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Biomedical subjects

R E Clatterbuck

Publications and source records attributed to R E Clatterbuck.

At least 37 records · Page 2Linked to original sources
PubMed2000

Reoperation for spinal restenosis in achondroplasia.

The characteristics of spinal restenosis in achondroplasia and its treatment are evaluated in this study. Radiologic and surgical findings were correlated to establish the causes of achondroplastic spinal restenosis and the benefits of its therapy. Eight patients (five men, three women) with spinal restenotic complications of achondroplasia were studied. The most common neurological sign of recurrent stenosis was impaired motor function. The mean interval between the most recent surgeries was 8.2 years (9.5 years for surgeries at the same levels). The most common causes of recurrent stenosis were facet hypertrophy and disk disease. The complications were a dural tear and cerebellar hemorrhage in one patient and transient neurological deterioration in another. One patient died after operation. Restenosis can occur many years after original decompression in the achondroplastic spine, and repeated operation can successfully lessen pain and neurological symptoms in most patients.

Achondroplasia↗
PubMed2000

Mutations in KRIT1 in familial cerebral cavernous malformations.

OBJECTIVES: The recognition of six unrelated Hispanic-American families in which cerebral cavernous malformations (CCM) segregated as an autosomal dominant trait established a genetic basis for this disease. Linkage analysis subsequently identified locus heterogeneity with disease genes for CCM at chromosomal regions 7q, 7p, and 3q. Recently, mutations in KRIT1, a gene on 7q at the CCM1 locus, were identified in French and Hispanic-American families with CCM. This study confirms the identity the KRIT1 founder mutation in Hispanic-Americans and reports a novel KRIT1 mutation in a Caucasian family. METHODS: Oligonucleotide primers were designed to allow amplification of genomic DNA sequences from four Hispanic-American families and five non-Hispanic families for all 12 exons of the KRIT1 gene using the polymerase chain reaction (PCR). The amplified DNA was then screened using single strand conformation polymorphism analysis (SSCP) and sequencing. The expression pattern of KRIT1 was analyzed by Northern blotting. RESULTS: Analysis of the KRIT1 gene revealed a point mutation in exon 6 that predicts the substitution of a premature termination codon for glutamine at codon 248 in all four Hispanic-American families, confirming previous findings. SSCP analysis and sequencing revealed an 11 base pair duplication in exon 7 leading to a premature termination codon in one Caucasian family. Northern analysis demonstrated widespread expression of this gene, however, the highest level of expression was in the brain. CONCLUSION: The common KRIT1 mutation causing the majority of CCM in Hispanic-Americans has been identified and independently confirmed, allowing efficient presymptomatic molecular diagnosis. In keeping with prior results, both newly identified mutations create a premature termination codon and are predicted to initiate degradation of the mutant mRNA through the nonsense-mediated mRNA decay pathway. These data strongly suggest loss of function as the relevant patho-genetic mechanism.

Brain Neoplasms↗
PubMed2000

Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome presenting as a primary calvarial lesion. Case report and review of the literature.

The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a recently described, currently evolving clinical entity that groups together several idiopathic disorders of bone and skin formerly described under a variety of names. Among the spectrum of possible locations for the bone lesions, there is no previous report in the literature of primary involvement of the skull vault. A patient with primary involvement of the calvaria in the setting of SAPHO syndrome is described here, which, to the authors' knowledge, is the first report of such localization. The clinically and radiologically benign evolution of the different stages of the bone lesions is presented. The authors suggest that the SAPHO syndrome should be considered in the differential diagnosis of lytic, sclerotic, or hyperostotic lesions of the skull, particularly before considering invasive diagnostic procedures.

Acquired Hyperostosis Syndrome↗
PubMed2000

Dynamic nature of cavernous malformations: a prospective magnetic resonance imaging study with volumetric analysis.

OBJECT: Although cavernous malformations (CMs) are not detected in angiographic studies, they have a characteristic appearance on magnetic resonance (MR) images. A number of reports published in the last decade have focused on the behavior of these lesions within the clinical environment. However, little has been published about the evolution of CMs over time, as observed in imaging studies. To understand imaging-documented changes in CMs over time, we analyzed MR images of 114 cavernous malformations in 68 patients who were followed prospectively. METHODS: For each CM the location, volume, and MR imaging signal characteristics were recorded. Volume data were available for 107 lesions from initial images. The mean volume of these 107 CMs was 2779 mm3. The lesions ranged in size from 0.5 to 46,533 mm3 (46.5 cm3). Volume data from a second set of images were available for 76 CMs (mean interval from first imaging session 26 months), and from a third set of images for 24 lesions (mean interval from second imaging session 18 months). Over the first follow-up interval, the mean volume change was -991 mm3 (a decrease of approximately 1 cm3) and over the second interval the mean volume change was -642 mm3. Although these mean volume changes appear modest, volume changes in single lesions during follow-up intervals were more dramatic, with decreases as large as 45,629 mm3 (45.6 cm3) and increases as large as 6,074 mm3 (6 cm3). Serial examinations of the MR imaging signal characteristics of these CMs demonstrate a trend for maturation of blood products from a subacute, to a mixed, and finally to a chronic appearance. Three lesions appeared de novo during the follow-up period. CONCLUSIONS: On the basis of their analysis, the authors conclude that CMs exhibit a range of dynamic behaviors including enlargement, regression, and de novo formation, as well as progression through a series of characteristic MR imaging appearances.

