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Biomedical subjects

W S Millar

Publications and source records attributed to W S Millar.

At least 19 recordsLinked to original sources
PubMed2006

Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). BACKGROUND: High levels of ventricular lactate, the brain spectroscopic signature of MELAS, correlate with more severe neurologic impairment. The authors hypothesized that chronic cerebral lactic acidosis exacerbates neuronal injury in MELAS and therefore, investigated DCA, a potent lactate-lowering agent, as potential treatment for MELAS. METHODS: The authors conducted a double-blind, placebo-controlled, randomized, 3-year cross-over trial of DCA (25 mg/kg/day) in 30 patients (aged 10 to 60 years) with MELAS and the A3243G mutation. Primary outcome measure was a Global Assessment of Treatment Efficacy (GATE) score based on a health-related event inventory, and on neurologic, neuropsychological, and daily living functioning. Biologic outcome measures included venous, CSF, and 1H MRSI-estimated brain lactate. Blood tests and nerve conduction studies were performed to monitor safety. RESULTS: During the initial 24-month treatment period, 15 of 15 patients randomized to DCA were taken off study medication, compared to 4 of 15 patients randomized to placebo. Study medication was discontinued in 17 of 19 patients because of onset or worsening of peripheral neuropathy. The clinical trial was terminated early because of peripheral nerve toxicity. The mean GATE score was not significantly different between treatment arms. CONCLUSION: DCA at 25 mg/kg/day is associated with peripheral nerve toxicity resulting in a high rate of medication discontinuation and early study termination. Under these experimental conditions, the authors were unable to detect any beneficial effect. The findings show that DCA-associated neuropathy overshadows the assessment of any potential benefit in MELAS.

Action Potentials↗
PubMed2004

A reliable and efficient method for cerebral ventricular volumetry in pediatric neuroimaging.

OBJECTIVES: Cerebral ventricular volume has the potential to become an important parameter in quantitative neurological diagnosis. However, no accepted methodology for routine clinical use exists to date. We sought a robust, reproducible, and fast technique to evaluate cerebral ventricular volume in young children. METHODS: We describe a novel volumetric methodology to segment and visualize intracerebral fluid spaces and to quantify ventricular volumes. The method is based on broadly available T1 weighted volumetric magnetic resonance (MR) imaging, an interactive watershed transform, and a fully automated histogram analysis. We evaluated this volumetric methodology with 34 clinical volumetric MR datasets from non-sedated children (age 6-7 y) with a history of prematurity and low birth weight (< or = 1500 g) obtained during a prospective study. RESULTS: The methodology, with adaptation for small ventricular size, was capable of evaluating all 34 of the pediatric datasets for cerebral ventricular volume. The method was a) robust for normal and pathological anatomy, b) reproducible, c) fast with less than five minutes for image analysis, and d) equally applicable to children and adults. CONCLUSIONS: Clinical brain ventricular volume calculations in non-sedated children can be performed using routine MR imaging besides efficient three-dimensional segmentation and histogram analysis with results that are robust and reproducible.

Algorithms↗
PubMed2003

Linking molecular imaging terminology to the gene ontology (GO).

The rapidly developing domain of molecular imaging represents the merging of current advances in the fields of molecular biology and imaging research. Despite this merger, an information gap continues to exist between the scientists who discover new gene products and the imaging scientists who can exploit this information. The Gene Ontology (GO) Consortium seeks to provide a set of structured terminologies for the conceptual annotation of gene product function, process and location in databases. However, no such structured set of concept-oriented terminology exists for the molecular imaging domain. Since the purpose of GO is to capture the information about the role of gene products, we propose that the mapping of GO's established ontological concepts to a molecular imaging terminology will provide the necessary bridge to fill the information gap between the two fields. We have extracted terms and definitions from an already published molecular imaging glossary as well as molecular imaging research articles, and developed molecular imaging concepts. We then mapped our molecular imaging concepts to the existing gene ontology concepts as a method to comprehensively represent molecular imaging.

Computational Biology↗
PubMed2000

Intracerebral aneurysms in human immunodeficiency virus infection: case report and literature review.

