Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease.

BACKGROUND: Chemerin is an adipokine that signals through the G protein-coupled receptor ChemR23 and is associated with inflammation, glucose homeostasis, lipid metabolism and renal function, all of which strongly influence cardiovascular risk. However, elevated chemerin provides a survival advantage in patients with chronic kidney disease (CKD), but how this relates to the cardiovascular phenotype is unknown. OBJECTIVES: The aim of the present study was to establish the association of chemerin with coronary calcification and to determine the effects of chemerin signalling, through ChemR23, in vascular smooth muscle cell (VSMC) calcification. METHODS: Plasma chemerin was measured in 113 patients with CKD and 50 healthy controls. All patients underwent computed tomography to determine coronary artery calcium (CAC) score. VSMCs were isolated from wild-type and ChemR23 knock-out mice and treated with chemerin. RESULTS: Multivariate analyses established creatinine, cholesterol, body mass index and tumour necrosis factor as significant confounders for circulating chemerin levels. Despite these positive associations with renal function, cardiometabolic risk factors and inflammation, chemerin was inversely associated with CAC both in an age- and sex-adjusted analysis and in a multivariate analysis adjusting for the aforementioned confounders. In addition, circulating chemerin levels were associated with the calcification inhibitors matrix gla protein (MGP) and fetuin-A. Finally, chemerin significantly reduced phosphate-induced calcification and increased MGP expression in VSMCs, whereas chemerin was devoid of these effects in VSMCs lacking ChemR23. CONCLUSION: In conclusion, these results suggest that chemerin signalling through ChemR23 in VSMCs protects against vascular calcification in CKD.

Texture analysis of computed tomography data using morphologic and metabolic delineation of esophageal cancer-relation to tumor type and neoadjuvant therapy response.

The prognostic values of image-based tumor texture analysis based on computed tomography (CT) and of limiting the segmented tumor volume to metabolically active regions using fludeoxyglucose-positron emission tomography (FDG-PET) were studied in 25 patients with esophageal adenocarcinoma and 11 patients with squamous cell carcinoma. The aims of this study are to describe their CT-image-based texture characteristics before and after neoadjuvant therapy and to evaluate whether limiting the examined tumor volume to metabolically active regions detected with FDG-PET image data would further improve their value. Textural parameters (homogeneity, energy, entropy, contrast, and correlation) based on gray-level co-occurrence matrices (GLCM) were calculated for 3D volumes of segmented esophageal tumors before and after neoadjuvant chemotherapy or radiochemotherapy. Histopathological data after surgical resection and textural parameters before and after neoadjuvant treatment were compared using the Mann-Whitney U test. Significant differences in the textural parameters were observed between adenocarcinoma and squamous cell carcinoma for homogeneity, energy, inertia, and correlation. The use of contrast media during scanning resulted in significant differences in homogeneity, energy, entropy, and inertia for adenocarcinoma but not squamous cell carcinoma. There was also a significant difference in all textural parameters between pathological T status for ypT0-ypT2 and ypT3-ypT4 adenocarcinomas, but not in squamous cell carcinoma patients. No additional value was found from using PET image data to aid segmentation of CT images.

Digital X-ray radiogrammetry of hand or wrist radiographs can predict hip fracture risk--a study in 5,420 women and 2,837 men.

