fu¨r Pneumologie und Thoraxchirurgie, Grosshansdorf, Germany. Manuscript received January 19, 2000; revision accepted October 15, 2001. Correspondence to: Detlef K. Kirsten, MD, FCCP, Krankenhaus Grohansdorf, Zentrum fu¨r Pneumologie und Thoraxchirurgie, Wo¨hrendamm 80, D-22927 Grosshansdorf, Germany; e-mail
[email protected] www.chestjournal.org
system, which has led to a rapid increase in the occurrence of tuberculosis. The extreme political and economic conditions resulted in an increased rate of immigration into Western Europe. These immigrants constitute an increasing and important proportion of all tuberculosis cases in Europe.3 It is well-known that tuberculosis can be associated with other diseases that depress the immune system, such as leukemia or HIV, and several studies have demonstrated an increased rate of incidence among HIV-infected patients.4 Therefore, tuberculosis remains a major problem in coinfected patients, irrespective of new and effective antiretroviral therapies, and continues to be a significant health issue challenging the medical community. Approximately 85% of all tuberculosis infections in Germany are found in the lungs.2 Of the remaining extrapulmonary infections, about 50% affect the lymph nodes. As a result of the low numbers of tuberculous lymphadenitis without pulmonary manifestation, the possibility of tuberculous infections often is ignored in the differential diagnosis of CHEST / 121 / 4 / APRIL, 2002
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21976/ on 01/27/2017
1177
lymphadenopathy, resulting in a significant delay of the appropriate treatment. Unfortunately, not much clinical data are available on the diagnosis and therapy of lymph node tuberculosis in Western countries.5 However, owing to the immigration that has occurred over the last decade, there is a renewed interest in lymph node tuberculosis. The aim of the present study was to supply data on patient profiles, diagnostic approaches, and treatment strategies that were encountered in a population of patients admitted to a large pulmonary referral hospital in Germany between 1992 and 1999.
in samples from lymph node excisions. Since 1997, polymerase chain reaction (PCR) has been available as an additional diagnostic procedure. Histologic analysis was performed on samples fixed in formalin. The initial therapy was started with a combination of isoniazid (5 mg/kg), rifampicin (10 mg/kg), and pyrazinamide (15 to 20 mg/kg), in accordance with the recommendations of the American Thoracic Society6 and the German Thoracic Society.7 When significant side effects occurred, the drug responsible for these effects was replaced by ethambutol (25 mg/kg). In case of drug resistance, the treatment was appropriately adjusted. Over the whole period of treatment, the enlarged lymph nodes were regularly controlled through ultrasound, and their sizes were measured. The duration of treatment recommended at the patient’s discharge from the hospital ranged between 6 and 12 months.
Materials and Methods
Results
We retrospectively analyzed all patients who were ⱖ 12 years of age with a diagnosis of lymph node tuberculosis who were hospitalized in our Medical Center between January 1, 1992, and December 31, 1999. Our facility specializes in treating patients with pulmonary diseases and provides care for the population of northern Germany (including Hamburg). The population of northern Germany has demographic and socioeconomic characteristics that are similar to those in other regions of Germany, with the percentage of immigrant patients ranging between 10% and 13% in the last decade. All patients gave a detailed medical history and received a physical examination. Mendel-Mantoux tests were performed in all patients starting with 0.1 tuberculin units (TU) and were manufactured by a German serum and vaccine institute (purified protein derivative; Chiron Behring; Marburg, Germany). Skin responses were evaluated 72 h after application, a transverse diameter of an induration of ⬎ 5 mm being judged as a positive reaction. In case the test result was negative, it was repeated using a higher tuberculin concentration (ie, up to 100 TU). Positive results to 0.1 and 1.0 TU were interpreted as strong responses, and those to 5, 10, and 100 TU as moderate responses. To detect a pulmonary manifestation, all subjects underwent chest radiographs and sputum analysis. Patients showing cavernous or disseminated patterns on the radiographs and patients with test (ie, Ziehl-Neelsen staining) results that were positive for the presence of acid-fast bacilli in sputum were excluded. To examine the tissue