The benefits of exercise for patients with haemophilia and recommendations for safe and effective physical activity.

Most health care professionals involved in the management of people with haemophilia (PWH) believe that exercise is beneficial and its practice is widely encouraged. This article aims to demonstrate that appropriate exercise (adapted to the special needs of the individual PWH) may be beneficial for all PWH through improved physical, psychosocial and medical status. Based on evidence gathered from the literature, many PWH, particularly those using long-term prophylaxis or exhibiting a mild/moderate bleeding phenotype, are as active as their healthy peers. PWH experience the same benefits of exercise as the general population, being physically healthier than if sedentary and enjoying a higher quality of life (QoL) through social inclusion and higher self-esteem. PWH can also gain physically from increased muscle strength, joint health, balance and flexibility achieved through physiotherapy, physical activity, exercise and sport. Conversely, very little data exist on activity levels of PWH in countries with limited resources. However, regarding specific exercise recommendations in PWH, there is a lack of randomized clinical trials, and consequently formal, evidence-based guidelines have not been produced. Based on published evidence from this review of the literature, together with the clinical experience of the authors, a series of recommendations for the safe participation of PWH in regular physical activities, exercises and sport are now proposed. In summary, we believe that appropriately modified programmes can potentially allow all PWH to experience the physical and psychosocial benefits of being physically active which may ultimately lead to an improved QoL.

Guidelines for the management of hemophilia.

Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

Genetic variability in Blanco Orejinegro breed cattle populations in Colombia.

We analyzed population structure and genetic diversity in Blanco Orejinegro Creole cattle with 12 microsatellite markers, genotyping 138 individuals belonging to 7 commercial and 3 conservation herds. These markers showed a high level of polymorphism; 171 alleles were identified. The mean number of alleles per locus was 5.63 (3.82-6.58). The total number of alleles per marker was 14.2 and ranged from 16 (TGLA126) to 22 (TGLA227). The mean expected heterozygosity (0.73) was higher than the observed heterozygosity (0.65), with a significant excess of heterozygosity in almost all populations (FIS = 0.09; P < 0.05). This may be due to crossing between different lines of this breed, affecting the inbreeding levels. Analysis of relationships among populations, assessed by principal component analysis and Nei's genetic distances, indicated a close relationship between some herds. Furthermore, analysis of population structure demonstrated a low probability of admixture with Zebu breeds, as it shows the cluster assignment and the FST values obtained. We conclude that there is high allelic diversity in this breed, even though a low effective population size has been maintained and the level of inbreeding has not been monitored. Therefore, appropriate conservation efforts should be undertaken, such as adopting strategies aimed at minimizing inbreeding, to avoid losing genetic variability.

[Bearing surfaces in primary hip arthroplasty. Is there any difference?] / Pares articulares en prótesis primaria de cadera. ¿Existe alguna diferencia?

INTRODUCTION: In primary hip replacement, different materials are used for bearing surfaces. In our medium metal or ceramic heads with highly crossed-linked polyethylene (PA) are the most used. These combinations have good results, but it is not clear which is clinically superior. The objective of this study is to determine whether there is any clinically significant difference based on a systematic review of the literature and national registries of arthroplasty. MATERIAL AND METHODS: We conduct a systematic review of the literature and national registries of arthroplasty and we were looking for studies comparing bearing surfaces: ceramic-highly cross-linked polyethylene (CP) and metal-highly cross-linked polyethylene (MP); describing the revision rate according to the surface type with a minimum 10-year follow-up. The outcome evaluated was: review rate for any cause depending on surface type. RESULTS: Two out of fifteen national registries were included. The Australian registry shows a difference in the 15-year revision rate: CP: 6.3 (IC 5.8, 6.7) vs MP: 5.1 (IC 4.6, 5.7). The New Zealand registry shows no differences in revision rate/100 components/year: CP 0.54 (0.48-0.61) vs MP 0.61 (0.57-0.66). We do not find clinical studies with inclusion criteria that answer the research question. CONCLUSION: The results of this review show a high survival rate with the use of highly cross-linked polyethylene, the results are similar when using ceramic or metal heads.

