Acute respiratory insufficiency associated with the ingestion of central nervous system depressants]

The study of twenty patients with poisoning by central nervous system depressant drugs is reported. The authors emphasized clinical aspects, complications and mainly the lung function impairment. Barbiturates were the most common drugs, at least in 60% of the cases, used alone or in combination with sedatives and tranquilizers. In 55% of patients the amount of the drug ingested could not be measured. In 60% of the cases we didn't know the period of time between drug ingestion by the patients and their admission to the hospital. On admisson all patients were in coma. The coma was of varying degrees and the deeper the coma the worse was lung function and complications were more frequent. Whenever a cardiovascular collapse was present there was also a high mortality rate. The authors emphasized the importance of a follow-up of these patients in intensive care units, mainly with cardiovascular and ventilatory support.     

Drug and multidrug resistance among Mycobacterium leprae isolates from Brazilian relapsed leprosy patients

Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary.     

Pleural plaques in asbestos-exposed workers: reproducibility of a new high-resolution CT visual semiquantitative measurement method

OBJECTIVE: To assess the reproducibility of a new high-resolution computed tomography (CT) visual semiquantitative method for pleural plaques in asbestos-exposed workers. MATERIAL AND METHODS: We performed thin-section CT in 752 chrysotile asbestos mining workers and ex-workers. Institutional review board approval and signed written informed consent from subjects were obtained. Two readers independently evaluated the 752 CT scans and identified 57 workers (mean age +/- SD, 61.8 years +/- 8.1; range, 37 to 81 years) who had pleural plaques and no other pleural or parenchymal abnormality. Three independent radiologists then quantified the plaque burden in these 57 workers using a scoring system based on the evaluation of the maximum thickness of parietal pleural plaques and percentage of parietal pleural surface involvement. We also calculated the proportion between the number of CT slices with diaphragmatic plaques and the total number of slices in which the diaphragm was seen (pdiaph). The intraobserver and interobserver agreements were analyzed using weighted Kappa coefficient. RESULTS: Interobserver agreements were good for the pleural plaque score (k = 0.61, 0.75, and 0.79) and ranged from good (k = 0.61) to excellent (k = 0.86) for the pdiaph. Intraobserver agreements ranged from good to excellent for the pleural plaque score (k = 0.79 and 1.00) and for the pdiaph (k = 0.79 and 0.93). CONCLUSION: The method proposed for high-resolution CT pleural plaque quantification in asbestos-exposed workers has a high reproducibility.     

Evaluation of real-time and conventional PCR targeting complex 85 genes for detection of Mycobacterium leprae DNA in skin biopsy samples from patients diagnosed with leprosy

In spite of the decrease in the number of registered leprosy patients, the number of new cases diagnosed each year (400,000) has remained essentially unchanged. Leprosy diagnosis is difficult due to the low sensitivity of current methodologies to identify new cases. In this study, conventional and TaqMan real-time PCR assays for detection of Mycobacterium leprae DNA were compared to current classification based on clinical, bacteriological, and histological evaluation. M. leprae DNA was extracted from frozen skin biopsy specimens from 69 leprosy patients enrolled in the study and was amplified using specific primers for either the antigen 85B-coding gene or the 85A-C intergenic region by using conventional and real-time PCR. The detection rate was 100% among multibacillary (MB) patients and ranged from 62.5% to 79.2% among paucibacillary (PB) patients according to the assay used. The TaqMan system for 85B gene amplification showed the highest sensitivity, although conventional PCR using the 85A-C gene as a target was also efficient. The cycle threshold (C(T)) values obtained using the TaqMan system were able to statistically (P < 0.0001) differentiate MB (mean C(T), 28.06; standard deviation [SD], 4.51) from PB (mean C(T), 33.06; SD, 2.24) patients. Also, there was a correlation between C(T) values and the bacteriological index for MB patients (Pearson's r, -0.444; P = 0.008). Within the PB patients' group, we tested normal skin from six patients exhibiting the pure neuritic form of leprosy (PNL). Five out of six PNL patients were positive for the presence of M. leprae DNA, even in the absence of skin lesions. In conclusion, the TaqMan real-time PCR developed here seems to be a useful tool for rapidly detecting and quantifying M. leprae DNA in clinical specimens in which bacilli were undetectable by conventional histological staining.     

