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Biomedical subjects

K F Faull

Publications and source records attributed to K F Faull.

At least 127 records · Page 7Linked to original sources
PubMed1983

Cerebrospinal fluid monoamine metabolites in narcolepsy and hypersomnia.

Two groups of patients with the common complaint of excessive daytime sleepiness were examined. One group fulfilled the criteria for narcolepsy. The other had the sole symptom of excessive daytime sleepiness, confirmed by sleep latency tests, which was unaccompanied by systemic illness. Spinal fluid examinations for homovanillic acid, 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 5-hydroxyindoleacetic acid were carried out before and after administration of probenecid on the 20 patients and 40 controls. Probenecid-corrected accumulation of the dopamine metabolites was significantly increased in each of the patient groups, suggesting an association between pathological sleepiness and elevated dopamine turnover in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

REM sleep eye movement activity and CSF concentrations of 5-hydroxyindoleacetic acid in psychiatric patients.

The relationship between rapid-eye-movement (REM) sleep tonic and phasic activity measures and the pre- and postprobenecid cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) was examined in a sample of 14 unmedicated psychiatric patients. The average duration of an eye movement burst and the average number of eye movements within a burst were found to be inversely related to the probenecid corrected accumulation of 5-HIAA in the CSF. These results are interpreted as indicating an association between REM burst eye movement activity and serotonin turnover in psychiatric subjects.

Adult↗
PubMed1983

Posttraumatic excessive daytime sleepiness: a review of 20 patients.

Twenty patients complaining of excessive daytime somnolence (EDS) secondary to significant head trauma were studied objectively. Several polygraphic recording protocols were performed over the 12-year study period. Eighteen of the 20 patients were objectively sleepy, 8 of them presented mixed sleep apnea syndrome that fragmented their sleep, 5 patients' sleep-related breathing problems improved over time, 9 patients presented daytime somnolence, and 1 reported abrupt bouts of muscle weakness and had two sleep onset rapid eye movement (REM) periods during daytime testing. Cerebrospinal fluid analysis for specific neurotransmitter metabolites' evaluation, pre- and postprobenecid, did not differentiate posttraumatic EDS patients from narcoleptics or other patients with EDS. Two patients (one with organic brain syndrome, the other depressed) reported subjective sleepiness, not confirmed by objective data. Objective testing in posttraumatic sleepiness is recommended because of the plurality of problems and medicolegal implications.

Adolescent↗
PubMed1982

Monoamine metabolite concentrations in the cerebrospinal fluid of normal and narcoleptic dogs.

Because of the similarity between human and canine narcolepsy, an animal model has emerged with which to investigate the neurochemical basis of the disease. In this study, in vivo differences in cerebral neurotransmitter function between normal and affected dogs were measured by comparing, before and after probenecid administration, the concentrations in cisternal cerebrospinal fluid of the monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol. Cisternal cerebrospinal fluid was collected from the cisterna magna of anaesthetized animals, and samples were analyzed for the metabolites and probenecid using combined gas chromatography-mass spectrometry. The concentrations of both the conjugated and non-conjugated forms of each of the metabolites were determined in all samples and the role of conjugation in cerebral monoamine metabolism is discussed. Before probenecid treatment, comparisons of metabolite concentrations in samples from normal versus narcoleptic dogs showed significantly lower amounts of the dopamine and of the 5-hydroxytryptamine metabolites in CSF from the affected animals. After probenecid administration, the concentrations in the CSF of all the metabolites increased. However, the amounts of 5-hydroxyindoleacetic acid, and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol, in samples from narcoleptic dogs were significantly lower than those found in samples from normal dogs. The implications of these results for our understanding of the neurochemical basis of REM sleep initiation and for treatment of narcolepsy/cataplexy are discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Tryptolines: artifact or reality? A new method of analysis using GC/MS.

Using adsorption to C-18 reverse phase resin we have developed a simple, fast and efficient procedure for extracting tryptolines from perchloric acid homogenates of brain tissue. Furthermore, using fused silica capillary chromatography coupled to negative chemical ionization mass spectrometry of heptafluorobutyl derivatives, we have developed a sensitive and specific procedure for identifying and quantitating tryptolines in extracts of brain tissue. Of the five members of the tryptoline class which have been studied by us, we have been able to find consistent evidence for the presence of only one, tryptoline. We find tryptoline to be present in extracts of whole rat brain in concentrations of approximately 370 pg/g of tissue. The finding of low concentrations of this compound mandates additional investigation to completely rule out artifactual formation.

Animals↗
PubMed1981

Alterations in cerebrospinal fluid dopamine metabolites following physostigmine infusion.

The effect of IV physostigmine administration on the cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in normal subjects was determined. After an adjustment for differing CSF concentrations of probenecid, physostigmine was found to elevate CSF HVA and DOPAC concentrations. The authors discuss these changes in CSF HVA and DOPAC and their possible relationship to the ability of physostigmine to decrease the symptoms of some patients with tardive dyskinesia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Neuroendocrine and neurochemical measurements in depression.

