Tratamiento mediante neurólisis ecoguiada con fenol 6 % acuoso del componente álgico por neuromas postamputación: a propósito de un caso / Treatment by ultrasound-guided neurolysis with 6 % aqueous phenol of the pain component for post-amputation neuromas: report of a clinical case

Introducción: El tratamiento del dolor producido por neuromas es en sí complejo. Las opciones de tratamiento una vez se ha descartado la vía quirúrgica son pocas, si bien el impacto que dicho dolor produce en la vida de los pacientes obliga a buscar en estos casos alternativas que ofrezcan un control aceptable del mismo. El objetivo es presentar la neurólisis como una alternativa eficaz para el dolor por neuromas. Caso clínico: Reporte de caso, descriptivo y retrospectivo, de paciente perteneciente al Sistema Nacional de Salud, llevado a cabo por la Unidad de Dolor del Servicio de Anestesiología y Reanimación del Hospital Universitario Joan XXIII.Paciente de 59 años a quien, tras rechazar la cirugía, se le realizó neurólisis ecoguiada con fenol al 6 % acuososo para el tratamiento del dolor por neuromas derivados de la amputación de ambos miembros superiores. Discusión: La infiltración con fenol 6 % acuoso puede llegar a disminuir considerablemente el dolor durante un tiempo igual o superior a los 6 meses, otorgando una mejoría significativa en la calidad de vida de los pacientes.(AU)

Introduction: Magement of pain caused by neuromas is in itself complex. The treatment options once the surgical route has been ruled out are few, although the impact that this pain produces in the lives of patients makes it necessary to look for alternative cases that offer acceptable control of it. The objective is to present neurolysis as an effective alternative for pain due to neuromas. Case report: Descriptive and retrospective case report of a patient belonging to the National Health System, carried out by the Pain Unit of the Anesthesiology and Resuscitation Service of the Hospital Universitario Joan XXIII. 59-year-old patient who, after refusing surgery, underwent ultrasound-guided neurolysis with 6 % aqueous phenol for the treatment of pain due to neuromas derived from the amputation of both upper limbs. Discusion: Infiltration with 6 % aqueous phenol can considerably reduce pain, for a time equal to or greater than 6 months, granting a significant improvement in the quality of life of patients.(AU)

The sequence of prenatal growth restraint and postnatal catch-up growth: normal heart but thicker intima-media and more pre-peritoneal fat in late infancy.

BACKGROUND: The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6 years. OBJECTIVES: To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2 years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. METHODS: Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1 year (N = 87), and again at age 2 years (N = 68). RESULTS: Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2 years, and more pre-peritoneal fat by age 2 years (all p values between <0.01 and <0.0001); all cardiac and endocrine-metabolic results were similar in AGA and SGA infants at ages 1 and 2 years. CONCLUSIONS: From late infancy onwards, catch-up SGA infants have a thicker cIMT and more pre-peritoneal fat than AGA controls, but their cardiac morphology and function remain reassuringly similar.

Ventana sagital paramedial oblicua para el acceso de la rama medial del nervio raquídeo posterior guiado ecográficamente / Ultrasound guided parasagittal obliqua aproach for lumbar medial branch block

