Bayesian analysis of parent-specific transmission ratio distortion in seven Spanish beef cattle breeds.

Transmission ratio distortion (TRD) is the departure from the expected Mendelian ratio in offspring, a poorly investigated biological phenomenon in livestock species. Given the current availability of specific parametric methods for the analysis of segregation data, this study focused on the screening of TRD in 602 402 single nucleotide polymorphisms covering all autosomal chromosomes in seven Spanish beef cattle breeds. On average, 0.13% (n = 786) and 0.01% (n = 29) of genetic markers evidenced sire- or dam-specific TRD respectively. There were no single nucleotide polymorphisms accounting for both sire- and dam-specific TRD at the same time, and only one marker (rs43147474) accounted for (sire-specific) TRD in all seven breeds. It must be noted that rs43147474 is located in the fourth intronic region of the GTP-binding protein 10 gene, and this locus has been previously linked to the maintenance of mitochondria and nucleolar architectures. Alternatively, other candidate genes surround this hot-spot for sire-specific TRD in the cattle genome, and they are related to embryonic and postnatal lethality as well as prostate cancer, among others. This research characterized the distribution of TRD in the bovine genome, highlighting heterogeneous results when comparing across breeds.

Evaluation of the potential use of a meta-population for genomic selection in autochthonous beef cattle populations.

This study investigated the potential application of genomic selection under a multi-breed scheme in the Spanish autochthonous beef cattle populations using a simulation study that replicates the structure of linkage disequilibrium obtained from a sample of 25 triplets of sire/dam/offspring per population and using the BovineHD Beadchip. Purebred and combined reference sets were used for the genomic evaluation and several scenarios of different genetic architecture of the trait were investigated. The single-breed evaluations yielded the highest within-breed accuracies. Across breed accuracies were found low but positive on average confirming the genetic connectedness between the populations. If the same genotyping effort is split in several populations, the accuracies were lower when compared with single-breed evaluation, but showed a small advantage over small-sized purebred reference sets over the accuracies of subsequent generations. Besides, the genetic architecture of the trait did not show any relevant effect on the accuracy with the exception of rare variants, which yielded slightly lower results and higher loss of predictive ability over the generations.

[Metastasis in maxilar sinus as only manifestation of disseminate renal adenocarcinoma]. / Metástasis en seno maxilar como única manifestación de adenocarcinoma renal diseminado.

Paranasal sinuses and nose metastasis are very uncommon. About 50 have been reported. Renal cell carcinoma is the primary neoplasm which most frequently metastasizes in the nasosinusal region, followed by breast and lug. Symptoms are unspecific, but the epistaxis constitutes the most common sign due to the significant vascularizations of the tumor. Prognosis is poor. The survival rate fluctuates between 15-30% at 5 years. Surgery is the elective treatment.

Genomic differentiation between Asturiana de los Valles, Avileña-Negra Ibérica, Bruna dels Pirineus, Morucha, Pirenaica, Retinta and Rubia Gallega cattle breeds.

The Spanish local beef cattle breeds have most likely common origin followed by a process of differentiation. This particular historical evolution has most probably left detectable signatures in the genome. The objective of this study was to identify genomic regions associated with differentiation processes in seven Spanish autochthonous populations (Asturiana de los Valles (AV), Avileña-Negra Ibérica (ANI), Bruna dels Pirineus (BP), Morucha (Mo), Pirenaica (Pi), Retinta (Re) and Rubia Gallega (RG)). The BovineHD 777K BeadChip was used on 342 individuals (AV, n=50; ANI, n=48; BP, n=50; Mo, n=50; Pi, n=48; Re, n=48; RG, n=48) chosen to be as unrelated as possible. We calculated the fixation index (F ST ) and performed a Bayesian analysis named SelEstim. The output of both procedures was very similar, although the Bayesian analysis provided a richer inference and allowed us to calculate significance thresholds by generating a pseudo-observed data set from the estimated posterior distributions. We identified a very large number of genomic regions, but when a very restrictive significance threshold was applied these regions were reduced to only 10. Among them, four regions can be highlighted because they comprised a large number of single nucleotide polymorphisms and showed extremely high signals (Kullback-Leiber divergence (KLD)>6). They are located in BTA 2 (5 575 950 to 10 152 228 base pairs (bp)), BTA 5 (17 596 734 to 18 850 702 bp), BTA 6 (37 853 912 to 39 441 548 bp) and BTA 18 (13 345 515 to 15 243 838 bp) and harbor, among others, the MSTN (Myostatin), KIT-LG (KIT Ligand), LAP3 (leucine aminopeptidase 3), NAPCG (non-SMC condensing I complex, subunit G), LCORL (ligand dependent nuclear receptor corepressor-like) and MC1R (Melanocortin 1 receptor) genes. Knowledge on these genomic regions allows to identify potential targets of recent selection and helps to define potential candidate genes associated with traits of interest, such as coat color, muscle development, fertility, growth, carcass and immunological response.

