Search PubMed⌕ Search

Biomedical subjects

Andrew J Waclawik

Publications and source records attributed to Andrew J Waclawik.

8 recordsLinked to original sources
PubMed2006

The astroglial cell that guides nerve fibers from growth cone to synapse in organotypic cultures of the fetal mouse spinal cord.

We present electron microscopic and autoradiographic studies done using organotypic cultures of spinal cord explants excised from 15 days of gestation mouse embryos. Nerve fibers growing from the spinal cord explant carry at their tips immature mitotic astrocytic cells that lead their growth cones. These glial cells divide only during the active phase of neuronal growth, and correspond ultrastructurally to radial glia. They provide a specific cellular substrate for neuronal growth. Some growth cones form axoglial synapses with smooth membranes of immature glial cells. In contrast, maturing glial cells sprout cytoplasmic processes that tightly wrap individual growth cones and effectively arrest their growth. Next, the processes gather nerve endings into islets and nerve fibers into bundles. After internalizing nerve endings, the glial processes withdraw, bringing the endings into contact with each other. The direct neuronal appositions lead to the transformation of growth cones into presynaptic endings, signaled by their collection of presynaptic vesicles. Clustering of the vesicles at presynaptic axoglial or axodendritic membranes indicates the onset of synaptogenesis-completed by differentiation of spinous and compound synapses. Concomitant with the progress of synaptogenesis, astrocytic investment within the neuropil progressively diminishes. The differentiating astrocytic processes show secretory and tethering activity toward nerve fibers and their endings. Our observations demonstrate that astroglial cells-depending on their developmental stage-first promote and then arrest neuronal growth, and induce synaptogenesis. Thus, at any time, the growing nerve fibers are not only supported but also controlled by the astroglial cells.

Animals↗
PubMed2005

Clinical utility of videofluorography with concomitant Tensilon administration in the diagnosis of bulbar myasthenia gravis.

Myasthenia gravis (MG) classically presents with ocular, bulbar, and predominantly proximal muscle weakness. Isolated bulbar symptoms occur in less than 25% of cases and can mimic stroke (1-3). If left untreated, MG can lead to significant morbidity and mortality, including myasthenic crisis and recurrent aspiration pneumonia. We describe a case of a 68-year-old man who presented with isolated bulbar symptoms. We used a novel approach to diagnosis which included a videofluorographic swallow study with concomitant Tensilon (edrophonium) injection.

Action Potentials↗
PubMed2004

Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation.

The background to this study began with the reporting of two Japanese kindreds with the S305N tau mutation. Although the pathological findings in the autopsied cases were well characterized, only limited ante-mortem data were presented. In this study, longitudinal characterization was carried out in two siblings of European ancestry found to have frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) through comprehensive neurobehavioural examinations and other scales at approximate 6-month intervals. Scales included the Mini-Mental State Examination, Short Test of Mental Status, modified motor subtest of the Unified Parkinson's Disease Rating Scale, detailed neuropsychological testing, and the Neuropsychiatric Inventory. Changes in whole-brain volume and ventricular volume were measured from serial MRI studies. All members of the kindred underwent molecular genetic analyses to elucidate the mechanism of inheritance. The missense mutation in tau, S305N, was detected in the proband (onset age 30), who has undergone serial evaluations for almost 4 years. Her older sister (onset age 36) was subsequently found to have the same mutation, and has undergone serial evaluations for 2 years. This mutation is absent in both parents and the only other sibling, and non-paternity was excluded by additional analyses. The siblings have exhibited cognitive and behavioural features typical of FTDP-17, which have proved challenging to manage despite aggressive pharmacological and behavioural therapies. The proband's sister has demonstrated an atypical profile of impairment on neuropsychological testing. Both siblings have developed striking atrophy of the anterior part of temporal lobes and moderate atrophy of the dorsolateral and orbitofrontal cortical regions, which in both cases is relatively symmetrical. The annualized changes in whole-brain volume and ventricular volume, respectively, were -35.2 ml/year (3.23% decrease per year) and +20.75 ml/year (16.93% increase per year) for the proband, and -30.75 ml/year (2.77% decrease per year) and +5.01 ml/year (3.11% increase per year) for the proband's sister. In conclusion, the mutation in these siblings may have arisen during oogenesis in the mother and probably represents germline mosaicism. Although both patients have exhibited the typical cognitive and behavioural features of FTDP-17, one patient is exhibiting an atypical neuropsychological profile. Also, despite a similar topographic pattern of progressive atrophy on MRI, the rates of change in whole-brain volume and ventricular volume between the two patients are quite different. These findings have implications for future drug trial development in FTDP-17 and the sporadic tauopathies.

