RESUMEN
Toxigenic Corynebacterium diphtheriae is an important and potentially fatal threat to patients and public health. During the current dramatic influx of refugees into Europe, our objective was to use whole genome sequencing for the characterization of a suspected outbreak of C. diphtheriae wound infections among refugees. After conventional culture, we identified C. diphtheriae using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and investigated toxigenicity by PCR. Whole genome sequencing was performed on a MiSeq Illumina with >70×coverage, 2×250 bp read length, and mapping against a reference genome. Twenty cases of cutaneous C. diphtheriae in refugees from East African countries and Syria identified between April and August 2015 were included. Patients presented with wound infections shortly after arrival in Switzerland and Germany. Toxin production was detected in 9/20 (45%) isolates. Whole genome sequencing-based typing revealed relatedness between isolates using neighbour-joining algorithms. We detected three separate clusters among epidemiologically related refugees. Although the isolates within a cluster showed strong relatedness, isolates differed by >50 nucleotide polymorphisms. Toxigenic C. diphtheriae associated wound infections are currently observed more frequently in Europe, due to refugees travelling under poor hygienic conditions. Close genetic relatedness of C. diphtheriae isolates from 20 refugees with wound infections indicates likely transmission between patients. However, the diversity within each cluster and phylogenetic time-tree analysis suggest that transmissions happened several months ago, most likely outside Europe. Whole genome sequencing offers the potential to describe outbreaks at very high resolution and is a helpful tool in infection tracking and identification of transmission routes.
Asunto(s)
Toxinas Bacterianas/genética , Corynebacterium diphtheriae/genética , Difteria/epidemiología , Brotes de Enfermedades , Infección de Heridas/epidemiología , Adolescente , Adulto , África/epidemiología , Toxinas Bacterianas/metabolismo , Técnicas de Tipificación Bacteriana , Corynebacterium diphtheriae/efectos de los fármacos , Corynebacterium diphtheriae/aislamiento & purificación , Difteria/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/genética , Femenino , Genes Bacterianos , Alemania/epidemiología , Humanos , Masculino , Familia de Multigenes , Tipificación de Secuencias Multilocus , Filogenia , Refugiados , Suiza/epidemiología , Siria/epidemiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Adulto JovenRESUMEN
Disorders that arise as a result of lysosomal dysfunction represent some of the most challenging diagnostic problems in medicine. Not only are these disorders infrequently seen, but they may also present with signs and symptoms that mimic perinatal injury, food intolerance, or the sequellae of neonatal infection. Misidentification can lead to significant delay in diagnosis. Ironically, as the prevailing economic climate places increasing time constraints on practicing physicians, medical research is providing treatment strategies and management techniques that are most effective if applied early in the course of the disease. Most lysosomal storage disorders can now be definitively diagnosed once the signs are recognized. In many cases the benefits of early diagnosis, enlightened management, and appropriate referral are considerable. The aim of this paper is to demystify this elusive class of diseases, to promote clinical vigilance in their detection, and to provide a systematic approach to diagnosis when clinical suspicion is aroused.
Asunto(s)
Enfermedades por Almacenamiento Lisosomal/diagnóstico , Gangliósidos/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Enfermedades por Almacenamiento Lisosomal/genética , Enfermedades por Almacenamiento Lisosomal/metabolismo , Lisosomas/metabolismo , FenotipoRESUMEN
CONTEXT: Fabry disease is a metabolic disorder without a specific treatment, caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-gal A). Most patients experience debilitating neuropathic pain and premature mortality because of renal failure, cardiovascular disease, or cerebrovascular disease. OBJECTIVE: To evaluate the safety and efficacy of intravenous alpha-gal A for Fabry disease. DESIGN AND SETTING: Double-blind placebo-controlled trial conducted from December 1998 to August 1999 at the Clinical Research Center of the National Institutes of Health. PATIENTS: Twenty-six hemizygous male patients, aged 18 years or older, with Fabry disease that was confirmed by alpha-gal A assay. INTERVENTION: A dosage of 0.2 mg/kg of alpha-gal A, administered intravenously every other week (12 doses total). MAIN OUTCOME MEASURE: Effect of therapy on neuropathic pain while without neuropathic pain medications measured by question 3 of the Brief Pain Inventory (BPI). RESULTS: Mean (SE) BPI neuropathic pain severity score declined from 6.2 (0.46) to 4.3 (0.73) in patients treated with alpha-gal A vs no significant change in the placebo group (P =.02). Pain-related quality of life declined from 3.2 (0.55) to 2.1 (0.56) for patients receiving alpha-gal A vs 4.8 (0.59) to 4.2 (0.74) for placebo (P =.05). In the kidney, glomeruli with mesangial widening decreased by a mean of 12.5% for patients receiving alpha-gal vs a 16.5% increase for placebo (P =.01). Mean inulin clearance decreased by 6.2 mL/min for patients receiving alpha-gal A vs 19.5 mL/min for placebo (P =.19). Mean creatinine clearance increased by 2.1 mL/min (0.4 mL/s) for patients receiving alpha-gal A vs a decrease of 16.1 mL/min (0.3 mL/s) for placebo (P =.02). In patients treated with alpha-gal A, there was an approximately 50% reduction in plasma glycosphingolipid levels, a significant improvement in cardiac conduction, and a significant increase in body weight. CONCLUSION: Intravenous infusions of alpha-gal A are safe and have widespread therapeutic efficacy in Fabry disease.