Objetivos: el método de abordaje ecográfico más utilizado para el bloqueo del ramo medial del nervio raquídeo posterior (RmNRp) requiere de la utilización de una técnica ecográfica biplanar con punción guiada en plano en ventana transversal, para situar la cánula perpendicular al RmNRp, limitando la realización de radiofrecuencia. La utilización de una ventana ecográfica parasagital oblicua permite el acceso al RmNRp permitiendo situar la cánula de forma paralela al nervio, logrando estímulos sensitivos y motores, y posibilitando la realización de radiofrecuencia térmica para segmentos lumbares por encima de L5.En el presente estudio valoramos la eficacia de este nuevo abordaje ecográfico mediante la comprobación fluoroscópica de la situación de la cánula y la comprobación de la obtención de estímulos sensitivos y motores. Material y métodos: se estudian 31 pacientes diagnosticados de síndrome facetario propuestos para la realización de bloqueos de RmNRp diagnósticos. Describimos cuatro ventanas ecográficas lumbares secuenciales necesarias para incluir los pacientes en el estudio. Una vez obtenidas, se localiza el punto objetivo utilizando una ventana parasagital oblicua para lograr la visualización de la cara externa de la apófisis articular superior y la parte más dorsal de la apófisis transversa. Se realiza punción guiada en plano hasta situar la punta en la unión entre apófisis articular superior y apófisis transversa. Una vez situada la cánula en el objetivo se procede a estímulo sensitivo 50 Hz y motor 2Hz para reposicionar la cánula en caso de no obtenerse estímulos. Una vez obtenido estímulo motor o sensitivo o ambos, se realiza una proyección fluoroscópica oblicua 30° y caudo-craneal para comprobar la localización de la punta de la aguja. Resultados: en el 16% de los pacientes no se pueden identificar las 4 ventanas ecográficas por lo que se aborta el procedimiento. En el 84% restante se consigue situar la aguja en el punto target en el 100% de los casos en el primer intento o con un sólo reposicionamiento de la aguja. Conclusión: la ventana ecográfica parasagital oblicua nos permite una aproximación tangencial al RmNRp lumbar con un alto índice de éxito para situar la cánula de radiofrecuencia de forma similar a cuando utilizamos fluoroscopia. La identificación de las cuatro ventanas ecográficas descritas en el estudio nos permite hacer un cribado de los pacientes tributarios a ecografía para el bloqueo de RmNRp (AU)

Objectives: The most used ultrasound guided medial branch block method requires the use of a biplane ultrasound technique. Using this technique the cannula is positioned not parallel to the medial branch by limiting their use to perform conventional radiofrequency. Using a sonographic parasagittal obliqua view allows placing the cannula parallel to the nerve, achieving sensory and motor stimuli and making possible radiofrequency above L5 lumbar segments. In the present study we determined the effectiveness of this new approach by using fluoroscopy and by obtention of sensory and motor stimuli. Material and methods: Thirty-one patients diagnosed with lumbar facet joint pain proposed for diagnostic medial branch blocks were studied. We describe four lumbar sequential sonographic views necessary to include patients in the study. Once obtained, the target point is located using a parasagittal oblique sonographic view to achieve the external face of the superior articular process and the more dorsal part of the transverse process. Puncture is performed guided in plane to place the tip at the junction between superior articular process and transverse process. Once the cannula located in the target proceeds to sensory stimulus 50 Hz and Motor 2 Hz to perform a cannula repositioning in case there were no stimuli. Once obtained either motor or sensory stimulus a caudal to craneal 30° oblique projection is performed by fluoroscopy to check the location of the needle tip. Results: In 16% of patients cannot identify the four ultrasound views so the procedure is aborted. In the remaining 84% is achieved by placing the needle into the target point at 100% of the cases on the first attempt or by once a repositioning of the needle. Conclusion: Ultrasound oblique parasagittal view allows us a tangential approach to the lumbar medial branch with a high rate of success to position the radiofrequency cannula similar to when using fluoroscopy. The sonographic identification of the four windows described in the study allows us to screening tributary patient for ultrasound medial branch blocks (AU)

Vasoespasmo coronario en la inducción de la anestesia general / Coronary vasospasm in general anaesthesia induction

El vasoespasmo de la arteria coronaria en la inducción de la anestesia general es una complicación poco documentada en nuestro entorno, por su baja incidencia o por pasar desapercibida. Presentamos el caso de una mujer previamente sana, programada para artroscopia de hombro, que en la inducción anestésica presentó taquicardia ventricular, que revirtió espontáneamente a ritmo sinusal con elevación de ST en cara lateral, y que se diagnosticó y trató con una angiografía inmediata. La importancia del caso se basa en la escasa bibliografía encontrada y en ser de los pocos comunicados en pacientes sanos durante la inducción de la anestesia general y, con diagnóstico y resolución angiográfico inmediato(AU)

Coronary artery vasospasm in the induction of general anaesthesia is a rarely reported complication in our environment, owing to its low incidence or due to having disappeared. We present a case of a previously healthy woman, scheduled for shoulder arthroscopy, who in the anaesthetic induction had a ventricular tachycardia, which spontaneously reverted to sinus rhythm with ST elevation on the left side, and which was diagnosed and treated immediately by using angiography. The importance of the case is based on the lack of references found, and on being rarely reported in health patients during the induction of general anaesthesia, and with an immediate diagnosis and resolving using angiography(AU)

[Coronary vasospasm in general anaesthesia induction]. / Vasoespasmo coronario en la inducción de la anestesia general.

