[Interest of several pharmaceutical activities to secure the care pathway of elderly patients?] / Sécurisation du parcours de soins du sujet âgé : intérêt d'une offre variée d'activités pharmaceutiques ?

OBJECTIVES: In order to prevent medication errors during patient's care pathway, all transition steps must be secured. The main objective of this study was to assess the interest of medication review at hospital discharge on the sustainability of therapeutic optimizations made during hospitalisation in a geriatric population. MATERIAL AND METHODS: This was a three months prospective, single-centre study performed in an acute geriatric unit of a university hospital. All patients hospitalized during the study were included. They were divided in two groups: the securing pathway (SP) group with admission reconciliation, step 3 prescription analysis (according to the French Society of clinical pharmacy) and medication review at hospital discharge were compared to the not concerned group (NSP) with only a step 2 (according to the French Society of clinical pharmacy) prescriptions analysis. The Medication Regimen Complexity Index was used to quantify the complexity of medication regimens. RESULTS: In total, 53 patients of the SP group and 44 patients of the NSP group got the benefit of whole clinical pharmaceutical activities put in places. The average medications on discharge's drug prescription is lower in SP group (SP 8.4±3.4 medications and NSP 9.6±3.2 medications, P=0.06). The discharge's drug prescription complexity index is lower in SP group compared to NSP group (SP 27.9±9.8 and NSP 32.7±11.5, P=0.02). The same trend is observed 30 days post discharge. CONCLUSION: A medication review at hospital discharge reduces the subsequent drug prescription's complexity score. This multidisciplinary dynamic makes easier the communication between health care professionals and contributes to strengthen the city-hospital link.

Clinical presentation of endometriosis identified at interval laparoscopic tubal sterilization: Prospective series of 465 cases.

OBJECTIVES: Women seeking sterilization are usually parous and have no major complains, such as pelvic pain. This could be a good model to indirectly assess the prevalence of endometriosis in the general population. Prevalence of endometriosis in women undergoing tubal sterilization by laparoscopy has been assessed in 17 published reports. Results indicate a surprising wide variation of prevalence of endometriosis, ranging from 1.4% to 43.3%. This clinical study describes the prevalence and clinical presentations of endometriosis identified at interval laparoscopic tubal sterilization, as a close representation of endometriosis in general population. MATERIAL AND METHODS: From July 1989 to February 2009, 465 women undergone interval laparoscopic tubal sterilization and were included in this series. Surgery was realised in a non universitary centre of gynecologic surgery. All patients were operated on by the same surgeon. A complete assessement of pelvic organs was achieved with a particular attention paid for endometriotic lesions. Endometriosis when present was staged according to r-AFS classification. Biopsies were sent for pathological examination to assess endometriosis. RESULTS: Mean age of women was 40.7 years (range 15-49 years). 20 women were nulliparous and 12 others had a past history of endometriosis. Endometriosis was visually identified in 55 patients (11.82%), and confirmed by histologic examination in most of cases (50/55: 90.9%). The mean age of women presenting endometriosis at the onset of tubal ligation was 41.27 years. Cases with endometriosis were classified according to the r-AFS. 39,7,8 and 1 cases corresponded to stages I, II, III and IV respectively. In the 20 nulliparous women, the prevalence of endometriosis was 20% (4/20). At the time of laparoscopic sterilization, 91 women presented a painfull condition (dysmenorrhea mainly or dyspareunia). Endometriosis was identified in 16 of them (17.58%). In the group of 360 asymptomatic parous women, the prevalence of endometriosis was 10% (36/360). Nulliparity, associated pelvic pain and retroverted uterus were associated with increased prevalence of endometriosis, without being significant. CONCLUSION: In our study, the prevalence of endometriosis identified at interval laparoscopic tubal sterilization was 11.82%. In parous asymptomatic women, the prevalence of endometriosis was 10%. The prevalence of endometriosis was slightly increased in nulliparous women, when pain was associated and in women with a retroverted uterus.

Risk factors of postoperative vomiting in children receiving continuous intravenous morphine.

