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Biomedical subjects

S Skare

Publications and source records attributed to S Skare.

At least 19 recordsLinked to original sources

Correction of MR image distortions induced by metallic objects using a 3D cubic B-spline basis set: application to stereotactic surgical planning.

Metallic implants in MRI cause spin-echo (SE) images to be distorted in the slice and frequency-encoding directions. Chang and Fitzpatrick (IEEE Trans Med Imaging 1992;11:319-329) proposed a distortion correction method (termed the CF method) based on the magnitude images from two SE acquisitions that differ only in the polarity of the frequency-encoding and slice-selection gradients. In the present study we solved some problems with the CF method, primarily by modeling the field inhomogeneities as a single 3D displacement field built by 3D cubic B-splines. The 3D displacement field was applied in the actual distortion direction in the slice/frequency-encoding plane. To account for patient head motion, a 3D rigid body motion correction was also incorporated in the model. Experiments on a phantom containing an aneurysm clip showed that the knot spacing between the B-splines is a very important factor in both the final image quality and the processing speed. Depending on the knot spacing and the image volume size, the number of unknowns range from a few thousands to over 100,000, leading to processing times ranging from minutes to days. Optimal knot spacing, a means of increasing the processing speed, and other parameters are investigated and discussed.

Algorithms↗

Abnormal brain white matter in schizophrenia: a diffusion tensor imaging study.

Fractional anisotropy and the mean diffusion coefficient were measured in the cerebral volume in 20 schizophrenic and 24 healthy subjects, men and women, using diffusion tensor imaging. In addition, 3D SPGR was used for segmentation of brain tissue into grey and white matter and cerebrospinal fluid. In schizophrenic patients, fractional anisotropy was reduced in the splenium of the corpus callosum and in adjacent occipital white matter. The segmentation revealed no tissue deficits in the volume of reduced fractional anisotropy. The mean diffusion was increased in the total white and grey matter volume of the schizophrenic patients compared with the healthy subjects. The findings support the view that global and regional white matter abnormalities occur in chronic schizophrenia.

Adult↗

On the effects of gating in diffusion imaging of the brain using single shot EPI.

To reduce image artifacts in diffusion tensor imaging using single shot EPI, cardiac gating may be performed to prevent brain motion induced signal void in the DWI data. In this work the necessity of performing cardiac gating with single shot echo planar imaging has been explored using F statistics of the variance in DWI data. Peripheral measurement of the cardiac cycle has been employed because of its greater convenience, and hence use, compared to ECG gating. Four volunteers have been studied. Six different trigger delays have been evaluated in the range 18-500 ms relative the peripheral pulse wave. Brain motion was found significant in and inferior to the corpus callosum area. A trigger delay of 500 ms was found to be optimal. However, a long delay allows only for one slice per R-R interval. Therefore, a minimum trigger delay may be the best choice in terms of SNR per unit of experiment time.

Artifacts↗

Condition number as a measure of noise performance of diffusion tensor data acquisition schemes with MRI.

Diffusion tensor mapping with MRI can noninvasively track neural connectivity and has great potential for neural scientific research and clinical applications. For each diffusion tensor imaging (DTI) data acquisition scheme, the diffusion tensor is related to the measured apparent diffusion coefficients (ADC) by a transformation matrix. With theoretical analysis we demonstrate that the noise performance of a DTI scheme is dependent on the condition number of the transformation matrix. To test the theoretical framework, we compared the noise performances of different DTI schemes using Monte-Carlo computer simulations and experimental DTI measurements. Both the simulation and the experimental results confirmed that the noise performances of different DTI schemes are significantly correlated with the condition number of the associated transformation matrices. We therefore applied numerical algorithms to optimize a DTI scheme by minimizing the condition number, hence improving the robustness to experimental noise. In the determination of anisotropic diffusion tensors with different orientations, MRI data acquisitions using a single optimum b value based on the mean diffusivity can produce ADC maps with regional differences in noise level. This will give rise to rotational variances of eigenvalues and anisotropy when diffusion tensor mapping is performed using a DTI scheme with a limited number of diffusion-weighting gradient directions. To reduce this type of artifact, a DTI scheme with not only a small condition number but also a large number of evenly distributed diffusion-weighting gradients in 3D is preferable.

Algorithms↗

Noise considerations in the determination of diffusion tensor anisotropy.

In this study the noise sensitivity of various anisotropy indices has been investigated by Monte-Carlo computer simulations and magnetic resonance imaging (MRI) measurements in a phantom and 5 healthy volunteers. Particularly, we compared the noise performance of indices defined solely in terms of eigenvalues and those based on both the eigenvalues and eigenvectors. It is found that anisotropy indices based on both eigenvalues and eigenvectors are less sensitive to noise, and spatial averaging with neighboring pixels can further reduce the standard deviation. To reduce the partial volume effect caused by the spatial averaging with neighboring voxels, an averaging method in the time domain based on the orientation coherence of eigenvectors in repeated experiments has been proposed.

