Biomedical subjects

D L Arnold

Publications and source records attributed to D L Arnold.

At least 91 records · Page 5Linked to original sources

PubMed1998

Effects of Great Lakes fish consumption on the immune system of Sprague-Dawley rats investigated during a two-generation reproductive study.

The effects of Great Lakes fish on food consumption, body and organ weights, and hematological parameters were investigated in the first- (F1) and second- (F2) generation Sprague-Dawley rats assigned to immunological studies. The parent- (F0) generation rats were fed either a control diet or diets containing 5 or 20% lyophilized chinook salmon from Credit River (Lake Ontario, LO) or Owen Sound (Lake Huron, LH). The F1 and F2 pups were exposed to the fish diet in utero, through the dam's milk to 21 days of age and through the respective diets to 13 weeks of age. The study included an F1-reversibility (F1-R) phase in which rats at 13 weeks of exposure to fish or control diets were switched to the control diet for 3 months. Statistically significant effects included increased growth rates in the F1 male rats fed the LH fish diets compared to those fed the LO fish diets; increased liver weights in the F2-generation male rats fed the LH-20% and LO-20% diets compared to those fed the 5% fish diets; reduced thymus weights in the F1-R female rats fed the LO-20% fish diet compared to those fed the LO-5% or LH-20% fish diets and in the F2 male rats fed the LO diets compared to those fed the LH diets; increased kidney weights in the F2 male rats fed the LH-20% diet compared to those fed the LH-5% or LO-20% diets; reduced but reversible effects on red blood cell (RBC), white blood cell (WBC), neutrophil, lymphocyte, and monocyte numbers in the F1-generation female rats fed the fish diets; reduced red blood cell (RBC), white blood cell (WBC), and lymphocyte numbers in the F2 male rats fed the LO diets compared to those fed the LH diets; and reduced WBC and lymphocyte numbers in the F2 female rats fed the LO-20% diet compared to those fed the LH-20% fish diet. These results suggested that long-term exposure to Great Lakes fish contaminants may have adverse effects on some immune-related parameters. The impact of such changes on the functional aspects of the immune system of rats and consequently on human health needs to be further investigated.

Animal Feed↗

PubMed1998

Effects of Great Lakes fish consumption on the immune system of Sprague-Dawley rats investigated during a two-generation reproductive study.

The effects of Great Lakes fish contaminants on several quantitative and functional aspects of the immune system were investigated in the first (F1) and second (F2) generations of Sprague-Dawley rats. The F0 rats were fed either a control diet or diets containing 5 or 20% lyophilized chinook salmon from the Credit River of Lake Ontario (LO) and Owen Sound point of Lake Huron (LH). The F1 and F2 pups were exposed to fish in utero, through the dam's milk to 21 days old, and through the dam's respective diets to 13 weeks of age. The study included an F1-reversibility (F1-R) phase in which rats at 13 weeks of exposure to fish or control diets were switched to the control diet for 3 months. The most outstanding finding was a statistically significant increase in absolute spleen leukocytes and absolute and percentage lymphocytes in the F2 male rats fed the LH fish diets compared to the control and to those fed the LO fish diets with the 20% fish diets having higher cell numbers compared to the LO-5% fish diets. A parallel increase in the T-helper/inducer T-lymphocyte subset numbers was observed. Increased but statistically insignificant plaque-forming cell (PFC) numbers were obtained in the F2 male rats fed the LH fish diets compared to those fed the LO fish diets and in the F1-R female group of rats fed the LH fish diet compared to those fed the LO fish diets. Phagocytosis by resident peritoneal macrophages was significantly increased in the F1 male and F2 female rats fed the fish diets compared to the control. The phagocytic activity was significantly higher in the F2-generation male and female rats fed the LO diets compared to those fed the LH diets. Other parameters including lymphocyte transformation in response to mitogens, the number of Listeria monocytogenes bacteria surviving in the rat spleens, and the natural killer cell activity were not affected significantly by any of the treatments. Overall, the effects of diets containing chinook salmon from the LO and LH sources on the immune system of rats were minimal and were on quantitative rather than on functional aspects of the system. Further focused research would be required in order to establish conclusively that the immune system of cohorts who ingest Great Lakes fish frequently is at a greater risk for adverse effects.

Animal Feed↗

PubMed1998

Magnetic resonance spectroscopy guided brain tumor resection: differentiation between recurrent glioma and radiation change in two diagnostically difficult cases.