surrounding enlarged lymph nodes, an ultrasound of the affected area was performed. If this showed evidence for localized irregularities (ie, abscess, fistula, or inhomogeneous lymph node tissue), an additional CT scan was ordered to be performed. When a mediastinal lymphadenopathy was suspected in the chest radiograph, a thoracic CT scan also was performed. Lymph nodes with a diameter ⬎ 1 cm were documented as suspicious. In all patients, we conducted histologic and microbiological analyses for the presence of mycobacteria in lymph node tissue. Ultrasound-guided fine-needle aspiration (FNA) or lymph node excision was used to investigate superficial lymph nodes (ie, cervical, axillary, or inguinal lymph nodes). Similarly, tuberculosis was diagnosed in the mediastinal nodes by testing of specimens from a bronchoscopic fine-needle biopsy. Mediastinoscopy was not performed in any of the patients. One aliquot of FNA samples was fixed in 95% ethyl alcohol and was stained by Giemsa for cytologic analysis. A second aliquot was used for microscopic detection using Ziehl-Neelsen staining as well as agar and radioactive culture (BACTEC; Becton Dickinson; Franklin Lakes, NJ), and the same procedure was followed
Epidemiology Sixty patients (41 women and 19 men) were included in the study, representing 5.1% of all inpatients with tuberculosis who were treated between January 1, 1992, and December 31, 1999 (n ⫽ 1,161). The mean (⫾ SD) age of patients with tuberculous lymphadenopathy was 40.9 ⫾ 16.9 years (age range, 13 to 88 years) [Table 1]. Thirty percent of the patients were natives (n ⫽ 18), and 70% were immigrants (n ⫽ 42). Two thirds had emigrated to Germany ⬎ 3 years before hospital admission. Most frequently, their country of origin was Afghanistan (n ⫽ 13), India (n ⫽ 9), and Pakistan (n ⫽ 5). The age of native patients was significantly (p ⬍ 0.05)
Table 1—Demographic Data of Patients* Characteristics Gender Female Male Age, yr All patients Natives Immigrants Origin of patients† Germany Afghanistan India Western Europe Pakistan Africa Southeast Asia Predisposing factors Diabetes mellitus Alcoholism HIV
Patients, No.
Values
41 19
68.3 31.7 40.9 ⫾ 16.9 (13–88) 53.8 ⫾ 21.6 (38–88) 35.5 ⫾ 10.9 (13–58)
18 13 9 7 5 5 4
30.0 21.0 15.0 10.7 8.3 8.3 6.7
5 4 1
8.3 6.7 1.6
*Values given as % or mean ⫾ SD (range). †Patients with origins outside Germany comprised 70% of all patients in the study.
1178
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21976/ on 01/27/2017
Clinical Investigations
higher (mean, 53.8 years; age range, 38 to 88 years) than that of foreign patients (mean, 35.5 years; age range, 13 to 58 years). Medical history revealed predisposing factors such as alcoholism or homelessness in four patients. None of the patients had used IV drugs. Diabetes mellitus was documented in five patients, and one patient was infected with HIV. In 44 patients, no prior tuberculous infection was known, whereas in 16 patients the reactivation of a previous infection was supposed. Clinical Symptoms and Diagnostic Findings Night sweats, weight loss, and weakness were found in all patients. The tuberculous infection most frequently affected the cervical lymph nodes (63.3%), followed by the mediastinal lymph nodes (26.7%) and the axillary lymph nodes (8.3%). In 35% of patients, lymph nodes were enlarged in more than one site (Fig 1). To identify mediastinal lymphadenopathy or local abnormalities surrounding the lymph nodes, CT scans were performed in 24 patients. Forty-seven patients received ultrasound examinations of their superficially enlarged lymph nodes. Most of the examined nodes were hypoechoic compared with the surrounding tissue, showed a homogeneous structure, and were well-defined. In almost one third of lymph nodes, a hyperechoic center or a hyperechoic hilum was found, and in ⬍ 10% of lymph nodes calcification was identified. In 26.7% of patients, the chest radiographs showed pulmonary infiltration with no characteristic pattern for tuberculosis. All patients except for the one HIV-positive patient showed positive responses to the tuberculin skin test. A positive reaction to 0.1 TU (1:10,000) was observed in 31.7% of patients, and a positive response to ⱕ 5 TU was observed in 75% of patients (Table 2). In 65% of patients, lymph node excision was performed. The remaining 35% of patients under-
Figure 1. Localization of lymph node swelling (percentage and total number) in 60 patients (pts) with lymph node tuberculosis. www.chestjournal.org
Table 2—Diagnostic Findings and Recommended Therapy Duration in Patients With Lymph Node Tuberculosis* Variable
Patients, No.
