Clinical value of myocardial performance index in patients with isolated diastolic dysfunction.

AIMS: The Doppler-derived myocardial performance index (MPI) has been considered as a diagnostic and prognostic Doppler marker for many different clinical conditions. The purpose of this study was to determine the diagnostic accuracy of traditional Pulsed-wave Doppler (PWD-MPI) and Pulsed-wave tissue Doppler imaging (TDI-MPI) and the degree of agreement between these methods in patients with grade-I diastolic dysfunction (DDI) and a normal ejection fraction. METHODS: Forty-seven consecutive ambulatory patients with DDI were compared to 51 healthy subjects with normal echocardiograms. All subjects underwent measurement of time intervals and MPI with PWD and pulsed TDI. RESULTS: TDI-MPI and PWD-MPI were significantly higher in patients with DDI than in control subjects: 0.49 ± 0.14 vs. 0.40 ± 0.09 (P < 0.001) and 0.45 ± 0.11 vs. 0.37 ± 0.08 (P < 0.001), respectively. Cutoff values of TDI-MPI > 0.42 and PWD-MPI > 0.40 identified DDI subjects, with sensitivities of 74 and 64%; specificities of 61 and 69%; positive likelihood ratios of 1.9 and 2.0; and negative likelihood ratios of 0.42 and 0.53, respectively; no significant difference was noted between the areas under the ROC curves of TDI-MPI and PWD-MPI (P = 0.77). Bland-Altman plots showed wide limits of agreement between these indices: - 0.17 to 0.23 in healthy subjects and - 0.24 to 0.32 in DDI patients. CONCLUSION: PWD-MPI and TDI-MPI showed poor clinical agreement and were not reliable parameters for the assessment of left ventricular diastolic function.

Variabilidade lipídica e risco cardiovascular / Lipid variability and cardiovascular risk

Introdução: As doenças cardiovasculares são a principal causa de óbito no mundo e geram um importante impacto econômico. Hipertensão arterial, diabetes mellitus, dislipidemia, tabagismo e obesidade são os fatores de risco modificáveis mais implicados no aparecimento de infarto agudo do miocárdio (IAM) e acidente vascular encefálico (AVE). A variabilidade nas medidas de parâmetros cardiovasculares tem surgido nos últimos anos como novo fator de risco cardiovascular. Nesse contexto, estudos têm mostrado que uma maior variabilidade de colesterol ligado à lipoproteína de baixa densidade (LDL-C) e colesterol ligado à lipoproteína de alta densidade (HDL-C) está associada com piores desfechos cardiovasculares. Entretanto, nenhum estudo até o momento avaliou o grupo específico de pacientes submetidos à cirurgia de revascularização miocárdica (CRM). Assim, elaborou-se este estudo com o intuito de avaliar se uma maior variabilidade nas medidas de LDL-C e HDL-C em pacientes submetidos à CRM está associada com eventos cardiovasculares maiores, definidos como: IAM não fatal, AVE não fatal, hospitalização por insuficiência cardíaca, hospitalização por angina, nova revascularização (cirúrgica ou percutânea) e morte. Métodos: A população do estudo foi composta de uma coorte de pacientes que foram submetidos à CRM isolada, no período 01 de janeiro de 2012 a 31 de dezembro de 2012. A variabilidade de LDL-C e HDL-C será avaliada por três índices: desvio padrão, coeficiente de variação e variabilidade corrigida independente da média. Resultados: Dos 568 pacientes submetidos à CRM isolada em 2012, 34 pacientes foram a óbito ainda na mesma internação. Também foram excluídos do estudo 50 pacientes que só tiveram uma coleta, e 133 pacientes que não tiveram nenhuma coleta de lípides séricos no período de seguimento, restando 351 pacientes que foram incluídos. Durante o período de seguimento, os pacientes incluídos tiveram total de 2090 coletas de lípides, sendo a média 5,9 coletas. No total, 46 pacientes tiveram somente 2 coletas, e um paciente teve o número máximo de coletas (18). Na primeira medida após a alta hospitalar, o valor médio de colesterol total foi de 155,7 mg/dL, 84,7 mg/dL para LDL-C, 41,8 mg/dL para HDL-C e 152 mg/dL para triglicerídeos. As análises de variabilidade estão sendo realizadas. Conclusão: Espera-se avaliar se uma maior variabilidade nas medidas de LDL-C e HDL-C em pacientes submetidos à CRM está associado com eventos cardiovasculares maiores.

