Multiantigen print immunoassay (MAPIA) for the diagnosis of neurocysticercosis: a single-center diagnostic optimization and accuracy study in Lima, Peru.

Neurocysticercosis (NCC) is the most common helminthic infection of the human central nervous system. The antibody detection assay of choice is the enzyme-linked immunoelectrotransfer blot assay using lentil-lectin purified parasite antigens (LLGP-EITB, Western blot), an immunoassay with exceptional performance in clinical samples. However, its use is mainly restricted to a few research laboratories because the assay is labor-intensive and requires sophisticated equipment, expertise, and large amounts of parasite material for preparation of reagents. We report a new immunoprint assay (MAPIA) that overcomes most of these barriers. We initially compared the performance of five different antigen combinations in a subset of defined samples in the MAPIA format. After selecting the best-performing assay format (a combination of rGP50 + rT24H + sTs14 antigens), 148 archived serum samples were tested, including 40 from individuals with parenchymal NCC, 40 with subarachnoid NCC, and 68 healthy controls with no evidence of neurologic disease. MAPIA using three antigens (rGP50 + rT24H + sTs14) was highly sensitive and specific for detecting antibodies in NCC. It detected 39 out of 40 (97.5%) parenchymal NCC cases and 40/40 (100%) subarachnoid cases and was negative in 67 out of 68 (98.53%) negative samples. MAPIA using three recombinant and synthetic antigens is a simple and economical tool with a performance equivalent to the LLGP-EITB assay for the detection of specific antibodies to NCC. The MAPIA overcomes existing barriers to adoption of the EITG LLGP and is a candidate for worldwide use.

Neurocysticercosis. A frequent cause of seizures, epilepsy, and other neurological morbidity in most of the world.

Neurocysticercosis is endemic in most of the world and in endemic areas it accounts for approximately 30% of cases of epilepsy. Appropriate diagnosis and management of neurocysticercosis requires understanding the diverse presentations of the disease since these will vary in regards to clinical manifestation, sensitivity of diagnostic tests, and most importantly, therapeutic approach. This review attempts to familiarize tropical neurology practitioners with the diverse types of neurocysticercosis and the more appropriate management approaches for each.

Pathogenesis of Taenia solium taeniasis and cysticercosis.

Taenia solium infections (taeniasis/cysticercosis) are a major scourge to most developing countries. Neurocysticercosis, the infection of the human nervous system by the cystic larvae of this parasite, has a protean array of clinical manifestations varying from entirely asymptomatic infections to aggressive, lethal courses. The diversity of clinical manifestations reflects a series of contributing factors which include the number, size and location of the invading parasites, and particularly the inflammatory response of the host. This manuscript reviews the different presentations of T. solium infections in the human host with a focus on the mechanisms or processes responsible for their clinical expression.

BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies.

Synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies have remained elusive. RNA-interference drug modifier screens identified antiapoptotic BCL-2 family members as potent 5-Azacytidine-sensitizing targets. In further dissecting BCL-XL, BCL-2 and MCL-1 contribution to 5-Azacytidine activity, siRNA silencing of BCL-XL and MCL-1, but not BCL-2, exhibited variable synergy with 5-Azacytidine in vitro. The BCL-XL, BCL-2 and BCL-w inhibitor ABT-737 sensitized most cell lines more potently compared with the selective BCL-2 inhibitor ABT-199, which synergized with 5-Azacytidine mostly at higher doses. Ex vivo, ABT-737 enhanced 5-Azacytidine activity across primary AML, MDS and MPN specimens. Protein levels of BCL-XL, BCL-2 and MCL-1 in 577 AML patient samples showed overlapping expression across AML FAB subtypes and heterogeneous expression within subtypes, further supporting a concept of dual/multiple BCL-2 family member targeting consistent with RNAi and pharmacologic results. Consequently, silencing of MCL-1 and BCL-XL increased the activity of ABT-199. Functional interrogation of BCL-2 family proteins by BH3 profiling performed on patient samples significantly discriminated clinical response versus resistance to 5-Azacytidine-based therapies. On the basis of these results, we propose a clinical trial of navitoclax (clinical-grade ABT-737) combined with 5-Azacytidine in myeloid malignancies, as well as to prospectively validate BH3 profiling in predicting 5-Azacytidine response.

