Long-term treatment of aggregating brain cell cultures with low concentrations of lead acetate.

Aggregating brain cell cultures were used as a model to study the effect of chronic exposure to low levels of lead acetate. Long-term maintenance of cultures could be improved by supplementation of the medium with albumin-bound lipids. Exposure for 9 days to 10(-6)-10(-4) M lead acetate caused a decrease of GABAergic (glutamic acid decarboxylase) and astrocytic (glutamine synthetase) markers which was also found after prolonged treatment (50 days) with 10(-7) M lead acetate. Total protein content and choline acetyltransferase were not changed. The results show that prolonged exposure of aggregating brain cell cultures to a low concentration of lead acetate causes distinct changes of cell type-specific parameters.

Incubation methods for assessing mineralizable nitrogen in soils under sugarcane

Considering nitrogen mineralization (N) of soil organic matter is a key aspect for the efficient management of N fertilizers in agricultural systems. Long-term aerobic incubation is the standard technique for calibrating the chemical extraction methods used to estimate the potentially mineralizable N in soil. However, the technique is laborious, expensive and time-consuming. In this context, the aims of this study were to determine the amount of soil mineralizable N in the 0-60 cm layer and to evaluate the use of short-term anaerobic incubation instead of long-term aerobic incubation for the estimation of net N mineralization rates in soils under sugarcane. Five soils from areas without previous N fertilization were used in the layers 0-20, 20-40 and 40-60 cm. Soil samples were aerobically incubated at 35 ºC for 32 weeks or anaerobically incubated (waterlogged) at 40 ºC for seven days to determine the net soil N mineralization. The sand, silt and clay contents were highly correlated with the indexes used for predicting mineralizable N. The 0-40 cm layer was the best sampling depth for the estimation of soil mineralizable N, while in the 40-60 cm layer net N mineralization was low in both incubation procedures. Anaerobic incubation provided reliable estimates of mineralizable N in the soil that correlated well with the indexes obtained using aerobic incubation. The inclusion of the pre-existing NH4+-N content improved the reliability of the estimate of mineralizable N obtained using anaerobic incubation.

Impact of chlorhexidine-impregnated sponges on catheter-related infections rate

INTRODUCTION. Multimodal strategy targeted at prevention of catheter-related infection combine education to general measures of hygiene with specific guidelines for catheter insertion and dressing (1). OBJECTIVES. In this context, we tested the introduction of chlorhexidine(CHX)-impregnated sponges (2). METHODS. In our 32-beds mixed ICU, prospective surveillance of primary bacteremia and of microbiologically documented catheter-related bloodstream infections (CRBSI) is performed according to standardized definitions. New guidelines for central venous catheter (CVC) dressing combined a CHX-impregnated sponge (BioPatch_) with a transparent occlusive dressing (Tegaderm _) and planning for refection every 7 days. To contain costs, Biopatch_ was used only for internal jugular and femoral sites. Other elements of the prevention were not modified (overall compliance to hand hygiene 65-68%; non coated catheters except for burned patients [173 out of 9,542 patients];maximal sterile barriers for insertion; alcoholic solution ofCHXfor skin disinfection). RESULTS. Median monthly CVC-days increased from 710, to 749, 855 and 965 in 2006, 2007, 2008 and 2009, respectively (p\0.01). Following introduction of the new guidelines (4Q2007), the average monthly rate of infections decreased from 3.7 (95% CI: 2.6-4.8) episodes/1000 CVC-days over the 24 preceding months to 2.2 (95% CI: 1.5-2.8) over the 24 following months (p = 0.031). Dressings needed to be changed every 3-4 days. The decrease of catheter-related infections we observed in all consecutive admitted patients is comparable to that recently showed in a placeborandomized trial2. Further generalization to all CVC and arterial catheters access may be justified. CONCLUSIONS. Our data strongly suggest that combined with occlusive dressings, CHXimpregnated sponges for dressing of all CVC catheters inserted in internal jugular and/or femoral sites, significantly reduces the rate of primary bacteremia and CRBSI. REFERENCES. (1) Eggimann P, Harbarth S, Constantin MN, Touveneau S, Chevrolet JC, Pittet D. Impact of a prevention strategy targeted at vascular-access care on incidence of infections acquired in intensive care. Lancet 2000; 355:1864-1868. (2) Timsit JF, Schwebel C, Bouadma L, Geffroy A, Garrouste-Org, Pease S et al. Chlorhexidine- impregnated sponges and less frequent dressing changes for prevention of catheter-related infections in critically ill adults: a randomized controlled trial. JAMA 2009; 301(12):1231-1241.

