Expression of deletion-containing dystrophins in mdx muscle: implications for gene therapy and dystrophin function

The expression of full-length dystrophin and various dystrophin deletion mutants was monitored in mdx mouse muscle after intramuscular injection of dystrophin-encoding plasmid DNAs. Recombinant dystrophin proteins, including those lacking either the amino terminus, carboxyl terminus, or most of the central rod domain, showed localization to the plasma membrane. This suggests that there are multiple attachment sites for dystrophin to the plasma membrane. Only those constructs containing the carboxyl terminus were able to stabilize dystrophin-associated proteins (DAP) at the membrane, consistent with other studies that suggest that this domain is critical to DAP binding. Colocalization with DAP was not necessary for membrane localization of the various dystrophin molecules. However, stabilization and co-localization of the DAP did seem to be a prerequisite for expression and/or stabilization of mutant dystrophins beyond 1 wk and these same criteria seemed important for mitigating the histopathological consequences of dystrophin deficiency.     

A risk-benefit assessment of growth hormone use in children

Growth hormone prepared by recombinant DNA technology (somatropin) has been commercially available for over 11 years. More than 38,000 children have been treated with different growth hormone products. While the best response to treatment occurs in children with severe growth hormone deficiency, therapy with growth hormone will increase the rate of statural growth in children with short stature of many different aetiologies. There are few studies of the effect of growth hormone treatment of final adult height, and the magnitude of this effect is harder to gauge, particularly in children with idiopathic short stature. Other benefits of growth hormone treatment in children include improvement in psychosocial functioning and physiological parameters, such as bone mineral density. Adverse effects associated with growth hormone treatment have been relatively uncommon. Most of the safety data on growth hormone have come from large postmarketing databases maintained by 2 pharmaceutical companies. The adverse event profile reported in children treated with growth hormone is different from that found in adults. Peripheral oedema and carpal tunnel syndrome, which are common in adults treated with growth hormone and frequently result in treatment discontinuation, are rare in children. Intracranial hypertension is rare, but can occur in children with growth hormone deficiency, Ullrich-Turner syndrome or renal insufficiency during the first 8 to 12 weeks after the start of growth hormone treatment; it has seldom been reported in adults with growth hormone deficiency. Children with growth hormone deficiency, Ullrich-Turner syndrome or renal insufficiency are prone to develop slipped capital femoral epiphyses both before and during growth hormone treatment. Therefore, limping and complaints of hip or knee pain should be carefully investigated.     

A comparative clinical evaluation of the Wisdom Straight, Plaque Control and Angled toothbrushes compared to the Oral-B 35

PURPOSE: Many patients attend orthopedic departments complaining of pain on the plantar aspect of the calcaneum. The symptoms may subside spontaneously, but often persist. Treatment is usually by local injection of a corticosteroid, orthopedic devices or other standard treatment. If these methods fail, X-ray treatment may be considered. The efficacy of radiotherapy of the calcaneal spur was evaluated. PATIENTS AND METHODS: From April 1981 through December 1991, 18 patients with painful heel were irradiated mostly with the caesium or telecobalt unit, usually with a dose of 4 times 0.5 Gy. Among these patients, 12 could be followed up during a prolonged period on the basis of questionnaires. RESULTS: According to the categories of v. Pannewitz 17% of the patients were pain-free by the end of the treatment course, 22% showed marked improvement, 33% showed improvement and in 28% the pain was not influenced. Over an average of 41.5 months 58% of the patients reported freedom from pain. CONCLUSIONS: Low-dose radiotherapy appears to relieve the painful heel syndrome in a high proportion of patients. The overall treatment risk appears to be very small. The mechanism of low-dose radiotherapy is unknown.     

Phosphorus-31 magnetic resonance brain spectroscopy of children at risk for a substance use disorder: preliminary results

The purpose of this exploratory investigation was to evaluate the heuristic potential of 31P magnetic resonance spectroscopy (MRS) in elucidating a neurobiologic component of the liability for a substance use disorder (SUD). We investigated 31P MRS spectra employing chemical shift imaging (CSI) derived from four distinct anatomic brain locations (i.e. frontal, occipital, right parietal, left parietal) in three groups of peripubertal children who are hypothesized to be at increasing levels of familial SUD risk. Specifically, we studied children with a positive paternal family history of SUD and a disruptive behavior disorder (DBD) diagnosis (SUD+/DBD+; n = 10), in contrast, to those with a positive paternal SUD history in the absence of other psychopathology (SUD+/DBD-; n = 13) and matched control children from normal families (SUD-/DBD-; n = 13). In addition, we examined neurocognitive tests of our subjects to determine any associations between cognitive capacities with regional 31P MRS spectra. The highest-risk sample (SUD+/DBD+) demonstrated a diminished proportion of phosphodiesters confined to the right parietal voxel. This right parietal phosphodiester proportion correlated only with the Information Scale score on a standard intelligence test for children. This suggested a relationship between general learning ability and motivation for academic achievement and right parietal physiology in the highest-risk sample. Variations in synaptic pruning could account for this observation.     

Paget bone disease involving young adults in 3 generations of a Korean family

Pancreatic cancer is an aggressive disease with a dismal prognosis. It has long been regarded as one of the most difficult cancers to accurately diagnose and stage preoperatively. The purpose of this review is to provide an update of the state-of-the-art for early detection, diagnosis, and staging of pancreatic cancer. These methods include spiral CT scans, magnetic resonance imaging, positron emission tomography (PET) imaging, laparoscopy, endoscopic ultrasound, CA 19-9 serology, fine needle aspiration cytology, ERCP brush cytology, and screening for p53 and ras oncogenes. These advanced techniques should help us to detect pancreatic cancers in high-risk populations at a curative stage and to decrease pancreaticoduodenectomies for benign disease which could otherwise be treated with less morbid procedures. In addition, these tests will help reliably diagnose pancreatic cancer preoperatively.