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Biomedical subjects

Dirk M Dhossche

Publications and source records attributed to Dirk M Dhossche.

6 recordsLinked to original sources

A capillary liquid chromatographic/tandem mass spectrometric method for the quantification of gamma-aminobutyric acid in human plasma and cerebrospinal fluid.

A sensitive and reliable method for the determination of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, in human plasma and cerebrospinal fluid (CSF) has been developed. The method is based on capillary liquid chromatography (LC)/tandem mass spectrometry (MS/MS) using deuterium-labeled GABA (gamma-aminobutyric acid-2,2-D(2), GABA-d(2)) as internal standard. Pre-column derivatization with 7-fluoro-4-nitrobenzoxadiazole (NBD-F) was deployed, allowing both effective in-line pre-concentration and sensitive tandem MS detection of the analyte. An extraction column (10 mm x 0.25 mm, 7 microm, C(18)) was used for preconcentrating and stacking the sample. Separation was carried out on an analytical column (50 mm x 0.25 mm, 5 microm, C(18)). Characteristic precursor-to-product ion transitions, m/z 267--> 249 (for NBD-GABA) and m/z 269--> 251 (for NBD-GABA-d(2)) were monitored for the quantification. A linear calibration curve from 10 to 250 ng/mL GABA with an r(2) value of 0.9994 was obtained. Detection limit was estimated to be 5.00 ng/mL GABA (S/N = 3). Human plasma and CSF samples were analyzed. The concentrations of GABA were found to be 98.6 +/- 33.9 ng/mL (mean +/- S.D., n = 12), and 44.3 +/- 10.0 ng/mL (n = 6) in plasma and CSF, respectively.

Calibration↗

Autism as early expression of catatonia.

BACKGROUND: Reports indicate that catatonia often occurs in autism. The association lacks a conceptual basis. Modern classificatory schemes define autism and catatonia separately and are not conducive to study areas of overlap. The exploration of the relation between autism and catatonia may be important because autism is increasingly recognized but effective treatments are lacking. Catatonia, on the other hand, is thought to be treatable, but is poorly recognized. MATERIAL/METHODS: The literature on autism and catatonia are reviewed to identify areas of overlap. A hypothesis is formulated that, in some cases, autism may the early expression of catatonia. RESULTS: Several areas of overlap between autism and catatonia are found. Catatonic symptoms are common in autism. Effects of anti-catatonic treatments on autistic symptoms are unknown. Abnormal gamma-aminobutyric acid (GABA) function has been implicated in both disorders. Neuroimaging studies show small cerebellar structures in both disorders. There is genetic evidence that susceptibility genes for autism and catatonia are located on the long arm of chromosome 15. Differences between autism and catatonia of age-of-onset, symptoms, and illness course, do not exclude a common genetic etiology. CONCLUSIONS: Focused research is needed to further evaluate the phenomenological, biological, and genetic overlap between autism and catatonia and to test the hypothesis that a subgroup of autism is early-onset catatonia.

Adolescent↗

Could ECT be effective in autism?

Autism is increasingly diagnosed, but therapeutic options are limited in many children. ECT is considered as a safe, effective, and life-saving treatment in people of all ages who suffer from affective disorders, acute psychosis, and, in particular, catatonia. There are recent speculations that certain types of autism may be the earliest expression of catatonia and that both disorders have identical risk factors. Therefore, ECT may improve autism and, if started early enough, may prevent further development of autistic symptoms in some children. The use of ECT in autism has never been systematically assessed. There have been two large ECT studies in children in the 1940s. Autism was not assessed in these studies because the autistic syndrome was just then being recognized as a separate entity. Findings from these studies add little to the hypothesis that ECT may be effective in autistic children, but attest to the safety and feasibility of ECT in children. Another limitation is the use of older ECT techniques. What may well be the greatest deterrent to use ECT in autism is widespread anti- ECT sentiment not only among the public but within the medical community as well. All child specialists--psychiatrists, neurologists, psychologists, and developmental pediatricians--should independently review the feasibility, potential, and risk of using ECT in autism. Unless anti-ECT prejudice can be overcome, it is unlikely that any ECT trial in autism is forthcoming. Research areas that may support the hypothesis that ECT is effective in autism should be pursued. First, any link between autism and catatonia should be further explored in clinical and biochemical studies. A GABA theory of autism and catatonia may be pivotal. Second, the role of abnormal GABAA receptor subunit genes in autism and catatonia should be further assessed. Candidate loci for autism and catatonia have been found on the long arm of chromosome 15 where three GABAA receptor subunits genes are located. The GABAA receptor beta 3 subunit gene (GABRB3) was the leading candidate gene for a subgroup of autism in two independent studies. Third, a novel genetic mouse model of autism should be tested. Mutant mice with a targeted deletion of the GABRB3 gene have a complete deficit of the beta 3 subunit of the GABAA receptor. This knockout mouse model seems promising to study developmental effects of altered GABAA receptor function as it relates to certain developmental disorders including autism.

Autistic Disorder↗

Toxicology of suicide: touchstone for suicide prevention?

BACKGROUND: Systematic studies of consecutive suicides show that risk for suicide concentrates heavily in people with psychiatric illness, particularly depressive disorders and substance abuse. It is generally assumed that suicide is preventable although there is currently no conclusive evidence for efficacy of any preventive action, including use of psychotropic prescription medications. The low base-rate of suicide and ethical concerns of studying suicidal people in controlled trials of medications or psychotherapy are the two most important obstacles for progress in suicide research. No prevention suicide program currently includes routine toxicological monitoring of suicide or other violent death. The use of toxicological monitoring in suicide was examined in this study. MATERIAL/METHODS: Review of the literature on toxicological studies of suicide, in particular of a study done in consecutive suicides in Mobile County, Alabama, between 1990-1998. RESULTS: Toxicological studies in suicides support that there is undertreatment of depressive disorders in people who are at risk for suicide and that substance abuse is an important risk factor. Higher detection rates of antidepressants in recent suicide samples may indicate higher treatment rates of depression. CONCLUSIONS: Surveillance of psychoactive substances among suicides may be a novel and practical way to assess efficacy of selected medical interventions aimed at reducing the number of suicides. Use of toxicological monitoring in suicide should be explored in future studies.

Age Factors↗

Psychiatric consultations in a southern university hospital.

BACKGROUND: Differences in psychiatric referral rates among demographic groups of general hospital patients between 1995 and 1998 in a southern university setting were studied. The contribution of suicide attempts to referral rates was assessed. METHODS: The study was done by analysis of hospital admission and psychiatric consultation data. RESULTS: Psychiatric consultations were done in 844 (2%) of 41,681 admissions. Among patients without suicide attempts, those between ages 30 and 59, whites, and internal medicine admissions had higher referral rates. Age, race, and admitting service were independently associated with psychiatric referral rates. CONCLUSIONS: Findings support previous research showing that psychiatric referral depends on a variety of factors that may be patient-related, disease-related, and/or physician-related. Physicians' motivations to refer or not, organizational barriers or facilitators, disease-related, and/or patient-related factors (eg, age and race) need to be assessed further as determinants for requesting psychiatric consultation.

Adolescent↗