Novel anesthetics and other treatment strategies for refractory status epilepticus

Refractory status epilepticus (RSE)-that is, seizures resistant to at least two antiepileptic drugs (AEDs)-is generally managed with barbiturates, propofol, or midazolam, despite a low level of evidence (Rossetti, 2007). When this approach fails, the need for alternative pharmacologic and nonpharmacologic strategies emerges. These have been investigated even less systematically than the aforementioned compounds, and are often used, sometimes in succession, in cases of extreme refractoriness (Robakis & Hirsch, 2006). Several possibilities are reviewed here. In view of the marked heterogeneity of reported information, etiologies, ages, and comedications, it is extremely difficult to evaluate a given method, not to say to compare different strategies among them. Pharmacologic Approaches Isoflurane and desflurane may complete the armamentarium of anesthetics,' and should be employed in a ''close'' environment, in order to prevent intoxication of treating personnel. c-Aminobutyric acid (GABA)A receptor potentiation represents the putative mechanism of action. In an earlier report, isoflurane was used for up to 55 h in nine patients, controlling seizures in all; mortality was, however, 67% (Kofke et al., 1989). More recently, the use of these inhalational anesthetics was described in seven subjects with RSE, for up to 26 days, with an endtidal concentration of 1.2-5%. All patients required vasopressors, and paralytic ileus occurred in three; outcome was fatal in three patients (43%) (Mirsattari et al., 2004). Ketamine, known as an emergency anesthetic because of its favorable hemodynamic profile, is an N-methyl-daspartate (NMDA) antagonist; the interest for its use in RSE derives from animal works showing loss of GABAA efficacy and maintained NMDA sensitivity in prolonged status epilepticus (Mazarati & Wasterlain, 1999). However, to avoid possible neurotoxicity, it appears safer to combine ketamine with GABAergic compounds (Jevtovic-Todorovic et al., 2001; Ubogu et al., 2003), also because of a likely synergistic effect (Martin & Kapur, 2008). There are few reported cases in humans, describing progressive dosages up to 7.5 mg/kg/h for several days (Sheth & Gidal, 1998; Quigg et al., 2002; Pruss & Holtkamp, 2008), with moderate outcomes. Paraldehyde acts through a yet-unidentified mechanism, and appears to be relatively safe in terms of cardiovascular tolerability (Ramsay, 1989; Thulasimani & Ramaswamy, 2002), but because of the risk of crystal formation and its reactivity with plastic, it should be used only as fresh prepared solution in glass devices (Beyenburg et al., 2000). There are virtually no recent reports regarding its use in adults RSE, whereas rectal paraldehyde in children with status epilepticus resistant to benzodiazepines seems less efficacious than intravenous phenytoin (Chin et al., 2008). Etomidate is another anesthetic agent for which the exact mechanism of action is also unknown, which is also relatively favorable regarding cardiovascular side effects, and may be used for rapid sedation. Its use in RSE was reported in eight subjects (Yeoman et al., 1989). After a bolus of 0.3 mg/kg, a drip of up to 7.2 mg/kg/h for up to 12 days was administered, with hypotension occurring in five patients; two patients died. A reversible inhibition of cortisol synthesis represents an important concern, limiting its widespread use and implying a careful hormonal substitution during treatment (Beyenburg et al., 2000). Several nonsedating approaches have been reported. The use of lidocaine in RSE, a class Ib antiarrhythmic agent modulating sodium channels, was reviewed in 1997 (Walker & Slovis, 1997). Initial boluses up to 5 mg/kg and perfusions of up to 6 mg/kg/h have been mentioned; somewhat surprisingly, at times lidocaine seemed to be successful in controlling seizures in patients who were refractory to phenytoin. The aforementioned dosages should not be overshot, in order to keep lidocaine levels under 5 mg/L and avoid seizure induction (Hamano et al., 2006). A recent pediatric retrospective survey on 57 RSE episodes (37 patients) described a response in 36%, and no major adverse events; mortality was not given (Hamano et al., 2006 Verapamil, a calcium-channel blocker, also inhibits P-glycoprotein, a multidrug transporter that may diminish AED availability in the brain (Potschka et al., 2002). Few case reports on its use in humans are available; this medication nevertheless appears relatively safe (under cardiac monitoring) up to dosages of 360 mg/day (Iannetti et al., 2005). Magnesium, a widely used agent for seizures elicited by eclampsia, has also been anecdotally