Public Prevention Plans to Manage Climate Change and Respiratory Allergic Diseases. Innovative Models Used in Campania Region (Italy): The Twinning Aria Implementation and the Allergy Safe Tree Decalogue.

In recent years, climate change has been influenced by air pollution, and this destructive combination has justifiably sounded an alarm for nations and many institutional bodies worldwide. Official reports state that the emission of greenhouse gases produced by human activity are growing, and consequently also the average temperature. The World Health Organization (WHO) believes that health effects expected in the future due to climate change will be dramatic, and has invited international groups to investigate potential remedies. A task force has been established by the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC), with the aim to actively work on correlation between pollution and climate change. The Task Force provided prevention tools to suggest city leaders how to improve the health conditions of allergic people in public urban parks. The "Allergy Safe Tree Decalogue" suggests the preparation and maintenance of public low allergy-impact greenery. Through the Twinning ARIA project, the Division for the Promotion and Enhancement of Health Innovation Programs of Campania Region (Italy), sought to promote the implementation of the project in the regional Health System. The main objective will be to investigate the current use and usefulness of mobile phone Apps in the management of allergic respiratory disease, through Mobile Airways Sentinel networK (MASK), the Phase 3 of the ARIA initiative, based on the freely available MASK App (the Allergy Diary, Android and iOS platforms). The effects of these prevention activities will be registered and compared with monitoring efforts thanks to the Aerobiology Units, located throughout the Campania area. A joint effort between researchers and public administrations for the implementation of prevention plans coherently with the two models proposed in a specific area, i.e. the Decalogue for public administrations and the MASK Allergy Diary app for individual patients suffering from allergy, will be implemented as a pilot.

Prediction and evaluation of resting energy expenditure in a large group of obese outpatients.

BACKGROUND/OBJECTIVES: The aim of this study was to compare resting energy expenditure (REE) measured (MREE) by indirect calorimetry (IC) and REE predicted (PREE) from established predictive equations in a large sample of obese Caucasian adults. SUBJECTS/METHODS: We evaluated 1851 obese patients (body mass index (BMI)>30 kg m-2) aged between 18a and 65 years. Data were obtained by comparing MREE with PREE, derived from different equations, within and between normal weight and obese groups. The mean differences between PREE and MREE as well as the accuracy prediction within ±10% level were investigated in the whole sample and in three subgroups, classified by BMI (Group 1=30-39.9 kg m-2; Group 2=40-49.9 kg m-2; Group 3>50 kg m-2). RESULTS: We observed that FAO, Henry and Muller3 (body composition (BC)) equations provided good mean PREE-MREE (bias -0.7, -0.3 and 0.9%; root mean standard error (RMSE) 273, 263 and 269 kcal per day, respectively); HB and Henry equations were more accurate individually (57 and 56.9%). Only the Muller1 (BC) equation gave the lowest PREE-MREE difference (bias -1.7%; RMSE 228 kcal per day) in females, while Johnstone and De Lorenzo equations were the most accurate (55.1 and 54.8%). When the sample was split into three subgroups according to BMI, no differences were found in males; however, the majority of the equations included in this study failed to estimate REE in severely obese females (BMI>40 kg m-2). Overall, prediction accuracy was low (~55%) for all predictive equations, regardless of BMI. CONCLUSIONS: Different established equations can be used for estimating REE at the population level in both sexes. However, the accuracy was very low for all predictive equations used, particularly among females and when BMI was high, limiting their use in clinical practice. Our findings suggest that the validation of new predictive equations would improve the accuracy of REE prediction, especially for severely obese subjects (BMI>40 kg m-2).

Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells.