Tuberculin skin test, TU 0.1 1.0 5.0 10 100 Negative Morphologic diagnostic findings FNA LN excision Cytologic/histologic findings Epitheloid cells Multinucleated giant cells Caseous necrosis Necrotic cells Granulamatous inflammation Mycobacteria detection in LN LN excision FNA Recommended treatment duration, mo 6 9 12
%
19 2 24 12 2 1
31.7 3.3 40.0 20.0 3.3 1.7
21 39
35.0 65.0
53 33 26 22 3
88.3 55.0 43.3 36.7 5.0
17/39 9/21
43.6 42.9
3 33 24
5.0 55.0 40.0
*LN ⫽ lymph node.
went FNA. Both methods were similarly effective in obtaining sufficient lymph node tissue for histologic and microbiological examinations and diagnoses (Table 2). The cytologic and histologic analyses revealed epithelioid cells in 88.3% of cases, multinucleated giant cells in 55% of cases, caseous necrosis in 43.3% of cases, and necrotic cells in 36.7% of cases (Table 2). In 5% of tissue samples, the cytologic analysis showed a granulomatous inflammation. Mycobacterium tuberculosis was identified in 26 patients who supplied lymph node tissue for microbiological testing (43.3% of 60 patients). FNA and lymph node excision showed similar efficiency in the detection of mycobacteria (Table 2). No atypical mycobacteria were identified. The agar or radioactive culture (BACTEC) showed the highest sensitivity (40% of 60 patients) in identifying M tuberculosis compared to that with microscopic detection by Ziehl-Neelsen or fluorescence staining (13.3%). Samples from 15 patients were tested by PCR, and M tuberculosis was detected in samples from 3 of those patients, with negative test results microscopically and in culture in 2 patients (Fig 2). In 9 of the 60 patients with lymph node tuberculosis (15%), sputum sample tests were microscopically negative for tuberculosis, but, unexpectedly, cultures were positive for tuberculosis after 8 weeks. At the same time, these patients had no signs of CHEST / 121 / 4 / APRIL, 2002
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21976/ on 01/27/2017
1179
Figure 2. Number of times that M tuberculosis was identified in lymph node tissue using microscopic staining (n ⫽ 60), agar culture (n ⫽ 60), agar and radioactive culture (BACTEC) [n ⫽ 60], and PCR (n ⫽ 15).
