Behavioural and emotional disturbances associated with sleep-disordered breathing symptomatology in children with Down's syndrome.

BACKGROUND: Down's syndrome (DS) predisposes to sleep-disordered breathing (SDB). In children with DS, behavioural and emotional disturbances secondary to SDB are often assumed to result from cognitive impairment alone. Our aim was to explore the relationship of behavioural and emotional disturbances with SDB in a population of children with DS. METHODS: A modified sleep questionnaire, Epworth Sleepiness Scale (ESS), Paediatric ESS and the short form of the developmental behaviour checklist (DBC-P24) were sent to 261 carers of children aged 4 to 15 years with DS in 2012. RESULTS: Of 120 participants, 25% had probable SDB. In children with probable SDB compared to those without nocturnal symptoms, the total behaviour problem score (TBPS) was significantly higher (20.3 ± 8.6/48 vs. 12 ± 7.5/48; P = 0.002) as was the PaedESS (7.7 ± 5.6/24 vs. 2.8 ± 3.5/24; P = 0.002). For every increase in frequency of choking attacks, snoring and night awakenings, the TBPS increased by 1.37, 1.28 and 1.75 points, respectively, indicating worsening behaviour. The TBPS was found to decrease by 1.31 points for every hour more of self-reported sleep duration (r = -0.25, P = 0.017). CONCLUSIONS: SDB symptoms and shorter self-reported sleep duration are highly prevalent among children with DS and are independently associated with worsening behaviour using the TBPS.

Use of near-infrared spectroscopy to identify trends in regional cerebral oxygen saturation in horses.

REASONS FOR PERFORMING STUDY: Alterations in cerebral haemodynamics may contribute to perianaesthetic complications in horses. Near-infrared spectroscopy (NIRS) is frequently used intraoperatively in man to provide information regarding cerebral perfusion. OBJECTIVES: To determine whether NIRS can identify trends in regional cerebral oxygen saturation (rSO2) in horses and whether there is a correlation between rSO2 and venous oxygen tensions. METHODS: A cerebral oximeter sensor recorded rSO2 from the dorsal sagittal sinus of 6 healthy horses. Values for rSO2, arterial and venous oxygen and carbon dioxide tensions (PaO2, PvO2, PaCO2 and PvCO2 respectively), along with arteriovenous oxygen saturations (SavO2) were recorded in unsedated (recording period [RP] 1), sedated (RP2) and anaesthetised horses (RP3-5) and during recovery (RP6-8). During anaesthesia, horses were ventilated to achieve states of normo- (RP3), hyper- (RP4) and hypocapnoea (RP5). Data were evaluated descriptively and analysed using linear mixed-effects models and Pearson's correlation coefficient. RESULTS: Overall mean ± s.d. values for rSO2, PaO2, PvO2, PaCO2, SavO2 and mean arterial pressure varied significantly by RP (P<0.001). Significant decreases in rSO2 were identified between RP1 and the post anaesthetic periods (P<0.001). No significant differences in rSO2 values were identified between RP1 and the intra-anaesthesia periods or between RP3, RP4 and RP5. Significant correlations were identified between rSO2 and PaO2 (r = 0.448, P<0.001), rSO2 and PvO2 (r = 0.512, P<0.001) and rSO2 and SavO2 (r = 0.469, P<0.001). CONCLUSIONS: This is the first study to identify trends in rSO2 in horses using NIRS. A positive correlation was identified between rSO2 and PvO2, suggesting that alterations in cerebral oxygenation may be reflected in PvO2 . POTENTIAL RELEVANCE: Near-infrared spectroscopy may be used to monitor trends in rSO2 during equine anaesthesia. Decreasing rSO2 values may act as an early warning signal, alerting clinicians to potential cerebral desaturation events and indicating a need for intervention.

Atypical diverticular disease: surgical results.