reported in RSE (Fisher et al., 1988; Robakis & Hirsch, 2006), but with scarce results even at serum levels of 14 mm. The rationale may be found in the physiologic blockage of NMDA channels by magnesium ions (Hope & Blumenfeld, 2005). Ketogenic diet has been prescribed for decades, mostly in children, to control refractory seizures. Its use in RSE as ''ultima ratio'' has been occasionally described: three of six children (Francois et al., 2003) and one adult (Bodenant et al., 2008) were responders. This approach displays its effect subacutely over several days to a few weeks. Because ''malignant RSE'' seems at times to be the consequence of immunologic processes (Holtkamp et al., 2005), a course of immunomodulatory treatment is often advocated in this setting, even in the absence of definite autoimmune etiologies (Robakis & Hirsch, 2006); steroids, adrenocorticotropic hormone (ACTH), plasma exchanges, or intravenous immunoglobulins may be used alone or in sequential combination. Nonpharmacologic Approaches These strategies are described somewhat less frequently than pharmacologic approaches. Acute implantation of vagus nerve stimulation (VNS) has been reported in RSE (Winston et al., 2001; Patwardhan et al., 2005; De Herdt et al., 2009). Stimulation was usually initiated in the operation room, and intensity progressively adapted over a few days up to 1.25 mA (with various regimens regarding the other parameters), allowing a subacute seizure control; one transitory episode of bradycardia/asystole has been described (De Herdt et al., 2009). Of course, pending identification of a definite seizure focus, resective surgery may also be considered in selected cases (Lhatoo & Alexopoulos, 2007). Low-frequency (0.5 Hz) transcranial magnetic stimulation (TMS) at 90% of the resting motor threshold has been reported to be successful for about 2 months in a patient with epilepsia partialis continua, but with a weaning effect afterward, implying the need for a repetitive use (Misawa et al., 2005). More recently, TMS was applied in a combination of a short ''priming'' high frequency (up to 100 Hz) and longer runs of low-frequency stimulations (1 Hz) at 90-100% of the motor threshold in seven other patients with simple-partial status, with mixed results (Rotenberg et al., 2009). Paradoxically at first glance, electroconvulsive treatment may be found in cases of extremely resistant RSE. A recent case report illustrates its use in an adult patient with convulsive status, with three sessions (three convulsions each) carried out over 3 days, resulting in a moderate recovery; the mechanism is believed to be related to modification of the synaptic release of neurotransmitters (Cline & Roos, 2007). Therapeutic hypothermia, which is increasingly used in postanoxic patients (Oddo et al., 2008), has been the object of a recent case series in RSE (Corry et al., 2008). Reduction of energy demand, excitatory neurotransmission, and neuroprotective effects may account for the putative mechanism of action. Four adult patients in RSE were cooled to 31_-34_C with an endovascular system for up to 90 h, and then passively rewarmed over 2-50 h. Seizures were controlled in two patients, one of whom died; also one of the other two patients in whom seizures continued subsequently deceased. Possible side effects are related to acid-base and electrolyte disturbances, and coagulation dysfunction including thrombosis, infectious risks, cardiac arrhythmia, and paralytic ileus (Corry et al., 2008; Cereda et al., 2009). Finally, anecdotic evidence suggests that cerebrospinal fluid (CSF)-air exchange may induce some transitory benefit in RSE (Kohrmann et al., 2006); although this approach was already in use in the middle of the twentieth century, the mechanism is unknown. Acknowledgment A wide spectrum of pharmacologic (sedating and nonsedating) and nonpharmacologic (surgical, or involving electrical stimulation) regimens might be applied to attempt RSE control. Their use should be considered only after refractoriness to AED or anesthetics displaying a higher level of evidence. Although it seems unlikely that these uncommon and scarcely studied strategies will influence the RSE outcome in a decisive way, some may be interesting in particular settings. However, because the main prognostic determinant in status epilepticus appears to be related to the underlying etiology rather than to the treatment approach (Rossetti et al., 2005, 2008), the safety issue should always represent a paramount concern for the prescribing physician. Conclusion The author confirms that he has read the Journal's position on issues involved in ethical publication and affirms that this paper is consistent with those guidelines.