tuberculosis in their radiographs. However, in none of the patients did radiographic or sputum culture findings lead to the diagnosis of pulmonary tuberculosis prior to that of lymph node tuberculosis. Therapy In 70% of patients, the triple therapy led to a reduction of lymph node swellings without complications, and 20% of patients experienced either initial enlargement of the lymph node or additional swollen lymph nodes within the first 2 months of treatment. In the remaining 10% of patients, local complications including ulcerations, fistulas, or abscesses occurred (Table 2). Before patient discharge from the hospital, local complications had disappeared in all patients. In 91.7% of patients, lymph nodes had returned to their normal size, and in 8.3% of patients the results of control examinations showed no further enlargement of the lymph nodes after 6 months of treatment. Drug-dependent side effects (eg, allergic reactions, GI intolerance, or increased levels of liver enzymes, mostly related to pyrazinamide therapy), occurred in ⬍ 20% of patients. One patient each showed a monoresistance to isoniazid and rifampicin. A short-course triple treatment (duration, 6 months) was recommended in three patients, and a 9-month course of chemotherapy was recommended in 55% of patients. In patients with HIV, drug resistance, or treatment complications, a 12-month course of therapy was recommended (40% of patients). Discussion According to the German Public Health Organization,2 the reporting of new tuberculosis infections
has declined steadily over time, and in 1997 only 11,600 new cases were documented compared to 14,100 new cases in 1993. Correspondingly, the incidence rate of tuberculosis dropped from 17.5 to 13.6 per 100,000 population and per year. Despite the reduction in the incidence of pulmonary tuberculosis, there has been no decrease in the frequency of lymph node tuberculosis, which still remains at approximately 800 new infections per year and accounts for about 7.5% of all patients infected by M tuberculosis. Owing to the low number of cases, the knowledge of tuberculous lymphadenopathy seems to not be well-developed in Western countries. Therefore, the differential diagnosis of lymph node swellings often is performed without taking into account lymph node tuberculosis as a major possibility. In our study, 70% of patients were immigrants of Afghani, Pakistani, or Indian origin. The native/ immigrant ratio was similar to the overall ratio regarding lymph node tuberculosis in Germany. According to the German Central Bureau of Statistics,2 the incidence of lymph node tuberculosis among immigrants is significantly higher (6.6 cases per 100,000 population) than that in the native population (0.9 per 100,000 population). Unexpectedly, about 50% of patients in our sample were from southeast Asia, and none were from the former Soviet Union. Being countries with almost the same overall incidence of tuberculosis, one potential explanation could be a predisposition for lymph node tuberculosis in the populations of southeast Asia and the Indian subcontinent, or different environmental or behavioral factors among persons in those populations. In countries with a high prevalence of tuberculosis, people are exposed more intensively, on average, and show tuberculosis at an earlier age. The fact that tuberculous lymphadenitis is an early postprimary complication, as well as the fact that the prevalence of tuberculosis is rather low in Germany, might explain why the average age of native patients was higher than that of foreign patients. Regarding the male/female ratio, there was a slightly higher proportion of women, which is in accordance with the results of previous studies.8 In contrast, pulmonary tuberculosis is found more often in men.2,9 Again, a genetic predisposition or different environmental or behavioral factors might be the underlying cause. Several studies have described a correlation between predisposing factors such as an impaired immune response owing to alcoholism or diabetes mellitus and tuberculosis.10 –12 In our sample, about 15% of patients showed this condition, and only one patient was infected with HIV. This result probably does not represent the average comorbidity rate of
1180
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21976/ on 01/27/2017
Clinical Investigations
