Computer-assisted Parkinson's disease diagnosis using fuzzy optimum- path forest and Restricted Boltzmann Machines.

Parkinson's disease (PD) is a progressive neurodegenerative illness associated with motor skill disorders, affecting thousands of people, mainly elderly, worldwide. Since its symptoms are not clear and commonly confused with other diseases, providing early diagnosis is a challenging task for traditional methods. In this context, computer-aided assistance is an alternative method for a fast and automatic diagnosis, accelerating the treatment and alleviating an excessive effort from professionals. Moreover, the most recent studies proposing a solution to this problem lack in computational efficiency, prediction power, reliability among other factors. Therefore, this work proposes a Fuzzy Optimum Path Forest for automated PD identification, which is based on fuzzy logic and graph-based framework theory. Experiments consider a dataset composed of features extracted from hand-drawn images using Restricted Boltzmann Machines, and results are compared with baseline models such as Support Vector Machines, KNN, and the standard OPF classifier. Results show that the proposed model outperforms the baselines in most cases, suggesting the Fuzzy OPF as a viable alternative to deal with PD detection problems.

A Multi-Objective Demand Response Optimization Model for Scheduling Loads in a Home Energy Management System.

Demand Response (DR) aims to motivate end consumers to change their energy consumption patterns in response to changes in electricity prices or when the reliability of the electrical power system (EPS) is compromised. Most of the proposals found in the literature only aim at reducing the cost for end consumers. However, this article proposes a home energy management system (HEMS) that aims to schedule the use of each home appliance based on the price of electricity in real-time (RTP) and on the consumer satisfaction/comfort level in order to guarantee the stability and the safety of the EPS. Thus, this paper presents a multi-objective DR optimization model which was formulated as a multi-objective nonlinear programming problem subjected to a set of constraints and was solved using the Non-Dominated Sorted Genetic Algorithm (NSGA-II), in order to determine the scheduling of home appliances for the time horizon. The multi-objective DR optimization model not only to minimize the cost of electricity consumption but also to reduce the level of inconvenience for residential consumers. Moreover, a priori, it is expected to obtain a more uniform demand with fewer peaks in the system and, potentially, achieving a more reliable and safer EPS operation. Thus, the energy management controller (EMC) within the HEMS determines an optimized schedule for each home appliance through the multi-objective DR model presented in this article, and ensures a more economic scenario for end consumers. In this paper, a performance evaluation of HEMS in 15 Brazilian families between 1 January and 31 December 2016 is presented with different electric energy consumption patterns in the cities of Belém-PA, Teresina-PI, Cuiabá-MT, Florianópolis-SC and São Paulo-SP, with three families per city, located in the regions north, northeast, central west, south and the southeast of Brazil, respectively. In addition, a total of 425 home appliances were used in the simulations. The results show that the HEMS achieved reductions in the cost of electricity for all the Scenarios used while minimally affecting the satisfaction/comfort of the end consumers as well as taking into account all the restrictions. The largest reduction in the total cost of electricity occurred for the couple without children, resident in the city of Teresina-PI; with a drop from US$ 99.31 to US$ 90.72 totaling 8.65% savings in the electricity bill. Therefore, the results confirm that the proposed HEMS effectively improves the operating efficiency of home appliances and reduces electricity costs for end consumers.

Energy Efficient Management of Pipelines in Buildings Using Linear Wireless Sensor Networks.

The efficient and safe management of air conditioner (AC), Piped Natural Gas (PNG) and water pipelines in large buildings is a major challenge for the safety of these buildings. In recent years, Linear Wireless Sensor Networks (LWSN) are being used extensively for monitoring of long natural gas, water, and oil pipelines. LWSNs can also be used for efficient and safe management of AC, PNG and water pipelines in large buildings. In this paper, a scheme for optimal placement of sensors and base stations in a linear fashion to monitor the various pipelines used in large buildings has been proposed. The proposed scheme utilizes the Lion Optimization Algorithm (LOA) and has been compared with three strategies, namely Ant Colony Optimization (ACO), Genetic Algorithm (GA) and Greedy Approach with respect to throughput, lifetime and end-to-end delay. The simulation results show that the proposed scheme exhibits better performance in comparison to the other three considered techniques for all the three parameters. The most striking feature of the proposed approach is that optimization is more effective when the length of the pipeline is more as far as end-to-end delay is concerned. The lifetime of the network is significantly improved using the proposed approach, especially when the length of the pipeline is of medium size, which makes the proposed scheme suitable for energy efficient buildings.