Comparative effects of oleoyl-estrone and a specific b3-adrenergic agonist (CL316, 243) on the expression of genes involved in energy metabolism of rat white adipose tissue

Background: The combination of oleoyl-estrone (OE) and a selective b3-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves (lipid). Methods: In the present study we investigated the effect of OE (oral gavage) and/or B3A (subcutaneous constant infusion) administration for 10 days to overweight male rats, compared with controls, on three distinct white adipose tissue (WAT) sites: subcutaneous inguinal, retroperitoneal and epididymal. Tissue weight, DNA (and, from these values cellularity), cAMP content and the expression of several key energy handling metabolism and control genes were analyzed and computed in relation to the whole site mass. Results: Both OE and B3A significantly decreased WAT mass, with no loss of DNA (cell numbers). OE decreased and B3A increased cAMP. Gene expression patterns were markedly different for OE and B3A. OE tended to decrease expression of most genes studied, with no changes (versus controls) of lipolytic but decrease of lipogenic enzyme genes. The effects of B3A were widely different, with a generalized increase in the expression of most genes, including the adrenergic receptors, and, especially the uncoupling protein UCP1. Discussion: OE and B3A, elicit widely different responses in WAT gene expression, end producing similar effects, such as shrinking of WAT, loss of fat, maintenance of cell numbers. OE acted essentially on the balance of lipolysislipogenesis and the blocking of the uptake of substrates; its decrease of synthesis favouring lipolysis. B3A induced a shotgun increase in the expression of most regulatory systems in the adipocyte, an effect that in the end favoured again the loss of lipid; this barely selective increase probably produces inefficiency, which coupled with the increase in UCP1 expression may help WAT to waste energy through thermogenesis. Conclusions: There were considerable differences in the responses of the three WAT sites. OE in general lowered gene expression and stealthily induced a substrate imbalance. B3A increasing the expression of most genes enhanced energy waste through inefficiency rather than through specific pathway activation. There was not a synergistic effect between OE and B3A in WAT, but their combined action increased WAT energy waste.

Pediatric emergencies admitted in the resuscitation room of a Swiss university hospital.