PURPOSE: Patients with diverticular disease may present with chronic symptoms but never develop diverticulitis. The purpose of this research was to review the outcome of surgical intervention in this subgroup of patients with atypical "smoldering" diverticular disease. METHODS: Records of 930 patients who underwent sigmoid resection for diverticular disease during a ten-year period at the Mayo Clinic in Rochester, Minnesota, were reviewed. Forty-seven patients (5 percent) fit our inclusion criteria for smoldering diverticular disease and underwent sigmoid colectomy with primary anastomosis. A minimum of 12 months of follow-up was completed in 68 percent of these patients. RESULTS: Evidence of acute or chronic inflammatory changes was present in 76 percent of resected specimens. Complete resolution of symptoms occurred in 76.5 percent, with 88 percent being pain free. CONCLUSIONS: We conclude that the diagnosis and presentation of atypical smoldering diverticular disease is an uncommon and poorly defined entity. However, sigmoid resection in this subgroup of patients is safe and is associated with resolution of symptoms in the majority of cases.

Advantages of laparoscopic resection for ileocolic Crohn's disease. Improved outcomes and reduced costs.

BACKGROUND: Laparoscopic colorectal procedures are considered to be technically challenging, and there is a lack of consensus regarding the magnitude of their benefits. The laparoscopic approach is generally held to be more expensive. Using a model of a single procedure performed for a single indication (ileocolic resection for Crohn's disease [CD]), we set out to demonstrate the feasibility of this procedure by determining the conversion rate, documenting the patient benefits, and performing a formal cost analysis. METHODS: Consecutive cases of laparoscopic ileocolic resection for CD were identified (LAP). Case-match methodology identified a series of open laparotomy controls (OPEN) that were matched for five potential confounding criteria: age, gender, diagnosis, type of resection, and date of operation. Pre-, intra-, and postoperative details were gathered. Medical resource utilization was tracked using a standardized database, and all costs were reported in 1999 dollars. RESULTS: The conversion rate was 5.9%. Resolution of ileus occurred more rapidly in the LAP than in the OPEN group. The time to clears in the LAP group was a median of 0 days (range, 0-4) vs 3.0 days (range, 2-8) in the OPEN group (p = 0.0001). Time to regular diet was 2.0 days (range, 1-6) in the LAP group vs 5.0 days (range, 3-12) in the OPEN group (p = 0.0001). Length of hospital stay was significantly reduced in the LAP group (4.0 days [range, 2-8], vs 7.0 days [range, 3-14], p = 0.0001). The LAP group had significantly lower direct costs ($8684 vs $11,373) and indirect costs ($1358 vs $2349) than the OPEN group (p < 0.001). This resulted in total costs of $9895 for LAP vs $13,268 for OPEN (p < 0.001). CONCLUSION: Laparoscopic ileocolic resection for CD is feasible. There are significant postoperative benefits in terms of resolution of ileus, narcotic use, and hospital stay. This approach translates into cost savings of >$3300 for laparoscopic patients.

Pharmacological and immunohistochemical characterization of calmodulin-stimulated (Ca(2+)+Mg(2+))-ATPase in cultured porcine aortic endothelial cells.

