Low aerobic capacity in McArdle disease: A role for mitochondrial network impairment?

BACKGROUND: McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO2peak)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. METHODS: We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO2peak in patients (both sexes, N = 145) and healthy controls (N = 133). RESULTS: Besides corroborating very poor VO2peak values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. CONCLUSIONS: In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses.

Non-osteogenic muscle hypertrophy in children with McArdle disease.

INTRODUCTION: McArdle disease is an inborn disorder of muscle glycogen metabolism that produces exercise intolerance, and has been recently associated with low values ​​of lean mass (LM) and bone mineral content (BMC) and density (BMD) in affected adults. Here we aimed to study whether this bone health problem begins in childhood. METHODS: Forty children and adolescents were evaluated: 10 McArdle disease and 30 control children (mean age of both groups, 13 ± 2y). Body composition was evaluated by dual-energy X-ray absorptiometry and creatine kinase (CK) levels were determined in the patients as an estimate of muscle damage. RESULTS: Legs bone mass was significantly lower in patients than in controls (-36% for BMC and -22% for BMD). Moreover, patients had significantly higher LM values in the legs than controls, whereas no difference was found for fat mass. CK levels were positively associated with LM in McArdle patients. A correlation was found between LM and BMD variables in the control group but not in McArdle patients. CONCLUSION: We have identified a 'non-osteogenic muscle hypertrophy' in children with McArdle disease. This phenomenon warrants special attention since low osteogenesis at an early age predicts a high risk for osteoporosis later in life.

Clasificación radiológica y manejo de las lesiones mamarias / Radiological classification and management of breast lesions

La mamografía es el único método diagnóstico aceptado como técnica de despistaje para el cáncer de mama permitiendo su detección precoz y el único que ha demostrado una reducción de las tasas de mortalidad por cáncer de mama. El sistema Breast Imaging Reporting and Data System (BI-RADS) es un método para clasificar los hallazgos mamográficos que actualmente se considera el idioma universal en el diagnóstico de la patología mamaria. Permite estandarizar la terminología y la sistemática del informe mamográfico y categorizar las lesiones estableciendo el grado de sospecha y asignar la actitud a tomar en cada caso. En esta revisión se analizan los hallazgos mamográficos que configuran cada una de las categorías BIRADS así como las implicaciones pronósticas y forma de manejo más frecuente de cada una de ellas (AU)

Mammography is the only diagnostic method accepted as a screening technique in breast cancer, allowing early detection, and is the only method that has been shown to reduce mortality rates from breast cancer. The Breast Imaging Reporting and Data System (BI-RADS) is a method for classifying mammographic findings and is currently considered a universal language in the diagnosis of breast disease. This system allows terminology to be standardized, mammographic reports to be systematized and lesions to be categorized, thus establishing the degree of suspicion and the approach to be adopted in each case. The present review analyzes the mammographic findings that appear in each of the BI-RADS categories, as well as the prognostic implications and most frequent type of management in each category (AU)

Embolización selectiva de las arterias uterinas en el tratamiento de miomas sintomáticos: dos años de seguimiento / Selective uterine artery embolization in the treatment of symptomatic myomas: A two-year follow-up

El leiomioma es el tumor ginecológico más frecuente. Entre las opciones terapéuticas, la embolización de arterias uterinas (EAU) se emplea como alternativa a la miomectomía o a la histerectomía. Resumen El objetivo es conocer las características epidemiológicas y clínicas de las pacientes sometidas a EAU y analizar los resultados a los dos años. Material y métodos Estudio observacional y descriptivo de 93 pacientes que fueron sometidas a EAU para el tratamiento del mioma uterino. A las pacientes se les realizó una anamnesis completa, exploración clínica y analítica. Además un seguimiento en consulta a los 2, a los 6, a los 12 y a los 24 meses. Resultados La media de días de sangrado fue de 6,74 (4–14). La tasa media de hemoglobina fue de 11,94g/dl (7–16). La media de los días de ingreso fue de 4,2 (2–10) y la media de los días de dolor posterior fue de 5,8 (1–15). Hubo 3 casos de amenorrea transitoria (3,2%) y 3 casos de amenorrea definitiva (3,2%).Resultados En el volumen uterino y en el tamaño del mioma se apreciaba una reducción significativa en cada revisión hasta los dos años de la embolización. Respecto a la variación clínica, se aprecia una disminución significativa en la sintomatología, el sangrado y el dolor. Discusión En el estudio, la EAU se revela como una técnica bien tolerada y eficaz con una respuesta estadísticamente significativa de todos los parámetros clínicos y ecográficos. Sus indicaciones deben ser especificadas y respetadas para mantener su eficacia y utilidad (AU)

