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Oral high-dose methylprednisolone treatment is efficacious in acute optic neuritis (ON) and attacks of multiple sclerosis (MS). The responses to treatment in subgroups of patients participating in two randomized, controlled trials were assessed. Fifty-eight patients with ON and 51 patients with attacks of MS were treated with placebo or oral methylprednisolone (500 mg daily for five days with a 10-day tapering period). A gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan was obtained at baseline in 66 patients, and 29 patients underwent repeated MRI studies. Seventy-four patients underwent lumbar puncture before treatment. The odds ratio (OR) of improvement after methylprednisolone treatment (a one point change in the visual function system score of the Kurtzke Expanded Disability Status Scale (EDSS) in ON or in the EDSS score in attacks of MS) was higher in patients with enhancing lesions on baseline MRI (one week: OR 15, P =0.02; eight weeks: OR 4.6, P =0.02). Methylprednisolone treatment suppressed Gd-enhancement after one week (P<0.001) and three weeks (P =0.001). Cerebrospinal fluid measures of intrathecal inflammation correlated with the area of Gd-enhancement but did not correlate as closely with the treatment response as did the results of Gd-enhanced MRI. These findings suggest that the resolution of intrathecal inflammation as assessed by Gd-enhanced MRI is a major effect of oral high-dose methylprednisolone. [ABSTRACT FROM AUTHOR]

We have detected the methanol dimer, trimer, and tetramer at equilibrium conditions at room temperature in the gas phase using direct absorption Fourier transform infrared spectroscopy. The infrared intensity of the OH-stretching transitions are enhanced upon hydrogen bonding and are increasingly red-shifted with increasing cluster size, facilitating identification and quantification of the various clusters. We calculate the intensities of the bound OH-stretches, OH b , for all clusters with a range of reduced dimensional vibrational models with different levels of electronic structure theory. Partial pressures of the clusters are obtained by scaling the measured integrated absorbance of the OH b -stretching bands by the calculated intensities of the associated vibrational transitions. We estimate the methanol dimer equilibrium constant, K D , to be 0.033, at 298.15 K, which is comparable to that of the water dimer. For the methanol trimer and tetramer, we estimate equilibrium constants for aggregation of monomers of K T ∼ 0.04 and K Q ∼ 0.6, respectively.

We present a conceptually simple model for understanding the significant spectral changes that occur with the temperature in the infrared spectra of hydrogen-bound complexes. We have measured room-temperature spectra of the methanol dimer and two deuterated isotopologues in the OH(D)-stretching region. We correctly predict spectral changes observed in the gas phase for the bound OH stretch in the methanol dimer from jet-cooled to room temperature and corroborate this with experimental and theoretical results for deuterated isotopologues. The origin of the observed spectral features is explained based on a reduced-dimensional vibrational model, which includes the two high-frequency OH stretches, the two methyl torsions, and the six intermolecular low-frequency vibrations. Key to the success of the model is a new coordinate definition to describe the intrinsic large-amplitude curvilinear motion of low-frequency vibrations. Despite the deceivingly simple appearance of the room temperature bound OH-stretching fundamental band, it consists of ∼10 7 vibrational transitions.

We have detected the tert -butyl hydroperoxide dimer, ( t -BuOOH) 2 , in the gas phase at room temperature using conventional FTIR techniques. The dimer is identified by an asymmetric absorbance band assigned to the fundamental hydrogen-bound OH b -stretch. The weighted band maximum of the dimer OH b -stretch is located at ∼3452 cm -1 , red-shifted by ∼145 cm -1 from the monomer OH-stretching band. The gas-phase dimer assignment is supported by Ar matrix isolation FTIR experiments at 12 K and experiments with a partially deuterated sample. Computationally, we find the lowest energy structure of ( t -BuOOH) 2 to be a doubly hydrogen bound six-membered ring with non-optimal hydrogen bond angles. We estimate the gas-phase constant of dimer formation, K , to be 0.4 (standard pressure of 1 bar) using the experimental integrated absorbance and a theoretically determined oscillator strength of the OH b -stretching band.

Objective(s): To investigate dysphagia and quality of life (QoL) outcomes 3 years after treatment of oropharyngeal cancer with either primary trans oral robotic surgery (TORS) or radiotherapy (RT)., Methods: A prospective cohort study conducted at the Copenhagen University Hospital. Endpoints were objective swallowing function, examined using fiberoptic endoscopic evaluation of swallowing (FEES) and video fluoroscopy (VF). QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30), Head & Neck Module (EORTC QLQ-HN35), and MD Anderson Dysphagia Inventory (MDADI). A comparison was made between 1-, and 3-year results., Results: Forty-four patients were included prior to treatment, 31 treated with TORS and 13 with RT. One-year results for this cohort have previously been published (https://doi.org/10.1080/00016489.2020.1836395). Significant improvement on FEES in retention at the piriform sinus was noted in both groups. Patients treated with TORS had improved safety scores as well as dynamic imaging grade of swallowing toxicity (DIGEST) and efficiency scores, whereas patients treated with RT only had improvements in the latter two. Improvement in QoL scores was only noted for patients treated with TORS in composite MDADI scores., Conclusion: We found significant improvements in objective swallowing function from one to 3 years after treatment, particularly in patients treated with TORS. However, these improvements were not reflected as clinically meaningful improvements in QoL., Level of Evidence: 3, cohort follow-up study Laryngoscope, 133:1893-1898, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Patients with neuroendocrine neoplasms (NEN) engage in lifelong follow-up with frequent somatostatin receptor PET, e.g. [ 64 Cu]Cu-DOTATATE PET, and continued measures to reduce radiation exposures should be in pursued in accordance with the as-low-as-reasonably-achievable (ALARA) principle. We therefore aimed to determine the lowest achievable [ 64 Cu]Cu-DOTATATE dose while maintaining image quality and lesion detection rate., Procedures: We included scans from 38 patients with NEN referred to routine [ 64 Cu]Cu-DOTATATE PET/CT. Using reconstruction of under-sampled PET list-mode data, we simulated [ 64 Cu]Cu-DOTATATE activity dose-reduced PET equivalents with median [range] 142 MBq [127;157], 95 MBq [85;105], and 48 MBq [42;52], corresponding to 75% (PET 75% ), 50% (PET 50% ), and 25% (PET 25% ) of the full-dose 191 MBq [169;209] (PET 100% ). Three blinded readers independently assessed image quality (scores 1-5), lesion confidence (scores 0-2), and counted lesions grouped by organs and regions. Number of lesions, proportions of patients with diagnostic image quality (reader-median image quality ≥ 4), diagnostic lesion confidence (reader-median lesion confidence ≥ 1), and per-patient sensitivities and specificities for organ-specific disease on PET 75-25% were compared with PET 100% ., Results: The median [ 64 Cu]Cu-DOTATATE activity dose could be reduced from 191 to 142 MBq without decline in diagnostic image quality (P = 0.62), diagnostic lesion confidence (P = 1.0), or number of lesions detected in major organs or regions (P = 0.19-0.71). Sensitivity and specificity for detection of liver disease were 100% (26/26 patients) and 100% (12/12), respectively, for both PET 75% and PET 50% . Overall sensitivity for detection of NEN was 100% (26/26) for both PET 75% and PET 50% , and overall specificities were 92% (11/12) and 100% (12/12) for PET 75 and PET 50 , respectively. Following dose-blinded post hoc review, the PET 75% specificity was adjusted to 100% (12/12)., Conclusions: The [ 64 Cu]Cu-DOTATATE activity dose can be reduced from 191 MBq to at least 142 MBq without losing image quality or lesion detection ability and further reduced to 95 MBq without loss of clinically relevant information., (© 2022. World Molecular Imaging Society.)

