A Breast Lump in an Elderly Lady - Carcinoma or else ?.

Breast tuberculosis (TB) is rare form of extra-pulmonary TB. It is most commonly seen in women of reproductive age group, especially in young, multiparous women who are breast feeding. In geriatric women, breast TB in some cases simulates with breast carcinoma due to common signs which include hard breast lump with nodular surface, ulceration, fixity to skin, discharging sinus, retraction of nipple, axillary lymphadenopathy etc. Hence, it is very difficult to differentiate breast TB from breast cancer, especially in elderly women on clinical ground only, and therefore, histopathological diagnosis is mandatory. Fine needle aspiration cytology is frequently inconclusive due to very small amount of tissue material, and open biopsy or lumpectomy followed by histopathological examination is necessary to confirm the diagnosis of breast TB. Six-month course of anti-tuberculous therapy - ATT (rifampicin, isoniazid, pyrazinamide and ethambutol) is adequate for complete resolution. Here, we report a case of breast TB in an elderly women presenting with left sided breast lump with ulceration of overlying skin and ipsilateral axillary lymphadenopathy. This case of tuberculous mastitis was suspected to be carcinoma due to presence of hard, tender, breast lump with irregular margin, nodular surface, ulceration, purulent discharge and ipsilateral axillary lymphadenopathy in absence of any constitutional symptoms of TB, and heterogenous, hypoechoic mass on USG, which was confirmed by histopathological examination of resected breast lump and responded fully to ATT.

High mortality associated with retreatment of tuberculosis in a clinic in Kampala, Uganda: a retrospective study.

The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having ≤ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses.

Intermolecular interactions, charge-density distribution and the electrostatic properties of pyrazinamide anti-TB drug molecule: an experimental and theoretical charge-density study.

An experimental charge-density analysis of pyrazinamide (a first line antitubercular drug) was performed using high-resolution X-ray diffraction data [(sin θ/λ)max = 1.1 Å(-1)] measured at 100 (2) K. The structure was solved by direct methods using SHELXS97 and refined by SHELXL97. The total electron density of the pyrazinamide molecule was modeled using the Hansen-Coppens multipole formalism implemented in the XD software. The topological properties of electron density determined from the experiment were compared with the theoretical results obtained from CRYSTAL09 at the B3LYP/6-31G** level of theory. The crystal structure was stabilized by N-H...N and N-H...O hydrogen bonds, in which the N3-H3B...N1 and N3-H3A...O1 interactions form two types of dimers in the crystal. Hirshfeld surface analysis was carried out to analyze the intermolecular interactions. The fingerprint plot reveals that the N...H and O...H hydrogen-bonding interactions contribute 26.1 and 18.4%, respectively, of the total Hirshfeld surface. The lattice energy of the molecule was calculated using density functional theory (B3LYP) methods with the 6-31G** basis set. The molecular electrostatic potential of the pyrazinamide molecule exhibits extended electronegative regions around O1, N1 and N2. The existence of a negative electrostatic potential (ESP) region just above the upper and lower surfaces of the pyrazine ring confirm the π-electron cloud.

Leprosy and tuberculosis co-infection: clinical and immunological report of two cases and review of the literature.

A review of the records of patients seen between 2004 and 2011 at the Dermatology Clinic of the São Paulo University Medical School showed that only two leprosy patients had been co-infected with tuberculosis (TB). One patient showed a type 1 leprosy reaction during the first 3 months of treatment of pleural TB and in the other patient, pulmonary TB was diagnosed during the first 3 months of treatment of a type 1 leprosy reaction. Both patients showed normal cellular immune response tests, including those of the interferon-gamma (IFN-γ)/interleukin 12 (IL-12) axis. Although both mycobacterial infections are endemic in developing countries like Brazil, the co-infection has hardly been reported in the last decade. There is no suitable explanation for this observation. The reports on the interaction between the two mycobacteria are highly speculative: some studies suggest that leprosy, especially the anergic form, would predispose to TB, whereas other investigations suggested an antagonism between the two diseases.

Evaluation of modified short course chemotherapy in active pulmonary tuberculosis patients with human immunodeficiency virus infection in University College Hospital, Ibadan, Nigeria--a preliminary report.

