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1.
Neuropathology ; 2024 May 12.
Article in English | MEDLINE | ID: mdl-38736183

ABSTRACT

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity. Among the patients, 66.7% were MBSHH, 13.0% MBWNT, 7.3% MBGrp3, and 13.0% MBGrp4. Among the 63 variants found, 54% were classified as Tier I/II and 31.7% as oncogenic/likely oncogenic. We observed 33.3% of cases harboring at least one mutation. TP53 (23.2%, 16/69) was the most mutated gene, followed by PIK3CA (5.8%, 4/69), KIT (4.3%, 3/69), PDGFRA (2.9%, 2/69), EGFR (1.4%, 1/69), ERBB2 (1.4%, 1/69), and NRAS (1.4%, 1/69). Approximately 41% of MBSHH tumors exhibited mutations, TP53 (32.6%) being the most frequently mutated gene. Tier I/II and oncogenic/likely oncogenic TP53 variants were associated with relapse, progression, and lower survival rates. Potentially actionable variants in the PIK3CA and KIT genes were identified. Latin-Iberian medulloblastomas, particularly the MBSHH, exhibit higher mutation frequencies than other populations. We corroborate the TP53 mutation status as an important prognostic factor, while PIK3CA and KIT are potential therapeutic targets.

2.
Front Oncol ; 13: 1237170, 2023.
Article in English | MEDLINE | ID: mdl-37746264

ABSTRACT

Purpose: Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%-90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics. Methods: A total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively. Results: WNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants. Conclusion: We observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.

3.
Surg Neurol Int ; 14: 230, 2023.
Article in English | MEDLINE | ID: mdl-37560559

ABSTRACT

Background: Meningiomas are slow-growing neoplasms, accounting for 20% of all primary intracranial neoplasms and 25% of all intraspinal tumors. Atypical and anaplastic meningiomas are infrequent, representing fewer than 5% of all meningiomas. Unusually, they can show aggressive behavior, and extracranial metastases are extremely rare, representing approximately 0.1% of all reported cases. Case Description: Fifty-six-year-old male patient diagnosed with atypical basal frontal meningioma with multiple resections, both endoscopic endonasal and transcranial. After hypofractionated radiosurgery, the patient showed new tumor recurrence associated to right cervical level II ganglionic metastasis. We opted for complete resection of the meningioma and reconstruction with anterior rectus abdominis muscle flap, as well as selective cervical ganglionectomy. Anatomical pathology showed neoplastic proliferation of meningothelial cells in syncytial cytoplasm, oval or spherical nuclei with slight anisocariosis and hyperchromasia, and intranuclear vacuoles, all compatible with anaplastic meningioma. Conclusion: Due to a lack of consensus on how to treat a metastatic malignant meningioma, this pathology requires a multidisciplinary approach, and treatment needs to be adapted to each particular case. Complete resection of the lesion is the primary goal, and this requires complex procedures involving endocranial as well as extracranial surgeries, which result in composite defects difficult to resolve. Microvascular free flaps are considered the gold standard in reconstructions of large skull base defects, with high success rates and few complications.

4.
Neurologist ; 28(4): 270-272, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-36728655

ABSTRACT

INTRODUCTION: Cerebral vasculitides are often devastating conditions that require immediate diagnosis and treatment. CASE REPORT: We report a pathologically proven clinical case of primary central nervous system vasculitis in a 50-year-old man with a diagnosis of relapsing-remitting multiple sclerosis after alemtuzumab therapy, which required additional immunosuppression to control this life-threatening condition. CONCLUSION: In patients presenting subacute neurological deterioration after alemtuzumab therapy, primary central nervous system vasculitis should be considered as a differential diagnosis among other autoimmune conditions.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Male , Humans , Middle Aged , Alemtuzumab/adverse effects , Multiple Sclerosis/diagnosis , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Diagnosis, Differential , Immunosuppression Therapy
5.
J Neurooncol ; 157(1): 27-35, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35166989

ABSTRACT

PURPOSE: Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. METHODS: It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training (n = 50) and validation (n = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN. nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. RESULTS: The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ([Formula: see text] + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. CONCLUSION: We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.