Leiomyoma is the most common gynecologic tumor. Uterine artery embolization (UAE) is used as an alternative to myomectomy or hysterectomy to treat uterine leiomyoma. Objective To determinate the epidemiological and clinical characteristics of patients undergoing UAE and to analyze the results of UAE at 2 years. Material and methods An observational, descriptive study was carried out in 93 patients who underwent UAE for the treatment of uterine myoma. A complete history and physical examination were performed and laboratory data were collected. Follow-up visits were performed at 2, 6, 12 and 24 months after the procedure. Results The mean number of days of bleeding was 6.74 (4–14). The mean hemoglobin was 11.94g/dl (7–16). The mean length of hospital stay was 4.2 days (2–10), and the number of subsequent days of pain was 5.8 (1–15). There were three cases of transient amenorrhea (3.2%) and three of permanent amenorrhea (3.2%).Results The volume and size of uterine myoma were significantly reduced at each follow-up visit until 2 years after the embolization. A significant decrease in symptoms, bleeding and pain was confirmed in this period. Discussion UAE is a well-tolerated and effective technique, with a statistically significant response of all clinical and ultrasonographic parameters. The indications for UAE should be clearly defined and followed to maintain the efficacy and utility of this procedure (AU)

Time trial exertion traits of cycling's Grand Tours.

We examined 26 professional riders during time trial (TT) competitions of the Grand Tours of cycling (Tour de France and Vuelta Espana; 1997-2003) for the exertional characteristics of contending vs. non-contending (i.e., support) riders. We categorized HR time during TT into training impulse (TRIMP) defined from seasonal VO2max testing [Phase I (RCP]. Races were: Short TT (<15 km; 8.9+/-2.9 km); Individual TT (>15 km; 48.12+/-8.7 km); Uphill TT (20.0+/-8.7 km) and Team TT (44.1+/-20.9 km). We observed statistically significant event-by-contender interactions for all TT (all, P<0.0001) except the short TT. During uphill TT, contenders exerted fewer total TRIMP (P<0.01), more Zone 3 TRIMP (P<0.05), and fewer Zone 2 TRIMP (P<0.01) vs. non-contenders. For individual TT, contenders accumulated more Total and Zone 3 TRIMP vs. non-contenders (all, P<0.05). Interestingly, during the team TT, contenders accumulated more Zone 3, and fewer Zone 2 TRIMP (all, P<0.05), despite having the opportunity to draft behind other riders while in paceline race formation. During TT events, contending riders compete at a level of exertion corresponding to a higher metabolic demand during the uphill TT, individual TT and team TT.

Genética de la osteoporosis posmenopáusica: Nuevos conocimientos y nuevos conceptos sobre su relación con los polimorfismos genéticos en la ruta estrogénica / The genetics of postmenopausal osteoporosis: New understanding and new concepts of its relationship with genetic polymorphisms

La osteoporosis posmenopáusica es una enfermedad compleja, sujeta a fuertes influencias ambientales pero con una base genética no menos importante, tanto en la manera de adquisición como de pérdida de la masa ósea. El estudio genético nos está permitiendo identificar a pacientes con riesgo de padecer enfermedades comunes como ésta, y en su evolución como herramienta clínica hemos pasado de la búsqueda de genes candidatos al análisis unilocus de sus polimorfismos genéticos y sus relaciones con determinados factores ambientales. El siguiente paso será analizar las posibles interacciones génicas y la relación entre los hallazgos genéticos y la respuesta a los tratamientos más comunes

