The association of new-onset diabetes with subsequent diagnosis of pancreatic cancer-novel use of a large administrative database.

BACKGROUND: Screening options for pancreatic ductal adenocarcinoma (PDAC) are limited. New-onset type 2 diabetes (NoD) is associated with subsequent diagnosis of PDAC in observational studies and may afford an opportunity for PDAC screening. We evaluated this association using a large administrative database. METHODS: Patients were identified using claims data from the OptumLabs® Data Warehouse. Adult patients with NoD diagnosis were matched 1:3 with patients without NoD using age, sex and chronic obstructive pulmonary disease (COPD) status. The event of PDAC diagnosis was compared between cohorts using the Kaplan-Meier method. Factors associated with PDAC diagnosis were evaluated with Cox's proportional hazards modeling. RESULTS: We identified 640 421 patients with NoD and included 1 921 263 controls. At 3 years, significantly more PDAC events were identified in the NoD group vs control group (579 vs 505; P < 0.001). When controlling for patient factors, NoD was significantly associated with elevated risk of PDAC (HR 3.474, 95% CI 3.082-3.920, P < 0.001). Other factors significantly associated with PDAC diagnosis were increasing age, increasing age among Black patients, and COPD diagnosis (P ≤ 0.05). CONCLUSIONS: NoD was independently associated with subsequent diagnosis of PDAC within 3 years. Future studies should evaluate the feasibility and benefit of PDAC screening in patients with NoD.

Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa.

BACKGROUND: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets. METHODS: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. RESULTS: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target. CONCLUSIONS: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic.

Radiographic assessment of pulmonary fluid clearance and lung aeration in newborn calves delivered by elective Caesarean section.

The aim of this study was to develop a radiographic standard for the assessment of pulmonary fluid clearance and lung aeration in newborn calves. Caesarean-delivered mature calves (n = 9) underwent lung assessment by thoracic radiography as well as arterial and venous blood gas analysis within the first 30 min, 1, 2, 3, 6, 12 and 24 hr after birth. The results indicated that newborn calves delivered by elective Caesarean section suffered from a physiological combined respiratory and metabolic acidosis with the dominance of respiratory acidosis, and an improvement in these conditions was recorded within 24 hr after birth. Concerning the radiographic results, clear lung fields, improvement in lung expansion, air content of the lung and absence of lung opacification occurred within 24 hr of birth. Furthermore, the ventral lung quadrant showed an improvement in radiographic opacification and lung expansion earlier than the dorsal lung regions. The findings of this study support the potential role of thoracic radiography in the assessment of pulmonary fluid clearance and lung aeration in newborn calves.

[A New Diagnostic Tool for Apraxia in Patients with Right-Hemisphere Stroke: The Revised Cologne Apraxia Screening (KAS-R)]. / Das revidierte Kölner Apraxie-Screening (KAS-R) als diagnostisches Verfahren für Patienten mit rechtshemisphärischem Schlaganfall.

The Cologne Apraxia Screening (KAS) was developed to diagnose apraxia following left-hemisphere (LH) stroke. The present study aims at developing a diagnostic tool for patients with right-hemisphere (RH) stroke (KAS-R) by modifying the test material of the KAS and reducing the test items based on psychometric analyses.A total of 100 patients with RH stroke and 77 healthy control participants were tested. Psychometric analyses led to the exclusion of 8 KAS items. The final KAS-R, consisting of 12 items, shows good internal consistency (α = 0.795) as well as high sensitivity (79.4 %) and specificity (84.4 %). Applying a cut-off value of ≤ 46 (out of 48) points, 39 RH stroke patients were diagnosed with apraxia. Significant correlations were found between the KAS-R and an imitation test as well as expert ratings, indicating high construct validity. The results suggest that the KAS-R is a reliable and valid diagnostic tool for apraxic deficits after RH stroke.

