Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology.

OBJECTIVES: Current repair procedures for articular cartilage (AC) cannot restore the tissue's original form and function because neither changes in its architectural blueprint throughout life nor the respective biological understanding is fully available. We asked whether two unique elements of human cartilage architecture, the chondrocyte-surrounding pericellular matrix (PCM) and the superficial chondrocyte spatial organization (SCSO) beneath the articular surface (AS) are congenital, stable or dynamic throughout life. We hypothesized that inducing chondrocyte proliferation in vitro impairs organization and PCM and induces an advanced osteoarthritis (OA)-like structural phenotype of human cartilage. METHODS: We recorded propidium-iodine-stained fetal and adult cartilage explants, arranged stages of organization into a sequence, and created a lifetime-summarizing SCSO model. To replicate the OA-associated dynamics revealed by our model, and to test our hypothesis, we transduced specifically early OA-explants with hFGF-2 for inducing proliferation. The PCM was examined using immuno- and auto-fluorescence, multiphoton second-harmonic-generation (SHG), and scanning electron microscopy (SEM). RESULTS: Spatial organization evolved from fetal homogeneity, peaked with adult string-like arrangements, but was completely lost in OA. Loss of organization included PCM perforation (local micro-fibrillar collagen intensity decrease) and destruction [regional collagen type VI (CollVI) signal weakness or absence]. Importantly, both loss of organization and PCM destruction were successfully recapitulated in FGF-2-transduced explants. CONCLUSION: Induced proliferation of spatially characterized early OA-chondrocytes within standardized explants recapitulated the full range of loss of SCSO and PCM destruction, introducing a novel in vitro methodology. This methodology induces a structural phenotype of human cartilage that is similar to advanced OA and potentially of significance and utility.

Risk and risk factors for epilepsy in shunt-treated children with hydrocephalus.

OBJECT: Epilepsy is a major comorbidity in children with hydrocephalus (HC) and has a serious impact on their developmental outcomes. There are variable influencing factors, thus the individual risk for developing epilepsy remains unclear. Our aim was to analyse risk factors for developing epilepsy in children with shunted HC. METHODS: A retrospective, single-centre analysis of 361 patients with the diagnosis of HC was performed. Age at HC diagnosis, shunt treatment, development of epilepsy, epilepsy course, and the aetiology of HC were considered. The influence of shunt therapy, including its revisions and complications, on the development of epilepsy was investigated. RESULTS: One-hundred forty-three patients with HC (n = 361) had a diagnosis of epilepsy (39.6%). The median age at the first manifestation of epilepsy was 300 days (range:1-6791; Q1:30, Q3: 1493). The probability of developing epilepsy after HC decreases with increasing age. The most significant influence on the development of epilepsy is that of the HC itself and its underlying aetiology (HR 5.9; 95%-CI [3-10.5]; p < 0.001). Among those, brain haemorrhage is associated with the highest risk for epilepsy (HR 7.9; 95%-CI [4.2-14.7]; p < 0.01), while shunt insertion has a lower influence (HR 1.5; 95%-CI [0.99; 2.38]; p = 0.06). The probability of epilepsy increases stepwise per shunt revision (HR 2.0; p = 0.03 after 3 or more revisions). Five hundred days after the development of HC, 20% of the children had a diagnosis of epilepsy. Shunt implantation at a younger age has no significant influence on the development of epilepsy nor does sex. CONCLUSION: Children with HC are at high risk for developing epilepsy. The development of epilepsy is correlated mainly with HC's underlying aetiology. The highest risk factor for the development of epilepsy seems to be brain haemorrhage. The age at shunt implantation appears to be unrelated to the development of epilepsy, while structural brain damage at a young age, shunt revisions and complications are independent risk factors. The onset of epilepsy is most likely to take place within the first 500 days after the diagnosis of HC.

Epileptic phenotypes, electroclinical features and clinical characteristics in 17 children with anti-NMDAR encephalitis.