Isolated Cardiac Sarcoidosis: Establishing the Diagnosis With Electroanatomic Mapping-Guided Endomyocardial Biopsy

Diagnosing isolated cardiac sarcoidosis can be challenging, and requires a high index of suspicion. We report a case of a young woman who presented with sustained ventricular tachycardia, intermittent atrioventricular block and epsilon wave on electrocardiogram. Although the patient fulfilled Task Force criteria for arrhythmogenic right ventricular cardiomyopathy, sarcoidosis was suspected because of the presence of intermittent atrioventricular block. As illustrated in this report, the use of electroanatomic mapping-guided endomyocardial biopsy can be decisive in achieving the diagnosis and is a valuable approach in cases of suspected isolated cardiac sarcoidosis.     

siRNA knock-down of mutant torsinA restores processing through secretory pathway in DYT1 dystonia cells

Most cases of the dominantly inherited movement disorder, earlyonset torsion dystonia (DYT1) are caused by a mutant form oftorsinA lacking a glutamic acid residue in the C-terminal region(torsinAE). TorsinA is an AAA+ protein located predominantlyin the lumen of the endoplasmic reticulum (ER) and nuclear envelopeapparently involved in membrane structure/movement and processingof proteins through the secretory pathway. A reporter proteinGaussia luciferase (Gluc) shows a reduced rate of secretionin primary fibroblasts from DYT1 patients expressing endogenouslevels of torsinA and torsinAE when compared with control fibroblastsexpressing only torsinA. In this study, small interfering RNA(siRNA) oligonucleotides were identified, which downregulatethe levels of torsinA or torsinAE mRNA and protein by over 65%following transfection. Transfection of siRNA for torsinA messagein control fibroblasts expressing Gluc reduced levels of luciferasesecretion compared with the same cells non-transfected or transfectedwith a non-specific siRNA. Transfection of siRNA selectivelyinhibiting torsinAE message in DYT fibroblasts increased luciferasesecretion when compared with cells non-transfected or transfectedwith a non-specific siRNA. Further, transduction of DYT1 cellswith a lentivirus vector expressing torsinA, but not torsinB,also increased secretion. These studies are consistent witha role for torsinA as an ER chaperone affecting processing ofproteins through the secretory pathway and indicate that torsinAEacts to inhibit this torsinA activity. The ability of allele-specificsiRNA for torsinAE to normalize secretory function in DYT1 patientcells supports its potential role as a therapeutic agent inearly onset torsion dystonia.     

Various pfcrt and pfmdr1 Genotypes of Plasmodium falciparum Cocirculate with P. malariae, P. ovale spp., and P. vivax in Northern Angola

Artemisinin-based combination therapy for malaria has become widely available across Africa. Populations of Plasmodium falciparum that were previously dominated by chloroquine (CQ)-resistant genotypes are now under different drug selection pressures. P. malariae, P. ovale curtisi, and P. ovale wallikeri are sympatric with P. falciparum across the continent and are frequently present as coinfections. The prevalence of human Plasmodium species was determined by PCR using DNA from blood spots collected during a cross-sectional survey in northern Angola. P. falciparum was genotyped at resistance-associated loci in pfcrt and pfmdr1 by real-time PCR or by direct sequencing of amplicons. Of the 3,316 samples collected, 541 (16.3%) contained Plasmodium species infections; 477 (88.2%) of these were P. falciparum alone, 6.5% were P. falciparum and P. malariae together, and 1.1% were P. vivax alone. The majority of the remainder (3.7%) harbored P. ovale curtisi or P. ovale wallikeri alone or in combination with other species. Of 430 P. falciparum isolates genotyped for pfcrt, 61.6% carried the wild-type allele CVMNK at codons 72 to 76, either alone or in combination with the resistant allele CVIET. No other pfcrt allele was found. Wild-type alleles dominated at codons 86, 184, 1034, 1042, and 1246 of the pfmdr1 locus among the sequenced isolates. In contrast to previous studies, P. falciparum in the study area comprises an approximately equal mix of genotypes associated with CQ sensitivity and with CQ resistance, suggesting either lower drug pressure due to poor access to treatment in rural areas or a rapid impact of the policy change away from the use of standard monotherapies.     

CD163 favors Mycobacterium leprae survival and persistence by promoting anti‐inflammatory pathways in lepromatous macrophages

Lepromatous macrophages possess a regulatory phenotype that contributes to the immunosuppression observed in leprosy. CD163, a scavenger receptor that recognizes hemoglobin–haptoglobin complexes, is expressed at higher levels in lepromatous cells, although its functional role in leprosy is not yet established. We herein demonstrate that human lepromatous lesions are microenvironments rich in IDO+CD163+. Cells isolated from these lesions were CD68+IDO+CD163+ while higher levels of sCD163 in lepromatous sera positively correlated with IL‐10 levels and IDO activity. Different Myco‐bacterium leprae (ML) concentrations in healthy monocytes likewise revealed a positive correlation between increased concentrations of the mycobacteria and IDO, CD209, and CD163 expression. The regulatory phenotype in ML‐stimulated monocytes was accompanied by increased TNF, IL‐10, and TGF‐β levels whereas IL‐10 blockade reduced ML‐induced CD163 expression. The CD163 blockade reduced ML uptake in human monocytes. ML uptake was higher in HEK293 cells transfected with the cDNA for CD163 than in untransfected cells. Simultaneously, increased CD163 expression in lepromatous cells seemed to be dependent on ML uptake, and contributed to augmented iron storage in lepromatous macrophages. Altogether, these results suggest that ML‐induced CD163 expression modulates the host cell phenotype to create a favorable environment for myco‐bacterial entry and survival.