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1.
Pathol Res Pract ; 248: 154333, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37393666

RESUMEN

BACKGROUND: The etiopathogenesis of accompanying inflammatory phenomena and consequences of immunomodulation constitute a challenging and innovative field in the medical treatment of patients with autoimmune diseases. AIM: Based on i) clinical management experience gained from this challenging clinical case and ii) selective references of reports published in the scientific medical literature, we present an unusual counterfactual scientific case report. A patient diagnosed with ulcerative colitis undergoing januskinase (JAK)-inhibitor therapy developed acuteappendicitis as an unusual complication or as a visceral side effect of immunosuppressive/anti-inflammatory therapy. METHOD: Scientific case report. RESULTS: (case description): Medical history: A 52-year-old male presented with spasmodic pain in the right lower abdomen lasting for two days (no fever, no bowel movement changes (no stool irregularities), no vomiting). MEDICATION USED TO DATE: Steroid-resistant ulcerative colitis treated with immunosuppressive therapy (Adalimumab administered for 10 months [next generation anti-TNFα mAb], Vendolizumab for 9 months [α4ß7 integrin antagonist], Tofacitinib for 6 months); fructose intolerance, no previous abdominal surgery; medication: XeljanzTM (Tofacitinib, 5 mg 2x1; JAK-inhibitor; PFIZER PHARMA GmbH, Berlin,Germany); MutaflorTM (1x1; Ardeypharm GmbH, Herdecke, Germany). CLINICAL FINDINGS: Pressure pain in the right lower abdomen with local muscular defense (Mc-Burney's/Lanz's point positive), no peritonism, Psoas-muscle sign positive. DIAGNOSTIC MEASURES: Laboratory parameters: standard value of white blood cell count, CrP: 25 mg/l.-Transabdominal ultrasound revealed hypertrophic 'appendix vermiformis' with detectable target-phenomenon and surrounding fluid. DECISION-MAKING: Indication for laparoscopic exploration. THERAPY: Under perioperative single-shot antibiotic administration with UnacidTM, the patient underwent emergency laparoscopic appendectomy due to confirmed acute appendicitis with additional lavage and placement of local drainage. CLINICAL COURSE: The postoperative phase was uneventful (sufficient analgetic therapy, removal of local drainage on the 2nd postoperative day). The patient was discharged four days after surgery. Histopathology confirmed ulcero-phlegmonous, acute purulent appendicitis with fibrinous purulent mesenteriolitis. FURTHER MEASURES: Immunosuppressive therapy was continued. CONCLUSION: Based on the paradoxon of an acute inflammatory disease (acute appendicitis) seen in the case of a patient undergoing immunosuppressive/anti-inflammatory treatment using a JAK-Inhibitor for ulcerative colitis, we consider this case worthy of publication although this side effect has previously been described in patients with rheumatoid arthritis. This might be the manifestation of i) an immunomodulatory effect that reduced or at least altered mucosal defense, including an increased risk of opportunistic infections, presenting as a specific visceral 'side effect' of the JAK-Inhibitor and/or as a consequence; ii) an induced alternative inflammatory mechanism/proinflammatory signal transduction and - theoretically - an intestinal drainage defect in the segment of right colic artery with consecutive collection of necrotic cells and activation of inflammatory mediators.


Asunto(s)
Apendicitis , Colitis Ulcerosa , Masculino , Humanos , Persona de Mediana Edad , Colitis Ulcerosa/complicaciones , Apendicitis/tratamiento farmacológico , Apendicitis/diagnóstico , Apendicitis/cirugía , Inmunosupresores , Antiinflamatorios/uso terapéutico , Dolor/complicaciones , Dolor/tratamiento farmacológico
2.
J Neurol ; 257(1): 91-7, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19649685

RESUMEN

Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid alpha-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers' maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers' test, the CK levels and the 6-min walk test (341 +/- 149.49 m, median 342.25 m at baseline; 393 +/- 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.


Asunto(s)
Terapia de Reemplazo Enzimático/métodos , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , alfa-Glucosidasas/uso terapéutico , Adulto , Edad de Inicio , Anciano , Creatina Quinasa/metabolismo , Terapia de Reemplazo Enzimático/efectos adversos , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo II/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Población Blanca , Adulto Joven , alfa-Glucosidasas/administración & dosificación , alfa-Glucosidasas/efectos adversos
4.
Nervenarzt ; 80(6): 708-11, 2009 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-19347264

RESUMEN

Neuromuscular diseases accompanying thymoma include myasthenia gravis, polymyositis, dermatomyositis, and neuromyotonia. Usually 50% of patients with thymoma develop myasthenia gravis. However, only 5% show polymyositis as an accompanying paraneoplastic phenomenon. We report the case of a patient with thymoma showing myasthenia gravis as well as polymyositis. Due to the simultaneous occurrence of these paraneoplastic diseases, the criteria for exact diagnosis (serum creatine kinase, EMG, ocular involvement) overlap. This diagnostic dilemma can appreciably complicate the therapeutic approach.


