Microbiological changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in individuals with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection.

OBJECTIVES: Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213-26]. METHODS: Respiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied. RESULTS: Sputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13-1.40) versus 0.54 (95% CI 0.89-0.19) log10 CFU/g for placebo (second period) to 2.07 (95% CI 2.45-1.69) versus 0.70 (95% CI 1.11-0.29) log10 CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC50 increased from 0.5 to 1 mg/L, MIC90 increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected. CONCLUSION: Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit.

Extended International Normalized Ratio testing intervals for warfarin-treated patients.

Essentials Warfarin typically requires International Normalized Ratio (INR) testing at least every 4 weeks. We implemented extended INR testing for stable warfarin patients in six anticoagulation clinics. Use of extended INR testing increased from 41.8% to 69.3% over the 3 year study. Use of extended INR testing appeared safe and effective. SUMMARY: Background A previous single-center randomized trial suggested that patients with stable International Normalized Ratio (INR) values could safely receive INR testing as infrequently as every 12 weeks. Objective To test the success of implementation of an extended INR testing interval for stable warfarin patients in a practice-based, multicenter collaborative of anticoagulation clinics. Methods At six anticoagulation clinics, patients were identified as being eligible for extended INR testing on the basis of prior INR value stability and minimal warfarin dose changes between 2014 and 2016. We assessed the frequency with which anticoagulation clinic providers recommended an extended INR testing interval (> 5 weeks) to eligible patients. We also explored safety outcomes for eligible patients, including next INR values, bleeding events, and emergency department visits. Results At least one eligible period for extended INR testing was identified in 890 of 3362 (26.5%) warfarin-treated patients. Overall, the use of extended INR testing in eligible patients increased from 41.8% in the first quarter of 2014 to 69.3% in the fourth quarter of 2016. The number of subsequent out-of-range next INR values were similar between eligible patients who did and did not have an extended INR testing interval (27.3% versus 28.4%, respectively). The numbers of major bleeding events were not different between the two groups, but rates of clinically relevant non-major bleeding (0.02 per 100 patient-years versus 0.09 per 100 patient-years) and emergency department visits (0.07 per 100 patient-years versus 0.19 per 100 patient-years) were lower for eligible patients with extended INR testing intervals than for those with non-extended INR testing intervals. Conclusions Extended INR testing for stable warfarin patients can be successfully and safely implemented in diverse, practice-based anticoagulation clinic settings.

Detection of delayed cerebral ischemia (DCI) in subarachnoid haemorrhage applying near-infrared spectroscopy: elimination of the extracerebral signal by transcutaneous and intraparenchymatous measurements in parallel.

BACKGROUND: Detection of delayed cerebral ischemia (DCI) in high-grade subarachnoid haemorrhage (SAH) is an unsolved issue. Conventional near-infrared spectroscopy (NIRS) with optodes applied over the skin is controversial because the NIRS signal is contaminated by extracerebral tissue. The objective is to quantify and subtract the contribution from extracerebral tissue from the signal by using measurements in parallel with a NIRS brain tissue probe and conventional NIRS. METHODS: In a patient with high-grade SAH, two approaches for NIRS were applied. First, a conventional brain tissue probe for intracranial pressure (ICP) monitoring, supplied by optical fibres, was placed into the brain tissue 2 cm deep from the dura. Second, for conventional NIRS, a plaster-based patch carrying optodes (one emitter, two detectors) was attached to the skin. Central venous injections of 0.3 mg/kg body weight (bw) indocyanine green (ICG) were performed. ICG dye dilution curves obtained with the probe and patch were collected simultaneously and analysed for blood flow values. RESULTS: Twelve measurements in parallel with the probe and patch were performed. Mean cerebral blood flow (CBF) for the probe was higher (24.8 ± 9.1 ml/100 g/min) compared with the values obtained with the patch (for detector 1, extra-cerebral blood flow [ECBF] mean 5.1 ± 1.8 ml/100 g/min; p = 0.002; for detector 2, 6.6 ± 2.1 ml/100 g/min; p = 0.002). CBF values obtained with the probe correlated with blood flow values obtained with the patch (for CBF vs. ECBF detector 1, r = 0.72 [p = 0.008]; ECBF detector 2, r = 0.79 [p = 0.002]). CONCLUSIONS: Blood flow values obtained with conventional NIRS correlated significantly with absolute CBF values obtained directly within the brain tissue. Simultaneous measurements with the NeMo Probe and NeMo Patch allow quantification and subtraction of the contribution from extracerebral tissues from the signal obtained with conventional NIRS.