Plasma membrane (Ca(2+)+Mg(2+))-ATPase and Ca(2+) transport activities, best characterized in human erythrocytes, are stimulated by calmodulin and thought to play a crucial role in the termination of cellular Ca(2+) signaling in all cells. In plasma membranes isolated from cultured porcine aortic endothelial cells, the (Ca(2+)+Mg(2+))-ATPase was not readily measured. This is in part because of an overabundance of nonspecific Ca(2+)- and/or Mg(2+)-activated ecto-5'-nucleotide phosphohydrolases. Moreover, addition of exogenous calmodulin (10(-9) to 10(-6) mol/L) produced no measurable stimulation of ATPase activities, suggesting a permanently activated state or, alternatively, a complete lack thereof. To establish and verify the presence of a calmodulin-regulated (Ca(2+)+Mg(2+))-ATPase activity in these endothelial cells, immunohistochemical localization using a monoclonal mouse anti-(Ca(2+)+Mg(2+))-ATPase antibody (clone 5F10) was applied to intact pig aorta endothelium, cultured endothelial monolayers, and isolated endothelial plasma membrane fractions. This approach clearly demonstrated Ca(2+) pump immunoreactivity in each of these preparations. To confirm functional calmodulin stimulation of the (Ca(2+)+Mg(2+))-ATPase, 10(-5) mol/L calmidazolium (R24571) was added to the isolated plasma membrane preparation, which lowered the (Ca(2+)+Mg(2+))-ATPase activity from 143.0 to 78.15 nmol P(i)/mg protein x min(-1). This calmidazolium-reduced activity could then be stimulated 113.1+/-0.8% in a concentration-dependent manner by the addition of exogenous calmodulin (10(-7) to 2 x 10(-6) mol/L) with an EC(50) of 3.45+/-0.04 x 10(-7) mol/L (n=4). This represents a competitive lowering of the apparent calmodulin affinity by approximately 100 compared with other unopposed calmodulin-stimulated processes. Together, these findings support evidence for the presence of a calmodulin-stimulated plasma membrane (Ca(2+)+Mg(2+))-ATPase activity in cultured porcine aortic endothelial cells.

Inhibition of calmodulin-stimulated (Ca2+ + Mg2+)-ATPase activity by dimethyl sulfoxide.

Membrane-bound (Ca2+ + Mg2+)-ATPase activity from human erythrocyte white ghosts in the calmodulin-activated state was inhibited by DMSO in concentrations of 3% (v/v) and above. At 10%, DMSO inhibited calmodulin activation by 47.7%, while basal, calmodulin-independent (Ca2+ + Mg2+)-ATPase and (Mg2+)-ATPase activity remained unaffected. (Na+ + K+)-ATPase activity was also reduced but exhibited a greater IC50. Concentration-effect analyses showed the inhibition by 10% DMSO to be a reversible, non-competitive effect with regard to calmodulin, Ca2+, and substrate activation. Calmodulin-stimulated processes may be more susceptible to inhibition by DMSO than related enzymatic catalysis, and thus may help explain the multitude of reported cellular events caused by the solvent. Furthermore, DMSO affected membrane-associated enzymatic mechanisms opposite to those reported for purified enzyme outside its native membrane environment.

Irreversible inhibition of plasma membrane (Ca2+ + Mg2+)-ATPase and Ca2+ transport by 4-OH-2,3-trans-nonenal.

4-OH-2,3-trans-nonenal (HNE), a major aldehydic lipid peroxidation product, has been shown to cause cellular toxicities and has been linked to a number of pathophysiological processes including atherogenesis. Specifically, in vitro exposure of erythrocyte plasma membrane preparations to HNE resulted in the inhibition of membrane transport function and integrity. To characterize the nature of the inhibitory effects of HNE on plasma membrane regulatory mechanisms, we investigated its effects on substrate and calmodulin (CaM) stimulation on erythrocyte Ca2+ transport and (Ca2+ + Mg2+)-ATPase activities. Concentration-effect relationship analysis in erythrocyte membrane "ghosts" and inside-out vesicles (IOVs) yielded purely noncompetitive kinetics for Ca2+, ATP, and CaM activation of (Ca2+ + Mg2+)-ATPase and Ca2+ transport. Reductions of Vmax from direct addition of 0.1 mM HNE to the assay incubation mixtures ranged from 23 to 41%. Similarly, pretreatment with HNE of both membrane ghosts and IOVs resulted in a concentration-dependent inactivation of ATPase and transport activities without changes in affinity for Ca2+, ATP, or CaM. Conversely, pretreatment of CaM itself did not impair its ability to stimulate (Ca2+ + Mg2+)-ATPase activity threefold. Moreover, HNE-pretreated membranes exhibited unaltered acetylcholinesterase activity compared to sham-pretreated membranes. Together, these results suggest that HNE may structurally, and thus irreversibly, modify one or more functionally important sites on the transport protein itself.