OBJECTIVES: To assess whether digital X-ray radiogrammetry (DXR) analysis of standard clinical hand or wrist radiographs obtained at emergency hospitals can predict hip fracture risk. METHODS: A total of 45,538 radiographs depicting the left hand were gathered from three emergency hospitals in Stockholm, Sweden. Radiographs with insufficiently included metacarpal bone, fractures in measurement regions, foreign material or unacceptable positioning were manually excluded. A total of 18,824 radiographs from 15,072 patients were analysed with DXR, yielding a calculated BMD equivalent (DXR-BMD). Patients were matched with the national death and inpatient registers. Inclusion criteria were age ≥ 40 years, no prior hip fracture and observation time > 7 days. Hip fractures were identified via ICD-10 codes. Age-adjusted hazard ratio per standard deviation (HR/SD) was calculated using Cox regression. RESULTS: 8,257 patients (65.6 % female, 34.4 % male) met the inclusion criteria. One hundred twenty-two patients suffered a hip fracture after their radiograph. The fracture group had a significantly lower DXR-BMD than the non-fracture group when adjusted for age. The HR/SD for hip fracture was 2.52 and 2.08 in women and men respectively. The area under the curve was 0.89 in women and 0.84 in men. CONCLUSIONS: DXR analysis of wrist and hand radiographs obtained at emergency hospitals predicts hip fracture risk in women and men. KEY POINTS: • Digital X-ray radiogrammetry of emergency hand/wrist radiographs predicts hip fracture risk. • Digital X-ray radiogrammetry (DXR) predicts hip fracture risk in both women and men. • Osteoporosis can potentially be identified in patients with suspected wrist fractures. • DXR can potentially be used for selective osteoporosis screening.

Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA: a pilot study.

OBJECTIVES: To develop and evaluate a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA and Gd-EOB-DTPA using dynamic contrast-enhanced (DCE) MRI. METHODS: Ten healthy volunteers were prospectively recruited and 21 patients with suspected hepatobiliary disease were retrospectively evaluated. All subjects were examined with DCE-MRI using 0.025 mmol/kg of Gd-EOB-DTPA. The healthy volunteers underwent an additional examination using 0.05 mmol/kg of Gd-BOPTA. The signal intensities (SI) of liver and spleen parenchyma were obtained from unenhanced and enhanced acquisitions. Using pharmacokinetic models of the liver and spleen, and an SI rescaling procedure, a hepatic uptake rate, K (Hep), estimate was derived. The K (Hep) values for Gd-EOB-DTPA were then studied in relation to those for Gd-BOPTA and to a clinical classification of the patient's hepatobiliary dysfunction. RESULTS: K (Hep) estimated using Gd-EOB-DTPA showed a significant Pearson correlation with K (Hep) estimated using Gd-BOPTA (r = 0.64; P < 0.05) in healthy subjects. Patients with impaired hepatobiliary function had significantly lower K (Hep) than patients with normal hepatobiliary function (K (Hep) = 0.09 ± 0.05 min(-1) versus K (Hep) = 0.24 ± 0.10 min(-1); P < 0.01). CONCLUSIONS: A new procedure for quantifying the hepatocyte-specific uptake of T (1)-enhancing contrast agent was demonstrated and used to show that impaired hepatobiliary function severely influences the hepatic uptake of Gd-EOB-DTPA. KEY POINTS: • The liver uptake of contrast agents may be measured with standard clinical MRI. • Calculation of liver contrast agent uptake is improved by considering splenic uptake. • Liver function affects the uptake of the liver-specific contrast agent Gd-EOB-DTPA. • Hepatic uptake of two contrast agents (Gd-EOB-DTPA, Gd-BOPTA) is correlated in healthy individuals. • This method can be useful for determining liver function, e.g. before hepatic surgery.

Screening for women with increased risk of fragility fractures in a general female population using digital X-ray radiogrammetry (DXR).