Subject(s)
Brain Neoplasms , Cerebellar Neoplasms , Medulloblastoma , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Brazil , Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/pathology , Child , Humans , Medulloblastoma/genetics , Medulloblastoma/pathology , N-Myc Proto-Oncogene Protein/genetics
7.
Eur J Med Genet ; 62(11): 103571, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30414531

ABSTRACT

Malformations of cortical development are a frequent cause of drug-resistant Epilepsy and developmental delay. Hemimegalencephaly is a Malformation of cortical development characterized by enlargement of all or a part of one cerebral hemisphere. Germline and somatic mutation in genes belonging to the Mammalian Target of Rapamycin (mTOR) pathway has been identified in patients suffering from epilepsy secondary to Hemimegalencephaly and focal cortical dysplasia. We present here a patient suffering from severe neonatal Epilepsy since 3 h of life secondary to Hemimegalencephaly, requiring an anatomic hemispherectomy surgical procedure for seizure control, where by means of next-generation sequencing at an ultra-high depth coverage, we were able to identify a novel somatic mutation in the RHEB gene (NM_005614: c.119A > T: p. Glu40Val). The histopathological diagnosis was Cortical Dysplasia type IIB determined by the presence of dysmorphic neurons of variable size with nuclear alteration and balloon cells in the context of Hemimegalencephaly, which are similar to that have been demonstrated in hyperactivating RHEB models. This is the first report of a somatic mutation in RHEB gene in a patient suffering from Epilepsy secondary to Hemimegalencephaly. It highlights different current topics in the fields of genetics of Malformations of cortical development: a-somatic mosaicism is not uncommon in these neurodevelopmental disorders; b-the molecular diagnostic approach should involve the use of state-of-the-art methods and the sampling of different tissues; c-new findings might facilitate therapeutics discoveries while providing an improved understanding of normal brain development.


Subject(s)
Drug Resistant Epilepsy/genetics , Hemimegalencephaly/genetics , Malformations of Cortical Development/genetics , Ras Homolog Enriched in Brain Protein/genetics , Drug Resistant Epilepsy/pathology , Female , Hemimegalencephaly/pathology , High-Throughput Nucleotide Sequencing , Humans , Infant, Newborn , Malformations of Cortical Development/pathology , Mutation , TOR Serine-Threonine Kinases/genetics
8.
Rev. argent. reumatol ; 29(4): 30-34, dic. 2018. graf, tab
Article in Spanish | LILACS | ID: biblio-1003294

ABSTRACT

El objetivo de este estudio fue evaluar la utilidad de la rebiopsia renal en pacientes con glomerulonefritis ANCA en la toma de decisiones. Se incluyeron en forma retrospectiva todos los pacientes con glomerulonefritis ANCA diagnosticados por biopsia renal entre enero de 2002 y mayo de 2017. Se revisó la histología de las rebiopsias y fue correlacionada con los hallazgos clínicos (hematuria, proteinuria y caída del filtrado) y resultados histológicos de la primera y segunda biopsia. Sesenta pacientes (77% mujeres) fueron incluidos. De ellos, 15 (25%) fueron sometidos a una rebiopsia durante el seguimiento. La media de tiempo hasta la rebiopsia fue de 38,4 meses (DS 20,4). En el grupo de rebiopsia, la presencia de hematuria, proteinuria y caída del filtrado glomerular se observó en el 73%, 73% y 60% de pacientes, respectivamente. No encontramos una correlación entre las lesiones activas (semilunas, necrosis) con la presencia de hematuria o caída del filtrado glomerular. En un gran porcentaje, la histología renal mostró progresión en términos de cronicidad y con menor frecuencia lesiones de actividad. A pesar de esto, en el 67% de los pacientes se realizó un cambio de tratamiento, iniciando una nueva terapia de inducción, alcanzando una respuesta renal en el 85% de los casos.