INTRODUCCIÓN: En un reemplazo total de cadera primario (RTC), diferentes materiales son los que se usan para las superficies de apoyo. En nuestro medio, las cabezas de metal o cerámica con polietileno altamente entrecruzado (PA) son los más utilizados. Estas combinaciones tienen buenos resultados, pero no es claro cuál es superior clínicamente. Basados en una revisión sistemática de la literatura y de los registros nacionales de artroplastía, el objetivo de este estudio es determinar si existe alguna diferencia significativa desde el punto de vista clínico. MATERIAL Y MÉTODOS: Realizamos una revisión sistemática de la literatura y de los registros nacionales de artroplastía. Buscamos estudios en los que se compararan los tipos de superficie de contacto: cerámica-polietileno altamente entrecruzado (CP) y metal-polietileno altamente entrecruzado (MP), además de los registros nacionales de artroplastía que describieran, con un seguimiento mínimo de 10 años, la tasa de revisión según el tipo de superficie. El desenlace evaluado fue: tasa de revisión por cualquier causa según el tipo de superficie. RESULTADOS: Dos de quince registros nacionales fueron incluidos: el registro australiano muestra una diferencia en la tasa de revisión a 15 años, comparando CP: 6.3 (IC 5.8, 6.7) contra MP: 5.1 (IC 4.6, 5.7). El registro de Nueva Zelanda no muestra diferencias en la tasa de revisión/100 componentes/año: CP de 0.54 (0.48-0.61) en comparación con MP de 0.61 (0.57-0.66). No encontramos estudios clínicos con los criterios de inclusión que respondan la pregunta de investigación. CONCLUSIÓN: Los resultados de esta revisión muestran una alta supervivencia cuando se usa polietileno altamente entrecruzado; asimismo, los resultados son similares cuando se utilizan cabezas de cerámica o metálicas.

[How to select a prosthesis for a primary hip replacement? Minimum acceptable survival: results of a consensus of experts]. / ¿Cómo seleccionar una prótesis para un reemplazo primario de cadera? Mínima supervivencia aceptable: resultados de un consenso de expertos.

BACKGROUND: One of the most critical points in the planning of hip replacement surgeries is the selection of the implant, since its survival significantly impacts the patients health. However, the ideal survival time that an implant must prove to be selected has not been defined. The objective of this consensus is to define minimum performance standards for the selection of conventional primary hip replacement prosthesis. MATERIAL AND METHODS: The consensus was carried out using the methodology of nominal group. This included: 1. A review of the available evidence and the issues to be evaluated, 2. Meeting for the vote and discussion, 3. Quantitative statistical analysis with median (M) and interquartile range (IQR) and qualitative one with proportions of the results to generate recommendations. RESULTS: The primary source of information for prosthesis selection (M: 8; IQR: 7-9), choice in the event of conflicting evidence (M: 8; IQR: 7-9), or limited evidence in the literature (M: 7; IQR: 4.75-825) should be national registries. The minimum acceptable follow-up is 10 years (M: 9; IQR: 8-9) and the minimum acceptable survival is 90% at 10 years (M: 8; IQR: 5-8.5). DISCUSSION: According to these results, the consensus of experts proposed that the selection of the implant for conventional primary hip replacement must be based on the information published in the national registries and that the prosthesis must have a minimum follow-up of 10 years and show a minimum survival of 90%.

