Comparison between nerve conduction study and high-resolution ultrasonography with color doppler in type 1 and type 2 leprosy reactions.

OBJECTIVE: To analyze the role of high-resolution ultrasonography with color Doppler (HRUS with CD) to diagnose inflammatory activity (IA) in nerves of leprosy patients under type 1 (RT1) and 2 (RT2) reactions compared to Nerve Conduction Studies (NCS). METHODS: Leprosy patients with signs or symptoms suggestive of neuritis (RT1 and RT2) without corticosteroids use were selected. They were evaluated by NCS and subsequently by HRUS with CD. Subacute segmental demyelination and the presence of blood flow, respectively, were considered signs of IA. The two methods were compared for their ability to diagnose patients with leprosy reactions. RESULTS: A total of 257 nerves from 35 patients were evaluated. NCS and HRUS with CD diagnosed IA in 68% and 74% of patients, respectively. When both methods were used concomitantly, the diagnosis rate was 91.4%. HRUS with CD was particular helpful when there was minimal neurophysiological compromise in NCS or when motor potentials were not detected. CONCLUSION: HRUS with CD was able to detect leprosy reactions, especially when combined with NCS. It was especially useful in two opposite situations: nerves with only minor changes and those without motor response in NCS. SIGNIFICANCE: Our data shows the usefulness of HRUS and CD, similar to NCS, as a tool to diagnose leprosy reactions.

Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation.

We have examined the mechanism of thalidomide inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production and found that the drug enhances the degradation of TNF-alpha mRNA. Thus, the half-life of the molecule was reduced from approximately 30 to approximately 17 min in the presence of 50 micrograms/ml of thalidomide. Inhibition of TNF-alpha production was selective, as other LPS-induced monocyte cytokines were unaffected. Pentoxifylline and dexamethasone, two other inhibitors of TNF-alpha production, are known to exert their effects by means of different mechanisms, suggesting that the three agents inhibit TNF-alpha synthesis at distinct points of the cytokine biosynthetic pathway. These observations provide an explanation for the synergistic effects of these drugs. The selective inhibition of TNF-alpha production makes thalidomide an ideal candidate for the treatment of inflammatory conditions where TNF-alpha-induced toxicities are observed and where immunity must remain intact.

Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients.

10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3-7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide.

Matrix metalloproteinase gene polymorphisms: lack of association with chronic obstructive pulmonary disease in a Brazilian population.

There are many candidate genes for chronic obstructive pulmonary disease (COPD). One such candidate is the group of genes that code for matrix metalloproteinases (MMPs), which play an essential role in tissue remodeling and repair associated with COPD. We tested the hypothesis that polymorphic variation in MMP genes influences the risk of developing COPD by examining functional polymorphisms in the promoters of MMP-3, MMP-9 and MMP-12 genes in 111 COPD patients and 101 controls. The -1171 5A/6A MMP-3, -1562 C/T MMP-9 and -82 A/G MMP-12 polymorphisms were analyzed by polymerase chain reaction, followed by restriction digestion. No significant differences were observed in allele and genotype frequencies between COPD patients and controls. Haplotype analysis also did not reveal differences between COPD patients and controls. We found that MMP polymorphisms had no significant impact on the risk of developing COPD in this Brazilian sample.

Committee II: Guidelines for cytologic sampling techniques of lung and mediastinal lymph nodes.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pulmonary cytology including indications for bronchial brushings, washings, and endobronchial ultrasound guided transbronchial fine-needle aspiration (EBUS-TBNA), technical recommendations for cytological sampling, recommended terminology and classification schemes, recommendations for ancillary testing and recommendations for post-cytological management and follow-up. All recommendations are based on the expertise of the authors, an extensive literature review and feedback from presentations at national and international conferences. This document selectively presents the results of these discussions. The present document summarizes recommendations regarding techniques used to obtain cytological and small histologic specimens from the lung and mediastinal lymph nodes including rapid on-site evaluation (ROSE), and the triage of specimens for immunocytochemical and molecular studies.

Brain death caused by electric shock and organ donation in children.

INTRODUCTION: There are still few publications about brain death caused by electric shock and the use of organs for donation in this situation. We sought to present our experience, with brain dead pediatric donors caused by electric shock. MATERIAL AND METHODS: Notification registers of potential donors were analyzed from 1998 to 2005. RESULTS: During this period, 2086 potential donors were secured, of whom 307 (14.7%) were less than 18 years old. Four pediatric potential donors (1.3%) suffered brain death due to anoxia by electric shock. Six kidneys, three livers, six corneas, and three heart valves were used for transplantation. The hearts and the lungs were not offered, because of a lack of compatible patients on the waiting list. The pediatric donors showed significant alterations of cardiac enzymes and two had altered liver enzymes. CONCLUSION: Brain death caused by electric shock is not a contraindication for organ donation. Follow-up of the recipients is necessary to determine if the transplants were successful.

