Propofol and Sevoflurane in Subanesthetic Concentrations Act Preferentially on the Spinal Cord: Evidence from Multimodal Electrophysiological Assessment

Background: Animal experiments in recent years have shown that attenuation of motor responses by general anesthetics is mediated at least partly by spinal mechanisms. Less is known about the relative potency of anesthetic drugs in suppressing cortical and spinal electrophysiological responses in vivo in humans, particularly those, but not only those, connected with motor responses. Therefore, we studied the effects of sevoflurane and propofol in humans using multimodal electrophysiological assessment.

Methods: We studied nine healthy volunteers in two sessions during steady state sedation with 0.5, 1.0, and 1.5 [mu]g/l (targeted plasma concentration) propofol or 0.2 and 0.4 vol% (end-tidal) sevoflurane. Following a 15-min equilibration period, motor responses to transcranial magnetic stimulation and peripheral (H-reflex, F-wave) stimulation were recorded, while electroencephalography and auditory evoked responses were recorded in parallel.

Results: At concentrations corresponding to two thirds of C50 awake, motor responses to transcranial magnetic stimulation were reduced by approximately 50%, H-reflex amplitude was reduced by 22%, F-wave amplitude was reduced by 40%, and F-wave persistence was reduced by 25%. No significant differences between sevoflurane and propofol were found. At this concentration, the Bispectral Index was reduced by 7%, and the middle-latency auditory evoked responses were attenuated only mildly (Nb latency increased by 11%, amplitude PaNb did not change). In contrast, the postauricular reflex was suppressed by 77%.     

Velocity and flow quantitation in the superior sagittal sinus with ungated and cine (gated) phase-contrast MR imaging

Normal blood flow and velocity in the superior sagittal sinus were measured in 30 patients. A fast two-dimensional ungated phase-contrast (PC) pulse sequence was compared with a peripherally gated cine PC technique for velocity and flow quantitation. The same imaging parameters were used for both methods. Measured values for mean velocity and flow obtained with the two methods were compared by using regression analysis and t testing. For blood flow, the correlation coefficient was 0.976. For velocity measurements, r was 0.950. Mean flow was 285 mL/min ± 19 with the ungated PC method and 281 mL/min ± 19 with the cine PC method. The mean velocities measured with the two methods were 12.94 cm/sec ± 1.1 and 13.59 cm/sec ± 1.1, respectively. There was no significant difference (paired t test) between the methods for mean flow or velocity data. This was true even though flow in the superior sagittal sinus is moderately pulsatile, as shown with the cine PC technique. The ungated PC method provided these data in 13 seconds versus 3.5 minutes for the cine PC method.     

Fibre type characteristics of the lumbar paraspinal muscles in normal healthy subjects and in patients with low back pain

A knowledge of the alteration in the fibre type profile of paraspinal muscle associated with low back pain is essential for the design of successful rehabilitation programmes. In attempting to compare the muscles of patients with low back pain with those of controls, few previous studies have considered factors such as gender, age, and size of the subjects, each of which can potentially confound interpretation of the results. We obtained samples of lumbar paraspinal muscle during spinal surgery from 21 patients with low back pain and, using the percutaneous biopsy technique, from 21 control volunteers matched for gender, age, and body mass. The samples were subject to routine histochemicsl typcal analysis to determine characteristics of muscle fibre type. Compared with controls, the muscle of the patients had a significantly higher proportion of type-IIB (fast-twitch glycolytic) fibres than type- I (slow oxidatve) fibres. The mean size of a given fibre type did not differ between the patients and the controls. Consequently, the relative area of the muscle iccupied by type-IIB fibres was higher and that by type-I fibres Was lower in the patients. The patients had a greater number of muscle samples with more than 1% type-IIC fibres, and abnormalities that could be described as pathological were more marked in the patients than in the controls. In conclusion, the paraspinal muscles of patients who have low back pain display a more glycolytic (faster) profile; this can be expected to render them less resistant to fatigue.     

Manic episode with psychotic symptoms induced by subthalamic nucleus stimulation in a patient with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy for Parkinson's disease (PD). A manic episode with psychotic symptoms induced by STN-DBS occurred in a previously psychiatrically healthy patient, focusing on the role of STN-DBS in influencing not only motor but also emotional behaviour.     

