Biomedical subjects

T A Glauser

Publications and source records attributed to T A Glauser.

At least 55 records · Page 3Linked to original sources

PubMed1995

Reversible metabolic myopathy in biotinidase deficiency: its possible role in causing hypotonia.

A 5-year-old girl diagnosed with biotinidase deficiency at 9 months of age demonstrated limb and axial hypotonia which improved on biotin therapy. In this patient, electromyographic (EMG) studies prior to treatment were compatible with a mild myopathic process. Serial EMGs performed on biotin therapy demonstrated a gradual resolution of the myopathy. This is the first documented case of a reversible myopathy in a patient with biotinidase deficiency, which may contribute to the clinical findings of hypotonia.

Amidohydrolases↗

PubMed1995

Felbamate in the treatment of acquired epileptic aphasia.

A previously healthy six year old boy developed severe receptive and expressive aphasia, multifocal epileptiform discharges, and refractory clinical seizures consistent with acquired epileptic aphasia. The patient experienced complete seizure control and almost complete return of language skills following the addition of felbamate. This is the first case of successful treatment of acquired epileptic aphasia using felbamate.

Anticonvulsants↗

PubMed1995

Comparison of erythrocyte antioxidant enzyme activities and embryologic level of neural tube defects.

Increased exposure to oxidant-derived free radicals or inadequate systems for antioxidant defense could alter cellular response at critical points in development. We measured 5 antioxidant enzymes, glutathione peroxidase (GSH-Px), glutathione reductase, glutathione-S-transferase, catalase and superoxide dismutase in erythrocytes and their plasma cofactor trace elements (Se, Zn, Cu) in 37 children with myelomeningocele and in 37 age-matched controls. We placed the patients into 3 groups according to motor level of the lesion at birth. We found significantly lower GSH-Px activities (p = 0.007) in children with myelomeningocele. For paired comparisons among the 3 patient groups and controls, there were significant differences (p < 0.05) between controls and both high (thoracic) and raid (lumbar) level embryologic lesions. The finding of antioxidant enzyme variations in our patients with myelomeningocele may indicate a role for abnormal oxidative metabolism in the development of this defect. The contribution of oxidative stress to human birth defects warrants investigation. We discuss potential relationships between oxidative stress and energy metabolism during primary neurulation.

Adolescent↗

PubMed1995

Pediatric epilepsy syndromes.

The development of an international classification for epilepsies and epileptic syndromes has led to substantial progress in the understanding and treatment of patients with epilepsy. Epilepsies and epileptic syndromes are partitioned first by seizure type and then by etiology. This manuscript describes recent advances in six major pediatric epilepsy syndromes. The first three discussed (benign childhood epilepsy with centrotemporal spikes, juvenile myoclonic epilepsy, and childhood absence epilepsy) are the three most common epilepsy syndromes, and each has been the focus of significant research. Patients with benign childhood epilepsy with centrotemporal spikes (benign rolandic epilepsy) may not require anticonvulsant therapy, and their seizures always remit by midadolescence. Juvenile myoclonic epilepsy was the first major epilepsy syndrome for which a gene locus was found. The underlying neuronal pathways and cellular mechanisms of the generalized absence seizures of childhood absence epilepsy are well delineated. The last three syndromes discussed (West syndrome, Lennox-Gastaut syndrome, and acquired epileptic aphasia) are devastating catastrophic epileptic syndromes. The focus of research in West syndrome (infantile spasms) has been to develop better therapeutic interventions (both medical and surgical) and an improved understanding of its pathogenesis. New effective medications are available for patients with Lennox-Gastaut syndrome (childhood epileptic encephalopathy), but one of them (felbamate) has been associated with previously unrecognized serious side effects. Lastly, acquired epileptic aphasia is an example of a poorly understood epilepsy syndrome. A multicenter group has been organized to reexamine this syndrome and produce a better understanding of its pathogenesis and treatment.

Child↗

PubMed1995

Noninvasive central nervous system imaging in sickle cell anemia. A preliminary study comparing transcranial Doppler with magnetic resonance angiography.