BACKGROUND: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis is a rare disorder characterized by seizures, neuropsychiatric symptoms, dyskinesia and autonomic instability. OBJECTIVE: Aim of the present study was to evaluate the seizure phenotypes and electroencephalogram (EEG) features in children with anti-NMDAR encephalitis. METHODS: Seizure types, electroclinical features and clinical characteristics of 17 children with anti-NMDAR encephalitis were analysed in a retrospective case series from nine centres in Europe. RESULTS: Nearly half (8/17) of the children presented with psychiatric symptoms, whereas in 4/17 patients seizures were the first symptom and in 5/17 both symptoms occurred at the same time. During the following course seizures were reported in 16/17 children. The first EEG detected generalized slowing in 11/17 patients, focal slowing in 3/17 and normal background activity in only 3/17 children. The extreme delta brush (EDB) pattern was detected in 9/17 (53%) patients. CONCLUSION: In addition to psychiatric symptoms, children with anti-NMDAR encephalitis often show generalized slowing in EEG with or without seizures at initial presentation. EDB is present in half of all children and is potentially a helpful tool for early detection of this immune-mediated disease.

Upper extremity blood flow in collegiate and high school baseball pitchers A preliminary report.

The arterial and venous volume blood flow in the dominant and nondominant upper extremities of five male pitchers, ages 16 to 21, was measured using color flow duplex ultrasound. Blood-flow measurements were obtained at baseline, after warm-up, and after each sequence of 20 pitches until 100 pitches were thrown. Blood flow was additionally determined 1 hour after the last pitch. The velocity of each pitch was recorded with a speed gun. Anthropomorphic measurements of the upper extremity were obtained at baseline and immediately after Pitch 100 using a standard measuring tape. The highest average arterial volume flow in the pitching arm occurred after 40 pitches, reaching a peak of 549 ml/min (56% increase from baseline). Thereafter, the average arterial blood flow steadily declined, reaching an average of 402 ml/min after the 100th pitch (14% increase from baseline). In contrast, the arterial blood flow in the nonpitching arm increased only slightly from baseline, reaching a maximal volume flow of 448 ml/min immediately after the warm-up period (10% increase from baseline). The volume flow then persistently fell to a level 30% below baseline after the 100th pitch. Although this small pilot study does not demonstrate causation between a decline in pitching performance and arterial blood flow, it suggests arterial flow in the dominant extremity falls as the pitch count increases.

The effects of concentric versus eccentric isokinetic strength training of the rotator cuff in the plane of the scapula at various speeds.

This study compares the effects of three modes of isokinetic resistance training at the shoulder--concentric, eccentric, and a combination of both concentric and eccentric, with a group that received no training at all. Twenty-eight healthy volunteers (male and females), 18 to 36 years of age, with no history of shoulder pathology, were randomly assigned to one of four groups; concentric training, eccentric training, a combination of both concentric and eccentric training, or control (no training). Testing and training of the dominant shoulder was performed on an isokinetic dynamometer. All subjects were pretested and post-tested both concentrically and eccentrically for humeral internal/external rotation and abduction at speeds of 60 degrees/sec and 120 degrees/sec. Each training session consisted of a total of twelve sets of ten maximal repetitions, and was repeated three times a week for four weeks. The absolute and percent difference in peak force and peak torque for each group between the pretest and post-test was calculated for each combination of position, mode, and speed. A significant difference between the concentric/eccentric group and the eccentric group was found for abduction (p < 0.05). The eccentric group showed a significantly greater increase from the pretest to post-test for absolute differences in peak force and peak torque compared to the concentric/eccentric group (p < 0.05).

Nonoperative treatment for minimally and nondisplaced lateral humeral condyle fractures in children.

The radiographic and clinical records of 95 children with nondisplaced or minimally displaced fractures of the lateral humeral condyle treated on a nonoperative protocol were reviewed. Acute nondisplaced or minimally displaced fractures were defined as < 24 h old on initial evaluation and displaced < 2 mm in three radiographic planes (anteroposterior, lateral, and internal oblique). Closed treatment and close follow-up in a long-arm cast or splint resulted in a union rate of 98% in 3-7 weeks. Two of the fractures displaced required open reduction and internal fixation and then subsequently went on to union without complications.