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Biomedical subjects

N Lange

Publications and source records attributed to N Lange.

At least 19 recordsLinked to original sources
PubMed1998

D-serine added to antipsychotics for the treatment of schizophrenia.

BACKGROUND: Hypofunction of N-methyl-D-aspartate (NMDA) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. D-serine is a full agonist of the glycine site of NMDA receptor, an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor. Supplementation of D-serine may improve the symptoms of schizophrenia. METHODS: Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-serine (30 mg/kg/day), which was added to their stable antipsychotic regimens. Of these, 28 completed the trial. Measures of clinical efficacy, side effects, and serum levels of amino acids and D-serine were determined every other week. Wisconsin Card Sorting Test (WCST) was performed at the beginning and end of the trial. RESULTS: Patients who received D-serine treatment revealed significant improvements in their positive, negative, and cognitive symptoms as well as some performance in WCST. D-serine levels at week 4 and 6 significantly predicted the improvements. D-serine was well tolerated and no significant side effects were noted. CONCLUSIONS: The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia. Given the effects of D-serine on positive symptoms, a trial of D-serine alone in schizophrenia should be considered.

Adult↗
PubMed1998

Reduction in BOLD fMRI response to primary visual stimulation following alcohol ingestion.

The physiology of alcohol's effects on brain function is poorly understood. Emission tomographic imaging has revealed both acute and chronic alterations in resting cerebral hemodynamics and metabolism following alcohol ingestion. However, cerebral functional integrity under these conditions has received less attention. Functional magnetic resonance imaging (fMRI) offers a non-invasive method for assessing brain functional activation. In order to assess its utility for studying the effect of alcohol on brain function, we performed fMRI with photic stimulation before and after administration of either 0.7 mg/kg alcohol (N = 12) or placebo (N = 5), resulting in peak breath alcohol levels averaging 0.069 g/dl. We found that the amplitude of visual cortical activation in response to photic stimulation was significantly reduced by approximately 33% following alcohol administration (4.0 +/- 1.7% vs. 2.7 +/- 1.3%, P = 0.02), but not following placebo (4.2 +/- 1.5% vs. 4.1 +/- 1.4%, P = 0.7). The results also suggest that the baseline right hemispheric predominance of activation in response to photic stimulation may be reduced following alcohol, suggesting a greater effect on the right hemisphere, consistent with previous studies and alcohol's known effects on visuospatial processing. In addition, through the course of each activation session, there was a progressive reduction in response following alcohol. These data demonstrate that the cerebral effects of alcohol intoxication can be studied with fMRI, and that the effects on brain function of even moderate alcohol intoxication may be widespread, may be lateralized, and may include the visual system.

Adult↗
PubMed1998

Cocaine-induced cerebral vasoconstriction detected in humans with magnetic resonance angiography.

CONTEXT: Clinical observations and case reports suggest that there are important cerebrovascular complications of cocaine use, but no studies have documented a direct link. OBJECTIVE: To determine whether low-dose cocaine administration induces cerebral vasoconstriction in healthy cocaine users. DESIGN: Randomized controlled trial. SUBJECTS: Twenty-four healthy and neurologically normal men (mean age, 29 years) reporting median cocaine use of 8 lifetime exposures (range, 3 to >40). INTERVENTION: Double-blind intravenous administration of cocaine (0.4 or 0.2 mg/kg) or placebo, with cerebral magnetic resonance angiography performed at baseline and 20 minutes following infusion. MAIN OUTCOME MEASURE: Cocaine-induced angiographic change indicative of vasoconstriction, as independently and concordantly rated by 2 reviewers blind to treatment condition. RESULTS: Cocaine-induced cerebral vasoconstriction in a dose-related fashion (P=.03), with angiograms indicative of vasoconstriction found in 5 of 8 and 3 of 9 subjects receiving 0.4- and 0.2-mg/kg cocaine, respectively, compared with 1 of 7 subjects administered placebo. Outcome stratification by frequency of self-reported lifetime cocaine use (3-10 times, 11-40 times, or >40 times) revealed a statistically stronger dose-related effect (P<.001), suggesting that greater lifetime cocaine use was associated with a greater likelihood of vasoconstriction. CONCLUSIONS: Cocaine administration induced dose-related cerebral vasoconstriction on magnetic resonance angiograms. These changes occurred at low cocaine doses and in the absence of other risk factors, including polydrug abuse, hypertension, or cerebrovascular disease. Outcome stratification by prior cocaine use statistically strengthened the relationship between cocaine administration and vasoconstriction, suggesting that cocaine may have a cumulative residual effect in promoting cerebrovascular dysfunction.

Adult↗
PubMed1998

Gyri of the human neocortex: an MRI-based analysis of volume and variance.