BACKGROUND: Risk factors of postoperative vomiting (POV) have been less extensively explored in children compared to adults. We analyzed the risk factors of POV in children receiving continuous intravenous (i.v.) morphine in a standardized manner without POV prophylaxis after major surgery. METHODS: This observational retrospective study included 235 children aged from 2 to 216 months (91 F:144 M, 11.5% <6 months, 31.5% 6-11 months). The primary end point was the occurrence of at least one episode of POV recorded on the nursing chart. The independent predictors of POV were determined by univariate analysis followed by a multivariate analysis by logistic regression. The data are presented as either medians (25th-75th percentile) or as values with a 95% confidence interval. RESULTS: Continuous i.v. morphine was administered over 42 (22-60) h with an initial infusion rate of 20 µg x kg(-1) x h(-1) in 63% of cases, which was increased in 31.5% of cases and was accompanied by an additional bolus in 39.2% of children. At least one episode of POV occurred in 22.6% of children. The following three independent factors were associated with POV: female gender (OR 3.324 [1.695-6.519], P=0.0005), urological surgery (OR 5.605 [1.291-24.340], P=0.0214) and age (OR 1.012 [1.006-1.018], P<0.0001). The discriminating characteristics of the model were good with an ROC curve AUC of 0.778, sensitivity of 71.7% and specificity of 71.4% for a 0.22 cut-off value of POV incidence. The positive predictive value was 42.2%, and the negative predictive value was 89.6%. CONCLUSION: Female gender, which is usually considered a risk factor after puberty, should be taken into account independent of age to guide the POV prophylaxis in children receiving a postoperative continuous i.v. morphine infusion.

Task-related environment alters the cuticular hydrocarbon composition of harvester ants.

Within a colony of harvester ants (Pogonomyrmex barbatus), workers in different task groups differ in the hydrocarbon composition of the cuticle. Foragers and patrollers, which spend extended periods of time outside the nest, have a higher proportion of saturated, unbranched hydrocarbons (n-alkanes) on the cuticle than nest maintenance workers, which spend only short periods of time outside the nest. We tested whether these task-related differences in ant cuticular chemistry arise from exposure to conditions outside the nest. Nest maintenance workers experiencing daily, short-term outside exposure developed a higher proportion of n-alkanes on the cuticle than workers kept inside the lab. Independent manipulations of ultraviolet radiation, relative humidity, and temperature revealed that only the combination of high temperature (ca. 38 degrees C) and low relative humidity (ca. 8%) increased the proportion of cuticular n-alkanes. The results indicate that warm dry conditions, such as those encountered when an ant leaves the nest, trigger changes in cuticular chemistry.

Qualitative and quantitative differences in cuticular hydrocarbons between laboratory and field colonies of Pogonomyrmex barbatus.

Ants held in the laboratory and field ants of the species Pogonomyrmex barbatus have quantitative differences in their cuticular hydrocarbons and a qualitative difference in their methyl-branched hydrocarbons. Laboratory-held workers showed twice the hydrocarbon content as field ants. This difference was mainly due to higher amounts of straight-chain alkanes and methyl-branched alkanes in laboratory ants, whereas the proportion of the alkenes remained the same for both groups. In addition to the absence of some hydrocarbons in the field colonies, one of the methyl-branched hydrocarbons differed in amount and branching pattern between the two groups of ants. Whereas, notable peaks of 2-methylalkanes were identified in ants kept in the laboratory, these compounds could not be identified in ants living in their natural habitat. However, a trace amount of 4-methyltriacontane was found in lieu of the 2-methyltriacontane counterpart in field ants. Possible explanations for both qualitative and quantitative differences are discussed.

Pharmacological properties of peptides derived from stromal cell-derived factor 1: study on human polymorphonuclear cells.

