Pulmonary Tuberculous Lesions Research Articles

Monitoring the immune response of macrophages in tuberculous granuloma through the expression of CD68, iNOS and HLA-DR in naturally infected beef cattle

Bovine tuberculosis still represents a universal threat that creates a wider range of public and animal health impacts. One of the most important steps in the pathogenesis of this disease and granuloma formation is the phagocytosis of tuberculous bacilli by macrophages. Mycobacteria replicate in macrophages, which are crucial to the pathophysiology of mycobacterial infections; however, scarce information is available about the dynamics of the granuloma-stage immunological response. Therefore, immunohistochemistry was used in this work to evaluate the expression of CD68, iNOS, and HLA-DR in different stages of TB granulomas from naturally infected cattle with tuberculosis. Two thousand, one hundred and fifty slaughtered beef cattle were examined during the period from September 2020 to March 2022. Sixty of them showed gross tuberculous pulmonary lesions and samples were collected from all of them for histopathological examination, Ziehl-Neelsen (ZN) staining, and bacteriological culturing. Selected samples that yielded a positive result for ZN and mycobacterial culturing were subjected to an immunohistochemical study of CD68, iNOS, and HLA-DR expression by macrophages according to granuloma stages. Immunohistochemical analysis revealed that the immunolabeling of CD68+, iNOS+, and HLA-DR+ macrophages significantly reduced as the stage of granuloma increased from stage I to stage IV (P < 0.003, P < 0.002, and P < 0.002, respectively). The distribution of immunolabeled macrophages was similar for the three markers, with immunolabeled macrophages distributed throughout early-stage granulomas (I, II), and surrounding the necrotic core in late-stage granulomas (III, IV). Our results suggest a polarization to the pro-inflammatory environment and increased expression of CD68+, iNOS+, and HLA-DR+ macrophages in the early stages of granulomas (I, II), which may play a protective role in the immune response of naturally infected beef cattle with tuberculosis.

Clinical characteristics in 26 children with congenital tuberculosis in Central Southern China: a retrospective study

ABSTRACT Background Congenital tuberculosis (CTB) is relatively rare and most patients are described in case reports. Aim To investigate the clinical characteristics of CTB in 26 children. Methods A retrospective analysis of 26 children with CTB from January 2013 to December 2021 in Changsha Central Hospital in Central Southern China was undertaken. Results The median age at onset was 25 days (17–33) and within 4 weeks of age in approximately 73% of cases. Of 24 mothers (including two mothers of twins), 18 (75.0%) were asymptomatic during pregnancy, and four were diagnosed with tuberculosis prenatally. The numbers of tuberculous meningitis, tuberculous encephalitis and liver TB were 17 (65.4%), five (19.2%) and four (15.4%), respectively. The main symptoms were fever (n = 18, 69.2%) and cough (n = 16, 61.5%). Positive rates of T-SPOT.TB, acid-fast bacilli smear, culture of Mycobacterium tuberculosis and GeneXpert MTB/RIF test were, respectively, 84.2% (16/19), 42.3% (11/26), 43.5% (10/23) and 83.3% (5/6). Radiograph or computed tomography demonstrated typical pulmonary tuberculous lesions in all cases and the head magnetic resonance imaging (MRI) showed marked meningeal enhancement or parenchymal lesions in seven cases (26.9%). One case had drug-resistant TB. During follow-up, nine cases had varying degrees of liver injury, and one had delayed growth and development. Eight died and 18 recovered satisfactorily. Conclusion Maternal TB status during pregnancy, the epidemiological history, T-SPOT.TB and other TB-related aetiological tests and imaging are important for the early diagnosis and treatment of CTB, and are associated with a favourable outcome. Abbreviations AFB: acid-fast bacilli; Amk: amikacin; Cs: cycloserine; CT: computed tomography; E: ethambutol; GeneXpert MTB/RIF: GeneXpert Mycobacterium tuberculosis and rifampicin resistance; H: isoniazid; IVF-ET: in-vitro fertilization-embryo transfer; Lzd: linezolid; Mfx: moxifloxacin; MTB: Mycobacterium tuberculosis; mNGS: next generation sequencing; MTB-DNA: Mycobacterium tuberculosis-deoxyribonucleic acid; Pto: protionamide; R: rifampicin; TB: tuberculosis; T-SPOT.TB: spot test of mycobacterium TB infection T-lymphocytes; Z: pyrazinamide.