[Pretreatment mass casualty incident workflow analysis : Comparison of two level 1 trauma centers]. / Prätherapeutische Ablaufanalyse bei einem Massenanfall von Verletzten : Vergleich von zwei Traumazentren der höchsten Versorgungsstufe.

BACKGROUND: Mass casualty incidents (MCI) have particularly high demands on patient care processes but occur rather rarely in daily hospital routine. Therefore, it is common to use simulations to train staff and to optimize institutional processes. OBJECTIVES: Aim of study was to compare the pre-therapeutic in-house workflow of two differently structured level 1 trauma sites in the case of a simulated mass casualty incident (MCI). MATERIALS AND METHODS: A MCI of 70 patients was simulated by actors in a manner that was as realistic as possible. The on-site triage assigned 7 cases to trauma site A with relatively long in-house distances and 4 patients to an independent trauma site B in which these distances were relatively short. During in-house treatment, time intervals for reaching milestones were measured and compared using the Mann-Whitney U test. RESULTS: As no simultaneous patient arrival occurred, the Patient Distribution Matrix proved to be effective. Site A needed more time (minutes) from admission to endpoints (A: 31.85 ± 7.99; B: 21.62 ± 4.76; p = 0.059). In detail, the time intervals were particularly longer for both patient stay in trauma room (A: 8.46 ± 3.02; B: 2.73 ± 0.78, p < 0.01) and transfer time to the CT room (A: 1.81 ± 0.62; B: 0.06 ± 0.03, p < 0.01). A shorter stay in the CT room did not compensate these effects (A: 8.86 ± 1.84; B: 10.40 ± 2.89, p = 0.571). For both sites, image calculation and distribution were relatively time consuming (17.36 ± 3.05). CONCLUSIONS: Although short in-house distances accelerated pretherapeutic treatment processes significantly, both sites remained clearly within the "golden hour". The strongest potential bottleneck was the time interval until images were available at the endpoints.

[Changing the internal cost allocation (ICA) on DRG shares : Example of computed tomography in a university radiology setting]. / Umstellung der internen Leistungsverrechnung (ILV) auf DRG-Anteile : Beispiel der Computertomographie einer universitären Radiologie.

BACKGROUND: In hospitals, the radiological services provided to non-privately insured in-house patients are mostly distributed to requesting disciplines through internal cost allocation (ICA). In many institutions, computed tomography (CT) is the modality with the largest amount of allocation credits. OBJECTIVES: The aim of this work is to compare the ICA to respective DRG (Diagnosis Related Groups) shares for diagnostic CT services in a university hospital setting. MATERIALS AND METHODS: The data from four CT scanners in a large university hospital were processed for the 2012 fiscal year. For each of the 50 DRG groups with the most case-mix points, all diagnostic CT services were documented including their respective amount of GOÄ allocation credits and invoiced ICA value. As the German Institute for Reimbursement of Hospitals (InEK) database groups the radiation disciplines (radiology, nuclear medicine and radiation therapy) together and also lacks any modality differentiation, the determination of the diagnostic CT component was based on the existing institutional distribution of ICA allocations. RESULTS: Within the included 24,854 cases, 63,062,060 GOÄ-based performance credits were counted. The ICA relieved these diagnostic CT services by € 819,029 (single credit value of 1.30 Eurocent), whereas accounting by using DRG shares would have resulted in € 1,127,591 (single credit value of 1.79 Eurocent). The GOÄ single credit value is 5.62 Eurocent. CONCLUSIONS: The diagnostic CT service was basically rendered as relatively inexpensive. In addition to a better financial result, changing the current ICA to DRG shares might also mean a chance for real revenues. However, the attractiveness considerably depends on how the DRG shares are distributed to the different radiation disciplines of one institution.

In vitro effects of Yunnan Baiyao on canine hemangiosarcoma cell lines.