Software-assisted quantitative analysis of small bowel motility compared to manual measurements.

AIM: To validate a newly developed software prototype that automatically analyses small bowel motility by comparing it directly with manual measurement. MATERIAL AND METHODS: Forty-five patients with clinical indication for small bowel magnetic resonance imaging (MRI) were retrospectively included in this institutional review board-approved study. MRI was performed using a 1.5 T system following a standard MR-enterography protocol. Small bowel motility parameters (contractions-per-minute, luminal diameter, amplitude) were measured three times each in identical segments using the manual and the semiautomatic software-assisted method. The methods were compared for agreement, repeatability, and time needed for each measurement. All parameters were compared between the methods. RESULTS: A total of 91 small-bowel segments were analysed. No significant intra-individual difference (p > 0.05) was found for peristaltic frequencies between the methods (mean: 4.14/min manual; 4.22/min software-assisted). Amplitudes (5.14 mm; 5.57 mm) and mean lumen diameters (17.39 mm; 14.68) differed due to systematic differences in the definition of the bowel wall. Mean duration of single measurement was significantly (p < 0.01) shorter with the software (6.25 min; 1.30 min). The scattering of repeated measurements was significantly (p < 0.05) lower using the software. CONCLUSION: The software-assisted method accomplished highly reliable, fast and accurate measurement of small bowel motility. Measurement precision and duration differed significantly between the two methods in favour of the software-assisted technique.

Gadoxetate uptake as a possible marker of hepatocyte damage after liver resection-preliminary data.

AIM: To determine the feasibility of evaluating surgically induced hepatocyte damage using gadoxetate disodium (Gd-EOB-DTPA) as a marker for viable hepatocytes at magnetic resonance imaging (MRI) after liver resection. MATERIAL AND METHODS: Fifteen patients were prospectively enrolled in this institutional review board-approved study prior to elective liver resection after informed consent. Three Tesla MRI was performed 3-7 days after surgery. Three-dimensional (3D) T1-weighted (W) volumetric interpolated breath-hold gradient echo (VIBE) sequences covering the liver were acquired before and 20 min after Gd-EOB-DTPA administration. The signal-to-noise ratio (SNR) was used to compare the uptake of Gd-EOB-DTPA in healthy liver tissue and in liver tissue adjacent to the resection border applying paired Student's t-test. Correlations with potential influencing factors (blood loss, duration of intervention, age, pre-existing liver diseases, postoperative change of resection surface) were calculated using Pearson's correlation coefficient. RESULTS: Before Gd-EOB-DTPA administration the SNR did not differ significantly (p = 0.052) between healthy liver tissue adjacent to untouched liver borders [59.55 ± 25.46 (SD)] and the liver tissue compartment close to the resection surface (63.31 ± 27.24). During the hepatocyte-specific phase, the surgical site showed a significantly (p = 0.04) lower SNR (69.44 ± 24.23) compared to the healthy site (78.45 ± 27.71). Dynamic analyses revealed a significantly lower increase (p = 0.008) in signal intensity in the healthy tissue compared to the resection border compartment. CONCLUSION: EOB-DTPA-enhanced MRI may have the potential to be an effective non-invasive tool for detecting hepatocyte damage after liver resection.