Biodiversity monitoring at the community scale is a critical element of assessing and studying species distributions, ecology, diversity, and movements, and it is key to understanding and tracking environmental and anthropogenic effects on natural ecosystems. 1-4 Vertebrates in terrestrial ecosystems are experiencing extinctions and declines in both population numbers and sizes due to increasing threats from human activities and environmental change. 5-8 Terrestrial vertebrate monitoring using existing methods is generally costly and laborious, and although environmental DNA (eDNA) is becoming the tool of choice to assess biodiversity, few sample types effectively capture terrestrial vertebrate diversity. We hypothesized that eDNA captured from air could allow straightforward collection and characterization of terrestrial vertebrate communities. We filtered air at three localities in the Copenhagen Zoo: a stable, outside between the outdoor enclosures, and in the Rainforest House. Through metabarcoding of airborne eDNA, we detected 49 vertebrate species spanning 26 orders and 37 families: 30 mammal, 13 bird, 4 fish, 1 amphibian, and 1 reptile species. These spanned animals kept at the zoo, species occurring in the zoo surroundings, and species used as feed in the zoo. The detected species comprise a range of taxonomic orders and families, sizes, behaviors, and abundances. We found shorter distance to the air sampling device and higher animal biomass to increase the probability of detection. We hereby show that airborne eDNA can offer a fundamentally new way of studying and monitoring terrestrial communities., Competing Interests: Declaration of interests M.S.J. is Chief Science Officer at AirLabs, the company that designed and built the 3D-printed housings for the particle samplers used in this study. The blueprints of these housings are freely available and provided in Figure S1. All other air sampling equipment, i.e., the water vacuum, blower fans used for the 24 V and 5 V particle samplers, and batteries, are available in commercial companies not related to Airlabs. Thereby, the current study is not of direct commercial value to Airlabs. The remaining authors declare that they have no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The infrared (IR) spectrum of tert-butyl hydroperoxide (TBHP) in the region of the first OH-stretching overtone has been observed under jet-cooled and thermal (300 K, 3 Torr) conditions at ∼7017 cm -1 . The jet-cooled spectrum is recorded by IR multiphoton excitation with UV laser-induced fluorescence detection of OH radical products, while direct IR absorption is utilized under thermal conditions. Prior spectroscopic studies of TBHP and other hydroperoxides have shown that the OH-stretch and XOOH (X = H or C) torsion vibrations are strongly coupled, resulting in a double well potential associated with the torsional motion about the OO bond that is different for each of the OH-stretching vibrational states. A low barrier between the wells on the torsional potential results in tunneling split energy levels, which leads to four distinct transitions associated with excitation of the coupled OH-stretch-torsion states. In order to interpret the experimental results, two theoretical models are used that include the OH-stretch-torsion coupling in TBHP. Both methods are utilized to compute the vibrational transitions associated with the coupled OH-stretch-torsion states of TBHP, revealing the underlying transitions that compose the experimentally observed features. A comparison between theory and experiment illustrates the necessity for treatments that include OH-stretch and COOH torsion in order to unravel the spectral features observed in the first OH-stretching overtone region of TBHP.

The vibrational spectra of gas phase tert-butyl hydroperoxide have been recorded in the OH-stretching fundamental and overtone regions (Δv OH = 1-5) at room temperature using conventional Fourier transform infrared (Δv OH = 1-3) and cavity ring-down (Δv OH = 4-5) spectroscopy. In hydroperoxides, the OH-stretching and COOH torsion vibrations are strongly coupled. The double-well nature of the COOH torsion potential leads to tunneling splitting of the energy levels and, combined with the low frequency of the torsional vibration, results in spectra in the OH-stretching regions with multiple vibrational transitions. In each of the OH-stretching regions, both an OH-stretching and a stretch-torsion combination feature are observed, and we show direct evidence for the tunneling splitting in the OH-stretching fundamental region. We have developed two complementary vibrational models to describe the spectra of the OH-stretching regions, a reaction path model and a reduced dimensional local mode model, both of which describe the features of the vibrational spectra well. We also explore the torsional dependence of the OH-stretching transition dipole moment and show that a Franck-Condon treatment fails to capture the intensity in the region of the stretch-torsion combination features. The accuracy of the Franck-Condon treatment of these features improves with increasing Δv OH .