Coronary artery vasospasm in the induction of general anaesthesia is a rarely reported complication in our environment, owing to its low incidence or due to having disappeared. We present a case of a previously healthy woman, scheduled for shoulder arthroscopy, who in the anaesthetic induction had a ventricular tachycardia, which spontaneously reverted to sinus rhythm with ST elevation on the left side, and which was diagnosed and treated immediately by using angiography. The importance of the case is based on the lack of references found, and on being rarely reported in health patients during the induction of general anaesthesia, and with an immediate diagnosis and resolving using angiography.

Effects of added fermentable carbohydrates in the diet on intestinal proinflammatory cytokine-specific mRNA content in weaning piglets.

There is increasing evidence showing that dietary supplementation with prebiotics can be effective in the treatment of intestinal inflammation. Because weaning time is characterized by rapid intestinal inflammation, this study investigated the effect of a diet supplemented with a combination of 4 fermentable carbohydrates (lactulose, inulin, sugarbeet pulp, and wheat starch) on the mRNA content of proinflammatory cytokines in newly weaned piglets. Cytokines (IL-1beta, IL-6, IL-8, IL-12p40, IL-18, and tumor necrosis factor-alpha) were analyzed using a semiquantitative reverse-transcription PCR technique on d 1, 4, and 10 in the ileum and colon of piglets fed either a test diet (CHO) or a control diet. In addition to the diet, the effect of enforced fasting on cytokine mRNA content was also evaluated. No effect of fasting was observed on the pro-inflammatory cytokine mRNA content. Our results showed that the CHO diet induced an up-regulation of IL-6 mRNA content in the colon of piglets 4 d postweaning. This up-regulation was specific for the animals fed the CHO diet and was not observed in animals fed the control diet. An increase in IL-1beta mRNA content was also observed on d 4 postweaning in all of the piglets. Correlations between proinflammatory cytokines and the end-products of fermentation indicated that the regulation of cytokines may be linked with some of the fermentation end-products such as branched-chain fatty acids, which are in turn end-products of protein fermentation.

[Oral analgesia versus posterior tibial nerve block for postoperative pain in ambulatory open hallux valgus surgery: a randomized clinical trial]. / Analgesia postoperatoria en la intervención abierta de hallux valgus en Cma. comparación entre analgesia oral y bloqueo perineural contínuo del nervio tibial posterior.

INTRODUCTION: This trial assessed the safety and efficacy of a continuous posterior tibial nerve block in the ankle provided in the patient's home by elastomeric pump infusion of 0.375% ropivacaine after ambulatory hallux valgus surgery. MATERIAL AND METHODS: Patients were randomized to 2 groups of 20 each to receive either the conventional oral analgesia prescribed by our team after outpatient surgery (metamizole 575 mg/6 h p.o.) or perineural analgesia with a continuous infusion of 5 mL x h(-1) of 0.375% ropivacaine in the posterior tibial nerve. Surgery was performed under hyperbaric spinal anesthesia with mepivacaine and an injection of 0.25% bupivacaine into the joint. Both groups also received 50 mg/8 h p.o. of tramadol as rescue analgesia. Assessment during visits by the home care team 12, 24, and 48 hours after surgery included the following variables: pain on a visual analog scale (VAS, 0-10), sleep quality, need for rescue analgesia, acceptance of the technique, side effects and adverse events. Descriptive statistics were calculated and comparisons were performed with the Mann-Whitney U test; sleep quality and need for rescue analgesia were compared by applying the chi2 statistic with a test of linear trend. RESULTS: The perineural analgesia group had significantly lower VAS scores at 4, 12, and 24 hours and less need for rescue analgesia. No differences in sleep quality were found (P0.07). The incidence of side effects did not differ, and there were no readmissions. The patients expressed a high level of acceptance of the technique. CONCLUSION: Continuous perineural analgesia in the home setting was found to be effective and safe in our patients.