BACKGROUND: Multiple lines of evidence support that the Hedgehog (Hh) signalling has a role in the maintenance and progression of different human cancers. Therefore, inhibition of the Hh pathway represents a valid anticancer therapeutic approach for renal cell carcinoma (RCC) patients. NVP-LDE225 is a Smoothened (Smo) antagonist that induces dose-related inhibition of Hh and Smo-dependent tumour growth. METHODS: We assayed the effects of NVP-LDE225 alone or in combination with everolimus or sunitinib on the growth and invasion of human RCC models both in vitro and in vivo. To this aim, we used a panel of human RCC models, comprising cells with acquired resistance to sunitinib - a multiple tyrosine kinase inhibitor approved as a first-line treatment for RCC. RESULTS: NVP-LDE225 cooperated with either everolimus or sunitinib to inhibit proliferation, migration, and invasion of RCC cells even in sunitinib-resistant (SuR) cells. Some major transducers involved in tumour cell motility, including paxillin, were also efficiently inhibited by the combination therapy, as demonstrated by western blot and confocal microscopy assays. Moreover, these combined treatments inhibited tumour growth and increased animal survival in nude mice xenografted with SuR RCC cells. Finally, lung micrometastasis formation was reduced when mice were treated with NVP-LDE225 plus everolimus or sunitinib, as evidenced by artificial metastatic assays. CONCLUSIONS: Hedgehog inhibition by NVP-LDE225 plus sunitinib or everolimus bolsters antitumour activity by interfering with tumour growth and metastatic spread, even in SuR cells. Thus, this new evidence puts forward a new promising therapeutic approach for RCC patients.

The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models.

BACKGROUND: Cetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance. METHODS: Different human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo. RESULTS: Treatment with PKI-587 enhances sensitivity to cetuximab in vitro, even in the condition of epidermal growth factor receptor (EGFR) resistance. The combination of the two drugs inhibits cells survival, impairs the activation of signalling pathways and induces apoptosis. Interestingly, although significant inhibition of proliferation is observed in all cell lines treated with PKI-587 in combination with cetuximab, activation of apoptosis is evident in sensitive but not in resistant cell lines, in which autophagy is pre-eminent. In nude mice xenografted with resistant Kyse30 cells, the combined treatment significantly reduces tumour growth and prolongs mice survival. CONCLUSIONS: Phosphoinositide 3-kinase/mammalian target of rapamycin inhibition has an important role in the rescue of cetuximab resistance. Different mechanisms of cell death are induced by combined treatment depending on basal anti-EGFR responsiveness.

Antigen-triggered interferon-γ and interleukin-10 pattern in cured mucosal leishmaniasis patients is shaped during the active phase of disease.

An exacerbated type 1 response to leishmanial antigens is the basis of tissue destruction observed in mucosal leishmaniasis (ML). After therapy, a persistent production of high levels of inflammatory cytokines can confer a poor prognosis. Herein we investigated whether the clinical conditions defined during the active phase of ML affect the magnitude of long-term anti-Leishmania immune response. Twenty clinically cured ML cases were studied. Peripheral blood mononuclear cells (PBMC) were cultured with L. braziliensis antigens (Lb-Ag), Toxoplasma gondii antigens (Tg-Ag), concanavalin-A (Con-A) or medium alone, and the lymphocyte proliferative response and cytokine secretion were quantified. Medical records were reviewed for Montenegro skin test (MST) during diagnosis, duration of ML disease or time elapsed after clinical cure. The duration of disease was correlated positively with MST (r = 0·61). Lb-Ag induced interferon (IFN)-γ was correlated positively with duration of illness (r = 0·69) as well as the frequency of secreting cells [enzyme-linked immunospot (ELISPOT)] assay. No association was observed for Tg-Ag or Con-A. Disease duration was correlated negatively with interleukin (IL)-10 production (r = -0·76). Moreover, a negative correlation between length of time after clinical cure and TNF levels (r = -0·94) or the IFN-γ : IL-10 ratio (r = -0·89) were also seen. We suggest that the magnitude of the IFN-γ inflammatory response triggered by ML can be driven by the time of leishmanial antigens exposition during the active phase of the disease. This pattern could persist even long-term after cure. However, despite IFN-γ levels, the decrease of the TNF and IFN-γ : IL-10 ratio reflects the control of proinflammatory responses achieved by cure of ML, possibly preventing disease relapses.

Wnt4 inhibits cell motility induced by oncogenic Ras.

Aberrant motility and invasive ability are relevant hallmarks of malignant tumor cells. Pathways regulating the movement of cancer cells from the site of primary tumor toward adjacent and/or distant tissues are not entirely defined. By using a model of malignant transformation induced by Ras, we identified Wnt4 as an early target of Ras oncogenic signaling. Here we show that Wnt4 is repressed by Ras and that forced Wnt4 expression inhibits Ras-induced cell motility. Accordingly, we found that Wnt4 is downregulated in human anaplastic thyroid carcinomas, the most malignant and metastatic thyroid cancer histotype. Wnt4 interferes with Ras-induced actin cytoskeleton reorganization through non-canonical pathways, by altering the balance between the activation of different Rho-family small guanosine triphosphatases (GTPases). Finally, we demonstrate that Wnt4 is post-transcriptionally repressed by miR-24, a Ras-induced micro RNA (miRNA) targeting the 3'-untranslated region (UTR) of Wnt4. Taken together our data highlight a novel Ras-regulated miRNA-dependent circuitry regulating the motile phenotype of cancer cells.