Diagnostic value of ultrasound-guided transbronchial lung biopsy in peripheral tuberculous pulmonary lesions.

To investigate the diagnostic value of bronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) in tuberculous peripheral pulmonary lesions. A total of 770 patients who completed CT imaging and ultrasound bronchoscopy were retrospectively analyzed. All patients underwent biopsy sampling as well as alveolar lavage under the guidance of ultrasound. Pathological analysis and molecular biological detection of pulmonary tuberculosis were performed in both pathological tissues and bronchoalveolar lavage fluid (BALF), and the diagnostic positive rate and diagnostic sensitivity were statistically analyzed. Of the 44 patients who were found to have lesions by EBUS-TBLB, 26 patients were able to achieve a definite diagnosis of PPLs, with an overall diagnostic yield of 59.1%. Of the 33 patients with all diagnosed benign lesions, 22 were diagnosed with active pulmonary tuberculosis with the diagnostic yield of 66.7%. Among above 22 cases, the overall positive rate of BALF diagnosis was as high as 95.6%, and the highest diagnostic rate of a single test was BALF XpertMTB/RIF, 59.1%. Compared with pathological tissues, the diagnostic positive rate of BALF as a diagnostic specimen was higher (p < .05). In addition, the diagnostic yield of EBUS-TBLB in pulmonary tuberculosis was not affected by patient's age, lesion extent size, EBUS probe position, presence or tracheal grade, or characteristics of lesions (all p > .05). Transbronchial radial ultrasound-guided lung biopsy of tuberculous PPLs possesses higher diagnostic rate, fewer complications and less interference, exerts potential application value in the diagnosis of tuberculous peripheral pulmonary lesions.

The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4) Macrophages in Response to Mycobacterium tuberculosis.

DC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages [M(IL-4)], which historically represent the most studied subset within the M2 spectrum of macrophage activation. Although DC-SIGN plays important roles in Mycobacterium tuberculosis (Mtb) interactions with dendritic cells, its contribution to the Mtb–macrophage interaction remains poorly understood. Since high levels of IL-4 are correlated with tuberculosis (TB) susceptibility and progression, we investigated the role of DC-SIGN in M(IL-4) macrophages in the TB context. First, we demonstrate that DC-SIGN expression is present both in CD68+ macrophages found in tuberculous pulmonary lesions of non-human primates, and in the CD14+ cell population isolated from pleural effusions obtained from TB patients (TB-PE). Likewise, we show that DC-SIGN expression is accentuated in M(IL-4) macrophages derived from peripheral blood CD14+ monocytes isolated from TB patients, or in macrophages stimulated with acellular TB-PE, arguing for the pertinence of DC-SIGN-expressing macrophages in TB. Second, using a siRNA-mediated gene silencing approach, we performed a transcriptomic analysis of DC-SIGN-depleted M(IL-4) macrophages and revealed the upregulation of pro-inflammatory signals in response to challenge with Mtb, as compared to control cells. This pro-inflammatory gene signature was confirmed by RT-qPCR, cytokine/chemokine-based protein array, and ELISA analyses. We also found that inactivation of DC-SIGN renders M(IL-4) macrophages less permissive to Mtb intracellular growth compared to control cells, despite the equal level of bacteria uptake. Last, at the molecular level, we show that DC-SIGN interferes negatively with the pro-inflammatory response and control of Mtb intracellular growth mediated by another CLR, Dectin-1 (CLEC7A). Collectively, this study highlights a dual role for DC-SIGN as, on the one hand, being a host factor granting advantage for Mtb to parasitize macrophages and, on the other hand, representing a molecular switch to turn off the pro-inflammatory response in these cells to prevent potential immunopathology associated to TB.

