RESUMEN
BACKGROUND: Patients with neuromuscular disorders are at increased risk of suffering perioperative complications. Current knowledge concerning this topic is based on small retrospective studies and expert opinion. Therefore, an individualized multidisciplinary approach to perioperative anaesthesia planning is invaluable to anticipate difficulties and to optimize outcomes. OBJECTIVE: To evaluate current practice regarding preoperative counselling and perioperative care of neuromuscular patients, with the aim to facilitate standardization and improvement of perioperative care for neuromuscular patients. METHODS: A questionnaire-based cross-sectional, observational study was conducted between July, 1st 2020 and December, 31st, 2020 in Dutch anaesthesia, neurology and clinical genetics departments. Main outcome measures were 1.) frequency of consultation requests for neuromuscular patients prior to surgery, 2.) current practice, educational activities and departmental approach to this topic and 3.) preoperative counselling of neuromuscular patients. RESULTS: A total of 83 departments participated. Consultations for a neuromuscular patient scheduled for anaesthesia were requested from anaesthesia and neurology department only infrequently. Local guidelines concerning perioperative care of neuromuscular patients were available in 36.4% of the participating departments. Quality of specific training for residents and staff anaesthetists/neurologists covering perioperative care of neuromuscular patients was rated as 'very good' or 'good' by 42.9%. Neuromuscular patients scheduled for surgery were 'always' or 'often' discussed in multidisciplinary meetings involving anaesthesiologists and neurologists in 20.8% of the participating departments. CONCLUSION: Perioperative care for neuromuscular patients in the Netherlands is highly variable and might benefit from guidelines, education of health care professionals and multidisciplinary meetings between anaesthesiologists and neurologists on a regular basis.
Asunto(s)
Neurólogos , Enfermedades Neuromusculares , Humanos , Estudios Transversales , Países Bajos , Estudios Retrospectivos , Atención Perioperativa , Encuestas y Cuestionarios , Enfermedades Neuromusculares/complicacionesRESUMEN
BACKGROUND: The variable clinical presentation of malignant hyperthermia (MH), a disorder of calcium signalling, hinders its diagnosis and management. Diagnosis relies on the caffeine-halothane contracture test, measuring contraction forces upon exposure of muscle to caffeine or halothane (FC and FH, respectively). Patients with above-threshold FC or FH are diagnosed as MH susceptible. Many patients test positive to halothane only (termed 'HH'). Our objective was to determine the characteristics of these HH patients, including their clinical symptoms and features of cytosolic Ca2+ signalling related to excitation-contraction coupling in myotubes. METHODS: After institutional ethics committee approval, recruited patients undergoing contracture testing at Toronto's MH centre were assigned to three groups: HH, doubly positive (HS), and negative patients (HN). A clinical index was assembled from musculoskeletal symptoms and signs. An analogous calcium index summarised four measures in cultured myotubes: resting [Ca2+]cytosol, frequency of spontaneous cytosolic Ca2+ events, Ca2+ waves, and cell-wide Ca2+ spikes after electrical stimulation. RESULTS: The highest values of both indexes were found in the HH group; the differences in calcium index between HH and the other groups were statistically significant. The principal component analysis confirmed the unique cell-level features of the HH group, and identified elevated resting [Ca2+]cytosol and spontaneous event frequency as the defining HH characteristics. CONCLUSIONS: These findings suggest that HH pathogenesis stems from excess Ca2+ leak through sarcoplasmic reticulum channels. This identifies HH as a separate diagnostic group and opens their condition to treatment based on understanding of pathophysiological mechanisms.