BACKGROUND: It is often difficult to differentiate a recurrent glioma from the effects of post-operative radiotherapy by means of conventional neurodiagnostic imaging. Proton magnetic resonance spectroscopic imaging (1H-MRSI), that allows in vivo measurements of the concentration of brain metabolites such as choline-containing phospholipids (Cho), may provide in vivo biochemical information helpful in distinguishing areas of tumor recurrence from areas of radiation effect. PATIENTS AND METHODS: Two patients who had undergone resection and post-operative radiotherapy for a cerebral glioma became newly symptomatic. Computed tomographic (CT) and magnetic resonance imaging (MRI) performed after the intravenous infusion of contrast material, and in one case, [18F]fluorodeoxyglucose positron emission tomography (PET), could not differentiate between the possibilities of recurrent glioma and radiation effect. The patients underwent 1H-MRSI prior to reoperation and the 1H-MRSI results were compared to histological findings originating from the same locations. RESULTS: A high Cho signal measured by 1H-MRSI was seen in areas of histologically-proven dense tumor recurrence, while low Cho signal was present where radiation changes predominated. CONCLUSIONS: The differentiation between the recurrence of a cerebral glioma and the effects of post-operative irradiation was achieved using 1H-MRSI in these two patients whose conventional neurodiagnostic imaging was equivocal for such a distinction. Where these two conditions are present, metabolite images from 1H-MRSI, such as that based on Cho, can be co-registered with other imaging modalities such as MRI and may also be integrated with functional MRI or functional PET within a multimodal imaging-guided surgical navigation system to assure maximal resection of recurrent tumor while minimizing the risk of added neurological damage.

Adult↗

PubMed1998

Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis.

Recent magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) techniques have focused the attention of the multiple sclerosis (MS) research community on reanalysis of classic pathological approaches that have suggested significant axonal injury in this demyelinating disease. There now is abundant evidence from animal work that substantial "innocent bystander" damage to axons can occur with central nervous system (CNS) inflammation. Given the close interactions between axons and glia, it is no surprise that glial damage leads to secondary axonal changes. MRI, MRS, and MRS imaging studies have emphasized that axonal loss or damage in MS can be both substantial and early. The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between these axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.

Atrophy↗

PubMed1998

Imaging axonal damage of normal-appearing white matter in multiple sclerosis.

The current study was designed to determine the relative distribution of decreases of N-acetylasparate (NAA), a marker of axonal damage, between lesions and normal-appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine/phosphocreatine (NAA:Cr) in those compartments and changes in disability. Data were collected from a 30-month longitudinal study of 28 patients with either a relapsing course with partial remissons and no progression between attacks (relapsing/remitting) (11 patients) or a course of progressively increasing disability, following a period of relapsing/remitting disease (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic imaging (MRSI) and conventional MRI examinations were performed at 6-8-month intervals with concurrent clinical assessments of disability. General linear models were used to test associations between MRSI, MRI, lesion volume and clinical data. Analysis confirmed that the NAA:Cr ratio is lower in lesions than in the normal-appearing white matter (-15.3% in relapsing/remitting multiple sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower NAA:Cr ratio per unit lesion volume previously observed for secondary progressive relative to relapsing/remitting patients was found to result from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter rather than from any differences within lesions. The importance of changes in the normal-appearing white matter was emphasized further with the observation that the NAA:Cr ratio in the normal-appearing white matter accounted for most of the observed 15.6% (P < 0.001) decrease in the NAA:Cr ratio in the brains of relapsing/remitting patients over the period of study. The decrease in the NAA:Cr ratio in normal-appearing white matter correlated strongly (P < 0.001) with changes in disability in the relapsing/remitting subgroup. These results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis. The accumulation of secondary axonal damage in the normal-appearing white matter may be of particular significance for understanding chronic disability in this disease.

Aspartic Acid↗

PubMed1998

Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study.

It has been difficult to establish a strong correlation between total brain T2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, in part because of the lack of pathological specificity of T2-weighted MRI signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements of the resonance intensity of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index of axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsing or a secondary progressive clinical course. Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations were obtained at intervals of 6-8 months with concurrent clinical evaluation. At the onset of the study, the brain N-acetylaspartate:creatine resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate:creatine ratio for the 11 relapsing patients and a significant (P < 0.001) correlation between changes in the brain N-acetylaspartate:creatine ratio and expanded disability scale scores for the patients in this group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (seven of 11 patients). Increases in T2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences between the subgroups) did not correlate with disability either in the group of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability. Total T2-weighted lesion volumes, although more sensitive to changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.

Aspartic Acid↗

PubMed1998

Spectroscopic imaging of frontal neuronal dysfunction in hyperekplexia.