Differentiation between active and chronic Crohn's disease using MRI small-bowel motility examinations - initial experience.

AIM: To evaluate the influence of locally active Crohn's disease on systemic small-bowel motility in patients with chronic Crohn's disease compared to healthy individuals. MATERIAL AND METHODS: Fifteen healthy individuals (11 men, four women; mean age 37 years) and 20 patients with histopathologically proven active (n = 15; 10 women, 5 men; mean age 45 years) or chronic (n = 5; four women, one man; mean age 48 years) Crohn's disease were included in this institutional review board-approved, retrospective study. Magnetic resonance imaging (MRI; 1.5 T) was performed after standardized preparation. Two-dimensional (2D) cine sequences for motility acquisition were performed in apnoea (27 s). Motility assessment was performed using dedicated software in three randomly chosen areas of the small-bowel outside known Crohn's disease-affected hotspots. The main quantitative characteristics (frequency, amplitude, occlusion rate) were compared using Student's t-test and one-way analysis of variance (ANOVA). RESULTS: Three randomly chosen segments were analysed in each participant. Patients with active Crohn's disease had significantly (p < 0.05) reduced contraction frequencies (active Crohn's disease: 2.86/min; chronic: 4.14/min; healthy: 4.53/min) and luminal occlusion rates (active: 0.43; chronic: 0.70; healthy: 0.73) compared to healthy individuals and patients with chronic Crohn's disease. Contraction amplitudes were significantly reduced during active Crohn's disease (6.71 mm) compared to healthy participants (10.14 mm), but this only reached borderline significance in comparison to chronic Crohn's disease (8.87 mm). Mean bowel lumen diameter was significantly (p = 0.04) higher in patients with active Crohn's disease (16.91 mm) compared to healthy participants (14.79 mm) but not in comparison to patients with chronic Crohn's disease (13.68). CONCLUSION: The findings of the present study suggest that local inflammatory activity of small-bowel segments in patients with active Crohn's disease alters small-bowel motility in distant, non-affected segments. The motility patterns revealed reduced contraction-wave frequencies, amplitudes, and decreased luminal occlusion rates. Thus evaluation of these characteristics potentially helps to differentiate between chronic and active Crohn's disease.

MR imaging in Crohn's disease: correlation of MR motility measurement with histopathology in the terminal ileum.

BACKGROUND: The objective of the study was to correlate MR-detectable motility alterations of the terminal ileum with biopsy-documented active and chronic changes in Crohn's disease. METHODS: This IRB approved retrospective analysis of 43 patients included magnetic resonance enterography (MRE) and terminal ileum biopsies (<2 weeks apart). Motility was measured at the terminal ileum using coronal 2D trueFISP pulse sequences (1.5T MRI,TR 83.8,TE1.89) and dedicated motility assessment software. Motility grading (hypermotility, normal, hypomotility, complete arrest) was agreed by two experienced readers. Motility was compared and correlated with histopathology using two-tailed Kruskal-Wallis test and paired Spearman Rank-Order Correlation tests. KEY RESULTS: Motility abnormalities were present in 27/43 patients: nine hypomotility and 18 complete arrest. Active disease was diagnosed on 15 biopsies: eight moderate and seven severe inflammatory activity. Chronic changes were diagnosed on 17 biopsies: 13 moderate and four severe cases. In four patients with normal motility alterations on histopathology were diagnosed. Histopathology correlated with presence (P = 0.0056 for hypomotility and P = 0.0119 for complete arrest) and grade (P < 0.0001; P = 0.0004) of motility alterations. A significant difference in the motility was observed in patients with active or chronic CD compared with patients without disease (P < 0.001; P = 0.0024). CONCLUSIONS & INFERENCES: MR-detectable motility changes of the terminal ileum correlate with histopathological findings both in active and chronic CD. Motility changes may indicate the presence pathology, but do not allow differentiation of active and chronic disease.