PURPOSE: We evaluated the accuracy of transcranial Doppler (TCD) and magnetic resonance angiography (MRA) as a screening modality for cerebral infarct in patients with sickle cell disease. PATIENTS AND METHODS: Twenty-four patients with sickle cell disease were assessed for a cerebral infarct. Each patient underwent neurologic examination, psychometric evaluation, magnetic resonance imaging (MRI), MRA, and TCD. Presence of a cerebral infarct was determined by an MRI and supported by neurologic and neuropsychometric evaluation. All investigators were unaware of the patient's status. Cerebral vasculature by MRA was categorized as being occluded, stenotic, or normal. The maximum TCD velocity of the right and left middle cerebral artery were assessed. Various cutoffs were used to determine the sensitivity and specificity of TCD. RESULTS: MRA had a sensitivity and specificity of 100% and 92%, respectively. At a maximum velocity cutoff of 180 cm/s, the sensitivity and specificity of TCD were 20% and 67%, respectively. No maximum velocity on TCD produced both sensitivity and specificity > 50%. CONCLUSION: MRA is more sensitive than TCD when the middle cerebral artery for maximum velocity is compared. Prospective evaluation is warranted to determine if TCD is useful as a screening technique for cerebral infarction in children with SCD.

Anemia, Sickle Cell↗

PubMed1995

Cerebral infarction in sickle cell disease: transcranial Doppler US versus neurologic examination.

PURPOSE: To evaluate flow velocity measurements in the middle cerebral artery (MCA) and/or neurologic examination for detection of cerebral infarction in sickle cell disease (SCD). MATERIALS AND METHODS: Twenty-four pediatric patients aged 6 1/2-17 years with SCD underwent magnetic resonance (MR) imaging, MR angiography, neurologic examination, and transcranial Doppler ultrasonography (US). Transcranial Doppler studies were evaluated for maximum flow velocity in the right and left MCAs. Combinations of cut-off values were used to determine the sensitivity and specificity of transcranial Doppler US for detection of infarction. RESULTS: Neurologic examination had 58% sensitivity and 92% specificity for cerebral infarction. Maximal flow velocity > 200 cm/sec or < 100 cm/sec (including no flow) helped identify nine of 12 patients with infarcts proved at MR imaging, with only one false-positive result (sensitivity, 75%; specificity 92%). The combination of neurologic examination and transcranial Doppler US produced 92% sensitivity and 83% specificity for cerebral infarction. CONCLUSION: The combination of transcranial Doppler US and neurologic examination has potential as a screening technique for infarction in SCD.

Adolescent↗

PubMed1995

Accuracy of neurologic examination and history in detecting evidence of MRI-diagnosed cerebral infarctions in children with sickle cell hemoglobinopathy.

We determined the accuracy of neurologic examination and the history of a previous neurologic event in detecting clinical evidence of a magnetic resonance imaging (MRI)-diagnosed cerebral infarction in 30 children with sickle cell hemoglobinopathy. Each patient had an MRI of the brain, neurologic examination, chart review, and psychometric evaluation. Seventeen children (57%) had MRI evidence of cerebral infarction based on demonstration of parenchymal abnormalities in a vascular distribution. Among the 17 children with MRI evidence of cerebral infarction, only 12 (71%) had an abnormal neurologic examination, and 11 (65%) had a history of a prior neurologic event. In contrast, among the 13 children with normal MRIs, 12 (92%) had normal neurologic examinations, and no child had a previous history of a neurologic event. Multiple, bilateral, heterogeneous cerebral infarctions frequently occur without overt neurologic signs or symptoms in children with sickle cell hemoglobinopathy. Previous studies that relied on a focal neurologic examination or a history of a neurologic event to identify cerebral infarctions in patients with sickle cell hemoglobinopathy most likely underrepresented the true frequency of cerebral infarctions in this population. Future prospective studies of cerebral infarctions in children with sickle cell hemoglobinopathy should include MRIs for identification and classification, rather than neurologic examination or clinical history alone.

Adolescent↗

PubMed1994

Neurologic complications of pediatric heart transplantation.