Yunnan Baiyao is a Chinese herbal medicine that has been utilized for its anti-inflammatory, haemostatic, wound healing and pain relieving properties in people. It has been utilized in the veterinary profession to control bleeding in dogs with hemangiosarcoma (HSA) and has been anecdotally reported to prolong survival times in dogs with this neoplasm. This study evaluated the in vitro activity of Yunnan Baiyao against three canine HSA cell lines after treatment with increasing concentrations of Yunnan Baiyao (50, 100, 200, 400, 600 and 800 µg mL(-1) ) at 24, 48 and 72 h. Mean half maximum inhibitory concentration (IC50 ) at 72 h for DEN, Fitz, SB was 369.9, 275.9 and 325.3 µg mL(-1) , respectively. Caspase-3/7 activity increased in correlation with the IC50 in each cell line which was confirmed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL, APO-BRDU Kit; BD Biosciences, San Jose, CA, USA) assay. VEGF in cell supernatant was also quantified. Overall, the study found that Yunnan Baiyao causes dose and time dependent HSA cell death through initiation of caspase-mediated apoptosis, which supports future studies involving Yunnan Baiyao.

The effect of exposure to wood smoke on outcomes of childhood pneumonia in Botswana.

SETTING: Tertiary hospital in Gaborone, Botswana. OBJECTIVE: To examine whether exposure to wood smoke worsens outcomes of childhood pneumonia. DESIGN: Prospective cohort study of children aged 1-23 months meeting clinical criteria for pneumonia. Household use of wood as a cooking fuel was assessed during a face-to-face questionnaire with care givers. We estimated crude and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for treatment failure at 48 h by household use of wood as a cooking fuel. We assessed for effect modification by age (1-5 vs. 6-23 months) and malnutrition (none vs. moderate vs. severe). RESULTS: The median age of the 284 enrolled children was 5.9 months; 17% had moderate or severe malnutrition. Ninety-nine (35%) children failed treatment at 48 h and 17 (6%) died. In multivariable analyses, household use of wood as a cooking fuel increased the risk of treatment failure at 48 h (RR 1.44, 95%CI 1.09-1.92, P = 0.01). This association differed by child nutritional status (P = 0.02), with a detrimental effect observed only among children with no or moderate malnutrition. CONCLUSIONS: Exposure to wood smoke worsens outcomes for childhood pneumonia. Efforts to prevent exposure to smoke from unprocessed fuels may improve pneumonia outcomes among children.

A lytic enzyme cocktail from Streptomyces sp. B578 for the control of lactic and acetic acid bacteria in wine.

Beside yeasts, lactic acid bacteria (LAB) are the most abundant microbes in must during vinification. Whereas Oenococcos oeni is commercially used as a starter culture for the biological acid reduction in wines, other species are responsible for different types of wine spoilage. Members of the genera Pediococcus, Weissella, Leuconostoc, and Lactobacillus are producers of exopolysaccharide slimes, biogenic amines, acetic acid, and other off-flavors. In order to control microbial growth, different procedures such as heating of must and addition of sulfite or lysozyme from egg white are generally applied. Yet, because of health risks, the application of sulfite should be reduced and lysozyme is not effective against all LAB. In this study, we describe exoenzymes from a Streptomyces sp. strain B578 lysing nearly all wine-relevant strains of LAB and Gram-negative acetic acid bacteria. The lytic enzymes were active under wine-making conditions, such as the presence of sulfite and ethanol, low temperatures, and low pH values. The analysis of the exoenzyme composition revealed a synergistic action of different cell wall hydrolases. In conclusion, the lytic cocktail of Streptomyces sp. B578 is a promising tool for the control of wine-spoiling bacteria.

Response of growth and myogenic factors in human skeletal muscle to strength training.