OBJECTIVES: Pediatric resuscitation is an intense, stressful, and challenging process. The aim of this study was to review the life-threatening pediatric (LTP) emergencies admitted in a Swiss university hospital with regards to patients' demographics, reason for admission, diagnosis, treatment, significant events, critical incidents, and outcomes. METHODS: A retrospective observational cohort study of prospectively collected data was conducted, including all LTP emergencies admitted over a period of 2 years in the resuscitation room (RR). Variables, including indication for transfer, mode of prehospital transportation, diagnosis, and time spent in RR, were recorded. RESULTS: Of the 60,939 pediatric emergencies treated in our university hospital over 2 years, a total of 277 LTP emergencies (0.46%) were admitted in the RR. They included 160 boys and 117 girls, aged 6 days to 15.95 years (mean, 6.69 years; median, 5.06). A medical problem was identified in 55.9% (n = 155) of the children. Of the 122 children treated for a surgical problem, 35 (28.3%) went directly from the RR to the operating room. Hemodynamic instability was noted in 19.5% of all LTP emergencies, of which 1.1% benefited from O negative transfusion. Admission to the intensive care unit was necessary for 61.6% of the children transferred from another hospital. The average time spent in the RR was 46 minutes. The overall mortality rate was 7.2%. CONCLUSIONS: The LTP emergencies accounted for a small proportion of all pediatric emergencies. They were more medical than surgical cases and resuscitation measures because of hemodynamic instability were the most frequent treatment.

State Legislation Monitoring Report, FY 2003

The Division of Criminal and Juvenile Justice Planning issued its first state legislation monitoring report in February 2002, covering the first six month’s impact of Senate File 543 on the justice system. SF 543, enacted during the 2001 legislative session, changed the maximum penalty for first-offense Burglary-3rd degree, and established new sentencing options available to the court: * An alternative determinate prison sentence for certain Class D felons * Extended felony sentence reconsideration from 90 days to one year

State Legislation Monitoring Report, FY 2006

The Division of Criminal and Juvenile Justice Planning issued its first state legislation monitoring report in February 2002, covering the first six month’s impact of Senate File 543 on the justice system. SF 543, enacted during the 2001 legislative session, changed the maximum penalty for first-offense Burglary-3rd degree, and established new sentencing options available to the court: * An alternative determinate prison sentence for certain Class D felons * Extended felony sentence reconsideration from 90 days to one year

State Legislation Monitoring Report, FY 2007

The Division of Criminal and Juvenile Justice Planning issued its first state legislation monitoring report in February 2002, covering the first six month’s impact of Senate File 543 on the justice system. SF 543, enacted during the 2001 legislative session, changed the maximum penalty for first-offense Burglary-3rd degree, and established new sentencing options available to the court: * An alternative determinate prison sentence for certain Class D felons * Extended felony sentence reconsideration from 90 days to one year

State Legislation Monitoring Report, FY 2008

The Division of Criminal and Juvenile Justice Planning issued its first state legislation monitoring report in February 2002, covering the first six month’s impact of Senate File 543 on the justice system. SF 543, enacted during the 2001 legislative session, changed the maximum penalty for first-offense Burglary-3rd degree, and established new sentencing options available to the court: * An alternative determinate prison sentence for certain Class D felons * Extended felony sentence reconsideration from 90 days to one year

Esophageal and pharyngeal strictures: report on 1,862 endoscopic dilatations using the Savary-Gilliard technique

Treatment of symptomatic pharyngeal and esophageal strictures requires endoscopic dilatation. The Savary-Gilliard bougienage was developed by our department and has been used since 1980 for this purpose. We report our experience using this technique. The records of patients seen from January 1, 1963 to December 31, 2005, who had pharyngeal and esophageal strictures needing dilatation, were reviewed. The prevalence of different etiologies, and the incidence of complications using the Savary-Gilliard dilators were assessed. Efficiency of dilatation was assessed over a 17-year segment of this period, using number of dilatations and time intervals between dilatations until resolution of symptoms as outcome measures. Of the 2,652 pharyngeal and esophageal strictures reviewed, 90% were of organic origin (45% benign and 55% malignant stenoses), and 10% were of functional etiology. The most common etiologies were peptic strictures before the era of proton pump inhibitors, and postoperative anastomotic strictures thereafter. A total of 1,862 dilatations using the Savary-Gilliard technique were analyzed. Complication and mortality rates were 0.18 and 0.09% for benign and 4.58 and 0.81% for malignant etiologies, respectively. The number of dilatations per stricture and the time interval between different sessions were dependent on the type of strictures, varying from 1 to 23 dilatations and 7 days to 16 years, respectively. Pharyngeal and esophageal dilatations using the Savary-Gilliard technique were safe when used together with fluoroscopy. Overall, the efficiency of the dilatation procedure was good, but some types of strictures (e.g., caustic, post-surgical and/or post radiotherapy) were refractory to treatment and required repeated dilatations.