Analgesia postoperatoria en la intervención abierta de hallux valgus en CMA. Comparación entre analgesia oral y bloqueo perineural continuo del nervio tibial posterior / Oral analgesia versus posterior tibial nerve block for postoperative pain in ambulatory open hallux valgus surgery: a randomized clinical trial

INTRODUCCIÓN: El presente trabajo valora la seguridady eficacia del bloqueo continuo del nervio tibial posterioren el tobillo, mediante la infusión domiciliaria porelastómero de ropivacaína al 0,375%, en pacientes intervenidosde hallux valgus en cirugía ambulatoria (CMA).MATERIAL Y MÉTODO: Se compara la analgesia oralconvencional de la unidad de CMA, metamizol 575 mgVO c/6h (AC) con la analgesia perineural (AP), infusióncontinua a 5 mL h-1 de ropivacaína 0,375% en nerviotibial posterior, en dos grupos de 20 pacientes, distribuidosaleatoriamente. Intervenciones realizadas bajo anestesiaintradural con mepivacaína hiperbara e infiltraciónintra-articular con bupivacaína al 0,25%. Ambos gruposutilizaron tramadol 50 mg VO c/8h como analgésico derescate. El servicio de atención domiciliaria realizó loscontroles: valoración del dolor según la escala analógicavisual (EVA 0-10), calidad sueño, necesidad de analgesiade rescate, aceptación de la técnica, incidencias y efectossecundarios, a las 12, 24 y 48 h de la intervención. Trabajodescriptivo, comparaciones mediante prueba U deMann Whitney; para el análisis de calidad del sueño ynecesidad de analgesia se utilizó el test de tendencia linealChi cuadrado.RESULTADOS: El grupo AP presentó valores de EVAsignificativamente menores a las 4 h, 12 h y 24 h y menornecesidad de analgesia de rescate. No diferencias en calidaddel sueño (p=0,07). No incidencias ni efectos secundarios.No hubo casos de reingreso. Los pacientes manifestaronun alto grado de aceptación de la técnica.CONCLUSIÓN: La analgesia perineural continua domiciliariase muestra efectiva y segura en nuestro ámbito

INTRODUCTION: This trial assessed the safety and efficacyof a continuous posterior tibial nerve block in theankle provided in the patient’s home by elastomericpump infusion of 0.375% ropivacaine after ambulatoryhallux valgus surgery.MATERIAL AND METHODS: Patients were randomizedto 2 groups of 20 each to receive either the conventionaloral analgesia prescribed by our team after outpatientsurgery (metamizole 575 mg/6 h p.o.) or perineuralanalgesia with a continuous infusion of 5 mL.h-1 of0.375% ropivacaine in the posterior tibial nerve. Surgerywas performed under hyperbaric spinal anesthesiawith mepivacaine and an injection of 0.25% bupivacaineinto the joint. Both groups also received 50 mg/8 hp.o. of tramadol as rescue analgesia. Assessment duringvisits by the home care team 12, 24, and 48 hours aftersurgery included the following variables: pain on avisual analog scale (VAS, 0-10), sleep quality, need forrescue analgesia, acceptance of the technique, sideeffects and adverse events. Descriptive statistics werecalculated and comparisons were performed with theMann-Whitney U test; sleep quality and need for rescueanalgesia were compared by applying the ÷2 statisticwith a test of linear trend.RESULTS: The perineural analgesia group had significantlylower VAS scores at 4, 12, and 24 hours and lessneed for rescue analgesia. No differences in sleep qualitywere found (P0.07). The incidence of side effectsdid not differ, and there were no readmissions. Thepatients expressed a high level of acceptance of thetechnique.CONCLUSION: Continuous perineural analgesia in thehome setting was found to be effective and safe in ourpatients

Catéter epidural anudado espontáneamente / Spontaneous kinking of an epidural catheter

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[Convulsions induced by ropivacaine after brachial plexus block]. / Convulsiones inducidas por ropivacaína tras la realización de un bloqueo del plexo braquial.

Ropivacaine is a local anesthetic frequently used to provide regional blocks because its toxicity threshold is favorable and it is highly selective for sensory nerve fibers. Few reports of adverse events and complications related to use of ropivacaine have been published. We report 2 cases of central nervous system toxicity. Each occurred after a brachial plexus block with 0.75% ropivacaine, one performed by an axillary approach and one by an infraclavicular approach with nerve stimulation.

Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets.

Cytokines play a central role in immune cell response, but they also participate in the maintenance of tissue integrity. Changes in the cytokine network of the pig gut may be expected at weaning, because abrupt changes in dietary and environmental factors lead to important morphological and functional adaptations in the gut. This study measured the gene expression of 6 inflammatory cytokines along the small intestine (SI) and the proximal colon in 28-d-old piglets (n = 45) at different time points (0, 1, 2, 5 and 8 d) postweaning, using RT-PCR. Villus-crypt architecture and enzymatic activities of lactase and sucrase in the SI were also examined. The results confirmed that weaning is associated with morphological and enzymatic changes in the SI. In addition, the data indicated that cytokine response in the gut could be divided into two periods: an early acute response (0 to 2 d postweaning) and a late long-lasting response (2 to 8 d postweaning). Between d 0 and d 2, the levels of IL-1beta, IL-6, and TNF-alpha messenger RNA (mRNA) increased. Marked upregulation of IL-1beta mRNA occurred in most parts of the intestine, whereas IL-6 and TNF-alpha mRNA markedly increased only at specific sites in the intestine. Between d 2 and d 8, the levels of IL-1beta, IL-6, and TNF-alpha mRNA rapidly returned to preweaning values, except that the level of TNF-alpha mRNA remained high in the distal SI. Levels of IL-12 subunit p40 (IL-12p40) and IL-18 mRNA also decreased, compared to those on d 0. Taken together, these results demonstrate that weaning in piglets is associated with an early and transient response in gene expression of inflammatory cytokines in the gut.

[Laryngeal mask for intubation (Fastrach)]. / Mascarilla laríngea para intubación (Fastrach).

The laryngeal mask for intubation (MLI), or "Fastrach", is a new device designed by Brain for airway management. The MLI, a modified version of the conventional laryngeal mask, allows for blind intubation through the device using endotracheal tubes up to 8 mm in diameter. Insertion with the head in a neutral position makes this system useful for managing the airway when neck injury is present. The device has been used successfully in patients assessed as having difficult-to-manage airways and its use in emergencies inside or outside the hospital is promising. The MLI has been used with high rates of success in combination with other techniques such as fiberoptic bronchoscopy (success rate 99 to 100%) and transillumination (95 to 100% success rate) in patients whose airways have been considered difficult to manage. Given such high rates of success for MLI placement (95 to 100%) and for blind orotracheal intubation (81 to 100%), the Fastrach may offer an alternative to the conventional laryngeal mask in algorithms for airway management.

Mascarilla laríngea para intubación (Fastrach) / The laryngeal face mask (Fastrach) for intubation

La mascarilla laríngea para intubación o Fastrach (MLI) es un nuevo dispositivo diseñado por Brain para el control de la vía aérea. Se trata de una modificación de la mascarilla laríngea convencional que permite la intubación a través de la misma con un tubo endotraqueal de hasta 8 mm. Su inserción con la cabeza en posición neutra la convierte en un sistema de utilidad en el control de la vía aérea de pacientes con traumatismo cervical. Se ha utilizado con éxito en pacientes con criterios de dificultad en el manejo de la vía aérea y es un dispositivo prometedor para el uso en urgencias extrahospitalarias o en departamentos de urgencias. Se ha utilizado combinada con otras técnicas como la fibrobroncoscopia y las técnicas de transiluminación en pacientes con criterios de dificultad en el control de la vía aérea con unas tasas de éxito elevadas (entre el 99 y el 100 por ciento para la primera combinación y el 95 y el 100 por ciento para la segunda).Dado el elevado índice de éxito en la inserción de la MLI (95-100 por ciento) y en la intubación orotraqueal "a ciegas" (81100 por ciento) es un sistema que puede sustituir la mascarilla laríngea convencional en los algoritmos de manejo de la vía aérea (AU)

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[Elective cesarean section with epidural anesthesia in a pregnant woman with obstructive hypertrophic myocardiopathy]. / Cesárea electiva con anestesia epidural a una gestante con miocardiopatía hipertrófica obstructiva.