We used proton magnetic resonance spectroscopic imaging (MRSI) to assess in vivo cortical neuronal involvement in hyperekplexia. Cerebral neuronal function was measured using proton MRSI in four unrelated patients with hyperekplexia and 20 healthy controls. All patients had the major form of hyperekplexia, with additional atypical clinical features in two of them. Family history was positive in three patients and absent in one. The neuronal marker N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine (Cr) were measured in frontal, central and parietal areas. The MRSI showed a reduction of the relative resonance intensity of NAA/(Cr + Cho) in frontal and central regions in three patients, and in the right frontal region of the fourth. In one patient a second MRSI showed normal relative NAA resonance intensities over both temporal lobes as well as in the brainstem. In two subjects the topography of EEG abnormalities in the frontal lobes coincided with the MRSI findings. This proton MRSI study indicates the presence of frontal neuronal dysfunction in hyperekplexia. Whether this represents cortical dysfunction or an epiphenomenon of diencephalic or brainstem abnormalities remains open. However, the observation of normal proton MRSI in the temporal regions and brainstem in one of the patients seems to concur with the hypothesis of a facilitatory role of cortical dysfunction within areas of sensorimotor representation in the generation of the pathological startle reaction in hyperekplexia.

Adolescent↗

PubMed1998

Proton magnetic resonance spectroscopic imaging in patients with extratemporal epilepsy.

PURPOSE: Reduced levels of N-acetylaspartate (NAA) in temporal lobes responsible for temporal lobe epilepsy have been observed consistently in proton magnetic resonance spectroscopy (MRS) studies. METHODS: We investigated the potential of proton MRS to detect low NAA outside of the temporal lobes in patients with non-lesional partial extratemporal epilepsy. Proton MR spectroscopic imaging (MRSI) data of both frontal lobes and central/postcentral regions were obtained in 20 such patients and 16 normal control subjects. The epileptogenic region was determined by an extensive clinical-EEG investigation, including the recording of habitual seizures in each patient, and intracranial EEG recordings in 10 patients. RESULTS: The relative NAA resonance intensities (i.e., NAA/phosphocreatine plus creatine (CR(t)), NAA/choline-containing metabolites (Cho(t)) and NAA/Cr(t) + Cho(t)), were all significantly reduced throughout the spectroscopic image as compared with that of the controls. Furthermore, reduction of the NAA ratios was greater in the epileptogenic region as compared with the nonepileptogenic regions, on EEG investigation. CONCLUSIONS: In vivo proton MRSI of patients with nonlesional partial extratemporal epilepsy detected evidence of widespread neuronal damage or dysfunction that was greatest in the region of seizure focus.

Adult↗

PubMed1998

Neuronal metabolic dysfunction in patients with cortical developmental malformations: a proton magnetic resonance spectroscopic imaging study.

Cortical developmental malformations are best diagnosed by MRI and are often the cause of refractory epilepsy. Little is known about the metabolic cell function on MR spectroscopy of these types of brain anomaly. We studied 23 patients with cortical developmental malformations and refractory epilepsy using proton MR spectroscopic imaging. Mean age was 28 years (range, 9 to 47 years). The lesions examined were focal cortical dysplasia (n = 5), heterotopia (four band, six periventricular, two subcortical), polymicrogyria (n = 3), tuberous sclerosis (n = 2), and polymicrogyria and periventricular nodular heterotopia (n = 1). We measured the relative signal intensity of N-acetylaspartate/creatine (NAA/Cr) in the lesion, in the perilesional region, and in the region remote from the visible lesion. The values were compared with those from similar brain regions of 25 normal control subjects. The mean NAA/Cr z score values for the 23 patients were as follows: lesion, -2.20 +/- 0.32 (mean +/- SE), n = 21; perilesional region, -1.01 +/- 0.38, n = 15; and distant region, -0.03 +/- 0.34, n = 18 (p < 0.0002). Despite the presence of a large number of neurons, heterotopia showed a relative decrease of NAA in some patients, suggesting that the neurons present were dysfunctional. The maximal NAA/Cr decrease, indicating metabolic dysfunction, colocalized to the structural malformation as defined by MRI and extended to normal-appearing regions adjacent to the visible lesion.

Adolescent↗

PubMed1998

Effects of aerobic training in patients with mitochondrial myopathies.