Thoracic spinal stenosis and myelopathy: report of two rare cases and review of the literature.

The authors report two cases of thoracic spinal canal stenosis (SCS) and myelopathy. One is extremely unusual because of degenerative changes occurred in the upper thoracic spine. The other because of its multiple etiology among which calcification and ossification of the ligamentum flavum (OLF) in a Caucasian man. Both patients presented with an history of slowly progressive spastic paraparesis. In the first case computed tomography (CT) scans and magnetic resonance (MR) images revealed hypertrophy of the legamentum flavum and laminae causing compression of the spinal cord at T2-T3. In the second case diagnostic imaging showed three levels of stenosis in the lower thoracic spine due to degenerative changes, calcification and OLF with cord damage at T9-T10. A decompressive laminectomy and medial facetectomy was performed in both patients. The ligamentum flavum, hypertrophied and infolded in the first case and calcified and ossified in the second, was removed with careful dissection of the dural adhesions. Both patients showed a rapid post-operative recovery and regained autonomous walking within 1 month of surgery. Thoracic spinal cord stenosis is a rare and complex disorder because of differential diagnosis, neuroimaging features and treatment options. Regardless of its cause, prompt surgical decompression plays a key role in improving the functional outcome of myelopathy.

Are the severe injuries of cutaneous leishmaniasis caused by an exacerbated Th1 response?

American tegumentary leishmaniasis (ATL) is a disease whose clinical features are strongly related to the type of immune response it induces. Herein we report an atypical presentation of cutaneous leishmaniasis in a woman with a severe and extensive sore located in her leg, and we describe the differences between the usual local immune response in ATL and the local immune response in this patient. We observed an intense inflammatory response characterized by Th1 cells and cytokines with conspicuous expression of Toll-like receptor 3 (TLR-3). Few parasites were present, but there was an extensive tissue damage. We also discuss the immunological factors that could be related to the atypical presentation.

TRPV4 in the sensory organs of adult zebrafish.

TRPV4 is a nonselective cation channel that belongs to the vanilloid (V) subfamily of transient receptor potential (TRP) ion channels. While TRP channels have been found to be involved in sensing temperature, light, pressure, and chemical stimuli, TPRV4 is believed to be primarily a mechanosensor although it can also respond to warm temperatures, acidic pH, and several chemical compounds. In zebrafish, the expression of trpv4 has been studied during embryonic development, whereas its pattern of TPRV4 expression during the adult life has not been thoroughly analyzed. In this study, the occurrence of TRPV4 was addressed in the zebrafish sensory organs at the mRNA (RT-PCR) and protein (Westernblot) levels. Once the occurrence of TRPV4 was demonstrated, the TRPV4 positive cells were identified by using immunohistochemistry. TPRV4 was detected in mantle and sensory cells of neuromasts, in a subpopulation of hair sensory cells in the macula and in the cristae ampullaris of the inner ear, in sensory cells in the taste buds, in crypt neurons and ciliated sensory neurons of the olfactory epithelium, and in cells of the retina. These results demonstrate the presence of TRPV4 in all sensory organs of adult zebrafish and are consistent with the multiple physiological functions suspected for TRPV4 in mammals (mechanosensation, hearing, and temperature sensing), but furthermore suggest potential roles in olfaction and vision in zebrafish.

Leishmania (Viannia) braziliensis identification by PCR in the state of Para, Brazil.

The incidence of cutaneous leishmaniasis (CL) is increasing and there is limited surveillance of Leishmania species throughout the world. We identified the species associated with CL in a region of Amazonia, an area recognized for its Leishmania species variability. Clinical findings were analyzed and correlated with the species identified in 93 patients. PCR assays were based on small subunit ribosomal DNA (SSU-rDNA) and G6PD, and were performed in a laboratory located 3,500km away. Leishmania (V.) braziliensis was identified in 53 patients (57%). The other 40 patients (43%) carried a different species (including six cases of L. (L.) amazonensis). Molecular methods can be employed, using special media, to allow transport to distant laboratories. L. (V.) braziliensis is the most common species in the area of Para. The location of ulcers can suggest CL species.