INTRODUCCIÓN: Uno de los puntos más críticos en la planeación de las artroplastías de cadera es la selección del implante, puesto que su supervivencia impacta significativamente la salud de los pacientes. Sin embargo, hasta el momento no se ha definido cuál es la supervivencia ideal que debe demostrar un implante para ser seleccionado. El objetivo de este consenso es definir los estándares mínimos de desempeño para la selección de prótesis en reemplazo primario convencional de cadera. MATERIAL Y MÉTODOS: El consenso se realizó mediante la metodología de «grupo nominal¼. Esto incluyó: 1. Revisión de la evidencia disponible y definición de los temas a evaluar, 2. Reunión para la votación y discusión y 3. Análisis estadístico cuantitativo con medianas (M) y rangos intercuartílicos (RIC) y cualitativo con proporciones de los resultados obtenidos para generar recomendaciones. RESULTADOS: La fuente primaria de información para la selección de prótesis (M: 8; RIC: 7-9) y de elección en caso de evidencia contradictoria (M: 8; RIC: 7-9) o limitada en la literatura (M: 7; RIC: 4.75-825) son los registros nacionales. El mínimo seguimiento aceptable es 10 años (M: 9; RIC: 8-9) y el mínimo de supervivencia aceptable es 90% a 10 años (M: 8; RIC: 5-8.5). DISCUSIÓN: De acuerdo con estos resultados, el consenso de expertos propone que la selección del implante en el reemplazo articular primario convencional de cadera se realice con base en la información publicada en los registros nacionales y que dicha prótesis tenga un seguimiento mínimo de 10 años y demuestre una supervivencia mínima de 90%.

Pares articulares en prótesis primaria de cadera. ¿Existe alguna diferencia? / Bearing surfaces in primary hip arthroplasty. Is there any difference?

Resumen: Introducción: En un reemplazo total de cadera primario (RTC), diferentes materiales son los que se usan para las superficies de apoyo. En nuestro medio, las cabezas de metal o cerámica con polietileno altamente entrecruzado (PA) son los más utilizados. Estas combinaciones tienen buenos resultados, pero no es claro cuál es superior clínicamente. Basados en una revisión sistemática de la literatura y de los registros nacionales de artroplastía, el objetivo de este estudio es determinar si existe alguna diferencia significativa desde el punto de vista clínico. Material y métodos: Realizamos una revisión sistemática de la literatura y de los registros nacionales de artroplastía. Buscamos estudios en los que se compararan los tipos de superficie de contacto: cerámica-polietileno altamente entrecruzado (CP) y metal-polietileno altamente entrecruzado (MP), además de los registros nacionales de artroplastía que describieran, con un seguimiento mínimo de 10 años, la tasa de revisión según el tipo de superficie. El desenlace evaluado fue: tasa de revisión por cualquier causa según el tipo de superficie. Resultados: Dos de quince registros nacionales fueron incluidos: el registro australiano muestra una diferencia en la tasa de revisión a 15 años, comparando CP: 6.3 (IC 5.8, 6.7) contra MP: 5.1 (IC 4.6, 5.7). El registro de Nueva Zelanda no muestra diferencias en la tasa de revisión/100 componentes/año: CP de 0.54 (0.48-0.61) en comparación con MP de 0.61 (0.57-0.66). No encontramos estudios clínicos con los criterios de inclusión que respondan la pregunta de investigación. Conclusión: Los resultados de esta revisión muestran una alta supervivencia cuando se usa polietileno altamente entrecruzado; asimismo, los resultados son similares cuando se utilizan cabezas de cerámica o metálicas.

Abstract: Introduction: In primary hip replacement, different materials are used for bearing surfaces. In our medium metal or ceramic heads with highly crossed-linked polyethylene (PA) are the most used. These combinations have good results, but it is not clear which is clinically superior. The objective of this study is to determine whether there is any clinically significant difference based on a systematic review of the literature and national registries of arthroplasty. Material and methods: We conduct a systematic review of the literature and national registries of arthroplasty and we were looking for studies comparing bearing surfaces: ceramic-highly cross-linked polyethylene (CP) and metal-highly cross-linked polyethylene (MP); describing the revision rate according to the surface type with a minimum 10-year follow-up. The outcome evaluated was: review rate for any cause depending on surface type. Results: Two out of fifteen national registries were included. The Australian registry shows a difference in the 15-year revision rate: CP: 6.3 (IC 5.8, 6.7) vs MP: 5.1 (IC 4.6, 5.7). The New Zealand registry shows no differences in revision rate/100 components/year: CP 0.54 (0.48-0.61) vs MP 0.61 (0.57-0.66). We do not find clinical studies with inclusion criteria that answer the research question. Conclusion: The results of this review show a high survival rate with the use of highly cross-linked polyethylene, the results are similar when using ceramic or metal heads.

