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Biomedical subjects

T P Bohan

Publications and source records attributed to T P Bohan.

34 records · Page 2Linked to original sources
PubMed1989

The CT and MR evaluation of migrational disorders of the brain. Part I. Lissencephaly and pachygyria.

The migrational disorders are a rare group of congenital malformations of the brain. They consist of the following entities--lissencephaly (agyria-pachygyria), pachygyria, schizencephaly, heterotopia and polymicrogyria. We studied 40 children with migrational disorders radiologically with CT and MR. This article (part I) deals with our patients their characteristic CT and MR findings along with their clinical presentation and course. These patients presented with one or a combination of the following symptoms, hypotonia, seizures, failure to thrive, microcephaly and occasionally hydrocephalus. These two groups of migrational disorders have abnormalities affecting the gyral-sulcal pattern of the cortex and gray-white matter distribution of the brain. MR provided better delineation of these disorders than CT. Because some forms of the migrational disorders can be inherited, it is extremely important for the radiologist to understand the characteristic findings for correct diagnosis which is essential for parental counseling.

Brain↗
PubMed1988

The CT and MR evaluation of lissencephaly.

Lissencephaly is a rare congenital malformation of the brain that has characteristic radiographic and clinical findings. Fifteen cases of lissencephaly were studied with CT and/or MR, and a classification was developed based on these cases and the description of this abnormality found in the literature. These findings can be divided into two groups, primary and secondary. The primary findings consist of (1) a cerebral surface that is agyric or agyric with pachygyric areas, (2) a cerebral contour that is oval or "hourglass" due to lack of or incomplete opercularization of the brain, and (3) an abnormal gray-white-matter distribution in the cerebral hemispheres. The primary findings are necessary to make the diagnosis, which can be made with either CT or MR; however, MR provided better delineation than CT of the cerebral surface and contour as well as better gray-white-matter differentiation in the lissencephalic brains. We believe MR is the technique of choice for evaluating patients with lissencephaly because it is safer and more versatile than CT and provides better delineation of the brains of children.

Brain↗
PubMed1988

The clinical and radiological evaluation of lissencephaly.

Lissencephaly is a rare congenital malformation of the brain that has characteristic clinical and radiographic findings. Thirteen cases of lissencephaly were studied clinically and radiographically with computed tomography and magnetic resonance imaging. A classification was developed based on the findings in these cases and the literature. The clinical and radiographic evaluation of lissencephaly is emphasized, with a thorough discussion of the clinical spectrum of each type, radiographic findings, prognosis, survival, and associated genetic abnormalities.

Brain↗
PubMed1985

Valproylcarnitine: a novel drug metabolite identified by fast atom bombardment and thermospray liquid chromatography-mass spectrometry.

Urine samples from three children at different stages of chronic valproate therapy were partially purified using a cation exchange column. A signal consistent with either valproylcarnitine or octanoylcarnitine was observed in one of these extracts by direct fast atom bombardment-mass spectrometry analysis. These isomeric acylcarnitines were synthesized, separated and characterized by thermospray high performance liquid chromatography-mass spectrometry. This new technique was then employed to positively identify intact valproyl-carnitine in the patients' urine samples. The implications of this finding with regard to a mechanism to account for carnitine deficiency in patients receiving valproate are discussed.

Adolescent↗
PubMed1985

Diagnostic and therapeutic implications of medium-chain acylcarnitines in the medium-chain acyl-coA dehydrogenase deficiency.

The medium-chain acyl-coA dehydrogenase deficiency is one of several metabolic disorders presenting clinically as Reye syndrome. Evidence is presented for a characteristic organic aciduria that distinguishes this disorder from Reye syndrome and other masqueraders characterized by dicarboxylic aciduria. The key metabolites, suberylglycine and hexanoylglycine, are excreted in high concentration only when the patients are acutely ill. More significantly, using novel techniques in mass spectrometry, the medium-chain defect is shown to be characterized by excretion of specific medium-chain acylcarnitines, mostly octanoylcarnitine, without significant excretion of a normal metabolite, acetylcarnitine, in four patients with documented enzyme deficiency. Similar studies on the urine of two patients reported with Reye-like syndromes of unidentified etiology have suggested the retrospective diagnosis of medium-chain acyl-coA dehydrogenase deficiency. Administration of L-carnitine to medium-chain acyl-coA dehydrogenase deficiency patients resulted in the enhanced excretion of medium-chain acylcarnitines. Octanoylcarnitine is prominent in the urine both prior to and following L-carnitine supplementation. The detection of this metabolite as liberated octanoic acid, following ion-exchange chromatographic purification and mild alkaline hydrolysis, provides a straightforward diagnostic procedure for recognition of this disorder without subjecting patients to the significant risk of fasting. In view of the carnitine deficiency and the demonstrated ability to excrete the toxic medium-chain acyl-coA compounds as acylcarnitines, a combined therapy of reduced dietary fat and L-carnitine supplementation (25 mg/kg/6 h) has been devised and applied with positive outcome in two new cases.