We describe a child with human immunodeficiency virus infection who presented with a large subarachnoid hemorrhage. She had multiple saccular and fusiform aneurysms in the proximal cerebral arterial circulation and no evidence of bacterial or fungal infection. The arteriopathy coincided with a high human immunodeficiency virus RNA load. Human immunodeficiency virus may cause cerebral arteriopathy with potentially life-threatening complications.

AIDS Dementia Complex↗
PubMed1999

Leukoencephalopathy and raised brain lactate from heroin vapor inhalation ("chasing the dragon")

BACKGROUND: Inhalation of heated heroin vapor ("chasing the dragon"), which is gaining popularity among drug users seeking to avoid the risks of parenteral drug administration, can produce progressive spongiform leukoencephalopathy. METHODS: We studied the clinical phenotype and course, MRI, MRS, and brain pathology in the first American patients described with this syndrome. RESULTS: Two of the three heroin users studied inhaled heroin pyrolysate together daily over the course of 2 weeks. They developed ataxia, dysmetria, and dysarthria. Patient 1 progressed to an akinetic mute state with decorticate posture and subsequent spastic quadriparesis. Patient 2 developed a mild spastic quadriparesis and gait freezing. Patient 3 was asymptomatic following less heroin exposure. Brain MRI showed diffuse, symmetrical white matter hyperintensities in the cerebellum, posterior cerebrum, posterior limbs of the internal capsule, splenium of the corpus callosum, medial lemniscus, and lateral brainstem. MRS showed elevated lactate. Brain biopsy (Patient 1) showed white matter spongiform degeneration with relative sparing of U-fibers; electron microscopy revealed intramyelinic vacuolation with splitting of intraperiod lines. Progressive deterioration occurred in Patients 1 and 2 over 4 weeks. Both were treated with antioxidants including oral coenzyme Q, and clinical improvement occurred. Patient 1 recovered nearly completely over 24 months. Patient 2 improved, but developed a delayed-onset cerebellar hand tremor. Both still have white matter abnormalities on MRI and MRS. CONCLUSIONS: Elevated lactate in white matter and the possible response to antioxidants suggests mitochondrial dysfunction in progressive spongiform leukoencephalopathy following inhalation of heated heroin vapor.

Administration, Inhalation↗
PubMed1997

The effects of neonatal jaundice and respiratory complications on learning and habituation in 5- to 11-month-old infants.

The influences of neonatal hyperbilirubinemia and respiratory complications were examined in 5- to 11-month-old infants in two studies. One study focused on habituation performance and the other on contingency learning. In both experiments, three neonatal jaundice conditions (no jaundice history, measured bilirubin, phototherapy) were crossed with two levels of neonatal respiratory risk (no oxygen intervention, oxygen intervention). For low respiratory risk subjects there were increasingly adverse effects for both habituation and learning the more severe the jaundice history. A complex pattern emerged for the high respiratory risk groups. Only for the learning task were the results consistent with a summative effect of neonatal jaundice and respiratory risk factors.

Arousal↗
PubMed1997

Magnetic resonance imaging of optic perineuritis.

Optic perineuritis, an uncommon variant of orbital pseudotumor, may be clinically indistinguishable from retrobulbar optic neuritis. Because treatment and prognosis for these two entities are different, early diagnosis is important. We report a case of a 47 year-old woman with clinical findings suggestive of retrobulbar optic neuritis, but whose magnetic resonance images suggested optic perineuritis. A dramatic clinical response to oral corticosteroids was observed. Optic perineuritis should be considered in cases of presumed retrobulbar optic neuritis. MRI may differentiate these two entities in the acute stage, and should be considered before treatment is decided.

Contrast Media↗
PubMed1996

Central nervous system medulloepithelioma: a series of eight cases including two arising in the pons.