Effects of trkB and trkC neurotrophin receptor agonists on thermal nociception: a behavioral and electrophysiological study.

Nerve-growth factor (NGF), a member of the neurotrophin family, plays an important role in nociceptor function. Prompted by a previous uinexpected finding that NT-4/5, as well as NGF sensitizes single nociceptors to noxious heat, we have explored the relative potency of all neurotrophins in eliciting thermal hyperalgesia. NGF, brain-derived neurotrophic factor (BDNF), NT-4/5 and NT-3 were injected locally into the hind paw of rats, and the behavioral response to noxious heat was compared with that from the other paw that received an identical injection of vehicle. Like NGF, agonists of tyrosine kinaseB (trkB) receptors (NT-4/5 and BDN F) induced thermal hyperalgesia in the first 5 h after treatment (NT-4/5 > BDNF) but the effect had worn off by 24 h. In contrast, the trkC agonist NT-3 had no effect on the response to noxious heat. Electrophysiological recordings from single C-fibres in the in vitro skin-saphenous nerve preparation revealed sensitization to noxious heat stimuli after direct application of BDNF to the receptive field, as previously noted for NT-4/5, and in parallel with the behavioral findings. NT-3 was ineffective as in the behavioral studies. These results suggest that trkB agonists BDNF and NT-4/5 as well as the trkA agonist NGF can regulate nociceptive responses to noxious heat.

Identification of a critical period for motor development in neonatal rats.

Manipulation of the developing nervous system has provided valuable insights into nervous system function. One important concept to arise from this type of study has been the identification of specific "critical periods" for the development of various functions. A critical period has been most clearly shown for the visual system where monocular eye closure for a few weeks led to functionally significant changes in visually guided behaviors and the connectivity of the visual cortex. Critical periods have also been defined for other sensory systems. Although studies of the effect of manipulating sensory systems during development are sometimes difficult to interpret (e.g. Ref. 7), this difficulty is compounded in the case of the motor system. Problems arise because manipulations of the postnatal motor system are difficult to implement and usually require invasive procedures such as tenotomy, neurotomy, and nerve crush (for review, see Ref. 17). We have approached the problem of manipulating the motor environment by adapting a paradigm widely used to study the experimental effects of simulated weightlessness in adult rats: namely, tail suspension. This method has several advantages for manipulating the motor system: (i) because it is noninvasive, it is less discomforting than neurotomy, tenotomy or nerve crush; (ii) it does not immobilize the animals, they move about the cage and extend and flex their hindlimbs; and (iii) it specifically examines the importance of load-bearing on the development of antigravity muscles and their neuronal circuits.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of valgus tibial angulation on cartilage degeneration in the rabbit knee.

Thirteen adult female rabbits underwent unilateral osteotomy of the proximal tibia. In nine animals, 30 degrees of valgus angulation was created; in four animals, osteotomy without angulation was performed. After a 12-week survival period, the knee joints were processed for histology by staining with hematoxylin and eosin and safranin O. Additionally, the chondroitin sulphate epitopes 3-B-3(-) and 7-D-4 were evaluated immunohistochemically as markers of osteoarthritis. Changes of the articular surface of the tibia were visualized by scanning electron microscopy. Light microscopic evaluation by the Mankin et al. scoring system revealed mild or moderate damage of the cartilage in the lateral compartment of angulated extremities when compared with the control side. Immunohistology with the monoclonal 3-B-3 and 7-D-4 antibodies showed no increased expression of these epitopes in the lateral compartments of the knee. Scanning electron microscopic evaluation of the tibial surfaces revealed slight surface damage localized to the central, weight-bearing portion of the lateral tibial plateau of angulated extremities. Angulation of 30 degrees led to only mild degenerative changes of the cartilage. These results indicate that, in the short term, cartilage has considerable capacity to withstand the effects caused by severe angulation of the limb.

