RÉSUMÉ
Infection by Trypanosoma cruzi (Chagas disease [ChD]) affects around 7 million people in the Americas, most of whom are unaware of their status due to lack of clinical manifestations and poor access to diagnosis. Rapid diagnostic tests (RDTs) are widely used for screening for different infections (HIV, hepatitis B, and syphilis), and their application for ChD would facilitate access to diagnosis, especially in remote areas where health services have scarce resources. We conducted a prospective intervention study in 2018 to evaluate in the field two in vitro RDTs for ChD, authorized by the National Administration of Medicaments, Aliments, and Medical Technologies of Argentina (ANMAT), in areas of endemicity and nonendemicity in Argentina. We recruited 607 volunteers older than 18 years in Salta province and the city of Buenos Aires. The RDTs Ab Standard Diagnostics SD Bioline (SD) and Check Chagas Wiener Lab (WL) were performed in situ with whole-blood samples, and confirmatory serology was done at a reference center. The rate of infection with T. cruzi was 17.8% (108/607). The SD test showed 97.2% sensitivity (95% confidence interval [CI], 93.5 to 100) and 91.7% specificity (95% CI, 96.2 to 99.2%), and the WL test showed 93.4% sensitivity (95% CI, 88.2 to 98.6%) and 99.1% specificity (95% CI, 91.9 to 100%). The sensitivity and specificity for the two RDTs tested were higher than previously reported. These results encourage the use of the tested RDTs in Salta province and for further field studies for the implementation of these RDTs in other epidemiological scenarios. This will be very important to improve access to diagnosis of Chagas and its clinical management as a neglected disease, especially in remote areas with health access barriers.
Sujet(s)
Maladie de Chagas , Trypanosoma cruzi , Argentine/épidémiologie , Maladie de Chagas/diagnostic , Maladie de Chagas/épidémiologie , Tests diagnostiques courants , Humains , Études prospectives , Sensibilité et spécificitéRÉSUMÉ
CDK8 is a cyclin-dependent kinase that forms part of the mediator complex, and modulates the transcriptional output from distinct transcription factors involved in oncogenic control. Overexpression of CDK8 has been observed in various cancers, representing a potential target for developing novel CDK8 inhibitors in cancer therapeutics. In the course of our investigations to discover new CDK8 inhibitors, we designed and synthesized tricyclic pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives, by introduction of chemical complexity in the multi-kinase inhibitor Sorafenib taking into account the flexibility of the P-loop motif of CDK8 protein observed after analysis of structural information of co-crystallized CDK8 inhibitors. In vitro evaluation of the inhibitory activity of the prepared compounds against CDK8 led us to identify compound 2 as the most potent inhibitor of the series (IC50 = 8.25 nM). Co-crystal studies and the remarkable selectivity profile of compound 2 are presented. Compound 2 showed moderate reduction of phosphorylation of CDK8 substrate STAT1 in cells, in line with other reported Type II CDK8 inhibitors. We propose herein an alternative to find a potential therapeutic use for this chemical series.
Sujet(s)
Cyclin-Dependent Kinase 8/antagonistes et inhibiteurs , Oxazépines/pharmacologie , Inhibiteurs de protéines kinases/pharmacologie , Pyridines/pharmacologie , Sorafénib/analogues et dérivés , Sorafénib/pharmacologie , Lignée cellulaire tumorale , Conception de médicament , Humains , Structure moléculaire , Oxazépines/synthèse chimique , Inhibiteurs de protéines kinases/synthèse chimique , Pyridines/synthèse chimique , Relation structure-activitéRÉSUMÉ
No disponible
Sujet(s)
Humains , Mâle , Adulte d'âge moyen , Mycobacterium marinum/pathogénicité , Infections , Infections à mycobactéries non tuberculeuses/diagnostic , Infections à mycobactéries non tuberculeuses/physiopathologie , Rectocolite hémorragique/complications , Rectocolite hémorragique/traitement médicamenteux , Syndrome métabolique X , InfliximabRÉSUMÉ
No disponible
Sujet(s)
Humains , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Maladie de Crohn/traitement médicamenteux , Méthotrexate/effets indésirables , Pneumopathie infectieuse/induit chimiquement , Maladie de Crohn/complications , Lymphadénopathie/imagerie diagnostique , Pneumopathie infectieuse/diagnostic , Pneumopathie infectieuse/traitement médicamenteux , Thorax/imagerie diagnostique , Thorax/malformations , Granulome/complications , Granulome/imagerie diagnostiqueRÉSUMÉ
No disponible
Sujet(s)
Humains , Mâle , Femelle , Adolescent , Adulte d'âge moyen , Colite/diagnostic , Kystes/diagnostic , Hémorragie gastro-intestinale/étiologie , Muqueuse intestinale/anatomopathologie , Tumeurs du rectum/diagnostic , Diagnostic différentiel , Études de suiviRÉSUMÉ