Ethambutol Partitioning in Tuberculous Pulmonary Lesions Explains Its Clinical Efficacy.

ABSTRACTClinical trials and practice have shown that ethambutol is an important component of the first-line tuberculosis (TB) regime. This contrasts the drug's rather modest potency and lack of activity against nongrowing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value. Here, we hypothesized that this apparent contradiction may be explained by favorable penetration of the drug into TB lesions. First, we utilized novel in vitro lesion pharmacokinetic assays and predicted good penetration of the drug into lesions. We then employed mass spectrometry imaging and laser capture microdissection coupled to liquid chromatography and tandem mass spectrometry (LCM and LC/MS-MS, respectively) to show that ethambutol, indeed, accumulates in diseased tissues and penetrates the major human-like lesion types represented in the rabbit model of TB disease with a lesion-to-plasma exposure ratio ranging from 9 to 12. In addition, ethambutol exhibits slow but sustained passive diffusion into caseum to reach concentrations markedly higher than those measured in plasma at steady state. The results explain why ethambutol has retained its place in the first-line regimen, validate our in vitro lesion penetration assays, and demonstrate the critical importance of effective lesion penetration for anti-TB drugs. Our findings suggest that in vitro and in vivo lesion penetration evaluation should be included in TB drug discovery programs. Finally, this is the first time that LCM with LC-MS/MS has been used to quantify a small molecule at high spatial resolution in infected tissues, a method that can easily be extended to other infectious diseases.