OBJECTIVE: To evaluate the predictive ability of digital X-ray radiogrammetry (DXR) for fracture in women attending general mammography screening. STUDY DESIGN: In a nested case-control study, women aged between 40 and 75 years, who attended the regional mammography screening program, had their bone mass assessed with DXR and provided information regarding clinical risk factors for osteoporosis. Follow-up was done through cross-referencing with National Patient Registers. Associations between DXR, clinical risk factors and fracture risk were examined. Receiver operating characteristics curves for DXR T-score and different fracture types were plotted, and their respective AUC calculated. MAIN OUTCOME MEASURES: Fractures (hip, major osteoporotic and any clinical facture). Fracture diagnoses were retrieved from National Patient Registers. RESULTS: 14,841 women had their bone mass examined in conjunction with mammography. Of these women, 10,967 returned fully completed questionnaires regarding clinical risk factors. In total 605 fractures (including 355 major osteoporotic fractures and 18 hip fractures) occurred during the follow-up period (median follow-up time was 3.3 years). Women with fractures were older and had lower DXR T-score compared with those without. DXR T-score correlated with fracture risk. HR/SD T-score decrease was 2.15 (CI 1.55-3.00) for hip, 1.47 (CI 1.36-1.59) for major osteoporotic and 1.33 (CI 1.26-1.42) for any clinical fracture. The AUCs for the different fracture types were 0.79 (hip), 0.69 (major osteoporotic) and 0.65 (any clinical). CONCLUSIONS: DXR T-score is negatively correlated with risk of fracture in a general female population. This indicates a potential use of DXR in population-based screening for osteoporosis.

Liver vessel enhancement by Gd-BOPTA and Gd-EOB-DTPA: a comparison in healthy volunteers.

BACKGROUND: A thorough understanding of magnetic resonance (MR) contrast media dynamics makes it possible to choose the optimal contrast media for each investigation. Differences in visualizing hepatobiliary function between Gd-BOPTA and Gd-EOB-DTPA have previously been demonstrated, but less has been published regarding differences in liver vessel visualization. PURPOSE: To compare the liver vessel and liver parenchymal enhancement dynamics of Gd-BOPTA (MultiHance) and Gd-EOB-DTPA (Primovist). MATERIAL AND METHODS: The signal intensity of the liver parenchyma, the common hepatic artery, the middle hepatic vein, and a segmental branch of the right portal vein was obtained in 10 healthy volunteers before contrast media administration, during arterial and portal venous phases, and 10, 20, 30, 40, and 130 min after intravenous contrast medium injection, but, due to scanner limitations, not during the hepatic venous phase. The doses of contrast media were 0.1 mmol/kg for Gd-BOPTA and 0.025 mmol/kg for Gd-EOB-DTPA. RESULTS: Maximum enhancement of liver parenchyma was observed from the portal venous phase until 130 min after Gd-BOPTA administration and from 10 min to 40 min after Gd-EOB-DTPA. There was no difference in maximum enhancement of liver parenchyma between the two contrast media. When using Gd-BOPTA, the vascular contrast enhancement was still apparent 40 min after injection, but had vanished 10 min after Gd-EOB-DTPA injection. The maximum difference in signal intensity between the vessels and the liver parenchyma was significantly greater with Gd-BOPTA than with Gd-EOB-DTPA (P<0.0001). CONCLUSION: At the dosage used in this study, Gd-BOPTA yields higher maximum enhancement of the hepatic artery, portal vein, and middle hepatic vein during the arterial and the portal venous phase and during the delayed phases than Gd-EOB-DTPA does, whereas there is no difference in liver parenchymal enhancement between the two contrast agents.

Is training essential for interpreting cardiac computed tomography?

BACKGROUND: Cardiac computed tomography (CT) has gained increasing acceptance for diagnosing obstructive coronary artery disease (CAD). Several guidelines have been published on required education for proficiency in the interpretation of these examinations. PURPOSE: To describe the learning-curve effect of the interpretation of 100 consecutive cardiac CT examinations aimed at diagnosing CAD. The diagnostic accuracy of radiologists and radiographers was also compared. MATERIAL AND METHODS: Two radiologists and two radiographers, all with no prior experience in evaluation of cardiac CT, independently underwent a dedicated training program of 100 examinations randomized into 10 blocks (sessions), with 10 cases in each. They independently evaluated the coronary arteries regarding significant obstructive CAD. After every session, individual feedback on diagnostic accuracy and comparison with the corresponding invasive coronary angiography (currently regarded as the gold standard to detect coronary lesions) was given. The time required for interpretation was recorded. RESULTS: The mean review time decreased (P<0.0001) successively during the 10 sessions for all the observers together. The first session had a mean review time of 32 min, and the last session 16 min. No significant improvement in sensitivity, specificity, or negative predictive value (NPV) was observed. For positive predictive value (PPV), there was an improvement for the radiologists (P<0.05), but not for the radiographers. The radiographers had a higher total specificity compared to the radiologists (P<0.01). CONCLUSION: The review time for novices in cardiac CT was approximately halved during the first 100 cases, with maintained accuracy. There was a learning-curve effect in PPV for the radiologists. The diagnostic accuracy of dedicated radiographers indicates that they might be considered to be included as part of the evaluation team.