Crohn's disease: small bowel motility impairment correlates with inflammatory-related markers C-reactive protein and calprotectin.

BACKGROUND: To evaluate the correlation between the levels of C-reactive protein (CRP), calprotectin, and small bowel motility in patients with Crohn's disease assessed with MRI. METHODS: This prospective institutional review board approved study included magnetic resonance imaging enterography (MRE) and analyses of inflammatory markers in blood (C-reactive protein) and feces (calprotectin). For cine MRE, a coronal 2D-T2w sequence was used on a 1.5 T MRI system. Small bowel motility was analyzed in 13 patients using dedicated magnetic resonance MR-motility assessment software (Motasso). Contraction frequency, amplitude, amplitude diameter ratio, and luminal diameter were determined as well as the blood levels of CRP (mg L(-1) ) and fecal levels of calprotectin (ug g(-1) ). Statistics were calculated using Pearson's correlation coefficient. KEY RESULTS: A significant inverse linear correlation was found between the contraction frequency and both the level of CRP (r = -0.701, P = 0.008) and calprotectin (r = -0.805, P = 0.001). Dilatation of small bowel diameter significantly correlated with calprotectin levels (r = 0.857, P =< 0.001) but not with CRP (r = 0.447, P = 0.126). The absolute amplitude of the contractions did not correlate neither with the level of CRP (r = -0.527, P = 0.064) nor with calprotectin (r = -0.612, P = 0.026). The ratio describing the contraction amplitude relatively to the individual luminal diameter significantly correlated with calprotectin (r = 0.736, P = 0.004) and with CRP (r = 0.577, P = 0.039). CONCLUSIONS & INFERENCES: Alterations of small bowel motility during CD flares significantly correlate with the level of calprotectin and CRP indicating that they represent inflammatory activity.

Influence of clinical presentation on the outcome of acute B aortic dissection: evidences from IRAD.

AIM: In-hospital outcome of acute type B dissection (ABAD) is strongly related to preoperative aortic conditions. In order to clarify the influence of the clinical presentation on the outcome, we analyzed the patients of the International Registry of Acute Aortic Dissection (IRAD). All patients affected by complicated ABAD, enrolled in the IRAD from 1996-2004, were included. Complications were defined as the presence of shock, periaortic hematoma, spinal cord ischemia, preoperative mesenteric ischemia/infarction, acute renal failure, limb ischemia, recurrent pain, refractory pain or refractory hypertension (group I). All other patients were categorized as uncomplicated (group II). A comprehensive analysis was performed of all clinical variables in relation to in-hospital outcome. RESULTS: The overall in-hospital mortality among 550 patients was 12.4%. Mortality in group I (250 patients) was 20.0 %, compared to 6.1% in group II (300 patients) (P<0.001). Univariate predictors of ABAD complications were Marfan syndrome, abrupt onset of pain, migrating pain, any focal neurological deficits, need for higher number of diagnostic examinations and use of magnetic resonance and/or aortogram, abdominal vessels involvement at aortogram, larger descending aortic diameter, especially >6 cm, pleural effusion, and widened mediastinum on chest X-ray. Univariate predictors of a non complicated status were normal chest X-ray and medical management. In group I, in-hospital mortality following surgical and endovascular intervention were 28.6% and 10.1% (P=0.006), respectively. Independent predictors of overall in-hospital mortality included age >70 years, female gender, ECG showing ischemia, preoperative acute renal failure, preoperative limb ischemia, periaortic hematoma, and surgical management. The only independent variable protective for mortality was magnetic resonance as diagnostic test. CONCLUSION: ABAD is a heterogeneous disease that produces dissimilar clinical subsets, each of which can have specific clinical signs, management and in-hospital results. In IRAD ABAD uncomplicated patients, medical therapy was associated with best hospital outcome, while endovascular interventions were associated with better results than surgery when invasive treatments were required. Although selection bias may be possible, and irrespective of treatments, knowledge of significant risk factors for mortality may contribute to a better management and a more defined risk-assessment in patients affected by ABAD.

