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.

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.

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.

New surgical approach to palliate tricuspid atresia in infants.

An experimental surgical technique is proposed to increase pulmonary blood flow in tricuspid atresia with normally related great arteries. The method consists of the creation of ventricular septal defect in the infundibular septum by means of a closed surgical procedure. The expected advantage would be the growth of the right ventricular cavity. This would permit performance of a Fontan's procedure later, using the right atrium and the right ventricle. Microscopic sections from the hearts of 4 infants showed no damage in the conduction system. When performed in the beating hearts of dogs, the feasibility of the procedure was tested repeatedly without production of rhythm disturbances.

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.

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.

Thrombotic obstruction of Bjork-Shiley tricuspid valve prosthesis. Report of three cases reoperated with success.

Three patients presented subacute right heart failure, 6, 12 and 22 months after replacement of the tricuspid valve with a Björk-Shiley prosthesis. The principal finding encountered on clinical examination was a tricuspid filling murmur with inspiratory accentuation. The mean prosthetic gradient found at cardiac catheterization was 7, 8 and 10 mm Hg. At surgery, the three prostheses were thrombosed on their ventricular aspect and all the three were replaced with new ones of the same model. The patients are alive and in good condition, 21, 17 and 8 months after the operation. Problems which relate to the surgical management of tricuspid valve disease are discussed.

[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.