Adolescent↗
PubMed2000

Intradural cervical disc herniation and Brown-Séquard's syndrome. Report of three cases and review of the literature.

Although cervical disc herniation commonly requires surgical intervention, the intradural sequestration of a herniated cervical disc fragment is rare. In searching the world literature on this topic, the authors found six case reports. They report three new cases of intradural cervical disc herniation in which the patients presented with Brown-Séquard's syndrome and they review the literature. Although Brown-Séquard's syndrome is a rare clinical finding in extradural disc herniation, six of the nine patients with intradural cervical disc herniation (our cases and those from the literature) presented with symptoms of this syndrome. The remaining patients presented with para- or quadriparesis. This suggests that intradural disc herniation should be considered preoperatively in patients in whom there is magnetic resonance imaging or myelographic evidence of cervical disc herniation and Brown-Séquard's syndrome. In patients who underwent anterior cervical discectomy for the treatment of intradural cervical disc herniations, better outcomes were demonstrated than in those in whom posterior procedures were performed.

Adult↗
PubMed1999

The natural history of cavernous malformations.

This article reviews general information about cavernous malformations, including histology, radiology, epidemiology, and symptomatology. Rates of hemorrhage as reported in the literature are presented. Familial cavernous malformations and their genetic basis are discussed. Finally, the variations in the biological behavior of cavernous malformations in different regions of the central nervous system are discussed and outcomes are assessed.

Brain Stem↗
PubMed1998

Peripheral nerve grafts exert trophic and tropic effects on anterior thalamic neurons.

Peripheral nerve grafting into the central nervous system (CNS) has been used to study the regenerative capabilities of central neurons given access to a peripheral nervous system (PNS) environment. It is well documented that many CNS neurons regenerate axons along peripheral nerve grafts placed in close proximity to their cell bodies and that these grafts can ameliorate axotomy-induced retrograde degeneration. In the present study, we placed peripheral nerve grafts in proximity to axotomized neurons of the anterior thalamus. Standard histological and retrograde tracing techniques were used to examine these preparations 2 months after grafting. Three effects of these grafts were observed: amelioration of retrograde degeneration of axotomized anterior thalamic neurons, hypertrophy of many thalamic neurons in the local environment of the graft, and ingrowth of axons of axotomized anterior thalamic neurons as well as nonaxotomized neurons from surrounding nuclei. We conclude from these studies that peripheral nerve grafts not only provide a matrix for axonal outgrowth but also exert marked trophic and tropic effects on axotomized anterior thalamic neurons.

Animals↗
PubMed1998

Transitional cell carcinoma presenting as a solitary brain lesion: a case report and review of the world literature.

Transitional cell carcinoma of the urinary tract will account for roughly 50,000 new cases of cancer in the US this year. Metastatic involvement to the brain is uncommon with this malignancy. When it does occur, it is usually in the setting of widespread metastatic disease. A rare case of transitional cell carcinoma of the bladder presenting as a solitary brain lesion is reported. In addition, we reviewed the world literature regarding transitional cell carcinoma metastatic to the central nervous system. Our review suggests that metastatic transitional cell carcinoma of the central nervous system has become increasingly common as more effective chemotherapeutic regimens have been developed to control the primary disease. The recent literature also suggests that, much like other metastatic disease to the brain, outcome and survival in patients without widespread disease is improved by aggressive surgical and oncological management.

Aged↗
PubMed1997

The efficient calculation of neurosurgically relevant volumes from computed tomographic scans using Cavalieri's Direct Estimator.