Adult↗
PubMed2003

Myeloneuropathy from nitrous oxide abuse: unusually high methylmalonic acid and homocysteine levels.

A 23-year-old patient developed diffuse paresthesias and sensory loss. He had mildly reduced serum vitamin B12 (B12) concentration with unusually high levels of methylmalonic acid (MMA) and homocysteine and no evidence of B12 malabsorption. Following parenteral B12 administration, his neurological deficit promptly resolved and B12 and MMA levels normalized, but elevated levels of homocysteine persisted. One year later, he admitted to inhaling nitrous oxide (N2O). After halting N2O abuse his homocysteine level normalized. This case demonstrates the importance of serum homocysteine level measurements in cases of suspected N2O toxicity [corrected].

Adult↗
PubMed2002

Unilateral calf hypertrophy seen in lumbosacral stenosis: case report and review of the literature.

STUDY DESIGN: A case report of a patient with neurogenic unilateral calf hypertrophy and review of the literature are reported. OBJECTIVES: To provide further evidence that S1 radiculopathy is predisposed to develop neurogenic muscle hypertrophy. SUMMARY OF BACKGROUND DATA: Calf hypertrophy, specifically hypertrophy of the gastrocnemius muscle, is a rare but recognized presentation of S1 and less commonly L5 radiculopathies. The pathophysiology of this is incompletely understood. METHODS: We present a 59-year-old patient with painless progressive distal right leg weakness and calf enlargement. Electrodiagnostic studies and MAGNETIC RESONANCE IMAGING scanning were performed to evaluate the extent and cause of radicular damage as the etiology for unilateral calf hypertrophy. RESULTS: Examination and electrodiagnostic studies revealed right L5, right S1, and left L5 radiculopathies. Imaging studies demonstrated lumbar stenosis at L3-L4, L4-L5, and L5-S1 vertebral levels as well as L4-L5 and L5-S1 foraminal stenosis. After decompressive surgery the progressive nature of the patient's symptomatology halted, and he had partial resolution of his deficits. CONCLUSION: Although the patient had bilateral L5 radiculopathies, he only had hypertrophy in the distribution of his right S1 radiculopathy. This supports the hypothesis that dysfunction of the S1 nerve root or its distribution is a predisposing factor to develop neurogenic muscle hypertrophy. Furthermore, patients presenting with unilateral calf hypertrophy need a careful diagnostic evaluation for S1 radiculopathy as well as to exclude asymmetric presentation of systemic neuromuscular conditions.

Electrodiagnosis↗
PubMed2002

Friedreich's ataxia associated with mitochondrial myopathy: clinicopathologic report.

A 13-year-old boy with clinical and electrophysiologic findings of Friedreich's ataxia developed unusually prominent myopathy. Skeletal muscle biopsy showed mitochondrial proliferation and structural abnormalities. No mutation was found in skeletal muscle mitochondrial DNA to explain this finding. Molecular genetic and pathologic studies confirmed a diagnosis of Friedreich's ataxia in the proband and affected relatives. Although the Friedreich's ataxia phenotype results from decreased expression of a mitochondrially targeted protein, frataxin, mitochondrial myopathy has not been described as a feature of the disease. The association between the frataxin gene mutation and mitochondrial myopathy in this case suggests that severe or cumulative insults to mitochondrial function may produce myopathic changes in some cases of Friedreich's ataxia. The patient also responded clinically to carnitine supplementation, suggesting a potential palliative therapy for the disease.

Adolescent↗