RESUMO
Ozonation is a viable option to improve the removal of micropollutants (MPs) in wastewater treatment plants (WWTPs). Nevertheless, the application of ozonation is hindered by its high energy requirements and by the uncertainties regarding the formation of toxic transformation products in the process. Energy requirements of ozonation can be reduced with a pre-ozone treatment, such as a biological activated carbon (BAC) filter, that removes part of the effluent organic matter before ozonation. This study investigated a combination of BAC filtration followed by ozonation (the BO3 process) to remove MPs at low ozone doses and low energy input, and focused on the formation of toxic organic and inorganic products during ozonation. Effluent from a WWTP was collected, spiked with MPs (approximately 1 µg/L) and treated with the BO3 process. Different flowrates (0.25-4 L/h) and specific ozone doses (0.2-0.6 g O3/g TOC) were tested and MPs, ecotoxicity and bromate were analyzed. For ecotoxicity assessment, three in vivo (daphnia, algae and bacteria) and six in vitro CALUX assays (Era, GR, PAH, P53, PR, andNrf2 CALUX) were used. Results show that the combination of BAC filtration and ozonation has higher MP removal and higher ecotoxicity removal than only BAC filtration and only ozonation. The in vivo assays show a low ecotoxicity in the initial WWTP effluent samples and no clear trend with increasing ozone doses, while most of the in vitro assays show a decrease in ecotoxicity with increasing ozone dose. This suggests that for the tested bioassays, feed water and ozone doses, the overall ecotoxicity of the formed transformation products during ozonation was lower than the overall ecotoxicity of the parent compounds. In the experiments with bromide spiking, relevant formation of bromate was observed above specific ozone doses of approximately 0.4 O3/g TOC and more bromate was formed for the samples with BAC pre-treatment. This indirectly indicates the effectivity of the pre-treatment in removing organic matter and making ozone more available to react with other compounds (such as MPs, but also bromide), but also underlines the importance of controlling the ozone dose to be below the threshold to avoid formation of bromate. It was concluded that treatment of the tested WWTP effluent in the BO3 process at a specific ozone dose of 0.2 g O3/g TOC, results in high MP removal at limited energy input while no increase in ecotoxicity, nor formation of bromate was observed under this condition. This indicates that the hybrid BO3 process can be implemented to remove MPs and improve the ecological quality of this WWTP effluent with a lower energy demand than conventional MP removal processes such as standalone ozonation.
Assuntos
Ozônio , Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Carvão Vegetal , Bromatos , Brometos , Poluentes Químicos da Água/análiseRESUMO
A 73-year-old man with a history of marginal zone lymphoma was admitted to the emergency room for diplopia and ipsilateral headache. The Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) demonstrated intense and symmetrical hypermetabolism of the cavernous sinuses, and hypermetabolic lesions diffusely in the lymph nodes and bones. The diagnosis of high-grade relapse of lymphomatous disease was made. In this context, the homogenous and symmetric lesion of the cavernous sinuses, without any other encephalic or meningeal lesions, raised the hypothesis of a paraneoplastic origin. A plausible paraneoplastic link between the neuro-ophthalmological lesion and the malignant disorder is IgG4-related disease, a condition that may be associated with lymphoma. As in our case, this diagnosis is often presumptive because histopathological confirmation is difficult to obtain.
RESUMO
We present a case of a right perirenal Eikenella corrodens abscess in a patient with chronic pancreatitis and poor dental hygiene. Endoscopic Retrograde CholangioPancreaticography (ERCP) revealed a pancreatic fistula draining to the right perirenal loge. The patient was treated with broad-spectrum antibiotics, percutaneous drainage and endoscopic stenting of the duct of Wirsung, stopping the supply of the fistula. A full recovery in our patient was observed. Considering the uncommon location of the abscess, a review of the different aetiologies of perirenal abscesses and their distrubution patterns, and the endoscopic treatment of symptomatic pancreatic fistulas seemed worthwhile.