Small compounds capable of blocking the stromal cell-derived factor 1 (SDF-1) receptor CXCR4 may be potentially useful as anti-inflammatory, antiallergic, immunomodulatory, and anti-human immunodeficiency virus (HIV) agents. SDF-1-derived peptides have proven to target CXCR4 efficiently despite a 100-fold lower affinity (or more) than SDF-1. Here we studied the binding and antiviral properties of a series of substituted SDF-1-derived N-terminal peptides and tested their functional effects on human polymorphonuclear cells, because these cells are very reactive to chemokines and chemoattractants. All peptides bound to CXCR4 and inhibited HIV entry in a functional assay on CD4(+) HeLa cells. A 10-residue substituted dimer, derived from the 5-14 sequence of SDF-1, displayed the highest affinity for CXCR4 (K(i) value of 290 nM, a reduction of only 15-fold compared with SDF-1) and was also the best competitor for HIV entry (IC(50) value of 130 nM). Whereas most peptides displayed CXCR4-independent functional effects on human polymorphonuclear cells, including the modulation of calcium fluxes and the activation of superoxide anion production at high concentration (10 microM), the peptide dimer was devoid of these nonspecific effects at antiviral concentrations. Overall, this study shows that appropriate modifications of SDF-1-derived N-terminal peptides may ameliorate their binding and viral blocking properties without generating significant unspecific side effects.

Novel wax esters and hydrocarbons in the cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus.

The cuticular surface lipids of the red harvester ant, Pogonomyrmex barbatus, were found to contain minor amounts of novel wax esters, in addition to the major components, hydrocarbons. The wax esters ranged in carbon number from C19 to C31 and consisted of esters of both odd- and even-numbered alcohols and acids. Each wax ester with a given carbon number eluted at several different retention times indicating possible methyl branching in either the fatty acid or alcohol moiety, or in both moieties. Each eluting peak of wax esters consisted of a mixture of wax esters of the same carbon number in which the fatty acid moiety ranged from C8 to C18, and the alcohol moiety ranged from C8 to C17. Some wax esters were largely found on the head indicating they may be of a glandular origin. The hydrocarbons consisted of: n-alkanes, C23 to C33; odd-numbered n-alkenes, C27 to C35; and the major components, methyl-branched alkanes, C26 to over C49. Notable components of the methyl-branched alkanes were 2-methyltriacontane, and the novel trimethylalkanes with a single methylene between the first and second branch points, 13,15,19-trimethylhentriacontane and 13,15,21-trimethyltritriacontane.

Metamorphosis in drosophila and other insects: the fate of neurons throughout the stages.

The nervous system of insects is profoundly reorganised during metamorphosis, affecting the fate of different types of neuron in different ways. Almost all adult motor neurons derive from larval motor neurons that are respecified for adult functions. A subset of larval motor neurons, those which mediate larval- or ecdysis-specific behaviours, die before and immediately after eclosion, respectively. Many adult interneurons develop from larval interneurons, whereas those related to complex adult sense organs originate during larval life from persisting embryonic neuroblasts. Sensory neurons of larvae and adults derive from essentially two distinct sources. Larval sensory neurons are formed in the embryonic integument and - with few exceptions - die during metamorphosis. Their adult counterparts, on the other hand, arise from imaginal discs. Special emphasis is given in this review to the metamorphic remodelling of persisting neurons, both at the input and output levels, and to the associated behavioural changes. Other sections deal with the programmed death of motor neurons and its causes, as well as with the metamorphic interactions between motor neurons and their target muscles. Remodelling and apoptosis of these two elements appear to be under independent ecdysteroid control. This review focusses on the two most thoroughly studied holometabolous species, the fruitfly Drosophila melanogaster and the tobacco hornworm moth Manduca sexta. While Manduca has a long tradition in neurodevelopmental studies due to the identification of many of its neurons, Drosophila has been increasingly used to investigate neural reorganisation thanks to neurogenetic tools and molecular approaches. The wealth of information available emphasises the strength of the insect model system used in developmental studies, rendering it clearly the most important system for studies at the cellular level.

Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins.