Novel Virtual Environment for Alternative Treatment of Children with Cerebral Palsy.

Cerebral palsy is a severe condition usually caused by decreased brain oxygenation during pregnancy, at birth or soon after birth. Conventional treatments for cerebral palsy are often tiresome and expensive, leading patients to quit treatment. In this paper, we describe a virtual environment for patients to engage in a playful therapeutic game for neuropsychomotor rehabilitation, based on the experience of the occupational therapy program of the Nucleus for Integrated Medical Assistance (NAMI) at the University of Fortaleza, Brazil. Integration between patient and virtual environment occurs through the hand motion sensor "Leap Motion," plus the electroencephalographic sensor "MindWave," responsible for measuring attention levels during task execution. To evaluate the virtual environment, eight clinical experts on cerebral palsy were subjected to a questionnaire regarding the potential of the experimental virtual environment to promote cognitive and motor rehabilitation, as well as the potential of the treatment to enhance risks and/or negatively influence the patient's development. Based on the very positive appraisal of the experts, we propose that the experimental virtual environment is a promising alternative tool for the rehabilitation of children with cerebral palsy.

Characterization of the immune response of human cord-blood derived gamma/delta T cells to stimulation with aminobisphosphonate compounds.

Vγ9Vδ2 T lymphocytes have been shown to respond to a variety of non-peptide antigens including alkylamines and phosphoantigens. Recently, aminobisphosphonates have also been shown to stimulate this subset of γδ+ T cells. In this study we analyzed the proliferative responses of freshly isolated γδ T lymphocytes obtained from human cord blood when challenged with pyrophosphomonoesters or aminobisphosphonates. Nitrogen-containing aminobisphopsphonates, in contrast to phoshoantigens, readily stimulated expansion of Vδ2Vγ9 cells in human cord blood. Expanded cells displayed an activated mature phenotype, and were capable of producing TNFalpha and IFNgamma but not perforin following secondary stimulation, consistent with the development of a regulatory, as opposed to cytotoxic, phenotype. This approach may provide a useful strategy for a new approach to the treatment of neonatal pathologies.

Assessment of the multiple components of the variability in the adenoma detection rate in sigmoidoscopy screening, and lessons for training.

BACKGROUND AND STUDY AIMS: The determinants of the observed variability of adenoma detection rate (ADR) in endoscopy screening have not yet been fully explained. PATIENTS AND METHODS: Between November 1999 and November 2006 13 764 people (7094 men, 6670 women; age range 55-64) underwent screening flexible sigmoidoscopy at five hospital endoscopy units in Turin. To study the determinants of the ADR for distal adenomas, accounting for patient, examiner, and hospital characteristics, we applied a multivariate multilevel regression model. RESULTS: Average ADRs for all adenomas and for advanced adenomas (size > or = 10 mm, villous component > 20 %, high grade dysplasia) were 13.5 % (range 5.2 %-25.0 %) and 6.4 % (3.1 %-10.7 %) for men, and 8.0 % (2.5 %-14.0 %) and 3.7 % (0.2 % - 7.4 %) for women. In multivariate analysis, increased ADR of advanced adenomas was associated with male gender (odds ratio [OR] 1.78, 95 %CI 1.49 - 2.11), self-report of one first-degree relative with colorectal cancer (CRC) (1.44, 1.11-1.86), or of recent-onset rectal bleeding (1.73, 1.24-2.40). Adjusting for these variables, a significantly lower ADR was found for endoscopists with either a lower rate of incomplete sigmoidoscopy (< 9 %; OR 0.59, 95 %CI 0.41-0.87) or a higher rate (> 12 %; 0.64, 0.45-0.91), or with low activity volume (< 85 sigmoidoscopies/year; 0.66, 0.50-0.86). Residual variability explained by the endoscopy center effect was about 1 % and statistically significant. CONCLUSIONS: Endoscopist performance in flexible sigmoidoscopy CRC screening is highly variable. Low volume of screening activity independently predicts lower ADR, suggesting that operators devoting more time to screening sigmoidoscopy may perform better. Variability among pathologists in adenoma classification might explain part of the residual variability across endoscopy units.

Radiological aspects of diffuse alveolar haemorrhage.