Asunto(s)
Polimiositis/complicaciones , Polimiositis/diagnóstico , Timoma/complicaciones , Timoma/diagnóstico , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Polimiositis/terapia , Timoma/terapia , Neoplasias del Timo/terapia
5.
Thorax ; 64(5): 430-5, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19158119

RESUMEN

BACKGROUND: It is understood that chronic allograft failure occurs as a result of alloimmune and non-alloimmune injury. Dendritic cells (DC) are thought to be crucial in regulating (allo)immune airway damage and interactions with epithelial cells are likely. Studies in human lung transplantation are limited, however, and the available literature on DC is inconsistent. This study focused on the ex vivo influence of primary bronchial epithelial cells derived from lung allografts on DC differentiation. METHODS: Epithelial cell conditioned media (ECCM) were added to monocytes differentiating into DC under the influence of interleukin-4 and granulocyte macrophage-colony stimulating factor. The resultant cells were compared with DC cultured without ECCM and with monocyte-derived macrophages. Expression of typical DC (eg, CD1a) and macrophage (eg, CD14) markers was assessed by flow cytometry. Phenotypical assessments were complemented by functional studies of mannose receptor-mediated phagocytosis (FITC-dextran uptake) and antigen-presenting capability (mixed lymphocyte reactions). RESULTS: Cells exposed to ECCM expressed significantly lower levels of CD1a than unexposed DC. CD14 expression and phagocytic function were increased. ECCM cultured cells also expressed lower levels of T cell co-stimulatory molecules, secreted an anti-inflammatory cytokine profile and had significantly reduced antigen-presenting capability. CONCLUSION: Using phenotypic and functional approaches, this study has shown that ECCM from lung allografts drives the production of macrophage-like cells from monocytes rather than DC. The data suggest that epithelial cells may restrain airway DC and potential alloimmunity. It is unclear whether the observed effect is specifically seen in lung transplant recipients or is a general property of bronchial epithelial cells. This may reflect a homeostatic inter-relationship between airway epithelial and DC populations relevant both to lung allografts and the lung more generally.


Asunto(s)
Bronquios/citología , Células Dendríticas/citología , Células Epiteliales/citología , Trasplante de Pulmón , Macrófagos/citología , Monocitos/citología , Diferenciación Celular , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Supervivencia de Injerto , Humanos , Enfermedades Pulmonares/cirugía , Persona de Mediana Edad , Fenotipo , Trasplante Homólogo
6.
Neurology ; 71(10): 758-65, 2008 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-18765652

RESUMEN

OBJECTIVE: To compare muscle imaging findings in different subtypes of myofibrillar myopathies (MFM) in order to identify characteristic patterns of muscle alterations that may be helpful to separate these genetic heterogeneous muscular disorders. METHODS: Muscle imaging and clinical findings of 46 patients with MFM were evaluated (19 desminopathy, 12 myotilinopathy, 11 filaminopathy, 1 alphaB-crystallinopathy, and 3 ZASPopathy). The data were collected retrospectively in 43 patients and prospectively in 3 patients. RESULTS: In patients with desminopathy, the semitendinosus was at least equally affected as the biceps femoris, and the peroneal muscles were never less involved than the tibialis anterior (sensitivity of these imaging criteria to detect desminopathy in our cohort 100%, specificity 95%). In most of the patients with myotilinopathy, the adductor magnus showed more alterations than the gracilis muscle, and the sartorius was at least equally affected as the semitendinosus (sensitivity 90%, specificity 93%). In filaminopathy, the biceps femoris and semitendinosus were at least equally affected as the sartorius muscle, and the medial gastrocnemius was more affected than the lateral gastrocnemius. The semimembranosus mostly showed more alterations than the adductor magnus (sensitivity 88%, specificity 96%). Early adult onset and cardiac involvement was most often associated with desminopathy. In patients with filaminopathy, muscle weakness typically beginning in the 5th decade of life was mostly pronounced proximally, while late adult onset (>50 years) with distal weakness was more often present in myotilinopathy. CONCLUSIONS: Muscle imaging in combination with clinical data may be helpful for separation of distinct myofibrillar myopathy subtypes and in scheduling of genetic analysis.