High frequency of spinal involvement in patients with basal subarachnoid neurocysticercosis.

OBJECTIVE: To determine the frequency of spinal neurocysticercosis (NCC) in patients with basal subarachnoid NCC compared with that in individuals with viable limited intraparenchymal NCC (≤20 live cysts in the brain). METHODS: We performed a prospective observational case-control study of patients with NCC involving the basal cisterns or patients with only limited intraparenchymal NCC. All patients underwent MRI examinations of the brain and the entire spinal cord to assess spinal involvement. RESULTS: Twenty-seven patients with limited intraparenchymal NCC, and 28 patients with basal subarachnoid NCC were included in the study. Spinal involvement was found in 17 patients with basal subarachnoid NCC and in only one patient with limited intraparenchymal NCC (odds ratio 40.18, 95% confidence interval 4.74-340.31; p < 0.0001). All patients had extramedullary (intradural) spinal NCC, and the lumbosacral region was the most frequently involved (89%). Patients with extensive spinal NCC more frequently had ventriculoperitoneal shunt placement (7 of 7 vs 3 of 11; p = 0.004) and tended to have a longer duration of neurologic symptoms than those with regional involvement (72 months vs 24 months; p = 0.062). CONCLUSIONS: The spinal subarachnoid space is commonly involved in patients with basal subarachnoid NCC, compared with those with only intraparenchymal brain cysts. Spinal cord involvement probably explains serious late complications including chronic meningitis and gait disorders that were described before the introduction of antiparasitic therapy. MRI of the spine should be performed in basal subarachnoid disease to document spinal involvement, prevent complications, and monitor for recurrent disease.

Serological diagnosis of paracoccidioidomycosis through a Western blot technique.

Paracoccidioidomycosis (PCM) is a serious infectious disease that progresses toward death if untreated. Its confirmatory diagnosis is made by the detection of the fungus Paracoccidioides brasiliensis in a direct mycological examination or by histopathology. However, these techniques are of low sensitivity. Serological tests seem to be more promising. The objective of this study was to test Western blot (WB) analysis using sera from patients suspected of PCM to determine whether it represents a safe and sensitive serological technique for a rapid and effective diagnosis for this disease. Sera from 517 patients were analyzed through WB analysis and double-immunodiffusion (DID) techniques using a crude exoantigen of P. brasiliensis 339. DID gave positive reactions for 140 sera (27%) and WB for 250 sera (48.4%). All sera that had a positive reaction by DID also had a positive result with a 43-kDa glycoprotein by WB analysis. Among the 377 samples that were negative by DID, 29.1% were reactive in WB analysis. For the cutoff dilution used (1:400), a positive reaction was not observed with any of the 102 sera from patients with other diseases in regions where such diseases are endemic and 30 healthy individuals tested as negative controls. These results prove WB analysis to be a sensitive technique and suggest its inclusion among routine laboratory assays as a safe method for PCM diagnosis.

Neurocysticercosis: unraveling the nature of the single cysticercal granuloma.

A single enhancing lesion in the brain parenchyma, also called an inflammatory granuloma, is a frequent neurologic diagnosis. One of the commonest causes of this lesion is human neurocysticercosis, the infection by the larvae of the pork tapeworm, Taenia solium. Following the demonstration that viable cysticercosis cysts survive in good conditions for several years in the human brain, single cysticercal granulomas have been consistently interpreted as representing late degeneration of a long-established parasite. On the basis of epidemiologic, clinical, and laboratory evidence detailed in this article, we hypothesize that in most cases these inflammatory lesions correspond to parasites that die in the early steps of infection, likely as the natural result of the host immunity overcoming mild infections.