Insula-specific responses induced by dental pain. A proton magnetic resonance spectroscopy study.

OBJECTIVES: To evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate. METHODS: Ten male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87-92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy. RESULTS: Significant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (-9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate. CONCLUSION: The insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed.

Neuromonitoring in intensive care: a new brain tissue probe for combined monitoring of intracranial pressure (ICP) cerebral blood flow (CBF) and oxygenation.

BACKGROUND: the benefits of monitoring cerebral blood flow (CBF) in stroke patients are apparent. New techniques combining near infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution to estimate cerebral hemodynamics are available. However, with transcutaneous NIRS and optodes applied over the skin, the signal is contaminated by extracerebral tissues. The objective is to develop a new brain tissue probe for combined monitoring of intracranial pressure (ICP), CBF and cerebral blood volume (CBV). METHODS: conventional intraparenchymal probes for ICP monitoring are supplied with optical fibers. The light is coupled into the brain tissue and collected after absorption and scattering with a light detector. Venous injections of 0.2 mg/kgbw ICG are performed. The mean transit time of ICG (mttICG), CBF and CBV are calculated. RESULTS: with a prototype of the probe in a first patient with subarachnoid hemorrhage 6 pairs of repetitive measurements were performed. Mean values were for mttICG 5.6 ± 0.2 s, CBF 22.3 ± 2.8 ml/100 g/min and CBV 2.1 ± 0.3 ml/100 g. CONCLUSIONS: NIR spectroscopy allows the synchronous determination of multiple parameters with one single device. By measurements in parallel with the NeMo Probe and NIRS optodes placed over the skin, new algorithms can be developed to subtract the extracerebral contamination from the NIRS signal.

What aspects of human alcohol use disorders can be modeled using selectively bred rat lines?

The use of selective breeding to produce animal models for the study of alcohol abuse and alcoholism represents one of the major advances in the field of alcohol research. Rats selectively bred for alcohol preference and alcohol nonpreference have been useful to both preclinical and clinical investigators in the alcohol research community for studying the behavioral, neurobiological, and molecular basis of alcohol drinking, for identifying the genes that may contribute to the development of alcohol abuse and alcoholism, and for evaluating the utility of drugs aimed at reducing alcohol intake and preventing alcohol relapse. Rats selectively bred for alcohol preference (alcohol preferring or "P" line) have enhanced responsiveness to the low dose reinforcing effects of alcohol, less aversion to moderate/high doses of alcohol, and are able to develop tolerance to the aversive effects of alcohol more rapidly and to maintain tolerance longer than rats selectively bred for alcohol nonpreference (alcohol nonpreferring or "NP" line). The increased potency of low-dose alcohol as a reinforcer for P rats might be expected to foster and maintain alcohol drinking. Weaker aversion to the pharmacological effects of moderate/high doses of alcohol in the P line would allow P rats to drink more alcohol than NP rats before the postingestional effects become aversive. Rapid induction of tolerance to the aversive effects of alcohol with repeated bouts of voluntary alcohol drinking, as well as persistence of alcohol tolerance in rats of the P line might serve to maintain alcohol drinking. These are powerful mechanisms that may serve to promote and maintain a high alcohol drinking behavior. Although these rat lines have been used to address several characteristics of excessive alcohol consumption in humans, they have not yet been used to model several aspects of human alcohol use disorders. New applications of these selectively bred rat lines are discussed which may further our understanding of the factors contributing to alcohol abuse and alcoholism.

Screening for renal insufficiency following ESUR (European Society of Urogenital Radiology) guidelines with on-site creatinine measurements in an outpatient setting.