Over the period, 1st October 1999 to 30th April 2002 a clinical trial of the modified short-course chemotherapy (SCC) in newly diagnosed cases of pulmonary tuberculosis with human immunodeficiency virus (HIV) infection in Ibadan, Nigeria was carried out. The modified SCC used was adopted by World Health Organisation (WHO)/International Union against Tuberculosis and Lung Diseases (IUALTD) for developing countries and also by the Nigerian National Tuberculosis and Leprosy Control Programmed (NTLCP). The regimen used consisted of ethambutol (E), isoniazid (H), rifampicin (R) and pyrazinamide (Z) in the intensive phase of 2 months. The continuation phase was 6 months of ethambutol (E) and isoniazid(H), i.e. 2EHRZ/6EH. Sputum conversion was 90% at the second month of treatment and there was no bacteriological relapse after 18 months of follow-up. Side effects were few and consisted mainly of acne vulgaris in 20 (22.5%) of 89 patients during the continuation phase. It is concluded that this modified 8-month chemotherapy regimen adopted by NTLCP is efficacious in treatment of smear positive pulmonary tuberculosis (PTB) patients with background HIV infection.

Modified short-course chemotherapy of pulmonary tuberculosis in Ibadan, Nigeria--a preliminary report.

Over a 3 year period 3rd of April 1995 and 6th of April 1998 a controlled clinical trial of the modified short-course chemotherapy (SSC) in newly diagnosed cases of pulmonary tuberculosis in Nigeria was carried out. Between The SCC used was the one adopted from World Health Organisation/International Union Against Tuberculosis and Lung Diseases for developing countries by the Nigerian National Tuberculosis and Leprosy Control Programme (NTLCP). The regimen used consisted of streptomycin (S), isoniazid (H), Rifampicin (R) and pyrazinamide (Z) in the initial or intensive phase of 2 months. Ethambutol (E) was sometimes substituted for streptomycin. The continuation phase was 6 months of thiacetazone, (T) and isoniazid (H), i.e., 2SHRZ/6TH or 2EHRZ/6TH. Sputum conversion was 90% at the second month of treatment and there was no bacteriological relapse after 18 months of follow-up. Side effects were few and consisted mainly of acne vulgaris which occurred in twenty (20.6%) of 97 patients during the continuation phase. It is concluded that the 8-month chemotherapy regimen adopted by NTLCP is efficacious in treatment of smearpositive pulmonary tuberculosis (PTB).

Therapy of tuberculosis in mice by DNA vaccination.

Mycobacterium tuberculosis continues to kill about 3 million people every year, more than any other single infectious agent. This is attributed primarily to an inadequate immune response towards infecting bacteria, which suffer growth inhibition rather than death and subsequently multiply catastrophically. Although the bacillus Calmette-Guerin (BCG) vaccine is widely used, it has major limitations as a preventative measure. In addition, effective treatment requires that patients take large doses of antibacterial drug combinations for at least 6 months after diagnosis, which is difficult to achieve in many parts of the world and is further restricted by the emergence of multidrug-resistant strains of M. tuberculosis. In these circumstances, immunotherapy to boost the efficiency of the immune system in infected patients could be a valuable adjunct to antibacterial chemotherapy. Here we show in mice that DNA vaccines, initially designed to prevent infection, can also have a pronounced therapeutic action. In heavily infected mice, DNA vaccinations can switch the immune response from one that is relatively inefficient and gives bacterial stasis to one that kills bacteria. Application of such immunotherapy in conjunction with conventional chemotherapeutic antibacterial drugs might result in faster or more certain cure of the disease in humans.

Tuberculosis chemotherapy and sputum conversion among HIV-seropositive and HIV-seronegative patients in south-eastern Uganda.