La acromegalia es un síndrome clínico producido por la secreción excesiva de hormona del crecimiento. Conlleva una gran morbilidad y un aumento significativo de la mortalidad, principalmente por complicaciones cardiovasculares, respiratorias, así como un aumento en la prevalencia del cáncer. La mortalidad se equipara a la de la población general cuando se consigue la curación de la enfermedad, esto es, la normalización analítica de los valores de IGF-I (factor de crecimiento similar a la insulina tipo I) y hormona del crecimiento. No todos los tumores asociados a esta entidad son subsidiarios de programas coste-efectivos para su diagnóstico temprano. La mejor estrategia terapéutica y de seguimiento en estos pacientes es el conocimiento por el médico responsable de la morbimortalidad asociada a esta entidad, adelantándonos en muchos de los casos al curso evolutivo esperable
Acromegaly is a clinical syndrome caused by the excessive production of growth hormone. It is associated with high morbidity and significantly increased mortality, mainly due to cardiovascular and respiratory complications, and cancer. Mortality is reduced to that of the general population following successful treatment, in other words, when insulin-like growth factor (IGF-I) and growth hormone values return to normal levels. Not all tumours associated with this syndrome benefit from cost-effective early diagnosis programmes. An in-depth knowledge on the part of clinicians of the morbidity and mortality associated with acromegaly, allowing them in many cases to anticipate the expected clinical course of the disease, is the best therapeutic and follow-up strategy in these patients
Sujet(s)
Humains , Acromégalie/complications , Tumeurs/complications , Hormone de croissance/usage thérapeutique , Hormone de croissance/déficit , Tumeurs colorectales/épidémiologie , Tumeurs de l'appareil digestif/épidémiologieRÉSUMÉ
Acromegaly is a clinical syndrome caused by the excessive production of growth hormone. It is associated with high morbidity and significantly increased mortality, mainly due to cardiovascular and respiratory complications, and cancer. Mortality is reduced to that of the general population following successful treatment, in other words, when insulin-like growth factor (IGF-I) and growth hormone values return to normal levels. Not all tumours associated with this syndrome benefit from cost-effective early diagnosis programmes. An in-depth knowledge on the part of clinicians of the morbidity and mortality associated with acromegaly, allowing them in many cases to anticipate the expected clinical course of the disease, is the best therapeutic and follow-up strategy in these patients.
Sujet(s)
Acromégalie/complications , Tumeurs gastro-intestinales/étiologie , Acromégalie/diagnostic , Acromégalie/thérapie , Algorithmes , Gastroentérologie , HumainsSujet(s)
Colite/diagnostic , Tumeurs colorectales/diagnostic , Kystes/diagnostic , Erreurs de diagnostic , Adolescent , Colite/traitement médicamenteux , Colite/anatomopathologie , Colite/chirurgie , Rectocolite hémorragique/complications , Kystes/traitement médicamenteux , Kystes/anatomopathologie , Kystes/chirurgie , Femelle , Études de suivi , Hémorragie gastro-intestinale/étiologie , Humains , Immunosuppresseurs/usage thérapeutique , Mâle , Mésalazine/usage thérapeutique , Adulte d'âge moyen , Maladies du rectum/étiologie , Récidive , Procédures superfluesRÉSUMÉ
No disponible
Sujet(s)
Humains , Mâle , Adulte d'âge moyen , Épanchement pleural/diagnostic , Fistule pancréatique/diagnostic , Pancréatite chronique/complications , Dyspnée/étiologie , Maladies asymptomatiquesSujet(s)
Fistule pancréatique/complications , Pancréatite chronique/complications , Maladies de la plèvre/complications , Épanchement pleural/étiologie , Fistule de l'appareil respiratoire/complications , Maladies asymptomatiques , Calcinose/imagerie diagnostique , Calcinose/étiologie , Cholangiopancréatographie rétrograde endoscopique , Cholangiopancréatographie par résonance magnétique , Sténose pathologique , Humains , Mâle , Adulte d'âge moyen , Conduits pancréatiques/anatomopathologie , Conduits pancréatiques/chirurgie , Pseudokyste du pancréas/étiologie , Pancréatite chronique/imagerie diagnostique , Épanchement pleural/imagerie diagnostique , Endoprothèses , TomodensitométrieRÉSUMÉ
Polycystic liver disease (PLD) is a hereditary disease inherited by autosomal dominant trait that occurs as a frequent extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). We report a case of a 59-year-old woman diagnosed with ADPKD associated with PLD. End-stage chronic renal failure with a secondary Budd-Chiari syndrome developed during the patient's clinical course. She underwent combined liver and kidney transplantation, with a successful response over a 9-year follow-up period.