OBJECTIVE: To report the results and implications for workflow following introduction of ESUR guidelines to screen for potential renal insufficiency (RI) in private practice with on-site creatinine measurements. METHODS: A total of 1,766 consecutive outpatients scheduled for contrast-enhanced CT (CECT) completed the ESUR questionnaire enquiring about kidney disease, renal surgery, proteinuria, diabetes mellitus, hypertension, gout or use of nephrotoxic drugs. Patients with positive risk factors underwent on-site creatinine measurement and calculation of estimated glomerular filtration rate (eGFR). Attending radiologists adapted subsequent imaging depending on renal function and presence of risk factors. RESULTS: One or more ESUR risk factors were present in 796 (45.1%) patients, including hypertension (37.7%), nephrotoxic medication (21.3%), diabetes mellitus (8.0%), proteinuria (3.9%), renal disease (4.1%), gout (3.1%) and renal surgery (2.6%). Pre-procedural creatinine measurements revealed severe RI (eGFR < 30 ml min(-1) 1.73 m(-2)) in 10 (1.3%) and moderate RI (eGFR 30-59 ml min(-1) 1.73 m(-2)) in 106 (13.8%). Imaging work-up was adapted in 132 (16.6%) as follows: reduction of contrast material dose (n = 85), CT without contrast (n = 40), changeover to MRI (n = 3) or scintigraphy (n = 4). CONCLUSION: Screening for RI following ESUR guidelines requires creatinine measurements in nearly half of outpatients scheduled for CECT and reveals moderate to severe renal impairment in 6.6%.

USPIO-enhanced magnetic resonance imaging of the knee in asymptomatic volunteers.

The aim of this study was to compare signal characteristics of the synovium in knees of asymptomatic volunteers before and after intravenous administration of ultrasmall superparamagnetic iron oxide particles (USPIO). Ten knees of 10 asymptomatic volunteers were examined before and 36 h after intravenous administration of USPIO on a 1.5-T MR system using T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo (GRE), and short inversion time inversion-recovery sequences. In addition, synovial perfusion was measured using Gd-enhanced GRE imaging during the first imaging session. Images were analyzed qualitatively for any visual changes before and after USPIO administration. Signal-to-noise ratios (SNR) of the synovium were determined on unenhanced and USPIO-enhanced sequences. All MR images were reviewed for presence of any degenerative changes. Qualitative image analysis revealed no visually detectable changes of any knee joint before and after USPIO administration. The SNR values of the synovium on T1w, T2w, and T2*w images before and after USPIO administration showed no significant difference (T1, P = 0.86; T2, P = 0.95; T2*, P = 0.86). None of the volunteers showed any relevant degenerative changes of the knee and synovial perfusion was within normal limits. In knees of asymptomatic volunteers without any relevant degenerative changes and normal synovial perfusion neither visual changes nor changes of SNR values of the synovium can be depicted after USPIO administration. This means that USPIO-enhanced MRI may be used for assessment of knee disorders with increased macrophage activity.

Dose optimization of contrast-enhanced carotid MR angiography.

The purpose of this work was to compare the diagnostic performance of a single-contrast or a double-contrast dose of carotid contrast-enhanced MR angiography (MRA). One-hundred nineteen patients (mean age 65+/-14.4 years) underwent carotid contrast-enhanced MRA with a standardized protocol (repetition time/echo 3.73 ms/1.38 ms, flip-angle 25 degrees, acquisition-time 19 s, voxel size 1.2 x 1.2 x 0.9 mm3) on a 1.5-T scanner (Sonata, Siemens-Medical-Systems) using a neck phased-array coil. Contrast agent was administered intravenously at a rate of 3.0 ml/s, either as a single dose (n=57; 0.1 mmol/kg body weight) or as a double dose (n=62; 0.2 mmol/kg body weight) of meglumine gadoterate (0.5 M/l), followed by 30 ml saline. Qualitative image analysis was performed on maximum intensity projections using a five-point scale. Signal intensities were measured at three different vascular levels on both sides to assess the contrast-to-noise ratios (CNRs). Image quality was rated as good or excellent in all cases. A double dose did not influence the efficacy of carotid enhancement (CNR single dose 69.12+/-19.8; CNR double dose 70.01+/-20.7; p = 0.81) compared with a single dose. In both dose groups the mean CNRs were inversely related to bodyweight, despite adjusted contrast volumes (p=0.0005). Double-dose contrast-enhanced carotid MRA is not superior to single-dose MRA, as overall diagnostic performance and quantitative contrast enhancement are equal. Being more cost-efficient, a single-dose administration of contrast agent is recommended for MRA of the carotid arteries.

