El tratamiento del dolor agudo pediátrico en España EN 2021: resultado de una encuesta nacional entre anestesiólogos pediátricos / The management of paediatric acute pain in Spain IN 2021: Results of a national survey among paediatric anaesthesiologists

Objetivo: Mejorar el conocimiento acerca de la práctica clínica habitual en el tratamiento del dolor agudo pediátrico en España.MétodosSe llevó a cabo una encuesta telemática a través de Internet en una muestra representativa de profesionales sanitarios involucrados en el tratamiento del dolor agudo pediátrico (concretamente anestesiólogos) en España. La encuesta incluyó 28 cuestiones acerca de su práctica clínica habitual en la valoración y el tratamiento del dolor agudo, así como aspectos formativos y organizativos en el dolor agudo pediátrico.ResultadosLa encuesta fue completada durante el mes de marzo de 2021 por 150 especialistas en anestesiología. Los encuestados presentaron una amplia experiencia en el tratamiento del dolor agudo pediátrico (media de años de experiencia: 14,3; DE: 7,8) y básicamente en dolor agudo postoperatorio (97% casos). Aunque el 80% de los mismos utilizaba de modo habitual escalas validadas de valoración de dolor agudo pediátrico, solo el 2,6% utilizaba las específicas adaptadas para pacientes con discapacidad cognitiva. La mayoría de los encuestados empleaba habitualmente fármacos analgésicos como el paracetamol (99%) o el metamizol (92%), pero solo el 84% los complementaba con alguna técnica de bloqueo loco-regional u otra medicación tipo antiinflamatorio no esteroideo (62%). Además, únicamente un 62,7% reconocía haber recibido formación específica en dolor agudo pediátrico, solo un 45% seguía protocolos institucionales hospitalarios y un escaso 28% lo hacía a través de unidades de dolor infantil.ConclusionesLa encuesta identificó importantes puntos de mejora en la formación y organización del tratamiento del dolor agudo de los pacientes españoles en edad pediátrica. (AU)

Objective: To improve knowledge about routine clinical practice in the management of paediatric acute pain in Spain.MethodsA telematic survey was conducted via the Internet on a representative sample of healthcare professionals involved in the management of paediatric acute pain (specifically anaesthesiologists) in Spain. The survey included 28 questions about their usual clinical practice in the assessment and treatment of acute pain, and also training and organisational aspects in paediatric acute pain.ResultsThe survey was completed during March 2021 by 150 specialists in anaesthesiology. The respondents widely experienced in the management of acute paediatric pain (mean years of experience: 14.3: SD: 7.8), essentially in acute postoperative pain (97% of cases). Although 80% routinely used validated paediatric acute pain assessment scales, only 2.6% used specific scales adapted for patients with cognitive impairment. Most of the respondents routinely used analgesic drugs such as paracetamol (99%) or metamizole (92%), but only 84% complemented these drugs with a loco-regional blocking technique or other non-steroidal anti-inflammatory drugs (62%). Furthermore, only 62.7% acknowledged having received specific training in paediatric acute pain, only 45% followed hospital institutional protocols, and a scant 28% did so through paediatric pain units.ConclusionsThe survey identified important points for improvement in the training and organisation of acute pain management in Spanish paediatric patients. (AU)

The management of paediatric acute pain in Spain in 2021: Results of a national survey among paediatric anaesthesiologists.

OBJECTIVE: To improve knowledge about routine clinical practice in the management of paediatric acute pain in Spain. METHODS: A telematic survey was conducted via the Internet on a representative sample of healthcare professionals involved in the management of paediatric acute pain (specifically anaesthesiologists) in Spain. The survey included 28 questions about their usual clinical practice in the assessment and treatment of acute pain, and also training and organisational aspects in paediatric acute pain. RESULTS: The survey was completed during March 2021 by 150 specialists in anaesthesiology. The respondents widely experienced in the management of acute paediatric pain (mean years of experience: 14.3: SD: 7.8), essentially in acute postoperative pain (97% of cases). Although 80% routinely used validated paediatric acute pain assessment scales, only 2.6% used specific scales adapted for patients with cognitive impairment. Most of the respondents routinely used analgesic drugs such as paracetamol (99%) or metamizole (92%), but only 84% complemented these drugs with a loco-regional blocking technique or other non-steroidal anti-inflammatory drugs (62%). Furthermore, only 62.7% acknowledged having received specific training in paediatric acute pain, only 45% followed hospital institutional protocols, and a scant 28% did so through paediatric pain units. CONCLUSIONS: The survey identified important points for improvement in the training and organisation of acute pain management in Spanish paediatric patients.