Asunto(s)
Enfermedad de Fabry/tratamiento farmacológico , alfa-Galactosidasa/uso terapéutico , Adulto , Análisis de Varianza , Arritmias Cardíacas , Peso Corporal , Método Doble Ciego , Esquema de Medicación , Enfermedad de Fabry/fisiopatología , Frecuencia Cardíaca , Humanos , Infusiones Intravenosas , Pruebas de Función Renal , Masculino , Dimensión del Dolor , Trihexosilceramidas/metabolismo , alfa-Galactosidasa/administración & dosificaciónRESUMEN
We assessed the cutaneous silent period (CSP) in 24 patients with Fabry disease with small-fiber sensory neuropathy and 12 normal subjects to test the hypothesis that small-diameter afferents are responsible for producing the CSP. Sensory nerve conduction studies and quantitative sensory testing for cold and vibration detection thresholds were also measured. Overall, Fabry patients had impaired thermal, but not vibration, detection thresholds, with greatest impairment in the feet. In the upper extremity, CSP latencies, duration, and suppression of electromyographic activity (EMG) did not differ. In the lower extremity, patients had reduced suppression of EMG during the CSP compared to normal controls. CSP durations exhibited a bimodal distribution in patients, including a subset of seven patients with durations shorter than all controls. This subset had profound loss of thermal sensation in the feet, but this was also true of some patients who had normal CSPs. Patients with shortened CSPs had modestly elevated vibration thresholds and reduced sensory potentials in comparison to patients with normal CSPs. Reduced CSPs in Fabry patients are associated with, but not entirely explained by, the severity of small-fiber neuropathy as measured by quantitative sensory testing. The possibility that large-diameter fibers provide a minor contribution to producing the CSP should be considered.
Asunto(s)
Electromiografía , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/fisiopatología , Conducción Nerviosa/fisiología , Potenciales de Acción/fisiología , Adolescente , Adulto , Frío , Estimulación Eléctrica , Pie/inervación , Mano/inervación , Humanos , Masculino , Persona de Mediana Edad , Inhibición Neural/fisiología , Neuronas Aferentes/fisiología , Tiempo de Reacción/fisiología , Umbral Sensorial/fisiología , Nervio Sural/fisiología , VibraciónRESUMEN
In this comprehensive investigation, we studied three different neurorrhaphy models in an attempt to elucidate the potential of termino-lateral nerve repair to original and adjacent nerves. In experimental group 1, the peroneal nerve was sectioned and then attached to the posterior tibial nerve in a termino-lateral fashion. In experiment group 2, the motor nerves to the gastrocnemius muscle were sectioned and then attached to the posterior tibial nerve in a termino-lateral fashion. In experimental group 3, the obturator nerve (L2-4) was sectioned and attached to the sciatic nerve (L4-6) in a termino-lateral fashion. For the control in each group, the same type of nerve used in each respective group was transected without repair. Experimental groups 1 and 2 showed viable axons in the peroneal nerve distal to the neurorrhaphy site. Experimental group 3 showed no viable axons at these sites. No regeneration was observed in the transected nerve without repair in all three control groups. This study suggests that termino-lateral neurorrhaphy is a viable means of repairing damaged nerves if the distal segment of the sectioned nerve is reattached to its original trunk distal to its original branch point. However, the results from experimental group 3 demonstrate that termino-lateral neurorrhaphy cannot be used to repair nerves when the donor and recipient nerves originate from different spinal cord levels.
Asunto(s)
Nervios Periféricos/cirugía , Anastomosis Quirúrgica/métodos , Animales , Axones/fisiología , Músculo Esquelético/inervación , Regeneración Nerviosa , Nervio Obturador/patología , Nervio Obturador/cirugía , Nervios Periféricos/patología , Nervios Periféricos/fisiología , Nervio Peroneo/patología , Nervio Peroneo/fisiología , Nervio Peroneo/cirugía , Ratas , Ratas Sprague-Dawley , Nervio Ciático/cirugía , Nervio Tibial/cirugíaRESUMEN
A prospective, double-blinded study of 30 consecutive face lift patients was conducted to determine if the administration of corticosteroid medication would reduce postoperative facial edema. Half the patients received steroid medications in a random fashion. Three independent plastic surgeons who were blinded to the study rated facial swelling by comparing preoperative and postoperative photographs using a scale of 1 to 4. The data were tabulated and subjected to statistical analysis. There were no significant differences in facial swelling between the steroid-treated group and the untreated patients on any occasion.
Asunto(s)
Edema/prevención & control , Glucocorticoides/administración & dosificación , Hemisuccinato de Metilprednisolona/administración & dosificación , Ritidoplastia/efectos adversos , Triamcinolona/administración & dosificación , Administración Tópica , Adulto , Anciano , Método Doble Ciego , Quimioterapia Combinada , Edema/etiología , Humanos , Inyecciones Intravenosas , Cuidados Intraoperatorios , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Premedicación , Estudios ProspectivosRESUMEN
To establish a standard method for producing experimental cutaneous injuries caused by contact with corrosive liquids, we modified an apparatus and method recommended by Walker and Mason in 1967 to produce experimental thermal burns. The resulting procedure proved to be safe, reproducible, humane and efficient and can be used with a wide variety of corrosive liquids.