[Computed tomography for the assessment of posterior pelvic injuries in patients with isolated fractures of the pubic rami in conventional radiography]. / Häufigkeit hinterer Läsionen bei vorderen Beckenringfrakturen Ergebnisse der Computertomographie bei der Erstdiagnose "isolierte vordere Beckenringfraktur" im konventionellen Röntgenbild.

To investigate the incidence of occult posterior injuries of the pelvic ring in patients with isolated fractures of the pubic rami, additional computed tomography (CT) was performed. Data from 70 patients were collected within a prolective study. Solitary fractures of the anterior pelvic ring based on conventional radiographic diagnosis were included. Spiral CT, slice thickness 5 mm, was carried out in all patients. In only 47% of cases was the diagnosis of isolated fractures of the pubic rami confirmed. A further 35 fractures of the sacrum and two partial disruptions of the sacroiliac joint were diagnosed using CT. All sacral fractures were incomplete, most were found at the anterior part of the bone. Furthermore, CT revealed three acetabular fractures. Dorsal injuries were significantly more frequent after high energy accidents. Clinical examination did not assist in the prediction of posterior injuries of the pelvic ring. There was no correlation between the extent of the anterior injuries in conventional x-ray and incidence of the posterior injuries in CT. None of the patients with dorsal injuries underwent operative treatment. In conclusion, CT is not required for the routine diagnosis of supposed isolated fractures of the pubic rami.

Inverse genetic association between alcohol preference and severity of alcohol withdrawal in two sets of rat lines selected for the same phenotype.

BACKGROUND: The purpose of the present study was to determine whether alcohol-naïve rats selectively bred for alcohol preference or nonpreference differ in alcohol withdrawal severity using two sets of rat lines selectively bred for the same phenotype. METHODS: Alcohol-naïve male rats from the high alcohol drinking (HAD1) and low alcohol drinking (LAD1) rat lines and from the alcohol preferring (P) and nonpreferring (NP) rat lines received an intragastric infusion of alcohol (4.0 g/20.3 ml/kg; 25% v/v) or an equal volume of water once a day for 10 consecutive days. Alcohol withdrawal severity was assessed at using a behavioral rating scale and a radiant heat assay measured analgesia at 10, 12, 14, 16, 18, and 24 hrs following infusion of alcohol or water on days 1, 5, and 10 of treatment. RESULTS: Data were analyzed using body weight as a co-factor to correct for differences in body weight between the HAD1/LAD1 and P/NP lines. Acute (1 day) but not repeated alcohol treatment (5 or 10 days) produced mild behavioral signs of withdrawal in LAD1 but not in HAD1 rats. HAD1 and LAD1 rats showed alcohol-induced analgesia after 1 and 5 days of alcohol treatment that disappeared by day 10 in both lines. Repeated alcohol treatment (5 days) produced mild behavioral signs of withdrawal in NP but not in P rats. Neither P nor NP rats showed alcohol-induced analgesia after 1, 5, or 10 days of alcohol treatment. CONCLUSIONS: An inverse genetic association was found between alcohol preference and severity of alcohol withdrawal in two sets of rat lines selected for the same phenotype. The pattern of alcohol withdrawal that emerged over the course of the 10 days of alcohol treatment differed between the two lines selected for low alcohol drinking (LAD1 and NP), suggesting that unique sets of genes may influence alcohol withdrawal severity in the two lines.

