Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.

BACKGROUND: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. METHODS/DESIGN: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. DISCUSSION: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02105714 .

MR imaging of intracranial hemangiopericytomas.

OBJECTIVE: To describe the MR features of primary intracranial hemangiopericytomas (HPCs) on conventional imaging, diffusion and MR spectroscopy and aim to determinate distinguishing features from meningiomas. METHODS: From 2006 to 2012, seven patients with pathologically confirmed primary intracranial HPCs were included. The clinical data, conventional MR findings (n=7), DWI features (n=7) and MR spectroscopy (n=5) were retrospectively analyzed. ADC values of the HPCs (n=7) were measured on ADC map and were compared with that of contralateral normal white matter. RESULTS: Of the seven HPCs, four were anaplastic HPCs (WHO grade III) and three were HPCs (WHO grade II). MR pattern consisted in lobulated or irregular margin tumors in all cases with cross-leaf growth on both side of the falx in two cases. The lesions showed mainly iso signal (n=4) on T1 WI and heterogeneous high signal (n=5) on T2 WI. Heterogenity was mainly related to intra tumoral hemorrhage (n=4), and proeminent intratumoral flow voids (n=3). Marked heterogeneous enhancement (n=5) with dural tail (n=4) was noted. All tumours showed significant peritumoral edema. ADC values of the tumor tissue component range between 0.638 and 1.50×10(-3)mm/s(2) (average = 1,02). Three grade II HPCs showed higher values compared to normal parenchyma ADC (range between 0.772 and 0.930×10(-3)mm/s(2) with average of 0.830), whereas grade III HPCs showed either equal (three cases) or decreased ADC values (one case). MRS showed in all cases markedly increased Cho with lip/lac peak, decreased Cr and almost absent NAA. High mI peak with large glutamine/glutamate were noted in the three grade II HPCs. CONCLUSION: Conventional MR pattern when combined with DWI and MRS findings are highly suggestive of HPC and appear valuable data to differentiate HPCs from meningiomas.

Clinical and molecular characterization of a combined 17p13.3 microdeletion with partial monosomy 21q21.3 in a 26-year-old man.

We led a clinical and molecular characterization of a patient with mild mental delay and dysmorphic features initially referred for cytogenetic exploration of an azoospermia. We employed FISH and array CGH techniques for a better definition and refinement of a double chromosome aberration associating a 17p microdeletion with partial monosomy 21q due to 1:3 meiotic segregation of a maternal reciprocal translocation t(17;21)(p13.3;q21.2) revealed after banding analysis. Brain MRI depicted partial callosal and mild diffuse cerebral atrophies, but without expected signs of lissencephaly. The patient's karyotype formula was: 45,XY,der(17)t(17;21)(p13.3;q21.2)mat,-21. FISH study confirmed these rearrangements and array CGH analysis estimated the loss sizes to at least 635 kb on chromosome 17 and to 15.6 Mb on chromosome 21. The absence of lissencephaly and major brain malformations often associated with 17p terminal deletions could be attributed to the retention of PAFAH1B1, YWHAE and CRK genes. Dysmorphic features, moderate mental impairment and minor brain malformations could result from the 21q monosomy and particularly the partial deletion of the APP-SOD1 region. Azoospermia should result from gamete apoptosis induced by a control mechanism triggered in response to chromosome imbalances. Our study provides an additional case for better understanding and delineating both 17p and 21q deletions.

[CT imaging features of pulmonary involvement in connective tissue disorders]. / Sémiologie tomodensitométrique de l'atteinte pulmonaire des connectivites.

Connective tissue disorders correspond to a heterogeneous group of inflammatory diseases characterized by abnormal immune system activity leading to connective tissue alterations in multiple parts of the body. In adults, connective tissue disorders include rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, systemic lupus erythematosus, dermatomyositis and polymyositis, ankylosing spondylitis, and mixed connective tissue disease. Broncho-pulmonary involvement may be variable with involvement of all anatomical components of the lung. Involvement of other intrathoracic structures (pleura, respiratory muscles, heart, rib cage) is frequent. The most specific manifestations include interstitial lung diseases and pulmonary hypertension. During follow-up, progressive respiratory diseases may occur due to the treatment, infections, pulmonary embolism or neoplasms.