HIV and lymph node tuberculosis in Germany, since most HIV-infected patients in our region are treated in specialized medical facilities. Ultrasound and CT examinations are known to be effective for detecting enlarged lymph nodes.13 Additionally, the sonographic texture of lymph nodes and their delineation against the surrounding tissue are helpful in the differential diagnosis. A hyperechoic center might be an indicator for central necrosis or calcification. However, this sonographic texture was detectable in only about one third of patients. The cervical lymph nodes were found to be the ones most frequently infected in the patients included in our study, whereas the mediastinal, axillary, and inguinal lymph nodes were less involved, findings that are in accord with those of other studies.14 The tuberculin skin test is a basic tool in the diagnosis of tuberculosis infection.15 Accordingly, all patients except one showed a positive response. The false-negative reaction was probably due to the suppression of the type IV response and T-lymphocyte dysfunction that are caused by HIV infection. Several studies investigated the relationship between the likelihood of M tuberculosis infections and the magnitude of the tuberculin response. Lau and coworkers16 graded skin reactions into strong, moderate, and negative using a standard tuberculin concentration. To minimize the risk of skin lesions due to testing, such as vesiculation or scarring, we used more than one concentration of tuberculin, using 0.1 mL standard tuberculin 1:10,000 as the lowest dilution. Whereas 75% of patients showed positive reactions to a skin tests using ⱕ 5 TU, which is a concentration proposed as a single-concentration test standard,17 32% of patients already had demonstrated a sufficient response to 0.1 TU, which is comparable to a strong reaction in the scale proposed by Lau et al.16 Therefore, the titration of the skin test is likely to have avoided skin lesions in a substantial number of patients. In our study, lymph node excision and FNA were similarly effective in obtaining sufficient tissue for histologic and microbiological analysis. Previous studies already found a high sensitivity5,16,18,19 and specificity5,16 for FNA. A combination of FNA and tuberculin skin testing increased the sensitivity to 90%.18 Therefore, being less invasive than lymph node excision, FNA appears to be preferable in order to minimize local complications. The microbiological identification of M tuberculosis is known to show a sensitivity between 40% and 60%.19,20 In our study, microbiological methods were capable of identifying tuberculous bacilli in 43.3% of lymph node tissue samples. Culture techniques were more sensitive than simple microscopic evaluations. www.chestjournal.org
As cultural investigations also provide information about drug sensitivity, these methods are to be considered as the primary diagnostic standard. The role of PCR in the detection of mycobacteria is still controversial,14,21–23 with its sensitivity for the detection of mycobacteria ranging between 55% and 100%.24,25 Data regarding the clinical value of this method have been limited until now. It is worth noting that in our study two patients whose tissue samples had negative microscopic findings, and who had cultures that were negative for M tuberculosis, turned out to have PCR findings that were positive. Obviously, the fact that bacilli were not detected did not exclude lymph node tuberculosis. Overall, the combination of tuberculin skin testing and cytologic examinations seems to be the best approach in the assessment of lymph node tuberculosis. In most patients, the triple therapy of isoniazid, rifampicin, and pyrazinamide led to the reduction of lymph node swelling without any complications. As reported in different studies,26 –28 lymph node enlargement can occur during therapy, which might lead to doubts about the proper diagnosis in inexperienced observers. In our study, 20% of patients showed an initial enlargement of lymph nodes within the first 2 months of treatment. In most of them, lymph nodes had returned to their normal size by the time of discharge from the hospital. Therefore, enlargement of the lymph nodes during therapy was not unusual, and by no means was it a sign of treatment failure. Ulceration, fistulas, or abscesses occurred in only 10% of patients and disappeared before hospital discharge. In conclusion, our data underline the fact that lymph node tuberculosis is still an important health issue in Western countries, especially among the immigrant population, and has to be considered seriously in the differential diagnosis of lymphadenopathy. In the population that we studied, tuberculosis infection most frequently involved the cervical lymph nodes, followed in frequency by the mediastinal, axillary, and inguinal lymph nodes, which are results that are in accordance with previous data. A culture of M tuberculosis, as a standard diagnostic method, was the most important method for detection and resistance analysis. Despite this, negative microbiological results did not exclude lymph node tuberculosis in a substantial number of patients (57.7%). To maximize the success rate of diagnoses, a combination of culture, cytologic examination of FNA samples, and tuberculin skin testing seemed to be the most effective strategy. ACKNOWLEDGMENT: We thank R.A. Jo¨ rres and J. Meiners for their valuable comments regarding the manuscript. CHEST / 121 / 4 / APRIL, 2002