Frictional forces when rectangular guiding arches with varying edge bevel are employed

In orthodontic treatment employing arch guided tooth movement, rectangular wires are usually used to achieve three-dimensional controlled tooth movement. In the intention to optimize sliding mechanics and to improve the comfort of patients, edge beveled rectangular orthodontic wires are offered by different manufacturers. The objective of the study presented was to investigate the influence of differing but defined wire roundings on sliding mechanics of canine retraction. Employing the 0.018″ slot system, 0.016″×0.022″ standard steel wires (Remaloy and Remanium, Dentaurum Comp.) were tested. Force loss due to friction during canine retraction was determined using the Orthodontic Measurement and Simulation System (OMSS). In the arch guided distalization of canines, the average loss of force caused by friction was determined to be approximately 50%. Comparing wires with different edge bevel, the rounded wire in contrast to the wire with sharpest edge configuration results in a reduction of friction. Even a moderate wire rounding of the 0.016″×0.022″ steel wire results in about 10% reduction in frictional losses. However, dynamic analysis of tooth movement with the OMSS shows that there is no further improvement of sliding mechanics using wires with edge bevel exceeding the standard rounding of rectangular wires. In contrast, a strong edge bevel may result in a considerable loss of leveling.     

Epileptogenic actions of xanthines in relation to their affinities for adenosine A1 receptors in CA3 neurons of hippocampal slices (guinea pig)

In order to analyze the epileptogenic mechanisms of caffaine and related xanthines, putative effects of these drugs were studied on adenosine receptors of CA3 neurons in hippocampal slices. Epileptogenic concentrations of different xanthine derivatives strongly correlated with their affinities for the inhibitory A₁ adenosine receptor subtype. The A₁ receptor agonists adenosine and R-PIA reversibly depressed xanthine-induced epileptic activity without effects on the resting membrane potential or on spontaneously occuring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A₁ receptors through an abnormal rise of intracellular cAMP and to the excessive transmembrane calcium fluxes underlying paroxysmal depolarization shifts.     

The orthopan tomoscintigram — a new application of emission computed tomography for facial bone scanning

The exact regional correlation of findings of facial bone scans, planar or SPECT, to dental orthopan X-ray films (OPT) is difficult because of the very different projection techniques. To improve correlative imaging in this regard a projection algorithm was developed that uses SPECT data of the skull for reconstructing an orthopan tomoscintigraphic projection. Fourteen conventional SPECT slices of the upper and lower jaws were obtained during bone scanning. All mandibular slices were superimposed resulting in a horseshoe shaped structure, which was marked by an ROI which was divided into segments. All 14 SPECT slices were then masked by this segmental ROI, thereby marking the teeth-carrying bone in all slices. The information from this horseshoe like ROI is then transformed into lines. Line by line arrangement results in an orthopan projection, the orthopan tomoscintigram. This new display allows 1:1 true scale superimposition with the X-ray OPT and markedly facilitates correlative imaging.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Dyspepsie und Helicobacter-pylori-Infektion bei Besch?ftigten eines gro?en Industrieunternehmens Ergebnisse der prospektiven BASF-Helicobacter-pylori-Vorsorgeaktion