Concurrent Tuberculosis and Influenza, South Korea

To the Editor: The concurrence of active pulmonary tuberculosis (TB) and influenza in immunocompetent hosts is rarely reported. Such concurrence could distract clinicians from diagnosing TB during an influenza epidemic. We describe 7 cases of concurrent active pulmonary TB and influenza A(H1N1)pdm09 virus infection in South Korea. At 2 teaching hospitals in Seoul, medical records were reviewed retrospectively. Among the 12,196 patients for whom A(H1N1)pdm09 infection was confirmed by real-time reverse transcription PCR from May 2009 through May 2011, a total of 7 (0.06%) were co-infected with newly diagnosed active pulmonary TB (Table). Patients who had a history of TB diagnosis were excluded. Table Case summary of concurrent active pulmonary TB and influenza A(H1N1)pdm09 infection* Among the 7 co-infected patients, 6 (85.7%) were <30 years of age. All but 1 patient, who had colon cancer, had been previously healthy. No patients had diabetes mellitus or HIV infection. One patient was a current smoker. For 5 patients, pulmonary TB was diagnosed within 1 week from the date of influenza diagnosis; initial chest radiographic findings were suggestive of active TB or pneumonia. Another 2 patients, for whom radiographic examination was not performed at the first visit, experienced worsening cough and blood-tinged sputum after improvement of influenza; laboratory tests for TB were performed, and pulmonary TB was diagnosed 17 days after the date of influenza diagnosis. For 4 patients, computed tomography of the chest was performed, and multiple nodular lesions, cavities, and tree-in-bud appearance were found. Lymphopenia at initial visit was detected in 2 patients. All Mycobacterium tuberculosis isolates were sensitive to anti-TB drugs, and clinical outcomes were good for all patients. For persons infected with M. tuberculosis, lifetime risk for development of active TB is 5%–10%; this risk increases for those with immunocompromising conditions (1). One study reported that pulmonary TB was a risk factor for A(H1N1)pdm09 infection (2). However, the concurrence of influenza and pulmonary TB has been reported only a few times, and the findings have been mostly descriptive and somewhat contradictory. An old report, from 1919, describes TB diagnoses for patients who were not recovered completely from influenza pneumonia (3). During 1957–1958, Lofgren and Callans (4) observed 46 patients with newly detected TB that had been diagnosed shortly after Asian influenza; among them, 4 had a history of typical influenza. In South Africa, among 72 patients who died of A(H1N1)pdm09 infection, 7 also had active TB (5). In Taiwan, TB and A(H1N1)pdm09 infection in a lung cancer patient was reported (6). In Japan, a fatal case of influenza pneumonia combined with Streptococcus pneumoniae and M. tuberculosis infection in a patient with diabetes mellitus was reported (7). Although the 2 patients from Taiwan and Japan had concurrent illnesses, 6 of the 7 patients in our study had been healthy (6,7). Radiographic abnormalities for the patients reported here were similar to those reported for other patients, but more cavitary lesions were found for the patients reported here. Although it is not clear whether influenza accelerates emergence of TB, some animal studies suggest that influenza-associated TB is possible. In mouse studies, simultaneous injection of tubercle bacilli into the peritoneum and intranasal inoculation with influenza A virus (PR8) resulted in more rapid and extensive development of pulmonary tuberculous lesions than did infection with tubercle bacilli only (8). In a mouse model of chronic infection with M. bovis BCG, acute infection with influenza virus moderately increased the load of acid-fast bacilli in the liver, although this change was not significant (9). It is possible that temporary suppression of T-cell immunity by A(H1N1)pdm09 virus might alter the course of M. tuberculosis infection. Among influenza patients, CD4+ T cells were depleted and a subset of Th17 cells were preferentially lost at an early stage of infection; Th17 cells that produce proinflammatory cytokine interleukin-17 are associated with a protective immune response (10). Among 4 patients for whom laboratory examination was conducted at initial visit, 2 were lymphopenic. However, individual lymphocyte subsets were not checked, and a functional assay of lymphocytes was not conducted. Further studies of serial quantification and functional assay of lymphocytes at the acute stage of influenza and its effect on host susceptibility to TB in animals and humans are needed. The concurrence of TB and influenza could be a simple overlap. In 2009, the case notification rate of pulmonary TB in South Korea was 58.2 cases per 100,000 population; in 2010, it was 56.5. However, if influenza actually amplifies TB, TB might be underestimated and missed in influenza patients. Thus, large-scale observational epidemiologic studies on the changing incidence of TB during the influenza postpandemic era are needed. Especially in TB-endemic areas, physicians should consider a concurrent pulmonary TB diagnosis for influenza patients with radiologic abnormalities consistent with TB or with prolonged respiratory symptoms.

Intercostal Muscle Flap in Post Tuberculous Pneumonectomy: A New Technique

Objective: There are many risk factors for postoperative bronchopleural fistula (BPF), including extensive resection, diabetes, chronic infection, perioperative steroid therapy, preoperative chemotherapy, and radiotherapy, the risk of bronchopleural fistula increases with resection for inflammatory diseases, especially Mycobacterium tuberculosis (MTB). The aim of this study is to evaluate the efficacy and safety of using double pedicled intercostal muscle flaps with dual blood supply to buttress the bronchial stump after pneumonectomy for tuberculous lesions as a prophylactic new technique from post-pneumonectomy BPF. Methods: Between 2007 and 2011, 47 patients with pneumonectomy for post tuberculous lesions in the department of cardiothoracic surgery, Zagazig University Hospital were divided into two groups. Group A: 28 patients with single pedicled intercostal muscle flap used and applied on the bronchial stump after pneumonectomy. Group B: 19 patients with double pedicled intercostal muscle flaps used and applied on the bronchial stump. The mean age of the patients was 42.9 years (range 27 - 67 years) in Group A, 44.8 years (range 36 - 71 years) in Group B. Results: Bleeding in one patient in Group A (3.5%) and two patients in Group B (10.5%); empyema in two patients (7.1%) in Group A only one of them developed bronchopleural fistula; arrhythmias in one patients (3.5%) in Group A and one patient in Group B (5.2%); chylothorax in one patients (3.5%); Chronic chest pain in one patient in Group A (3.5%) and two patients in Group B (10.5%). The mean follow up period was 32.7 ± 12.9 months (range between 3 and 48 months). All patients remained symptom free with no evidence of late bronchopleural fistula in Group B. Conclusions: Double pedicled intercostal muscle flaps with dual blood supply buttressing the bronchial stump is new prophylactic technique from BPF after pneumonectomy for pulmonary tuberculous lesions in high risk patients.