Common carotid artery and tracheal injury from shoulder strap seat belt.

Carotid artery injuries from seat belt shoulder straps have been reported involving primarily the internal carotid artery. This paper describes a case of common carotid artery disruption and tracheal transection after a shoulder strap seat belt injury. A successful method for management of this rare injury is presented. Repair involved autogenous arterial replacement in a contaminated field using an interposition graft of superficial femoral artery.

Effects of 4-OH-2,3-trans-nonenal on human erythrocyte plasma membrane Ca2+ pump and passive Ca2+ permeability.

Structural and functional alterations of cell membranes caused by free radicals leading to lipid peroxidation and increases in intracellular Ca2+ concentrations have been implicated in atherogenesis. The objective of this study was to directly measure the effects of a major aldehydic lipid peroxidation product, 4-OH-nonenal (HNE), on plasma membrane Ca2+ regulatory mechanisms. This was attained by measuring passive Ca2+ permeability, primary active Ca2+-transport, and (Ca2+ + Mg2+)-ATPase activity in a human red cell model system. Using this three-pronged approach it could be shown that HNE increases passive Ca2+ permeability significantly beyond the typically low basal flux, while at the same time inhibiting the active Ca2+ extrusion pump and associated (Ca2+ + Mg2+)-ATPase activity. We conclude that this deleterious combination of effects by HNE in this plasma membrane model system may be indicative of plasma membrane changes in cells directly involved in atheroma formation and thus may represent causative factors in the early stages of atherogenesis.

Decreased beta-adrenergic receptors in rat brain after chronic administration of the selective serotonin uptake inhibitor fluoxetine.

Fluoxetine, a novel antidepressant compound that potently and selectively inhibits serotonin uptake, was chronically administered to laboratory rats. Using in vitro receptor autoradiographic techniques, we found that the binding of [3H]-dihydroalprenolol [( 3H]-DHA) decreased significantly in frontal cortex layers. Analysis of saturation experiments indicated that the reduction was due to a change in number but not affinity of [3H]-DHA binding sites. The data support the hypothesis that the mechanism of action of most antidepressant compounds involves a change in beta-adrenergic receptor function.

Chronic administration of sertraline, a selective serotonin uptake inhibitor, decreased the density of beta-adrenergic receptors in rat frontoparietal cortex.

Sertraline, a potent and selective inhibitor of serotonin uptake, was chronically administered to laboratory rats. Using in vitro receptor autoradiographic techniques, we found that the binding of [3H]dihydroalprenolol ([3H]DHA) was reduced in cortex layers IV-VI. Results of a saturation experiment indicated that the reduction in cortex layer IV was due to a change in number but not affinity of beta-adrenergic receptors.

Receptor alterations associated with serotonergic agents: an autoradiographic analysis.

Controversy exists concerning whether receptor down-regulation is involved in the efficacy of antidepressants. Many investigators believe that norepinephrine (NE) receptor down-regulation is more important than serotonin (5-HT) receptor down-regulation. The ability to accurately determine which receptor types or subtypes have been down-regulated has been impaired by the lack of sufficiently specific ligands for labeling these receptor subtypes. Studies that have attempted to examine 5-HT2 receptor down-regulation have used [3H]-ketanserin as the ligand of choice to label 5-HT2 receptors, but this ligand also labels a nondescript site. The binding of [3H]-ketanserin to sites other than 5-HT2 receptors can be examined and controlled for by autoradiographic techniques. The authors briefly review potential problems involved in analyzing receptor binding after antidepressant treatment and present new findings of receptor alterations in rat brain as examined by autoradiographic techniques following chronic exposure to fluoxetine (a selective 5-HT uptake inhibitor that has been shown to be an effective antidepressant). Laboratory animals injected with fluoxetine showed receptor down-regulation (reduced density) in the serotonergic system. A provocative and potentially important finding of this study is that this selective 5-HT uptake blocker also down-regulates beta-adrenergic receptors in the CNS.