OBJECTIVE: To investigate the response to different strength training techniques of growth and myogenic factors in human skeletal muscle, with particular emphasis on satellite cell (SC) activation. METHODS: 24 volunteers were divided into two groups and performed a 6-week strength training (group A trained with maximum contraction and group B had training combined with maximum contractions, ballistic movement and stretching-shortening cycles). Muscle biopsies were obtained from triceps brachii 3 days before and 7 days after training. For estimating gene expression of insulin-like growth factor (IGF-1), mechano growth factor (MGF), MyoD and myogenin, real-time RT-PCR was performed. RESULTS: In group A, there was an increase in the 1 repeat maximum (1RM), but no change in V(max) (maximum movement velocity) and an increase in MHC (myosin heavy chain) IIa and a decrease in MHC IIx; in group B both 1RM and V(max) increased significantly along with an increase in MHC IIa and a decrease in MHC I. The MGF gene expression increased significantly in both groups (by 1160% and 59%, respectively), and IGF-1 increased only in group A (by 335%). MyoD and myogenin gene expression increased in group A (by 107% and 94%, respectively) but did not change in group B. CONCLUSIONS: Response of growth and myogenic factors occurs during muscular adaptation to a prolonged training, and strength training with different strategies caused different responses with respect to gene expression of these factors. These results suggest that SC activation is involved in the muscular adaptation process to training and might be attributed to MHC isoform transition.

Different effects on human skeletal myosin heavy chain isoform expression: strength vs. combination training.

Myosin heavy chain (MHC) isoform expression changes with physical training. This may be one of the mechanisms for muscular adaptation to exercise. We aimed to investigate the effects of different strength-training protocols on MHC isoform expression, bearing in mind that alpha- MHC(slow) (newly identified MHC isoform) mRNA may be upregulated in response to training. Twelve volunteers performed a 6-wk strength training with maximum contractions (Max group), and another 12 of similar age performed combination training of maximum contractions and ballistic and stretch-shortening movements (Combi group). Muscle samples were taken from triceps brachii before and after training. MHC isoform composition was determined by SDS-PAGE silver staining, and mRNA levels of MHC isoforms were determined by RT-PCR. In Max group, there was an increase in MHC(2A) (49.4 to 66.7%, P < 0.01) and a decrease in MHC(2X) (33.4 to 19.5%, P < 0.01) after training, although there was no significant change in MHC(slow). In Combi group, there was also an increase in MHC(2A) (47.7 to 62.7%, P < 0.05) and a decrease in MHC(slow) (18.2 to 9.2%, P < 0.05) but no significant change in MHC(2X). An upregulation of alpha-MHC(slow) mRNA was, therefore, found in both groups as a result of training. The strength training with maximum contractions led to a shift in MHC isoform composition from 2X to 2A, whereas the combined strength training produced an MHC isoform composition shift from slow to 2A.

[Incidence and prevalence of postoperative acute confusion in heart surgery patients after coronary artery bypass and heart valve replacement surgeries]. / Inzidenz und Prävalenz postoperativer akuter Verwirrtheit kardiochirurgischer Patienten nach Bypassoperationen sowie Herzklappenersatz.

Compared to foreign countries, Germany does not have data about the occurrence of acute confusion following heart-surgery. However, the occurrence of acute confusion does extend the hospital length of stay for up to 13 days. Thus, this phenomenon is of high relevance to nursing. This prevalence/incidence study was implemented with the goal of obtaining exact information on the incidence rate of acute postoperative confusion after a heart surgery through a multicenter evaluation. The data evaluation took place in the form of a convenience sample survey in three different German clinics specializing on heart surgeries. The observation period lasted from the day of the surgery up to the fifth postoperative day. In the context of this prospective Cohort-study all patients aged 18 and older who had heart surgery between February 1st and April 30th, 2000, were considered suitable as participants in the study. In the end, 860 patients were included in this study. 152 patients (17.4%) showed symptoms of acute confusion (confidence interval 14-20%). Certain circumstances seemed to predispose patients to acute confusion. A widespread occurrence could be observed particularly at night. Patients aged 81-91 were mainly affected. A confusion rate of 43.5% could be determined for this group. These results confirm the clinical importance and suggest interdisciplinary approaches for solution.

Pharmacological characterisation of novel kinin B2 receptor ligands.