OBJECTIVE: To investigate if there is a difference in response to tuberculosis treatment between HIV seronegative and HIV seropositive patients following two months of intensive phase tuberculosis treatment. DESIGN: Prospective cohort study. SETTING: St. Francis Leprosy Centre, south-east Uganda. SUBJECTS: Four hundred fifty seven patients with never previously treated sputum smear-positive tuberculosis admitted during a two-year period in 1991/1993. INTERVENTION: Intensive phase treatment with streptomycin, isoniazid, rifampicin and pyrazinamide. MAIN OUTCOME MEASURES: Sputum conversion from a positive to a negative smear at eight weeks of treatment. RESULTS: HIV seropositivity prevalence was 28%. Among HIV seronegative patients, conversion to a negative smear status occurred in 76% persons compared to 78% in HIV seropositive patients. This difference was not statistically significant (OR = 0.9; 95% CI, 0.6-1.5). HIV seropositive patients, however, were more likely to die (p = 0.017). A high prevalence of resistance to isoniazid and streptomycin was found. Isoniazid resistance was more likely in HIV seronegative patients with M. tuberculosis strains compared to HIV seropositive persons (p < 0.005). Initial resistance to antituberculosis drugs did not have a significant effect on smear conversion. CONCLUSION: This study demonstrates that HIV-seropositive status is not a principal factor in delaying sputum conversion among patients receiving intensive phase tuberculosis treatment.

PIP: A prospective cohort study was undertaken to investigate the response of HIV-seropositive and -seronegative patients at St. Francis Leprosy Center, southeastern Uganda, to tuberculosis chemotherapy. The study population included 457 patients without a history of prior tuberculosis therapy between 1991 and 1993. The subjects were exposed to an intensive phase therapy of rifampicin, streptomycin, isoniazid, and pyrazinamide. After the treatment, sputum culture and sensitivity tests were conducted. Findings showed that 77% of the patients who never received tuberculosis treatment in the past converted to a negative smear status after the 8-week treatment. There was no significant difference in sputum conversion rates between HIV-seropositive and -seronegative patients. The study also revealed that HIV seropositivity prevalence was 28%. Among HIV-seronegative patients, conversion to a negative smear status occurred in 76% compared to 78% HIV-seropositive patients. Moreover, a significant number of HIV-seronegative patients died during the initial course of the therapy. Also, a high prevalence of isoniazid and streptomycin resistance was noted; however, this result never affected the conversions of smears. In conclusion, the study clearly demonstrates that other factors outside the seropositive status may be the principal causes of the delay in sputum conversion among patients receiving intensive tuberculosis chemotherapy.

Pyrazinamide as a part of combination therapy for BL and LL patients--a preliminary report.

Pyrazinamide in a dose of 1500 mg was given to 63 borderline lepromatous (BL) and lepromatous (LL) leprosy patients on different drug regimens for the initial 2 months of therapy. Fifty-one BL and LL patients were put on the same drug regimens without pyrazinamide. There was a rapid and good clinical improvement in the patients in both of the groups. At the end of 2 years, the patients who received pyrazinamide had a morphological index (MI) of zero as compared to those patients who did not receive pyrazinamide, some of whom still had solidly staining bacilli. One out of 20 (5%) scrotal (smooth muscle) biopsies of the patients who received pyrazinamide had growth in the mouse foot pad as compared to 9 out of 38 (23.7%) smooth muscle biopsies of the patients who did not receive pyrazinamide. At the end of 5 years, the patients who received pyrazinamide had slightly better results compared with the non-pyrazinamide group. Pyrazinamide appears to have some effect against persisters in multibacillary leprosy. A well-controlled, randomized trial with longer duration of pyrazinamide therapy in a larger group of patients needs to be carried out to unequivocally determine the exact role of pyrazinamide in leprosy.

Role of rifampicin in arthralgia induced by pyrazinamide

Arthralgia during daily treatment with chemotherapy regimens containing pyrazinamide was found to be considerably less in patients who received rifampicin concomitantly...

The penetration of dapsone, rifampicin, isoniazid and pyrazinamide into peripheral nerves.

1 Dapsone, rifampicin, isoniazid and pyrazinamide were shown to penetrate readily into the sciatic nerves of the dog and sheep. 2 These findings suggest that the continued persistence of viable drug-sensitive leprosy bacilli in the peripheral nerves of patients treated for long periods with either dapsone or rifampicin is not due to inadequate intraneural drug penetration.