Funcionamiento cognitivo y rendimiento deportivo en jóvenes futbolistas: Una revisión sistemática / Funcionamento cognitivo e desempenho esportivo em jovens jogadores de futebol: uma revisão sistemática / Cognitive functioning and sports performance in young soccer players: A systematic review

El funcionamiento cognitivo está adquiriendo especial relevancia a la hora de estudiar los factores que influyen en el rendimiento en fútbol. Si bien la relación entre funciones cognitivas y rendimiento deportivo cuenta con una literatura extensa en futbolistas adultos, no ocurre lo mismo en jugadores de edades tempranas, donde dicha asociación no se ha explorado en profundidad. Este trabajo surge con el propósito de conocer el estado de la cuestión y profundizar en esta línea de investigación en categorías infantiles y juveniles, de edades comprendidas entre los 8 y 19 años. Para ello, se ha llevado a cabo una revisión sistemática sobre las relaciones existentes entre el funcionamiento cognitivo y el rendimiento deportivo en jóvenes futbolistas. Para la realización de dicha revisión sistemática se analizaron los artículos publicados sobre esta cuestión en los últimos 10 años siguiendo el método PRISMA. Para una búsqueda exhaustiva de la literatura existente se han utilizado las bases de datos Web of Science (WoS), SCOPUS, Dialnet, PubMed y Google Scholar, entre otras, incluyendo artículos publicados tanto en lengua castellana como inglesa. Finalmente, 12 artículos fueron analizados e incluidos en la revisión. Los resultados mostraron que existen relaciones significativas entre las funciones cognitivas y el rendimiento en jóvenes futbolistas, de entre las cuales destacan variables como la atención, el control inhibitorio, la flexibilidad cognitiva o la toma de decisiones, encontrándose diferencias entre las puntuaciones obtenidas por futbolistas de élite y las obtenidas por deportistas amateurs o población general, siendo significativamente mayores en el primer grupo. (AU)

Cognitive functioning is acquiring special relevance when studying the factors that influence soccer performance. Although the relationship between cognitive functions and sport performance has an extensive literature in adult soccer players, the same does not happen in young players, where this association has not been explored in depth. This work arises with the objective of knowing the state of the issue and going in depth in this line of research in youth categories, between 8 and 19 years old. For this purpose, a systematic review has been carried out on the existing relationship between cognitive functioning and sports performance in youth soccer players. In order to carry out this systematic review, the articles published on this issue in the last 10 years were analyzed following the PRISMA method. For an exhaustive search of the literature, the database Web of Science (WoS), SCOPUS, Dialnet, PubMed and Google Scholar, among others, were used, including articles published both Spanish and English. Finally, 12 articles were analyzed and included in the review. The results showed significant relationship between cognitive functions and performance in youth soccer players, highlighting variables such as attention, inhibitory control, cognitive flexibility or decision making, finding differences between scores obtained by elite soccer players and those obtained by amateur athletes or general population, being significantly higher in the first group (AU)