Adult↗

Tickling expectations: neural processing in anticipation of a sensory stimulus.

Predictions of the near future can optimize the accuracy and speed of sensory processing as well as of behavioral responses. Previous experience and contextual cues are essential elements in the generation of a subjective prediction. Using a blocked fMRI paradigm, we investigated the pattern of neural activation in anticipation of a sensory stimulus and during the processing of the somatosensory stimulus itself. Tickling was chosen as the somatosensory stimulus rather than simple touch in order to increase the probability to get a high degree of anticipation. The location and nature of the stimulus were well defined to the subject. The state of anticipation was initiated by attributing an uncertainty regarding the time of stimulus onset. The network of activation and deactivation during anticipation of the expected stimulus was similar to that engaged during the actual sensory stimulation. The areas that were activated during both states included the contralateral primary sensory cortex, bilateral areas in the inferior parietal lobules, the putative area SII, the right anterior cingulate cortex and areas in the right prefrontal cortex. Similarly, common decreases were observed in areas of sensorimotor cortex located outside the area representing the target of stimulus, i.e., areas that process information which is irrelevant to the attended process. The overlapping pattern of change, during the somatosensory stimulation and the anticipation, furthers the idea that predictions are subserved by a neuronal network similar to that which subserves the processing of actual sensory input. Moreover, this study indicates that activation of primary somatosensory cortex can be obtained without intra-modal sensory input. These findings suggest that anticipation may invoke a tonic top-down regulation of neural activity.

Adult↗

Convergent and criterion-related validity of the Behavior Assessment System for Children-Parent Rating Scale.

Examined aspects of the validity of the Behavior Assessment System for Children (BASC; Reynolds & Kamphaus, 1992) Parent Rating Scale (BASC-PRS) in 156 children with cross-setting disruptive behavior. The BASC-PRS is a recently published multidimensional measure composed of conceptually derived scales created for use in conjunction with psychiatric and educational classification systems. Convergent validity was assessed through correlations of BASC-PRS scale scores with scale scores on the Child Behavior Checklist/4-18 (CBCL/4-18; Achenbach, 1991b). Criterion-related validity was evaluated as the ability of BASC-PRS and CBCL/4-18 scales to predict membership in diagnostic groupings (no diagnosis, attention deficit hyperactivity disorder [ADHD] only, and ADHD with a comorbid externalizing disorder) derived via structured interviews based on the third, revised edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). Results showed the validity of the BASC-PRS to be comparable to that of the CBCL/4-18. Given its conceptually derived scales, the BASC-PRS may prove to be a useful-tool for assessing childhood disruptive behavior.

Attention Deficit Disorder with Hyperactivity↗

Distribution of peripheral lymphocytes in Alzheimer patients and controls.

Deficient immunoregulation has been postulated to play a role in the pathogenesis of Alzheimer's dementia. Recently, lymphopenia was reported to be more prevalent in Alzheimer patients than in control subjects. In addition, a decreasing number of total lymphocytes was found to be significantly correlated with increasing severity of dementia. In an attempt to replicate these findings, we studied 55 Alzheimer patients and 41 healthy controls of comparable age and gender, but found no significant difference in the distribution of total lymphocytes between these groups. Furthermore, total lymphocytes were not significantly correlated with dementia severity. Our findings, therefore, do not lend further support to an immune hypothesis for Alzheimer's dementia.

Adult↗

Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type.

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients.

Acetamides↗

Haloperidol decanoate pharmacokinetics in red blood cells and plasma.

Red blood cell (RBC) and plasma concentrations of haloperidol (H) and reduced haloperidol (RH) were determined in nine patients (five men, four women) who had been receiving monthly injections of haloperidol decanoate (HD) for at least 3 months. A very sensitive high performance liquid chromatography method was used to measure H and RH, which could be detected at levels as low as 0.1 ng/ml. Blood samples for H and RH were drawn at the end of weeks 1, 2, 3, and 4 of a 4-week cycle. Monthly HD dosages ranged from 50 mg to 200 mg. At each time point RBC H did not differ significantly from plasma H. RBC RH and plasma RH did not change significantly over time and were consistently lower than RBC H and plasma H. However, RBC RH levels were higher than plasma RH levels. Also, the ratios of RBC RH/H were higher than were the ratios of plasma RH/H, which reflect an accumulation of RH intracellularly. HD dosage was highly correlated with both RBC H and plasma H, but RBC RH and plasma RH were not significantly related to dosage at any time point. Significant correlations were observed between HD dosage and prolactin concentration at week 1 and between prolactin concentration and RBC H and plasma H at weeks 1 and 4. Blood concentrations of H and RH and the corresponding standardized areas under the curve were not significantly related to smoking.