OBJECTIVE: To determine the type and frequency of acquired neurologic complications in survivors of pediatric heart transplantation (HT). DESIGN: Retrospective study. SETTING: Tertiary care children's hospital. PARTICIPANTS: Fourteen survivors of 17 consecutive patients who underwent HT during a 60-month period beginning in January 1986. INTERVENTIONS: None. MEASUREMENTS OR MAIN RESULTS: Three distinct subgroups of patients who had undergone HT were identified: six infants with uncorrected hypoplastic left heart syndrome (HLHS), three infants with HLHS who had undergone previous stage 1 Norwood repair, and eight older children with end-stage cardiomyopathy. Fourteen (82%) of 17 children were alive at follow-up. Only one patient (7%) had a significant acquired neurologic deficit (left temporal lobe stroke with subsequent seizures in an infant with uncorrected HLHS). The remaining subjects had normal results of post-HT neurologic examinations (n = 7), minor post-HT neurologic abnormalities (n = 3), no significant change in preexisting neurologic abnormalities (n = 1), or normal neurologic status by report (n = 2). The minor neurologic abnormalities noted post-HT were dysmetria, tremor, and absent reflexes. No episodes of choreoathetosis or cyclosporine-related seizures were seen. CONCLUSIONS: Pediatric HT is associated with both a high survival rate and a low incidence of severe acquired neurologic deficits despite a significant incidence of severe systemic and metabolic derangements in the pretransplantation and posttransplantation periods. In infants with HLHS, HT seems to carry a lower incidence of severe neurologic morbidity (12%) than other surgical treatments.

Acute Kidney Injury↗

PubMed1993

Neuropsychologic effects of stroke in children with sickle cell anemia.

We examined the nature and extent of neuropsychologic impairment in children with sickle cell anemia (SCA) with or without stroke. Twenty-nine children with SCA received cranial magnetic resonance imaging. Strokes were classified into three groups: diffuse cortical stroke (n = 11), anterior stroke (n = 6), or none (n = 12). Children with SCA and 20 age-matched sibling control subjects then received a neurologic examination and a neuropsychologic battery of tests that included motor, verbal, spatial, attentional, and memory measures. Tests of spatial function showed that children with diffuse cortical strokes were impaired, whereas children with anterior lesions had intrusions of irrelevant material during list recall. There were no significant differences between children with stroke and sibling control subjects on motor, verbal, or memory measures. Six children had evidence of stroke on magnetic resonance imaging without any history of a damaging neurologic event. These children had impaired neuropsychologic performance relative to that of sibling control subjects in a pattern similar to that of children with overt stroke. Children with SCA without stroke did not differ from sibling control subjects on any measure. Our results indicate that overt and silent strokes result in lesion-specific neuropsychologic deficits in children with SCA.

Adolescent↗

PubMed1993

Human liver microsomal thiol methyltransferase: inhibition by arylalkylamines.

1. Thiol methyltransferase (TMT) is a microsomal enzyme catalyzing the S-methylation of aliphatic sulphydryl drugs and xenobiotics. Studies of the functional significance of S-methylation catalysed by TMT have been hampered by lack of a potent, relatively specific, non-toxic inhibitor of the enzyme. 2. Human hepatic microsomal TMT was inhibited by the arylalkylamine 2,3-dichloro-alpha-methylbenzylamine (DCMB), and by a series of arylalkylamines, as well as the arylamine, aniline. 3. Inhibition kinetic studies with DCMB, benzylamine, aniline, phenylethylamine and phenylethanolamine, five compounds with a wide range of IC50 values, showed 'mixed' inhibition of TMT with respect to the methyl acceptor substrate, 2-mercaptoethanol. Kis and Kii values were, respectively, 1.1 and 0.29 microM for DCMB, 160 microM each for benzylamine, 680 and 370 microM for aniline, 1640 and 1380 microM for phenylethylamine, and 2300 and 1400 microM for phenylethanolamine. Inhibition was at least partially reversible. 4. H.p.l.c. analyses were carried out with the products of enzyme reactions performed in the presence of aniline, benzylamine, and phenylethylamine to ascertain whether these compounds inhibited TMT by acting as methyl acceptors. Results showed that they did not act as methyl acceptor substrates.

Aniline Compounds↗

PubMed1993

Diethyldithiocarbamate S-methylation: evidence for catalysis by human liver thiol methyltransferase and thiopurine methyltransferase.