Introduction: Ventilation and perfusion single-photon emission computed tomography combined with computed tomography (SPECT/CT) is a powerful tool to assess the state of the lungs in chronic obstructive pulmonary disease (COPD). 81mKrypton is a gaseous ventilation tracer and distributes similarly to air, but is not widely available and relatively expensive. 99mTc-Technegas is cheaper and has wider availability, but is an aerosol, which may deposit in hot spots as the severity of COPD increases. In this study, 81mKrypton and 99mTc-Technegas were compared quantitatively in patients with severe COPD., Methods: The penetration ratio, the heterogeneity index (with and without band filtering for relevant clinical sizes) and hot spot appearance were assessed in eleven patients with severe COPD that underwent simultaneous dual-isotope ventilation SPECT/CT with both 99mTc-Technegas and 81mKrypton., Results: Significant differences were found in the penetration ratio for the medium energy general purpose (MEGP) collimators, but not for the low energy general purpose (LEGP) collimators. The difference in the overall and the band filtered heterogeneity index was significant in most cases. All patients suffered from 99mTc-Technegas hot spots in at least one lung. Comparison of MEGP 81mKrypton and LEGP Technegas scans revealed similar results as the comparison for the MEGP collimators., Conclusion: Caution should be taken when replacing 81mKrypton with 99mTc-Technegas as a ventilation tracer in patients with severe COPD as there are significant differences in the distribution of the tracers over the lungs. Furthermore, this patient group is prone to 99mTc-Technegas hot spots and might need additional scanning if hot spots severely hamper image interpretation., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Functional and QoL outcomes were compared longitudinally in a cohort of patients treated for oropharyngeal squamous cell carcinoma (OPSCC) with primary transoral robotic surgery (TORS) or radiotherapy (RT). Forty-four patients undergoing primary TORS (n = 31) or RT (n = 13) for any stage OPSCC were included. Only low-stage disease was treated with TORS. Functional outcomes were: salivary flow rate, image-based swallowing function, and a self-reported 10-point scale comparing current swallowing function to baseline (CvB scale). QoL was assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30), Head & Neck Module (EORTC QLQ-HN35), and MD Anderson Dysphagia Inventory (MDADI). Shoulder impairment was assessed with Neck Dissection Impairment Index (NDII) and Oxford Shoulder Score (OSS). In the RT group, salivary flow rates had significantly declined at 12-month follow-up, with the biggest declines in QoL subscale scores recorded in the RT group for dry mouth and sticky saliva. Swallowing function on imaging studies was overall good, with no severe dysphagia within 1 year although, both treatment groups showed significant deterioration relative to baseline at the 12-month follow-up with increased DIGEST scores and pharyngeal retention. Shoulder impairment was rare at 1 year in both groups. A comprehensive examination of this cohort treated for OPSCC showed overall good functional and QoL outcomes 1 year after treatment. However, persistent impairment was seen in both groups with regards to swallowing function. In the TORS group, at 12-months follow-up, the QoL questionnaires showed worse scores in only one subscale (sticky saliva)., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Right ventricular dysfunction (RVD) is an important prognostic factor of 30-day mortality in patients with acute pulmonary embolism (PE). The aim of our study was to evaluate whether non-electrocardiogram (ECG)-gated cardiovascular parameters attained during computed tomography pulmonary angiography (CTPA) could predict RVD in patients suspected of PE using ECG-gated cardiac CT angiography as reference., Methods: Consecutive patients suspected of PE were referred to a ventilation/perfusion single-photon emission tomography (V/Q-SPECT) as first-line imaging procedure. Patients had a V/Q-SPECT/CT, a CTPA and an ECG-gated cardiac CT angiography performed the same day., Results: A total of 71 patients were available for analysis. Seventeen patients (24%) had RVD. The non-ECG-gated dimensions of left and right ventricle and the major vessels were correlated with ECG-gated cardiac dimensions. The size of the pulmonary trunk could identify patients with RVD: AUC (0·67, 95% confidence intervals (CIs) 0·52-0·82) as seen in the ROC curve (P<0·05). With a cut-off value of the pulmonary trunk of 29 mm, the sensitivity and specificity were 70·6% and 55·5%, respectively. The positive predictive and negative predictive values for detection of RVD were 59·1% and 85·7%, respectively., Conclusion: In the present study, we demonstrated correlation between ECG-gated cardiac dimensions and non-ECG-gated cardiovascular parameters, however with only moderate diagnostic accuracies. We demonstrated that the dimension of the pulmonary trunk might be of value in detection of patients with RVD. We suggest further studies on the potential value of non-ECG-gated cardiac dimensions in patients suspected of PE., (© 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Introduction: The non-invasive prenatal test (NIPT) was introduced in the North Denmark Region in March 2013. NIPT is offered as an alternative to invasive tests if the combined first trimester risk of trisomy 21 (T21) is ≥ 1:300. The purpose of this study was to investigate the effect of NIPT implementation among high-risk pregnancies in a region with existing first-trimester combined screening for T21. The primary objective was to examine the effect on the invasive testing rate., Methods: This was a retrospective observational study including high-risk singleton pregnancies in the North Denmark Region. The women were included in two periods, i.e. before and after the implementation of NIPT, respectively. Group 1 (before NIPT): n = 253 and Group 2 (after NIPT): n = 302., Results: After NIPT implementation, the invasive testing rate fell from 70% to 48% (p < 0.01), and the number of high-risk women refusing further testing dropped from 26% to 3% (p < 0.01). NIPT successfully detected four cases of T21; however, two out of three sex-chromosomal abnormalities were false positives. No false negative NIPT results were revealed in this study., Conclusions: In the North Denmark Region, the implementation of NIPT in high-risk pregnancies significantly reduced the rate of invasive testing. However, the proportion of high-risk women who opted for prenatal tests increased as the majority of women who previously refused further testing now opted for the NIPT., Funding: none., Trial Registration: The study was approved by the Danish Data Protection Agency (No. 2015-104)., (Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Recent research supports the efficacy of various plasma biomarkers in diagnosing pulmonary embolism (PE) including E-selectin, MMP-9, MPO, sVCAM-1, sICAM-1, adiponectin, hs-CRP and tPAI-1., Objective: We hypothesized that these biomarkers, which are affected in both venous and arterial thromboembolic diseases, have a limited potential of diagnosing PE in patients with concomitant coronary atherosclerosis, as assessed from a low-dose CT scan of the thorax, compared to patients without atherosclerosis., Methods: Consecutive patients suspected of PE were referred. All patients had a ventilation/perfusion single photon emission tomography (V/Q-SPECT), low-dose pulmonary CT, pulmonary multidetector computer tomography angiography, blood samples and ECG-gated cardiac CT performed the same day., Results: A total of 69 patients were included, of which 28 (41%) had PE. In patients without coronary calcium, MMP-9 and tPAI-1 were significantly elevated (P<0·042 and P<0·049) in patients diagnosed with PE. From the receiver operating curves, we chose a cut-off value for MMP-9 at 164·4 ng l(-1) , which yielded sensitivity, specificity, positive and negative predictive values of 63%, 78%, 71% and 70%, respectively. With a chosen cut-off value for tPAI-1 at 56·3 ng l(-1) , the sensitivity, specificity, positive and negative predictive values were 88%, 89%, 88% and 89%, respectively. In patients with coronary calcium, none of the biomarkers could discriminate between PE and no PE., Conclusion: Plasma levels of tPAI-1 and MMP-9 are potentially useful in patients suspected of PE, however, not in the presence of the coronary atherosclerosis., (© 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Objective: Intensive care unit admission is associated with muscle wasting and impaired physical function. We investigated the effect of early transcutaneous electrical muscle stimulation on quadriceps muscle volume in patients with septic shock., Design: Randomized interventional study using a single-legged exercise design with the contralateral leg serving as a paired control., Setting: A mixed 18-bed intensive care unit at a tertiary care university hospital., Patients: Eight adult male intensive care unit patients with septic shock included within 72 hrs of diagnosis., Interventions: After randomization of the quadriceps muscles, transcutaneous electrical muscle stimulation was applied on the intervention side for 7 consecutive days and for 60 mins per day. All patients underwent computed tomographic scans of both thighs immediately before and after the 7-day treatment period. The quadriceps muscle was manually delineated on the computed tomography slices, and muscle volumes were calculated after three-dimensional reconstruction., Measurements and Main Results: Median age and Acute Physiology and Chronic Health Evaluation II score were 67 years (interquartile range, 64-72 years) and 25 (interquartile range, 20-29), respectively. During the 7-day study period, the volume of the quadriceps muscle on the control thigh decreased by 16% (4-21%, p=.03) corresponding to a rate of 2.3% per day. The volume of the stimulated muscle decreased by 20% (3-25%, p=.04) corresponding to a rate of 2.9% per day (p=.12 for the difference in decrease). There was no difference in muscle volume between the stimulated and nonstimulated thigh at baseline (p=.10) or at day 7 (p=.12). The charge delivered to the muscle tissue per training session (0.82 [0.66-1.18] coulomb) correlated with the maximum sequential organ failure assessment score., Conclusions: We observed a marked decrease in quadriceps volume within the first week of intensive care for septic shock. This loss of muscle mass was unaffected by transcutaneous electrical muscle stimulation applied for 60 mins per day for 7 days.