Rinderpest eradication: challenges for remaining disease free and implications for future eradication efforts.

In 2011, the World Organisation for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) declared global freedom from rinderpest, formally announcing that rinderpest virus infections had been eliminated from susceptible livestock populations. At the same time, it was recognised that rinderpest virus, and material containing rinderpest virus, remained stored in an unspecified number of facilities across the world. Although natural infections had been eliminated, there remained a risk that rinderpest could reoccur if such infectious material accidentally leaked or was intentionally released from one of these facilities into a susceptible animal population. To minimise this risk, the OIE and FAO, with the support of international partners, set in place a framework to: reduce the quantity of remaining rinderpest-virus-containing material; ensure that such material was only stored in high-security facilities; regulate any handling or manipulation of the virus; maintain vigilance amongst livestock keepers and Veterinary Services in the post-eradication era; and develop contingency plans to deal with any suspected or actual reoccurrence of rinderpest disease. In 2016, five years after the declaration of global freedom from rinderpest, official reports to the OIE show that virus and virus-containing material remain stored in 21 countries worldwide in 22 separate facilities, of which only five have been inspected and approved for holding rinderpest virus or vaccine. There is still much work to be done to further reduce the risk of a reoccurrence.

En 2011, l'Organisation mondiale de la santé animale (OIE) et l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) ont annoncé officiellement l'élimination de l'infection due au virus de la peste bovine dans les populations d'animaux d'élevage sensibles, déclarant ainsi la planète indemne de cette maladie. Parallèlement, les deux organisations faisaient état de l'existence d'un nombre indéterminé d'établissements dans le monde détenant des stocks du virus bovipestique ainsi que des produits contenant ce virus. Malgré l'élimination de l'infection chez ses hôtes naturels, un risque de réapparition de la peste bovine subsiste en cas de fuite accidentelle ou d'émission délibérée de ces produits infectieux dans les populations animales sensibles à partir de l'un de ces établissements. Afin de minimiser ce risque, l'OIE et la FAO soutenus par leurs partenaires internationaux ont mis en place un cadre visant plusieurs objectifs : réduire les quantités restantes de produits contenant le virus de la peste bovine dans le monde ; veiller à ce que ces produits ne soient stockés que dans des établissements de haute sécurité ; réglementer les conditions de détention et de manipulation du virus ; poursuivre la surveillance exercée par les éleveurs et les Services vétérinaires au cours de la phase post-éradication ; concevoir des plans d'urgence visant à faire face à toute réapparition suspectée ou confirmée de la peste bovine. En 2016, soit cinq ans après la déclaration de l'éradication mondiale de la peste bovine, il ressort des rapports officiels adressés à l'OIE que 21 pays détiennent encore des stocks du virus de la peste bovine ou des produits contenant ce virus, répartis en 22 établissements distincts dont seulement cinq ont fait l'objet d'une inspection et ont été dûment habilités à détenir des stocks de virus de la peste bovine ou de vaccins contre cette maladie. Il reste donc encore beaucoup à faire pour continuer à réduire le risque de réapparition de la peste bovine.