O funcionamento cognitivo está adquirindo especial relevância no estudo dos fatores que influenciam o desempenho no futebol. Embora a relação entre funções cognitivas e desempenho esportivo seja extensa na literatura em jogadores de futebol adulto, o mesmo não ocorre em jogadores de tenra idade, onde essa associação ainda não foi explorada em profundidade. Este trabalho surge com o objetivo de conhecer o estado da questão e aprofundar esta linha de pesquisa nas categorias infanto-juvenil, na faixa etária entre 8 e 19 anos. Para tanto, foi realizada uma revisão sistemática sobre as relações entre funcionamento cognitivo e desempenho esportivo em jovens jogadores de futebol. Para a realização desta revisão sistemática, os artigos publicados sobre o assunto nos últimos 10 anos foram analisados segundo o método PRISMA. Para uma busca exaustiva da literatura existente, foram utilizadas as bases de dados Web of Science (WoS), SCOPUS, Dialnet, PubMed e Google Scholar, entre outras, incluindo artigos publicados em espanhol e inglês. Por fim, 12 artigos foram analisados e incluídos na revisão. Os resultados mostraram que existemrelações significativas entre funções cognitivas e desempenho em jovens jogadores de futebol, entre as quais se destacam variáveis como atenção, controle inibitório, flexibilidade cognitiva ou tomada de decisão, encontrando diferenças entre os escores obtidos por jogadores de futebol de elite e aqueles. obtidos por atletas amadores ou pela população em geral, sendo significativamente maior no primeiro grupo. (AU)

La Final 4 de balonmano: análisis del juego combinativo masculino y femenino mediante coordenadas polares / Handebol Final 4: análise do jogo combinatório masculino e feminino por meio de coordenadas polares / Handball Final 4: analysis of the male and female combinatorial game using polar coordinates

El objetivo de este estudio fue analizar mediante el análisis de Coordenadas Polares la eficacia de las conductas que se muestran durante el juego combinativo ofensivo en el balonmano de élite masculino y femenino a nivel internacional. Se realizaron 16 sesiones de observación a los 8 equipos, 4 masculinos y 4 femeninos, participantes en la Final Four de la Liga de Campeones de balonmano del año 2019, para ello se utilizó una herramienta de observación que fue diseñada ad hoc y que estaba formada por 12 criterios y 62 categorías. Con un diseño observacional Nomotético/Puntual/Multidimensional, se seleccionaron tres conductas focales para el análisis de Coordenadas Polares: los medios tácticos colectivos simples, la combinación de los medios tácticos y las transformaciones. Los resultados evidenciaron diferencias en el flujo de comportamientos entre el juego femenino y masculino. Destaca que en la categoría femenina las jugadoras logran el desequilibrio mediante los medios tácticos colectivos simples y sus combinaciones. Sin embargo, en categoría masculina se logra el desequilibrio e incluso la obtención de situaciones de lanzamiento ventajoso mediante las transformaciones. El juego masculino se asocia con la combinación de medios tácticos en desventaja en el marcador, mientras que en la categoría femenina se asocia con los medios tácticos simples. Ambas categorías muestran mayor utilización de los medios tácticos colectivos simples en los primeros minutos de juego, y las combinaciones de medios tácticos en los últimos. Las diferencias sugieren intervenir en la preparación de ambas categorías con una orientación específica hacia las mejoras en el desempeño del juego táctico colectivo ofensivo mediante la aportación activa de cada puesto específico y la adaptación eficiente a cambios en los sistemas de ataque en función de las necesidades del juego. (AU)