Long-term outcome after spinal fusion for isthmic spondylolisthesis in adults.

BACKGROUND CONTEXT: Data on the long-term outcome after fusion for isthmic spondylolisthesis are scarce. PURPOSE: To study patient-reported outcomes and adjacent segment degeneration (ASD) after fusion for isthmic spondylolisthesis and to compare patient-reported outcomes with a control group. STUDY DESIGN/SETTING: A prospective study including a cross-sectional control group. PATIENT SAMPLE: Patients with isthmic spondylolisthesis underwent posterior lumbar interbody fusion (PLIF) (n=86) or posterolateral fusion (PLF) (n=77). Patient-reported outcome data were available for 73 patients in the PLIF group and 71 in the PLF group at a mean of 11 (range 5-16) years after baseline. Seventy-seven patients in the PLIF group and 54 in the PLF group had radiographs at a mean of 14 (range 9-19) years after baseline. One hundred thirty-six randomly selected persons from the population served as controls for the patient-reported outcomes. OUTCOME MEASURES: Patient-reported outcomes include the following: global outcome, Oswestry Disability Index, Disability Rating Index, and Short Form 36. The ASD was determined from radiographs using the University of California Los Angeles (UCLA) grading scale. METHODS: The chi-square test or analysis of covariance (ANCOVA) was used for group comparisons. The ANCOVA was adjusted for follow-up time, smoking, Meyerding slippage grade, teetotaler (yes/no) and, if available, the baseline level of the dependent variable. RESULTS: There were no significant patient-reported outcome differences between the PLIF group and the PLF group. The prevalence of ASD was 42% (32/77) in the PLIF group and 26% (14/54) in the PLF group (p=.98). The patient-reported outcome data indicated lower physical function and more pain in individuals with surgically treated isthmic spondylolisthesis compared to the controls. CONCLUSIONS: PLIF and PLF groups had similar long-term patient-reported and radiological outcomes. Individuals with isthmic spondylolisthesis have lower physical function and more pain several years after surgery when compared to the general population.

Calcaneus BMD short-term precision in young and elderly subjects using the DXL Calscan.

In this study, the short-term reproducibility and agreement between individual units of dual X-ray and laser (DXL) Calscan (version 2), a new bone densitometry device based on dual X-ray absorptiometry and Laser technique, were evaluated. The variations in bone mineral density (BMD) and T-score between the right and the left foot were also studied retrospectively in 334 individuals. The short-term CV%, based on 19 healthy individuals scanned twice on 4 different units, was 2.1%, and the average CV% per scanner ranged from 1.1% to 1.8%. The short-term CV% in 33 elderly individuals (aged 83+/-6 yr) was 3.9% and in a subgroup with a calcaneal T-score of -2.5 or below (n=16) 5.1%. There was no statistical difference between the average BMD of the right and left foot, and (r2) between the right and left side was 0.84. The observed short- and long-term reproducibilities, as well as the acceptable variation between individual machines, show that this version of Demetech DXL Calscan is suitable for measuring BMD.

Implant density is not related to patient-reported outcome in the surgical treatment of patients with idiopathic scoliosis.