Background: The aim of this study was to predict right ventricular dysfunction (RVD) using plasma concentration of D-dimer, pro-atrial natriuretic peptide (pro-ANP), brain natriuretic peptide (BNP), endothelin-1 (ET-1) and cardiac troponin I (TNI) in patients with pulmonary embolism (PE)., Methods: Patients suspected of PE had a ventilation/perfusion-single-photon emission-tomography (V/Q-SPECT), pulmonary multidetector computer tomography (MDCT) angiography, blood samples and ECG-gated cardiac CT performed the same day., Results: Pro-ANP, BNP and D-dimer are associated with significantly elevated levels in PE patients with RVD. ROC curves demonstrated that D-dimer, pro-ANP and BNP were accurate for detection of RVD., Conclusion: Because measurements of cardiac biomarkers are inexpensive and easily obtained they may prove useful in the clinical diagnosis of RVD. However because of the small sample size, the results need to be confirmed in larger studies., (© 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

The aim of our study was to perform a prospective study that compared the diagnostic ability of V/Q single photon emission computer tomography (V/Q-SPECT), V/Q-SPECT combined with low-dose computed tomography (CT) and pulmonary multidetector computed tomography(MDCT)-angiography in patients suspected of having pulmonary embolism (PE) using a dedicated combined SPECT/MDCT-scanner. V/Q-SPECT in combination with low-dose CT had a sensitivity of 97% and a specificity of 100%. MDCT angiography had a sensitivity of 68% and a specificity of 100%. We conclude that V/Q-SPECT in combination with low-dose CT without contrast has an excellent diagnostic performance and should be considered the first-line imaging technique in the work-up of PE in most cases.

Purpose: Planar ventilation/perfusion (V/Q) scintigraphy is currently the standard method for the diagnosis of pulmonary embolism (PE) in most nuclear medicine centers. However, recent studies have shown a superior sensitivity and specificity when applying V/Q single photon emission computed tomography (SPECT) in diagnosing PE. This study evaluated the diagnostic performance of three-dimensional V/Q SPECT in comparison with planar V/Q scintigraphy., Materials and Methods: Consecutive patients suspected of acute PE from June 2006 to February 2008 were referred to the Department of Nuclear Medicine at Frederiksberg Hospital, Denmark to a V/Q SPECT, as the first-line imaging procedure. Patients with positive D-dimer (>0.5 mg/l) or after clinical assessment with a Wells score of more than 2 were included and had a V/Q SPECT, low-dose CT, planar V/Q scintigraphy, and pulmonary multidetector computer tomography angiography performed the same day. Ventilation studies were performed using Kr. Patient follow-up was at least 6 months., Results: A total of 36 patient studies were available for analysis, of which 11 (31%) had PE. V/Q SPECT had a sensitivity of 100% and a specificity of 87%. Planar V/Q scintigraphy had a sensitivity of 64% and a specificity of 72%., Conclusion: We conclude that V/Q SPECT has a superior diagnostic performance compared with planar V/Q scintigraphy and should be preferred when diagnosing PE.