The aim of this study was to evaluate usefulness of renal re-biopsy in patients with ANCA glomerulonephritis in treatment decisions. We included retrospectively all patients with biopsy-proven ANCA glomerulonephritis between January 2002 and May 2017. We analysed patient's baseline characteristics at the time of re-biopsy, presence of microscopic hematuria, proteinuria and/or decline in glomerular filtration rate (GFR) and time to renal relapse/rebiopsy. Data of physicians' decisions after rebiopsy was collected. 60 patients (77% females) were included. Of those, 15 (25%) underwent renal re-biopsy during the follow up based on clinical manifestations. Mean time until re-biopsy was 38.4 months (SD 20.4). In the re-biopsy group, 73% of patients had new onset hematuria, 73% had new onset or worsening proteinuria (40% and 33% respectably), and 60% had decline in the GFR. When analysing histological changes in the repeat biopsy we didn't find a correlation between active lesions (crescents, necrosis etc.) and hematuria. All patients that underwent repeat biopsy were considered to be active but renal histology showed progression in terms of chronicity and rare active histological lesions. Despite this, in 67% of patients, physicians made a treatment change, initiating a new induction therapy regimen and achieving renal response in 85% of patients.


Subject(s)
Vasculitis , Biopsy , Glomerulonephritis
9.
Medicina (B Aires) ; 78(3): 199-202, 2018.
Article in Spanish | MEDLINE | ID: mdl-29940548

ABSTRACT

Paracoccidioidomycosis is endemic in subtropical rainforests of Latin America. Acute/subacute presentations involve an aggressive dissemination throughout the lymphatic system, while chronic forms (more frequent) arise as differential diagnosis for other conditions involving lung, oropharynx, skin, and eventually the brain. We present the case of a man referred for evaluation and treatment of a possible lung tumor with brain metastasis. The finding of multibudded yeasts and the microbiological isolation of a dimorphic fungus identified as Paracoccidioides sp. from a brain biopsy prompted a cardinal change in prognosis and treatment. This case alerts on the importance of considering systemic fungal diseases as differential diagnosis of compatible clinical presentations in patients who had lived in, or visited, endemic areas.


Subject(s)
Brain Neoplasms/diagnosis , Lung Neoplasms/diagnosis , Paracoccidioidomycosis/diagnosis , Biopsy , Diagnosis, Differential , Humans , Immunocompetence , Male , Middle Aged , Tomography, X-Ray Computed
10.
Medicina (B Aires) ; 78(3): 194-196, 2018.
Article in Spanish | MEDLINE | ID: mdl-29940546

ABSTRACT

IgG4-related disease (IgG4-RD) is a recently described systemic entity of unknown origin. It predominantly affects older men and has distinctive histopathologic features as storiform fibrosis, obliterative phlebitis, dense lymphoplasmacytic infiltrate with immunostaining for IgG4, and it may be associated with elevated serum levels of IgG4. Although any organ can be affected, pituitary gland is rarely involved. We describe the case of a 36-year-old man who presented with headaches, impaired vision, panhypopituitarism with diabetes insipidus and an infiltrative lesion mainly of infundibulum and pituitary. We arrived at diagnosis of IgG4-RD by pituitary biopsy. A successful response to treatment with immunosuppressive doses of corticosteroids was achieved.


Subject(s)
Hypopituitarism/etiology , Immunoglobulin G4-Related Disease/complications , Scotoma/etiology , Adult , Biopsy , Humans , Hypopituitarism/diagnosis , Immunoglobulin G4-Related Disease/diagnosis , Magnetic Resonance Imaging , Male , Scotoma/diagnosis
11.
Medicina (B.Aires) ; 78(3): 194-196, jun. 2018. ilus
Article in Spanish | LILACS | ID: biblio-954976

ABSTRACT

La enfermedad relacionada a IgG4 (IgG4-RD) constituye una entidad sistémica recientemente descrita, de causa desconocida. Afecta predominantemente a hombres mayores y presenta características histopatológicas distintivas, como fibrosis estoriforme, flebitis obliterante y denso infiltrado linfoplasmocitario con inmunomarcación para IgG4, pudiendo estar asociada a elevación sérica de dicha inmunoglobulina. Si bien cualquier órgano puede estar afectado, el compromiso de la hipófisis es infrecuente. Describimos el caso de un hombre de 36 años que se presentó con cefaleas, alteración del campo visual, panhipopituitarismo, diabetes insípida y una imagen que mostraba una lesión infiltrativa infundíbulo-panhipofisaria extendida. Arribamos al diagnóstico de IgG4-RD a través de biopsia hipofisaria. La respuesta al tratamiento con dosis inmunosupresoras de corticoides fue exitosa.


