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.     

Strategy for development of a pre-erythrocytic Plasmodium falciparum DNA vaccine for human use

Data generated in the Plasmodium yoelii rodent model indicated that plasmid DNA vaccines encoding the P.yoelii circumsporozoite protein (PyCSP) or 17 kDa hepatocyte erythrocyte protein (PyHEP17) were potent inducers of protective CD8+ T cell responses directed against infected hepatocytes. Immunization with a mixture of these plasmids circumvented the genetic restriction of protective immunity and induced additive protection. A third DNA vaccine encoding the P. yoelii sporozoite surface protein 2 (PySSP2) also induced protection. The P. falciparum genes encoding the homologues of these three protective P. yoelii antigens as well as another P. falciparum gene encoding a protein that is expressed in infected hepatocytes have been chosen for the development of a human vaccine. The optimal plasmid constructs for human use will be selected on the basis of immunogenicity data generated in mice and nonhuman primates. We anticipate that optimization of multi-gene P. falciparum DNA vaccines designed to protect against malaria by inducing CD8+ T cells that target infected hepatocytes will require extensive clinical trials during the coming years.     

Prevalence and effectiveness of self-regulatory techniques used to avoid drunk driving

Research suggests that drinkers often use personal self-regulatory techniques to avoid drunk driving. A population-representative sample of 427 people at high risk of drunk driving were interviewed to examine the extent to which they used self-regulatory techniques. Most popular techniques were limiting drinks to a predetermined number, organizing another driver, catching a taxi, and spontaneously delaying or avoiding driving after alcohol has been consumed. After controlling exposure to demographic and drinking behavior variables, limiting drinks to a predetermined number was the only technique associated with a reduced likelihood of drunk driving. Respondents who used taxis and drank low-alcohol beer were more likely to report drunk driving, as were those who spontaneously decided to delay or avoid driving after drinking. Although interpretation of the findings is constrained by the cross-sectional survey methodology, further investigations may lead to the development of countermeasures which promote the use of appropriate techniques.     

Unfolding and inactivation of Penaeus penicillatus acid phosphatase during denaturation by guanidine hydrochloride

Neuromuscular terminals of a single motoneuron to four muscles (CPV7a, GM5a, CV2, and CV3) in the stomach of the blue crab Callinectes sapidus showed structural evidence for the exocytotic release of dense-core vesicles exclusively at synapses. The primary evidence was the appearance of dense cores in the synaptic cleft, accompanied by indentations of the presynaptic or postsynaptic membrane. In their simplest form, these consisted of an omega-shaped figure of the presynaptic membrane enclosing one dense core, denoting release of a single dense-core vesicle. A larger indentation of the presynaptic membrane enclosing several dense cores denoted multiple release. A more complex form of multiple release was where the presynaptic membrane was normal, but the postsynaptic membrane elaborated into a sac projecting into the granular sarcoplasm and filled with dense cores. The postsynaptic sac in some instances was compressed into a thin, fingerlike extension, which lacked dense cores and, at its distal end, separated into small cisternae, suggesting a mechanism for membrane recycling. Profiles depicting single and multiple releases of dense-core vesicles were found more frequently at neuromuscular terminals that release relatively large amounts of transmitter with a single stimulus, such as CV2 and CV3, compared to those releasing smaller amounts, such as CPV7a and GM5a. The disparity in release sites among the four muscles of this single motor unit and the fact that many of the multiple-release figures were closely adjacent to the active zones for transmitter release suggest a possible modulatory role for dense-core vesicles in synaptic transmission. Such modulation may be long lasting, as implied by the postsynaptic sacs, which may permit prolonged release of the contents of their dense cores into the synaptic cleft. This is in keeping with the functional role of these stomach muscles, which is to be continuously active for long periods of time.     

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.     

Ganglioside GT1b inhibits keratinocyte adhesion and migration on a fibronectin matrix

Highly sialylated gangliosides have been shown to alter cellular adhesion to a fibronectin matrix. The effect of these gangliosides on the adhesion, spreading, and migration of cultured keratinocytes on a fibronectin matrix has not been explored. Ganglioside GT1b significantly prevented attachment of keratinocytes to fibronectin and also detached previously adherent keratinocytes in a concentration-dependent manner without cell toxicity. GT1b did not affect adhesion of keratinocytes to wells coated with laminin, type I or type IV collagen, 804G extracellular matrix, or albumin. GT1b also inhibited keratinocyte migration on fibronectin in a concentration-dependent manner at concentrations as low as 5 nM GT1b, but had no effect on migration of keratinocytes plated on other matrices. GT1b binds to intact fibronectin and to the 120-kD RGDS-containing cell-binding fibronectin fragment, but not to the heparin- or gelatin-binding fragments of fibronectin. Although RGDS competes with GT1b in inhibiting adhesion, GT1b does not diminish binding of keratinocytes to a derivatized RGDS substratum, suggesting that the GT1b effect involves a non-RGDS site in the cell-binding region that modulates RGDS/alpha 5 beta 1 integrin receptor interaction. Through a specific effect on keratinocyte interaction with fibronectin, GT1b may participate in the regulation of cell adhesion and migration on a fibronectin substratum, which are important events during wound healing and the spreading of cutaneous neoplasia.     

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.     

Contrasting two approaches in a community-based nursing practice with older adults: the medical model and Parse''s nursing theory

In 1988, a report of a genetic linkage between schizophrenia and markers on chromosome 5 caused considerable excitement. Many hoped that a cause for schizophrenia had been found. Unfortunately, subsequent results failed to replicate the finding, and there was little progress in the molecular understanding of the disorder over the next five years. However, within the past two years, there have been reports of positive linkages on chromosome arms 22q and 6p that, unlike previous reports, have received support from several teams. Here, we review the evidence for these linkages, as well as findings from association studies that have not yet received as much independent confirmation.