The expression of TLR9 in human cutaneous leishmaniasis is associated with granuloma.

The Toll-like receptor (TLR) signalling pathway is the first system that defends against Leishmania. After recognising Leishmania as nonself, TLRs trigger NF-κB expression.NF-κB proceeds to the nucleus and promotes the transcription of pro-inflammatory cytokines. TLR9 is thus an important factor in the induction of an effective immune response against Leishmania. We examined the pattern of TLR9 expression in 12 patients with cutaneous leishmaniasis caused by Leishmania braziliensis detected by polymerase chain reaction. Normal skin was analysed as a negative control. TLR9 expression was examined in the dermis and epidermis by immunohistochemical analysis of paraffin-embedded biopsy tissue. TLR9 expression was primarily observed in the granuloma. The protein was detected in a few cells in the dermis. A lower expression level was detected in the epidermis of patients with leishmaniasis when compared with normal skin. The presence of TLR9 in the skin of patients with cutaneous leishmaniasis is associated with granuloma and expressed by macrophages.

Expression of brain-derived neurotrophic factor and TrkB in the lateral line system of zebrafish during development.

The neuromasts of the lateral line system are regarded as a model to study the mechanisms of hearing, deafness, and ototoxicity. The neurotrophins (NTs), especially brain-derived neurotrophic factor (BDNF), and its signaling receptor TrkB are involved in the development and maintenance of neuromasts. To know the period in which the BDNF/TrkB complex has more effects in the neuromast biology, the age-related changes were studied. Normal zebrafish from 10 to 180 days post-fertilization (dpf), as well as transgenic ET4 zebrafish 10 and 20 dpf, was analyzed using qRT-PCR, western blot, and immunohistochemistry. BDNF and TrkB mRNAs followed a parallel course, peaking at 20 dpf, and thereafter progressively decreased. Specific immunoreactivity for BDNF and TrkB was found co-localized in all hairy cells of neuromasts in 20 and 30 dpf; then, the number of immunoreactive cells decreased, and by 180 dpf BDNF remains restricted to a subpopulation of hairy cells, and TrkB to a few number of sensory and non-sensory cells. At all ages examined, TrkB immunoreactivity was detected in sensory ganglia innervating the neuromasts. The present results demonstrate that there is a parallel time-related decline in the expression of BDNF and TrkB in zebrafish. Also, the patterns of cell expression suggest that autocrine/paracrine mechanisms for this NT system might occur within the neuromasts. Because TrkB in lateral line ganglia did not vary with age, their neurons are potentially capable to respond to BDNF during the entire lifespan of zebrafish.

Doppler-derived myocardial performance index in patients with impaired left ventricular relaxation and preserved systolic function.

BACKGROUND: The Doppler-derived myocardial performance index (MPI) has been used in the evaluation of left ventricular (LV) function in several diseases. In patients with isolated diastolic dysfunction, the diagnostic utility of this index remains unclear. The aim of this study was to determine the diagnostic utility of MPI in patients with systemic hypertension, impaired LV relaxation, and normal ejection fraction. METHODS: Thirty hypertensive patients with impaired LV relaxation were compared to 30 control subjects. MPI and its components, isovolumetric relaxation time (IRT), isovolumetric contraction time (ICT), and the ejection time (ET), were measured from LV outflow and mitral inflow Doppler velocity profiles. RESULTS: MPI was higher in patients than in control subjects (0.45 +/- 0.13 vs 0.37 +/- 0.07 P < 0.0029). The increase in MPI was due to the prolongation of IRT without significant change of ICT and ET. MPI cutoff value of > or =0.40 identified impaired LV relaxation with a sensitivity of 63% and specificity of 70% while an IRT >94 ms had a sensitivity of 67% and specificity of 80%. Multivariate analysis identified relative wall thickness, mitral early filling wave velocity (E), and systolic myocardial velocity (Sm) as independent predictors of MPI in patients with hypertension. CONCLUSIONS: MPI was increase in patients with hypertension, diastolic dysfunction, and normal ejection fraction but was not superior to IRT to detect impaired LV relaxation.