Surgery for hemoptysis in various pulmonary tuberculous lesions: a prospective study

Hemoptysis due to pulmonary tuberculous lesions is a common cause of morbidity, and occasionally mortality. The aim of this study is to evaluate the surgical outcome of hemoptysis in patients with various tuberculous pulmonary lesions. A total of 45 cases who underwent surgical procedures for various pulmonary tuberculous lesions with hemoptysis were included in this study. Sixteen patients underwent surgical management within one week of the attack of hemoptysis (group A), the other 29 patients underwent surgery one week after the attack (group B). Hemoptysis was classified into minor, major and massive hemoptysis. Major and massive hemoptysis were the common presentation of group A and tuberculous cavities were the most common lung lesions in both groups (37.7%). Lobectomy was the main surgical procedure performed in both groups (51.1%). Bronchopleural fistula occurred in one case in each group after right pneumonectomy. There was one case (6.2%) of mortality in group A. Tuberculous cavity is the common pulmonary lesion which can result in major and massive hemoptysis, therefore, we recommend early surgical resection of tuberculous cavities to avoid life-threatening hemoptysis. Limited resection should be avoided to prevent recurrence.

原発性上咽頭結核例

We report a case of primary nasopharyngeal tuberculosis in a 27-year-old woman who had immigrated to Japan from Vietnam. She initially complained of right cervical swelling. A red granular mass with ulcer was observed in the nasopharyx. A biopsy from the nasopharynx showed tuberculous changes. Tubercle bacilli were detected in a smear of pharyngeal discharge. Since there were no apparent pulmonary tuberculous lesions, we diagnosed the case as primary nasopharyngeal tuberculosis with tuberculous cervical lymphadenitis.The nasopharyngeal lesion disappeared after three weeks anti-tuberculosis chemotherapy. Tuberculous cervical lymphadenitis increased despite chemotherapy, and required dissection and drainage.Anti-tuberculosis chemotherapy was administered by a short course of carefully monitored treatment.

Pathology of natural Mycobacterium bovis infection in European badgers (Meles meles) and its relationship with bacterial excretion

Sixteen European badgers (Meles meles) from three statutory removal operations were studied. Samples of tracheal aspirate, pooled lymph nodes and urine were cultured for mycobacteria. Seven of the badgers were...

Prévalence des lésions tuberculeuses pulmonaires chez le bétail

Une enquête sur la tuberculose chez le bétail a été réalisée dans quatre abattoirs situés à Maiduguri, Damboa, Damaturu et Gashua au nord-est du Nigeria, de 1994 à 1998. Sur un total de 1 698 000 bovins abattus examinés post mortem, 2,8 (intervalle de confiance de 95 p. 100 : 2,76–2,84) avaient des lésions tuberculeuses pulmonaires. La prévalence a varié de 1,9 p. 100 à l’abattoir de Damaturu à 20 p. 100 à celui de Damboa. Les prévalences annuelles durant la période de l’étude ont varié de 2,3 à 4,7 p. 100. Les prévalences mensuelles ont révélé de prévalences sporadiques élevées au-delà du seul endémique. En conclusion, il a été trouvé que la tuberculose bovine était encore endémique dans cette région et des indications ont montré qu’elle avait atteint des proportions épidémiques dans la zone de Damboa. Il est donc nécessaire que le gouvernement fédéral prenne et mette en oeuvre des mesures de lutte afin de limiter la propagation de la maladie dans les cheptels bovins et sa transmission à l’homme.