Pregnancy-associated anaplastic large-cell lymphoma of the breast: a rare mimic of ductal carcinoma.

Anaplastic large-cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults. It has been described in numerous sites; however, the breast is one of the least common locations. We herein report a case of ALCL arising in the breast of a 36-yr-old pregnant woman. To our knowledge this is the second such case in the English literature. We would like to highlight the cytologic and histologic features of ALCL, as this case was initially misdiagnosed as a ductal carcinoma. Differential diagnosis with other tumors is also discussed. This case serves to emphasize the importance of the triple test, and the need for correlation of fine-needle aspiration findings with core biopsy findings in breast tumor management.

DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2.

Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at single-nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, whereas PDX maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.

Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro.

Thalidomide is currently being evaluated for efficacy in alleviating some manifestations of HIV-1 infection. To determine whether thalidomide has any direct effects on HIV-1 infection, we investigated the effect of thalidomide and also of three structural analogs of thalidomide on HIV-1 replication in vitro in human monocyte-derived macrophages. The thalidomide analogs were previously shown to inhibit TNF-alpha production in vitro at much lower concentrations than thalidomide. In HIV-1-infected macrophages treated with thalidomide or thalidomide analogs, viral replication was reduced by 60 to 80% as determined by measuring viral RT activity in the culture supernatants. In all experiments the analogs inhibited HIV-1 replication more efficiently than did thalidomide. The drugs also reduced HIV-1 gag mRNA expression. Furthermore, the drugs caused a decrease in NF-kappaB-binding activity in nuclear extracts of HIV-1-infected macrophages. The role of NF-kappaB in the drug-induced inhibition of HIV-1 replication was confirmed using an NF-kappaB-defective mutant virus to infect macrophages.

Evaluation of chemiluminescence, procoagulant activity and antigen presentation by monocytes from lepromatous leprosy patients with or without reactional episodes.

In this study, we evaluated the activity of peripheral blood mononuclear cells (PBMC), isolated from treated and untreated lepromatous leprosy patients, from lepromatous leprosy patients during and after reactional episodes (erythema nodosum leprosum (ENL) and reversal reaction (RR)), and from normal healthy individuals. We determined reactive oxygen intermediate (ROI) production, procoagulant activity (PCA) and HLA-DR antigen expression of monocytes, besides lymphoproliferation, both in the presence and absence of various stimulatory agents. Phorbol myristate acetate (PMA) stimulated ROI production by monocytes from all the groups studied, with patients during reactional episodes (ENL and RR) showing a significantly higher response (p < 0.009 and p < 0.00001). Irradiated Mycobacterium leprae, although having little effect when added alone, strongly suppressed PMA-stimulated ROI production. Muramyl dipeptide (MDP) had no influence on either basal or on PMA-induced ROI production. Basal monocyte PCA, as well as M. leprae or concanavalin A (ConA)-induced monocyte PCA was comparable in monocytes from all the groups studied. ConA was able to induce mitogenic activity in mononuclear cells isolated from all the groups studied. M. leprae, although stimulatory for normal individuals, did not induce lymphoproliferation in lepromatous leprosy patients, except for cells from patients during RR, which responded equally to M. leprae and to ConA. The absence of M. leprae-induced lymphoproliferation in lepromatous leprosy patients is not caused by the lack of basal HLA-DR expression, as PBMC from all individuals studied showed the same level of this antigen. Our results suggest an increase of spontaneous or PMA-induced monocyte activity, as detected by ROI production, during the reactional episode; addition of M. leprae suppressed this response. The increase in monocyte activity could be correlated with the increase of lymphoproliferation response to M. leprae during RR, but not during ENL. The importance of a possible immune suppressive action of M. leprae is discussed.

Effect of treatment on immune responsiveness in lepromatous leprosy patients.

This study was performed in order to analyse whether the immune unresponsiveness to Mycobacterium leprae, largely seen in lepromatous patients, persisted after discharge from treatment. Lymphoproliferation and skin tests were performed using two mycobacterial antigens (M. leprae and BCG) in three groups of lepromatous patients grouped by treatment status. Forty-seven per cent of the lepromatous patients tested acquired reactivity to M. leprae after long-term treatment.

p53 Mutation in adenocarcinoma arising in retrorectal cyst hamartoma (tailgut cyst): report of 2 cases--an immunohistochemistry/immunoperoxidase study.