Assuntos
Abscesso Abdominal/microbiologia , Abscesso Abdominal/terapia , Eikenella corrodens/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/terapia , Fístula Pancreática/microbiologia , Fístula Pancreática/terapia , Pancreatite Crônica/microbiologia , Pancreatite Crônica/terapia , Abscesso Abdominal/diagnóstico por imagem , Doença Aguda , Terapia Combinada , Infecções por Bactérias Gram-Negativas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/diagnóstico por imagem , Pancreatite Crônica/diagnóstico por imagemRESUMO
Malignant lymphoma and other lymphoproliferative disorders represent a group of malignant hemopathies where immunotherapy has allowed spectacular progresses over the last ten years. The recent W.H.O. classification, based upon tumor immunology, and cytogenetical anomalies, allows a better identification of each lymphoma and the comparison of homogeneous populations within various clinical studies. The increase in the incidence of non-Hodgkin lymphoma is related to the aging of the population as well as to other factors that are still to be analysed - a real challenge for the future. We have tried to offer an overview of the latest therapeutical advances while focusing on the major role of general practitioner. The most frequency askeed questions will be discussed.
Assuntos
Drogas em Investigação/uso terapêutico , Clínicos Gerais , Linfoma/terapia , Papel do Médico , Humanos , Linfoma/patologia , Padrões de Prática Médica , Terapias em Estudo/métodosRESUMO
Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.
RESUMO
A 53-years-old man has a dysentery since two weeks. The blood test shows Coombs-positive hemolytic anemia and inflammation. Autoimmune hemolytic anemia (AIHA) is treated with corticosteroid. A colonoscopy reveals an ulcerative colitis. The evolution of the patient is complicated by a spontaneous digestive perforation treated by total proctocolectomy. After this intervention, there is a resolution of the AIHA and the patient is gradually weaned from corticosteroids. AIHA is a rare extra-intestinal manifestation of inflammatory bowel disease essentially ulcerative colitis. Identification of this cause of secondary AIHA is important for the therapeutic strategy. However treatment is nonspecific and based on low levels of evidence.
Assuntos
Anemia Hemolítica Autoimune/etiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Disenteria/complicações , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Abscesso Abdominal/etiologia , Doenças dos Ductos Biliares/etiologia , Carcinoma/cirurgia , Colonoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/cirurgia , Abscesso Abdominal/diagnóstico por imagem , Abscesso Abdominal/terapia , Dor Abdominal/etiologia , Idoso de 80 Anos ou mais , Doenças dos Ductos Biliares/diagnóstico por imagem , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Icterícia/etiologia , Masculino , Aderências Teciduais/complicaçõesRESUMO
We present the complex case of a 49-year-old woman who worked as a cook in a school cafeteria and has been suffering from widespread pain since 2002. This patient showed a very particular gait pattern with hips adduction, flexed hips and knees and bilateral equinus foot deformity. Clinical examinations conducted by various clinicians, such as physical medicine and rehabilitation (PM&R) physicians and neurologists, yielded very different diagnostic hypotheses, each being nevertheless quite "logical": fibromyalgia syndrome with dystonia, CNS injury, Little's disease, intramedullary spinal cord tumor or multiple sclerosis. The only abnormalities observed occurred during the quantitative sensory test presenting as severe widespread allodynia to cold and hot temperatures and during Laser Evoked Potentials shown as a dysfunctional pattern for central processing of nociceptive data. Gait analysis showed that parameters were in the norms. Considering these different tests and the excellent progression of the patient's gait and general posture, we must envision that the fibromyalgia syndrome hypothesis remained the most likely one. The generalized dystonia was probably due to the patient's analgesic protective attitude. The actual therapy is still based on the biopsychosocial approach.
Assuntos
Distonia/diagnóstico , Fibromialgia/diagnóstico , Fibromialgia/psicologia , Fenômenos Biomecânicos , Distonia/complicações , Distonia/reabilitação , Feminino , Fibromialgia/complicações , Fibromialgia/reabilitação , Marcha , Humanos , Pessoa de Meia-Idade , PosturaRESUMO
OBJECTIVE: To evaluate the preoperative detection of axillary metastasis combining ultrasound (US)-guided fine needle aspiration cytology (FNAC) and liquid-based cytology (Surepath(®)) to reduce sentinel node procedures. METHODS: In total, 148 patients with clinically negative lymph nodes and no preoperative therapy were included. All patients underwent preoperative ultrasound of the axilla with FNAC if suspicious lymph nodes were found. Complete axillary lymph node dissection was performed at primary surgery when FNAC was positive. All other patients underwent a sentinel node procedure. RESULTS: US-guided FNAC of the axilla revealed metastasis in 34 (23.0%) of the 148 patients. These 34 patients were 53.1% of all patients (n = 64) with proven axillary lymph node involvement. In 66 patients (44.6%), both ultrasound and histopathology were negative. Overall sensitivity of US-guided FNAC was 50.0%, specificity 100%, positive predictive value 100% and negative predictive value 70.2%. In T1 tumours, all patients referred for sentinel node procedure were node-negative. The correlation between malignant FNAC and histopathology was 100%. US-guided liquid-based FNAC in patients with no clinically positive lymph nodes reduced the necessity for a sentinel node procedure by 23.0%. CONCLUSIONS: We advocate that US-guided fine needle aspiration (FNA) combined with liquid-based cytology of axillary lymph nodes should be included in the preoperative staging of breast cancer.