Localization of intracellular monoclonal antibody specific for mycobacteria in experimentally induced pulmonary tuberculous lesion.

To determine the intracellular localization of intravenously injected infection-specific monoclonal antibodies (mAbs) in the infected cells, immunohistochemical staining was carried out in an animal model having pulmonary tuberculous lesions induced by inoculation of heat-killed Mycobacterium tuberculosis H37Rv. One milligram of intact mouse mAb against mycobacteria (group I, n = 10) and F(ab')2 (group II, n = 6) was intravenously injected to the rabbits of each group. Immunohistochemical staining using an antimouse Ab was performed at days 1, 3, 5, 7 and 8 in group I and at days 1, 2 and 3 in group II by the streptavidin-biotin method. For the control study, 1 ml of nonspecific polyclonal human IgG (group III, n = 10) and 100 micrograms of normal rabbit IgG F(ab')2 (group IV, n = 6) was injected to rabbits and guinea pigs having tuberculous inflammation, respectively. Both groups (group I and II) showed a positive antigen (Ag)-Ab reaction within the cytoplasm of monocytes. A weak but positive reaction was observed intracellularly in group III; however, no positive reaction was seen in group IV. Our results suggest that an intracellular Ag-Ab reaction plays an important role in the localization of infection by immunoscintigraphy using specific mAb fragments.

Trend of large bowel tuberculosis and the relation with pulmonary tuberculosis

From 1965 to 1989, 60 cases of large bowel tuberculosis among 116 cases of abdominal tuberculosis are reviewed and analyzed. Lesions located in the cecum or ileocecal region were found in 49 of the 60 cases. Most of the patients (50/60) received surgical intervention, but the definite diagnoses had never been proved until surgery. The diagnoses were proved by histopathologic examination in these 50 cases. Antituberculosis medications were given for at least nine months in all patients. Twenty-nine of the 50 patients who received operations had primary anastomosis during the operations, and no leakage occurred. Evidence of pulmonary tuberculous lesions could be found in 40 of the 60 cases. Positive findings of tubercle bacilli in sputum smear or culture were noted in 13 cases. The positive rate of sputum examinations decreased during 1980 to 1989; 25.6 percent (10/39) were positive from 1965 to 1979 and 14 percent (3/21) were positive from 1980 to 1989. In the meantime, there was a steady decline in the cases of large bowel tuberculosis in the most recent few years. An antituberculosis program has been carried out in the past 40 years with remarkable effect in the Taiwan area, but the possibility of intestinal tuberculosis still exists. The authors suggest that surgeons keep tuberculosis in mind when they are dealing with patients who suffer from intestinal obstruction of unknown origin with the suspected findings of pulmonary tuberculosis in chest x-ray films.

Review : Mycotic Complication in the Healed Pulmonary Tuberculous Lesions

Review : Mycotic Complication in the Healed Pulmonary Tuberculous Lesions

Diagnosis from radiograms of the age of tuberculous pulmonary lesions in adults.

151 cases of newly detected tuberculous pulmonary lesions in adults were investigated. In all cases, normal roentgenograms prior to the development of the fresh foci in the hitherto healthy pulmonary segments were available. The time interval elapsing between the date of the last normal and that of the first pathological radiograms provides information on the maximal age of the lesions in question: 6 days for bronchogenous dissemination (group D); 14 days for hematogenous and miliary pulmonary dissemination (group C and E); and 28 days for coin lesions and infiltrates up to a maximum size of 2×2 cm (group A and B). When comparing our results with those obtained by other authors dating from the time prior to the introduction of tuberculostatic treatment, we noted a distinct increase in the incidence of coin lesions.

Histogenesis of tuberculous pulmonary lesions. A study of reticulum patterns.

Histogenesis of tuberculous pulmonary lesions. A study of reticulum patterns.

A study of healing and repair of pulmonary tuberculous lesions with and without chemotherapy.