Effect of Prefrontal Cortex Stimulation on Regulation of Amygdala Response to Threat in Individuals With Trait Anxiety: A Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) is under clinical investigation as a treatment for major depressive disorder. However, the mechanisms of action are unclear, and there is a lack of neuroimaging evidence, particularly among individuals with affective dysfunction. Furthermore, there is no direct causal evidence among humans that the prefrontal-amygdala circuit functions as described in animal models (ie, that increasing activity in prefrontal cortical control regions inhibits amygdala response to threat). Objective: To determine whether stimulation of the prefrontal cortex reduces amygdala threat reactivity in individuals with trait anxiety. Design, Setting, and Participants: This community-based randomized clinical trial used a double-blind, within-participants design (2 imaging sessions per participant). Eighteen women with high trait anxiety (age range, 18-42 years) who scored greater than 45 on the trait measure of State-Trait Anxiety Inventory were randomized to receive active or sham tDCS of the DLPFC during the first session and the other intervention during the next session. Each intervention was followed immediately by a functional imaging scan during which participants performed an attentional task requiring them to ignore threatening face distractors. Data were collected from May 7 to October 6, 2015. Main Outcomes and Measures: Amygdala threat response, measured with functional magnetic resonance imaging. Results: Data from 16 female participants (mean age, 23 years; range, 18-42 years), with 8 in each group, were analyzed. Compared with sham stimulation, active DLPFC stimulation significantly reduced bilateral amygdala threat reactivity (z = 3.30, P = .04) and simultaneously increased activity in cortical regions associated with attentional control (z = 3.28, P < .001). In confirmatory behavioral analyses, there was a mean improvement in task accuracy of 12.2% (95% CI, 0.30%-24.0%; mean [SD] difference in number of correct answers, 2.2 [4.5]; t15 = 1.94, P = .04) after active DLPFC stimulation. Conclusions and Relevance: These results reveal a causal role for prefrontal regulation of amygdala function in attentional capture by threat in individuals with high trait anxiety. The finding that prefrontal stimulation acutely increases attentional control signals and reduces amygdala threat reactivity may indicate a neurocognitive mechanism that could contribute to tDCS treatment effects in affective disorders. Trial Registration: isrctn.org Identifier: ISRCTN78638425.

Prevalence of Giardia intestinalis Infection in Schistosomiasis-Endemic Areas in South-Central Mali.

Intestinal parasite infections are frequent causes of diarrhea and malnutrition among children in the tropics. Transmission of helminths and intestinal protozoa is intimately connected with conditions of poverty, including inadequate sanitation and hygiene. Concurrent infections with several intestinal pathogens may lead to excess morbidity. Yet, there is a paucity of epidemiological data from Mali. In this study, stool samples from 56 individuals, aged 2-63 years, from Bamako and Niono, south-central Mali were examined for intestinal parasites using stool microscopy. Additionally, stool samples were subjected to a rapid diagnostic test (RDT) and polymerase chain reaction (PCR) for the detection of Cryptosporidium spp. and Giardia intestinalis. The predominant pathogens were Schistosoma mansoni and G. intestinalis with prevalences of 41% and 38%, respectively. Hymenolepis nana was detected in 4% of the participants, while no eggs of soil-transmitted helminths were found. Concurrent infections with G. intestinalis and S. mansoni were diagnosed in 16% of the participants. For the detection of G. intestinalis, PCR was more sensitive (100%) than RDT (62%) and microscopy (48%). As helminth-protozoa coinfections might have important implications for morbidity control programs, future studies should employ diagnostic tools beyond stool microscopy to accurately assess the co-endemicity of giardiasis and schistosomiasis.

Life-threatening subglottic hemangioma in an infant successfully treated with propranolol.

Subglottic hemangioma is a rare benign tumor in children. It causes an obstruction of the upper airway and can be life-threatening. Several therapeutic options have been used in the literature, including surgery. Currently, the treatment is essentially based on propranolol. We report the case of a 2-month-old female infant hospitalized for severe obstructive dyspnea secondary to a subglottic hemangioma. Diagnosis was confirmed by laryngoscopy and magnetic resonance imaging. The child underwent a tracheotomy and was treated with propranolol. The progression was favorable with regression of the subglottic hemangioma and improvement of laryngotracheal airway obstruction.