Assuntos
Axila/diagnóstico por imagem , Biópsia por Agulha Fina/métodos , Neoplasias da Mama/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Estadiamento de Neoplasias/métodos , Ultrassonografia de Intervenção/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Axila/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Linfonodos/cirurgia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/métodosRESUMO
Inflammation and cancer are associated with impairment of T-cell responses by a heterogeneous population of myeloid-derived suppressor cells (MDSCs) coexpressing CD11b and GR-1 antigens. MDSCs have been recently implicated in costimulation blockade-induced transplantation tolerance in rats, which was under the control of inducible NO synthase (iNOS). Herein, we describe CD11b+GR-1+MDSC-compatible cells appearing after repetitive injections of lipopolysaccharide (LPS) using a unique mechanism of suppression. These cells suppressed T-cell proliferation and Th1 and Th2 cytokine production in both mixed lymphocyte reaction and polyclonal stimulation assays. Transfer of CD11b+ cells from LPS-treated mice in untreated recipients significantly prolonged skin allograft survival. They produced large amounts of IL-10 and expressed heme oxygenase-1 (HO-1), a stress-responsive enzyme endowed with immunoregulatory and cytoprotective properties not previously associated with MDSC activity. HO-1 inhibition by the specific inhibitor, SnPP, completely abolished T-cell suppression and IL-10 production. In contrast, neither iNOS nor arginase 1 inhibition did affect suppression. Importantly, HO-1 inhibition before CD11b+ cell transfer prevented the delay of allograft rejection revealing a new MDSC-associated suppressor mechanism relevant for transplantation.
Assuntos
Endotoxinas/metabolismo , Heme Oxigenase-1/metabolismo , Células Mieloides/citologia , Animais , Antígeno CD11b/biossíntese , Proliferação de Células , Sistema Imunitário , Interleucina-10/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/imunologia , Linfócitos T/citologia , Células Th1/citologia , Células Th2/citologiaRESUMO
Naturally occurring regulatory T-cells (Tregs) play a critical role in the homeostasis of healthy immune system. A Treg deficiency is responsible for immune system dysregulation, immune hyperreactivity and autoimmunity. Herein, we investigated the role of Tregs, either in the context of antibody-induced transplantation tolerance, mixed donor/recipient chimerism or in models of spontaneous graft acceptance without immunosuppression. We also investigated their capacities to control endotoxin-mediated immune response in the context of lymphopaenia-driven homeostatic T-cell proliferation. Finally, although Tregs adequately control Th1 and Th2 immunity, they are inefficient in regulating IL-17 producing T cells in vitro and in vivo and rather promote them.
Assuntos
Linfócitos T Reguladores/imunologia , Tolerância ao Transplante/imunologia , Transplante Homólogo/imunologia , Animais , Antígenos CD/imunologia , Humanos , Quimeras de Transplante/imunologiaRESUMO
The growing development of composite tissue allografts (CTA) highlights the need for tolerance induction protocols. Herein, we developed a mouse model of heterotopic limb allograft in a stringent strain combination in which potentially tolerogenic strategies were tested taking advantage of donor stem cells in the grafted limb. BALB/c allografts were transplanted into C57BL/6 mice treated with anti-CD154 mAb, nondepleting anti-CD4 combined to either depleting or nondepleting anti-CD8 mAbs. Some groups received additional rapamycin. Both depleting and nondepleting mAb combinations without rapamycin only delayed limb allograft rejection, whereas the addition of rapamycin induced long-term allograft survival in both combinations. Nevertheless, robust donor-specific tolerance, defined by the acceptance of a fresh donor-type skin allograft and simultaneous rejection of third-party grafts, required initial CD8(+) T-cell depletion. Mixed donor-recipient chimerism was observed in lymphoid organs and recipient bone marrow of tolerant but not rejecting animals. Tolerance specificity was confirmed by the inability to produce IL-2, IFN-gamma and TNF-alpha in MLC with donor antigen while significant alloreactivity persisted against third- party alloantigens. Collectively, these results show that robust CTA tolerance and mixed donor-recipient chimerism can be achieved in response to the synergizing combination of rapamycin, transient CD8(+) T-cell depletion and costimulation/coreceptor blockade.