The objective of this study was to analyze the effectiveness of the behaviors shown during the offensive combinatorial game in elite male and female handball at an international level through the analysis of Polar Coordinates. 16 observation sessions were carried out on the 8 teams, 4 male and 4 female, participants in the Final Four of the Handball Champions League in 2019, for this an observation tool was used that was designed ad hoc and that was formed by 12 criteria and 62 categories. Three focal behaviors were selected forthe analysis of Polar Coordinates: simple collective tactical means, the combination of tactical means and transformations with a Nomothetic/Punctual/Multidimensional observational design. The results showed differences in the flow of behaviors between the female and male game. It stands out that in the female category the players achieve imbalance through simple collective tactical means and their combinations. However, in the male category, the imbalance is achieved and even the obtaining of advantageouslaunch situations through the transformations. The men's game is associated with the combination of tactical means at a disadvantage on the scoreboard, while in the female category it is associated with simple tactical means. Both categories show greater use of simple collective tactical means in the first minutes of play, and combinations of tactical means in the last minutes. The differences suggest intervening in the preparation of both categories with a specific orientation towards improvements in the performance of the offensive collective tactical game through the active contribution of each specific position and the efficient adaptation to changes in the attack systems depending on the needs of the team play. (AU)

O objetivo deste estudo foi analisar, por meio da análise de Coordenadas Polares, a eficácia dos comportamentos demonstrados durante o jogo combinativo ofensivo no handebol de elite masculino efeminino em nível internacional. Foram realizadas 16 sessões de observação nas 8 equipas, 4 masculinas e 4 femininas, participantes nas Quartas Finais da Liga dos Campeões de Andebol em 2019, para isso foi utilizado um instrumento de observação que foi desenhado ad hoc e que foi formado por 12 critérios e 62 categorias. Com um desenho observacional Nomotético/Pontual/Multidimensional, três comportamentos focais foram selecionados para a análise das Coordenadas Polares: os meios táticos coletivos simples, acombinação dos meios táticos e as transformações. Os resultados mostraram diferenças no fluxo de comportamentos entre o jogo feminino e o masculino. Destaca-se que na categoria feminina as jogadoras alcançam o desequilíbrio por meio de simples meios táticos coletivos e suas combinações. Porém, na categoria masculina, o desequilíbrio é alcançado e até mesmo a obtenção de situações vantajosas de lançamento através das transformações. O jogo masculino está associado à combinação de meios táticos em desvantagem no placar, enquanto no feminino está associado a meios táticos simples. Ambasas categorias apresentam maior utilização de meios táticos coletivos simples nos primeiros minutos de jogo e combinações de meios táticos nos últimos minutos. As diferenças sugerem intervir na preparação de ambas as categorias com uma orientação específica para melhorias no desempenho do jogo tático coletivo ofensivo através da contribuição ativa de cada posição específica e da adaptação eficiente às mudanças nos sistemas de ataque em função das necessidades da equipe jogar. (AU)

[Application of a critical incident reporting and analysis system in an anesthesiology department]. / Utilización de un sistema de comunicación y análisis de incidentes críticos en un servicio de anestesia.

OBJECTIVES: To ascertain the changes in anesthesia-related morbidity and mortality after application of a scheme for reporting critical incidents and to assess the effect of implementing preventive measures against the detected errors. PATIENTS AND METHODS: We defined a critical incident to be any situation in which the margin of safety for the patient was reduced or might have been reduced. We analyzed data from the period between January 1999 and December 2004. RESULTS: The number of critical incidents was 547 (0.79% of 68627 anesthetic procedures). Human error was identified in 279 incidents (51%). The most frequent factors underlying errors were wrong diagnosis of the situation, communication problems, and failure to check equipment and drugs. The patient suffered no adverse effect in 81.8% of the incidents; 78.9% were considered preventable. Introducing an equipment checklist before anesthesia reduced the number of incidents from 90 events in 21809 cases in 31 months to 34 events out of 22064 cases in 29 months; chi2 test, P < 0.05; odds ratio (OR), 2.68; 95% confidence interval (CI), 1.80-3.98). Labeling syringes reduced errors in the administration of medications from 45 errors in 21 809 cases in 31 months to 27 in 22064 cases in 29 months; chi2, P < 0.05; OR, 1.68; 95% CI, 1.04-2.72. CONCLUSIONS: Corrective measures were adopted as a result of the incident reporting scheme. Some of the measures led to a statistically significant reduction in equipment and drug administration errors.

[Esthesioneuroblastoma. Description of a case and review of the literature]. / Estesioneuroblastoma. Presentación de un caso clínico y revisión de la bibliografía.