IgG4-related disease (IgG4-RD) is a recently described systemic entity of unknown origin. It predominantly affects older men and has distinctive histopathologic features as storiform fibrosis, obliterative phlebitis, dense lymphoplasmacytic infiltrate with immunostaining for IgG4, and it may be associated with elevated serum levels of IgG4. Although any organ can be affected, pituitary gland is rarely involved. We describe the case of a 36-year-old man who presented with headaches, impaired vision, panhypopituitarism with diabetes insipidus and an infiltrative lesion mainly of infundibulum and pituitary. We arrived at diagnosis of IgG4-RD by pituitary biopsy. A successful response to treatment with immunosuppressive doses of corticosteroids was achieved.


Subject(s)
Humans , Male , Adult , Scotoma/etiology , Immunoglobulin G4-Related Disease/complications , Hypopituitarism/etiology , Scotoma/diagnosis , Biopsy , Magnetic Resonance Imaging , Immunoglobulin G4-Related Disease/diagnosis , Hypopituitarism/diagnosis
13.
Medicina (B Aires) ; 77(3): 242-244, 2017.
Article in Spanish | MEDLINE | ID: mdl-28643686

ABSTRACT

Hypertrophic pachymeningitis is an infrequent disorder. It can be idiopathic or secondary to infectious, autoimmune or neoplastic disease. The recently described 〈IgG4-related disease〉 could be the origin of many cases considered cryptogenic. We present the case of a 60-year-old man, with a history of headache and episcleritis in both eyes, with partial response to corticoid therapy. The brain MR study with gadolinium showed enhancement and thickening of the dura mater, extending from lateral wall of left temporal and occipital lobes to ipsilateral tentorium. Meningeal biopsy showed fibrosis and lymphoplasmacytic infiltrate, with more than 10 IgG4+ plasma cells per high power field. After treatment with rituximab there was clinical improvement accompanied by the virtual disappearance of the alterations detected in neuroimaging. Hypertrophic pachymeningitis as a manifestation of IgG4-related disease can be based on MRI findings if plasma IgG4 are elevated.


Subject(s)
Autoimmune Diseases of the Nervous System/diagnosis , Autoimmune Diseases of the Nervous System/etiology , Immunoglobulin G , Meningitis/diagnosis , Meningitis/etiology , Biopsy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Tomography, X-Ray Computed
14.
Medicina (B.Aires) ; 77(3): 242-244, jun. 2017. ilus
Article in Spanish | LILACS | ID: biblio-894467

ABSTRACT

La paquimeningitis hipertrófica es una enfermedad infrecuente. Puede ser idiopática, secundaria a infección o enfermedad oncológica. Recientemente se la describió asociada a la enfermedad por IgG4, pudiendo ser esta la causa de muchas clasificadas como idiopáticas. Se presenta el caso de un hombre de 60 años de edad con historia de cefalea y epiescleritis, con respuesta parcial a corticoides. La resonancia magnética con contraste evidenciaba refuerzo meníngeo a nivel temporal y occipital izquierdo con extensión a la tienda del cerebelo. La biopsia meníngea demostró fibrosis e infiltrado linfoplasmocitario con más de 10 células plasmáticas IgG4 positivas por campo de gran aumento. El tratamiento con rituximab provocó mejoría clínica y radiológica. La paquimeningitis hipertrófica es una manifestación de la enfermedad por IgG4 y debe ser sospechada con la resonancia magnética y niveles plasmáticos altos de IgG4.


Hypertrophic pachymeningitis is an infrequent disorder. It can be idiopathic or secondary to infectious, autoimmune or neoplastic disease. The recently described ‹IgG4-related disease› could be the origin of many cases considered cryptogenic. We present the case of a 60-year-old man, with a history of headache and episcleritis in both eyes, with partial response to corticoid therapy. The brain MR study with gadolinium showed enhancement and thickening of the dura mater, extending from lateral wall of left temporal and occipital lobes to ipsilateral tentorium. Meningeal biopsy showed fibrosis and lymphoplasmacytic infiltrate, with more than 10 IgG4+ plasma cells per high power field. After treatment with rituximab there was clinical improvement accompanied by the virtual disappearance of the alterations detected in neuroimaging. Hypertrophic pachymeningitis as a manifestation of IgG4-related disease can be based on MRI findings if plasma IgG4 are elevated.