PURPOSE: This paper describes chest X-ray (CXR) and computed tomography (CT) findings of diffuse alveolar haemorrhage (DAH). MATERIALS AND METHODS: We retrospectively reviewed 23 episodes of DAH in 20 patients, 17 of known aetiology and three of unknown aetiology. All cases were studied by CXR and 15 also by CT. Parenchymal consolidations and ground-glass opacities were evaluated after dividing each lung into three regions (upper, middle, lower) for a total of six zones. RESULTS: Consolidations or ground-glass opacities were identified on CXR in 16/20 patients, mainly in the middle fields (73%). In 4/20 patients, all with Wegener's granulomatosis, CXR was negative or demonstrated only nodular opacities; in two of these cases, CT revealed ground-glass opacities. A complete follow-up was available for ten patients: initially, they showed consolidation opacities in 36/60 zones, which persisted in 16/60 after 7 days and in 11/60 after 15 days. Conversely, ground-glass opacities increased after 7 days owing to the partial regression of consolidation opacities, and they markedly diminished after 15 days. CONCLUSIONS: DAH is radiologically characterised by a nonspecific alveolar-filling pattern. Diagnosis or suspicion of DAH needs to be supported by the evidence of haemoptysis and/or rapid-onset anaemia. CT is superior in detecting ground-glass opacities and is required in cases of suspected DAH with normal CXR findings.

Role of chest radiography in the diagnosis of allergic bronchopulmonary aspergillosis in adult patients with cystic fibrosis.

PURPOSE: This study aimed to verify the usefulness of chest radiography in the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in adult patients with cystic fibrosis. MATERIALS AND METHODS: Eleven patients (with a total of 14 episodes) affected by ABPA were selected from among subjects attending a Regional Cystic Fibrosis Centre. For each episode, we retrospectively reviewed the baseline chest radiographs obtained before the diagnosis of ABPA, those obtained during the course of ABPA and those obtained during follow-up. Radiographs were assessed for the presence of bronchial wall thickening, bronchiectasis, infiltrates, atelectasis, mucoid impaction, lymphadenopathy, pleural effusion and fluid levels. Radiographic findings that had appeared at the time of ABPA diagnosis and disappeared after treatment were considered related to ABPA and thus useful for a correct diagnosis of the disease. Chest radiograph abnormalities were compared with changes on the respiratory function tests [forced expiratory volume in 1 s (FEV1)] during the different stages of the disease. RESULTS: Radiographic findings at the time of ABPA diagnosis appeared to have deteriorated in 8/14 cases when compared with the baseline films; after treatment, the radiographic findings deteriorated in 6/14 cases and improved in 6/14. The most significant among the radiographic signs considered (infiltrates and mucoid impaction) appeared at the time of ABPA diagnosis in 7/14 and 4/14 cases, respectively, and in some patients, they were also present at baseline and persisted during follow-up. FEV1 values were significantly decreased (>10%) in 9/14 cases at the time of ABPA diagnosis. CONCLUSIONS: Our results demonstrate the limited usefulness of chest radiography in the diagnosis of ABPA in patients with cystic fibrosis. The most significant abnormalities are nonspecific and commonly seen on baseline films in cystic fibrosis without ABPA and persist after treatment in most cases.

P2X7 receptors and apoptosis in tuberculosis infection.

Immune cells express P2 purinoceptors of the P2Y and P2X subtypes. Evidence accumulated has shown that many different cell types are killed by sustained exposure to high concentrations of extracellular ATP. Depending on the ATP dose, length of stimulation and receptor subtype, P2X receptor stimulation may cause necrosis or apoptosis. Triggering of apoptosis, in response to intracellular infection, has been identified for a wide range of pathogens and host organisms, and there is now emerging interest about mechanism mediating host cell death and its role in pulmonary tuberculosis. The physiological meaning of P2X receptor-dependent cell death is not completely understood, but and involvement in immune-mediated reactions is postulated.

Evidence for a role of gammadelta T cells in demyelinating diseases as determined by activation states and responses to lipid antigens.

In this report we review current information on the phenotypic and functional properties of gammadelta T cells in demyelinating disorders. The results support the conclusion that although gammadelta T cells show evidence of activation in patients with either multiple sclerosis (MS) or Guillain Barrè syndrome (GBS), differences exist in the phenotypic and functional properties of these cells between the two diseases. In particular, our data indicate that in patients with MS the Vdelta2 subset is activated and that these cells can be induced to secrete high levels of proinflammatory cytokines. In contrast, in patients with GBS, the Vdelta1 subset is expanded and can be induced to secrete cytokines more associated with a humoral response.

