Effects of endurance and strength-directed electrical stimulation training on the performance and histological properties of paralyzed human muscle: a pilot study

Electrical stimulation (ES) improves muscle properties after spinal cord injury (SCI), but cycling power output (PO) remains low. We investigated the effect of endurance and strength ES training on these parameters. Assessments of quadriceps strength and fatigue resistance, cycling PO, and muscle biopsies were made in four well-trained SCI subjects (three cyclists and one rower) before and after additional weight training in the cyclists and once in the rower. Weight training improved muscle strength, but cycling PO was low in all subjects. There was no effect of training type on biopsy data. Biopsies showed non-specific signs of pathology, predominance of type IIa fibers, and uniform metabolic activity. Oxidative activity was low, as were capillary:fiber ratios in the cyclists. Cycling PO is limited by factors other than muscle strength. Future ES training studies should attempt to improve muscle oxidative capacity to optimize the potential benefits of ES exercise.     

Deliberate self-harm within an international community sample of young people: comparative findings from the Child & Adolescent Self-harm in Europe (CASE) Study

Background:  Deliberate self-harm among young people is an important focus of policy and practice internationally. Nonetheless, there is little reliable comparative international information on its extent or characteristics. We have conducted a seven-country comparative community study of deliberate self-harm among young people.
Method:  Over 30,000 mainly 15- and 16-year-olds completed anonymous questionnaires at school in Australia, Belgium, England, Hungary, Ireland, the Netherlands and Norway. Study criteria were developed to identify episodes of self-harm; the prevalence of self-harm acts and thoughts, methods used, repetition, reasons given, premeditation, setting for the act, associations with alcohol and drugs, hospitalisation, and whether other people knew, were examined.
Results:  Self-harm was more than twice as common among females as males and, in four of the seven countries, at least one in ten females had harmed herself in the previous year. Additional young people had thought of harming themselves without doing so. More males and females in all countries except Hungary cut themselves than used any other method, most acts took place at home, and alcohol and illegal drugs were not usually involved. The most common reasons given were 'to get relief from a terrible state of mind' followed by 'to die', although there were differences between those cutting themselves and those taking overdoses. About half the young people decided to harm themselves in the hour before doing so, and many did not attend hospital or tell anyone else. Just over half those who had harmed themselves during the previous year reported more than one episode over their lifetime.
Conclusions:  Deliberate self-harm is a widespread yet often hidden problem in adolescents, especially females, which shows both similarities and differences internationally.     

Pineal cysts—A benign association with familial retinoblastoma

Patients with familial/heritable retinoblastoma (RB) are at increased risk of developing second malignancies throughout life, including a pineoblastoma (trilateral RB [TRB]) in early childhood. Current guidelines recommend regular surveillance brain imaging for those with heritable RB until 5 years of age. The presence of pineal cysts has been reported in patients with RB. Pineal cysts are thought to arise due to focal degeneration of the pineal gland and can be found incidentally. The finding of pineal abnormalities including cysts in children with RB on imaging is disconcerting, as it raises the possibility of an underlying malignancy, specifically a pinealoblastoma. The authors reviewed the imaging findings and clinical significance of pineal cysts in 69 patients diagnosed with RB at our center between December 1999 and November 2015. Twenty-six patients had pineal cysts found on brain magnetic resonance imaging (MRI) scans performed either at diagnosis or follow-up. Thirty-eight of 69 patients had underlying heritable RB. Nineteen of 38 familial RB patients had a pineal cyst compared with 3 out of 26 with sporadic RB (P = .004). In the majority, the imaging characteristics and size of the cysts remained stable or resolved. In this cohort, pineal cysts were detected at significantly increased frequency in heritable RB. This may be a benign association or may reflect abnormal underlying biology of pineal tissue in individuals highly susceptible to malignancy. Imaging characteristics can be helpful in distinguishing between benign and malignant lesions. The presence of a pineal cyst in patients with unilateral disease may be a useful indicator of underlying heritable RB.     

A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p

The limb-girdle muscular dystrophies are a clinically and geneticallyheterogeneous group of disorders. We have ostudied two largeinbred families of different ethnic origin and excluded linkageto LGMD2 on chromosome 15q and SCARMD on chromosome 13. Proceedingto a genomic linkage search, we have now identified linkageto markers D2S134 and D2S136 on chromosome 2p (maximum lod score3.57 at zero recombination). The phenotype in the two familieswas similar, with onset in the pelvic girdle musculature inthe late teens and usually relatively slow progression. Thiswork Identifies a second locus for autosomal recessive limb-girdlemuscular dystrophy.     

Antitumour evaluation of dolastatins 10 and 15 and their measurement in plasma by radioimmunoassay

Dolastatins 10 and 15 are small peptides isolated from the marine sea hare Dolabella auricularia that have been shown to interact with tubulin. Their growth-inhibitory properties were compared using panels of human ovarian and colon-carcinoma cell lines. Both agents were very potent inhibitors of cell growth, with dolastatin 10 being an average of 9.1-fold more potent than dolastatin 15 [mean 50% inhibitory concentrations (IC₅₀ values) 2.3×10^–10 and 2.1×10^–9 M, respectively; P <0.05] and more potent than paclitaxel or vinblastine. While neither dolastatin exhibited marked cross-resistance in cisplatin- or etoposide-resistant cell lines, contrasting effects were observed using an acquired doxorubicin-resistant (CH1doxR, 100-fold resistant, P-glycoprotein overexpressing) cell line. Resistance was significantly higher to dolastatin 15 (12.7-fold) than to dolastatin 10 (only 3.2-fold; P <0.05) and was reversible in both cases by verapamil. In vivo, using a s.?c. advanced-stage human ovarian carcinoma xenograft and equitoxic doses, greater activity was observed with dolastatin 10 (6.1-day growth delay) versus 0.4 days for dolastatin 15. A radioimmunoassay for dolastatin 10 (limit of detection in mouse plasma 5 ng/ml) was developed. The rabbit antiserum also cross-reacted by 65% with dolastatin 15. Comparative mouse pharmacokinetics following i.?v. administration of 1 mg/kg showed that both compounds are rapidly eliminated, but with a shorter second-phase half-life (t ¹ _{/2 β}) being observed for dolastatin 15 (being detectable for only up to 4 h post-administration), the t ¹ _{/2 β} being 3 times longer for dolastatin 10. In addition, areas under the plasma concentration-time curve (AUC values) were 1.6-fold higher for dolastatin 10 (333 versus 208 ng ml^–1 h). Plasma binding of dolastatin 10 exceeded 90%. The highly sensitive RIA will be useful for pharmacokinetic studies in conjunction with the planned phase I clinical trials of these novel, extremely potent, tubulin-binding agents, of which dolastatin 10 appears to possess the more promising preclinical features.