RÉSUMÉ
Inflammatory pseudotumor (IPT) of the liver is a rare benign tumor of unknown origin, it has the appearance of a malignant tumor but has a benign histology and clinical course. We report a case of a 63-year-old man diagnosed of IPT of the liver and followed for 10 years. During the clinical course, he developed a secondary Budd-Chiari syndrome, with a successful response to a transjugular intrahepatic portosystemic shunt over a 5-year follow-up period.
Sujet(s)
Syndrome de Budd-Chiari/étiologie , Granulome à plasmocytes/complications , Maladies du foie/complications , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Facteurs tempsRÉSUMÉ
El pseudotumor inflamatorio (PTI) hepático es una entidad rara, de origen desconocido y aunque puede tener apariencia maligna, su naturaleza es benigna. Presentamos el caso de un varón de 63 años diagnosticado de PTI hepático en seguimiento durante 10 años. En su evolución desarrolló un síndrome de Budd-Chiari, con buena respuesta tras la colocación de una derivación porto-sistémica transyugular, a los cinco años (AU)
Inflammatory pseudotumor (IPT) of the liver is a rare benign tumor of unknown origin, it has the appearance of a malignant tumor but has a benign histology and clinical course. We report a case of a 63-yearold man diagnosed of IPT of the liver and followed for 10 years. During the clinical course, he developed a secondary Budd-Chiari syndrome, with a successful response to a transjugular intrahepatic portosystemic shunt over a 5-year follow-up period (AU)
Sujet(s)
Humains , Mâle , Adulte d'âge moyen , Syndrome de Budd-Chiari/complications , Syndrome de Budd-Chiari/diagnostic , Cholangiocarcinome/complications , Cholangiocarcinome/diagnostic , Laparotomie/méthodes , Laparotomie , Biopsie/méthodes , Syndrome de Budd-Chiari/physiopathologie , Syndrome de Budd-Chiari/chirurgie , Syndrome de Budd-Chiari , Immunoglobulines/analyse , Immunoglobulines/isolement et purification , Imagerie par résonance magnétique/instrumentation , Imagerie par résonance magnétique/méthodesRÉSUMÉ
Primary sclerosing cholangitis is an infrequent extraintestinal manifestation of ulcerative colitis. Damage to bile ducts is irreversible and medical therapies to prevent progression of the disease are usually ineffective. We describe a patient with long-standing ulcerative colitis, which was refractory to corticosteroid therapy who developed primary sclerosing cholangitis (biochemical stage II/IV) in the course of his pancolitis. Treatment with infliximab (5 mg/kg as an induction dose followed by maintenance doses every two months) was indicated because of steroid-dependent disease associated to primary sclerosing cholangitis as well as sacroiliitis and uveitis and previous episode of severe azathioprine-related hepatic toxicity. At present, after two years of follow-up, the patient is asymptomatic with normal liver tests and complete resumption of daily life activities. This case draws attention to the usefulness of anti-tumor necrosis factor-alpha therapy for the management of primary sclerosing cholangitis as extraintestinal manifestation of inflammatory bowel disease.