Aims: There is little information about the optimum number of implants to be used in the surgical treatment of idiopathic scoliosis. Retrospective analysis of prospectively collected data from the Swedish spine register was undertaken to discover whether more implants per operated vertebra (implant density) leads to a better outcome in the treatment of idiopathic scoliosis. The hypothesis was that implant density is not associated with patient-reported outcomes, the correction of the curve or the rate of reoperation. Patients and Methods: A total of 328 patients with idiopathic scoliosis, aged between ten and 20 years at the time of surgery, were identified in the Swedish spine register (Swespine) and had patient reported outcomes including the Scoliosis Research Society 22r instrument (SRS-22r) score, EuroQol 5 dimensions quality of life, 3 level (EQ-5D-3L) score and a Viual Analogue Score (VAS) for back pain, at a mean follow-up of 3.1 years and reoperation data at a mean follow-up of 5.5 years. Implant data and the correction of the curve were assessed from radiographs, preoperatively and a mean of 1.9 years postoperatively. The patients were divided into tertiles based on implant density. Data were analyzed with analysis of variance, logistic regression or log-rank test. Some analyses were adjusted for gender, age at the time of surgery, the flexibility of the major curve and follow-up. Results: The mean number of implants per operated vertebra in the low, medium and high-density groups were 1.36 (1.00 to 1.54), 1.65 (1.55 to 1.75) and 1.91 (1.77 to 2.00), respectively. There were no statistically significant differences in the correction of the curve, the SRS-22r total score, EQ-5D-3L index or number of reoperations between the groups (all p > 0.34). In the SRS-22r domains, self-image was marginally higher in the medium implant density group (p = 0.029) and satisfaction marginally higher in the high implant density group (p = 0.034). Conclusion: These findings suggest that there is no clear advantage in using a high number of implants per operated vertebra in the surgical treatment of patients with idiopathic scoliosis. Cite this article: Bone Joint J 2018;100-B:1080-6.

Phase synchronization between alpha and beta oscillations in the human electroencephalogram.

Coordination of neuronal oscillations generated at different frequencies has been hypothesized to be an important feature of integrative brain functions. The present study aimed at the evaluation of the cross-frequency phase synchronization between electroencephalographic alpha and beta oscillations. The amplitude and phase information were extracted from electroencephalograms recorded in 176 healthy human subjects using an analytic signal approach based on the Hilbert transform. The results reliably demonstrated the presence of phase synchronization between alpha and beta oscillations, with a maximum in the occipito-parietal areas. The phase difference between alpha and beta oscillations showed characteristic peaks at about 2 and -1 radians, which were common for many subjects and electrodes. A specific phase difference might reflect similarity in the organization and interconnections of the networks generating alpha and beta oscillations across the entire cortex. Beta oscillations, which are phase-locked to alpha oscillations--alpha-synchronous beta oscillations--were largest in the occipito-parietal area with a second smaller maximum in the frontal area, thus demonstrating a topography, which was different from the conventional alpha and beta oscillations. The strength of the alpha-synchronous beta oscillations was not exclusively defined by the amplitude of the alpha rhythm indicating that they represent a distinct feature of the spontaneous electroencephalogram, which allows for a refined discrimination of the dynamics of beta oscillations.

Three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective analysis of feasibility and adverse reaction to contrast material.

BACKGROUND: Computed Tomography Cholangiography (CTC) is a fast and widely available alternative technique to visualise hepatobiliary disease in patients with an inconclusive ultrasound when MRI cannot be performed. The method has previously been relatively unknown and sparsely used, due to concerns about adverse reactions and about image quality in patients with impaired hepatic function and thus reduced contrast excretion. In this retrospective study, the feasibility and the frequency of adverse reactions of CTC when using a drip infusion scheme based on bilirubin levels were evaluated. METHODS: The medical records of patients who had undergone upper abdominal spiral CT with subsequent three-dimensional rendering of the biliary tract by means of CTC during seven years were retrospectively reviewed regarding serum bilirubin concentration, adverse reaction and presence of visible contrast media in the bile ducts at CT examination. In total, 153 consecutive examinations in 142 patients were reviewed. RESULTS: Contrast media was observed in the bile ducts at 144 examinations. In 110 examinations, the infusion time had been recorded in the medical records. Among these, 42 examinations had an elevated bilirubin value (>19 micromol/L). There were nine patients without contrast excretion; 3 of which had a normal bilirubin value and 6 had an elevated value (25-133 micromol/L). Two of the 153 examinations were inconclusive. One subject (0.7%) experienced a minor adverse reaction - a pricking sensation in the face. No other adverse effects were noted. CONCLUSION: We conclude that drip infusion CTC with an infusion rate of the biliary contrast agent iotroxate governed by the serum bilirubin value is a feasible and safe alternative to MRC in patients with and without impaired biliary excretion. In this retrospective study the feasibility and the frequency of adverse reactions when using a drip infusion scheme based on bilirubin levels has been evaluated.

