Idiopathic pulmonary fibrosis and mutation of TGF-beta gene, codon 10

Idiopathic pulmonary fibrosis [IPF] is associated with histological appearance of usual interstitial pneumonia. These fibrotic changes in lung interstitium are mostly attributed to cytokine production such as TGFbeta which stimulate migration and differentiation of fibroblast to myofibroblasts. The polymorphism of TGFbeta gene was found to be associated with development of IPF. We investigated whether TGFbeta1 gene polymorphism in codon 10 is associated with interstitial pulmonary fibrosis in Iranian population. The different genotypes of TGFbeta1 at [+ 870] position [in codon 10] was studied in41 cases and 83 control subjects. The allele specific PCR method was used for genotyping. In the patient group, the frequency of T allele [NO: 58] was 70.7% and C allele [NO: 24] was 29.3%. The frequency of TT genotype [NO: 20] was 48.8%, followed by T/C [NO: 18] 43.9% and CC [No. 3] 7.3% while in the control group, the frequency of T allele [N:117] was approximately 70.5% and C allele [NO: 49] was 29.5%. The frequency of TT genotype in control group [NO: 41] was 49.4%, followed by T/C [NO: 35] 42.2% and C/C [NO: 7]8.4% In comparison with the control group, there was no association between TGFbeta1 codon 10 T/C polymorphism in our cases with IPF

Evaluation of pseudoadrenal insufficiency in tuberculosis patients

Adrenal insufficiency following initial treatment of active tuberculosis [TB] is a rare phenomenon. It is also one of the most important causes of mortality within the first few days of TB treatment. The present study evaluated this adverse effect of anti-tuberculous treatment. A prospective study was performed on TB patients hospitalized in Masih Daneshvari Hospital between 2004 and 2005. All patients had received standard anti-TB drug regimen. We evaluated pseudo-adrenal insufficiency in these patients. The study group included 429 patients out of which 6[1.4%] developed adrenal insufficiency following anti-TB treatment. In all 6 patients, basal serum cortisol levels were measured which were below the normal range after treatment. No patient had clinical findings of adrenal insufficiency before initiation of anti-TB therapy. After treatment with dexamethasone, the general condition of patients improved. [The average response to treatment was 3.1 +/- 1.7 days]. No mortality was reported during the treatment course or follow-up period. In TB patients, the adrenal reserve/ serum cortisol reserve level is low. Standard anti-TB drug regimen including rifampicin causes rapid catabolism of cortisol in tissues specially in the liver and lungs; therefore, serum cortisol level will be more decreased and consequently the patient develops adrenal insufficiency. As a whole, despite of the low incidence rate of this adverse effect, early diagnosis and treatment is essential to save the patient's life

Pneumocystis pneumonia in patients with human immunodeficiency virus

Pneumocystis Pneumonia [PCP] caused by Pneumocystis Jjirovecii [formerly called P.Carinii] is one of the most common opportunistic infections in patients with human immunodeficiency virus [HIV]. The aim of this study was to assess PCP in HIV-infected patients at the "National Research Institute of Tuberculosis and Lung Disease" [NRITLD]. A retrospective study was performed on 12 HIV-infected patients who were hospitalized at the Masih Daneshvari Hospital [NRITLD] and diagnosed as having PCP during 2003- 2007. In patients suspected of PCP with symptoms such as exertional dyspnea, fever, cough and related radiological findings, bronchoscopy including bronchoalveolar lavage [BAL] and transbronchial lung biopsy [TBLB] were performed and high resolution computed tomography [HRCT] was obtained from all patients. Mean age of the understudy patients was 32.8 +/- 5.02 yrs. The most common symptom was exertional dyspnea [91.7% of cases]. Mean duration from the onset of symptoms until diagnosis was 27.4 +/- 18.7 days. All patients were treated with Co-Trimoxazole and no adverse effects were detected. Mortality rate was 25%. In Iran PCP is one of the common opportunistic infections in HIV-positive patients which is accompanied by a high mortality rate