Phenotypic and functional properties of gamma delta T cells from patients with Guillain Barré syndrome.

In this study we have examined the phenotypic and functional properties of circulating gamma delta T cells in patients with Guillain Barre syndrome (GBS), in normal healthy controls, and in patients with active multiple sclerosis (MS). Cells expressing the Vdelta2 T cell receptor showed elevated expression of the C-lectin receptor NKRP1A in both GBS and MS, suggestive of an activated state. However, in patients with GBS these cells failed to respond to pyrenil-pyrophosphate derivatives and Vdelta2 + T cell clones derived from these patients released lower levels of IFNgamma than Vdelta2 + clones derived from controls and MS patients. In contrast, in patients with GBS the Vdelta1 + subset was expanded, showed elevated expression of NKRPIA and Vdelta1 + clones derived from these patients secreted high levels of IL-4. Our findings of expanded NKRP-1A +, IL-4-producing Vdelta1 T cells in the GBS patients suggests the possibility that these cells are activated by the recognition of non-protein antigens in an MHC-unrestricted manner and contribute to the humoral response to glycolipids that is a hallmark of this disease.

Activation of C-C beta-chemokines in human peripheral blood gammadelta T cells by isopentenyl pyrophosphate and regulation by cytokines.

Human gammadelta T lymphocytes respond to viral, bacterial, protozoal, and tumoral antigens, but their precise function remains unknown. In adults the major circulating gammadelta T-cell subset expresses the Vgamma9Vdelta2 T-cell receptor and responds to protease-resistant phosphorylated derivatives found in many pathogens. In this study we show that activation of Vdelta2(+) cells with the nonpeptidic antigen isopentenyl pyrophosphate (IPP) rapidly induces (within 4-12 hours) the C-C chemokines MIP-1alpha, MIP-1beta, and lymphotactin but not MCP-1. The most robust response was obtained for MIP-1beta. IPP induction of MIP-1alpha and MIP-1beta was not affected by costimulation with interleukin-4 (IL-4), IL-10, TGF-beta, or interferon-gamma (INF-gamma). However, IL-12 significantly enhanced IPP-induced expression and release of MIP-1alpha that was down-regulated by TGF-beta whereas the induction of MIP-1beta by IPP+IL-12 was refractory to cotreatment with TGFbeta indicating that these chemokines are differentially regulated by these cytokines. Vdelta2(+) T cells also expressed a wide range of C-C chemokine receptors including CCR1, CCR5, and CCR8, all of which were down-regulated following activation. We conclude that Vdelta2(+) cells can be rapidly induced by components of bacterial cell walls to express high levels of proinflammatory chemokines, supporting an important role for these cells in the early stages of the inflammatory responses to many common pathogens. (Blood. 2000, 95:39-47)

[Treatment of acute biliary pancreatitis in the aged in the endolaparoscopic era]. / Il trattamento della pancreatite acuta biliare nell'anziano nell'era endolaparoscopica.

BACKGROUND: Acute biliary pancreatitis (ABP) still retains high morbidity (15-50%) and mortality (20-35%). Therefore it appears to be crucial to clearly assess the aetiological factors (50% of idiopathic are in fact biliary pancreatitis) and to establish the severity in order to plan the appropriate treatment. METHODS: In this study we have considered 61 patients divided into 2 groups. Group 1 had 29 ABP patients aging less than 65 years, group 232 patients aging more than 65 years; the diagnosis was made by ultrasound and serological values in 78.5% of cases, while in the remaining 21.5% was only serological. Following Ranson and APACHE II scoring 18 cases (29.5%) were classified as severe [6 (20.6%) in group 1; 12 (37.5%) in group 2: p < 0.01], 43 (70.4%) as mild. All patients with severe ABP had emergency ERCP + ES (within 24-48 hrs) followed by LC (< or = 10 days). Patients with mild ABP had LC within 10 days; in these cases IOC was always done. RESULTS: In severe cases operative endoscopy cured pancreatic inflammation in 13 cases. Subsequent LC never showed serious morbidity, apart subcutaneous emphysema in one case. In 5 cases laparotomy was required since pancreatic necrosis was present, with 60% mortality. In patients with mild pancreatitis LC was successfully performed in all cases, with 6.9% morbidity. IOC showed choledochal stones in 32.5% of cases, while in severe cases stones in the biliary tree were showed in 88.8% of cases. No significant differences were detected between group 1 and 2. CONCLUSIONS: In conclusion ABP treatment is always surgical, and almost always with minimally-invasive procedures in severe cases (ERCP + ES with LC < or = 10 days) if surgery is performed within 24-48 hrs as well as in mild cases (LC + IOC) when surgery is done within 10 days, independently from the age of the patients.

IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V delta 2+ TCR gamma delta+ T lymphocytes from healthy donors and multiple sclerosis patients.

Gamma delta T lymphocytes are thought to play a role in the pathogenesis of multiple sclerosis (MS) contributing to demyelinization and fibrosis in the central nervous system. In this study, we show that, in MS patients with active disease, the percentage of circulating V delta 2+ gamma delta T cells coexpressing NKRP1A is significantly increased compared with healthy donors. V delta 2+ and V delta 1+ T cells were sorted from MS patients and healthy volunteers and cloned. At variance with V delta 1+ clones, all V delta 2+ clones expressed NKRP1A, which was strongly up-regulated upon culture with IL-12; this effect was neutralized by specific anti-IL-12 Abs. No up-regulation of NKRP1A by IL-12 was noted on V delta 1+ clones. RNase protection assay showed that IL-12R beta 2 subunit transcript was significantly less represented in V delta 1+ than V delta 2+ clones. This finding may explain the different effect exerted by IL-12 on these clones. In transendothelial migration assays, V delta 2+ NKRP1A+ clones migrated more effectively than V delta 1+ clones, and this migratory potential was enhanced following culture with IL-12. Migration was strongly inhibited by the F(ab')2 of an anti-NKRP1A Ab, suggesting that this lectin is involved in the migration process. We also show that, in freshly isolated PBMC from MS patients, the migrated population was enriched for V delta 2+ NKRP1A+ cells. We conclude that the expression of NKRP1A on V delta 2+ cells is associated with increased ability to migrate across the vascular endothelium and that this phenomenon may be regulated by IL-12 present in the microenvironment.

Enhanced production of tumor necrosis factor-alpha and interleukin-6 due to prolonged response to lipopolysaccharide in human macrophages infected in vitro with human immunodeficiency virus type 1.

Elevated levels of circulating tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 have been detected in human immunodeficiency virus (HIV) type 1 infection. The overproduction of these cytokines could contribute to AIDS pathogenesis. Thus, the expression of TNF-alpha and IL-6 in human macrophages infected with HIV-1 was investigated. HIV-1 infection, per se, did not induce any TNF-alpha or IL-6 production or cytokine-specific mRNA expression. In contrast, HIV-1 primed macrophages to a prolonged TNF-alpha and IL-6 response to lipopolysaccharide (LPS) stimulation with respect to uninfected cells. Time-course analysis and flow cytometry demonstrated that cytokine production stopped at 6 h in uninfected macrophages but continued up to 24 h in HIV-1-infected cells. RNA studies suggested that HIV-1 interfered with late steps of cytokine synthesis. No modulation of membrane CD14 was found to account for the enhanced response to LPS. Finally, the effect of HIV-1 on cytokine response could not be abolished by the antiviral compound U75875.

HIV-1 does not alter in vitro and in vivo IL-10 production by human monocytes and macrophages.

The present study analyses the ability of HIV-1 to modulate IL-10 production in cells of monocyte-macrophage lineage cultured in the presence of macrophage colony-stimulating factor (M-CSF). Both monocytes and macrophages spontaneously produced low amount of IL-10. Lipopolysaccharide (LPS) induced a strong IL-10 response in fresh monocytes and in M-CSF-treated macrophages. In contrast, macrophages cultured in the absence of M-CSF exhibited a marked decrease in their susceptibility to LPS stimulation. M-CSF increased the IL-10 response of macrophages to LPS by enhancing both the expression of membrane-bound CD14, the protein that serves as LPS receptor, and the sensibility of CD14-expressing cells to LPS stimulation. Neither spontaneous nor LPS-induced expression of IL-10 was modulated in monocytes and macrophages by infection with eight monocytotropic strains, as demonstrated by ELISA and cytofluorimetric analysis. In contrast, all the HIV-1 strains primed macrophages for an increased IL-6 response to LPS stimulation. To determine whether IL-10 production was associated with in vivo infection, monocytes from AIDS individuals were analysed for IL-10 production. We found that neither spontaneous nor LPS-induced IL-10 production were different between healthy controls and HIV-infected patients. Taken together, these data strongly suggest that HIV-1 infection of monocytes-macrophages does not play a significant role in the regulation of IL-10 in infected patients. This study also emphasizes the role of M-CSF activation in the regulation of the cytokine response in macrophages.