Postmenopausal osteoporosis is a complex disease, which is subject to strong environmental influences but with a no less important genetic basis, both in the manner of acquisition and loss of bone mass. Genetic studies are enabling us to identify patients at risk of suffering from common diseases like this, and in its evolution as a clinical tool we have advanced from the search for candidate genes to unilocus analysis of their genetic polymorphisms and their relationships with certain environmental factors. The next step will be to analyse possible gene interactions and the relationship between genetic findings and the response to the most common treatments (AU)

Donación de ovocitos / Oocyte donation

Objetivo: Conocer el marco legal y científico, indicaciones, resultados, aspectos emocionales y controversias existentes relacionadas con la técnica de donación de ovocitos en reproducción asistida. Material y métodos: Revisión de las principales guías de práctica clínica publicadas en la bibliografía internacional (ESHRE, American Society for Reproductive Medicine, Royal College of Obstetricians and Gyneacologist [RCOG]). Resultados: La tasa de embarazo obtenida mediante esta técnica varía entre el 30 y 50% en función de las fuentes consultadas. La prestación asumida por el Servicio Andaluz de Salud sólo cubre el 17% de las indicaciones que se hacen en sanidad privada. Conclusiones: La donación de ovocitos es una técnica que obtiene buenos resultados en el segmento poblacional con peor pronóstico reproductivo. Su extensión difiere sustancialmente entre el sector privado y el público. Con la generalización de la técnica han aparecido nuevas controversias no del todo resueltas. El escaso número de donantes y los aspectos morales son los dos principales factores que limitan la extensión de la técnica (AU)

Objective: To determine the legal and scientific framework, indications, results, emotional issues, and current debates related to oocyte donation in assisted reproduction. Material and methods: We reviewed the main clinical practice guidelines published in the international literature (ESHRE, American Society for Reproductive Medicine, Royal College of Obstetricians and Gynecologists). Results: The pregnancy rate obtained by this technique varied between 30% and 50%, depending on the sources consulted. The services provided by the Andalusian Health Service covered only 17% of the indications covered by private health providers. Conclusions: Oocyte donation provides good results in the segment of the population with the worst reproductive prognosis. The use of this technique differs substantially between the private and public sectors. With the widespread use of this technique, new controversies have appeared that have not been entirely resolved. The two main factors limiting wider use of oocyte donation are the low number of donors and moral issues (AU)

Infección de la herida quirúrgica. Prevención y tratamiento / Surgical site infection. Prevention and treatment

Objetivo: Conocer los factores implicados en la aparición de infecciones en la herida quirúrgica y las principales medidas de control de éstos en la cirugía en general y en la cirugía ginecológica en particular. Material y métodos: Revisión de las principales guías de práctica clínica publicadas en la bibliografía internacional (Centers for Disease Control and Prevention, National Institutes of Health) y nacional. Resultados: Según el Ministerio de Sanidad y Consumo en España se estima una prevalencia global de infecciones de la herida quirúrgica (IHQ) del 5-10%. La mortalidad directa por IHQ es del 0,6% y la mortalidad asociada a IHQ, del 1,9%. En Estados Unidos se estima que una IHQ prolonga la estancia 7,3 días, con un coste adicional diario de 3.200 dólares. Se identifican varios factores de riesgo para IHQ que dependen del paciente, del acto quirúrgico y del cuidado postoperatorio. Conclusiones: A pesar de los grandes avances surgidos en cirugía, la IHQ continúa siendo un problema frecuente, grave y costoso. La prevención, mediante el adecuado conocimiento de los factores de riesgo para la aparición de ésta, así como de las medidas que disminuyen su incidencia, es la medida más eficaz para su reducción. El lavado quirúrgico, el uso de antibióticos y, sobre todo, la depurada técnica quirúrgica son los principales factores de riesgo identificado (AU)