Subject(s)
Humans , Male , Middle Aged , Immunoglobulin G , Autoimmune Diseases of the Nervous System/diagnosis , Autoimmune Diseases of the Nervous System/etiology , Meningitis/diagnosis , Meningitis/etiology , Biopsy , Magnetic Resonance Imaging , Tomography, X-Ray Computed
15.
Clin Exp Rheumatol ; 35 Suppl 103(1): 55-58, 2017.
Article in English | MEDLINE | ID: mdl-28229825

ABSTRACT

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN. METHODS: We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded. RESULTS: Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036). CONCLUSIONS: In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Complement System Proteins/analysis , Glomerulonephritis/immunology , Immunoglobulin G/analysis , Kidney Glomerulus/immunology , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/physiopathology , Argentina/epidemiology , Biomarkers/blood , Biopsy , Creatinine/blood , Female , Fluorescent Antibody Technique , Glomerular Filtration Rate , Glomerulonephritis/diagnosis , Glomerulonephritis/epidemiology , Glomerulonephritis/physiopathology , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/epidemiology , Granulomatosis with Polyangiitis/immunology , Hematuria/diagnosis , Hematuria/epidemiology , Hematuria/immunology , Humans , Kidney Glomerulus/pathology , Kidney Glomerulus/physiopathology , Male , Microscopic Polyangiitis/diagnosis , Microscopic Polyangiitis/epidemiology , Microscopic Polyangiitis/immunology , Prevalence , Proteinuria/diagnosis , Proteinuria/epidemiology , Proteinuria/immunology , Retrospective Studies
16.
J Pediatr Gastroenterol Nutr ; 65(3): 278-280, 2017 09.
Article in English | MEDLINE | ID: mdl-27984348

ABSTRACT

OBJECTIVES: The aim of the study was to determine whether esophageal baseline impedance (BI) values in children could be predictive of esophagitis. MATERIALS AND METHODS: Multichannel intraluminal impedance (MII) tracings of children 3 to 17 years of age suspected of having gastroesophageal reflux and esophagitis, who had also undergone upper endoscopy with multiple esophageal biopsies, were reviewed. Patients with eosinophilic esophagitis were excluded. Esophagitis was assessed by macroscopic and microscopic parameters. Esophageal histology was reported by 2 blinded independent pathologists unaware of the MII results. Mean BI was automatically calculated in the different MII channels (ch) by the specific software without removing any episode of increased/decreased BI. BI results were plotted against macroscopic and histological scores for each channel. RESULTS: Tracings of 87 children, 53 boys, were evaluated. Mean age was 7.4 years: 45 had histologic esophagitis, 8 macroscopic. Histologic mild esophagitis (grade 1) was observed in 30, and 15 had moderate to severe esophagitis (grade 2-3). Ten had grade 3 esophagitis. Eight had macroscopic esophagitis as well. RESULTS: in channel 6 of the MII, all 10 patients with grade 3 esophagitis and the 8 with macroscopic esophagitis had a BI <900 Ω/s (positive predictive value 100% and negative predictive value 100%), whereas none of those having a biopsy score of 0 to 2 or no endoscopic evidence of esophagitis had a mean BI below 2000 Ω/s. CONCLUSIONS: The evaluation of the BI measured in channel 6 gave us 100% prediction of grade 3 and macroscopic esophagitis. BI on channel 6 may be useful to predict severe esophageal mucosa inflammation and could potentially be used for follow-up evaluation, rather than repeating an upper endoscopy. In addition, it would seem that grade 3 esophagitis even in the absence of macroscopic esophagitis affects the integrity of the esophageal epithelium.