Increased activation and expansion of a CD57+ subset within peripheral CD8+ T lymphocytes in mycobacterium tuberculosis-infected patients

Mycobacterium tuberculosis-specific CD8+ and CD4+ T lymphocyte responses restrict the spread of extracellular pathogens by limiting M.tuberculosis replication. Alterations in cytolytic function, inappropriate maturation/differentiation, and limited proliferation could reduce their ability to control M.tuberculosis replication. In an attempt to further characterize the immune responses during M.tuberculosis infection, we enumerated delta and alpha beta receptor-bearing T cells expressing CD8 or CD4 phenotype and analyzed the differentiation phenotypes of CD8+ and CD4+ T lymphocyte subpopulations in 47 cases [23 new cases and 24 multidrug resistant patients] and 20 control subjects, using flowcytometry. We found that the CD4/CD8 ratio was significantly lower in newly-diagnosed M.tuberculosis patients compared to multidrug resistant and control subjects [P < 0.003]. Also, we found that a large proportion of CD8+ T lymphocytes in newly-diagnosed patients was defined by increased surface expression of CD57 as compared to the two other settings [P < 0.002]. This increase was more profound in patients with an inverted CD4/CD8 ratio. Analysis of the late activation antigen revealed that this was predominantly HLA-DR+ [P < 0.003]. No significant changes were observed in the percentages of CD8+CD57+ T cells between the different settings. Moreover, the co-stimulatory molecule CD28+ tended to be underexpressed by CD8+ T cells in multidrug resistant patients when compared to newly-diagnosed subjects [P < 0.002], but not to the control subjects. In contrast, the frequency of CD28+ marker on CD4+ T cells was higher in the setting of multidrug resistant compared with those of new cases [P < 0.0001]. No significant changes were observed in percentages of delta receptor-bearing T cells between different groups. We suggest that the increase in the proportion of CD57+ within CD8+ T cells in newly-diagnosed patients results from M.tuberculosis antigenic stimulation, which is a hallmark of many infections and that the protracted accumulation of CD57+ T lymphocytes might reflect an end-stage differentiation phenotype

Detection of epstein barr virus DNA in thymic epithelial tumor using nested PCR

Thymus is a lymphoepithelial organ composed of epithelial cells and lymphocytes. Primary tumors of the thymus are uncommon and a definite risk factor has not been found. There are some reports regarding the association of the [EBV] Epstein Barr Virus with thymic epithelial tumors. This study was conducted to evaluate the presence of EBV genome in thymic epithelial tumor. EBV genome, EBNA2 was examined from DNA extracts of 41 paraffin embedded specimens including 16 thymic epithelial tumors as subject cases and 25 mediastinal lymph nodes as controls. Nested PCR assay revealed that 31.25% of cases were positive for EBV genome. The presence of EBV genome EBNA2 in thymic epithelial tumor suggesting that this association may be due to the endemic nature of EBV infection

Diagnostic value of Adenosine deaminase isoenzyme [ADA2] and total ADA in tuberculous pleural effusion

Determination of adenosine deaminase [ADA] activity is one of the most promising markers in diagnosing of tuberculous pleural effusion. ADA has two main isoenzymes: ADA1 and ADA2.The ADA2 is the predominant isoform in tuberculous pleural effusion, suggesting its important role as a diagnostic marker. This study was conducted to determine the diagnostic value of ADA and ADA2 measurement in tuberculous pleural effusion. Total ADA and ADA2 isoenzyme activities were measured in 93 case of pleural effusion, including tuberculosis [26males/5females], malignancy [22males/8females], empyema and para-pneumonic [11males/4females], transudate [6males/4females], rheumatoid arthritis and idiopathic [4males/3females]. ADA levels were determined by Giusti and Galanti methods. ADA2 was measured with a potent inhibitor of ADA1 isoenzyme. Total ADA and ADA2 activities in tuberculous exudates were 96.6 +/- 29.1 and 74.4 +/- 29 U/L, respectively. With diagnostic thresholds of 46 and 42 U/L, the sensitivities of ADA and ADA2 for tuberculous exudates were 100% and 97%; their specificities 82 and 88%; and their efficiencies 88% and 93.5%, respectively. All tuberculous exudates, 2 neoplastic, 8 para- infective [including 4 empyemas] and one rheumatoid arthritis had total ADA levels > 46 U/L; of these, only one lymphoma and one rheumatoid arthritis had ADA2/ADA activity ratio > 50%. Considering simultaneous criteria of total ADA more than 46U/L, ADA2 > 42 U/L and ADA2/ADA more than 50%, we had only two false positive results, rising the specificity up to 96%. 1. ADA2 is a more efficient diagnostic marker for Tuberculous pleural effusion compared with total ADA. 2. Overall, diagnostic value of ADA would be enhanced by the determination of its isoenzymes, especially for distinguishing between the tuberculous and para-infective effusions