Mucosal leishmaniasis: description of case management approaches and analysis of risk factors for treatment failure in a cohort of 140 patients in Brazil.

BACKGROUND: Mucosal leishmaniasis is caused mainly by Leishmania braziliensis and it occurs months or years after cutaneous lesions. This progressive disease destroys cartilages and osseous structures from face, pharynx and larynx. OBJECTIVE AND METHODS: The aim of this study was to analyse the significance of clinical and epidemiological findings, diagnosis and treatment with the outcome and recurrence of mucosal leishmaniasis through binary logistic regression model from 140 patients with mucosal leishmaniasis from a Brazilian centre. RESULTS: The median age of patients was 57.5 and systemic arterial hypertension was the most prevalent secondary disease found in patients with mucosal leishmaniasis (43%). Diabetes, chronic nephropathy and viral hepatitis, allergy and coagulopathy were found in less than 10% of patients. Human immunodeficiency virus (HIV) infection was found in 7 of 140 patients (5%). Rhinorrhea (47%) and epistaxis (75%) were the most common symptoms. N-methyl-glucamine showed a cure rate of 91% and recurrence of 22%. Pentamidine showed a similar rate of cure (91%) and recurrence (25%). Fifteen patients received itraconazole with a cure rate of 73% and recurrence of 18%. Amphotericin B was the drug used in 30 patients with 82% of response with a recurrence rate of 7%. The binary logistic regression analysis demonstrated that systemic arterial hypertension and HIV infection were associated with failure of the treatment (P < 0.05). CONCLUSION: The current first-line mucosal leishmaniasis therapy shows an adequate cure but later recurrence. HIV infection and systemic arterial hypertension should be investigated before start the treatment of mucosal leishmaniasis. Conflicts of interest The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g. pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).

Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World.

BACKGROUND: Comorbidity from tegumentary leishmaniasis and AIDS is poorly characterized. OBJECTIVES: To describe a series of patients coinfected with Leishmania and human immunodeficiency virus (HIV). METHODS: Clinical records from patients were analysed by demographic data, clinical manifestations, diagnoses, treatments and outcomes. RESULTS: Fifteen cases of AIDS/tegumentary leishmaniasis were found. The diagnosis of leishmaniasis was confirmed by the detection of Leishmania amastigotes or antigens from the cutaneous or mucosal lesions. The mean CD4+ T-cell count was 84 cells mm(-3) (range 8-258) and all patients were classified as having AIDS according to the Centers for Disease Control and Prevention. A wide range of manifestations was found, varying from a single ulcer to multiple and polymorphic lesions. Mucosal lesions were present in 80% and cutaneous lesions in 73% of patients (53% with mucocutaneous form), disseminated lesions in 60% and genital lesions in 27% of patients. All patients received anti-Leishmania therapy and 53% showed relapses. Sixty-seven per cent received highly active antiretroviral therapy but showed no difference in outcomes and relapses compared with those not using medication. Forty per cent died during the study period. In these patients, the anti-Leishmania antibody and Montenegro skin test were useful in the diagnosis of leishmaniasis, probably because leishmaniasis preceded immunosuppression due to HIV infection. CONCLUSIONS: Clinical manifestations of tegumentary leishmaniasis in HIV-infected patients are diverse. Our data emphasize possible unusual manifestations of this disease in HIV-infected patients, particularly in severely immunosuppressed cases (< 200 CD4+ cells mm(-3)).

In situ immune responses to interstitial pneumonitis in human visceral leishmaniasis.

Lung disease during active human visceral leishmaniasis is frequently reported. As such, studies have associated pulmonary symptoms to interstitial pneumonitis with a mononuclear infiltrate. However, the immune response in this condition has never been described before. The aim of this study was to determine the immunophenotypic pattern and cytokine profile of lung involvement (IPL) in human visceral leishmaniasis. Quantitative methods of analysis were performed using immunohistochemistry, and were compared with a control group of normal lung. Interstitial macrophages and cd8 cells were increased in IPL, and IL-4 as well as TNF-alpha displayed increased expression when compared to the control group. This inflammatory process with a Th2 pattern, as suggested by increased IL-4 and low IFN-gamma expression, is consistent with the immune response in other organs of visceral leishmaniasis. The microenvironment of the immune response in this condition is associated with lung disease in patients with interstitial pneumonitis related to visceral leishmaniasis, increasing the chance of bacterial infection.