Peptide and nonpeptide compounds have been shown to interact specifically with B2 receptors of three different species, namely human, rabbit, and pig. Peptide agonists and nonpeptide antagonists show marked differences in potencies and suggest the existence of B2 receptor subtypes. This conclusion is based on data obtained with the modified agonist peptide LF 150943 whose potency (pEC50 9.4) is at least 100-fold higher in rabbit than in humans (7.4) and pig (6.7). The same conclusion can be drawn from data obtained with antagonists that are more potent in humans (LF 160687, pA2 9.2) than in rabbit (8.7) and pig (8.2) or with antagonists (S 1567) that show the opposite potency order, being much weaker in humans (pA2 6.9) than in rabbit (7.6) and pig (9.4). Two other compounds (FR 173657 and FR 172357) show similar pharmacological spectra as S 1567 and differ from LF 160687.

Treatment and prophylaxis of severe infections in neutropenic patients by granulocyte transfusions.

Bacterial and fungal infections are the main cause of morbidity and mortality in neutropenic patients. To resolve infections, an adequate number of functional granulocytes is required. Successful treatment of severe infections with granulocyte transfusions is strongly dependent on an adequate number of transfused cells. In this study, 42 neutropenic patients received rhG-CSF-stimulated granulocyte transfusions (GTXs). Of these patients, 18 with severe infections during neutropenia and 8 in a high-risk situation, as defined by severe infections during previous periods of neutropenia or increasing infectious parameters during prolonged neutropenia, received a median of three GTXs (range 1-25), containing a median total of 2.62x10(10) leukocytes (range 0.3-8.61x10(10)). A further 16 patients in a pilot study received prophylactic GTX, consisting of a median of three GTXs (range 1-4) containing a median total of 3.20x10(10) leukocytes (range 0.73-8.51x10(10)). Out of 18 patients with severe infections, 12 improved clinically or showed a resolution of infection after GTX. All 8 patients in a high-risk situation showed a stable clinical course without serious infections. Prophylactic GTX did not result in significant differences with regard to infectious parameters. The median number of transfused platelet units during the course of cytopenia was significantly reduced (13.5 units vs 22.0 units, P<0.02) compared to the control group. For the treatment of infections during neutropenia, rhG-CSF-stimulated granulocyte transfusions are safe and a promising approach.

Effects of K(ATP) channel modulators on acetylcholine release from guinea-pig isolated atria and small intestine.

The effects of K(ATP) channel blockers (glibenclamide, HMR 1883, HMR 1372) and openers (cromakalim, pinacidil, diazoxide) on the electrically-evoked (5 Hz) release of [(3)H]acetylcholine were studied in isolated guinea-pig atria and myenteric plexus-longitudinal muscle preparations which had been preincubated with [(3)H]choline. Atria: Cromakalim (0.3 microM and 1 microM), pinacidil (10 microM) and diazoxide (30 microM) significantly reduced the stimulation-evoked release of [(3)H]acetylcholine. The inhibition produced by cromakalim and pinacidil was prevented by 1 microM of either HMR 1883, HMR 1372 or glibenclamide. The blockers alone significantly increased the release at concentrations of 30 microM, whereas 1 microM and 10 microM had no effect. Myenteric plexus-longitudinal muscle preparation: The electrically-evoked release of [(3)H]acetylcholine was not affected by K(ATP) channel blockers or openers. In contrast, the contractions of the longitudinal muscle caused by electrical stimulation or by carbachol were strongly inhibited by 1 microM cromakalim which suggests that the relaxant effect of the K(ATP) channel openers is exclusively a direct effect on intestinal smooth muscle. The findings suggest that blockade of activated K(ATP) channels in vagal nerves of guinea-pig atria stimulates acetylcholine release, and that this effect may contribute to the antiarrhythmic actions of K(ATP) channel blockers. By contrast, release of acetylcholine from guinea-pig myenteric plexus is not modulated by K(ATP) channels which suggests heterogeneity of K(ATP) channel distribution in peripheral autonomic nerves.

A novel inhibitor of the Na+/H+ exchanger type 3 activates the central respiratory CO2 response and lowers the apneic threshold.