Hypertrophic obstructive myocardiopathy (HOM) is characterised by left ventricular hypertrophy, which causes dynamic obstruction at the exit of the chamber and diastolic dysfunction of the myocardium. The use of epidural anesthesia in patients with HOM is controversial due to the hemodynamic repercussions of reduced preloading and postloading that occur. A 28-year-old woman with HOM was scheduled for cesarean delivery at 36.5 weeks because of delayed intrauterine growth. Satisfactory epidural anesthesia was provided with 0.5% bupivacaine with prior invasive hemodynamic monitoring. Analgesic and anesthetic management of a full-term parturient with HOM is a major challenge for the anesthesiologist. Although elective cesarean under general anesthesia is traditionally suggested for such patients, vaginal delivery with epidural analgesia is currently also being used. However, experience in using epidural anesthesia for cesarean delivery is scarce. For our patient, epidural anesthesia with appropriate hemodynamic monitoring allowed surgery to take place without complications. We therefore believe that the technique might be useful for such patients.

Cesárea electiva con anestesia epidural a una gestante con miocardiopatía hipertrófica obstructiva / Elective cesarean section with epidural anesthesia in a parturient with myocardiopathy

La miocardiopatía hipertrófica obstructiva se caracteriza por una hipertrofia del ventrículo izquierdo que ocasiona una obstrucción dinámica a la salida del mismo y una disfunción diastólica del miocardio. La utilización de la anestesia epidural en pacientes afectados de miocardiopatía hipertrófica obstructiva es un tema de controversia debido a las repercusiones hemodinámicas ocasionadas por la reducción de la precarga y de la poscarga que produce.Paciente de 28 años, gestante de 36 semanas y media afectada de miocardiopatía hipertrófica obstructiva a la que se decide practicar una cesárea debido a un retraso de crecimiento intrauterino. Se realizó anestesia epidural con bupivacaína al 0,5 por ciento previa monitorización hemodinámica invasiva con resultados satisfactorios.El manejo analgésico y anestésico de una paciente gestante a término con miocardiopatía hipertrófica obstructiva constituye uno de los mayores retos para el anestesiólogo. Aunque clásicamente se proponía la cesárea electiva para este tipo de pacientes bajo anestesia general, hoy día también se acepta la progresión del parto vaginal con analgesia por vía epidural. Sin embargo la experiencia en la utilización de la anestesia epidural para la cesárea es escasa. En nuestro caso la anestesia epidural junto con una monitorización hemodinámica adecuada permitió llevar a cabo la intervención sin complicaciones, por lo que creemos que puede ser una técnica útil para este tipo de pacientes (AU)

Th1 response in Salmonella typhimurium-infected mice with a high or low rate of bacterial clearance.

Previous studies have shown that the capacity to clear an attenuated strain of Salmonella typhimurium after the second week of infection varies widely among mouse strains. Bacterial clearance is mediated by CD4+ T cells and is regulated in part by the H-2 complex. The aim of the present study was to compare the patterns of cytokine mRNA expression in the spleens of C57BL/6 (H-2b) and CBA (H-2k) mice, which exhibit a low and a high rate of bacterial clearance, respectively. A transient increase in interleukin-12 (IL-12) mRNA levels was found in both mouse strains. Gamma interferon (IFN-gamma) gene expression was higher and more sustained in C57BL/6 than in CBA mice. No increase in IL-4 mRNA was detected. A transient increase in IL-10 mRNA was found in C57BL/6 mice. Separation of spleen cells into CD4+ and CD4- fractions showed that CD4+ T cells produced the bulk of IFN-gamma in both mouse strains and of IL-10 in C57BL/6 mice. Infection of H-2 congenic mice induced a higher level of IFN-gamma mRNA expression by CD4+ T cells in mice with a low rate of clearance (H-2b) than in mice with a high rate of clearance (H-2q). Treatment of infected C57BL/6 mice with anti-IFN-gamma or anti-CD4 monoclonal antibodies indicated that IFN-gamma participates in resistance in the early phase of infection, but not in bacterial clearance, and that CD4+ T cells mediate bacterial clearance during the 3rd week of infection. Taken together, these results suggest that defective bacterial clearance in H-2b mice is not linked to defective IFN-gamma production and that CD4+ T cells mediate bacterial clearance by an IFN-gamma-independent mechanism.