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Cafeína/farmacología , Calcio/fisiología , Halotano/farmacología , Hipertermia Maligna/diagnóstico , Contracción Muscular/efectos de los fármacos , Adulto , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/farmacología , Cafeína/administración & dosificación , Células Cultivadas , Susceptibilidad a Enfermedades , Relación Dosis-Respuesta a Droga , Femenino , Halotano/administración & dosificación , Humanos , Masculino , Contracción Muscular/fisiología , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaAsunto(s)
Hiperglucemia/epidemiología , Hipertermia Maligna/epidemiología , Adulto , Anciano , Animales , Bases de Datos Factuales , Modelos Animales de Enfermedad , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Masculino , Ratones , Persona de Mediana Edad , Ontario/epidemiologíaRESUMEN
Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic myopathy triggered by exposure to volatile anesthetics and/or depolarizing muscle relaxants. Susceptibility to MH is primarily associated with dominant mutations in the ryanodine receptor type 1 gene (RYR1). Recent genetic studies have shown that RYR1 variants are the most common cause of dominant and recessive congenital myopathies - central core and multi-minicore disease, congenital fiber type disproportion, and centronuclear myopathy. However, the MH status of many patients, especially with recessive RYR1-related myopathies, remains uncertain. We report the occurrence of a triplet of RYR1 variants, c.4711A>G (p.Ile1571Val), c.10097G>A (p.Arg3366His), c.11798A>G (p.Tyr3933Cys), found in cis in four unrelated families, one from Belgium, one from The Netherlands and two from Canada. Phenotype-genotype correlation analysis indicates that the presence of the triplet allele alone confers susceptibility to MH, and that the presence of this allele in a compound heterozygous state with the MH-associated RYR1 variant c.14545G>A (p.Val4849Ile) results in the MH susceptibility phenotype and a congenital myopathy with cores and rods. Our study underlines the notion that assigning pathogenicity to individual RYR1 variants or combination of variants, and counseling in RYR1-related myopathies may require integration of clinical, histopathological, in vitro contracture testing, MRI and genetic findings.
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Predisposición Genética a la Enfermedad , Heterocigoto , Hipertermia Maligna/genética , Miopatía del Núcleo Central/genética , Fenotipo , Canal Liberador de Calcio Receptor de Rianodina/genética , Adulto , Niño , Preescolar , Familia , Femenino , Estudios de Asociación Genética , Variación Genética , Humanos , Pierna/patología , Masculino , Hipertermia Maligna/metabolismo , Hipertermia Maligna/patología , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Miopatía del Núcleo Central/metabolismo , Miopatía del Núcleo Central/patología , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Población Blanca/genéticaRESUMEN
We present the case of a 20-year-old woman who developed rhabdomyolysis, disseminated intravascular coagulopathy and multi-organ failure induced by ecstasy. Following initial improvement, she developed delayed rhabdomyolysis then haloperidol-induced neuroleptic malignant syndrome, which was treated with a total of 50 mg.kg(-1) dantrolene. Subsequent genetic testing revealed a novel potentially pathogenic variant in the ryanodine receptor type 1 gene. However, caffeine-halothane contracture testing of the patient's mother who carried the same gene variant was negative for malignant hyperthermia.
Asunto(s)
Alucinógenos/efectos adversos , N-Metil-3,4-metilenodioxianfetamina/efectos adversos , Síndrome Neuroléptico Maligno/genética , Síndrome Neuroléptico Maligno/fisiopatología , Rabdomiólisis/inducido químicamente , Canal Liberador de Calcio Receptor de Rianodina/genética , Anestésicos por Inhalación , Antipsicóticos/efectos adversos , Temperatura Corporal , Cafeína , Estimulantes del Sistema Nervioso Central , Cromatografía Líquida de Alta Presión , Creatina Quinasa/sangre , Dantroleno/uso terapéutico , Coagulación Intravascular Diseminada/etiología , Femenino , Variación Genética , Haloperidol/efectos adversos , Halotano , Humanos , Insuficiencia Multiorgánica/inducido químicamente , Insuficiencia Multiorgánica/fisiopatología , Recurrencia , Rabdomiólisis/genética , Rabdomiólisis/fisiopatología , Análisis Espectral , Adulto JovenRESUMEN
AIMS: To determine the mechanism of action of antimicrobial protein, lactosporin, against Gardnerella vaginalis and to evaluate its safety in vitro. METHODS AND RESULTS: Bacillus coagulans ATCC 7050 was grown at 37°C for 18 h. The cell-free supernatant was concentrated 10-fold and screened for antimicrobial activity against indicator strain Micrococcus luteus. The mode of action of lactosporin was determined by measuring the potassium release and monitoring the changes in transmembrane potential (Δψ) and transmembrane pH (ΔpH) of the sensitive cells. Lactosporin caused the efflux of potassium ions from M. luteus cells and dissipation of ΔpH in G. vaginalis, while it had no effect on the Δψ. The safety of lactosporin was evaluated by using EpiVaginal(™) ectocervical (VEC-100) tissue model. Over 80% of the cells in the vaginal tissue remained viable after exposure to lactosporin for 24 h. CONCLUSIONS: Lactosporin potentially exerts its antimicrobial activity by selective dissipation of ΔpH and/or by causing leakage of ions from the sensitive cells. Safety studies suggest that lactosporin is a noncytotoxic antimicrobial for vaginal application. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that lactosporin is an effective and safe antimicrobial preparation with potential application for the control of bacterial vaginosis.
