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Biomedical subjects

J E Newton

Publications and source records attributed to J E Newton.

At least 19 recordsLinked to original sources
PubMed1998

Lithium visibility in rat brain and muscle in vivo by 7Li NMR imaging.

The apparent concentration of lithium (Li) in vivo was determined for several regions in the brain and muscle of rats by 7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determined in vitro by high-resolution 7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the 7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

Animals↗
PubMed1998

Prevalence of post traumatic stress disorder and other psychiatric diagnoses in three groups of abused children (sexual, physical, and both).

OBJECTIVE: The purpose of this study was to compare the prevalence of Post Traumatic Stress Disorder and other diagnoses in three groups of abused children, sexual only (N = 127), physical only (N = 43), and BOTH (N = 34). METHOD: The children, aged 7 to 13 years, were referred to the project from several sources at Arkansas Children's Hospital and from associated local agencies. The victims and caregivers were separately administered the Diagnostic Interview for Children and Adolescents, Revised Version (DICA). Additionally, caregivers and classroom teachers completed the Child Behavior Checklist (CBCL). Characteristics of the abuse were obtained from an investigative questionnaire. RESULTS: Both victims and caregivers endorsed high rates of disorders, with caregivers generally giving higher rates than children and boys having more externalizing diagnoses than girls. Children in the BOTH group had more diagnoses overall. Concordance between victims and caregivers was modest. PTSD was significantly comorbid with most affective disorders. On the CBCL, caregivers rated girls less disturbed than boys and the sexually abused only group less disturbed than the other groups. Teachers rated the boys more adversely than girls but did not see differences by abuse group. A younger age of onset of sexual abuse and coercion to maintain secrecy predicted a higher number of total diagnoses. Also, children who were physically abused by males had more diagnoses than those physically abused by females. CONCLUSIONS: Children who have been both physically/sexually abused appear to be at highest risk of psychiatric disturbance. PTSD, though common (circa one-third of victims), is generally comorbid with other affective disorders.

Adolescent↗
PubMed1997

The distribution of lithium in rat brain and muscle in vivo by 7Li NMR imaging.

The regional distribution of lithium (Li) in vivo was determined on a relative basis in the brain and muscle of rats by 7Li NMR imaging. Both high resolution 7Li NMR spectroscopy and atomic absorption spectrophotometry were performed on extracts of brain and muscle tissue from the same rats. The average in vivo results were generally in good agreement with the corresponding average in vitro results, despite the relatively low signal-to-noise ratio of the in vivo images. There was good agreement between the two in vitro methods of analysis, both on average and for individual animals. Significant differences were found in vivo among Li concentration ratios for the various brain regions and muscle by 7Li imaging, as well as by the in vitro methods.

Animals↗
PubMed1995

EEG power spectra of dysphonetic and nondysphonetic poor readers.

Two subtypes of poor readers, dysphonetic and phonetic, were compared on EEG spectral values obtained as they viewed strings of letters and short words. Dysphonetic poor readers had significantly higher values than phonetics in the theta and delta bands. Both phonetic and dysphonetic poor readers had lower beta values than adequate reading children with Attention Deficit Disorder. This evidence indicates that poor readers, especially dysphonetics, were less actively engaged in the task.

Achievement↗
PubMed1994

In vivo 19F spin relaxation and localized spectroscopy of fluoxetine in human brain.

Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo 19F spin-lattice relaxation time (T1) of fluoxetine for five patients by the inversion-recovery technique. The individual T1s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T1. The individual T1 correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo 19F resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active metabolite norfluoxetine, as demonstrated by the in vitro 19F NMR spectrum of the lipophilic extract of a small section of brain. In vitro quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 micrograms/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.

Adolescent↗
PubMed1994

Anticardiolipin antibodies in a sample of chronic schizophrenics receiving neuroleptic therapy.

Drug-induced antiphospholipid antibodies have been considered insignificant, a belief that has recently been questioned. Previous studies noted an association between chlorpromazine treatment and the presence of anticardiolipin antibodies (ACA), especially IgM ACA, and have suggested that thrombosis might be more likely in the presence of IgG ACA. We studied the cases of 27 patients receiving long-term neuroleptic therapy who had no history of cerebrovascular disease. IgG ACA was present in 7 (26%) of the 27, and IgM ACA was present in 5 (19%), yet none had shown any manifestations of cerebrovascular disease since initiation of neuroleptic therapy. These data suggest that drug-induced ACA do not predispose to cerebrovascular disease, even when IgG ACA is predominant.

Aged↗
PubMed1994

EEG power spectra of children with dyslexia, slow learners, and normally reading children with ADD during verbal processing.