En 2011, la Organización Mundial de Sanidad Animal (OIE) y la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) anunciaron oficialmente que las infecciones causadas por el virus de la peste bovina habían sido eliminadas de las poblaciones sensibles de ganado, declarando así que el mundo quedaba libre de la enfermedad. Al mismo tiempo, significaron que un número no especificado de instalaciones dispersas por el mundo albergaban muestras del virus y otros productos que lo contenían. Aunque las infecciones naturales habían quedado eliminadas, subsistía el riesgo de reaparición de la peste bovina si en una de esas instalaciones se producía una fuga accidental o una liberación intencionada de material infeccioso y este entraba en contacto con una población animal sensible. Para reducir al mínimo tal riesgo, la OIE y la FAO, con apoyo de colaboradores internacionales, definieron un dispositivo encaminado a: reducir el volumen de material restante con contenido viral de la peste bovina; garantizar que ese material fuera conservado únicamente en instalaciones de alta seguridad; reglamentar toda manipulación del virus; mantener la vigilancia entre cuidadores de ganado y Servicios Veterinarios en el periodo posterior a la erradicación; y elaborar planes de emergencia para responder a toda reaparición, presunta o confirmada, de la peste bovina. En 2016, cinco años después de la declaración de ausencia mundial de peste bovina, los informes oficiales remitidos a la OIE daban fe de que había virus y productos que lo contenían en 22 instalaciones situadas en 21 países del mundo, de las que solo cinco habían sido inspeccionadas y homologadas para albergar virus de la peste bovina o vacunas contra la enfermedad. Queda pues mucho trabajo por delante para reducir en mayor medida el riesgo de reaparición.

Peste des Petits Ruminants Virus.

Peste des petits ruminants virus (PPRV) causes a severe contagious disease of sheep and goats and has spread extensively through the developing world. Because of its disproportionately large impact on the livelihoods of low-income livestock keepers, and the availability of effective vaccines and good diagnostics, the virus is being targeted for global control and eventual eradication. In this review we examine the origin of the virus and its current distribution, and the factors that have led international organizations to conclude that it is eradicable. We also review recent progress in the molecular and cellular biology of the virus and consider areas where further research is required to support the efforts being made by national, regional, and international bodies to tackle this growing threat.

Early thromboelastometry variables predict maximum clot firmness in children undergoing cardiac and non-cardiac surgery.

BACKGROUND: Early clot amplitudes measured on thromboelastometry (ROTEM®) predict maximum clot firmness (MCF) in adults. In this multicentre, retrospective study, we aimed to confirm the suspected relationship between early ROTEM® variables and MCF, in children undergoing cardiac or non-cardiac surgery. METHODS: 4762 ROTEM® tests (e.g. EXTEM, INTEM, FIBTEM, APTEM, and HEPTEM) performed in children undergoing cardiac or non-cardiac surgery at three University hospitals between January 2011 and June 2014 were reviewed. To assess the correlation between clot amplitudes measured after 5, 10 and 15 min and MCF, each variable was compared with the corresponding MCF by calculating Spearman's correlation coefficient. RESULTS: For the EXTEM® test, we observed that amplitude measured after 5 min (A5: r=0.91, P<0.001), 10 min (A10: r=0.95, P<0.001) and 15 min (A15: r=0.96, P<0.001) were strongly correlated to MCF. The same correlations were observed for INTEM® test (A5: r=0.93, P<0.001; A10: r=0.97, P<0.001; A15: r=0.97, P<0.001), and FIBTEM® test (A5: r=0.93, P<0.001; A10: r=0.94, P<0.001; A15: r=0.96, P<0.001). In addition, the amplitudes measured after five, 10 and 15 min were also strongly correlated with MCF in the APTEM® and the HEPTEM® tests. Receiver operating characteristics (ROC) analysis confirmed that A5, A10, A15 strongly predicted decreased MCF on all ROTEM® tests. CONCLUSIONS: This study confirmed that early values of clot amplitudes measured as soon as five, 10 or 15 min after clotting time could be used to predict maximum clot firmness in all ROTEM® tests.

Development and testing of a field diagnostic assay for peste des petits ruminants virus.

We have developed an immunochromatographic test for the diagnosis of peste des petits ruminants (PPR) under field conditions. The diagnostic assay has been tested in the laboratory and also under field conditions in Ivory Coast, Pakistan, Ethiopia and Uganda. The test is carried out on a superficial swab sample (ocular or nasal) and showed a sensitivity of 84% relative to PCR. The specificity was 95% over all nasal and ocular samples. The test detected as little as 10(3) TCID50 (50% tissue culture infectious doses) of cell culture-grown virus, and detected virus isolates representing all four known genetic lineages of peste des petits ruminants virus. Virus could be detected in swabs from animals as early as 4 days post-infection, at a time when clinical signs were minimal. Feedback from field trials was uniformly positive, suggesting that this diagnostic tool may be useful for current efforts to control the spread of PPR.