Asunto(s)
Desmina/metabolismo , Músculo Esquelético/patología , Enfermedades Musculares/patología , Miofibrillas/patología , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Anciano , Femenino , Humanos , Proteínas con Dominio LIM , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Atrofia Muscular/patología , Enfermedades Musculares/clasificación , Enfermedades Musculares/genética , Mutación , Tomógrafos Computarizados por Rayos X , Cadena B de alfa-Cristalina/genética
7.
J Inherit Metab Dis ; 31 Suppl 2: S261-5, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18607768

RESUMEN

UNLABELLED: In patients with late-onset glycogen storage disease type II, one mutation, c.-32-13T>G, in the α-glucosidase (GAA) gene is identified frequently in European populations from different regions along with many rarer mutations. We have performed molecular genetic investigations in 18 German index patients with late-onset disease. The c.-32-13T>G, c.525delT (p.Glu176fsX45), and c.2481+102_2646+31del mutations were detected by PCR/restriction enzyme digest. Other mutations were detected by sequencing. All patients were compound heterozygous and 17 patients harboured the c.-32-13T>G mutation. Seven other previously described mutations (including the c.-32-13T>G) were identified, of which the p.C103G (c.307T>G) and the c.2481+102_2646+31del mutations were present each in three unrelated patients. Sequencing revealed five novel mutations. CONCLUSIONS: Genetic testing was able to identify the genetic defects in all patients and screening of the c.-32-13T>G mutation identified 94% of the cases. This is important for quick and reliable diagnosis, especially in view of enzyme replacement. Among the rarer mutations, c.2481+102_2646+31del and p.C103G are rather frequent in Germany.


Asunto(s)
Pruebas Genéticas , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Mutación , alfa-Glucosidasas/genética , Adulto , Edad de Inicio , Anciano , Estudios de Casos y Controles , Análisis Mutacional de ADN , Exones , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Alemania/epidemiología , Enfermedad del Almacenamiento de Glucógeno Tipo II/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo II/etnología , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Heterocigoto , Humanos , Intrones , Masculino , Persona de Mediana Edad , Fenotipo , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Adulto Joven
8.
Fortschr Neurol Psychiatr ; 76(1): 21-7, 2008 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-18189220

RESUMEN

Neuromyelitis optica (NMO; Devic's Syndrome) is an idiopathic, often relapsing, severe inflammatory disorder preferentially affecting optic nerves and spinal cord. The distinction of NMO from multiple sclerosis (MS) as a separate disease entity has been controversally discussed for a long time. Though both diseases show demyelinisation, they differ in typical clinical, imaging and immunopathological findings. The recent identification of serum aquaporin (AQP)-4 antibody clearly separates NMO from MS. In addition, the identification of AQP-4 antibodies supports peripheral humoral autoimmune pathogenesis in NMO and permits early initiation of effective therapy for prevention of attack-related disability.


Asunto(s)
Acuaporina 4/inmunología , Autoanticuerpos/inmunología , Neuromielitis Óptica/inmunología , Animales , Diagnóstico Diferencial , Humanos , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/patología , Neuromielitis Óptica/fisiopatología , Neuromielitis Óptica/terapia
9.
Pharmazie ; 62(3): 174-8, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17416192

RESUMEN

During the revision of the dimenhydrinate monograph of the European Pharmacopoeia a HPLC-UV method was developed. The procedure described allows a qualitative and quantitative determination of both dimenhydrinate compounds and of thirteen related substances. Furthermore a hitherto unknown impurity was identified and integrated into the purity check. Also 18 samples of dimenhydrinate have been tested. Thereby the relevant impurities of dimenhydrinate could be nominated and quantified.


Asunto(s)
Dimenhidrinato/análisis , Antagonistas de los Receptores Histamínicos H1/análisis , Cromatografía Líquida de Alta Presión , Contaminación de Medicamentos , Concentración de Iones de Hidrógeno , Reproducibilidad de los Resultados , Espectrofotometría Ultravioleta
10.
J Neural Transm (Vienna) ; 112(5): 649-60, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15517433

RESUMEN

UNLABELLED: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.


Asunto(s)
Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Riluzol/uso terapéutico , Vitamina E/administración & dosificación , Vitaminas/administración & dosificación , Esclerosis Amiotrófica Lateral/mortalidad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vitamina E/efectos adversos , Vitamina E/sangre , Vitaminas/efectos adversos , Vitaminas/sangre
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