The maturation of mismatch negativity networks in normal adolescence.

OBJECTIVE: We investigated the neurophysiological mechanisms underpinning the generation of the mismatch negativity (MMN) and its development from adolescence to early adulthood. METHODS: We used dynamic causal modelling (DCM) to study connectivity models for healthy adults and adolescents. MMN was elicited with an auditory oddball paradigm in two groups of healthy subjects with mean age 14 (n=52) and 26 (n=26). We tested models with different hierarchical complexities including up to five cortical nodes. RESULTS: We showed that the network generating MMN consisted of 5 nodes that could modulate all intra- and internodal connections. The inversion of this model showed that adolescents had reduced backward connection from rIFG to rSTG (p<0.04) together with increased excitatory activity in rSTG (p<0.02). There was a reduced modulation of excitability in rSTG (p<0.02) and of forward connectivity from lA1 to lSTG (p<0.03). CONCLUSION: The cortical network generating MMN continues to develop in adolescence up to adulthood. Cortical regions in the temporal and frontal lobes, involved in auditory processing, mature with increasing fronto-temporal connectivity together with increased sensitivity in the temporal regions for changes in sound stimuli. SIGNIFICANCE: This study may offer an explanation for the neurobiological maturation of the MMN in adolescence.

Long-range temporal correlations in electroencephalographic oscillations: Relation to topography, frequency band, age and gender.

Presence of long-range temporal correlations in neuronal oscillations is thought to be beneficial for a reliable transfer of information in neuronal networks. In the present study long-range temporal correlations in electroencephalographic (EEG) neuronal oscillations were characterized with respect to their topography, frequency-band specificity (alpha and beta oscillations), gender and age. EEG was recorded in 91 normal subjects (age 20-65 years) in a resting condition. The amplitude of ongoing alpha and beta oscillations was extracted with band-pass filtering and Hilbert transform, and long-range temporal correlations were analyzed with detrended fluctuation analysis. The topography of long-range temporal correlations was comparable for alpha and beta oscillations, showing largest scaling exponents in the occipital and parietal areas. This topography was partially similar to that of the power distribution and a weak positive correlation was observed between long-range temporal correlations and power of neuronal oscillations. Long-range temporal correlations were stronger in alpha than beta oscillations, but only in a few electrode locations in the left hemisphere. In both frequency bands long-range temporal correlations were stronger in males than in females and were largely unaffected by the age of the subjects. It is hypothesized that the idling state of the occipital areas in the closed-eyes condition may explain both large power values and pronounced long-range temporal correlations in this region.

Volume rendering of three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective study.

The purpose of this study was to evaluate the diagnostic potential of prolonged drip infusion CT cholangiography (DIC-CT) using meglumine iotroxate (Biliscopin) and 3D volume rendering in patients with suspected obstructive biliary disease. From a material of 142 patients who had undergone a drip infusion CT, all cases with a verified surgical or endoscopic retrograde cholangiography (ERC) diagnosis (n=33) were selected. Age-matched controls were selected from the remaining examinations. Three radiologists reviewed all 66 examinations in retrospect, independently as well as in consensus. The image quality and the estimated diagnostic quality were rated as good or moderate in 91% of the 198 reviews. The consensus sensitivity and specificity for diagnosing biliary stones was 88% and 94%, respectively (with sensitivities ranging from 88% to 94% for individual observers, and specificities from 86% to 96%). Two out of three strictures were observed. No false positive strictures were described. The use of volume rendering technique (VRT) improved diagnostic certainty in 28/198 (14%) of the evaluations. The visualization of ductal stones was improved in 18/48 (38%). No differences in diagnostic quality between single and multislice CT were observed. We conclude that a detailed image of the biliary tree with good sensitivity and specificity can be obtained by means of bilirubin-governed infusion time DIC-CT with volume rendering reconstruction.