Unlabelled: The diagnosis of pulmonary embolism (PE) is usually established by a combination of clinical assessment, D-dimer testing, and imaging with either pulmonary ventilation-perfusion (V/Q) scintigraphy or pulmonary multidetector CT (MDCT) angiography. Both V/Q SPECT and MDCT angiography seem to have high diagnostic accuracy. However, only limited data directly comparing these 2 modalities are available. Hybrid gamma-camera/MDCT systems have been introduced and allow simultaneous 3-dimensional lung V/Q SPECT and MDCT angiography, suitable for diagnosing PE. The aim of our study was to compare, in a prospective design, the diagnostic ability of V/Q SPECT, V/Q SPECT combined with low-dose CT, and pulmonary MDCT angiography obtained simultaneously using a combined SPECT/MDCT scanner in patients suspected of having PE., Methods: Consecutive patients from June 2006 to February 2008 suspected of having acute PE were referred to the Department of Nuclear Medicine at Rigshospitalet or Frederiksberg Hospital, Denmark, for V/Q SPECT as a first-line imaging procedure. The number of eligible patients was 196. Patients with positive D-dimer results (>0.5 mmol/mL) or a clinical assessment with a Wells score greater than 2 were included and underwent V/Q SPECT, low-dose CT, and pulmonary MDCT angiography in a single session. Patient follow-up was 6 mo., Results: A total of 81 simultaneous studies were available for analysis, of which 38% were from patients with PE. V/Q SPECT had a sensitivity of 97% and a specificity of 88%. When low-dose CT was added, the sensitivity was still 97% and the specificity increased to 100%. Perfusion SPECT with low-dose CT had a sensitivity of 93% and a specificity of 51%. MDCT angiography alone had a sensitivity of 68% and a specificity of 100%., Conclusion: We conclude that V/Q SPECT in combination with low-dose CT without contrast enhancement has an excellent diagnostic performance and should therefore probably be considered first-line imaging in the work-up of PE in most cases.

Background: The objectives of this study were to assess the frequency and severity of pulmonary hypertension (PH) and the effect of sildenafil treatment in patients with recalcitrant pulmonary sarcoidosis., Methods: This investigation was a single-center, retrospective study of all patients (n = 25) with end-stage pulmonary sarcoidosis referred for lung transplantation. Hemodynamic measurements were evaluated by right-side cardiac catheterization in 24 of 25 patients. Sildenafil treatment for patients with sarcoidosis-associated PH was introduced in April 2004., Results: The study group of 24 patients (16 men, 8 women) had a median age of 45 (range 35 to 58) years, and duration of sarcoidosis of 11 (range 2 to 38) years. Mean pulmonary arterial pressure (MPAP) was median 36 (range 18 to 73) mm Hg. PH (MPAP >25 mm Hg) was present in 19 of 24 patients (79%). Sildenafil was administered to 12 of 13 patients at a dose of 150 (range 75 to 225) mg/day for 4 (range 1 to 12) months. Sildenafil treatment was associated with reductions in MPAP of -8 mm Hg (CI -1 to -15 mm Hg), and PVR -4.9 Wood units (CI -7.2 to -2.6 Wood units). Cardiac output and cardiac index also increased during treatment (p = 0.01, respectively). There were no consistent changes in 6-minute walk distance., Conclusions: Patients with severe pulmonary sarcoidosis have a high prevalence of PH. Sildenafil treatment was associated with significant improvements in hemodynamic parameters.

A case of gastroduodenal intussusception caused by a duodenal lipoma is presented. The condition was characterized by severe upper gastrointestinal retention, epigastric pain and weight loss. The mass was diagnosed by CT scan. The diagnosis was confirmed by operation. The patient was treated successfully by manually reducing the intussusception and resection of the lipoma. Histopathology confirmed the mass to be a pedunculated submucosal lipoma. The patient had an uneventful recovery.

Transgenic mice, expressing fluorescent proteins in neurons and glia, provide new opportunities for real-time microscopic monitoring of degenerative and regenerative structural changes. We have previously validated and compared a number of quantifiable markers for neuronal damage and cell death in organotypic brain slice cultures, such as cellular uptake of propidium iodide (PI), loss of microtubule-associated protein 2 (MAP2), Fluoro-Jade (FJ) cell staining, and the release of cytosolic lactate dehydrogenase (LDH). An important supplement to these markers would be data on corresponding morphological changes, as well as the opportunity to monitor reversible changes or long-term effects in the event of minor damage. As a first step, we present: a) the developmental expression in organotypic hippocampal brain slice cultures of transgenic fluorescent proteins, useful for the visualisation of neuronal subpopulations and astroglial cells; and b) examples of excitotoxic, glutamate receptor-induced degeneration of hippocampal CA1 pyramidal cells, with corresponding astroglial reactivity in such cultures. The slice cultures were set up according to standard techniques, by using one-week old pups from four transgenic mouse strains which express fluorescent proteins in their neurons and/or astroglial cells. From the time of explantation, and subsequently for up to nine weeks in culture, the transgenic neuronal fluorescence displayed the expected characteristics of a developmental, in vivo-like increase, including both the number and localisation of cells, as well as the intensity of fluorescence. At that stage and later, the transgenic fluorescence clearly permitted the visualisation of cell bodies, larger and smaller dendritic branches, spines and axons. In separate experiments, with a 24-hour exposure of matured sliced cultures to 100 microM of the glutamate agonist, N-methyl-D-aspartate (NMDA), we observed, by time-lapse recording, a gradual, but rapid loss of fluorescent CA1 pyramidal cells, accompanied by astrogliosis of transgene fluorescent astroglial cells. Based on these results, we consider that organotypic brain slice cultures from transgenic mice, with fluorescent neurons and glia, combined with detailed visualisation by time-lapse fluorescence microscopy, have great potential for investigating both major irreversible and minor reversible structural changes in neurons and glia, induced by neurotoxins and other neurodegenerative compounds and conditions.

The objectives of this study were (1) to determine how cerebrospinal fluid (CSF) neurofilament heavy chain (NfH(SM134) and NfH(SM135)) levels relate to clinical outcome in optic neuritis (ON) and multiple sclerosis (MS) relapse patients treated with high dose oral methylprednisolone; and (2) to correlate neurofilament and myelin basic protein (MBP) concentrations, particularly as the latter was previously associated with clinical disability. Fifty subjects participated in two double-blind, randomized, placebo-controlled clinical trials. Eight/18 patients in the ON trial and 15/32 subjects in the MS attack trial were treated with oral methylprednisolone. In the MS attack trial group, CSF NfH(SM134) and NfH(SM135) measured at week 3 and deltaCSF NfH(SMI34) levels from baseline to week 3 were predictive of clinical outcome at week 8 and 52. In the ON group, no such association was seen. When both groups were combined, baseline CSF NfH(SHM134) and NfH(SM135) correlated positively with baseline enhancing lesion volume (ELV) (r(s) =0.50, P <0.01 and rS =0.53, P <0.01, respectively). Levels of NfH(SM135) at baseline and week 3 also strongly correlated with the MBP concentration. This study supports the view that acute inflammation in ON and MS results in axonal pathology and that the latter has a role in determining functional impairment.