Objective: To evaluate the principal risk factors for surgical site infections (SSI) and the main measures for their prevention in surgery in general and in gynecologic surgery in particular. Methods: We reviewed the main clinical practice guidelines published in the international (Center for Disease Control, National Institute of Health) and Spanish literature. Results: In Spain the prevalence of SSI is estimated at 5-10%. Mortality directly attributable to SSI is 0.6% per year and that associated with SSI is 1.9%. In the USA, SSI increases the length of hospital stay by an average of 7.3 days with an extra cost of $3200 per day. Several risk factors for SSI have been identified, involving the patient, the surgical intervention, and postoperative care. Discussion: Despite the advances made in surgical materials and techniques, SSI remain a frequent, severe and expensive problem. Knowledge of the risk factors involved in SSI and of the measures that reduce their incidence is the most important factor in their prevention. The main risk factors identified are related to surgical scrub, use of antibiotics, and adequate surgical skill (AU)

Effects of the rotor pedalling system on the performance of trained cyclists during incremental and constant-load cycle-ergometer tests.

The aim of this study was to determine the effects of Rotor, a new cycle crank configuration that effectively allows the pedals to move independently throughout the duty cycle, on indices of endurance cycling performance in trained cyclists. Ten cyclists (5 Rotor users and 5 non-users; age (mean +/- SD): 22 +/- 5 y; VO(2)max: 69.5 +/- 5.1 mL. kg(-1).min(-1)) volunteered to participate in the study. On four separate days, the subjects performed four cycle-ergometer tests, i.e. two incremental tests and two 20-min tests. An imposed crank rate of 75 rev.min(-1) was used during all tests. The incremental protocol started at 112.5 W, and the power output was increased by 37.5 W every 3 min until volitional exhaustion. The 20-min tests were performed at a fixed power output equivalent to 80 % of the highest power output that the cyclists maintained for a complete 3-min period during incremental tests. Both types of tests were performed with the conventional crank system and the Rotor following a counter-balanced, cross-over design. Gas exchange parameters were measured in all the tests and blood lactate was determined at the end of each 3-min period (incremental tests) and at the end of the 20-min tests. A three factor (pedalling system used during the tests x habitual pedalling system x power output [incremental tests] or time [20-min tests]) ANOVA with repeated measures on power output (incremental tests) or time (20-min tests) was used to analyse several indices of performance, e.g. peak power output, VO(2)max, lactate threshold, onset of blood lactate accumulation, economy, delta, and gross efficiency. No differences (p > 0.05) were found between the Rotor and conventional systems for any of the aforementioned variables. It seems that the theoretical advantage brought about by the Rotor system, i.e. improved contra-lateral cooperation of both legs, would be minimized in trained cyclists. Although field studies are needed to assess the possible implications, in terms of actual racing, of the new system, commonly used indicators of endurance cycling performance do not seem to be improved with the Rotor in trained cyclists.

Which laboratory variable is related with time trial performance time in the Tour de France?

OBJECTIVE: To investigate the relationship between several physiological variables that can be easily obtained during cycle ergometer gradual testing (for example, peak power output (W(peak)), Vo(2max), or ventilatory threshold (VT)) and actual (>50 km) time trials (TT) time performance during the Tour de France. METHODS: We collected data in professional cyclists from the first TT of the 1998 Tour de France (TT1, 58 km distance; n = 6 cyclists) and the first (TT2, 56.5 km; n = 5) and second TT of the 1999 Tour de France (TT3, 57 km; n = 5). RESULTS: A negative relationship was found between power output (W) at VT (VT(Watt)) and TT final time (s) in TT1 (r = -0.864; p = 0.026; standard error of estimate (SEE) of 73 s; and 95% confidence limits (95% CL) -0.98; -0.18), TT2 (r = -0.77; p = 0.27; SEE of 139 s; and 95% CL -0.98; 0.35), and TT3 (r = -0.923; p = 0.025; SEE of 94 s; and 95% CL -1.00; -0.22). CONCLUSIONS: Actual performance in long TT during the Tour de France (>50 km distance, performed after at least 1-2 weeks of continuous competition), in which some cumulative fatigue inevitably occurs, is related, at least in part, to the power output that elicits the VT. No other routine physiological variable (for example, Vo(2max) or W(peak)) is related to performance in this type of event.