Zusammenfassung Hintergrund: Die Assoziation zwischen Helicobacter-pylori-(H.-pylori-)Infektion und Dyspepsie wird kontrovers diskutiert. Im Rahmen der BASF-H.-pylori-Vorsorgeaktion wurde u. a. die Prävalenz von Dyspepsie bei arbeitsfähigen Personen ermittelt sowie der Zusammenhang mit der H.-pylori-Infektion und der Erfolg einer Eradikationstherapie untersucht. Probanden und Methodik: 6 132 Beschäftigte der BASF wurden untersucht und im Rahmen einer standardisierten Anamnese u. a. zu dyspeptischen Beschwerden befragt. Diese wurden entsprechend der führenden Symptomatik den Dyspepsiesubtypen vom Ulkustyp, Dysmotilitätstyp, Refluxtyp und unspezifischen Typ zugeordnet. Bei allen Beschäftigten wurde die Seroprävalenz (IgG-ELISA) der H.-pylori-Infektion bestimmt. Allen H.-pylori-positiven Personen mit Dyspepsie wurde weitere Diagnostik in Form einer Ösophagogastroduodenoskopie und einer Sonographie des Abdomens bei Fachärzten empfohlen und eine H.-pylori-Eradikationstherapie (Italian-Triple-Therapie) angeboten. In einer Untergruppe endoskopisch untersuchter Beschäftigter mit peptischer Ulkuskrankheit (PUD, n = 37) bzw. Non-Ulcer-Dyspepsie (NUD; n = 39) wurde der prognostische Wert der im Western Blot ermittelten Antikörper gegen CagA und VacA untersucht. Ergebnisse: 1 255 der 6 143 Beschäftigten (20,4%) berichteten über Dyspepsie. 492 Personen mit Dyspepsie (39,2%) waren gleichzeitig H.-pylori-positiv. Bei Personen ohne dyspeptische Symptome betrug die H.-pylori-Prävalenz 35,8%. Personen mit unterschiedlichen Dyspepsiesubtypen unterschieden sich nicht hinsichtlich der H.-pylori-Prävalenz. Personen, die häufige und intensive dyspeptische Beschwerden angaben, waren allerdings signifikant häufiger H.-pylori-positiv (OR 2,09, CI 1,43-3,05). Die Seroprävalenz von CagA und VacA bei Personen mit PUD unterschied sich nicht signifikant von derjenigen bei Personen mit NUD. 458 H.-pylori-positiven Personen wurde die Eradikation empfohlen. 330 Personen (72,1%) folgten der Empfehlung. 128 (27,9%) ließen sich nicht behandeln. An der Nachkontrolle nach 12 Monaten nahmen 402 Personen (87,8%) teil, davon waren 300 behandelt, 102 nicht. Der serologisch analysierte Eradikationserfolg lag bei 81,5%. 42,8% der erfolgreich behandelten Personen berichteten über Besserung ihrer Beschwerden, 33,2% über Beschwerdefreiheit. Bei den nicht behandelten Personen war dies nur in 16,7% bzw. in 37,3% der Fall. Vermehrte Refluxbeschwerden traten nach erfolgreicher Eradikation nicht auf. Schlussfolgerung: Wir konnten keinen generellen Zusammenhang zwischen Dyspepsie und H.-pylori-Infektion in einem großen Kollektiv arbeitsfähiger Personen erkennen. Häufige und intensive dyspeptische Symptome scheinen allerdings ein prädikativer Faktor für die H.-pylori-Seropositivität zu sein. Die serologisch bestimmbaren Virulenzfaktoren tragen nicht zur Unterscheidung PUD oder NUD bei. Die Eradikationstherapie führte nach 1 Jahr zwar häufiger zur Besserung, aber nicht häufiger zu Beschwerdefreiheit bei Beschäftigten mit dyspeptischen Beschwerden im Vergleich zu unbehandelten Personen. Abstract Background: The role of Helicobacter pylori (H. pylori) infection in dyspepsia is controversial. In the course of a health initiative within a large industrial corporation, we investigated the prevalence of both dyspepsia and positive H. pylori serology and the outcome of eradication therapy in symptomatic H. pylori positive employees. Test Persons and Methods: H. pylori serology (IgG ELISA) was determined in 6,143 employees of BASF AG Ludwigshafen/Germany who were also asked to complete a standardized health history administered by a physician. Peptic ulcer disease (PUD) and dyspepsia subgroups were defined based on past medical history and symptom profiles using the criteria of Heading. Upper GI endoscopy, abdominal ultrasound and eradication therapy (Italian Triple Therapy) was recommended for symptomatic H. pylori positive individuals. The prognostic value of antibodies against CagA and VacA was evaluated in 37 and 39 employees with PUD and non-ulcer dyspepsia (NUD) confirmed by endoscopy, respectively. Results: Of 6,143 employees, 1,255 (20.4%) were classified as dyspeptic, 492 (39.2%) of whom were H. pylori positive. The seroprevalence of H. pylori in asymptomatic employees was 35.8%. There were no significant differences in H. pylori seroprevalence among dyspepsia subgroups (reflux only, dysmotility only, reflux/dysmotility, ulcer-like and non-specific). However, individuals reporting severe dyspeptic symptoms were significantly more likely to be H. pylori positive (OR 2.09, CI 1.43-3.05). The seroprevalence of CagA and VacA was not significantly different among employees with NUD compared to referents or among employees with NUD compared to those with PUD. 330 (72%) of 458 employees with dyspepsia received eradication therapy, 128 persons refused therapy. Based on a 12-month follow-up of 402 individuals (300 of whom had received therapy), eradication success was 81.5% as judged by serology. Of the successfully treated employees, 33.2% reported a total absence and 42.8% reported a decrease in symptoms. Among the employees who refused therapy, the corresponding percentages were 37.3% and 16.7%, respectively. An increase in reflux complaints was not observed among treated employees. Conclusion: In a large active employee population, at most a very weak association was observed between the prevalence of H. pylori seropositivity and dyspepsia. Frequent and severe dyspeptic symptoms were associated with an increased rate of H. pylori seropositivity. The analysis of the virulence factors is not particularly helpful in discriminating PUD or NUD. Eradication of H. pylori infection leads to a decrease in dyspeptic symptoms after 12 months, but not more often to their complete absence compared to untreated individuals.