Sujet(s)
Anticorps monoclonaux/usage thérapeutique , Angiocholite sclérosante/traitement médicamenteux , Rectocolite hémorragique/traitement médicamenteux , Résistance aux substances , Immunosuppresseurs/usage thérapeutique , Stéroïdes/usage thérapeutique , Sujet âgé , Angiocholite sclérosante/diagnostic , Angiocholite sclérosante/étiologie , Rectocolite hémorragique/complications , Rectocolite hémorragique/diagnostic , Humains , Infliximab , Mâle , Résultat thérapeutiqueSujet(s)
Anti-inflammatoires/effets indésirables , Anticorps monoclonaux/effets indésirables , Rectocolite hémorragique/traitement médicamenteux , Pneumocystis carinii , Pneumonie à Pneumocystis/induit chimiquement , Anti-inflammatoires/administration et posologie , Anticorps monoclonaux/administration et posologie , Humains , Infliximab , Perfusions veineuses , Mâle , Adulte d'âge moyen , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Similarities between human inflammatory bowel disease (IBD) and ruminant paratuberculosis have fueled a heated discussion on the role of Mycobacterium avium subsp. paratuberculosis (MAP) in the etiology of IBD. METHODS: In order to determine microbiological and immunological evidence of an association between MAP and IBD, blood from 222 inflammatory bowel disease patients and 80 healthy donors from the Basque Country (Spain) were subjected to nested PCR for MAP-specific insertion sequence IS900, interferon-gamma (IFN-gamma) release test with PPA-3 MAP antigen (IFNMAP) or phosphate-buffered saline (IFNPBS), and antibody ELISA with PPA-3 MAP antigen (ABMAP). RESULTS: Highly significant differences in the proportion of PCR-positive IBD patients (17%) and healthy controls (43%) as well as lower IFNMAP and higher ABMAP and IFNPBS responses were observed. Treatment was associated with decreases in IFNMAP and PCR-positive frequency. CONCLUSIONS: These results indicate the existence of immune responses and treatment interactions with MAP that strongly support an etiological role of this agent in IBD.
Sujet(s)
ADN bactérien/sang , Maladies inflammatoires intestinales/microbiologie , Interféron gamma/métabolisme , Mycobacterium avium ssp. paratuberculosis/immunologie , Paratuberculose , Adulte , Anticorps antibactériens/sang , Éléments transposables d'ADN , Test ELISA , Femelle , Humains , Maladies inflammatoires intestinales/complications , Maladies inflammatoires intestinales/immunologie , Mâle , Adulte d'âge moyen , Mycobacterium avium ssp. paratuberculosis/génétique , Mycobacterium avium ssp. paratuberculosis/isolement et purification , Paratuberculose/complications , Paratuberculose/immunologie , Paratuberculose/microbiologie , Réaction de polymérisation en chaîne/méthodes , EspagneRÉSUMÉ
BACKGROUND: Mycobacteria, such as M. leprae and M. tuberculosis infect billions of humans. However, because of appropriate immune responses and antibiotic therapy, overt mycobacterial diseases occur far less frequently. M. avium subspecies paratuberculosis (MAP) causes Johne's disease in ruminants, an affliction evocative of inflammatory bowel disease (IBD). Several agents used to treat IBD (5-ASA, methotrexate, azathioprine and its metabolite 6-MP) have recently been shown to be antiMAP antibiotics. We herein evaluate the prevalence of MAP DNA in healthy individuals and compare them with IBD patients on antiMAP antibiotics. METHODS: We studied 100 healthy individuals (90 blood donors) and 246 patients with IBD. IS900 MAP DNA was identified using a nested primer PCR in the buffy coat of blood. Positive signal was confirmed as MAP by DNA sequence analysis. PCR positive results frequencies were compared according to medications used. Significance was accepted at p<0.05. RESULTS: 47% (47/100) healthy controls and 16% (40/246) IBD patients were IS900 positive (p<0.0001). MAP DNA was identified in 17% of 143 patients receiving mesalamine and 6% of 16 receiving sulfasalazine. None of the IBD patients receiving methotrexate (n = 9), 6-MP (n = 3), ciprofloxacin (n = 5) or Tacrolimus (n = 3) had MAP DNA detectable in their blood. DISCUSSION: We found a disquietingly large percentage of healthy individuals have MAP DNA in their blood, the significance of which remains to be determined. Counter-intuitively, the incidence of MAP DNA was significantly lower in patients with IBD. Agents with the most potent in vitro antiMAP activity were associated with clearance of blood MAP DNA. We posit that the use antiMAP antibiotics was responsible for the decreased prevalence of MAP DNA in patients with IBD.