Evaluation of patients with infective endocarditis in a pulmonary referral centre

Despite the decreased incidence of rheumatic fever and use of prophylactic antibiotic the incidence rate of infective endocarditis has not declined. In this research, we have studied the clinical feature and therapeutic response of patients with infective endocarditis presenting with pulmonary manifestations to a pulmonary referral center. All patients with diagnosis of endocarditis that had pulmonary manifestations [based on Duke Criteria] as their primary clinical presentation were entered in this study. Data in regard to individual information, clinical features, laboratory finding and therapeutic responses were noted. All data were analysed using SPSS software [version 11.5]. A total number of twenty patients here entered the study. Mean age was 34.8 +/- 11.6 yr. The commonest clinical features included: fever [95%], cough [65%] and dyspnea [65%]. Also the commonest signs were cardiac murmurs [65%], hepatomegaly [35%] and splenomegaly [35%]. Clubbing was seen in 10%. Sixty percent of the cases were intravenous drug users and 25% were infected with HIV. Also 50% of the patients did not have any background of valvular diseases. However, there was vegetations on one valve in 75% and multiple valves were involved in 25%. The commonest valves affected were trocuspid [50%], mitral [30%] and pulmonic valve [10%]. Staphylococcus aureus [47.3%] and Streptococcus viridans [27.3%] were the commonest microorganisms detected. Pericardial effusion was present in 30% which was higher in IV drug users [p. value=0.042]. Total mortality rate in hospital was 5%. Infective endocarditis should be considered in the list of differential diagnosis in patients suffering from pulmonary symptoms especially in IV drug users

study of Th1/Th2 cytokine profiles [IL-10, IL-12, IL-4, and IFNgamma] in PBMCs of patients with multidrug resistant tuberculosis and newly diagnosed drug responsive cases

Background: Multi-drug resistant tuberculosis [MDR-TB], which is a worldwide clinical problem, is associated with high morbidity and mortality, as well as long-term survival of infected immunocompetent patients. In this study, the PPD-induced production of IL-12, IL-10, IFNgamma, and IL-4 in peripheral blood mononuclear cells [PBMC] from patients with MDR-TB were investigated and compared with cytokine production capabilities in newly diagnosed, treated cases

Materials and Methods: This study investigated the profiles of IFN-gamma, IL-12, IL-10, and IL-4 in response to a purified protein derivative [PPD] in peripheral blood mononuclear cells [PBMC] from 15 HIV negative patients with multidrug-resistant tuberculosis [MDR-TB], 11 newly diagnosed, treated cases and compared those with 10 healthy negative tuberculin reactors as controls

Results: ELISA results showed that the following stimulation with PPD, IFNgamma production was significantly increased, whereas IL-10 was significantly reduced in MDR-TB patients compared with PPD negative controls. Production of IL-12 in MDR-TB patients showed elevation, induced by PPD stimulation of their PBMCs. However, MDR-TB patients were similar to healthy negative tuberculin controls in their IL-12 production and there was no statistically significant difference between them. IL-4 was detected to be in very low levels in three groups