Retrorectal cyst hamartoma (RCH) is a rare benign cystic lesion located in the retrorectal space. Malignancy arising in such lesions is very uncommon. In this study, 2 cases of mucinous adenocarcinoma arising in RCH are presented. In one case, dysplastic epithelium lined the cyst wall, surrounding the area of carcinoma and suggesting a dysplasia-carcinoma progression in RCH. Adenocarcinoma and the dysplastic epithelium were strongly positive for p53 and Ki-67 and showed negative staining for p21 by immunohistochemistry. These findings are suggestive of a mutation in the p53 gene in the adenocarcinoma and in dysplastic epithelium lining the cysts, similar to the dysplasia-carcinoma sequence described for the development of colonic adenocarcinoma.

Thalidomide protects mice against LPS-induced shock.

Thalidomide has been shown to selectively inhibit TNF-alpha production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-alpha has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-alpha and other cytokines and on animal survival. After injection of 100-350 micrograms LPS into mice, cytokines including TNF-alpha, IL-6, IL-10, IL-1 beta, GM-CSF and IFN-gamma were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-alpha levels were reduced by 93%, in a dose-dependent manner, and TNF-alpha mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1 beta, or IFN-gamma. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 micrograms to 300 micrograms in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death.

Extrapulmonary tuberculosis as a mimicker of neoplasia.

Despite the efforts for control and eradication of tuberculosis, new cases of the disease are diagnosed daily. The diagnosis of tuberculosis is easily made when the classical features of pulmonary necrotizing granulomatous inflammation are seen. However, extrapulmonary lesions may clinically and radiographically mimic a neoplastic process, and this may lead to misdiagnosis and delay in treatment. We studied 6 patients by aspiration biopsy, all recent immigrants and immunocompetent, who presented with weight loss and fatigue. Of these, 5 patients had a mass. One patient presented with a lytic lesion of bone. In all cases the clinical diagnosis was neoplasia. In all aspirates, the smears showed necrotic debris with neutrophils. No neoplastic cells or granulomas were seen. All cases were signed out descriptively with no specific diagnosis. A search for acid-fast organisms leading to the correct diagnosis of tuberculosis was prompted by clinical investigations that revealed pulmonary lesions, or by repeat aspiration biopsy, which showed granulomatous inflammation. Tuberculosis when present in atypical forms is still a challenging diagnosis. The finding of necrotic debris in a needle biopsy without the clinical signs of an abscess should prompt a search for acid-fast bacilli, since the correct diagnosis will eliminate a needless surgical procedure and will lead to timely and appropriate therapy.

Multiple synchronous bronchial carcinoid tumors: report of a case.

Peripheral bronchial carcinoids are uncommon. Their presentation as synchronous tumors is rare and limited to anecdotal cases.We report the case of a 62-year-old female with the radiological finding of multiple bilateral nodular lesions. Bilateral sequential thoracotomies were performed and all three nodules were treated by sublobar resections. Pathological examination revealed all specimens to be carcinoid tumors and subsequent investigation confirmed the lung as the primary site. A review of previous cases of multiple carcinoids is presented and the particularities of their management are discussed.

Clinical, immunological and histological aspects of an uncommon type II reaction in patients with lepromatous leprosy.

This study reports three cases of an unusual leprotic reaction characterized by superficial bullous ulcerative cutaneous lesions associated with high fever, malaise and oedema in patients with leprosy. Two patients responded to thalidomide treatment, with regression of the symptoms and skin ulcers. The third patient responded to thalidomide plus prednisone. Analysis of the ulcerated skin lesions showed dermal oedema with mononuclear cell infiltrate enriched for gammadelta-positive T lymphocytes and an increased number of Mycobaterium leprae bacilli within capillary endothelium. In contrast, gammadelta+ cells were decreased in or absent from the blood. Tumour necrosis factor-alpha and interleukin-6 were raised in the serum of the patients at the onset of the reaction. After the episode, cytokine levels and the percentage of gammadelta+ cells in the blood returned to normal. These cases characterize an uncommon leprotic reaction with clinical similarities to type II reaction and may indicate a significant role for gammadelta+ T cells in its pathogenesis.

[Morphological and functional characterization of adherent splenic cells of mice]. / Caracterização morfológica e funcional de células aderentes de baço de camundongo.

The separation, characterization and functional assay of the inflammatory infiltrate present in the site of the lesion has been useful in the study of many diseases. Histochemical techniques for esterase and acid phosphatase, as well as the Phagocytose test and the Giemsa staining were applied to the study of the spleen-cell population of ten mice. A good characterization of the components of the Phagocytic Mononuclear System and the identification and quantification of the total cell population were obtained.