Although the clinical effects of successful tuberculosis chemotherapy are obviously beneficial and dramatic, the anatomic and histologic changes are inconspicuous and subtle. They consist, for the most part, in the absence of those lesions and reactions found in patients dying of pulmonary tuberculosis. It is the purpose of this report to compare the findings in tissue surgically resected for pulmonary tuberculosis in a group of patients who did receive chemotherapy with a group of patients who did not receive chemotherapy. Feldman and Hinshaw (1) first reported the lack of lesions or the presence of a few abortive tubercles in guinea pigs treated with streptomycin after being injected with virulent tubercle bacilli. Mahon (2) stated that with streptomycin therapy, miliary tubercles healed more rapidly, cavities contained unusually vascular granulation tissue, and bronchi were surprisingly free of tubercles; however he also noted that fundamental tissue reactions were not altered by the treatment. Koyama (3) reported that chemotherapy prevented spread of the disease and prevented cavitation and empyema. Auerbach (4) believed that chemotherapy produced specific qualitative and quantitative differences in tissue reaction to infection, which included a rapid and extensive decrease in perifocal reaction, a decrease in the width of the capsule and thickness of cavity wall, a decrease in pulmonary fibrosis, emphysema, aneurysms and hemorrhage, and, frequently, an unusual mode of cavity healing (open healing). Laennec (5) had described open healing and clean cavities and, though not unknown since then, it was considered a rare event

The bacteriology of respected tuberculous pulmonary lesions. 2. Observations on bacilli which are stainable but which cannot be cultured.

The bacteriology of respected tuberculous pulmonary lesions. 2. Observations on bacilli which are stainable but which cannot be cultured.

Chemotherapy for radiographically stable tuberculous lesions

The effect of advising one year's prophylactic treatment with calcium benzoyl PAS and isoniazid was assessed in 27 patients with pulmonary tuberculous lesions which had been radiographically stable for at least three years. None of these patients had received chemotherapy before. A similar group of 28 patients was merely observed for one year. Only 18 had taken the drugs for nine months or more and 5 stopped taking them after less than five months or took an inadequate dose. Of the 27 patients in the treated group 3 showed radiographic improvement and none showed deterioration during the year. None of the 28 patients in the untreated group showed improvement and one showed deterioration. The figures are too small to indicate whether prophylactic chemotherapy ought to be more widely given to such cases. The results, however, suggest that the investigation of a larger series would be worth while.

Comparison of 4,4′-Diaminodiphenylsulfone and Its Thymolated Derivative in Experimental Tuberculosis in Guinea Pigs

SUMMARY AND CONCLUSIONS Each of 36 guinea pigs was infected intraperitoneally with virulent tubercle bacilli. After 16 days, six were killed and found to have tuberculous lesions. On the same day, the remaining animals were divided into three groups of 10 animals each, namely controls, those treated with 4,4′-diaminodiphenylsulfone (DDS), and those treated with DDS-thymol. Treatment continued for 116 days, at which time all survivors were killed. Six controls had died by this time. All controls, including four survivors, had extensive tuberculosis. Of those animals treated with DDS-thymol, two died prematurely; two others died after 53 and 81 days of treatment, respectively, and had extensive lesions. Of the surviving six animals, one had a few residual foci in the liver and lungs and two others had microscopically evident lesions in the lungs only. All had caseous lesions in lymph nodes. None of these animals showed any toxic effect from the drug. None of the animals given DDS died; four had evidence of pulmonary tuberculous lesions. All had caseous foci in the lymph nodes and enlarged cyanotic spleens with dilated sinusoids and many pigment-laden macrophages. The administration of DDS-thymol to tuberculous guinea pigs resulted in regression of the disease, but the beneficial effect was less than that of DDS. The hematotoxic effects of DDS, as determined by splenic changes, were not seen in animals given DDS-thymol. It was not determined whether DDS-thymol has a direct action or if it is active because of DDS liberated in vivo.