HIV type 1 pol gene diversity and antiretroviral drug resistance mutations in the Democratic Republic of Congo (DRC).

To study recombination and the natural polymorphism in pol of HIV-1 strains in the Democratic Republic of Congo (DRC) we sequenced the protease and RT genes for 70 HIV-1 strains previously characterized in the env V3-V5 region from a sentinel surveillance study in 2002. For 41 of the 70 (58.6%) strains, the same subtype/ CRF designations were observed in pol and env. Twenty-three (32.9%) of 70 pol sequences were complex recombinants involving two to five subtypes as well as fragments that could not be classified into any of the known subtypes. All subtypes were involved in recombination events. Unclassified (U) and env subtype H strains were very likely to be recombinant strains. Overall, many minor mutations were identified in the protease sequences. Although at the time of our study ARV use was not yet widespread in DRC, three strains were identified with one major mutation associated with drug resistance: L90M and M46L in protease and K103N in RT.

Measurement of tetanus antitoxin in oral fluid: a tool to conduct serosurveys.

BACKGROUND: Serosurveys that measure tetanus antitoxin can complement immunization coverage surveys to allow evaluation of immunization services in developing countries. Measurement of IgG tetanus antitoxin in oral fluid was investigated as a practical and noninvasive alternative to and correlate of serum antibodies. METHODS: Serum and oral fluid were collected from Malian infants, toddlers and adults (males without a history of tetanus vaccination). Specific IgG tetanus antitoxin was measured by enzyme-linked immunosorbent assay in serum (S-ELISA) and oral fluid (OF-ELISA). RESULTS: One hundred forty-two pairs of serum and oral fluid samples were collected from infants, 35 pairs from toddlers and 35 pairs from adults. IgG tetanus antitoxin titers measured by OF-ELISA were 100-fold lower than those measured by S-ELISA but they correlated strongly (r = 0.90, P < 0.001). All 35 toddlers who had received 2 or 3 doses of diphtheria-tetanus-pertussis (DTP) vaccine (100%) had serum tetanus antitoxin levels >or=0.15 IU/mL and 28 of 35 (80%) had oral fluid values >or=0.0015 IU/mL. Among adults lacking a history of tetanus immunization, only 6 of 35 (17.1%) had serum titers >or=0.15 IU/mL and 4 of 35 (11%) had oral fluid titers >or=0.0015 IU/mL in oral fluid. CONCLUSIONS: IgG tetanus antitoxin in oral fluid correlates well with levels in serum. OF-ELISA values >or=0.0015 IU/mL constitute protection against tetanus and in subjects >12 months of age imply multiple prior contacts with immunization services. IgG tetanus antitoxin measured by OF-ELISA provides a logistically practical alternative for performing seroprevalence surveys.

MGMT methylation assessment in glioblastoma: MS-MLPA versus human methylation 450K beadchip array and immunohistochemistry.

PURPOSE: The MGMT gene encodes a DNA repair enzyme that counteracts with chemotherapy efficiency, specifically with alkylating agents such as temozolomide (TMZ). It is well established that MGMT methylation should be screened as a predictive marker for TMZ in glioblastoma, and we thus aimed to determine a reliable and practical diagnostic method of MGMT methylation detection. PATIENTS AND METHODS: 55 glioblastomas were investigated for MGMT methylation status using methylation-specific multiplexed ligation probe amplification (MS-MLPA), illumina human methylation 450K BeadChip array (HM450 K) analysis, and compared to MGMT protein expression by immunohistochemistry (IHC) staining. The methylation status of promoter, intron and all MGMT CpG targeted sites were separately correlated to patient's survival. RESULTS: In addition to MS-MLPA and 450 K concordance, our results showed significantly higher overall survival (OS) of patients receiving TMZ and presenting MGMT methylated promoter (mean OS = 21.5 months, p = 0.046). Including all glioblastoma cases and regardless of chemotherapy, MS-MLPA showed significant survival difference between MGMT methylated and unmethylated cases (mean OS = 13, p = 0.021). CONCLUSION: We concluded that in glioblastoma, MGMT promoter methylation predicts TMZ sensitivity. This current comparative analysis leads to consider that MS-MLPA is a valuable as HM450 K array for MGMT methylation status screening.