Amplitude and phase relationship between alpha and beta oscillations in the human electroencephalogram.

The relationship between the electro-encephalographic (EEG) alpha and beta oscillations in the resting condition was investigated in the study. EEGs were recorded in 33 subjects, and alpha (7.5-12.5 Hz) and beta (15-25 Hz) oscillations were extracted with the use of a modified wavelet transform. Power, peak frequency and phase synchronisation were evaluated for both types of oscillation. The average beta-alpha peak frequency ratio was about 1.9-2.0 for all electrode derivations. The peak frequency of beta activity was within 70-90 % of the 95 % confidence interval of twice the alpha frequency. A significant (p < 0.05) linear regression was found between beta and alpha power in all derivations in 32 subjects, with the slope of the regression line being approximately 0.3. There was no significant difference in the slope of the line in different electrode locations, although the power correlation was strongest in the occipital locations where alpha and beta oscillations had the largest power. A significant 1:2 phase synchronisation was present between the alpha and beta oscillations, with a phase lag of about pi/2 in all electrode derivations. The strong frequency relationship between the resting beta and alpha oscillations suggests that they are generated by a common mechanism. Power and phase relationships were weaker, suggesting that these properties can be modulated by additional mechanisms as well as be influenced by noise. A careful distinction between alpha-dependent and alpha-independent beta activity should be considered when making statements about the possible significance of genuine beta activity in different neurophysiological mechanisms.

Glucocorticoids and Sarcoidosis: A Longitudinal Study on the Effects on Cortical and Trabecular Bone.

BACKGROUND: Glucocorticoid induced osteoporosis is a well-known side effect of glucocorticoid treatment. In sarcoidosis the impact on bone by glucocorticoid treatment is complex due to hormonal disturbances of calcium and vitamin-D, which by itself may cause bone loss. In this study we aimed to investigate the longitudinal impact of glucocorticoids on cortical and trabecular bone in patients with mild, recently diagnosed sarcoidosis. METHODS: Ten patients (8 females; mean age 44 (±13)) were studied during one year of glucocorticoid treatment. The assessment of mainly cortical to purely trabecular bone was made by dual X-ray absorptiometry (DXA) of the spine and hip, quantitative ultrasound of the calcaneus, and magnetic resonance relaxometry of the spine and calcaneus. Bone and hormonal measurements were performed at baseline, after 3, 6, and 12 months, and baseline, 3 weeks and 3 months, respectively. RESULTS: DXA of the spine, decreased from baseline at 6 months (P=0.01). R2' of the calcaneus decreased with time (B: -3.6;P=0.03). In the females (n=8) there was a significant decrease in DXA of the spine when comparing 3 months and 6 months (P=0.03), and 3 months and 12 months (P=0.02) and a decrease in R2'of the calcaneus from baseline to 12 months (P=0.01). There was no change in hormonal levels. CONCLUSION: Treatment of initial mild sarcoidosis with dose tapered glucocorticoid therapy only mildly affects the final trabecular and cortical bone and hormone levels. Dose tapering is an important part in glucocorticoid therapy, likely contributing to the mild effects on bone observed in this study.

Serum levels of insulin-like growth factor binding proteins (IGFBP)-4 and -5 correlate with bone mineral density in growth hormone (GH)-deficient adults and increase with GH replacement therapy.