Cultured CO2-sensitive neurons from the ventrolateral medulla of newborn rats enhanced their bioelectric activity upon intracellular acidification induced by inhibition of the Na+/H+ exchanger type 3 (NHE3). Now we detected NHE3 also in the medulla oblongata of adult rabbits. Therefore, this animal model was employed to determine whether NHE3 inhibition also affects central respiratory chemosensitivity in vivo. Seven anesthetized (pentobarbital), vagotomized, paralyzed rabbits were artificially ventilated with O2-enriched air. From the phrenic nerve compound discharge, integrated burst amplitude (IPNA), respiratory rate (fR), and phrenic minute activity (IPNA. fR) were taken as measures of central respiratory rhythm and drive. Effects of potent NHE3 inhibition with the novel brain permeant substance S8218 were studied by comparing respiratory characteristics before and after up to 9.2 +/- 1.1 mg/kg cumulative drug application, yielding average plasma concentrations of 0.9 +/- 0.2 microg/ml. In response to S8218, the baseline level of IPNA. fR was significantly enhanced by an average of 51.0 +/- 6.4% (n = 27, p < 0.0001). The influence of NHE3 inhibition on the respiratory CO2 response was studied at plasma concentrations of S8218 maintained in the range of 0.3 microg/ml (10(-6) M). Although the metabolic acid-base status thereby remained widely unchanged, the group mean apneic threshold PaCO2 was significantly lowered by 0.45 +/- 0.11 kPa (n = 7, p < 0.01), whereby in four of seven animals even strong hyperventilation failed to suppress phrenic nerve rhythmicity completely. Likewise, S8218 significantly augmented IPNA. fR, in the range of PaCO2 between 1 and 6 kPa above threshold, by an average of 38.0 +/- 8.5% (n = 35, p < 0.0001). These in vivo results are compatible with the effects of NHE3 inhibition on chemosensitive brainstem neurons in vitro. Moreover, rhythmogenesis is supported through NHE3 inhibition by lowering the threshold PCO2 for central apnea.

NHE1-inhibitor cariporide prevents the transient reperfusion-induced shortening of the monophasic action potential after coronary ischemia in pigs.

During myocardial ischemia intracellular acid load increases as a consequence of anaerobic metabolism. Exchange of excessive protons for sodium via the sodium proton exchanger type 1 (NHE1) is supposed to cause intracellular sodium accumulation. The NHE1 inhibitor cariporide has been shown to inhibit ischemia and reperfusion-induced ventricular fibrillation (VF) but the mechanisms are not fully understood. During early reperfusion transient shortening of the action potential has been reported, which renders the heart susceptible to reentrant arrhythmias. In anesthetized pigs subjected to 10 min of left circumflex coronary artery (LCX) occlusion and reperfusion we have investigated whether NHE1 is involved in reperfusion-induced shortening of the monophasic action potential (MAP) taken with an epicardial probe over the ischemic area. In control pigs (n = 7) a moderate decrease in the duration of the MAP at 50 % repolarization (MAPD50) occurred during ischemia reaching 78.8 +/- 5.0% of the pre-ischemic duration at 5 min (p < 0.01) and 87.3 +/- 7.6 % after 10 min. An additional, transient but marked shortening occurred during the first 2 min of reperfusion, which fully recovered after 4 min. At 50 sec of reperfusion MAPD50 fell to 53.1 +/- 8.2 % of the pre-ischemic value corresponding to 90.1 +/- 20.2 msec of reperfusion-induced shortening. Cariporide, 3 mg/kg i.v. 5 min before occlusion (n = 6), totally prevented reperfusion-induced MAP shortening while having no effect on MAPD50 during ischemia. In conclusion, our data suggest that the immediate, transient, but strong action potential shortening during early reperfusion after 10 min of coronary ischemia is due to the activity of the NHE1.

Differential effects of dofetilide, amiodarone, and class lc drugs on left and right atrial refractoriness and left atrial vulnerability in pigs.