Field methodology for lateral cranial radiography of nonhuman primates.

The historical lack of field-based radiographic studies of nonhuman primates within the field of anthropology is likely due to the perceived difficulty of transporting and operating X-ray equipment. Here we present a method for taking lateral cranial radiographs of nonhuman primates in the field that is simple to employ, and that produces exposed films suitable for collection of measurement data useful for growth and development studies, as well as for investigating bone and soft-tissue pathology. Several different X-ray units, film types, and portable power sources were used, all producing suitable images of similar quality, indicating that this methodology is likely not overly sensitive to these important parameters.

Effects of acamprosate on sensitization to the locomotor-stimulant effects of alcohol in mice selectively bred for high and low alcohol preference.

Sensitization to the locomotor-stimulant effects of drugs is thought to play an important role in the development of drug-seeking behaviour. We hypothesized that the ability of acamprosate to reduce alcohol relapse rates in recovering alcoholics, and alcohol consumption in rodents, may be related to its ability to reduce sensitization to the locomotor-stimulant effects of alcohol. The purpose of the present study was to determine whether acamprosate reduces the expression of sensitization to the locomotor-stimulant effects of alcohol in lines of mice selectively bred for high (HAP) and low (LAP) alcohol preference. Mice were given six intraperitoneal (i.p.) injections of alcohol (3 g/kg) or saline at 48 h intervals. The test for sensitization to the locomotor-stimulant effects of alcohol consisted of a challenge dose of 2 g/kg i.p. alcohol followed immediately by assessment of locomotor activity for 20 min. Mice were pretreated with either saline or acamprosate (400 mg/kg) at 14 h and again at 2 h before the alcohol challenge. Both HAP and LAP mice showed sensitization to the locomotor-stimulant effects of alcohol. Acamprosate reduced the expression of sensitization to the locomotor-stimulant effects of alcohol in HAP but not LAP mice. These data suggest complex effects of acamprosate on alcohol-stimulated locomotor activity that depend on genotype.

Colocalization of plastid division proteins in the chloroplast stromal compartment establishes a new functional relationship between FtsZ1 and FtsZ2 in higher plants.

Chloroplast division is driven by a macromolecular complex containing components that are positioned on the cytosolic surface of the outer envelope, the stromal surface of the inner envelope, and in the intermembrane space. The only constituents of the division apparatus identified thus far are the tubulin-like proteins FtsZ1 and FtsZ2, which colocalize to rings at the plastid division site. However, the precise positioning of these rings relative to the envelope membranes and to each other has not been previously defined. Using newly isolated cDNAs with open reading frames longer than those reported previously, we demonstrate here that both FtsZ2 proteins in Arabidopsis, like FtsZ1 proteins, contain cleavable transit peptides that target them across the outer envelope membrane. To determine their topological arrangement, protease protection experiments designed to distinguish between stromal and intermembrane space localization were performed on both in vitro imported and endogenous forms of FtsZ1 and FtsZ2. Both proteins were shown to reside in the stromal compartment of the chloroplast, indicating that the FtsZ1- and FtsZ2-containing rings have similar topologies and may physically interact. Consistent with this hypothesis, double immunofluorescence labeling of various plastid division mutants revealed precise colocalization of FtsZ1 and FtsZ2, even when their levels and assembly patterns were perturbed. Overexpression of FtsZ2 in transgenic Arabidopsis inhibited plastid division in a dose-dependent manner, suggesting that the stoichiometry between FtsZ1 and FtsZ2 is an important aspect of their function. These studies raise new questions concerning the functional and evolutionary significance of two distinct but colocalized forms of FtsZ in plants and establish a revised framework within which to understand the molecular architecture of the plastid division apparatus in higher plants.