Longevity differs among sexes but is not affected by repeated immune activation in voles (Microtus arvalis)

Investment of resources in immune defences, despite obvious short-term benefits, may be detrimental to long-term maintenance and thus decrease longevity in absence of parasites. In addition, females and males may differ in immune investment and intrinsic longevity because they are subjected to different degrees of sexual competition and extrinsic mortality. In order to test if sex-specific investment in mounting an immune response reduced longevity, we compared the longevity of captive male and female common voles Microtus arvalis regularly challenged with keyhole limpet haemocyanin, an antigen which elicits the production of antibodies, to the longevity of voles injected with the corresponding antigen-free buffer (phosphate-buffered saline). Injections were repeated every 28 days to mimic a chronic infection. The magnitude of immune response did not vary between males and females and did not affect longevity. Overall, females lived longer than males, independently of the immune challenge. Thus, the long-term costs of immunity seem small in voles. The longevity pattern is consistent with the prediction that male-biased predation or parasitism in the wild causes reduced intrinsic lifespan, but this reduction is not mediated by a decrease in male immunity

Unlicensed and off-label drug use in a Swiss paediatric university hospital.

BACKGROUND: Many medicines used in newborns, infants, children and adolescents are not licensed ("unlicensed") or are prescribed outside the terms of the marketing authorization ("off-label"). Several studies have shown that this is a common practice in various healthcare settings in the USA, Europe and Australia, but data are scarce in Switzerland. OBJECTIVES: The aim of our prospective study was to determine the proportion of unlicensed or off-label prescriptions in paediatric patients. METHODS: This pilot study was conducted prospectively over a six month period in the department of paediatrics of a university hospital. RESULTS: Sixty patients aged from three days to 14 years were included in the study. A total of 483 prescriptions were written for the patients. More than half of all prescriptions (247; 51%) followed the terms of the marketing authorization. 114 (24%) were unlicensed and 122 (25%) off-label. All patients received at least one unlicensed or offlabel medicine. CONCLUSION: The use of unlicensed or off-label medicines to treat children was found to be common. Co-operation between the pharmaceutical industry, national regulatory authorities, clinical researchers, healthcare professionals and parents is required in order to ensure that children do not remain "therapeutic orphans".

Calibration of Highway Safety Manual Work Zone Crash Modification Factors, TPF-5(081), 2014

The Highway Safety Manual is the national safety manual that provides quantitative methods for analyzing highway safety. The HSM presents crash modification factors related to work zone characteristics such as work zone duration and length. These crash modification factors were based on high-impact work zones in California. Therefore there was a need to use work zone and safety data from the Midwest to calibrate these crash modification factors for use in the Midwest. Almost 11,000 Missouri freeway work zones were analyzed to derive a representative and stratified sample of 162 work zones. The 162 work zones was more than four times the number of work zones used in the HSM. This dataset was used for modeling and testing crash modification factors applicable to the Midwest. The dataset contained work zones ranging from 0.76 mile to 9.24 miles and with durations from 16 days to 590 days. A combined fatal/injury/non-injury model produced a R2 fit of 0.9079 and a prediction slope of 0.963. The resulting crash modification factors of 1.01 for duration and 0.58 for length were smaller than the values in the HSM. Two practical application examples illustrate the use of the crash modification factors for comparing alternate work zone setups.

Transportation in Iowa: A Historical Summary, 1988

“This book traces the development of transportation in Iowa from territorial days to the 19 80s. It shows the evolution of the transportation systems; how they originated, progressed and functioned; their structural organizations; effectiveness in overcoming obstacles, under the guidance of state and federal legislation; and their impact upon the development of the state.” – From the Prologue, page xiii