Adult↗

Haloperidol and reduced haloperidol in saliva and blood.

A total of 18 outpatients (17 male, 1 female) ranging in age from 36-66 years old were on a constant dosage of haloperidol in equally divided doses at 9:00 a.m. and 9:00 p.m. for at least 1 month. DSM-III-R diagnoses included schizophrenia (N = 9), schizoaffective disorder (N = 3), bipolar disorder (N = 4), organic mental disorder (N = 1), and delusional disorder (N = 1). Blood samples for steady-state concentrations of plasma and red blood cell haloperidol (H) and reduced haloperidol (RH) were drawn at 9:00 a.m. (12 hr trough). The haloperidol dosage was held at 9:00 a.m. until samples of whole saliva and parotid saliva could be collected for flow rates and concentrations of H and RH. Haloperidol dosages ranged from 1 mg/day to 60 mg/day (mean 11 +/- 15). Correlation coefficients were calculated for saliva concentrations versus blood levels and for saliva secretion rates versus blood levels. The correlations between whole saliva measures and blood concentrations were all higher than the correlations between parotid saliva measures and blood concentrations. In one case the higher correlation reached statistical significance. There was only one case in which substitution of saliva secretion rate improved the correlation between measures with saliva concentration. Our findings suggest that saliva measures of H and RH are useful alternatives to plasma concentrations in monitoring maintenance haloperidol treatment.

Adult↗

Somatostatin, insulin and glucagon after arginine stimulation in active and treated acromegaly.

Ten acromegalic patients, 28-71 years old, were compared with 10 normal controls, 21-39 years old. In another study, 7 patients with active acromegaly, 19-70 years old, were investigated before and 4-9 months following transsphenoidal adenectomy and radiation. They were all investigated following an arginine infusion (0.5 g/kg/20 min). Although the mean plasma somatostatin (somatotrophin release inhibiting factor (SRIF] was somewhat higher in acromegalic patients compared to normal controls (mean basal values 21 +/- 3.8 and 16.6 +/- 2.1 pmol/l, respectively), the difference was not significant. The patients had higher serum insulin (peak values 118 +/- 23.9 and 63 +/- 11.8 mU/l, respectively) and lower plasma glucagon (peak values 171 +/- 29.0 and 310 +/- 52.7 pmol/l, respectively). Plasma SRIF increased during arginine infusion, but the concentrations were similar before and following the operation (mean basal values 18.2 +/- 2.6 and 15.2 +/- 2.3 pmol/l, respectively). Serum insulin was significantly higher before the operation (peak values 154 +/- 38.8 and 91 +/- 24.9 mU/l, respectively). Plasma glucagon was similar before and after the operation (peak values 143 +/- 23.4 and 127 +/- 22.7 pmol/l, respectively). Plasma SRIF is similar in active acromegaly and normal controls, and in acromegaly before and following treatment, despite differences in serum growth hormone (GH), serum insulin and plasma glucagon. This points towards a modulating role for GH on plasma SRIF, possibly by affecting the other islet cell hormones.

Acromegaly↗

Plasma somatostatin is elevated in primary hypothyroidism compared with hyperthyroidism.

Increased pancreatic somatostatin (somatotrophin release inhibiting factor (SRIF) has been found in hypothyroid rats. Therefore, we wanted to investigate plasma SRIF in patients with hypo- and hyperthyroidism. Two groups of patients, 7 cases with autoimmune hypothyroidism, 31-75 years old, and 7 cases with Graves' disease, 19-43 years old, were compared with regard to plasma SRIF before, during and after an arginine infusion (0.5 g/kg/20 min). None of the patients suffered from diabetes mellitus or obesity. Plasma SRIF was higher in the hypothyroid patients (mean basal value 21.5 +/- 3.9, peak value 28.7 +/- 5.1 pmol/l) compared with the hyperthyroid group (mean basal value 11.6 +/- 3.3, peak value 16.2 +/- 4.0 pmol/l). The hypothyroid group also had significantly higher serum insulin values during arginine stimulation. No difference was found in plasma glucagon, serum growth hormone (GH) or blood glucose. In conclusion, plasma SRIF is elevated in primary hypothyroidism compared with hyperthyroidism. The reason for this finding is uncertain, but a reduced SRIF clearance is a possible explanation. The association of our findings with the reduced glucose tolerance in hyperthyroidism is discussed.