Dugbe virus ovarian tumour domain interferes with ubiquitin/ISG15-regulated innate immune cell signalling.

The ovarian tumour (OTU) domain of the nairovirus L protein has been shown to remove ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host cell proteins, which is expected to have multiple effects on cell signalling pathways. We have confirmed that the OTU domain from the L protein of the apathogenic nairovirus Dugbe virus has deubiquitinating and deISGylating activity and shown that, when expressed in cells, it is highly effective at blocking the TNF-α/NF-κB and interferon/JAK/STAT signalling pathways even at low doses. Point mutations of the catalytic site of the OTU [C40A, H151A and a double mutant] both abolished the ability of the OTU domain to deubiquitinate and deISGylate proteins and greatly reduced its effect on cell signalling pathways, confirming that it is this enzymic activity that is responsible for blocking the two signalling pathways. Expression of the inactive mutants at high levels could still block signalling, suggesting that the viral OTU can still bind to its substrate even when mutated at its catalytic site. The nairovirus L protein is a very large protein that is normally confined to the cytoplasm, where the virus replicates. When the OTU domain was prevented from entering the nucleus by expressing it as part of the N-terminal 205 kDa of the viral L protein, it continued to block type I interferon signalling, but no longer blocked the TNF-α-induced activation of NF-κB.

Estudio descriptivo retrospectivo sobre la utilización de levosimendán en niños sometidos a corrección quirúrgica de cardiopatía congénita / Retrospective descriptive study about the use of levosimendan in children undergoing surgical correction for congenital heart disease

Objetivos. Describir la utilización de levosimendán en forma de uso compasivo en niños sometidos a corrección quirúrgica de cardiopatía congénita, la evolución de las variables hemodinámicas y analíticas estudiadas y la supervivencia. Material y métodos. Estudio observacional descriptivo retrospectivo. Datos fuente: revisión de historias clínicas (mayo 2005- enero 2010). Se evaluaron las variables hemodinámicas y analíticas pre- y postadministración de levosimendán, fármacos vasoactivos utilizados y sus dosis, así como las reacciones adversas. Resultados. Se incluyeron 42 niños, de ellos 38 quirúrgicos, entre 4 días y 5,75 años de edad (mediana: 92 días). Se registraron 46 administraciones, ya que 4 niños recibieron 2 veces el medicamento. El rango de dosis osciló entre 0,1-0,6μg×kg−1×min−1. Solo un paciente recibió dosis de carga. En 15 administraciones (32,6%), se mantuvo la misma dosis durante toda la infusión; en 19 casos (41,3%) la dosis inicial fue aumentando o disminuyendo según las necesidades de soporte vasoactivo. La supervivencia acumulada en los pacientes quirúrgicos a los 30 días postadministración, calculada por el método de Kaplan-Meier, fue del 80%. Solo el nivel plasmático de lactato tuvo significación estadística en relación con la mortalidad (p<0,001). Conclusiones. No hubo un criterio uniforme en la utilización de levosimendán, empleándose como agente de rescate. La supervivencia acumulada fue similar a la encontrada en los ensayos clínicos con levosimendán en adultos. Son necesarios ensayos clínicos en pacientes pediátricos para determinar el papel de levosimendán en el contexto quirúrgico, que permitan establecer protocolos clínicos para el uso de este medicamento en pediatría(AU)

Objectives. To describe the use of levosimendan for compassionate use in children undergoing surgery for congenital heart disease, as well as survival rates, and the variations in the haemodynamic and analytical variables studied. Material and methods. An observational retrospective descriptive study was performed, using a review of clinical histories, from May 2005 to January 2010. Haemodynamic and analytical variables pre- and post- levosimendan administration, drugs used, and their dosages, and any adverse reactions were recorded. Results. Forty two children, 38 of them undergoing surgical correction, between the ages of four days and 5.75 years (median 92 days) were included. The drug was infused on 46 occasions. Four children received two doses. The infusion rate was among 0.1 to 0.6 μg×kg−1×min−1. Only one patient received a loading dose. In 15 administrations (32.6%), the same dose was maintained throughout the infusion period. In 19 cases (41.3%), the dose was increased or decreased according to the need for vasoactive support. In surgical patients, overall survival after 30 days of the administration, calculated using the Kaplan-Meier method, was 80%. Blood lactate levels were statistically associated with mortality (P<.001). Conclusions. There were no uniform criteria for using levosimendan, and it was only used as a rescue drug. Overall survival was similar to that reported in adult clinical trials. Clinical trials also need to be carried out in paediatric patients to determine the role of levosimendan in surgical practice, in order to develop and establish a clinical protocol for its use in children(AU)