The authors performed dexamethasone suppression tests (DST), TRH infusions, 72-hour urine collections, and lumbar punctures on a group of male depressed patients. Approximately 60% of the patients were DST positive and 33% had a blunted TSH response. Two biologic variables, the 8 a.m. postdexamethasone cortisol and the postprobenecid CSF 5-hydroxyindoleacetic acid (5-HIAA), accounted for over half of the variance in the behavioral measure, the Hamilton score. Plasma cortisol elevation was associated with high 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion; TSH blunting was associated with low urinary MHPG excretion. Comprehensive biologic measures showed certain significant interrelationships and correlations with the severity of depression.

Adult↗
PubMed1981

Clinical application of the probenecid test for measurement of monoamine turnover in the CNS.

The probenecid-induced accumulation of the acidic metabolites of dopamine and serotonin is widely used to estimate the CNS turnover of these amines in human subjects. The theoretical basis of the probenecid test is discussed, including the assumptions on which the test is based, and the limitations of the procedure. Suggestions are offered on appropriate methods for analyzing test data. Available evidence suggests that maximal inhibition of the efflux of the acidic metabolites of dopamine and serotonin from the CSF is not achieved with probenecid doses up to 100 mg/kg. Therefore, before a comparison can be made between the accumulation of CSF metabolites from different groups of subjects, a correction for CSF probenecid concentrations is necessary. Moreover, in addition to the measurement of dopamine and serotonin turnover, the probenecid test can be extended to include comparisons of CNS turnover of other monoamines including octopamine, p-tyramine, and tryptamine.

Brain↗
PubMed1980

CSF monoamine metabolites in depression and schizophrenia.

The authors report cerebrospinal fluid (CSF) concentrations of five monoamine metabolites before and after probenecid administration in normal subjects and patients with depression and schizophrenia. No differences were found in baseline metabolite concentrations among the three groups. CSF metabolite and CSF probenecid concentrations were significantly correlated in depressed patients for all metabolites, and there was decreased postprobenecid accumulation of homovanillic acid in the CSF of depressed patients compared with schizophrenic patients and with normal subjects. The authors propose a method for correcting for probenecid concentrations. Data from normal subjects should be of value for other investigators using the probenecid technique.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Selected ion monitoring assay for biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid.

Details are presented of an improved selected ion monitoring assay for the major biogenic amine metabolites and probenecid in human lumbar cerebrospinal fluid (CSF). The metabolites and probenecid are simultaneously extracted with ethyl acetate from an acidified aqueous phase, and are simultaneously converted to pentafluoropropionyl esters by reaction with pentafluoropropionic anhydride and pentafluoropropanol. The esters of the metabolites are analyzed following a single injection of the derivatized sample onto the gas chromatographic column, while the ester of probenecid is analyzed following a separate injection onto the gas chromatographic column. Quantitation is achieved using for internal standards dueterated analogues of the metabolites and a chemical analogue of probenecid. Data are presented on the concentration of free and conjugated forms of the metabolites in lumbar CSF taken from healthy volunteers.

Biogenic Amines↗
PubMed1978

A selective ion monitoring assay for probenecid.

A selective ion monitoring assay for probenecid (p-(dipropylsulfamyl)benzoic acid) using m-(di-isobutylsulfamyl)benzoic acid as an internal standard is described. The method has been applied to the determination of probenecid concentrations in human cerebrospinal fluid and lends itself to incorporation into the selective ion monitoring procedures used to quantitate other acidic and neutral compounds in such samples.

Chromatography↗
PubMed1977

Metabolic studies on two patients with nonhepatic tyrosinemia using deuterated tyrosine loads.

Metabolic studies on two patients with defects in the tyrosine oxidation pathway are reported. Serum tyrosine was greatly elevated in both patients (1.37 and 1.52 mmol/liter, respectively) and both excreted large quantities of p-hydroxyphenylacetic acid, p-hydroxyphenyllactic acid, and p-hydroxyphenylpyruvic acid. Deuterated tyrosine loads were administered to both patients, before and after lowering of the serum tyrosine concentration by dietary treatment, and to a normal adult control subject. In one patient the excretion of the deuterated (D2)-tyrosine load was more than 300 times that found in the control subject whether the test was done at high or low serum tyrosine level and the pattern of metabolites indicated a persistent defect in p-hydroxyphenylpyruvic acid oxidase. Enzyme assays on needle liver biopsy supported this finding. In the second patient excretion of the D2 label was 300 times that of the control at high serum tyrosine levels, but only 5 times normal at low serum tyrosine levels. This finding was interpreted as indicating substrate inhibition of p-hydroxyphenylpyruvic acid oxidase. The primary defect has not been established in this patient, but the findings are compatible with a defect in hepatic-soluble tyrosine aminotransferase.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1976

The mass spectrometric identification of dipeptides in the urine of a patient suffering from chronic skin ulceration and oedema.

The identification of a complex ninhydrin positive mixture present in the urine of a child suffering from chronic skin ulceration and oedema by direct chemical ionisation mass spectrometric analysis is described. The compounds were shown to be dipeptides, of which glycylproline was the major constituent. At least 15 dipeptides were identified in the urine, most of which contained proline or hydroxyproline in the carboxy terminal position. The results suggested that the patient suffered from a defect in collagen metabolism. This hypothesis was subsequently confirmed by a grossly diminished level of prolidase in cultured fibroblasts and erythrocytes.

Amino Acids↗