Adult recurrent pilocytic astrocytoma: Clinical, histopathological and molecular study.

BACKGROUND: PA is a grade I glial tumor that mostly occurs in children. However, although apparently similar to paediatric PA, adult PA presents a different clinical follow-up that could arise from specific molecular alterations. A variety of genetic alterations have been identified as diagnostic or prognostic glioma molecular markers. MATERIAL AND METHODS: We describe a right infratentorial tumor that occurred in a 58-year-old man. Neuroimaging and neuropathological examination suggested PA as an initial diagnosis. The tumor was completely resected. Unexpectedly, two years later, a rapidly growing tumor on the operative site was observed with a second location in the pineal region. Immunohistochemical reactions (IHC), Multiplex ligation probe amplification (MLPA) and fluorescence in situ hybridization (FISH) was performed in both primary and relapse tumor. RESULTS: Neuroimaging and neuropathological examinations suggested an unusual diagnosis for adult patients: a recurrent PA. Both MLPA and FISH analysis contribute to diagnostic confirmation by KIAA1549: BRAF fusion detection. Additional genetic results revealed interesting findings that justified the tumor aggressivity. CONCLUSION: Molecular analysis of adult PA cases should be routinely combined with histopathological and neuroimaging examination to further refine prognostic diagnoses.

Evidence of stable HIV seroprevalences in selected populations in the Democratic Republic of the Congo.

OBJECTIVE: To determine current data on HIV infection and to document changes and trends of HIV seroprevalence in selected populations over time in the Democratic Republic of the Congo (DRC; former Zaïre). METHODS: In February 1997, a large serosurvey was conducted on selected population groups from Kinshasa (capital city), Mbuji-May (southeast) and Bwamanda (northwest). Samples obtained from pregnant women, tuberculosis patients, commercial sex workers, blood donors and sexually transmitted disease patients were screened for the presence of HIV antibodies by a rapid assay and a commercial enzyme-linked immunosorbent assay. All reactive specimens were confirmed and discriminated by a line immunoassay, and were further tested for the presence of HIV-1 group O antibodies. Our results were compared to data reported in previous studies in Kinshasa. RESULTS: Of a total 1970 samples collected, 219 (11.1%) were HIV-1-reactive and seven (0.3%) were dually reactive to HIV-1 and HIV-2. No case of HIV-1 group O or HIV-2 infection was diagnosed. HIV seroprevalence in pregnant women was 3.1% (16 out of 511), 6.3% (19 out of 300) and 1.5% (one out of 65) in Kinshasa, Mbuji-Mayi, and Bwamanda, respectively. HIV seroprevalence in tuberculosis patients was 26% (52 out of 200), 28% (17 out of 60), and 35.3% (29 out of 83), respectively. HIV seroprevalence among blood donors was 3.1% in Kinshasa and 2.8% in Mbuji-Mayi. Compared with data from previous studies performed in Kinshasa, no substantial change in HIV infection rates was observed among the selected population groups. CONCLUSIONS: Our results show that HIV prevalence rates have remained relatively unchanged in selected populations despite the political instability and poor environment observed since 1991 in DRC. It also shows the presence, still at very low rate, of dual HIV-1/HIV-2 seropositivity and a growing problem of HIV infection in rural areas. In contrast to other Central African countries, no HIV-1 group O infections were detected in DRC.

Juvenile hyaline fibromatosis: a case report.

Juvenile hyaline fibromatosis is a rare, hereditary disease with distinct clinical and histopathological features. Clinically, it presents with gingival hypertrophy, pappulonodular skin lesions and joint contractures. Bone involvement is usually an uncommon finding. We report a case of a 2-year-old patient, daughter of consanguineous parents, who presented since the age of 2 months with impairment of mental development, multiple joint contractures, motion limitation and nodules on the scalp. The calvarian lesions were surgically removed, and histopathological examination concluded to juvenile hyaline fibromatosis.