The esthesioneuroblastoma is a malignant and rare type of the nasal cavity. Affected patients usually present with a progressive nasal obstruction, rhinorrea and epistaxis. Metastasis occurs in about 30% of patiens, the most common sites for metastasis are the cervical lymph nodes, less frequent in anothers organs. The optimum management is probably surgery combined with radiotherapy, the chemotherapy is usually reserved for local advanced tumor

Linkage disequilibrium, persistence of phase, and effective population size in Spanish local beef cattle breeds assessed through a high-density single nucleotide polymorphism chip.

Linkage disequilibrium (LD) and persistence of phase are fundamental approaches for exploring the genetic basis of economically important traits in cattle, including the identification of QTL for genomic selection and the estimation of effective population size () to determine the size of the training populations. In this study, we have used the Illumina BovineHD chip in 168 trios of 7 Spanish beef cattle breeds to obtain an overview of the magnitude of LD and the persistence of LD phase through the physical distance between markers. Also, we estimated the time of divergence based on the persistence of the LD phase and calculated past from LD estimates using different alternatives to define the recombination rate. Estimates of average (as a measure of LD) for adjacent markers were close to 0.52 in the 7 breeds and decreased with the distance between markers, although in long distances, some LD still remained (0.07 and 0.05 for markers 200 kb and 1 Mb apart, respectively). A panel with a lower boundary of 38,000 SNP would be necessary to launch a successful within-breed genomic selection program. Persistence of phase, measured as the pairwise correlations between estimates of in 2 breeds at short distances (10 kb), was in the 0.89 to 0.94 range and decreased from 0.33 to 0.52 to a range of 0.01 to 0.08 when marker distance increased from 200 kb to 1 Mb, respectively. The magnitude of the persistence of phase between the Spanish beef breeds was similar to those found in dairy breeds. For across-breed genomic selection, the size of the SNP panels must be in the range of 50,000 to 83,000 SNP. Estimates of past showed values ranging from 26 to 31 for 1 generation ago in all breeds. The divergence among breeds occurred between 129 and 207 generations ago. The results of this study are relevant for the future implementation of within- and across-breed genomic selection programs in the Spanish beef cattle populations. Our results suggest that a reduced subset of the SNP panel would be enough to achieve an adequate precision of the genomic predictions.

Long-term outcome of allogeneic or autologous haemopoietic cell transplantation for acute lymphoblastic leukaemia in second remission in children. GETMON experience 1983-1998.

We present a retrospective study of long-term outcome and predictive factors of survival and relapse in 219 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. They received allogeneic (allo) or autologous (auto) haemopoietic cell transplantation (HCT) depending on the availability of a matched sibling donor. The probability of event-free survival (EFS) for the total patient group was 0.35+0.03 at 14 years. No significant differences were observed for EFS between allo- and auto-HCT: 0.39+0.05 vs 0.32+0.04 (P=0.43). A better EFS was seen in patients with a late relapse (LR) (P=0.06 and 0.02, for allogeneic and autologous respectively). Significantly better EFS was observed in allo-HCT patients under 10 years of age and in auto-HCT patients with leukocytes at diagnosis below 25 x 109/l and late relapse. Predictive factors of failure in both groups were early relapse (ER), medullary relapse and age over 10 years. The probability of relapse (RP) for the total group of patients was 0.57+0.03, and it was significantly higher in auto-HCT patients: 0.65+0.04 vs 0.42+0.06 (P=0.002). Factors predictive for relapse were medullary and early relapse, auto-HCT and WBC >25 x 109/l at diagnosis.

Splenectomy for poor graft function after allogeneic bone marrow transplantation in patients with chronic myeloid leukemia.