This magnetic resonance imaging (MRI)-based morphometric analysis of cortical topography in the human brain is based upon the segmentation and parcellation of volumetric T1-weighted MRI data for a set of 20 young adult brains including 10 males and 10 females. For the most part, each parcellation unit (PU) of the neocortex corresponds to a single or a portion of a single gyrus. The volumes of each PU were computed for each brain. Subsets of PUs were also grouped so as to represent the neocortex for the frontal, temporal, parietal and occipital lobes. The coefficient of variation of the mean volume of total neocortex and that of the neocortex assigned to individual lobes cluster around 10%, whereas that of neocortex assigned to the individual gyri (PU) is more than twice that value. Approximately 80% of the total variance in gyral volume arises from determinants interactive for individual and specific gyri, while only approximately 10% of the total variance appears to be a reflection of uniform scaling to total neocortical volume. Sexual dimorphism contributes a pervasive though relatively small component of this variance. These results have implications for the study of structure-function correlation, and the proper statistical methods of handling volumetric data in morphometric studies. In addition, the nature of the covariance structure of the data will lead to future hypotheses regarding the relationships between the various potential genetic and epigenetic gyral influencing factors.

Adult↗
PubMed1996

Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4-18 years.

The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders.

Adolescent↗
PubMed1996

Statistical approaches to human brain mapping by functional magnetic resonance imaging.

Proper use of functional neuro-imaging through effective experimental design and modern statistical analysis provides new insights in current brain research. This tutorial has two aims: to describe aspects of this technology to applied statisticians and to provide some statistical ideas to neuroscientists unfamiliar with quantitative analytic methods that accommodate randomness. Introductory background material and ample references to current literature on the physics of magnetic resonance imaging, Fourier methods for image reconstruction and measures of image quality are included. Two of the statistical approaches mentioned here are extensions of established methods for longitudinal data analysis to the frequency domain. A recent case study provides real-world instances of approaches, problems and open questions encountered in current functional neuro-imaging research and an introduction to the analysis of spatial time series in this context.

Algorithms↗
PubMed1996

Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder.

BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. METHODS: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. RESULTS: Subjects with ADHD had a 4.7% smaller total cerebral volume (P = .02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P = .006), smaller right globus pallidus (P = .005), smaller right anterior frontal region (P = .02), smaller cerebellum (P = .05), and reversal of normal lateral ventricular asymmetry (P = .03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. CONCLUSION: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.

Adolescent↗
PubMed1996

Visualizing cortical activation during mental calculation with functional MRI.

Cortical activation during arithmetic calculation (silent subtraction by sevens) was compared to that observed during a control condition for which subjects were required to count forward by ones. Nine normal subjects underwent 1.5-T functional magnetic resonance imaging while performing these tasks. All subjects showed bilateral premotor, posterior parietal, and prefrontal cortex activation during serial calculation. There was a large degree of individual variation in activation outside of these areas. These results confirm the role of posterior parietal cortex in arithmetic calculation and implicate other regions, including prefrontal cortex.

Adult↗
PubMed1996

[The effect of a low molecular weight synthetic humic substance on selected reproductive parameters of male rats].

Influences of the low molecular humic substance HS 1500 on parameters of organs (testis weight, epididymis weight), FSH-, and LH-levels in plasma as well as on the spermatogenesis of male rats were studied. After a daily oral application of 1000 mg/kg b.w. and 2000 mg/kg b.w., respectively over a period of 60 days (40th to 100th day of life) only 2 animals of the high dose group were observed with bilateral testicular atrophy. Despite of the two animals with testicular atrophy no significant differences between treated and control rats were observed with respect to testis morphology and spermatogenesis. There is no evidence whether the differences between the hormone levels and the testicular atrophy revealed is regarded to a HS 1500-effect or not. But otherwise a direct influence of HS 1500 can be ruled out with high certainty. Possibly because of the thin covering layer on the gastrointestinal mucous membrane formed by HS 1500, the absorption of nutritive substances is inhibited. Therefore the growth of sensitive organs like testis and epididymis, in the development period, can be decreased. Nevertheless, even after long time application the spermatogenesis is not influenced.

Administration, Oral↗
PubMed1996

[The effect of a low molecular weight synthetic humic substance on pre- and postnatal development in rats].

The influence of a low molecular synthetic humic substance (HS 1500) on pre- and postnatal development of rats was investigated. After oral application of 1000 mg/kg and 2000 mg/kg b. w. HS 1500 during the period of organogenesis (6th to 15th day p. c.) and from 16th day p. c. up to weaning neither adverse effects in the mothers nor in the fetuses were reported. The occurrence of a single malformation (gastroschisis) after application of 1000 mg/kg b. w. from day 6 to 15 of pregnancy, few ossifications of phalanges and differences in swimming behaviour are not regarded as the effect of the substance. In conclusion, the oral use of HS 1500 in the treatment of gastrointestinal diseases in animals during pregnancy is regarded to be riskless.

Administration, Oral↗
PubMed1996

[The resorptive behavior of a low-molecular weight humic substance after a single oral administration to the rat].