Asunto(s)
Antibacterianos/farmacología , Bacillus/metabolismo , Bacteriocinas/farmacología , Gardnerella vaginalis/efectos de los fármacos , Antibacterianos/metabolismo , Bacteriocinas/metabolismo , Femenino , Gardnerella vaginalis/crecimiento & desarrollo , Humanos , Concentración de Iones de Hidrógeno , Potenciales de la Membrana/efectos de los fármacos , Micrococcus luteus/efectos de los fármacos , Potasio/análisis , Fuerza Protón-Motriz , Vagina/citología , Vagina/efectos de los fármacos , Vagina/microbiología , Vaginosis Bacteriana/tratamiento farmacológicoRESUMEN
AIMS: To characterize the antimicrobial protein produced by Bacillus coagulans used in the probiotic dietary supplement (Lactospore) Probiotic, Sabinsa Corp., Piscataway, NJ, USA). METHODS AND RESULTS: Bacillus coagulans ATCC 7050 was grown at 37 degrees C for 18 h. The cell free supernatant was concentrated 10-fold (lactosporin preparation, LP). The antimicrobial activity of LP was confirmed against Micrococcus luteus ATCC 10420 in a well diffusion assay. The proteinaceous nature of LP was determined following exposure to different enzymes. The activity of LP was pH-dependent but stable to heat. The isoelectric point of LP was determined to be 3.5-4.0. PCR analyses showed no similarity between lactosporin and known antimicrobial proteins produced by the Bacillus spp. CONCLUSIONS: Lactosporin is a novel antimicrobial protein. Initial characterization indicates that it may fall outside of the conventional classification of class I and II bacteriocins. Loss of activity after exposure to a number of proteolytic enzymes and lipase suggest that lactosporin may posses a lipid moiety which contributes to its inhibitory activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The unique characteristics of lactosporin, including its antimicrobial activity against pathogenic micro-organisms, indicate that it may have potential for application in foods and personal care products.
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Antibacterianos/metabolismo , Bacillus/metabolismo , Bacteriocinas/metabolismo , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Bacillus/genética , Bacteriocinas/aislamiento & purificación , Bacteriocinas/farmacología , Electroforesis en Gel de Poliacrilamida , Concentración de Iones de Hidrógeno , Punto Isoeléctrico , Micrococcus luteus/efectos de los fármacos , Reacción en Cadena de la Polimerasa , Probióticos/farmacología , TemperaturaRESUMEN
BACKGROUND: Interscalene brachial plexus block (ISBPB) is an effective nerve block for shoulder surgery. However, a 100% incidence of phrenic nerve palsy limits the application of ISBPB for patients with limited pulmonary reserve. We examined the incidence of phrenic nerve palsy with a low-volume ISBPB compared with a standard-volume technique both guided by ultrasound. METHODS: Forty patients undergoing shoulder surgery were randomized to receive an ultrasound-guided ISBPB of either 5 or 20 ml ropivacaine 0.5%. General anaesthesia was standardized. Both groups were assessed for respiratory function by sonographic diaphragmatic assessment and spirometry before and after receiving ISBPB, and after surgery. Motor and sensory block, pain, sleep quality, and analgesic consumption were additional outcomes. Statistical comparison of continuous variables was analysed using one-way analysis of variance and Student's t-test. Non-continuous variables were analysed using chi(2) tests. Statistical significance was assumed at P<0.05. RESULTS: The incidence of diaphragmatic paralysis was significantly lower in the low-volume group compared with the standard-volume group (45% vs 100%). Reduction in forced expiratory volume in 1 s, forced vital capacity, and peak expiratory flow at 30 min after the block was also significantly less in the low-volume group. In addition, there was a significantly greater decrease in postoperative oxygen saturation in the standard-volume group (-5.85 vs -1.50, P=0.004) after surgery. There were no significant differences in pain scores, sleep quality, and total morphine consumption up to 24 h after surgery. CONCLUSIONS: The use of low-volume ultrasound-guided ISBPB is associated with fewer respiratory and other complications with no change in postoperative analgesia compared with the standard-volume technique.