Adult↗

Plasma somatostatin and plasma glucagon in long-term IDDM without residual B-cell function. No effect of different long-term metabolic control.

To further study the elevated plasma somatostatin (SRIF)--and reduced plasma glucagon concentrations found in IDDM patients without residual B-cell function compared to normal controls, we investigated 39 such patients, randomly assigned to three different insulin treatment regimens; conventional therapy with two injections a day (CTh), insulin pump (CSII) and multiple injections (MI), for 1 year. They were given an arginine infusion (0.5 g/kg/20 min). The mean basal plasma SRIF values in the CTh, CSII and MI groups were 20.8 +/- 3.3, 18.6 +/- 1.8 and 20.6 +/- 2.8 pmol/l and the mean basal plasma glucagon values were 30 +/- 5.7, 19 +/- 2.3 and 27 +/- 4.7 pmol/l, respectively. Both SRIF and glucagon increased in all groups in relation to arginine infusion. For both hormones, the mean values were highest in the CTh group, lowest in the CSII group, although the differences were not significant. The mean HbA1 values for the last 3 months within the test were 10.0 +/- 0.5, 8.8 +/- 0.3 and 9.1 +/- 0.5%, respectively, in the same order as above. The CTh group had significantly higher HbA1 values than the CSII group (p less than 0.02). We conclude that small differences in long-term blood glucose control are of inconsiderable importance for the islet hormonal response to arginine found in IDDM without B-cell function.

Adult↗

Effects of synthetic corticotropin-releasing factor in normal individuals and in patients with hypothalamic-pituitary-adrenocortical disorders.

Plasma adrenocortical hormone (ACTH) and cortisol response to four dose levels (25, 50, 100 and 300 micrograms) corticotropin-releasing factor (CRF) were studied in 5 healthy men, and the response to 100 micrograms CRF in 12 patients with various disorders of the hypothalamic-pituitary-adrenocortical function. In normals, mean plasma ACTH and cortisol concentration rose at all dose levels of CRF and peaked at 30 and 60 min respectively. The increment in plasma cortisol at 60 and 90 min was significantly higher on 100 and 300 micrograms CRF than on 25 micrograms, but the total cortisol concentration was not. Seven patients had Cushing's syndrome. In 2 patients with adrenocortical carcinoma the basal plasma ACTH was suppressed. After CRF a small increase was seen in plasma ACTH and cortisol in one patient successfully treated with mitotane, while the other patient did not respond. In 1 patient with ectopic ACTH syndrome an increase in plasma ACTH 15 min after CRF was not accompanied by any increase in plasma cortisol. One patient with bilateral multinodular adrenocortical hyperplasia did not respond to CRF. The plasma ACTH and cortisol response to CRF was supernormal in 2 patients with Cushing's disease, while a third patient responded in the normal range. In 2 patients with Nelson's syndrome the plasma ACTH response was excessive. Two out of three hypophysectomized patients did not respond to CRF, while one patient with a slightly positive response to hypoglycemia also responded (subnormally) to CRF. Our data indicate that CRF in doses of 50-100 micrograms will be a valuable substance in the differential diagnosis of Cushing's syndrome. Some overlap in the response is, however, seen between patients with Cushing's disease and other patients with Cushing' syndrome. CRF will possibly be of value also for the diagnosis of secondary adrenocortical failure.

Adrenocorticotropic Hormone↗

Increased peripheral venous somatostatin concentration and decreased glucagon response to arginine in patients with insulin dependent diabetes mellitus without residual B-cell function. Increased plasma SRIF in IDDM.

The glucagon response to insulin hypoglycaemia is frequently reduced in patients with IDDM. In the present study arginine infusion, thought to act directly on the islet cells, was used to stimulate somatostatin (SRIF) and glucagon in IDDM without residual B-cell function. Thirteen IDDM patients' were compared with 13 sex- and age matched normal controls following an arginine infusion. The plasma SRIF concentrations in the 'IDDM group' and normal controls increased from 24.2 +/- 2.5 to 31.1 +/- 3.9 pmol/l (P less than 0.01) and 19.7 +/- 1.7 to 23.9 +/- 3.4 pmol/l respectively after 10 min (P less than 0.01). The plasma glucagon concentrations increased from 27 +/- 4.7 to 176 +/- 23.1 pmol/l (P less than 0.01) and 36 +/- 5.0 to 302 +/- 31.9 pmol/l (P less than 0.01) respectively after 20 min. Thus, in long standing IDDM without residual B-cell function, increased plasma SRIF concentrations are found and the glucagon response to arginine is reduced. The last observation further explains why these patients are especially vulnerable to hypoglycaemia.

Adolescent↗