EEG power spectra were studied in two poor reader groups (with dyslexia and slow learning) and a normally reading clinic control group (with attention deficit disorder) as the children viewed strings of words and letters (seven categories). The children ranged in age from 7.5 to 12 years; 33 were girls, 86 were boys. Bilateral temporal and parietal sites and four midline sites were used. The major difference between groups was in the low beta band, where the ADD group had greater power at the parietal and midline sites. Also, the slow learner group had marginally greater low beta at the left than right temporal site, with the opposite trend found for the dyslexic and ADD groups. Across groups, power was greater at the right than at the left parietal site in the delta and alpha bands and at the right than at the left temporal site in the low beta band. Stimulus category effects were modest, with some alpha suppression to word strings, relative to letter strings, found in the poor readers. In correlational analyses, the combination of greater low beta and less theta power significantly predicted better reading and spelling. Results indicate that the adequate readers more actively processed the stimuli than did the poor readers.

Attention↗
PubMed1993

Inefficacy of propranolol in attenuation of drug-induced parkinsonian tremor.

We investigated the tremolytic effect of long-acting propranolol (propranolol-LA) in six subjects with drug-induced parkinsonism (DIP), using a double-blind, placebo-controlled, crossover experimental design. Subjects received propranolol-LA for 2 weeks and placebo for 2 weeks, with no change in neuroleptic treatment. Tremor frequency and amplitude were objectively quantified at the end of each 2-week period by computerized tremorgram recording. There were no significant differences in attenuation of DIP tremor by propranolol-LA and placebo. Previous investigations reported in the literature have found propranolol to attenuate the tremor of idiopathic parkinsonism (IPD). It is expected that DIP and IPD tremor would respond similarly to propranolol if a solely peripheral or spinal cord tremolytic action were operative. A possible differential attenuation of IPD tremor and DIP tremor provides support for the concept of a higher central tremolytic mechanism of beta-adrenergic receptor-blocking drugs.

Aged↗
PubMed1993

In vivo 7Li nuclear magnetic resonance study of lithium pharmacokinetics and chemical shift imaging in psychiatric patients.

New data are presented on the application of 7Li in vivo nuclear magnetic resonance (NMR) spectroscopy to human studies. The technique was used to monitor the between-dose pharmacokinetics of lithium (Li) in brain for three patients on Li therapy. Brain Li concentrations were at their highest from 0 to 2 hours after the peak occurred in serum concentration. Elimination from brain tissue took longer than elimination from muscle, and no signal could be detected from brain at 10 days after termination of therapy. A birdcage radiofrequency coil for 7Li was constructed and used to measure the 7Li spin-lattice relaxation time of 4.6 seconds in vivo in human head, and to acquire preliminary spectroscopic images of a phantom and human brain.

Blood-Brain Barrier↗
PubMed1993

Human brain fluoxetine concentrations.

Data on 22 subjects treated with fluoxetine suggest that magnetic resonance spectroscopy (MRS) of fluorine-19 can measure brain concentrations of fluoxetine/norfluoxetine in vivo. Fluoxetine accumulates in the human brain relative to plasma, with brain concentrations of fluoxetine/norfluoxetine ranging up to 10.7 micrograms/ml. Brain concentrations may reach a plateau between 6 and 8 months of treatment. The apparent concentration in brain relative to plasma is 20:1, roughly parallel to brain antidepressant concentration ratios in animal studies.

Adolescent↗
PubMed1992

In vivo 7Li NMR imaging and localized spectroscopy of rat brain.

Lithium-7 in vivo NMR spectroscopy and imaging techniques have been developed at 4.7 T for rat head. The pharmacokinetics of lithium (Li) uptake in rat head has been measured using STEAM localized spectroscopy for the whole brain, which showed relatively rapid uptake of Li and a steady level of Li from about 5 to 20 h. Localized spectroscopy on brain sections revealed no differences in Li concentration among the front, middle, and rear of the brain. The spin-lattice relaxation time showed a single exponential decay for the head. The spin-spin relaxation time for head showed a biexponential behavior. Using a 1H-7Li double coil assembly, 7Li images were generated for rat head, as was the corresponding 1H image for anatomic localization. The 7Li image (7-mm slice thickness, 4-mm in-plane resolution) recorded after the last dose in a multiple ip dose protocol shows the Li distribution in the head and neck. Based on 7Li images, the Li level in muscle was about twice that in the brain. Variations of 7Li intensity level across the brain were typically small.

Animals↗
PubMed1992

Fluoxetine and trifluoperazine in human brain: a 19F-nuclear magnetic resonance spectroscopy study.