HFE gene mutations and iron status of Brazilian blood donors

Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated. Subjects (N = 542) were recruited at the Hemocentro da Santa Casa de São Paulo, São Paulo, Brazil. Iron status was not influenced by HFE mutations in women and was independent of blood donation frequency. In contrast, men carrying the HFE 282CY genotype had lower total iron-binding capacity (TIBC) than HFE 282CC genotype carriers. Men who donated blood for the first time and were carriers of the HFE 282CY genotype had higher transferrin saturation values and lower TIBC concentrations than those with the homozygous wild genotype for the HFE C282Y mutation. Moreover, in this group of blood donors, carriers of HFE 63DD plus 63HD genotypes had higher serum ferritin values than those with the homozygous wild genotype for HFE H63D mutation. Multiple linear regression analysis showed that HFE 282CY leads to a 17.21 percent increase (P = 0.018) and a 83.65 percent decrease (P = 0.007) in transferrin saturation and TIBC, respectively. In addition, serum ferritin is influenced by age (3.91 percent, P = 0.001) and the HFE 63HD plus DD genotype (55.84 percent, P = 0.021). In conclusion, the HFE 282Y and 65C alleles were rare, while the HFE 63D allele was frequent in Brazilian blood donors. The HFE C282Y and H63D mutations were associated with alterations in iron status in blood donors in a gender-dependent manner.

HFE gene mutations and iron status of Brazilian blood donors.

Mutations of the HFE and TFR2 genes have been associated with iron overload. HFE and TFR2 mutations were assessed in blood donors, and the relationship with iron status was evaluated. Subjects (N = 542) were recruited at the Hemocentro da Santa Casa de São Paulo, São Paulo, Brazil. Iron status was not influenced by HFE mutations in women and was independent of blood donation frequency. In contrast, men carrying the HFE 282CY genotype had lower total iron-binding capacity (TIBC) than HFE 282CC genotype carriers. Men who donated blood for the first time and were carriers of the HFE 282CY genotype had higher transferrin saturation values and lower TIBC concentrations than those with the homozygous wild genotype for the HFE C282Y mutation. Moreover, in this group of blood donors, carriers of HFE 63DD plus 63HD genotypes had higher serum ferritin values than those with the homozygous wild genotype for HFE H63D mutation. Multiple linear regression analysis showed that HFE 282CY leads to a 17.21% increase (P = 0.018) and a 83.65% decrease (P = 0.007) in transferrin saturation and TIBC, respectively. In addition, serum ferritin is influenced by age (3.91%, P = 0.001) and the HFE 63HD plus DD genotype (55.84%, P = 0.021). In conclusion, the HFE 282Y and 65C alleles were rare, while the HFE 63D allele was frequent in Brazilian blood donors. The HFE C282Y and H63D mutations were associated with alterations in iron status in blood donors in a gender-dependent manner.

Primary peripheral primitive neuroectodermal tumors of the spinal cord: report of two cases and review of the literature.

Primary intraspinal peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare tumors with only seven reported cases in the literature. The histopathologic diagnosis of this tumor is complex and has led to a variety of treatment approaches. The distinction between central and peripheral type primary spinal cord PNETs has not always been made in the literature, leading to a paucity of data in this disease. We present here two young patients with primary intraspinal pPNET, their treatment and outcome. The first patient, a 27 year old male, presented with an intradural mass extending from L2 through L5, after multiple relapses, he is currently alive with disease after 72 months, the longest survival yet reported. The second patient, a 16 year old female, presented with an intradural mass at the cauda equina from L2 through L5, and is currently alive with responsive disease at 5 months after initial diagnosis. Here, we discuss the clinical course, the pathology and treatment for this disease and review the literature.