We report four patients with chronic myeloid leukemia (CML) that showed poor graft function after a non-T-depleted bone marrow transplantation (BMT) from an HLA-compatible sibling donor and who were successfully treated with splenectomy. Conditioning was done with cyclophosphamide (CY) and total body irradiation (TBI) without additional splenic irradiation. Three patients had enlarged spleens before BMT. The nucleated cell dose infused ranged from 2.3-3.2 x 10(8)/kg. Bone marrow (BM) examination prior to splenectomy showed BM aplasia (three cases) or hypocellularity (one case). At splenectomy no patient had evidence of cytomegalovirus (CMV) infection or severe acute GVHD; and three patients had moderately enlarged spleens. All patients were transfusion dependent. Complete hematological recovery was obtained in all patients. BM cellularity was normal 1 month after splenectomy. Complete chimerism of donor origin was documented. The four patients are alive (+16 to +58 months after BMT). Thus, in patients with CML, a poor graft function may be successfully corrected by splenectomy.

Porcine circovirus type 2 (PCV2) enteric disease: an independent condition or part of the systemic disease?

Intestinal disorders in growing and finishing pigs have been associated with several infectious agents, including Porcine circovirus type 2 (PCV2). This virus has been mainly related with PCV2-systemic disease (PCV2-SD); nevertheless, some authors have suggested a possible restricted intestinal infection of this virus associated with enteric clinical signs. This condition has been referred as PCV2-enteric disease (PCV2-ED). The present study analysed retrospectively, from a pathological point of view, the relation between intestinal disorders and PCV2 infection in nursery and growing-finishing pigs. Among the 96 selected pigs suffering from enteric disease and submitted for necropsy between 1998 and 2011, the most prevalent enteric lesions were catarrhal enteritis/colitis (77.1%), followed by fibrinous lesions (11.5%), granulomatous inflammation (4.2%) and other lesions such as haemorrhages or ulceration (4.2%). Seventy-two pigs (75%) were positive for PCV2 by in situ hybridization (ISH). Among positive pigs for PCV2 ISH, 39 animals suffered from PCV2-SD and 33 had no lymphoid lesions but low amount of viral nucleic acid in several lymphoid tissues, therefore, these animals did not qualify for PCVD-ED. In conclusion, all animals with enteric disorders that were positive to PCV2 by ISH had evidence of viral systemic infection. These results suggest that PCV2-ED is probably a negligible condition and PCV2 mainly contributes to enteric clinical disorders in relation to PCV2-SD occurrence.

Genetic diversity and divergence among Spanish beef cattle breeds assessed by a bovine high-density SNP chip.

The availability of SNP chips for massive genotyping has proven to be useful to genetically characterize populations of domestic cattle and to assess their degree of divergence. In this study, the Illumina BovineHD BeadChip genotyping array was used to describe the genetic variability and divergence among 7 important autochthonous Spanish beef cattle breeds. The within-breed genetic diversity, measured as the marker expected heterozygosity, was around 0.30, similar to other European cattle breeds. The analysis of molecular variance revealed that 94.22% of the total variance was explained by differences within individuals whereas only 4.46% was the result of differences among populations. The degree of genetic differentiation was small to moderate as the pairwise fixation index of genetic differentiation among breeds (F) estimates ranged from 0.026 to 0.068 and the Nei's D genetic distances ranged from 0.009 to 0.016. A neighbor joining (N-J) phylogenetic tree showed 2 main groups of breeds: Pirenaica, Bruna dels Pirineus, and Rubia Gallega on the one hand and Avileña-Negra Ibérica, Morucha, and Retinta on the other. In turn, Asturiana de los Valles occupied an independent and intermediate position. A principal component analysis (PCA) applied to a distance matrix based on marker identity by state, in which the first 2 axes explained up to 17.3% of the variance, showed a grouping of animals that was similar to the one observed in the N-J tree. Finally, a cluster analysis for ancestries allowed assigning all the individuals to the breed they belong to, although it revealed some degree of admixture among breeds. Our results indicate large within-breed diversity and a low degree of divergence among the autochthonous Spanish beef cattle breeds studied. Both N-J and PCA groupings fit quite well to the ancestral trunks from which the Spanish beef cattle breeds were supposed to derive.

Electroretinograms and visual evoked potentials in long-term monocularly deprived cats.