Conclusion: In this study MDR-TB patients have no dysregulation in IL-12 or IL-10 production during Mycobacterium tuberculosis infection, and profiles are prone to Th1 cytokines

Clinical and radiological presentation of adult tuberculous spondylitis

Tuberculous spondylitis is an uncommon form of extra-pulmonary TB. Delay in establishing diagnosis and management causes spinal cord compression and spinal deformity. We studied to determine clinical and radiological presentations of this dangerous form of TB diseases. During 2002-3 years, all patients over 14 years old who hospitalized with a probable diagnosis of TB spondylitis were evaluated. Everybody with mycobacteriologic or pathologic confirmation was enrolled in study. fourteen patients met our inclusion criteria. The mean age [SD] was 39[16] year. 57% were male. Treatment delay was 8.3 months. Fever reported in 7[50%] patients. Local tenderness was reported in 92.6% of cases. PPD was positive in half of the patients. The most regions involved were T8-T12 [43%] and L1-L3 [36%] respectively. Sputum smear was surprisingly positive in 50% of cases. Most of the patients had received anti-TB drugs for 9-12 months. CT guided aspiration and biopsy of spine lead to correct diagnosis in 93% of patients. Simultaneous pulmonary involvement is evident in half of them

Prevelance of Clinical Tuberculosis in HIV infected patients from Kermanshah Province, Iran

Tuberculosis is a common infection among HIV positive patients. It causes a lot of obstacles in diagnosis, and it can significantly affect the course of HIV infection. Between March 1997 and April 2001, we evaluated the rate of clinical tuberculosis among 638 HIV positive patients in Kermanshah province in IRAN. The study population was consisted of HIV infected patients who had been received anti tuberculosis drug regimen. Medical records of the patients were reviewed for age, gender, marital status, clinical presentation, infection source, and treatment outcome. Clinical tuberculosis was observed in 73 [11.4%] HIV- infected patients, 80.9% of whom were smear-positive, 10.9% were smear-negative, and the remaining 8.2% revealing to have extra-pulmonary tuberculosis. The patients were adapted to anti tuberculosis treatment with a cure rate of about 80%. The prevalence rate of clinical tuberculosis is high but underestimated, and it seems to be due to vulnerability of our patients to tuberculosis in the setting of intravenous drug usage as a major underlying factor for HIV among infected individuals and also residence in prisons due to illegal drug consumption

efficacy of interferon-alpha in the treatment of multidrug resistant tuberculosis

Tuberculosis is a major cause of infectious disease modality all over the world. Multidrug resistant tuberculosis [MDR-TB] is a major problem in the management of tuberculosis. With recent advances in understanding the immunopathogenesis of tuberculosis, the use of various cytokine therapies has been suggested. The objective of this study was to evaluate the efficacy of parenteral INF-alpha for treating MDR-TB patients. To conduct the study, 12 MDR- TB patients hospitalised in the clinical mycobacteriology ward of Massih Daneshvari hospital were selected randomly between October 2000 and March 2001. All had chest involvement in radiography, so they were smear and culture positive on two occasions. All had at least resistance to isoniazid and rifampin in antibio gram. They were divided in two groups. One group received INF-alpha; [3,000, 000U, three times a week, subcutaneously] in addition to anti-TB drugs, and the other group received only anti -TB medications as control group. Results indicate that the mean [ +/- SD] degree of sputum smear positivity at the beginning of therapy was 2.4 +/- 0.89 in the case group and 2 +/- 0.89 in the control group which showed no significant difference [p 0.132]. Also, at the beginning of our study, there was no significant difference in the degree of sputum culture positivity between the two groups. At the end of the 8th week, all cases became smear and culture negative, but all control subjects remained smear and culture positive [p= 0.017]. At the end of the 6th month; however, only two cases remained smear negative, one remained culture negative and the rest became positive. All control subjects had positive culture results [p 0.693]. We conclude that cytokines have at least temporary effect on disease remission and can be used as adjunctive therapy