The role of nitric oxide (NO) in multiple sclerosis (MS) is not clear. We found increased cerebrospinal fluid concentrations of the NO degradation products nitrate (NO(x)) in clinically definite MS but not in clinically isolated syndromes. High CSF concentrations of NO(x) correlated with long attack duration. Patients carrying the truncated CC chemokine receptor allele CCR5 Delta32 had lower serum concentration of NO(x) at later attack stages. NO(x) concentrations did not change after methylprednisolone treatment but high concentrations were associated with more pronounced treatment responses. These findings suggest an association of high CSF levels of NO(x) with more severe disease activity in relapsing-remitting MS.

Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials. Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls. The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9 and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation.

Introduction: Magnetic resonance imaging (MRI) lesion load is widely used in the clinical evaluation of patients with multiple sclerosis (MS), but little is known about the associated changes in cortical activation. For this purpose, we studied the association between the corticocerebral metabolic rate of glucose (CMRglc) and the MRI T2-weighted total lesion area (TLA). In addition, we investigated the correlation between cognitive and neurological disability and CMRglc., Methods: Twenty-three patients with clinically definite MS underwent measurements of the CMRglc, TLA, motor-evoked potentials (MEP), and cognitive and neurological disability. CMRglc was calculated with positron emission tomography (PET) and 18-F-deoxyglucose (FDG) and compared to that of nine healthy controls., Results: A reduction in CMRglc (p < 0.01) was found in cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (rho = -0.66; p = 0.001), and rCMRglc correlated with the regional lesion load in all cerebral lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability were also correlated (rho = 0.58; p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance, as well as the TLA. There was no correlation between CMRglc and neurological disability (expanded disability status scale [EDSS]) or MEP., Conclusion: Global and regional cortical CMRglc is significantly reduced in patients with MS compared to healthy controls. The reductions in CMRglc furthermore correlate with the TLA, as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on corticocerebral neural function.

We studied intrathecal IgG synthesis and autoantibody-secreting cells in 148 patients with possible onset symptoms of MS (POSMS) or clinically definite MS (CDMS). In POSMS intrathecal synthesis of IgG oligoclonal bands and abnormalities on T2-weighted magnetic resonance imaging were associated but the former were more prevalent. The cerebrospinal fluid (CSF) leukocyte count and the number of anti-protelipid protein antibody-secreting cells in cerebrospinal fluid (CSF) correlated with disease activity in POSMS. Intrathecal IgG synthesis levels and the number of anti-myelin basic protein antibody-secreting cells in CSF correlated with disease activity in CDMS. Our results support recent reports of pathogenetic heterogeneity and a pathogenetic role of the antibody response in MS.

Objective: To study the association between the cortical cerebral metabolic rate of glucose (CMRglc), MRI T2-weighted total lesion area (TLA), cognitive dysfunction, and neurologic disability in MS., Background: MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in cortical activation., Methods: Twenty-three patients with clinically definite MS underwent measurements of CMRglc, TLA, motor evoked potentials (MEPs), and cognitive and neurologic disability. CMRglc was calculated using PET and 18-F-deoxyglucose and compared with nine normal control subjects., Results: Reductions in CMRglc (p < 0.01) were found in the cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = -0.66, p = 0.001), and rCMRglc correlated with regional lesion load in all cerebral lobes (p < or = 0.05). Global cortical CMRglc and cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance as well as TLA. There was no correlation between CMRglc and neurologic disability (Expanded Disability Status Scale) or MEP., Conclusion: Global and regional cortical CMRglc is reduced significantly in MS patients compared with normal control subjects. Furthermore, the CMRglc reductions correlate with TLA as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on cortical cerebral neural function.

Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5 delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS.

Objective: To study the time-related changes in cerebral metabolic rate of glucose (CMRglc) in MS patients and to correlate these with changes in MRI lesion load and disability., Background: Measurements of MRI lesion load and neurologic disability are used widely to monitor disease progression in longitudinal studies of MS patients, but little is known about the associated changes in cerebral neural function., Methods: The authors studied 10 patients with clinically definite MS who underwent serial measurements of CMRglc, MRI T2-weighted total lesion area (TLA), and clinical evaluation of disability (Expanded Disability Status Scale [EDSS]) over a period of approximately 2 years (three examinations). CMRglc was calculated using PET and 18-fluorodeoxyglucose (FDG)., Results: The global cortical CMRglc decreased with time (p<0.001) and the most pronounced reductions of CMRglc were detected in frontal and parietal cortical areas. There was a statistically significant increase of disability (p<0.01) and TLA (p<0.05) measurements during the study, but changes in CMRglc were not correlated to changes in TLA and EDSS., Conclusions: Global cortical cerebral metabolism in MS is decreased significantly during a 2-year observation period, suggesting a deterioration of cortical activity with disease progression. The time-related changes of cortical CMRglc are statistically stronger than changes in TLA measurements and neurologic disability, and might be a useful secondary measure of treatment efficacy.

We wanted to assess whether intravenous immunoglobulin G (IVIG) decreases disease activity on MRI in relapsing MS. Previous trials of IVIG in relapsing-remitting MS demonstrated a reduction of acute relapses, but these studies did not include MRI. We treated 26 patients in a randomized, double-blind, crossover study of IVIG 1 g/kg daily or placebo on 2 consecutive days every month during two 6-month treatment periods. The primary end point was the number of gadolinium-enhancing lesions on monthly serial MRI. Secondary efficacy variables were the occurrence of exacerbations, clinical neurologic ratings, total MS lesion load on T2-weighted MRI, and multimodal evoked potentials. Eighteen patients completed the entire trial; eight patients did not. Twenty-one patients completed the first treatment period and at least two MRI examinations in the second treatment period and were included in the intention-to-treat analysis. On serial MRI, we observed fewer enhancing lesions per patient per scan during IVIG treatment (median, 0.4; range, 0 to 9.3) than during placebo treatment (median, 1.3; range, 0.2 to 25.7; p = 0.03). During IVIG treatment, 15 patients were exacerbation free compared with only 7 on placebo (p = 0.02). The total number of exacerbations in the IVIG period was 11 and in the placebo period, 19 (not significant). None of the remaining secondary efficacy measures were significantly different between the two treatment periods. The number of adverse events, in particular eczema, was significantly higher during IVIG therapy than during placebo treatment. These results suggest that IVIG treatment is beneficial to patients with relapsing MS.

