Évaluation médico-économique du baclofène intrathécal chez les patients présentant une spasticité chronique sévère

A medicoeconomic evaluation of continuous intrathecal baclofen (Lioresal^®) infusion for symptomatic treatment of severe spinal spasticity was realised using a monocentric, comparative, retrospective approach where subjects were their own controls (n = 22). Study results confirm the efficacy of baclofen on symptoms, functional status of patients and on a non specific quality of life scale. Conversely, use of baclofen lead to a 67% increase of average annual costs of care for these patients and reaches around 173,500 French francs (~29,000 US$)/year. Such a cost seems to be acceptable with respect to clinical benefits. © 1998 Elsevier, Paris     

Intramolecular domain-domain association/dissociation and phosphoryl transfer in the mannitol transporter of Escherichia coli are not coupled

The Escherichia coli mannitol transporter (II(Mtl)) comprises three domains connected by flexible linkers: a transmembrane domain (C) and two cytoplasmic domains (A and B). II(Mtl) catalyzes three successive phosphoryl-transfer reactions: one intermolecular (from histidine phosphocarrier protein to the A domain) and two intramolecular (from the A to the B domain and from the B domain to the incoming sugar bound to the C domain). A key functional requirement of II(Mtl) is that the A and B cytoplasmic domains be able to rapidly associate and dissociate while maintaining reasonably high occupancy of an active stereospecific AB complex to ensure effective phosphoryl transfer along the pathway. We have investigated the rate of intramolecular domain-domain association and dissociation in IIBA(Mtl) by using (1)H relaxation dispersion spectroscopy in the rotating frame. The open, dissociated state (comprising an ensemble of states) and the closed, associated state (comprising the stereospecific complex) are approximately equally populated. The first-order rate constants for intramolecular association and dissociation are 1.7 (+/-0.3) x 10(4) and 1.8 (+/-0.4) x 10(4) s(-1), respectively. These values compare to rate constants of approximately 500 s(-1) for A --> B and B --> A phosphoryl transfer, derived from qualitative line-shape analysis of (1)H-(15)N correlation spectra taken during the course of active catalysis. Thus, on average, approximately 80 association/dissociation events are required to effect a single phosphoryl-transfer reaction. We conclude that intramolecular phosphoryl transfer between the A and B domains of II(Mtl) is rate-limited by chemistry and not by the rate of formation or dissociation of a stereospecific complex in which the active sites are optimally apposed.     

Ambulatory blood pressure monitoring

Ambulatory blood pressure monitoring (ABPM) in adults is proving to be useful. The aim of this study was to determine if ABPM is accurate in the lower blood pressure range encountered in children and, equally important, whether it is acceptable to children. Thirty one children, between the ages of 6 and 18 years, were assessed using an ambulatory blood pressure monitor that uses an auscultatory method. Blood pressure was measured in the contralateral arm with a mercury sphygmomanometer and an oscillometric device at the beginning and end of the study for comparison. Over a blood pressure range of 90-130 mm Hg systolic and 40-80 mm Hg diastolic, a close agreement was found with the sphygmomanometer; the limits of agreement (+/- 2 SD) were 11.6 mm Hg for systolic blood pressure and 13.6 mm Hg for diastolic blood pressure. The bias was less than 1.0 mm Hg. The ambulatory device was worn by all patients for at least 16 hours with an average of 52 recordings per patient. The majority found the device comfortable to wear and were not woken from sleep.     

Lactobezoar and cows' milk protein intolerance

A baby girl of an atopic family who developed eczema, asthma, and cows' milk protein intolerance was found to have a gastric lactobezoar at age 9 1/2 months. She responded well to the removal of the bezoar and to the appropriate dietary treatment.     

Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats

Dietary fatty acid composition modifies hepatic lipid metabolism. To determine the effects of fatty acids on hepatic triglyceride storage, rats were fed diets enriched in carbohydrates (control), fish oil, or lard. After 4 weeks, the animals were fasted overnight. In the morning, the animals were either sacrificed or fed 8 g of their respective diets before sacrifice. Animals ingested more food calories with diets containing fish oil than with other diets. However, fish oil-fed animals weighed less and had less body fat. In fish oil-fed animals, liver triglyceride was lower by 27% (P <.05) and 73% (P <.01) than in control- and lard-fed animals, respectively. Fish oil altered the postprandial gene expression of hepatic regulators of fatty acid degradation and synthesis. Fish oil feeding blunted the normal postprandial decline in fatty acid degradation genes (PPARalpha, CPT1, and ACO) and blunted the normal postprandial rise in triglyceride synthesis genes (SREBP1-c, FAS, SCD-1). Therefore, the direct postprandial effect of fish oil ingestion decreases the propensity for hepatic triglyceride storage. In conclusion, n-3 polyunsaturated fatty acids decrease total body weight, total body fat, and hepatic steatosis.     

Mechanistic details of a protein–protein association pathway revealed by paramagnetic relaxation enhancement titration measurements

Protein–protein association generally proceeds via the intermediary of a transient, lowly populated, encounter complex ensemble. The mechanism whereby the interacting molecules in this ensemble locate their final stereospecific structure is poorly understood. Further, a fundamental question is whether the encounter complex ensemble is an effectively homogeneous population of nonspecific complexes or whether it comprises a set of distinct structural and thermodynamic states. Here we use intermolecular paramagnetic relaxation enhancement (PRE), a technique that is exquisitely sensitive to lowly populated states in the fast exchange regime, to characterize the mechanistic details of the transient encounter complex interactions between the N-terminal domain of Enzyme I (EIN) and the histidine-containing phosphocarrier protein (HPr), two major bacterial signaling proteins. Experiments were conducted at an ionic strength of 150 mM NaCl to eliminate any spurious nonspecific associations not relevant under physiological conditions. By monitoring the dependence of the intermolecular transverse PRE (Γ₂) rates measured on ¹⁵N-labeled EIN on the concentration of paramagnetically labeled HPr, two distinct types of encounter complex configurations along the association pathway are identified and dissected. The first class, which is in equilibrium with and sterically occluded by the specific complex, probably involves rigid body rotations and small translations near or at the active site. In contrast, the second class of encounter complex configurations can coexist with the specific complex to form a ternary complex ensemble, which may help EIN compete with other HPr binding partners in vivo by increasing the effective local concentration of HPr even when the active site of EIN is occupied.     

Which basal insulin should be used in patients with type 2 diabetes mellitus?

The initiation of insulin therapy is a significant event for patients with diabetes and the physicians who care for them. Reluctance to begin insulin is multifactorial, with major stumbling blocks being the perceived complexity of insulin and fear of hypoglycemia. Recent guidelines supporting earlier introduction of insulin to achieve glycemic goals in patients with type 2 diabetes mellitus will require that traditional approaches to insulin therapy be altered and a new paradigm be introduced into clinical practice. In particular, an understanding of the role of basal insulin in the regulation of glucose and the development of strategies to implement basal insulin therapy can provide a transition that is rational and highly effective in most patients. The strategy also offers a unique approach to diabetes education that permits a focused and patient-specific correction to glucose abnormalities.     

Identification of a binding site for the human immunodeficiency virus type 1 nucleocapsid protein.

The nucleocapsid (NC) protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is important for encapsidation of the virus genome, RNA dimerization, and primer tRNA annealing in vitro. Here we present evidence from gel mobility-shift experiments indicating that NCp7 binds specifically to an RNA sequence. Two complexes were identified in native gels. The more slowly migrating complex contained two RNA molecules and one peptide, while the more rapidly migrating one is composed of one RNA and one peptide. Further, mutational analysis of the RNA shows that the predicted stem and loop structure of stem-loop 1 plays a critical role. Our results show that NCp7 binds to a unique RNA structure within the psi region; in addition, this structure is necessary for RNA dimerization. We propose that NCp7 binds to the RNA via a direct interaction of one zinc-binding motif to stem-loop 1 followed by binding of the other zinc-binding motif to stem-loop 1, stem-loop 2, or the linker region of the second RNA molecule, forming a bridge between the two RNAs.