Disulfiram is used in the treatment of alcoholism to inhibit the enzyme aldehyde dehydrogenase. Disulfiram is rapidly reduced in vivo to form diethyldithiocarbamate (DDC), and DDC can undergo methyl conjugation to form S-methyl-DDC. Human tissues contain two separate genetically regulated enzymes that can catalyze thiol S-methylation. Thiol methyltransferase (TMT) is a microsomal enzyme that preferentially catalyzes, the S-methylation of alipathic sulfhydryl compounds, whereas thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds. Our experiments were performed to determine whether human liver microsomal and/or cytosolic preparations could catalyze the S-methylation of DDC, and, if so, to determine whether TMT or TPMT might be the enzymes involved. We found that both human liver microsomes and cytosol could catalyze DDC S-methylation. The microsomal activity displayed biphasic substrate kinetics, with apparent Km values for DDC of 7.9 and 1500 microM for the high- and low-affinity activities, respectively. The high-affinity activity had an apparent Km value for S-adenosyl-L-methionine, the methyl donor for the reaction, of 5.8 microM. The thermal inactivation profile and response to methyltransferase inhibitors of the high-affinity microsomal DDC S-methyltransferase activity were similar to those of human liver microsomal TMT. In addition, TMT activity and the activity catalyzing the S-methylation of DDC were highly correlated in 19 individual liver samples (rs = 0.956; P < .0001). Hepatic cytosolic DDC S-methyltransferase activity had an apparent Km value for DDC of 95 microM. The cytosolic enzyme which catalyzed DDC S-methylation and TPMT activity had similar thermal inactivation profiles, similar patterns of response to methyltransferase inhibitors and the two activities coeluted during ion exchange chromatography. Furthermore, the activities of TPMT and cytosolic DDC S-methyltransferase were highly correlated in 20 individual liver samples (rs = 0.963; P < .0001). These results were compatible with the conclusion that both TMT and TPMT could catalyze the S-methylation of DDC in the human liver. Because the activities of both TMT and TPMT are controlled by inheritance, our observations raise the possibility of pharmacogenetic variation in the biotransformation and therapeutic effect of DDC in humans.

Aldehyde Dehydrogenase↗

PubMed1992

Adequacy of routine EEG examinations in neonates with clinically suspected seizures.

This study identified the clinical and electroencephalographic (EEG) characteristics that distinguished neonates with EEG-confirmed seizures from those without, in order to assess the adequacy of routine short-term EEG examinations in neonates with clinically suspected seizures. Two different subgroups of tracings were analyzed: EEGs performed on therapeutically paralyzed (TP+) neonates and EEGs performed on non-therapeutically paralyzed (TP-) neonates. The rate of electrographic seizures, abnormal EEG background activity, and excessive sharp EEG transients (SETs) was significantly more common in the tracings performed on TP- neonates. In lethargic/comatose TP- neonates with clinically suspected seizures and abnormal EEG background activity, the rate of EEGs with excessive SETs (implying a "lowered seizure threshold") occurred equally in tracings with or without documented electrographic seizures. Consequently, we suspect that routine EEGs may be inadequate to electrographically confirm suspected seizures in some TP- neonates due to a large sampling error. In contrast, routine 40-minute EEGs are probably adequate to seek evidence of electrographic seizure activity in TP+ neonates because their seizure rate is low and most do not display background abnormalities or excessive SETs.

Cerebral Cortex↗

PubMed1992

Abnormal magnetic resonance images in hemorrhagic shock and encephalopathy syndrome.

Hemorrhagic shock and encephalopathy syndrome is an acute childhood illness that involves the rapid onset of multisystem failure, including central nervous system, renal, cardiovascular, hepatic, and hematologic dysfunction, and often leads to death or serious neurologic damage. We report the first case of a child with hemorrhagic shock and encephalopathy in which magnetic resonance imaging was used to define the cortical hemorrhagic involvement.

Brain↗

PubMed1991

Cognitive deficits in long-term survivors of childhood brain tumors.