Assuntos
Anticorpos Monoclonais/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Extremidades/transplante , Imunossupressores/farmacologia , Depleção Linfocítica , Sirolimo/farmacologia , Tolerância ao Transplante/efeitos dos fármacos , Animais , Linfócitos T CD8-Positivos/citologia , Sobrevivência de Enxerto/efeitos dos fármacos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Timectomia , Quimeras de Transplante , Transplante Homólogo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We report on a 60-year-old man, seen at the emergency department because of severe left flank pain. Clinical diagnosis was that of renal colic. Overnight he became haemodynamically unstable and haematuria became massive, so multidetector CT (MDCT) was performed. MDCT with reconstructions can represent complex imaging findings in a more straightforward way compared with transverse images. Rupture of a renal artery aneurysm into the left pelvis was seen on coronal reconstructed CT images. Nephrectomy was performed. Rupture of a renal artery aneurysm into the pelvis is unusual and death is likely if diagnosis and treatment are delayed. The initial clinical presentation may be very similar to renal colic. MDCT allows timely and correct diagnosis of this unusual condition.
Assuntos
Aneurisma Roto/diagnóstico por imagem , Artéria Renal/diagnóstico por imagem , Cólica/diagnóstico , Diagnóstico Diferencial , Humanos , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
Gastro-intestinal stromal tumors can present with gastro-intestinal hemorrhage, often with an acute episode of abdominal pain, weight loss, nausea and vomiting. We present a case of a young man who presented with gastrointestinal bleeding. The patient previously presented with gastro-intestinal bleeding but several investigations like gastroscopy, coloscopy, Ectopic gastric mucosa-scan, and computed tomography were reported as negative. A well-circumscribed submucosal tumoral mass in the duodenum with maximal thickness of 15 mm was however detected by CT-enteroclysis. Microscopic examination confirmed the presence of a gastro-intestinal stromal tumor.
Assuntos
Neoplasias Duodenais/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Meios de Contraste/administração & dosagem , Neoplasias Duodenais/patologia , Endoscopia Gastrointestinal/métodos , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Intensificação de Imagem Radiográfica/métodosRESUMO
Haploidentical transplant is now established as a procedure of choice for patients who lack a compatible donor. However, they are still referred too late, heavily pretreated, at very advanced stages. We initiated a three-step phase I study trying improve transplant-related mortality, relapse rate, and immunity: G-CSF + DLI, GM-CSF + DLI, patient- and disease-adapted strategy. Thirty-three consecutive leukemia patients, aged 18-55, were investigated (20 very poor risk, 11 poor risk, and 2 better risk). GvH type NK alloreactivity was chosen when possible (18/33) and balanced across the three groups. In the first nine patients, G-CSF was used and escalated prophylactic DLI started at month 1. Thus, G-CSF and 1-3 DLI (10(4) CD3/kg) is safe. It results in faster CD4 recovery and a low rate of infections. However, it was insufficient to induce a GVL effect. In the next 12 patients, GM-CSF was used plus 1 DLI (10(4) CD3/kg) at day 30 unless aGVHD (3 patients). The comparison between the two first groups can be summarized as follows: G-CSF + DLI: TRM at day 100: 0, RR: 6/9, severe aGVHD: 0. GM-CSF + 1 DLI group: RR: 1/12, TRM at day 100: 3, aGVHD > 1: 9/12, price to pay: GVHD resulting in five deaths in total. Step 3 (13 patients) consists of a patient-adapted strategy: no more aspecific DLI (selected anti-CMV and aspergillus DLI planned in all patients); in myeloid disorders with NK alloreactivity: no GF. In the other cases, GM-CSF (at a reduced total dose of 500 mug) is given the follow-up of these 13 patients, although promising is currently short (median 5 months). Overall, TRM at day 100 is 3/29, reflecting the good tolerance of the conditioning in a heavily pretreated population (median age: 43). NRR mortality (8/26) at 1 year is greater in the GM-CSF + DLI group, reflecting the impact of severe aGVHD. We conclude that the third strategy might improve the outcome without exposing patients to unnecessary severe GVHD.