[Retrospective descriptive study about the use of levosimendan in children undergoing surgical correction for congenital heart disease]. / Estudio descriptivo retrospectivo sobre la utilización de levosimendán en niños sometidos a corrección quirúrgica de cardiopatía congénita.

OBJECTIVES: To describe the use of levosimendan for compassionate use in children undergoing surgery for congenital heart disease, as well as survival rates, and the variations in the haemodynamic and analytical variables studied. MATERIAL AND METHODS: An observational retrospective descriptive study was performed, using a review of clinical histories, from May 2005 to January 2010. Haemodynamic and analytical variables pre- and post- levosimendan administration, drugs used, and their dosages, and any adverse reactions were recorded. RESULTS: Forty two children, 38 of them undergoing surgical correction, between the ages of four days and 5.75 years (median 92 days) were included. The drug was infused on 46 occasions. Four children received two doses. The infusion rate was among 0.1 to 0.6 µg × kg⁻¹ × min⁻¹. Only one patient received a loading dose. In 15 administrations (32.6%), the same dose was maintained throughout the infusion period. In 19 cases (41.3%), the dose was increased or decreased according to the need for vasoactive support. In surgical patients, overall survival after 30 days of the administration, calculated using the Kaplan-Meier method, was 80%. Blood lactate levels were statistically associated with mortality (P<.001). CONCLUSIONS: There were no uniform criteria for using levosimendan, and it was only used as a rescue drug. Overall survival was similar to that reported in adult clinical trials. Clinical trials also need to be carried out in paediatric patients to determine the role of levosimendan in surgical practice, in order to develop and establish a clinical protocol for its use in children.

Peste des petits ruminants: a suitable candidate for eradication?

This year will see the final announcement, accompanied by much justifiable celebration, of the eradication from the wild of rinderpest, the 'cattle plague' that has been with us for so many centuries. The only known rinderpest virus (RPV) remaining is in a relatively small number of laboratories around the world, and in the stockpiles of vaccine held on a precautionary basis. As we mark this achievement, only the second virus ever eradicated through human intervention, it seems a good time to look at rinderpest's less famous cousin, peste des petits ruminants ('the plague of small ruminants') and assess if it should, and could, also be targeted for global eradication.

Matrix protein and glycoproteins F and H of Peste-des-petits-ruminants virus function better as a homologous complex.

The matrix (M) protein of paramyxoviruses forms an inner coat to the viral envelope and serves as a bridge between the surface glycoproteins (F and H) and the ribonucleoprotein core. Previously, a marker vaccine (RPV-PPRFH) was produced for the control of peste des petits ruminants (PPR) disease, where the F and H genes of Rinderpest virus (RPV) were replaced with the equivalent genes from Peste-des-petits-ruminants virus (PPRV); however, this virus grew poorly in tissue culture. The poor growth of the RPV-PPRFH chimeric virus was thought to be due to non-homologous interaction of the surface glycoproteins with the internal components of the virus, in particular with the M protein. In contrast, replacement of the M gene of RPV with that from PPRV did not have an effect on the viability or replication efficiency of the recombinant virus. Therefore, in an effort to improve the growth of the RPV-PPRFH virus, a triple chimera (RPV-PPRMFH) was made, where the M, F and H genes of RPV were replaced with those from PPRV. As expected, the growth of the triple chimera was improved; it grew to a titre as high as that of the unmodified PPRV, although comparatively lower than that of the parental RPV virus. Goats infected with the triple chimera showed no adverse reaction and were protected from subsequent challenge with wild-type PPRV. The neutralizing-antibody titre on the day of challenge was approximately 17 times higher than that in the RPV-PPRFH group, indicating RPV-PPRMFH as a promising marker-vaccine candidate.