Variaçäo sazonal de macro e microelementos da Brachiaria decumbens sob pastejo contínuo em solos arenoso e argiloso / Seasonal changes of macro and microelements of Brachiaria decumbens on continuous grazing in sandy and clayey soils

Avaliaram-se mudanças sazonais dos minerais de cinco tipos de amostragens de B. decumbens sob pastejo contínuo (folhas, colmos, parte aérea, resíduo seco e simulaçäo do pastejo animal - SPA), oriundos de dois tipos de solos (arenoso e argiloso). Utilizou-se um esquema de parcela subdividida no qual os subtratamentos compreendiam 10 épocas de amostragens e o tipo de solo dois tratamentos. Os macro e microelementos estudados foram: Ca, P, K e Mg e Cu, Fe, Zn e Mn, respectivamente. A composiçäo dos minerais foi alterada em funçäo do tipo de amostragem. Amostras de folhas apresentaram maiores teores de Ca, P, K, Mg e Cu do que amostras de colmos. Amostras SPA tiveram valores ligeiramente inferiores aos das folha. O Ca foi o elemento menos translocável nas amostragens, P foi o mais móvel, seguido pelo K, com menor intensidade. A maior presença de resíduo seco nas amostragens colhidas na época das secas proporcionou teores reduzidos de P, K, Mg, Cu e Fe. O solo argiloso produziu forragens com teores elevados de K, Cu, Fe, Zn e Mn e o arenoso com Mg, em todos os tipos de amostragens

Patrón de masticación en las clases III de angle / Masticatory pattern in Angle class III patients

Se seleccionó una muestra de 12 pacientes (cuatro hombres y ocho mujeres) con edad promedio de 17.6 años, los cuales tenían diagnóstico de clase III de Angle y mordida cruzada posterior.- Los resultados mostraron que el 75 por ciento de los pacientes desplazaban la mandíbula hacia el lado de trabajo. El 66 por ciento de la muestra en masticación izquierda y el 75 por ciento en masticación derecha tenían desplazamiento condilar hacia el lado de no trabajo. No se encontró relación entre el desplazamiento del cóndilo con la situación de la mordida cruzada ni con la severidad de la misma...

[Oral premedication with clorazepate dipotassium. Comparison with oral premedication with flunitrazepam and intramuscular premedication with promethazine, pethidine and atropine in adults]. / Die orale Prämedikation mit Dikaliumclorazepat. Vergleich zur oralen Prämedikation mit Flunitrazepam und der intramuskulären Prämedikation mit Promethazin, Pethidin und Atropin beim Erwachsenen.

UNLABELLED: The purpose of premedication and the best form have been frequent subjects of controversy among anaesthetists in the past few years. Anxiolysis is now accepted as the main purpose. The preferred route of administration is by mouth. The intention of this study was to examine whether clorazepate dipotassium has the same sedative-hypnotic and anxiolytic effects as i.m. premedication with promethazine, pethidine and atropine. METHODS: A total of 100 patients aged 20-65 years and due to undergo arthroscopy took part in this study. Patients in group I were given 1 mg flunitrazepam p.o. on the evening before the operation and the i.m. premedication described above. The premedication for group II consisted in clorazepate dipotassium, 50 mg on the evening before operation and 25 mg on the morning of the day of the operation. The sedative-hypnotic effects were measured on a four-point scale. The Erlangen anxiety scale (EAS) and a visual analogue scale (VAS) were used to evaluate the anxiolytic effects according to the patient's own and the observer's evaluation of mood. In addition to this, we measured amnesia, heart rate and blood pressure. RESULTS: Clorazepate dipotassium or flunitrazepam p.o. significantly reduces anxiety 1 h after administration as measured by the EAS (P < 0.05) on the evening before the operation. This result was not, however, confirmed by the VAS for self-assessment. Patients who received premedication with clorazepate dipotassium are less anxious on the morning of the operation than patients given flunitrazepam the evening before the operation (P < 0.05); this, however, does not correspond to the VAS results. There were no differences in the other parameters compared. DISCUSSION: Oral premedication with clorazepate dipotassium has the same sedative-hypnotic, anxiolytic and amnestic effects as i.m. premedication with promethazine, pethidine and atropine. The results of this study are better than those obtained by Tolksdorf et al., owing to the higher dosage used in our study (50 mg as against 20 mg). Tolksdorf et al. [21] failed to show any improvement on a placebo. Our results correspond to those of Drautz et al. [2] who used 50 mg of clorazepate dipotassium on the evening before and 25 mg on the morning of the day of the operation.