We studied the physiologic adaptation of patients with mitochondrial myopathies to aerobic training. Ten patients underwent individually supervised, moderate-intensity aerobic training on a treadmill for 8 weeks. Biochemical and functional measures improved with training. Estimated aerobic capacity increased by 30%. Blood lactate concentrations at rest and after exercise decreased by 30%. Muscle phosphorus magnetic resonance spectroscopy measurements of adenosine diphosphate recovery after exercise improved by more than 60%. Fatigue and tolerance to daily activities also improved. Although the improvement in exercise tolerance may be due in part to reversal of the effects of secondary deconditioning, this uncontrolled clinical trial suggests that aerobic training can benefit patients with mitochondrial myopathies.

Activities of Daily Living↗

PubMed1998

The use of magnetic resonance spectroscopy in the evaluation of the natural history of multiple sclerosis.

Magnetic resonance spectroscopic imaging (MRSI) can be used to define specific chemical-pathological changes in the brain of patients with multiple sclerosis. Magnetic resonance spectroscopy offers promise for improved definition of the nature of individual lesions, the dynamics of their evolution, their effects on normal appearing white matter, and their relation to clinical disability. Combined multimodal MRSI studies of the brains of patients with multiple sclerosis therefore soon may provide efficient, specific, and quantitative new approaches to assessment of drug effects in therapeutic trials.

Axons↗

PubMed1997

Proton magnetic resonance spectroscopic imaging for discrimination of absence and complex partial seizures.

We performed proton magnetic resonance spectroscopic imaging of the temporal lobes between, during, and soon after nonconvulsive seizures in 20 patients with documented temporal lobe epilepsy, 5 patients with primary generalized epilepsy, and 2 patients with secondary generalized epilepsy. Our objective was to determine whether there were metabolic changes observable by magnetic resonance spectroscopic imaging during seizures and whether these changes were specific for focal or generalized nonconvulsive seizures. We found a significant increase in lactate to creatine plus phosphocreatine (lactate/creatine) values, reflecting an imbalance in energy supply and demand or an adaptation in response to ictal neuronal discharges, during and soon after complex partial seizures, but not during or soon after absence seizures associated with generalized epilepsy. In patients with temporal lobe epilepsy, the N-acetylaspartate resonance relative to creatine plus phosphocreatine was low in one or both temporal lobes, indicating neuronal loss or damage. This was not observed in patients with primary generalized epilepsy. The regions with abnormal lactate/creatine and N-acetylaspartate/creatine values corresponded to the epileptogenic focus as defined by clinical-electroencephalographic investigation. There was no change in the N-acetylaspartate/creatine values in the temporal lobes between the interictal, ictal, or postictal states. We conclude that (1) partial seizures are associated with abnormally high lactate levels, but absence seizures are not, and (2) no short-term changes of N-acetylaspartate occur during or soon after complex partial seizures or absence seizures. These findings may be related to the lack of postictal confusion in patients with absence seizures, as well as with the more benign course of primary generalized epilepsy with nonconvulsive attacks.

Adolescent↗

PubMed1997

Imaging of axonal damage in multiple sclerosis: spatial distribution of magnetic resonance imaging lesions.

We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2-weighted magnetic resonance images, and lesion distribution images were generated for, each patient. The conventional magnetic resonance and spectroscopic images were transformed into a standard brain-based stereotaxic coordinate space, allowing comparison of images from different patients on a voxel-by-voxel basis. The spatial distribution of lesions in the transformed magnetic resonance images did not differ significantly between the relapsing and the progressive disease groups. We then generated from the individual data sets, group lesion probability distribution images for the relapsing and the progressive disease groups. The spatial distribution of metabolites was characterized with respect to lesion distribution using the magnetic resonance spectroscopic images transformed into stereotaxic space and averaged. The neuronal marker N-acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects. Comparison of the averaged metabolite and T2-weighted lesion probability images confirmed loss of N-acetylaspartate in regions of both high and low lesion probability. This suggests that diffuse axonal volume loss or dysfunction extends beyond the inflammatory lesions of multiple sclerosis, perhaps due to microscopic disease or wallerian degeneration along projection pathways of axons traversing the lesions.

Adult↗

PubMed1997

Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: a series of 100 patients.