Assuntos
Leucemia/terapia , Transfusão de Linfócitos , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Adolescente , Adulto , Doença Enxerto-Hospedeiro/imunologia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Haplótipos , Humanos , Células Matadoras Naturais/imunologia , Leucemia/imunologia , Leucemia/reabilitação , Transfusão de Linfócitos/métodos , Transfusão de Linfócitos/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Engenharia Tecidual , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidadeRESUMO
New technologies are needed for manure treatment that can capture nutrients, reduce emissions of ammonia and nuisance odours, and kill harmful pathogens. A reactor concept was developed for simultaneous treatment of separately collected liquid and solid fractions of pig manure. The liquid fraction is concentrated by evaporating the water using energy from the composting system and at the same time scrubbing ammonia from the composting off-gas by acidifying the urine to pH 4 with nitric acid. This results in two marketable products, a concentrated liquid nitrogen fertiliser (NH4NO3) without phosphorus, and a stabilised, solid organic fertiliser, which is free of pathogens and weeds. By connecting the two reactor systems, emissions of ammonia and odours are abated as ammonia emitted from the composting is trapped in the liquid fraction and odorous compounds emitted from the liquid are degraded in the composting reactor. The concept was physically simulated by coupling a 80-L compost reactor to a 10-L bubble column. Operation of the bench-scale system showed that the concept is very promising. All nutrients were captured, and emissions of ammonia and odours were almost completely abated.
Assuntos
Amônia/isolamento & purificação , Reatores Biológicos , Esterco , Odorantes/prevenção & controle , Poluentes Atmosféricos/isolamento & purificação , Animais , Fertilizantes , Concentração de Íons de Hidrogênio , Suínos , Eliminação de Resíduos LíquidosRESUMO
We reviewed the 1996 issues of Radiology and American Journal of Roentgenology to appreciate the number of phantom studies published. There were 11 studies involving living animals and 51 other phantom studies. The categories chest, CT and MR, and musculoskeletal contained more than 10% of phantom studies in both journals. Design, advantages and limitations of different types of phantom studies are further addressed. Phantom studies offer several advantages over studies in patients in selected circumstances and have an important role in radiology research.
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Modelos Animais , Imagens de Fantasmas , Animais , Cadáver , Guias como Assunto , Humanos , EditoraçãoRESUMO
A 65-year-old woman who has been admitted after organophosphate-induced poisoning (Fenthion), develops pareses as a result of neuromuscular junctional dysfunction 7 days post-exposure. These findings are consistent with an intermediate syndrome, which may appear within 24 to 96 hours of exposure and subsides after 5 to 18 days. Delayed polyneuropathy develops within 1 to 3 weeks and abates after 6 to 12 months. A distal axonopathy can be demonstrated. Several authors have attempted EMG monitoring of pesticide-workers in agricultural and industrial settings. The electrophysiologic examination is an important diagnostic adjunct in the development and course of muscle paresis following organophosphate-ester poising.
Assuntos
Fention/intoxicação , Paralisia/diagnóstico , Idoso , Eletromiografia , Feminino , Humanos , Paralisia/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Intoxicação/complicações , Intoxicação/diagnóstico , Fatores de TempoRESUMO
A 65-year-old Caucasian female developed an intermediate syndrome seven days after an acute cholinergic crisis, caused by the ingestion of fenthion. Cholinesterase activity in the blood, plasma and red cells was monitored daily by the method according to Nenner and serial serum fenthion levels were measured by capillary gas chromatography. Electromyographic studies showed fade on tetanic stimulation by means of surface electrodes at 20 Hz of the left M. abductor digiti quinti at day 7, which could no longer be observed at day 19. Fade on low-frequency stimulation and post-tetanic facilitation were both absent. A biopsy of the N. suralis was normal. A biopsy of the M. tibialis anterior revealed a limited rhabdomyolysis with a very weak staining for cholinesterase. It is hypothesized that the pathophysiologic process underlying the syndrome is the result of a time-confined phenomenon, which includes both changes in the postsynaptic structures by a desensitization process and a gradually restoring ratio of acetylcholine to acetylcholinesterase. This hypothesis is suggested by the similarity in the EMG-findings of this patient and those in myasthenia gravis, which is known to be characterized by a postsynaptic transmission defect.