The effects of long-term monocular lid-suture deprivation on visual-evoked cortical potentials (VEPs) and flash- and pattern-evoked electroretinograms (FERGs and PERGs, respectively) were assessed in the cat. VEPs were virtually eliminated when recorded with the deprived eye, indicating that the lid suture produced a severe amblyopia in that eye. In contrast, FERGs and PERGs were more similar for both deprived and nondeprived eyes and comparable to those recorded in normal animals. The current findings demonstrate that long-term deprivation (3-4 yr) does not produce systematic changes in the electroretinogram.

Allogeneic BMT in a patient with CML and prior disseminated infection by mycobacterium avium complex.

A patient with chronic myeloid leukemia (CML) who developed a disseminated infection by mycobacterium avium complex (MAC) was successfully treated with rifampin, ethambutol, isoniazid, cycloserin and ciprofloxacin. Diagnosis was proven by histologic examination of hepatic biopsy and culture of the liver biopsy material. Two years later the patient underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor. Antimycobacterial prophylaxis to MAC with ethambutol, cycloserin and ciprofloxacin was given throughout the immediate post-transplant period. On day +25 post-BMT secondary prophylaxis was changed to ciprofloxacin and clarithromycin due to hepatic toxicity. Treatment was maintained until day 100 without side effects. There was no evidence of recurrent mycobacteriosis. Eight months after BMT the patient is well, with a good performance status and chronic graft-versus-host disease (GVHD) limited to the oral mucosa. Thus, MAC infection prior to transplant need not be a contraindication to successful BMT.

Disappearance of lupus anticoagulant after allogeneic bone marrow transplantation.

Lupus anticoagulant antibodies have never been reported to disappear after either allogeneic or autologous bone marrow transplantation in humans. We report the first case of disappearance of lupus anticoagulant antibodies in a patient without systemic lupus erythematosus or clinical evidence of other autoimmune disorders, who received an allogeneic bone marrow transplant as treatment for chronic myeloid leukemia. Although marrow transplantation is not a recognized therapy for antiphospholipid syndrome, our observation should be considered another example of the capability of intensive chemo-radiotherapy followed by stem cell transplantation to ablate a pathologic marrow clone resulting in an autoimmune disorder and improve, or even cure, some severe autoimmune diseases.

Recombinant human GM-CSF enhances T cell-mediated cytotoxic function after ABMT for hematological malignancies.

The interactions of GM-CSF with cells of lymphoid lineage are not well understood and their clinical use has been focused on the acceleration of hematopoietic recovery. However, several reports have shown that human GM-CSF can affect certain T lymphocyte in vitro cytotoxic functions. To assess whether recombinant human GM-CSF (rhGM-CSF) has a more broadly based activity in the immune system, we studied its in vivo effects on endogenously-generated killer function in patients undergoing ABMT for hematologic malignancies. Eleven patients received rhGM-CSF after ABMT: eight received rhGM-CSF as a 2-h infusion daily from days +3 to +17 and three received rhGM-CSF until reaching > 500 x 10(6)/l granulocytes. Eight patients not enrolled in the rhGM-CSF therapy protocol served as controls. Natural killer (NK) cell activity and activated killer (AK) cell activity were studied before conditioning, during rhGM-CSF therapy and after withdrawal of GM-CSF. rhGM-CSF therapy does not affect NK activity. Circulating lymphocytes with the ability to kill AK-sensitive targets appear spontaneously in control ABMT patients. AK activity was 1.6 +/- 0.8% before ABMT increasing to 9 +/- 2.5% and 14 +/- 2.1% at 2 and 3 weeks after ABMT, respectively (p = 0.002). In rhGM-CSF-treated patients this phenomenon also occurs. AK activity increased from 2.4 +/- 1.5% before ABMT to 33.6 +/- 8.1% during rhGM-CSF administration (p = 0.001) and 17.5 +/- 3.4% after withdrawal (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Invasive pulmonary aspergillosis prior to BMT in acute leukemia patients does not predict a poor outcome.