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Anestésicos Locales/administración & dosificación , Plexo Braquial/diagnóstico por imagen , Bloqueo Nervioso/métodos , Parálisis Respiratoria/etiología , Ultrasonografía Intervencional/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/administración & dosificación , Anestésicos Locales/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfina/administración & dosificación , Bloqueo Nervioso/efectos adversos , Dimensión del Dolor/métodos , Dolor Postoperatorio/prevención & control , Nervio Frénico/lesiones , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/prevención & control , Parálisis Respiratoria/prevención & control , Articulación del Hombro/cirugíaRESUMEN
Insulin-resistant, obese Zucker rats have blunted pressure natriuresis and are mildly hypertensive. This may involve inappropriate regulation of the renin-angiotensin-aldosterone system. To evaluate mechanisms underlying this defect, we employed the model of aldosterone escape. Male lean (L) and obese (O) Zucker rats were infused with aldosterone (2.8 mug/g body wt(3/4)) via osmotic minipump while being fed a 0.02% NaCl diet (LS). After 4 days, six rats of each type were switched to a high-NaCl (HS) diet (4%) for 4 additional days. Mean arterial blood pressure measured by radiotelemetry was significantly increased by the HS diet only in obese rats (final mean mmHg): 104 (LLS), 99 (LHS), 103 (OLS), and 115 (OHS). Obese rats had relatively increased renal cortical abundance of the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and whole kidney alpha- and beta-ENaC (epithelial sodium channel) relative to lean rats. However, band density for the thiazide-sensitive (Na-Cl) cotransporter (NCC) was similarly reduced by HS in lean and obese rats ( approximately 50%). Obese rats had relatively reduced creatinine clearances and plasma renin activities, effects exacerbated by HS. Furthermore, HS resulted in a 129% increase in urinary nitrates plus nitrites excretion in lean rats and led to, in contrast, a 46% reduction in obese rats. Plasma sodium and potassium concentrations were increased by HS in obese but not lean rats. Thus we demonstrate an impaired response to aldosterone infusion in obese relative to lean Zucker rats. This impairment may involve increased sodium reabsorption via NKCC2 or ENaC, decreased glomerular filtration rate, and/or nitric oxide bioavailability.