Beneficial effect of Salmonella typhimurium infection and of immunoglobulins from S. typhimurium-infected mice on the autoimmune disease of (NZB x NZW) F1 mice.

Various infections can precede or aggravate autoimmune diseases. Yet a beneficial effect of infection has also been described an various mechanisms have been postulated to explain this effect. The aim of this study was to examine the hypothesis that infection can have an immunoregulatory effect on the autoimmune process via the increased production of natural polyreactive antibodies. The effect of Salmonella typhimurium infection on the lupus-like disease of (NZB x NZW)F1 (B/W) mice was therefore studied. The effect of IgM and IgG preparations isolated from the serum of S. typhimurium-infected C57B1/6 and CBA mice on the autoimmune disease of B/W mice was also tested. C57B1/6 and CBA mice were chosen because they are respectively genetically susceptible and resistant to S. typhimurium infection and they differ in their antibody response during the early phase of infection. CBA mice can mount a specific anti-bacterium antibody response, whereas C57B1/6 mice present increased production of polyreactive antibodies. The infection effect was evaluated on several disease parameters, i.e. survival, incidence of high grade proteinuria and serum IgM and IgG antibody activity directed against a panel of autoantigens. Our main findings were: (i) infection of B/W mice with an attenuated strain of S. typhimurium delayed the course of the autoimmune disease when performed before the appearance of autoimmune symptoms; and (ii) IgM and IgG preparations from S. typhimurium-infected C57B1/6 mice had a similar effect whereas the IgM and IgG preparations from infected CBA mice, as well as from normal C57B1/6 and CBA mice, were ineffective. These results suggest that S. typhimurium infection can beneficially influence the development of the autoimmune disease of B/W mice. The immunoregulatory effect of the infection seems to be related at least partially, to the increase of a particular population of antibodies, the polyreactive antibodies.

Gamma interferon and interleukin-10 gene expression in innately susceptible and resistant mice during the early phase of Salmonella typhimurium infection.

Previous studies have shown that gamma interferon (IFN-gamma) plays a major role in natural resistance to Salmonella typhimurium during the early phase of infection. To assess whether the level of natural resistance in mice is related to the level of IFN-gamma gene expression, we compared IFN-gamma mRNA levels by means of reverse transcriptase-PCR in the spleens of genetically susceptible Itys (C57BL/6 and BALB/c) and resistant Ityr (CBA and DBA/2) mice during the first 5 days of infection. The mRNA expression of interleukin-10 (IL-10), a cytokine which antagonizes IFN-gamma effects, was also investigated. Mice were infected with 10(3) CFU of the virulent strain S. typhimurium C5, a dose which is lethal within a week for susceptible mice only. IFN-gamma mRNA increased to similar levels in both susceptible and resistant mice, suggesting that susceptibility to S. typhimurium infection is not related to defective IFN-gamma gene expression. In contrast, IL-10 mRNA reached much higher levels in susceptible than in resistant mice. Similar results were found in Ity congenic mice, confirming a link between the presence of the Itys allele and a high level of IL-10 gene expression during infection. High levels of IL-10 mRNA in susceptible mice correlated with high IL-10 serum levels (on day 5), whereas IL-10 was not detectable in the sera of resistant mice. However, administration of neutralizing anti-IL-10 monoclonal antibodies did not modify the course of infection. To evaluate the influence of bacterial multiplication on IL-10 mRNA expression, susceptible mice were infected with an attenuated strain of S. typhimurium. This strain induced a low level of IL-10 mRNA expression. When susceptible mice were immunized with an attenuated strain and challenged with the virulent strain, they inhibited the growth of the challenge bacteria and exhibited a low level of IL-10 mRNA. In contrast, when resistant mice were infected with a high (lethal) dose of the virulent strain, they exhibited a high level of IL-10 mRNA. Taken together, these results indicate that the level of IL-10 gene expression correlates with the level of bacterial multiplication in the organs and that the high level of IL-10 mRNA in Itys mice is a consequence rather than the cause of their susceptibility to S. typhimurium infection.