Eight patients with acute leukemia (AL) and invasive pulmonary aspergillosis (IPA) developing during previous antileukemic therapy underwent BMT (autologous in 6 cases and allogeneic 2). IPA was treated prior to BMT with full doses of amphotericin B, associated with surgical resection in three cases. One patient was treated with amphotericin B and itraconazole. Prior to BMT, seven patients had minimal residual pulmonary lesions. All patients received amphotericin B (0.5 mg/kg/day) during the aplastic period prior to engraftment. One patient died of Gram-negative septic shock before engraftment. Seven patients achieved complete hematological engraftment without any evidence of IPA reactivation. Amphotericin B was well tolerated with only minimal transient renal dysfunction in three patients. Later pulmonary complications related to IPA were observed in only one patient who developed a self-limited episode of hemoptysis. One patient died of CMV pneumonitis and two of leukemia relapse. Four patients survive disease-free and without complications related to IPA. We conclude that the reactivation of correctly treated IPA can be successfully prevented in BMT patients by use of prophylactic amphotericin B. With this approach, prior IPA is not a contraindication to BMT.

Autologous bone marrow transplantation in 22 adult patients with lymphoblastic lymphoma responsive to conventional dose chemotherapy.

In order to clarify the role of autologous bone marrow transplantation in adult lymphoblastic lymphoma (LBL) patients we have conducted a retrospective multi-institutional Spanish survey. Twenty-two adult patients, 20 males, two females, age 14-52 years (median 25.5) with LBL were treated with high-dose chemoradiotherapy and autologous bone marrow support. Fourteen cases were transplanted in first complete remission (CR1) and eight with other chemosensitive status (four later CR, two partial remissions and two sensitive relapses). From the 14 cases transplanted in CR1, four had previous bone marrow involvement and one meningeal infiltration; eight cases were Ann-Arbor stage IV and fulfilled accepted high-risk criteria for relapse. The conditioning regimen consisted of cyclophosphamide (60 mg/kg x 2) and total body irradiation (9-12 Gy) in 16 cases and high dose chemotherapy in six. The procedure-related mortality was 9% (7% in CR1 patients). The actuarial 2-year overall survival for CR1 patients was 85% at a median follow-up of 19 months. Disease-free survival (DFS) was 77%. In patients with less favourable disease status the 2-year overall and DFS were 73% and 50% respectively. In this study the DFS in CR1 patients was not influenced by bone marrow involvement or high-risk criteria predictive for relapse. These results support the effectiveness of this procedure, mainly for patients in CR1.

Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration after autologous bone marrow transplantation for acute myeloblastic leukemia enhances activated killer cell function and may diminish leukemic relapse.

Leukemic relapse is the major complication following autologous bone marrow transplantation (BMT) in acute myeloblastic leukemia (AML). Previously, we have shown that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) infusion after autologous BMT has the ability to augment endogenous activated killer (AK) cell function which may play a role in the eradication of minimal residual disease. However, the clinical application of rhGM-CSF in patients with AML has been limited by its potential stimulatory effect on the malignant clone. Here we report the effect of rhGM-CSF 5 micrograms/kg/day infusion on AK cell function in 20 patients with AML undergoing autologous BMT. AK cell function was investigated before autologous BMT, during rhGM-CSF therapy and after withdrawal. In addition, its influence on the actuarial risk of relapse is analyzed and compared with a historical control group of 20 patients transplanted immediately before initiation of this study. rhGM-CSF significantly enhanced AK cell function. During rhGM-CSF treatment, median AK cell function rose from 1.8% before autologous BMT (range 0-8%) to 35% (range 3-80%) and remained increased after cessation of rhGM-CSF (median 20%; range 0-36%; P < 0.001). After a median follow-up of 24 months, the actuarial risk of relapse is 37.4% in rhGM-CSF-treated patients compared with 49.5% in controls (P = 0.05). Interestingly, none of the 7 patients with an AK cell activity > or = 20% in the first 2-5 weeks after autologous BMT have relapsed compared with 6 of 9 patients with an AK cell activity < 20% (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)