Acyl-CoA Dehydrogenase↗
PubMed1984

L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia.

Treatment with L-carnitine greatly enhanced the formation and excretion of short-chain acylcarnitines in three patients with propionic acidemia and in three normal controls. The use of fast atom bombardment mass spectrometry and linked scanning at constant magnetic (B) to electric (E) field ratio identified the acylcarnitine as propionylcarnitine in patients with propionic acidemia. The normal children excreted mostly acetylcarnitine. Propionic acidemia and other organic acidurias are characterized by the intramitochondrial accumulation of short-chain acyl-Coenzyme A (CoA) compounds. The substrate specificity of the carnitine acetyltransferase enzyme and its steady state nature appears to facilitate elimination of propionyl groups while restoring the acyl-CoA:free CoA ratio in the mitochondrion. We suggest that L-carnitine may be a useful therapeutic approach for elimination of toxic acyl CoA compounds in several of these disorders.

Acyl Coenzyme A↗
PubMed1984

L-carnitine therapy in isovaleric acidemia.

Isovaleric acidemia, resulting from isovaleryl-coenzyme A dehydrogenase deficiency, is associated with marked reduction of free carnitine in both plasma and urine. Fast atom bombardment-mass spectrometry, hydrolysis, and gas chromatography/mass spectrometry have unequivocally identified the existence of isovalerylcarnitine, a new metabolite specific for this disorder. Administration of equimolar amounts of glycine or L-carnitine separately with leucine demonstrated that isovaleryl-coenzyme A is removed by supplemental L-carnitine in the form of isovalerylcarnitine as effectively as it is by glycine, in the form of isovalerylglycine. When L-carnitine is given alone, excretion of isovalerylglycine decreases in preference to enhanced excretion of isovalerylcarnitine and hippurate. Treatment with L-carnitine alone has proven effective in preventing further hospitalizations in a patient with this genetic disorder.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

Met-enkephalin: rapid separation from brain extracts using high-pressure liquid chromatography, and quantitation by binding assay.

Met-enkephalin can be rapidly separated with high recovery from leu-enkephalin, beta-endorphin, and enkephalin metabolites by high-pressure liquid chromatography on a Dupont SCX column. The technique permits separation of endogenous enkephalins from brain extracts for measurement by opiate-receptor binding assay, immunoassay, or for study of the incorporation of radiolabeled amino acids into enkephalin. Using this technique, met-enkephalin was separated from striatal extracts of rats killed by focused microwave irradiation and quantitated by the opiate-receptor binding assay. The concentration of met-enkephalin in the column eluate was 1.3 micron/g tissue. This value is comparable to that obtained by radioimmunoassay without purification of the extracts.

Animals↗
PubMed1975

Changes in cholinergic synaptic vesicle populations and the ultrastructure of the nerve terminal membranes of Narcine brasiliensis electron organ stimulated to fatigue in vivo.