Acute mental disorder in early Multiple Sclerosis (MS) is rare and little is known about the structural and metabolic changes in this relation. We present an MS patient with discrete motor and sensory deficits, who developed severe behavioral changes over a period of nine months during the initial course of the disease. The cerebral metabolic rate of glucose (CMRglc) was measured using positron emission tomography (PET), and the patient underwent MRI as well as a comprehensive battery of neuropsychological tests. Significantly reduced values of CMRglc were found bilaterally in the frontal and temporal cortex, the putamen, the thalamus and the hippocampus. The MRI revealed progression of MS lesions in the frontal lobes during the development of mental symptoms. Neuropsychological examination showed wide spread cognitive dysfunction, and a pronounced frontal lobe syndrome. The study demonstrates the remote metabolic effects of lesions affecting subcortical neural connections in an MS patient with severe cognitive dysfunction.

Several epidemiological studies of workers occupationally exposed to white spirit show that neuropsychiatric disorders are a frequent cause of early disability pension in this population compared with non-exposed controls. In the rat, we have demonstrated that exposure to different kinds of white spirit induces changes in neurotransmitter concentrations, indices of oxidative stress, and electrophysiological parameters. Others have confirmed that acute behavioural effects can be induced by short-term high-level exposure. With NMR spectroscopy technique it is possible to study neurochemical parameters in vivo, and to examine the same subjects repeatedly over time. NMR spectroscopy was used to study the effects of organic solvents in rats. Rats were exposed to 0, 400 ppm, or 800 ppm of aromatic white spirit 6 hr/day, 7 days/week for 3 weeks. During the first week, the rats showed signs of irritation of mucous membranes, and appeared to be sedated. Both types of effect gradually diminished during the second week. The rats were examined by single volume of interest (VOI) NMR spectroscopy. N-acetylaspartate, creatinine and phosphocreatinine, and choline containing compounds were measured in the hippocampus and surrounding regions. The concentration of N-acetylaspartate for the three groups was found to be in the range of 8.2-8.5 mM with a standard deviation of 0.6-0.9. There was no difference between the three groups. In a previous study no change in the number of astrocytes in hippocampus was found following exposure to white spirit for six months. Since N-acetylaspartate is thought to be a marker for neurons, the results of these two studies indicate that white spirit does not produce a marked neuronal loss. However, it was not possible to show effect of trimethyltin. In this study trimethyltin was used as a "positive control'. The NMR technique can be applied to the rat, and it is possible to obtain reasonable signal-to-noise ratios.

We enrolled 11 patients with secondary progressive MS in a randomized single-masked cross-over study of plasma exchange (PE) in combination with azathioprine 2 mg/kg. PE was performed once a week for 4 weeks and thereafter every second week for 20 weeks (14 treatments). Eight patients completed the whole trial, and three patients discontinued the trial, two during the run-in period of azathioprine treatment and one at the introduction of PE. The primary efficacy variables were the number of gadolinium-enhancing lesions and the occurrence of new enhancing lesions on serial MRI performed every 3 weeks during the PE and the control period. Secondary efficacy variables were the total MS lesion load on T2-weighted MRI, multimodal evoked potentials, and clinical neurologic ratings. No significant differences were found regarding the number of enhancing lesions or occurrence of new enhancing lesions in the two periods. Although the total MS lesion load on MRI was significantly lower (p < 0.02) and central motor conduction times decreased significantly (p < 0.05) during PE, this small study did not provide sufficient evidence for a significant beneficial effect of PE or encourage a subsequent large randomized parallel group study.

It is generally believed that a backrest facilitates lumbar lordosis. To test this, the spontaneously adopted postures of 12 healthy subjects were measured by a statometric method during 2-h sitting periods on three types of chairs in a stratified sequence. The only difference between the three workstations regarded backrest: 'A' had no backrest; 'B' had a vertical lumbar backrest; and 'C' had an anteriorly curved backrest. In general, the most lordotic postures were assumed with backrest C, whereas backrest B rather facilitated kyphosis as compared with sitting without a backrest. However, when specifically considering passive sitting, i.e. reading, both types of backrest facilitated kyphosis. Moreover, spinal shrinkage was evaluated by measuring exact height before and after each 2-h sitting period. This was done to assess spinal load. From this perspective, backrest C induced the greatest load on the spine. In conclusion, the traditional conception that a backrest facilitates lordosis is apparently not true. It seems rather that backrests actually facilitate the opportunity for the user to stabilize their lumbar spines by providing their lower backs with support, resulting in relative kyphotic increases. The practical ergonomic applications from this study are unclear. However, traditional concepts in backrest ergonomy should be re-considered.

In a randomized, observer-blind trial, 150 men and women, aged 21-64 years, with chronic/subchronic low-back pain, followed one of these three treatment regimens: 1) intensive, dynamic back-muscle exercises; 2) conventional physiotherapy, including isometric exercises for the trunk and leg muscles; and 3) placebo-control treatment involving semihot packs and light traction. Eight treatment sessions were given during the course of 4 weeks, each session lasting 1 hour. The short-term effect was evaluated at the end of the treatment period and 1 month later, and the long-term effect at 6 and 12 months. The evaluations included recording of changes in pain level and assessment of overall treatment effect, which were indicated on visual interval scales. Subgroups of patients could be identified according to their treatment responses: physiotherapy was the superior treatment for the male participants, whereas the intensive back exercises appeared to be most efficient for the female participants. Patients with moderate or hard physical occupations tended toward a better response with physiotherapy, whereas intensive back exercises seemed most effective for those with sedentary/light job functions.

