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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

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

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

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

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

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

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

Urine screening for abused drugs in new admissions to a VA hospital.

The urine samples from two groups of Veteran's Administration patients newly admitted to general psychiatry units were screened in 1985 and in 1987-88 for abused drugs. The results were compared with urine samples from controls with similar age distributions admitted to an alcohol and drug abuse unit or to medical-surgical units. About 40% of all newly admitted patients were positive for one or more controlled drugs, but there were no significant differences among patient groups in the percentage of urine samples positive for these drugs. Marijuana and benzodiazepines were detected frequently in all patient groups and often in combination, although opiates also were frequently detected in the urine samples from the medical-surgical patients. There was a clear decrease in drug-positive samples with age in all patient groups, much of which could be accounted for by decreased marijuana detection.

Adult

Effects of repeated drug holidays on serum haloperidol concentrations, psychiatric symptoms, and movement disorders in schizophrenic patients.

In a crossover experiment the authors investigated the effects of repeated weekly, 2-day, haloperidol drug holidays on serum haloperidol concentrations, mental status, and neuroleptic-induced movement disorders in seven chronic schizophrenic patients. Haloperidol concentrations decreased about 64% during the initial 36 hours of drug holiday and subsequently increased slightly during the next 24 hours of drug holiday. Two-day weekly drug holidays for 6 weeks resulted in an average reduction of 25% in serum haloperidol concentrations at all drug holiday points. Mental status and movement disorders scores, rated by observers blind to the drug-holiday condition, were not significantly affected by drug holidays.

Drug Administration Schedule

Drug holidays and serum haloperidol levels in schizophrenic patients.

Chronic hospitalized schizophrenic patients receiving haloperidol were placed on drug holidays for 2 days. Serum haloperidol levels in these patients decreased to about 60% of the levels seen just prior to the usual morning dosing during the drug holiday. Control subjects not given a drug holiday showed stable day-to-day serum haloperidol levels. The small drop in serum haloperidol blood levels may relate to the lack of relapse observed in such patients.

Adult

The effect of different planes of nutrition before mating on the reproductive performance of Masham ewes.

A total of 69 ewes were fed either on a low nutritional plane for six weeks prior to mating and for four weeks postmating (LL), or on a low nutritional plane for three weeks and then on a high nutritional plane (LH), or on a high nutritional plane throughout (HH). Ewes at mating were 49.3, 63.7 and 70.6 kg liveweight respectively and their body condition scores were 1.6, 2.9 and 3.8. There was a significant difference in ovulation rate: LL = 1.53, LH = 2.13 and HH = 2.27, and in lambing per cent: 77, 150 and 186 respectively. Under the system of indoor feeding practised at mating, there was no economic advantage to be gained from flushing, but normally ewes would be flushed outside.

Animal Nutritional Physiological Phenomena