Narcine brasiliensis electric organ was stimulated to fatigue in vivo. Electrical display of organ output and biochemical assay of bound acetylcholine (ACh) and ATP in isolated vesicles were used to assess the state of fatigue relative to denervated control organs of the same fish. A morphometric analysis of the fate of the synaptic vesicle populations in the nerve terminals was carried out. Statistically significant morphological changes in vesicle populations and plasma membranes were observed between control and fatigued electroplaque stacks from individual fish. Pooled data from several fish were used to evaluate the possible role of the different vesicle types in neurotransmission. Fatigue resulted in the loss of 49% of the total vesicle population and a 76% loss of vesicles with bound calcium (Ca). An approximately equivalent increase in the nerve-terminal plasma membrane area was measured. This was predominantly in the form of fingerlike protrusions and/or invaginations of the terminals which were present in the control organs but which were significantly increased by stimulation. Vesicle attachments to the nerve terminal membrane were reduced by 90%. This suggests that the failure in transmission may be due to reduction in the number of vesicles which are loaded with transmitter and can attach to the terminal membrane. The Ca-binding capacity of the lost vesicles was not transferred to the plasma membranes. This result was interpreted as support for the hypothesis that vesicle-bound ATP provides the Ca-binding site.

Acetylcholine↗
PubMed1974

Effects of calcium-containing fixation solutions on cholinergic synaptic vesicles.

Calcium (Ca)-containing fixation solutions applied to slices of electric organ of the electric ray, Narcine brasiliensis, have been shown to have three distinct ultrastructural effects on cholinergic synaptic vesicles of the nerve terminals. (a) An electron-dense particle (EDS) is observed within the vesicle; the particle is seen in unosmicated, unstained tissues and can be removed from thin sections by Ca-chelating agents. It is concluded that the EDS represents Ca bound by the vesicle. It is suggested that the bound ATP of the vesicle provides anionic Ca binding sites. (b) The vesicle membrane tends to 'crinkle' or collapse depending on the concentration of the other components of the fixative solution. The 'crinkling' or collapse are largely reversed by a wash step in the absence of Ca. (c) The presence of Ca results in the appearance of a population of vesicles which form characteristic fusions or 'tight' junctions with the terminal membrane. This appears to be morphological evidence for the proposal, which has been frequently put forward, that Ca facilitates such a fusion before discharge of vesicle-bound transmitter. With the discovery that the use of Ca-containing fixatives leads to the demonstration of a subpopulation of synaptic vesicles fused to the terminal membrane, we are led to propose that this is the ultrastructural location of the newly synthesized acetylcholine which has been shown by others to be preferentially released by stimulation.

Animals↗
PubMedDate not supplied

Estimation of CSF, white and gray matter volumes in hydrocephalic children using fuzzy clustering of MR images.

An algorithm and set of procedures for measuring volumes of cerebrospinal fluid (CSF), white matter, and gray matter from transaxial magnetic resonance images (MRI) of the brain are described. The algorithm is a variant of the fuzzy c-means clustering method for texture identification. This technique is used mainly to solve the problem of volume averaging of tissue compartments, but also has other advantages. It is fast, accurate, and relatively operator independent. Furthermore, it does not depend on statistical assumptions such as data normality, nor does it require any a priori heuristics. The procedure was tested successfully on imaged phantoms of known volume composition and compared with results achieved using a standard morphometric measurement approach. The procedure was also applied to brain MRIs of three clinically normal children and three age-matched children with hydrocephalus using both proton density and T2-weighted images. The algorithm was able to detect the expected increased amounts of CSF and decreased amounts of white matter characteristic of the hydrocephalic brain.

Algorithms↗
PubMedDate not supplied

MR imaging of neuronal migrational disorders.

Neuronal migrational disorders of the brain represent abnormalities in the formation of the neocortex caused by faulty migration of the subependymal neuroblasts. These migrational anomalies include lissencephaly (agyria/pachygyria), pachygyria, schizencephaly, heterotopias, hemimegalencephaly, and polymicrogyria. We used MR imaging (performed on a 0.5-T or 1.5-T scanner) to evaluate 21 patients who had neuronal migratory anomalies. Four patients had lissencephaly, seven had pachygyria, including one patient with hemimegalencephaly, seven had schizencephaly, and three had heterotopias. All MR scans included T1-weighted spin-echo sequences, and seven also had inversion-recovery sequences. The cortical surface, cortex, and gray-white matter interface were well evaluated with both sequences; however, the inversion-recovery images were superior. All but two patients were imaged in both the axial and coronal planes: both projections demonstrated well the migrational abnormalities. MR is an excellent method for diagnosing the migrational anomalies of lissencephaly, pachygyria, schizencephaly, heterotopias, and hemimegalencephaly; it appears to be the imaging method of choice for evaluating these disorders.

Adolescent↗