Subject(s)
Electric Impedance , Esophagitis/diagnosis , Gastroesophageal Reflux/complications , Adolescent , Biopsy , Child , Child, Preschool , Esophageal Mucosa/pathology , Esophagitis/etiology , Esophagitis/pathology , Esophagoscopy , Female , Gastroesophageal Reflux/pathology , Humans , Male , Predictive Value of Tests , Retrospective Studies
17.
J Neuroimmunol ; 299: 59-61, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27725122

ABSTRACT

Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies.


Subject(s)
Muscular Diseases/diagnosis , Muscular Diseases/immunology , Myasthenia Gravis/diagnosis , Myasthenia Gravis/immunology , Female , Humans , Male , Middle Aged , Muscular Diseases/complications , Myasthenia Gravis/complications
18.
Int J Endocrinol ; 2015: 587893, 2015.
Article in English | MEDLINE | ID: mdl-26106414

ABSTRACT

We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34-78 years, presenting aggressive pituitary tumors. In all the patients tested O(6)-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140-320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson's syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing's disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on-until now-incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.

20.
Rev. nefrol. diál. traspl ; 34(4): 191-198, dic. 2014.
Article in Spanish | LILACS | ID: biblio-908357

ABSTRACT

Introducción: las glomerulopatías primarias son causa de enfermedad renal crónica en receptores de trasplante renal (30%-50%), siendo un determinante importante en la sobrevida del injerto. Recientes estudios revelan que la recurrencia fue la tercer causa más frecuente de pérdida delinjerto a 10 años de seguimiento postrasplante. Objetivo: Analizar el impacto de las glomerulopatía postrasplante como predictor de pérdida del injerto. Material y métodos: Entre enero de 1990 y abril del 2013 se realizaron 849 biopsias renales en 375 pacientes trasplantados, diagnosticándose 50 casos de glomerulopatía. Se comparó dicha población con un grupo histórico de receptores de trasplante renal entre 2000 al 2011, sin glomerulopatía. Se analizó la sobrevida del injerto renal en ambas poblaciones. Resultados: Se diagnosticaron 50 glomerulopatías post trasplante en 47 pacientes. No encontramos diferencias estadísticamente significativas entre este grupo y el grupo histórico en: edad del receptor; sexo del donante; tipo del donante; n¿²mero de miss match; tiempo de isquemia del órgano; tasa de rechazo agudo; retardo de la función del injerto; ni en la mortalidad del receptor. Si hallamos diferencias significativa en sexo masculino, 88 vs 55% (p< 0.05). La tasa de pérdida del injerto renal fue significativamente más frecuente entre los pacientes que presentaron enfermedad glomerular 38 vs 8% (p< 0.01). Conclusión: En nuestra población, la aparición de glomerulopatía post trasplante se asoció a una disminución de la sobrevida del injerto observándose una mayor tasa de pérdida en la glomerulopatía membranoproliferativa.


Introduction: primary glomerulopathy is cause of renal chronic disease in renal transplant recipients (30%-50%), being an important determinant in graft survival. Recent studies reveal that recurrence was the third most frequent cause of graft lost after 10 years post-transplant monitoring process. Objective: To analyze posttransplant glomerulopathy impact as a graft lost predictor. Methods: Between January 1990 and April 2013, 849 renal biopsies were carried out on 375 transplanted patients, 50 glomerulopathy cases were diagnosed. This population was compared with an historical renal transplant recipients group between 2000 to 2011, without glomerulopathy. Renal graft survival was analyzed in both populations. Results: 50 post-transplant glomerulopathies were diagnosed in 47 patients. We did not find statistically significant differences between this group and the historical one concerning recipient age, donor sex, donor type, miss match number, organ ischaemia time, acute rejection rate, delayed graft function, and neither in the recipient mortality. We did find significant differences in male sex, 88% vs 55% (p< 0.05). Renal graft lost rate was significantly more frequent among patients presenting glomerular disease 38 vs 8 % (p< 0.01). Conclusion: In our population, post transplant glomerulopathy was associated to graft survival reduction and a higher membranoproliferative glomerulopathy lost rate was observed.


Subject(s)
Glomerulonephritis , Graft Rejection , Kidney Failure, Chronic , Kidney Transplantation , Kidney Glomerulus/pathology
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