Infection of human monocytes with Mycobacterium tuberculosis enhances human immunodeficiency virus type 1 replication and transmission to T cells.

Mycobacterium tuberculosis and human immunodeficiency virus type 1 (HIV-1) are virulent intracellular pathogens that invade and multiply within macrophages. The effect of M. tuberculosis on HIV-1 infection and replication was analyzed in vitro using human monocyte-derived macrophages (MDM) isolated from peripheral blood mononuclear cells by countercurrent centrifugal elutriation. Preinfection of MDM with M. tuberculosis followed by HIV-1 infection resulted in an increase in p24 release, reverse transcriptase activity, and infective virus production. In contrast, no increase in HIV-1 production was observed when MDM were infected with Mycobacterium avium complex or heat-killed M. tuberculosis. Coinfected MDM were potent stimulators of T cell proliferation, while HIV-1-infected MDM failed to present exogenous tuberculin to T cells. Furthermore, coinfected MDM showed an increased capacity to transmit HIV-1 to activated T cells. These results suggest that M. tuberculosis infection can both up-regulate HIV-1 infection and replication within MDM and increase the efficiency of virus transmission from infected MDM to T cells.

[Video laparoscopic cholecystectomy in acute cholecystitis: when,how and why?]. / La videolaparocolecistectomia nella colecistite acuta. Quando, come e perché?

Acute cholecystitis has been previously considered as contraindication for laparoscopic cholecystectomy (LC), but recently, several studies have demonstrated that the laparoscopic approach can also be effective in such cases, although iatrogenic lesions of the biliary tree have been increasingly reported. Aim of this study was to verify the effectiveness of LC in patients presenting with acute cholecystitis on the basis of preoperative and intraoperative findings, postoperative mortality and morbidity, in order to assess those conditions which still can be considered as contraindications for LC. From September 1992 to January 1995, 133 patients have been consecutively admitted and operated for LC. 46 cases (36.5%) had histologically proven acute cholecystitis. Moreover we have compared preoperative date (clinical history, laboratory findings, Rx and ultrasound evaluation) with intraoperative findings to assess a correlation with intraoperative difficult conditions evaluated according to De Manzini score. Our results demonstrate that clinical data significantly correlate with intraoperative difficult situations. Hepatobiliary ultrasound also has shown good correlation between the thickness of gallbladder wall and difficult operations (73.9 sensibility-70.1 specificity). Therefore, in patients with clinically severe acute cholecystitis, and thickened gallbladder demonstrated by ultrasound it is very likely that the surgeon will experience difficult in intraoperative situations. In these conditions laparoscopy may be considered mainly as a diagnostic procedure in order to evaluate the entity of inflammatory changes considering the possibility of an open conversion that must be done before any iatrogenic lesion occur. This policy has allowed us to avoid in our series postoperative complications such as lesions of the biliary tree. In conclusion we believe that LC for acute cholecystitis should be considered as a therapeutical option only for selected cases.

Apoptosis of human monocytes/macrophages in Mycobacterium tuberculosis infection.

Tuberculosis (TB) is still a major health problem, both as a single disease entity and as a cofactor in AIDS. The interaction between macrophage and Mycobacterium tuberculosis (MTB) is a critical step in the establishment of an early chronic infection. This study analyses the capacity of MTB to induce apoptosis in cells obtained by broncho-alveolar lavage (BAL) from patients with reactive pulmonary tuberculosis and from AIDS patients with disseminated pulmonary tuberculosis. Apoptosis was increased three-fold in BAL cells obtained from patients with pulmonary tuberculosis and even more markedly in alveolar macrophages of MTB-infected AIDS patients, compared with controls. Apoptosis was analysed and characterized by propidium iodide (PI) incorporation, terminal deoxy transferase (TDT)-mediated dUTP-biotin nick end labelling (TUNEL), and tissue transglutaminase (tTG) expression. The MTB-macrophage interaction was also investigated in vitro by infecting monocyte-derived macrophages (MDM) with MTB (virulent strain H37Rv). The induction of apoptosis by MTB required viable bacteria, was dose-dependent, and was restricted to H37Rv. Infection with either Mycobacterium avium complex (MAC) or HIV-1 and treatment with heat-killed MTB failed to induce apoptosis.