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Aldosterona/farmacología , Presión Sanguínea/efectos de los fármacos , Obesidad/fisiopatología , Cloruro de Sodio Dietético/administración & dosificación , Delgadez/fisiopatología , Animales , Regulación hacia Abajo , Canales Epiteliales de Sodio , Asa de la Nefrona/fisiología , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Potasio/sangre , Potasio/orina , Ratas , Ratas Zucker , Sodio/sangre , Sodio/orina , Canales de Sodio/metabolismo , Simportadores del Cloruro de Sodio/metabolismo , Simportadores de Cloruro de Sodio-Potasio/metabolismo , Miembro 1 de la Familia de Transportadores de Soluto 12RESUMEN
Diabetes mellitus is associated with natriuresis, whereas estrogen has been shown to be renoprotective in diabetic nephropathy and may independently regulate renal sodium reabsorption. The aim of this study was to determine the effects of 17-beta estradiol (E(2)) replacement to diabetic, ovariectomized (OVX) female rats on the expression of major renal sodium transporters. Female, Sprague-Dawley rats (210 g) were randomized into four groups: (1) OVX; (2) OVX+E(2); (3) diabetic+ovariectomized (D+OVX); and (4) diabetic+ovariectomized+estrogen (D+OVX+E(2)). Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg.body weight (bw)). Rats received phytoestrogen-free diet and water ad libitum for 12 weeks. E(2) attenuated hyperglycemia, hyperalbuminuria, and hyperaldosteronism in D rats, as well as the diabetes-induced changes in renal protein abundances for the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), and the alpha- and beta-subunits of the epithelial sodium channel (ENaC), that is, E(2) decreased NKCC2, but increased alpha- and beta-ENaC abundances. In nondiabetic rats, E(2) decreased plasma K(+) and increased urine K(+)/Na(+) ratio, as well as decreased the abundance of NKCC2, beta-ENaC, and alpha-1-Na-K-adenosine triphosphate (ATP)ase in the outer medulla. Finally, the diabetic, E(2) rats had measurably lower final circulating levels of E(2) than the nondiabetic E(2) rats, despite an identical replacement protocol, suggesting a shorter biological half-life of E(2) with diabetes. Therefore, E(2) attenuated diabetes and preserved renal sodium handling and related transporter expression levels. In addition, E(2) had diabetes-independent effects on renal electrolyte handling and associated proteins.
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Diabetes Mellitus Experimental/fisiopatología , Estradiol/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Riñón/efectos de los fármacos , Canales de Sodio/genética , Simportadores de Cloruro de Sodio-Potasio/genética , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Canales Epiteliales de Sodio , Estradiol/sangre , Femenino , Immunoblotting , Riñón/química , Riñón/patología , Riñón/fisiopatología , Ovariectomía , Potasio/sangre , Potasio/orina , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores de Droga/análisis , Receptores de Droga/genética , Receptores de Droga/fisiología , Sodio/orina , Canales de Sodio/análisis , Canales de Sodio/fisiología , Simportadores del Cloruro de Sodio/análisis , Simportadores del Cloruro de Sodio/genética , Simportadores del Cloruro de Sodio/fisiología , Intercambiador 3 de Sodio-Hidrógeno , Intercambiadores de Sodio-Hidrógeno/análisis , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/fisiología , Proteínas Cotransportadoras de Sodio-Fosfato/análisis , Proteínas Cotransportadoras de Sodio-Fosfato/genética , Proteínas Cotransportadoras de Sodio-Fosfato/fisiología , Simportadores de Cloruro de Sodio-Potasio/análisis , Simportadores de Cloruro de Sodio-Potasio/fisiología , ATPasa Intercambiadora de Sodio-Potasio/análisis , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/fisiologíaRESUMEN
Renal sodium reabsorption is a key determinant of final urine concentration. Our aim was to determine whether differences existed between aged and young rats in their response to water restriction with regard to the regulation of abundance of any of the major distal renal sodium transporter proteins. Male Fisher 344 x Brown Norway (F344 x BN) rats of 3-, 10-, 24-, or 31 months of age (3M, 10M, 24M, or 31M) were either water restricted (WR) for 5 days or control (ad libitum water). Major renal sodium transporters and channel subunits were evaluated by immunoblotting and immunohistochemistry. Age did not significantly affect plasma arginine vasopressin or aldosterone levels, but renin activity was only 8% in 31M-WR rats relative to 3M-WR (P<0.05). Extreme aging (31M) led to decreased outer medullary abundance of the bumetanide-sensitive Na-K-2Cl cotransporter and decreased cortical abundance of the beta- and gamma-subunits (70-kDa band) of the epithelial sodium channel (ENaC) (P<0.05). Water restriction significantly (P<0.05) increased the abundance of Na-K-2Cl cotransporter (NKCC2) and Na-Cl cotransporter (NCC) across ages. However, these increases were significantly blunted as rats aged. Mean band densities were increased in WR rats (relative to age controls) by 54 and 106% at 3M, but only 25 and 29% at 24M and 0 and 6% at 31M for NKCC2 and NCC, respectively. Aged F344 x BN rats have reduced basal distal tubular renal sodium transporter abundances and blunted upregulation during water restriction, which may contribute to decreased urinary concentrating capacity.