Effect of loading and fracture motions on diaphyseal tibial fractures.

A computerized motion sensor was used to record the three-dimensional components of interfragmentary motion during healing in three patients with closed, low-energy fractures of the tibial diaphysis treated with functional braces. At the first measurement session 2 weeks after fracture, the patients applied approximately 15 kg to the injured limb. Although this produced 1-4 mm of translation of the fragments, this was recovered when the load was removed. The maximum rotational and angulatory displacements often occurred as the patients rose from the chair with no weight applied to the limb and frequently were reduced as the 15 kg of load was applied. Under load, the maximum axial rotation was 3 degrees and the maximum angular displacement was 1 degree. As with the translations, the initial rotational and angulatory positions of the fragments were recovered when the load was removed and the patient returned to the seated position. At 8 weeks, the patient applied full body weight, producing a maximum interfragmentary translation of 0.5 mm and maximum axial rotation or angulation of 0.5 degrees. Abundant peripheral callus formed in all three fractures, and they healed by 15 weeks through typical gradual consolidation and mineralization of the callus, accompanied by a corresponding reduction in interfragmentary motions.

Technique for producing controlled closed fractures in a rabbit model.

We describe a new technique to produce a closed fracture of the rabbit tibia with reproducible location and shape of the fracture. The hindlimb of a New Zealand White rabbit was enclosed in a bivalved cast, a 1.5 mm diameter hole was drilled through the lateral tibial cortex, and the tibia was fractured by loading in three-point bending in an arbor press. The cast protected the soft tissues from being crushed while it concentrated the bending moment at the intended fracture site. The cortical hole functioned as a stress riser and fracture initiation site, such that the influence of the loading rate on the fracture characteristics was minimized. Transverse fractures or oblique fractures at any desired angle could be produced by variations of the position of the cortical drill hole relative to the central loading point. Thirty-four tibial fractures (18 transverse and 16 oblique) were produced. The rabbits were killed immediately, and the fracture angle and the extent of tissue damage were evaluated radiographically, as well as macroscopically. This method produced a consistent location of the fracture, with 88% reproducibility of the fracture angle and only minor damage to the adjacent soft tissues.

The cement mantle in total hip arthroplasty. Analysis of long-term radiographic results.

The correlation between the thickness of the cement mantle, the medullary canal fill, and the orientation of the stem and the long-term radiographic outcome of 836 cemented femoral components in patients who had a primary total hip replacement was assessed with use of survival analysis over a twenty-one-year follow-up period. The femoral stems of hips that had a two to five-millimeter-thick cement mantle in the proximal medial region had a better outcome than stems implanted with a thicker or thinner cement mantle. Stems in femora with less than two millimeters of proximal medial cancellous bone had a better outcome than stems in femora with thicker cancellous bone. Stems that filled more than half of the medullary canal had better radiographic results than those that filled half or less. Progressive loosening, fracture of the cement, and radiolucent lines at the stem-cement or bone-cement interfaces were more likely to develop in stems that were oriented in more than 5 degrees of varus than in those in neutral or valgus. The noted correlations were true whether the stem was made of titanium alloy or of stainless steel. The results of this study emphasize the importance of careful preoperative planning in total hip arthroplasty done with cement and provide guidelines for the selection of the shape, size, and position of the stem.

Healing and remodeling of articular incongruities in a rabbit fracture model.