Giro, Tour, and Vuelta in the same season.

The exercise volume and intensity are reported of a male professional cyclist (age 30; VO2max 75.0 ml/kg/min) who successfully completed the 2001 Giro d'Italia (May), Tour de France (July), and Vuelta a España (September). The total exercise time during the Giro, Tour, and Vuelta was 90 hours 44 minutes (5444 minutes), 88 hours 23 minutes (5303 minutes), and 72 hours 59 minutes (4379 minutes) respectively. Heart rate telemetry during the races allowed the exercise intensity to be classified into three phases: I, below the first ventilatory threshold (VT1); II, between VT1 and the second ventilatory threshold (VT2); III, above VT2. Compared with the Giro and Tour, the lower exercise volume of the Vuelta (about 20% less total time) was compensated for by a considerably lower and higher contribution of phases I and III respectively. As a result, the total load (volume x intensity) in the three races was comparable.

Effects of electrical stimulation on VO2 kinetics and delta efficiency in healthy young men.

OBJECTIVE: To determine the effects of electrical stimulation (ES) on oxygen uptake (VO(2)) kinetics and delta efficiency (DE) during gradual exercise. The hypothesis was that ES would attenuate the VO(2)-workload relation and improve DE. METHODS: Fifteen healthy, untrained men (mean (SD) age 22 (5) years) were selected. Ten were electrostimulated on both quadriceps muscles with a frequency of 45-60 Hz, with 12 seconds of stimulation followed by eight seconds recovery for a total of 30 minutes a day, three days a week for six weeks. The remaining five subjects were assigned to a control group. A standardised exercise test on a cycle ergometer (ramp protocol, workload increases of 20 W/min) was performed by each subject before and after the experimental period. The slope of the VO(2)-power output (W) relation (deltaVO(2)/deltaW) and DE were calculated in each subject at moderate to high intensities (above the ventilatory threshold-that is, from 50-60% to 100% VO(2)max). RESULTS: The mean (SEM) values for deltaVO(2)/deltaW and DE had significantly decreased and increased respectively after the six week ES programme (p<0.05; 9.8 (0.2) v 8.6 (0.5) ml O(2)/W/min respectively and 27.7 (0.9) v 31.5 (1.4)% respectively). CONCLUSIONS: ES could be used as a supplementary tool to improve two of the main determinants of endurance capacity, namely VO(2) kinetics and work efficiency.

Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists.

OBJECTIVE: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists. METHODS: Sixteen professional male road cyclists (mean (SD) age 26 (1) years) performed a ramp test on a cycle ergometer (workload increases of 5 W/12 s, averaging 25 W/min). Heart rate (HR), gas exchange parameters, and blood variables (lactate, pH, P(50) of the oxyhaemoglobin dissociation curve, and K(+)) were measured during the tests. RESULTS: A HRDP was shown in 56% of subjects at about 88% of their maximal HR (HRDP group; n = 9) but was linear in the rest (No-HRDP group; n = 7). In the HRDP group, the slope of the HR-workload regression line above the HRDP correlated inversely with levels of K(+) at the maximal power output (r = -0.67; p<0.05). CONCLUSIONS: The HRDP phenomenon is associated, at least partly, with exercise induced hyperkalaemia.

Caffeine ingestion attenuates the VO(2) slow component during intense exercise.