Mel 1a melatonin receptors belong to the super-family of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors. So far, interest in Mel 1a receptor signaling has focused mainly on the modulation of the adenylyl cyclase pathway via pertussis toxin (PTX)-sensitive G proteins. To further investigate signaling of the human Mel 1a receptor, we have developed an antibody directed against the C terminus of this receptor. This antibody detected the Mel 1a receptor as a protein with an apparent molecular mass of approximately 60 kDa in immunoblots after separation by SDS-PAGE. It also specifically precipitated the 2-[125I]iodomelatonin (125I-Mel)-labeled receptor from Mel 1a-transfected HEK 293 cells. Coprecipitation experiments showed that G(i2), G(i3), and G(q/11) proteins couple to the Mel 1a receptor in an agonist-dependent and guanine nucleotide-sensitive manner. Coupling was selective since other G proteins present in HEK 293 cells, (G(i1), G(o), G(s), G(z), and G12) were not detected in receptor complexes. Coupling of the Mel 1a receptor to G(i) and G(q) was confirmed by inhibition of high-affinity 125I-Mel binding to receptors with subtype-selective G protein alpha-subunit antibodies. G(i2) and/or G(i3) mediated adenylyl cyclase inhibition while G(q/11) induced a transient elevation in cytosolic calcium concentrations in HEK 293 cells stably expressing Mel 1a receptors. Melatonin-induced cytosolic calcium mobilization via PTX-insensitive G proteins was confirmed in primary cultures of ovine pars tuberalis cells endogenously expressing Mel 1a receptors. In conclusion, we report the development of the first antibody recognizing the cloned human Mel 1a melatonin receptor protein. We show that Mel 1a receptors functionally couple to both PTX-sensitive and PTX-insensitive G proteins. The previously unknown signaling of Mel 1a receptors through G(q/11) widens the spectrum of potential targets for melatonin.

Effect of piracetam on polyphosphoinositide metabolism, cytosolic calcium release, and oxidative burst in human polymorphonuclear cells: interaction with fMLP-induced stimulation.

We investigated the action of piracetam on human polymorphonuclear leukocyte (PMN) responsiveness in vitro. We first studied phosphoinositide metabolism and calcium release with and without fMLP (formyl-methionyl-leucyl-phenylalanine) stimulation. Piracetam at concentrations from 10(-4) to 10(-2) M induced a slight increase in inositol 1,4,5-trisphosphate (IP3) release and phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown. At concentrations above 10(-3) M, piracetam sensitized PMNs to subsequent stimulation by fMLP used at subliminal concentrations (10(-9) and 10(-8) M), inducing a significant increase in IP3 release and PIP2 breakdown similar to that obtained with cells stimulated by the highest effective concentrations of fMLP (10(-7) and 10(-6) M). In the same way, piracetam greatly enhanced calcium release induced by weak concentrations of fMLP. However, piracetam had no effect on oxidative metabolism. We then studied the binding of (3H)fMLP to the PMN membrane in the presence of various concentrations of piracetam. We were not able to demonstrate an obvious action of piracetam either on receptor recruitment or on receptor affinity to fMLP. The difference between the actions of piracetam on phosphoinositide metabolism and calcium release on the one hand and oxidative burst on the other could be explained by an uncoupling of the triggering and activating effects of piracetam on PMNs. The enhancement by piracetam of intracellular cyclic AMP levels rapidly induced termination of the PMN response and accounted for the lack of effect on superoxide production. Thus, piracetam was able to modulate human PMN reactivity and in particular to exert a "priming effect" (rather due to structural modifications of the membrane), which might be of importance in infectious episodes given the absence of deleterious actions such as oxygen free radical production leading to tissue injury.

Drosophila P[Gal4] lines reveal that motor neurons involved in feeding persist through metamorphosis.

Two P[Gal4] insertion lines in Drosophila melanogaster, MT11 and MT26, express GAL4 specifically in two to three pairs of pharyngeal motor neurons (PMN) in the suboesophageal ganglion. By using various secondary reporters, the architecture of the PMN, including their efferent axons in the pharyngeal nerve, was visualized. This allowed us to identify a pharyngeal dilator muscle as their target. To study the function of these neurons, we crossed line MT11 with a UAS-tetanus toxin gene construct (TNT-C) that inhibits all synaptic transmission. The offspring shows a reduction in food ingestion of 75% compared to the MT11 and TNT-C controls, demonstrating that PMN control food uptake. More important, lines MT11 and MT26 enabled us to follow PMN and their processes through metamorphosis, since labeling appears in the late third larval instar and persists up to adulthood. The motor axons innervate a pharyngeal muscle in the larva as well and extend through the maxillary nerve, proving that this nerve is homologous to the adult pharyngeal nerve. Efferent arborizations persist throughout metamorphosis, even though the larval muscle histolyzes by 20% of pupal life. Yet, some dedifferentiated structures remain, which may serve as a template for the formation of the adult muscle. Labeling of line MT26 with bromodeoxyuridine at embryonic or larval stages suggests that these neurons undergo their terminal mitosis in the mid to late embryo.

Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of polymorphonuclear leukocytes.

Dermaseptin (DRs S1), a 34-amino acid residue cationic antimicrobial peptide was studied for its effects on the production of reactive oxygen species (respiratory burst) and exocytosis of polymorphonuclear leukocytes (PMN). Treatment of PMN with DRs S1 (10-100 nM) stimulated significant production of reactive oxygen species (approximately a 2-fold increase relative to control) and release of myeloperoxidase. In addition, low DRs S1 concentrations (1-10 nM) primed the stimulation of respiratory burst induced by zymosan particles. In contrast to the native peptide, a dermaseptin fragment without either the COOH-terminal (DRs 1-10) or NH2 terminal (DRs 16-34) portion was inactive. The DRs S1-induced respiratory burst was inhibited by a selective protein kinase C inhibitor, GF 109203X, and was associated with early signalling events such as a rapid and transient elevation of cytosolic-free calcium concentration and phospholipase D activity. These data provide the first evidence of stimulating and priming properties of a peptide antibiotic on microbicidal activities of neutrophils, suggesting a potential role of dermaseptin in modulating host-defense mechanisms.

Mapping of the X-breakpoint involved in a balanced X;12 translocation in a female with mild mental retardation.

Balanced chromosomal abnormalities such as translocations and inversions have been identified in many genetic diseases. Cloning of the breakpoints involved in these abnormalities has led to the identification of the disease-related genes. Recent reports suggest the presence of a mental retardation locus at Xq11-12. We have identified a female patient with a balanced translocation t (X;12) (q11;q15) associated with mild mental retardation. We identified a yeast artificial chromosome spanning the X-chromosome breakpoint by using fluorescent in situ hybridization techniques. A cosmid library of this YAC has been constructed and the search for candidate genes is in progress.

Larval chemosensory projections and invasion of adult afferents in the antennal lobe of Drosophila.

We have studied the fate of olfactory afferents during metamorphic transformation of Drosophila melanogaster. Intracellular labeling of afferents from larval head chemosensilla suggests that the larval antennal lobe may be an olfactory target, whereas tritocerebral and suboesophageal centers are likely targets of gustatory sensilla. Application of monoclonal antibody 22C10 shows that the larval antennal nerve is the precursor of the adult antennal nerve and is used as a centripetal pathway for the adult afferents. Likely guidance cues are larval olfactory afferents that persist during early metamorphosis. P[GAL4] enhancer trap lines are introduced as efficient markers to follow the establishment of adult sensory projection. beta-Galactosidase and the bovine TAU protein were used as reporter proteins, and their expression patterns are compared. P[GAL4] lines MT14 and KL116 demonstrate that adult antennal afferents have arrived in the antennal lobe 24 h after pupariation and extend to the contralateral lobe 6 h later. Line MT14 expresses GAL4 mostly in basiconic sensilla and in certain trichoid sensilla, whereas KL116 is specific for trichoid and a small subset of basiconic sensilla. In the antennal lobe, largely complementary subsets of glomeruli are labeled by the two lines, in agreement with the observation that particular types of sensilla project to particular target glomeruli.

Effects of human low-density lipoproteins on superoxide production by formyl-methionyl-leucyl-phenylalanine activated polymorphonuclear leukocytes.