'Rescue' of mini-genomic constructs and viruses by combinations of morbillivirus N, P and L proteins.

Chloramphenicol acetyltransferase (CAT)-expressing negative-sense mini-genomic constructs of measles virus (MV) and rinderpest virus (RPV) were rescued by standard technology with helper plasmids expressing the nucleocapsid (N), phospho- (P) and large (L) proteins of MV, canine distemper virus (CDV) or RPV in order to determine whether the proteins of different viruses can function together. Homogeneous sets consisting of N, P and L plasmids derived from one virus were able to generate reporter gene expression from either mini-genomic construct. Heterogeneous sets of proteins from different viruses were not functional, with the exception that a low level of activity was obtained when MV N and P protein were combined with RPV L protein in the rescue of the MV mini-genomic construct, or CDV N was combined with RPV P and L in the rescue of the RPV mini-genome. However, only homogeneous sets of plasmids were able to rescue infectious virus from full-length anti-genome-expressing plasmids.

The Plowright vaccine strain of Rinderpest virus has attenuating mutations in most genes.

The currently used vaccine strain of Rinderpest virus was derived by serial passage of the highly virulent Kabete 'O' strain (KO). A full-length cDNA copy of the KO strain was made from which a virus identical in pathogenicity to the wild-type virus was rescued. A series of chimeric viruses was prepared in which the coding sequences for the N, P, F, H or L proteins were replaced with the corresponding sequences from the vaccine strain. The KO-based virus with the vaccine strain H gene and that with the carboxy-terminal half of the L gene replaced with the corresponding sequence from the vaccine strain retained all or almost all of the virulence of the original KO virus. Animals infected with the KO-based virus containing the vaccine strain N, P or F gene, or the amino-terminal half of the L gene, developed high and prolonged pyrexia and leukopenia, but with reduced or absent lesions and other clinical signs; although partially attenuated, none was nearly as attenuated as the vaccine strain itself. These data indicate that the high attenuation and stability of the current vaccine are due to the accumulation of a number of separate mutations, none of which is itself so sufficiently debilitating that there is strong selective pressure in favour of the revertant.

Development of new generation rinderpest vaccines.

Veterinary science has benefited much from the advances in biotechnology during the past 20 years. New and improved diagnostic techniques for infectious diseases have been developed and new and highly effective vaccines to prevent such diseases have been introduced and more have been, or are about to be, field-tested. The latest development in negative strand virology, reverse genetics, the ability to rescue live virus from a DNA copy of the RNA genome, is being used to address questions concerning virus pathogenicity at the molecular level and to produce "marker" vaccines, i.e. vaccines that allow serological identification of all vaccinated animals. Such a vaccine would greatly benefit the continuing campaign for the global eradication of rinderpest since it would then be possible, by serological means, to detect wild type virus circulating in local areas or regions where it is still necessary to vaccinate and where the vaccination levels are below those required to eliminate the virus. Here we describe different approaches we have taken to produce such a vaccine using reverse genetics to add a marker to the existing and widely used Plowright rinderpest vaccine.

[Post-surgical paediatric pain: Nursing- PCA vs continuous I.V. infusion of tramadol ]. / Dolor postoperatorio en lactantes y niños pequeños: nursing-PCA vs perfusión i.v. de tramadol.

AIM: To evaluate the efficiency in the control of the post-surgical paediatric pain of the combination of a weak opioid [tramadol (T)] and an NSAID (paracetamol), comparing its administration through "Nursing-PCA" (NCA) techniques or through continuous i.v. infusion. METHODS: The investigation has been carried out in 30 patients (mean 9.5 months) selected according to their foreseeable degree of moderate-hard pain. All of them consumed in the postoperative period: rectal paracetamol (20 mg/Kg) every 8 hours and tramadol in two groups. Group I: PCA pump with tramadol that was handled by the nurse. Initial dose: 0.5 mg/Kg NCA, bolus injection 0.3 mg/Kg with an interval of 10 minutes for security and a highest dose of 1.2 mg/Kg/4 h every 4 hours. Group II: continuous infusion i.v. of tramadol (6 mg/Kg/24 h). The pain was evaluated, as well as the sedative action, saturation oxygen, respiratory and hemodynamics parameters, adverse effects, and efficiency during the first 24 hours, as well as the number of total dose of drugs asked in the Nursing PCA group. RESULTS: Pain decreased in both groups. There were more sedative effects in group II and the total dose of tramadol was higher. There were no cases of respiratory depression. CONCLUSIONS: The combination of tramadol and paracetamol through "Nursing PCA" has turned out to be an efficient method in the treatment of the post-surgical pain in little children and those whose are in their lacteal period. It is a possible alternative of the continuous infusion of Morphine in these patients.