Surgery is a safe and effective treatment for drug-resistant temporal lobe epilepsy (TLE). However, bilateral electroencephalographic (EEG) abnormalities are frequently present, making presurgical lateralization difficult. New magnetic resonance (MR) techniques can help; proton magnetic resonance spectroscopic imaging (MRSI) can detect and quantify focal neuronal damage or dysfunction based on reduced signals from the neuronal marker N-acetylaspartate, and magnetic resonance imaging (MRI)-based measurements of amygdala-hippocampal volumes (MRIVol) can improve the detection of atrophy of these structures. We performed proton MRSI and MRIVol in 100 consecutive patients with medically intractable TLE to determine how well these techniques agreed with the lateralization by extensive EEG investigation. We found that the EEG, MRSI, and MRIVol findings were highly concordant. The MRSI was abnormal in 99 of 100 patients (bilateral in 54%). The MRIVol was abnormal in 86 of 98 patients (bilateral in 28%). We obtained lateralization in 83% of patients using MRIVol alone, in 86% using MRSI alone, and in 90% by combining MRSI and MRIVol (vs 93% lateralization by EEG). MRSI was abnormal in 12 patients with normal MRIVol. The combination of proton MRSI and MRIVol can lateralize TLE accurately and noninvasively in the great majority of patients. By reducing reliance on EEG, these imaging techniques could reduce prolonged presurgical evaluation and make seizure surgery available to more patients.

Adult↗

PubMed1997

Magnetic resonance spectroscopy in vivo: applications in neurological disorders.

Magnetic resonance (MR) spectroscopy (MRS) is performed using the same magnets and computers as conventional MR imaging (MRI). However, unlike conventional MRI, which provides structural information, MRS provides chemical information that represents pathologically specific measures useful for diagnosis and monitoring of patients affected by neurological disorders. This review will focus on selected clinical applications of MRS that have been demonstrated to have clinical use. These include phosphorus MRS of muscle to diagnose metabolic muscle disease, and proton MRS of brain to lateralize temporal lobe epilepsy, to classify brain tumors, and to evaluate the natural history and pathology of multiple sclerosis.

Brain↗

PubMed1997

Proton magnetic resonance spectroscopy in brain white matter disorders.

The advent of magnetic resonance imaging (MRI) has revolutionized the clinical approach to the evaluation of brain white matter disorders and has contributed significantly to expansion of the concept of these diseases. MRI is very sensitive at detecting white matter lesions, but conventional T1 and T2-weighted images do not provide specific pathological information about the lesions, and correlation between MRI lesion load and clinical disability is often weak. Proton magnetic resonance spectroscopy can provide chemical-pathological information of a given tissue in vivo. The use of this MR technique in brain white matter disorders has shown to improve diagnostic classification and to provide surrogate measures useful for monitoring disease evolution and response to therapeutic intervention.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Muscle high-energy phosphates in central nervous system disorders. The phosphorus MRS experience.

Phosphorus magnetic resonance spectroscopy (MRS) was used to study muscle phosphates metabolism in several brain disorders. Those with primary mitochondrial encephalomyopathies showed the typical pattern of impaired oxidative metabolism at rest and during recovery after exercise. In migraine, Parkinson's disease and alternating hemiplegia muscle MRS observations lend support to a possible mitochondrial dysfunction. Similar observations in multiple sclerosis are probably the result of secondary deconditioning. In post polio syndrome and in some of the hereditary ataxias, elevated intracellular inorganic phosphates may be the result of another, yet unknown, metabolic impairment. Thus, muscle phosphate metabolism may be altered in various central nervous system (CNS) disorders by different metabolic impairments. All these possibilities should be taken into account when evaluating MRS results in brain diseases.

Central Nervous System Diseases↗

PubMed1997

Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys and their nursing infants. Part 3: post-reproduction and pathological findings.

A group of 80 menstruating rhesus (Macaca mulatta) monkeys were randomly allocated to four similar rooms (20 monkeys/room) and then to one of five dose groups (four females/dose group/room). Each day the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 microg Aroclor 1254/kg body weight. After 25 months of continuous dosing, approximately 90% of the treated females had attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their nuchal fat pad. Concurrently, sebaceous glands were being examined for changes analogous to chloracne. Subsequently, the females were paired with untreated males. The infants' blood PCB levels at birth were not correlated with its dam's dose or blood PCB level. However, there was an association between an infants preweaning blood PCB levels and its dam's dose and PCB milk levels. After weaning, the infants were not dosed with PCB. The half-life for the PCB in the infants' blood was determined and found to be slightly more than 15 wk. After 6 yr on test, three monkeys from the 0, 5, 20 and 40 microg dose groups were randomly allocated to a depletion study to ascertain the half-lives of specific PCB congeners (Mes et al., Chemosphere 1995, 30, 789-800). Concurrently, necropsies began of the remaining females, and of seven infants from the treated dams and four infants from the control dams, which had attained an age of 2 yr. Approximately 3 yr later, the depletion monkeys were necropsied. The only statistically significant treatment-related pathological changes found during the study were in the adult females, in which an involution of the sebaceous glands and a dose related increase in liver weight due to hyperplasia were evident.

Administration, Oral↗