Neutrophils play a major role in the host defence by producing reactive oxygen species. These products are liberated by activated cells and are known to cause endothelial cell injury and damage. The present study shows that low-density lipoproteins increase superoxide anion production by twofold in polymorphonuclear leukocytes stimulated by formyl-Met-Leu-Phe in vitro. Moreover, LDL induced a large increase in phosphoinositides and cytosolic-free calcium. Data from experiments performed on neutrophils treated with pertussis toxin, staurosporine, propranolol or niflumic acid suggest that modulation of phospholipase D and A2 activities could be involved in the modification by LDL of leukocyte response to formyl-Met-Leu-Phe. LDL lipid moiety could play a key role in their action on polymorphonuclear functions because cholesterol was exchanged between lipoproteins and cells that can modify membrane fluidity and interact with the formyl-Met-Leu-Phe receptor.

Effects of plasma lipoproteins on the production of superoxide anion by human polymorphonuclear leukocytes in vitro.

Polymorphonuclear leukocytes (PMN) generate highly reactive oxygen derived free radicals that may cause lipoprotein lipid oxidation and so contribute to the pathogenesis of atherosclerosis. On the other hand it has been shown that lipoproteins can alter cell functions in vitro. We therefore studied the effects of atherogenic lipoproteins, VLDL and LDL, on the production of superoxide anion by human PMN in the presence or absence of formyl-methionyl-leucyl-phenylalanine (fMLP). VLDL and LDL stimulate PMN superoxide production and potentialize PMN stimulation by fMLP. The lipid moiety of the lipoproteins might be mainly involved in these effects. The binding of radio-labelled fMLP to its specific membrane receptor was significantly enhanced in the presence of VLDL and only slightly in the presence of LDL. The study of the signal transduction suggests that modulation of phospholipase D and A2 activities could be involved in the modification by LDL of PMN response to fMLP.

Expression of m1 and m4 muscarinic receptor mRNA in the striatum following a selective lesion of striatonigral neurons.

Cholinergic stimulation has opposing effects on striatopallidal and striatonigral neurons. Most striatal projection neurons express m1 muscarinic receptor mRNA with m4 mRNA found in 40-50%. Expression of m4 mRNA is found in most preprotachykinin neurons but only a subset of preproenkephalin neurons, suggesting preferential localization of m4 receptors to striatonigral neurons. A volkensin lesion of striatonigral neurons reduced striatal m4 mRNA by 63% and m1 mRNA by only 18%, suggesting that preferential expression of m4 receptors by striatonigral neurons may contribute to their differential response.

Immunomodulatory effects of ornithine alpha-ketoglutarate in rats with burn injuries.

OBJECTIVE: To investigate the influence of enterally administered ornithine alpha-ketoglutarate (OKG) on muscular amino acid content, eicosanoid release, and polymorphonuclear leukocyte responsiveness after induction of burn injury in rats. DESIGN: Experimental trial. MATERIALS AND METHODS: Four groups of rats were considered: (1) healthy rats that received a standard diet supplemented with 5 g/kg per day of OKG; (2) rats with burn injuries that received the same nutrition as group 1; (3) healthy rats that received standard diet supplemented with glycine in an isonitrogenous amount relative to OKG; and (4) rats with burn injuries that received the same nutrition as group 3. The thymus and 1 skeletal muscle were weighed. The oxidative metabolism of pleural polymorphonuclear leukocytes was measured by means of superoxide generation (O2-) and the chemiluminescent response to opsonized zymosan. Prostaglandin E2 and 6-keto-prostaglandin F1 alpha were measured in the supernatants of pleural and peritoneal cells. RESULTS: The weights of the thymus and the muscle from healthy rats were similar. Those of rats from group 4 were significantly lower (P < .05), whereas those of rats from group 2 were not. Metabolism of OKG led to enhanced amounts of arginine and glutamine in skeletal muscle. The metabolic bursts of polymorphonuclear leukocytes from healthy rats were similar. Those of glycine-treated rats with burn injuries were significantly depressed (P < .05), whereas those of the OKG-treated group were not. Pleural and peritoneal cells from the rats with burn injuries that received OKG generated significantly more prostaglandins (P < .01) than did cells from the other groups of rats. CONCLUSION: Ornithine alpha-ketoglutarate administered to rats with burn injuries displays immunomodulatory properties that can enhance host-defense mechanisms in animals that are affected by a severe injury.