Healing of 0.5 or 1.0-millimeter step-off defects associated with displaced intra-articular fractures of the medial femoral condyle was examined in fifty-four adult New Zealand White rabbits. The rabbits were treated with either immobilization for three weeks, intermittent active motion, or continuous passive motion for seven days. At twelve weeks, the healing and remodeling of the step-off defects were examined with use of contact-pressure maps on pressure-sensitive film, light microscopy (with hematoxylin and eosin or safranin-O staining), and scanning electron microscopy. Macroscopically, the sharp profile that had been present initially with both sizes of step-off defect had rounded off; however, there was less residual incongruity with the 0.5-millimeter step-offs than with the 1.0-millimeter step-offs. Among step-off defects of the same size, the method of treatment had no discernible effect on the macroscopic appearance of the surface of the joint. With fresh step-offs (the control group), the contact pressure of the cartilage on the elevated side was approximately three times greater than that at a distance from the step-off. On the depressed side, an unloaded zone extended approximately three times the height of the step-off, with an average width of 3.4 millimeters for the 1.0-millimeter step-offs and 1.6 millimeters for the 0.5-millimeter step-offs. After healing and remodeling, the unloaded zone still averaged 2.5 millimeters in width for the 1.0-millimeter step-offs but had decreased to only 0.35 millimeter in width for the 0.5-millimeter step-offs. For seven of the nine 0.5-millimeter step-offs, the contact pressure in the previously unloaded zone ranged from 0.5 to 1.5 megapascals, with a mean of 0.8 megapascal (40 per cent of the normal mean contact pressure at this location). Under light microscopy, the cartilage on the elevated side of the healed step-offs had decreased in thickness, was displaced toward the defect and tapered toward the depressed side, and ended in a hypocellular tissue flap. In contrast, the cartilage on the depressed side had thickened as a result of hyperplasia of the chondrocytes and hypertrophy of the cartilage and had failed to establish continuity between the sides of the defect. There was a marked increase in the subchondral vascular bed and re-establishment of the subchondral plate. With the exception of the aforementioned hypocellular tissue flap, safranin O stained the cartilage on both levels of the step-off uniformly, which indicated the absence of glycosaminoglycan depletion.(ABSTRACT TRUNCATED AT 400 WORDS)

Total hip replacement after failed hemiarthroplasty or mould arthroplasty. Comparison of results with those of primary replacements.

We compared the radiographic results of secondary total hip replacements, 99 following failed uncemented hemiarthroplasties and 21 following failed mould arthroplasties, with those of 825 primary cemented total hip replacements. The probability of occurrence of a number of radiological changes over time was calculated using survival analysis. The mean follow-up was 7.6 years (range one month to 20 years). The performance of the secondary total hip replacements varied with the preceding implant and was different for acetabular and femoral components. The incidence of radiological loosening was higher for femoral components implanted after failed hemiarthroplasties and for acetabular components after failed mould arthroplasties. However, the incidence of continuous radiolucent lines was lower for the acetabular components of converted hemiarthroplasties than for the primary replacements.

Characteristics of degeneration in an unstable knee with a coronal surface step-off.

To investigate the effect of instability on the remodelling of a minor articular surface offset, we created a 0.5 mm coronal step-off of the medial femoral condyle in 12 New Zealand white rabbits and transected the anterior cruciate ligament (ACL). A control group of 12 rabbits had only ACL resection and the opposite knee was used as the non-operated control. The osteoarthritic changes at 6, 12 and 24 weeks after surgery were evaluated histologically. In addition, changes in the immunological detection of 3-B-3(-) and 7-D-4 chondroitin-6-sulphate epitopes were determined because of the previous association of such changes with repair of cartilage and early osteoarthritis. In the instability/step-off group there was rapidly progressing focal degeneration of cartilage on the high side of the defect, not seen in previous step-off studies in stable knees. The rest of the femoral condyles and the tibial plateaux of the instability/step-off group had moderate osteoarthritis similar to that of the instability group. 3-B-3(-) was detectable in the early and the intermediate stages of osteoarthritis but no staining was seen in the severely damaged cartilage zones. Immunoreactivity with 7-D-4 increased as degeneration progressed.

Effects of tibial malalignment on the knee and ankle.

It is widely believed that excessive angulation of the tibia may predispose the ankle and knee to osteoarthritic degeneration. There is no general agreement, however, regarding the acceptable limits of angulation. The authors used cadaver models to measure the contact areas for the cartilage in the ankle, as well as the contact areas and pressures for the cartilage in the knee, as a function of the level and magnitude of simulated angular deformities of the tibia. The quantitative relationships between fracture angulation and joint contract conditions developed in these experiments may help in the formation of more specific guidelines for the treatment of tibial fractures.