Intracranial haemorrhage in von Willebrand disease: a report on six cases.

The incidence of intracranial haemorrhage (ICH) in von Willebrand disease (VWD) is not well documented. We describe our single centre experience regarding ICH in children with VWD and identify how such children presented and were managed. Thirty-three head trauma events leading to medical attention occurred in 24 of 153 children with VWD followed in our institution. In only 15 of these were computed tomography (CT) imaging studies performed; seven in children with type 1 VWD, one in a child with type 2N VWD and seven in children with type 3 VWD. In six of these 15 episodes an ICH was identified: two children with type 1 VWD, one child with type 2N VWD and three children with type 3 VWD. In two of the 6 cases an ICH was only confirmed following a second CT scan. Neurological symptoms, including vomiting (noted in all six), headache, irritability, lethargy and/or alteration in the level of consciousness were present in all children with confirmed ICH. In contrast vomiting, irritability and alterations in level of consciousness were never present in those children without confirmed ICH. All three children with type 3 VWD who experienced an ICH were commenced on long-term prophylaxis. ICH, although rare, does occur in children with VWD and particularly in children with type 3 VWD. A much larger cohort of patients with VWD experiencing an ICH is needed to make recommendations regarding treatment of such events, including the role of prophylaxis in patients with more severe forms of VWD.

No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis.

A double-blind randomized study was performed to evaluate the effect of oral ribose supplementation on repeated maximal exercise and ATP recovery after intermittent maximal muscle contractions. Muscle power output was measured during dynamic knee extensions with the right leg on an isokinetic dynamometer before (pretest) and after (posttest) a 6-day training period in conjunction with ribose (R, 4 doses/day at 4 g/dose, n = 10) or placebo (P, n = 9) intake. The exercise protocol consisted of two bouts (A and B) of maximal contractions, separated by 15 s of rest. Bouts A and B consisted of 15 series of 12 contractions each, separated by a 60-min rest period. During the training period, the subjects performed the same exercise protocol twice per day, with 3-5 h of rest between exercise sessions. Blood samples were collected before and after bouts A and B and 24 h after bout B. Knee-extension power outputs were approximately 10% higher in the posttest than in the pretest but were similar between P and R for all contraction series. The exercise increased blood lactate and plasma ammonia concentrations (P < 0.05), with no significant differences between P and R at any time. After a 6-wk washout period, in a subgroup of subjects (n = 8), needle-biopsy samples were taken from the vastus lateralis before, immediately after, and 24 h after an exercise bout similar to the pretest. ATP and total adenine nucleotide content were decreased by approximately 25 and 20% immediately after and 24 h after exercise in P and R. Oral ribose supplementation with 4-g doses four times a day does not beneficially impact on postexercise muscle ATP recovery and maximal intermittent exercise performance.

Late vitamin K deficiency bleeding leading to a diagnosis of cystic fibrosis: a case report.

Vitamin K deficiency bleeding (VKDB) in infants still occurs despite worldwide use of prophylaxis. Clinical manifestations can be dramatic with over 50% of patients presenting with intracranial haemorrhage and a mortality rate of 20% in late vitamin K deficiency bleeding. Special attention should be given to infants with a high risk profile (preterm, breast feeding, cholestasis, malabsorption). A tentative diagnosis can be made observing quick normalisation of some easy-to-perform haemostatic parameters (PT, aPTT) after administration of vitamin K. Nowadays, VKDB can still be the first clinical sign of diseases causing malabsorption of fat-soluble vitamins. In this case report, VKDB led to the diagnosis of cystic fibrosis, the most common fatal autosomal recessive disease among Caucasian people.

Human platelet pathology related to defects in the G-protein signaling cascade.

Platelets are highly responsive to signals from their environment. The sensing and processing of some of these stimuli are mediated by G-protein signal transduction cascades. It is well established that proteins involved in signal transduction may be targets for naturally occurring mutations resulting in human diseases. The best-studied molecules in platelets in relation to disease are the G-protein coupled receptors being the most platelet-specific. Many of the other signal transduction genes are often not only present in platelets but also in other tissues. Therefore, the clinical phenotype of signaling defects in platelets, apart from the membrane receptor defects, is seldom isolated to a hemostatic phenotype. Moreover, as platelets are easily accessible cells, and one of the best-studied models regarding signaling, platelets are easily applicable to investigate defects in ubiquitously expressed genes. Apart from a discussion on classical thrombopathies, this review will also deal with the less commonly known relation between platelet signaling defects and disorders with a broader clinical phenotype.

Effect of immobilization and retraining on torque-velocity relationship of human knee flexor and extensor muscles.

The effect of 2 weeks immobilization of the uninjured right knee and 10 weeks of retraining on muscle torque-velocity characteristics was investigated in nine young subjects. Left and right knee extension and flexion maximal voluntary isometric torque (Tmax) and dynamic torque at 60 degrees s(-1) (T60) and 180 degrees x s(-1) (T180) were measured before (PRE) and after immobilization (POST) and after 3 (R3) and 10 (R10) weeks of dynamic retraining. The torque-velocity relationship was quantified by expressing T60 and T180 relative to Tmax (NT60 and NT180, respectively). For the right extensor muscles, percutaneous biopsy samples were obtained from the vastus lateralis muscle and fibre type distribution was measured. POST extension and flexion torque (mean of Tmax, T60 and T180) decreased by 27% and 11%, respectively. During the course of the experiment, the changes in NT60 and NT180 were similar. POST extensor muscle NTV (mean of NT60 and NT180) was decreased significantly (12%, P<0.05), but no significant change was found for flexor muscle NTV (+ 3%). At R3 Tmax, dynamic torque and NTV were restored to normal. Unlike isometric torque, NTV did not change from R3 to R10. No changes in fibre type distribution were found. The adaptation of muscle length is suggested as the mechanism to explain the change in NTV.

Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans.

1. We investigated the effect of oral creatine supplementation during leg immobilization and rehabilitation on muscle volume and function, and on myogenic transcription factor expression in human subjects. 2. A double-blind trial was performed in young healthy volunteers (n = 22). A cast was used to immobilize the right leg for 2 weeks. Thereafter the subjects participated in a knee-extension rehabilitation programme (3 sessions x week(-1), 10 weeks). Half of the subjects received creatine monohydrate (CR; from 20 g down to 5 g daily), whilst the others ingested placebo (P; maltodextrin). 3. Before and after immobilization, and after 3 and 10 weeks of rehabilitation training, the cross-sectional area (CSA) of the quadriceps muscle was assessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee-extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters. 4. Immobilization decreased quadriceps muscle CSA (approximately 10 %) and Wmax (approximately 25 %) by the same magnitude in both groups. During rehabilitation, CSA and Wmax recovered at a faster rate in CR than in P (P < 0.05 for both parameters). Immobilization changed myogenic factor protein expression in neither P nor CR. However, after rehabilitation myogenin protein expression was increased in P but not in CR (P < 0.05), whilst MRF4 protein expression was increased in CR but not in P (P < 0.05). In addition, the change in MRF4 expression was correlated with the change in mean muscle fibre diameter (r = 0.73, P < 0.05). 5. It is concluded that oral creatine supplementation stimulates muscle hypertrophy during rehabilitative strength training. This effect may be mediated by a creatine-induced change in MRF4 and myogenin expression.