Fluorine-19 (19F) is a nonradioactive isotope that is well-suited to nuclear magnetic resonance spectroscopy (NMRS) and is a constituent of several medications used to treat psychiatric illnesses. Fluoxetine, a trifluorinated agent, generated a signal from brain that was readily measured by 19F-NMRS. Estimated brain concentrations ranged from 1.3-5.7 micrograms/ml in six subjects at a steady state dose of 40 mg/day. Enhanced sensitivity of 19F has been obtained by conforming the surface coil to the shape of the forehead. Hence, at the current state of development, 19F-NMRS can be applied to clinical questions relevant to concentrations of fluoxetine in brain. We also report observation of NMRS signals from fluorinated neuroleptics in a number of patients at steady state. These signals continue to be difficult to obtain, although a correlation between dose and estimated brain concentrations is suggested.

Adult↗
PubMed1990

Psychophysiological correlates of posttraumatic stress disorder in Vietnam veterans.

We measured event-related brain potential (ERP) component amplitudes and heart rate (HR) to four intensities of randomly presented tones in two matched groups of drug-free male Vietnam veterans: 12 patients diagnosed with posttraumatic stress disorder (PTSD) and 6 normal combat veterans. Subjects were evaluated with structured diagnostic interviews and anxiety and depression rating scales. We found a significant group X intensity interaction for P2 peak amplitude at CZ. Subjects were classified as augmenters or reducers: positive P2 slopes as a function of stimulus intensity implying augmentation and negative slopes implying reduction. Nine of 12 PTSD subjects were reducers (sensitivity of 75%) and 5 of 6 normals were augmenters (specificity of 83.3%). By the third and fourth second following tone onset, the mean HR of PTSD subjects increased more than twice that of the normals. HR change scores were significantly responsive to the manipulation of stimulus intensity and to the difference between our two groups. P2 reduction differentiates Vietnam veterans with combat-related PTSD from combat veteran controls, and PTSD subjects are more autonomically arousable than their combat veteran peers.

Auditory Threshold↗
PubMed1990

In vivo NMR spectroscopy of lithium-7 in humans.

The pharmacokinetics of lithium uptake was measured by 7Li NMR spectroscopy at 24.83 MHz in vivo in the brain and muscle of a normal subject and a patient suffering from bipolar affective disorder, using a modified General Electric Signa clinical magnetic resonance imaging system. Comparison was made to standard phantoms to estimate Li concentrations. The levels of Li in brain and muscle were similar, were typically less than the level in serum, and generally tracked the level in serum. The Li level at steady state in the brain of a patient suffering from schizoaffective disorder was measured over a 7-month period. Substantial variation was seen, which showed some correlation with serum level. Serum level peaked about 2 h after a single 300-mg dose at steady state, and muscle level, immediately thereafter. Brain level peaked considerably later at 4 h. Localized in vivo 7Li NMR spectroscopy was demonstrated by acquisition of a 125-cm3 DRESS slice from the occipital region in less than 7 min.

Adult↗
PubMed1990

HLA antigens in tardive dyskinesia.

Fifty-three male, Caucasian, neuroleptic-treated patients with chronic schizophrenia were examined for the presence of tardive dyskinesia (TD) and were tissue typed. The group with TD (n = 25) was compared to the group without TD (n = 28). HLA-DR4 was more prevalent in the group with TD than in the group without TD, with a relative risk of 3.04 for TD with HLA-DR4 present, although this finding is not statistically significant when corrected for the number of nonparametric comparisons. Other investigations reported an association between HLA-B44 and TD, or between HLA-B44 and neuroleptic-induced parkinsonism. Potential explanations relating the findings of these investigations are discussed.

Dyskinesia, Drug-Induced↗
PubMed1989

HLA antigens in drug-induced parkinsonism.

The results of two epidemiological studies suggest a hereditary predisposition to develop drug-induced parkinsonism. We investigated human leukocyte antigen (HLA) antigen prevalence rates in patients with neuroleptic-induced parkinsonism. Fifty-two male, white, neuroleptic-treated, chronic in-patients with DSM-III-diagnosed schizophrenia were examined for the presence of parkinsonism. Subjects were tested for 23 type A, 43 type B, 4 type C, and 10 type DR HLA antigens. The group of schizophrenic patients with parkinsonism (n = 29) was compared with the group of schizophrenic patients without parkinsonism (n = 23). There were no significant differences between the two groups with respect to age, duration of neuroleptic exposure, or anticholinergic drug exposure. One HLA antigen, B44, was significantly more prevalent in the group with parkinsonism than in the group without parkinsonism. We derived a relative risk of 7.16 for drug-induced parkinsonism with HLA-B44 present in this group of schizophrenic patients. These data indicate that HLA-B44 may play a role in genetic or immunologic susceptibility to develop drug-induced parkinsonism in white schizophrenic individuals.

Adult↗