Medulloepithelioma is an uncommon childhood tumor of the central nervous system (CNS) whose histopathological appearance has been confused with medulloblastoma and other childhood primitive neuroectodermal tumors (PNETs), but which has a vastly different clinical course. The authors have reviewed the clinical features and treatment responses of eight children with these rare tumors, the largest series to date. In this series, the medulloepitheliomas were equally distributed between supratentorial and infratentorial primary sites. Four patients underwent gross- or near-total resections, one patient's tumor was partially resected, and one patient had biopsy only. Biopsy and ablative surgery were not attempted in two children with pontine tumors. Treatment included both radiation and chemotherapy (four patients), radiation alone (one patient), chemotherapy alone (one patient), and no post-operative treatment (two patients). Six patients died with a mean survival of 10 months and two are disease free with neurological impairment. Both long-term survivors underwent gross-total resections of their tumors. Postmortem examination revealed diffuse CNS tumor dissemination in four patients. Medulloepithelioma, often confused with less aggressive PNETs, can mimic intrinsic brainstem glioma, responds poorly to treatment, and is prone to CNS dissemination at the time of tumor progression.

Brain Neoplasms↗
PubMed1995

MR of malignant optic glioma of adulthood.

A case of malignant optic glioma of adulthood is imaged in its early and late stages with high-resolution MR. The images show the mass to arise from the right optic nerve before invasion of the optic chiasm.

Astrocytoma↗
PubMed1992

The influence of perinatal risk status on contingency learning in six- to thirteen-month-old infants.

Learning of a manipulative response was examined in 6-13-month-old well babies and in risk infants who, in the perinatal period, had experienced a range of respiratory interventions (low- and high-risk). 2 contingency conditions (contingent and yoked) were crossed with 2 locations of feedback (local and remote). Both well-baby and low-risk groups reliably discriminated between contingent and noncontingent feedback when it was presented locally, whereas high-risk babies failed to make this distinction in the conditioning phase. Risk status reliably predicted the learning performance. No response acquisition was obtained in the remote feedback condition. In extinction, the well-baby and low-risk groups decreased their responding, but the high-risk group showed an initial response burst. The findings are discussed in the context of risk-related differences in contingency awareness and frustrative nonreward. Overall, the results confirm that the effects of perinatal compromise involving respiratory complications influence infants' processing of contingency information during the first year of life.

Age Factors↗
PubMed1991

The relationship between encoding, discriminative capacities and perinatal risk status in 4-12-month old infants.

Response decrement and recovery to a novel visual stimulus was examined in 4-12-mth old infants. High (HR) and low (LR) perinatal risk groups were compared to well babies. For abstract stimuli, well babies showed response decrement and recovery to novelty; LR infants revealed some decrement, but no recovery; and the HR group failed to show either. Using face stimuli (Experiment 2) all groups showed decrement and recovery. Cluster analyses revealed that HR infants were more likely to be found in low information-gain clusters. Infants of lower GA who required perinatal respiratory intervention showed less efficient encoding and poorer discrimination of abstract stimuli.

Attention↗
PubMed1985

The effect of proximal and distal feedback on the contingency learning of 6- and 12-month-old normal and perinatally compromised infants.

Acquisition of a manipulative response under proximal and distal contingent feedback was examined in 6- and 12-month-old normal infants, and infants who in the perinatal period had experienced either CNS-related risk or non-CNS-related risks. Both risk groups experienced marked difficulty with the proximal and distal contingency tasks. With proximal feedback 6-month-old CNS-related risk and non-CNS-related risk groups failed to learn to control the contingency, whereas at 12 months all groups learned. The distal feedback task also differentiated between the normal and atypical groups, though only at the 12-month level. The findings also revealed a lag in the performance of the 12-month CNS-related risk group. The results are discussed in terms of attentional factors and the possible use of contingency procedures for investigating the effects of compromise in early infancy is noted.

Age Factors↗
PubMed1979

The effect of delayed feedback on infant learning reexamined.

The study reexamines the effect of delayed reinforcement upon contingency behavior in 6- to 8-month-old infants and attempts to account for the temporal discrepancy between span of integration and contingency memory. A modified delayed-reinforcement scheduling procedure enabled a previous methodological criticism to be discounted. The findings confirmed that whereas infants revealed reliable acquisition under immediate reinforcement, a 3-sec delay (whether reset or nonreset) precluded response acquisition, as did 6-sec and 10-sec delay of reinforcement. The findings are interpreted in terms of an informational-load hypothesis which relates short-term memory to the integration and/or segregation of multimodal input.

Conditioning, Operant↗