By labeling HS 1500 with a radioactive 14C, it was proven that after oral application and under certain circumstances, low amounts of low molecular humic acids are for a short time absorbed from the gastrointestinal tract. But the biological availability of the substance is very low (less than 0.1% of the applied high doses). The plasma concentration curve assumes a first order kinetic for invasion and excretion. After oral application of 500 mg/kg b.w. HS 1500 the half life period was 1.5 hours and maximum plasma concentration was 3 micrograms/ml. The result obtained indicate that HS 1500 is toxicological riskless after oral administration. Taking into account the pharmacokinetic data, residues of the substance in animal tissues can be ruled out with high significance.

Administration, Oral↗
PubMed1994

Human postmortem interval estimation from vitreous potassium: an analysis of original data from six different studies.

The investigation of the postmortem interval (PMI) by determining potassium levels in the vitreous humor (KV) has been a subject of forensic pathology research for more than a quarter of a century. The numerous studies to date have yielded a variety of linear or piecewise-linear relationships between KV and PMI, i.e., different estimated intercepts and slopes of regression line(s) as well as different reliabilities of these estimates. This lack of agreement is due in part to the variable numbers of cases reported from study to study, differing observed ranges of KV and PMI, and the unaccommodated effects of factors on potassium concentration, including age of subject, amount of urea nitrogen, ambient temperature, and presence of illness. Original data from six of these studies, for a total of 790 cases, are reanalyzed together. The relationship between KV and PMI is not completely linear, and the residual variability of KV as a function of PMI is not constant. Thus, two main assumptions of the simple linear model, linearity and constant variance, are not supported by the data. It is clearly problematic to report statistical summaries such as the slope of an estimated regression line and the reliability of that estimate based on a model with faulty assumptions. Yet even after rescaling the data in an attempt to achieve linearity in the KV-PMI relationship and to stabilize residual variation, the relationship continues to be non-linear and its variability unstable. A new approach is developed for modeling KV and PMI that accommodates non-linearities and changing residual variability. A local regression model, specifically a loess smooth curve, is fitted separately to the data from each of the six studies. The loess smooth curve adapts locally to the changing and possibly non-linear relationship between KV and PMI across their observed ranges. The data from all six studies are then combined to yield a single loess curve with 95% confidence bands. The estimated loess curve and confidence bands are used in an inverse prediction method to construct low, middle and high PMI estimates at given values of KV. The reliability of estimated PMI decreases as KV increases. Although the confidence bands surrounding the overall curve widen in the extreme high end due to there being fewer available data in that region, PMI estimates are more precise over the entire range of KV and PMI than those obtained from any single study alone. A cross-validation procedure provides an independent check of the predictive performance of the method.

Age Factors↗
PubMed1994

Some computational and statistical tools for paired comparisons of digital images.

This article is a case-based review that introduces applied statisticians to a number of issues and methods that arise in clinical studies with paired digital images as outcomes. Single photon emission computed tomography (SPECT) is the imaging modality used in two examples. The first is a physical simulation of relevant clinical features of SPECT images using a customized head phantom scanned under different experimental conditions. The objective is to demonstrate and compare several current methods for image registration, i.e., image superimposition in some optimal manner to obtain a common frame of reference within which to make pixel-by-pixel comparisons. Image registration together with image normalization to correct for spurious differences in background activity levels enable quantification of differences in paired images. The physical simulation assesses quantification accuracy. The second example involves two SPECT images of the same brain tumour patient taken about two months apart. The objective here is to demonstrate several tools from morphological image analysis for image segmentation, i.e., separation of 'figure' and 'ground', and simple image regression to detect patterns of differences in time, again after registration and normalization. The clinical context of both examples helps to keep the review in practical focus and is a useful starting point for descriptions of many standard tools in applied medical image analysis. References to relevant literature are provided for readers wanting to study particular subjects in depth. As medical image analysis becomes more sophisticated, more cost-conscious and scrutinized more intensively, proper attention to the computational and statistical bases for practical conclusions become even more crucial.

Brain Neoplasms↗
PubMed1993

[The use of the HET-CAM test for the determination of the irritating effects of humic acids].

Using the synthetic humic acid product HS 1500 and the native product Sodium-Humate, the suitability of the HET-CAM-test to evaluate irritating effects was tested. Neither sensitizing nor irritating properties were detectable in concentrations of up to 10% in either humic acid solution. This leads us to the conclusion that both products are very mildly acting substances on mucous membranes and skin, causing no irritative effects. In order to improve the certainty of these results, it is still currently recommended to carry out the Draize-test in addition to the HET-CAM procedure (SPIELMANN, 1992). We are convinced that the HET-CAM-test can be a very useful first step in distinguishing between irritative and non irritative substances and in protecting animals from pain, even in the event that the results of both tests do not clearly correspond to each other. Taking into account the results of our experiments, a modified HET-CAM-test also seems to be useful to predict the antiphlogistic effects of chemical substances.

Animal Testing Alternatives↗