OBJECTIVES: Antiarrhythmic drugs have been shown to prolong right atrial refractoriness while data on the left atrium are not available. In pigs we have observed shorter effective refractory periods (ERP) of the left compared with the right atrium associated with a much higher left atrial vulnerability for tachyarrhythmias. Since this could suggest a different distribution of repolarizing ion channels in left and right atrium, we investigated whether antiarrhythmic drugs blocking different ion channels have a differential effect on left and right atrial ERP and left atrial vulnerability. METHODS: In pentobarbital-anesthetized pigs (n=40) we measured and compared ERPs in both atria before and after different drugs with the S1-S2 extrastimulus method at three basic cycle lengths (BCL) and assessed the inducibility of atrial fibrillation/flutter (AF/AFL) by the premature S2 stimulus. RESULTS: At the three BCL tested (240/300/400 ms) baseline ERPs were shorter in left vs. right atrium (112+/-2/124+/-2/129+/-2 ms vs. 147+/-2/163+/-2/167+/-2 ms, P<0.001). Mostly non-sustained AF/AFL induced by the S2 extrastimulus was very frequent in the left (68%) and nearly absent in the right atrium (3%). Only amiodarone, 5 mg/kg i.v., which showed a balanced increase of left and right atrial ERP (29+/-5/33+/-4/35+/-3% vs. 30+/-5/35+/-5/42+/-7%), decreased the inducibility of AF/AFL significantly (-72%, P<0.01). Dofetilide, 10 microg/kg i.v., had a stronger effect on right than left atrial ERP (36+/-4/39+/-5/46+/-10% vs. 23+/-2/22+/-7/22+/-5%, P<0.05), while flecainide, 1 mg/kg i.v., prolonged left more than right atrial ERP (58+/-15/36+/-7/40+/-7% vs. 26+/-5/24+/-5/21+/-4%, P<0.05) similar to 1 mg/ kg of propafenone (46+/-5/45+/-7/32+/-10% vs. 17+/-4/21+/-5/ 25+/-8%, P<0.05). CONCLUSION: The shorter refractoriness of the left compared with the right atrium observed in pigs was associated with a high left atrial vulnerability for tachyarrhythmias, which was reduced only by amiodarone showing a balanced increase of left and right atrial ERP. Dofetilide was stronger on right atrial ERP, flecainide and propafenone on left atrial ERP. These differences suggest a differential distribution of repolarizing ion channels between left and right atrium with possible relevance for the antiarrhythmic efficacy of drugs.

Effect of amphetamine on extracellular acetylcholine and monoamine levels in subterritories of the rat medial prefrontal cortex.

The present study sought to investigate the contributions of the dorsal prelimbic/anterior cingulate and ventral prelimbic/infralimbic cortices to the reverse microdialysis of amphetamine (1, 10, 100, 500, and 1000 microM) on dialysate acetylcholine, choline, norepinephrine, and serotonin levels. The results demonstrate that basal levels of acetylcholine, choline, and serotonin were homogeneous within subregions of the medial prefrontal cortex. In contrast, dialysate norepinephrine levels were significantly higher in the anterior cingulate cortex compared with the infralimbic cortex. Reverse microdialysis of amphetamine in both subareas of the medial prefrontal cortex produced a dose-dependent increase in norepinephrine and serotonin levels; the magnitude of this effect was similar in both subterritories of the medial prefrontal cortex. Microinfusion of amphetamine increased dialysate acetylcholine levels in a dose-dependent manner only in the infralimbic cortex. Finally, amphetamine decreased choline levels in both subregions of the medial prefrontal cortex. The magnitude of this effect was larger in the anterior cingulate cortex compared with its infralimbic counterpart. Since depletions of frontal cortical acetylcholine result in severe cognitive deficits, the present data raise the possibility that the type of neural integrative processes that acetylcholine mediates depends, at least in part, on the subterritories that characterize the medial prefrontal cortex.