Rinderpest virus H protein: role in determining host range in rabbits.

A major molecular determinant of virus host-range is thought to be the viral protein required for cell attachment. We used a recombinant strain of Rinderpest virus (RPV) to examine the role of this protein in determining the ability of RPV to replicate in rabbits. The recombinant was based on the RBOK vaccine strain, which is avirulent in rabbits, carrying the haemagglutinin (H) protein gene from the lapinized RPV (RPV-L) strain, which is pathogenic in rabbits. The recombinant virus (rRPV-lapH) was rescued from a cDNA of the RBOK strain in which the H gene was replaced with that from the RPV-L strain. The recombinant grew at a rate equivalent to the RPV-RBOK parental virus in B95a cells but at a lower rate than RPV-L. The H gene swap did not affect the ability of the RBOK virus to act as a vaccine to protect cattle against virulent RPV challenge. Rabbits inoculated with RPV-L became feverish, showed a decrease in body weight gain and leukopenia. High virus titres and histopathological lesions in the lymphoid tissues were also observed. Clinical signs of infection were never observed in rabbits inoculated with either RPV-RBOK or with rRPV-lapH; however, unlike RPV-RBOK, both RPV-L and rRPV-lapH induced a marked antibody response in rabbits. Therefore, the H protein plays an important role in allowing infection to occur in rabbits but other viral proteins are clearly required for full RPV pathogenicity to be manifest in this species.

Rinderpest virus C and V proteins interact with the major (L) component of the viral polymerase.

Rinderpest virus, like other Morbilliviruses, expresses three proteins from the single P gene. In addition to the P protein, which interacts both with the viral polymerase (L) and the nucleocapsid (N) protein, the virus expresses a C and a V protein from the same gene. The functions of these two proteins in the viral life cycle are not clear. Although both C and V proteins are dispensable, in that viable viruses can be made that express neither, each seems to play a role in optimum viral replication. We have used the yeast-two hybrid system, binding to coexpressed fusions of C and V to glutathione-S-transferase, and studies of the native size of these proteins to investigate interactions of the rinderpest virus C and V proteins with other virus-encoded proteins. The V protein was found to interact with both the N and L proteins, while the C protein was found to bind to the L protein, and to self-associate in high-molecular-weight aggregates.

Recombinant rinderpest vaccines expressing membrane-anchored proteins as genetic markers: evidence of exclusion of marker protein from the virus envelope.

Rinderpest virus (RPV) causes a severe disease of cattle resulting in serious economic losses in parts of the developing world. Effective control and elimination of this disease require a genetically marked rinderpest vaccine that allows serological differentiation between animals that have been vaccinated against rinderpest and those which have recovered from natural infection. We have constructed two modified cDNA clones of the vaccine strain RNA genome of the virus, with the coding sequence of either a receptor site mutant form of the influenza virus hemagglutinin (HA) gene or a membrane-anchored form of the green fluorescent protein (GFP) gene (ANC-GFP), inserted as a potential genetic marker. Infectious recombinant virus was rescued in cell culture from both constructs. The RPVINS-HA and RPVANC-GFP viruses were designed to express either the HA or ANC-GFP protein on the surface of virus-infected cells with the aim of stimulating a strong humoral antibody response to the marker protein. In vitro studies showed that the marker proteins were expressed on the surface of virus-infected cells, although to different extents, but neither was incorporated into the envelope of the virus particles. RPVINS-HA- or RPVANC-GFP-vaccinated cattle produced normal levels of humoral anti-RPV antibodies and significant levels of anti-HA or anti-GFP antibodies, respectively. Both viruses were effective in stimulating protective immunity against RPV and antibody responses to the marker protein in all animals when tested in a cattle vaccination trial.