Adults with growth hormone deficiency (GHD) exhibit low bone mineral density (BMD) which improves by growth hormone (GH) replacement therapy. The insulin-like growth factor (IGF) system has an established role in mediating the effects of GH on bone and IGF binding proteins (IGFBP)-4 and IGFBP-5 have been shown to modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP-4 and IGFBP-5 and their relationship to serum levels of bone biochemical markers and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum levels of IGFBP-5 and IGFBP-4 were measured on samples from 20 patients (11 males) 22-57 years of age. All had IGF-I serum values below -2 standard deviation score. The first 6 months were placebo controlled and all received 3 years of active treatment with the mean dose 0.23 +/- 0.01 IU/kg/week divided into daily subcutaneous injections. Serum IGFBP-5 levels in GHD adults were low at baseline and positively related to total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The mean serum IGFBP-5 level increased by about 2-fold within 3 months after the initiation of GH therapy and was correlated with serum IGF-I (r = 0.719, 0.801, and 0.722 before and after 18 and 36 months, respectively,p < 0.001). A positive correlation between serum IGFBP-5 levels and lumbar spine BMD was found during GH treatment but not before. The percentage increase of serum IGFBP-5 after GH therapy showed a positive correlation with the percentage increase of total alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP-5, serum IGFBP-4 levels were positively related to body mass index (r = 0.607, p < 0.01). Baseline serum IGFBP-4 levels also correlated with total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.502, 0.590, 0.612, and 0.471, respectively,p < 0.05). The mean serum IGFBP-4 level was increased by 25% within 3 months after initiation of GH therapy and did not correlate with serum IGF-I levels. Although the above findings are consistent with the idea that GH-induced changes in serum IGFBP-5 and IGFBP-4 levels may in part mediate the anabolic effects of GH on bone tissue in adults with GHD, further studies are needed to establish the cause and effect relationship.

Hearing loss from the acoustic artifact of the coil used in extracranial magnetic stimulation.

The stimulating coil used in extracranial magnetic field stimulation (EMFS) emits a high intensity impulse sound artifact that causes permanent threshold shifts in the unprotected ears of experimental animals. At magnetic stimulation levels of 50 to 100%, the magnetic coil acoustic artifact (MCAA) ranged from 145 to 157 dB peak sound pressure level at the eardrum. The magnetic field alone did not appear to cause hearing impairment since no threshold shifts were observed in ears that were plugged with ear protectors during exposure to the MCAA. These findings suggest that the acoustic artifact produced by EMFS in the clinic may pose some risk for hearing loss in patients and clinicians when held in close proximity to the unprotected ear. We recommend the use of ear protectors for the patient and clinician during EMFS as a precautionary measure to prevent hearing loss.

Effect of hypoxia on membrane potential and resting conductance in rat hippocampal neurons.

The present patch-clamp study describes the effect of hypoxia at 30-31 degrees C on membrane potential and resting conductance in pyramidal cells from the hippocampal CA1 region in rat brain slices. The initial effect of hypoxia was a gradual hyperpolarization; the peak change in membrane potential measured over 15 min was -5.3 +/- 0.22 mV (P < 0.0001). After reoxygenation followed a transient hyperpolarization measuring -1.8 +/- 0.24 mV (P < 0.0001) and a subsequent normalization of the membrane potential, which after 5 min did not differ from its level prior to the hypoxic episode. Voltage-clamp analysis showed that the hypoxic hyperpolarization was related to an outward current at the holding potential (-60 mV) and an increase in resting conductance. The effect was not influenced by intracellular Cl- concentration, which indicated that it was not due to an inward flow of Cl- ions. The addition of tolbutamide, glibenclamide and dantrolene sodium did not affect the hypoxic hyperpolarization, neither did the presence of ATP in the pipette solution. The presence/absence of glucose in the perfusion medium did not influence the initial hyperpolarization during hypoxia; however, glucose seemed to prevent the subsequent depolarization under hypoxia. It was concluded that hypoxia caused an initial hyperpolarization of CA1 cells which was related to an increase in the resting conductance. The results did not suggest the involvement of ATP-sensitive K+ channels.