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21976/ on 01/27/2017
1181
References 1 Sudre P, ten Dam G, Kochi A. Tuberculosis: a global overview of the situation today. Bull World Health Organ 1992; 70:149 –159 2 Deutsches Zentralkomitee zur Beka¨ mpfung der Tuberkulose. Annual report No. 24. Mainz, Germany: Informationsbericht, 1998 3 Rieder HL, Zellweger JP, Raviglione MC, et al. Tuberculosis control in Europe and international migration: report of a European task force. Eur Respir J 1994; 7:1545–1553 4 Mayaud C, Cadranel J. Tuberculosis in AIDS. past or new problem? Thorax 1999; 54:567–571 5 Thompson MM, Underwood MJ, Sayer RD, et al. Peripheral tuberculous lymphadenopathy: a clinical review of 67 cases. Br J Surg 1992; 79:763–764 6 American Thoracic Society. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149:1359 –1374 7 Deutsches Zentralkomitee zur Beka¨ mpfung der Tuberkulose (DZK). Richtlinien zur chemotherapie der tuberkulose. Pneumologie 1995; 49:217–225 8 Dandapat MC, Mishra BM, Dash SP, et al. Peripheral lymph node tuberculosis: a review of 80 cases. Br J Surg 1990; 77:911–912 9 Raviglione MC, Sudre P, Rieder HL, et al. Global epidemiology of tuberculosis: morbidity and mortality of a worldwide epidemic. JAMA 1995; 273:220 –226 10 Chaisson RE, Schecter GF, Theuer CP, et al. Tuberculosis in patients with the acquired immunodeficiency syndrome: clinical features, response to therapy and survival. Am Rev Respir Dis 1987; 136:570 –574 11 Graham NM, Chaisson RE. Tuberculosis, and HIV infection: epidemiology, pathogenesis and clinical aspects. Ann Allergy 1993; 71:421– 427 12 Shriner KA, Mathisen GE, Goetz MB. Comparison of mycobacterial lymphadenitis among persons infected with human immunodeficiency virus and seronegative controls. Clin Infect Dis 1992; 15:601– 605 13 Hajek PC, Salomonowitz E, Turk R, et al. Lymph nodes of the neck: evaluation with US. Radiology 1986; 158:739 –742 14 Manolidis S, Frenkiel S, Yoskowitch A, et al. Mycobacterial infections of the head and neck. Otolaryngol Head Neck Surg 1993; 109:427– 433
15 Rieder HL. How to combat tuberculosis in the year 2000? Respiration 1998; 65:423– 431 16 Lau SK, Wie WI, Hsu C, et al. Efficacy of fine needle aspiration cytology in the diagnosis of tuberculous cervical lymphadenopathy. J Laryngol Otol 1990; 104:24 –27 17 American Thoracic Society. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000; 161:1376 –1381 18 Lau SK, Wie WI, Kwan S, et al. Combined use of fine needle aspiration cytologic examination and tuberculin skin test in the diagnosis of cervical tuberculous lymphadenitis. Arch Otolaryngol Head Neck Surg 1991; 117:87–90 19 Deitel M, Bendago M, Krajeden S, et al. Modern management of cervical scrofula. Head Neck 1989; 1:60 – 66 20 Rieder HL, Snider DL, Cauthen GM. Extrapulmonary tuberculosis in the United States. Am Rev Respir Dis 1990; 141:347–351 21 Narita M, Shibata M, Togashi T, et al. Polymerase chain reaction for detection of mycobacterium tuberculosis. Acta Paediatr 1992; 81:141–144 22 Shankar P, Manjunath N, Lakshmi R, et al. Identification of mycobacterium tuberculosis by polymerase chain reaction. Lancet 1990; 335:423– 424 23 Brisson-Noel A, Gicquel B, Lecossier D, et al. Rapid diagnosis of tuberculosis by amplification of mycobacterial DNA in clinical samples. Lancet 1989; 2:1069 –1071 24 Del Prete R, Mosca A, D‘Alagni M, et al. Detection of Mycobacterium tuberculosis DNA in blood of patients with acute pulmonary tuberculosis by polymerase chain reaction and non isotopic hybridization assay. J Med Microbiol 1997; 46:495–500 25 Miller J, Jenny A, Rhyan J, et al. Detection of Mycobacterium bovis in formalin-fixed, paraffin-embedded tissue of cattle and elk by PCR amplification of an IS6110 sequence specific for Mycobacterium tuberculosis complex organism. J Vet Diagn Invest 1997; 9:244 –249 26 Chen YM, Lee PY, SU WJ, et al. Lymph node tuberculosis: 7 year experience in Veterans General Hospital Taipei, Taiwan. Tuber Lung Dis 1992; 73:368 –371 27 Carter EJ, Mates S. Sudden enlargement of a deep cervical lymph node during and after treatment for pulmonary tuberculosis. Chest 1994; 106:1896 –1898 28 Campell IA, Dyson AJ. Lymph node tuberculosis: a comparison of various methods of treatment. Tubercle 1977; 548: 171–179
1182
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21976/ on 01/27/2017
Clinical Investigations