Improvements in survival for patients who had childhood brain tumors has led to an increasing emphasis on the quality of life for these long-term survivors. Initial survival studies relied on global descriptions of functional abilities to assess cognitive deficits and reported that from 20% to 40% of long-term survivors had obvious partial disability and less than 10% were severely disabled. Formal neuropsychological testing has revealed that from 40% to 100% of long-term survivors have some form of cognitive deficit in various intelligence quotients, visual/perceptual skills, learning abilities, and adaptive behavior. Prospective, controlled studies have found a younger age at diagnosis, radiotherapy, methotrexate chemotherapy, tumor location and time interval to testing to be important (alone or in combination) and related to a high risk of subsequent cognitive deficits. Some variables play an as yet unresolved role. However, despite the progress of the last decade, future prospective studies are needed to define the role of certain variables in the development of cognitive deficits that maximize survival while minimizing cognitive deficits.

Brain Neoplasms↗

PubMed1990

Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors.

Thirty-six pediatric patients (ages 0.8-16.8 years) with recurrent intracranial ependymoma were treated for a total of 52 separate cases of relapse from 1970 to 1989. Therapy consisted of surgery in 33 cases and chemotherapy in 38 cases. Twelve patients received radiation at the time of first relapse, and five of these 12 who had initially been treated with surgery and chemotherapy alone were irradiated to full dose. The 2-year actuarial survival and progression-free survival (PFS) rates are 29% and 23%, respectively. Two-year survival after treatment of first relapse is 39%. Of the 52 cases, there have been 44 subsequent relapses (and one septic death), three of which have occurred in the five patients treated with definitive radiation. Twenty-seven relapses have occurred exclusively with local disease. Eight patients failed with disease outside as well as in the primary site. Survival was better for patients who had histologically benign lesions at relapse (53% versus 9%, P less than 0.02), and for patients in first versus subsequent relapse (p less than 0.005). Cisplatin and etoposide (VP-16) appeared to be the most active chemotherapeutic agents. The authors conclude that some patients with histologically benign ependymoma at first relapse may benefit from aggressive therapy, with occasional long-term, progression-free survival possible. Patients with malignant lesions, or patients who relapse a second time, are less likely to benefit from conventional therapy for a significant period of time.

Actuarial Analysis↗

PubMed1990

Gonococcal conjunctivitis in prepubertal children.

Four prepubertal children had confirmed gonococcal conjunctivitis. All were febrile and had hyperpurulent conjunctival discharge with periorbital inflammation. Cultures of pharyngeal, rectal, and genital specimens on selective media excluded infection at other sites. Detailed social evaluation revealed no evidence or suspicion of sexual abuse. Isolated gonococcal conjunctivitis occurs in prepubertal children. Unlike gonococcal infections at other locations, a nonsexual mode of transmission may exist. However, a careful physical examination and detailed social evaluation, looking for signs of sexual abuse, must be obtained in any prepubertal child with a gonococcal infection.

Child↗

PubMed1990

Relapse of infant botulism.

We report on 3 infants who had relapse of infant botulism after apparent resolution of clinical symptoms. This group represented 5% of the infants with confirmed infant botulism who were treated at our institution since 1976. The exact cause for these relapses was unclear, but three potential mechanisms are examined. There were no historical, clinical, or electrophysiological predictors of relapse. Although at the time of writing recovery from relapse appeared complete, close follow-up of patients recovering from a bout of infant botulism is necessary.

Botulism↗

PubMed1990

Cushing's ulcer as a consequence of adrenocorticotropic hormone administration for infantile spasms.

Adrenocorticotropic hormone (ACTH) is the treatment of choice for infantile spasms despite its multiple side effects. This case represents a previously unreported side effect, peptic ulceration, occurring during ACTH treatment of infantile spasms. Two pathophysiologic mechanisms are proposed and examined. A direct effect of ACTH on the duodenum is considered but deemed unlikely. Alternatively, the combination of the patient's communicating hydrocephalus and ACTH's central effects is proposed to have led to increased intracranial pressure and a Cushing's ulcer. The need for pretreatment neuroimaging and H2-receptor antagonist use during ACTH therapy in all cases, along with gastrin level measurements in selected cases, is recommended.

Adrenocorticotropic Hormone↗