Movement patterns in 10 healthy subjects sitting on an office chair with either a tiltable seat, a 5° forwards, or 5° backwards inclining seat were investigated; also the effect of a slanted tabletop desk were studied. The subjects were performing reading and writing tasks. They were investigated twice for one hour on each of two days. Movement pattern was evaluated using counting of movements from videotape recordings of the subjects. Also the subjects' impressions of comfort in the various settings were investigated using a five-point rating scale. The main conclusion is that there exist no significant differences in either the number of movements or in comfort evaluation between the four settings investigated., (Copyright © 1992. Published by Elsevier Ltd.)

The signal transduction system of the vasopressin receptor in cerebral microvessels is not known but appears not to be adenylate cyclase/cyclic AMP. We determined the effect of arginine vasopressin (AVP) on the intracellular free calcium concentration [Ca2+]i in endothelial cells of isolated hippocampal microvessels of rats, using the fura-2 fluorescence technique. AVP administration caused a rapid and transient rise of cytosolic free calcium which was absent after extracellular calcium was removed, and could be blocked with the vasopressin V1 receptor antagonist, d(CH2)5 Tyr(Me)AVP. The vasopressin V2 receptor agonist, 1-deamino-8,D-AVP, on the contrary, failed to affect the intracellular free calcium level, and was unable to inhibit the AVP-induced rise of [Ca2+]i in the preparation. Our results, therefore, demonstrate the presence of a calcium-signalling, i.e. V1 vasopressin receptor at the blood-brain barrier in the hippocampus of the rat.

In clinical trials, the methods for achieving an event or near-even distribution of important patient parameters have been tedious and often disappointing. In this paper, a computer program for minimizing differences between experimental groups with respect to such important parameters, based on a method described by Traves (Clin. Pharmacol. Ther. London 15, 443, 1974) is presented. The program is available from the author.

A quantitative autoradiographic study was made on the binding of the phosphatidylinositol system ligand [3H]inositol(1,4,5)-trisphosphate (IP3) to forebrain sections from rats decapitated various times after 10 min of forebrain ischemia. To investigate the effect of a deafferentation of the hippocampal CA1, kainic acid-induced CA3-lesioned rats with or without 10 min of cerebral ischemia, were also included. The highest binding was found in the hippocampal CA1. Ten min of cerebral ischemia did not change the binding significantly. Between 5 min and 1 h of recirculation there was a 25-35% binding decline in all regions. In the CA1, where the pyramidal cells became necrotic 6 days after ischemia, there was a further decline to 16% of control. In the cortex, where there is no necrosis in this model, binding did not return to control values until day 14. Four days after a selective CA3 lesion with kainic acid, there was a significant 25% decline in the cortex, dentate gyrus and CA1, whereas in the necrotic CA3 binding declined to 54% of control. Ten min of ischemia did not alter this binding significantly. This decrease in calcium mobilizing intracellular receptors after ischemia and seizures could be due to increased membrane degradation, or to a more specific down-regulation following increased intracellular concentration of calcium and IP3.

We have investigated the GABAergic system in rat hippocampus at 1 hour and up to 21 days following 20 min of global cerebral ischemia. Distribution of 3H-GABA (in excess of unlabeled baclofen) and 3H-Ro-15-1788 (benzodiazepine antagonist) binding sites in hippocampus was studied utilizing quantitative autoradiography. The 3H-GABA binding was unchanged (p greater than 0.01) after ischemia, whereas the 3H-Ro-15-1788 binding decreased significantly (p less than 0.01) in all hippocampal subfields 1-21 days after ischemia. Using microdialysis in CA1, we found that K(+)-stimulated GABA release at 1 hour and 1 day after ischemia was unchanged (p greater than 0.01) in comparison to preischemic controls. Electrophysiological recordings were made from CA1 of hippocampal slices prepared from rats sacrificed 1 hour, 1 day and 2 days after ischemia. Field potentials evoked by stimulation of the Schaffer collaterals showed no differences (p greater than 0.01) from those taken from controls. Postischemic intracellular recordings from the CA1 pyramidal cells showed that fast and slow inhibitory postsynaptic potentials were readily evoked on orthodromic stimulation. Together with our previous morphological results, demonstrating survival of hippocampal interneurons following ischemia, we conclude that hippocampal GABAergic interneurons preserve their inhibitory potential in the period preceding delayed CA1 pyramidal cell death. This conclusion taken together with the observation that postischemic 3H-Ro-15-1788 binding in hippocampus declined, suggest that benzodiazepines (by increasing the receptor affinity), GABA analogs, and GABA uptake inhibitors may be useful in the treatment of ischemic CA1 pyramidal cell death in the rat.

Cerebral microvessels were isolated from rat hippocampus with a modified, mild collagenase digestion and loaded with the calcium fluoroprobe, Fura-2. Using a fluorescence microscope with quartz optics and an image analyser, it was possible to measure the intracellular concentration of free calcium ions [Ca2+]i in single microvessels for the first time. A resting level of (90 +/- 28) nmol/l (+/- SD, n = 24) was calculated which immediately rose after ionomycin application. The temporal resolution for [Ca2+]i of our set-up was 0.7 s. By image processing, sequences of digitized fluorescence images of single microvessels were colour-coded in terms of [Ca2+]i with a spatial resolution up to 1.5 microns (pixel size). Both the temporal and spatial resolution make our system suitable for investigation of calcium-mobilizing receptors of the blood-brain barrier.

Sitting postures on a knee-support (Balans®) chair and a tiltable chair were investigated with 12 healthy subjects during office work and simulated assembly work. After at least 3 weeks' adaptation to each chair, the subjects were investigated for 1 hour on each chair in stratified sequence. Postures were evaluated by means of a statometric method. Spinal load was further estimated by measuring stature shrinkage over each sitting period. Energy consumption was roughly assessed by pulse measurements. Finally, subjective acceptability was rated by a 5-point scale. Posture effects of the Balans® chair, taken in relation to the tiltable chair, were primarily a forward tilt of the pelvis and a change toward lumbar lordosis. Secondly, the trunk was vertical compared to the slightly backward-inclined position in the tiltable chair. The head was most vertical in the Balans® chair. No effect on spinal shrinkage or pulse was observed. The subjective rating seemed to favour the tiltable chair if used over longer periods. However, the Balans(®) chair may be a good alternative for some seated periods and special tasks., (Copyright © 1988. Published by Elsevier Ltd.)