The purpose of this study was to analyze the effects of caffeine ingestion on the slow component of oxygen uptake (DeltaVO(2)) during high-intensity endurance exercise. Nine subjects (8 male and 1 female; age: 21 +/- 1 years; VO(2 max): 57.9 +/- 1.5 ml kg(-1) min(-1)) performed two 9-min tests on a treadmill at a running velocity eliciting 90% of their VO(2 max), 60 min after ingesting either a placebo capsule (PLAC) or a capsule containing a caffeine dose of 5 mg (kg body mass)(-1) [CAFF]. The mean values of DeltaVO(2) were significantly lower in CAFF than in PLAC (83 +/- 31 ml min(-1) vs. 167 +/- 26 ml min(-1), respectively; p < 0.05). These findings suggest that the ergogenic effect of caffeine in a high-intensity endurance exercise shown in previous research may be partly mediated by a possible attenuation of the VO(2) slow component.

[A mid-term clinical and hemodynamic evaluation of the Wessex and Hancock II bioprostheses]. / Valoración clínica y hemodinámica a medio plazo de las bioprótesis de Wessex y Hancock II.

The purpose of this study is to compare clinically and hemodynamically the Wessex and Hancock II porcine bioprostheses. We compared functional class and data from echo-Doppler in 34 Wessex bioprostheses (group A) with those in 42 Hancock II bioprostheses (group B). We subdivided group A into A1 and A2. A1 was made up of 23 Wessex manufactured since 1986. A2 constituted 11 Wessex made before 1986 which belonged to a series with some variations in the manufacturing process, and in which some early dysfunctions have been described. We compared data from these sub-groups between each other as well as with those of group B. The groups were homogeneous in age, sex, patients body surface and the time elapsed since the prosthetic implant. The mean mitral gradient, the mitral area, the peak aortic gradient and the regurgitation incidence were similar in groups A and B. In A2 the mean mitral gradient was significantly superior to that of group B (7.1 +/- 1.1 mmHg vs 5.4 +/- 1.4 mmHg; p less than 0.01), and the mitral area showed a tendency to be inferior, although with no statistical significance. The functional class of the patients was similar in all the groups. We conclude that the Wessex bioprosthesis presents hemodynamic data and functional class similar to those of the Hancock II, with the exception of a sub-group of Wessex manufactured before 1986 which presents mean mitral gradients superior to the others and which would warrant further studies.

[Transluminal angioplasty for aortic coarctation in newborns and infants]. / Angioplastia transluminal en la coartación aórtica del recién nacido y lactante.

It has been done transluminal angioplastic with catheter balloon in 14 patients who are under 1 year of age and who are affected by aortic coarctation. For this study, they were divided in two groups. The first one was formed by newborn children whose transcoarctation gradient was 52 mm Hg in average. The second group was integrated by 9 newborn children whose transcoarctation gradient was 59 mm Hg. After this experience was done the gradient descended to 9 and 15 mm Hg respectively. Twenty four hours later, two months later and over two more months, there were follow-up of the clinical situation, the evolution of the pulse, differential arterial pressure and the need of surgery. Of the first group only one of the patients, who is now 2 years old, is in good clinical condition; the others needed to be surgically intervened. Of the second group 4 patients, all of whom were over 3 months old at the time of the angioplastic had positive results. The rest needed surgical intervention.

[Comparative observations of the behavior of ethephon in fruit, coffee and paprika]. / Vergleichende Betrachtungen zum Rückstandsverhalten von Ethephon in Obst, Kaffee und Paprika.

After application of Flordimex to soft and stone fruit for fruit abscission and acceleration of ripening obvious Ethephon residues have been found. Therefore, the dose rate has to be restricted to keep the maximum residue limit. The same is true for the use of Flordimex for fruit abscission in apples, whereas for yield regulation residues are far below 0.05 mg/kg in apples. A typical feature of the active ingredient is the large quantity of its residues in juice and wine, which is as high as Ethephon concentration in fruits or even higher. Finally, Ethephon is demonstrated to enter the pulp of bananas, mandarin, grapefruit and mango as a result of treating harvested tropical fruit. The residue situation after treatment of pineapple, sweet pepper and coffee is discussed.