OBJECTIVE: Because decision making in the daily practice of neurosurgery requires judgments about changes in the volume of spatially complex three-dimensional objects, we sought a simple, rapid, and accurate method for extracting this information from standard computed tomographic (CT) scans. METHODS: Volume measurements were made by using a transparent template to overlay a grid of regularly-spaced points over CT scans of randomly selected patients with hydrocephalus or malignant gliomas. The volume of an object appearing on a scan is the product of the sum of points that fell on the object, the area associated with each point, and the distance between scan slices. This method is known as the Cavalieri Direct Estimator. We assessed the potential clinical applicability of this technique by measuring interobserver correlation for ventricular volume measurements in hydrocephalic patients, correlating brain tumor volume measurements with those obtained using the ISG Allegro system (ISG Technologies, Inc., Mississauga, Ontario) (a three-dimensional reconstruction software package), and measuring the time required for volumetric analyses. RESULTS: Tumor volume estimates using this method correlated highly (r = 0.999) with those made by the ISG Allegro System. Interobserver correlation for ventricular volume estimates was also high (r = 0.968). We found that the time required for application of this technique to CT scans ranged from 4 to 10 minutes. CONCLUSIONS: We conclude that the Cavalieri Direct Estimator can be easily applied to acquire volume measurements from standard CT scans and requires only a few minutes and no additional expense, making it ideal for daily use in clinical practice.

Brain Mapping↗
PubMed1997

Endothelial cell expression of intercellular adhesion molecule 1 in experimental posthemorrhagic vasospasm.

OBJECTIVE: The exposure of large intracranial arteries to blood after an aneurysmal subarachnoid hemorrhage leads to a cascade of morphological and physiological changes in the vessels, a condition generally described as vasospasm. This response to the periadventitial deposition of blood is mediated in part by the endothelial layer of the vessel. This study was undertaken to examine the role of endothelial cell expression of intercellular adhesion molecule 1 (ICAM-1) in the initiation and regulation of this response. METHODS: The femoral artery model of vasospasm was used in rats (65 animals, 130 arteries). In each rat, one artery was exposed to blood and the contralateral vessel was exposed to saline, so that each animal served as its own control. Animals were perfused and killed at sequential time points, from 1 hour to 20 days after blood exposure. The vessels were examined immunohistochemically and histologically for the presence of ICAM-1 and morphological features of vasospasm, respectively. RESULTS: Endothelial cell ICAM-1 immunoreactivity was extensively increased in only the blood-exposed vessels, beginning 3 hours after clot placement and persisting for 24 hours. ICAM-1 immunoreactivity returned to baseline by 48 hours after blood exposure. The influx of inflammatory cells correlated directly with the time and location of increased ICAM-1 expression. Peak arterial remodeling was observed on the blood-exposed side 8 to 12 days after clot placement, as quantified by measurements of increased wall thickness, decreased lumen size, and increased collagen content. CONCLUSION: Endothelial cell ICAM-1 expression seems to be an early and specific signal used by a vessel in response to the deposition of blood periadventitially. This molecule may be a marker for vessels likely to undergo subsequent morphological remodeling and vasospasm.

Animals↗
PubMed1996

Ciliary neurotrophic factor stimulates the expression of glial fibrillary acidic protein by brain astrocytes in vivo.

Ciliary neurotrophic factor is a cytokine that has effects on neuronal survival and phenotype in vitro and in vivo. Ciliary neurotrophic factor has also been shown to have effects on microglia and oligodendrocytes in vitro and in vivo. In this study, we demonstrate in vivo effects of ciliary neurotrophic factor on astrocytes in both the injured and uninjured central nervous system. Ciliary neurotrophic factor increases the expression of glial fibrillary acidic protein and induces concomitant morphological changes in central nervous system astrocytes. Messenger RNA for both ciliary neurotrophic factor and the alpha-component of the ciliary neurotrophic factor receptor is demonstrated in the optic nerve, an essentially pure population of central nervous system glia. We also report here that the promoter region of the glial fibrillary acidic protein gene contains sequences thought to confer direct ciliary neurotrophic factor modulation of glial fibrillary acidic protein gene transcription. Although it is thought that astrocytes are a source of endogenous ciliary neurotrophic factor in the central nervous system and that neurons express the alpha-component of the ciliary neurotrophic factor receptor, the results of the present investigation suggest that astrocytes themselves respond to ciliary neurotrophic factor and that ciliary neurotrophic factor may also be important in glial cell-cell interactions.

Animals↗
PubMed1994

Motor neurons in Onuf's nucleus and its rat homologues express the p75 nerve growth factor receptor: sexual dimorphism and regulation by axotomy.

The present study establishes that populations of neurons in the lumbosacral cord, which innervate pelvic striated muscles, express p75NGFR throughout their life spans. These neuronal groups comprise the Onuf's nucleus in humans and its principal rat homologues, dorsolateral (DL) and dorsomedial (DM) nuclei, as well as the cremasteric (CRE) nucleus. The p75NGFR in these neurons is localized in the rough endoplasmic reticulum, Golgi complex, and lysosomes. Almost all neurons that project to striated perineal muscles in the male rat express p75NGFR; very low levels of p75NGFR are detected in neurons that innervate perineal sphincters of the female. In the female rat, p75NGFR expression is masculinized with perinatal androgen treatment. In addition, the expression of p75NGFR in DM and DL neurons in the adult is up-regulated by injury (i.e., pudendal axotomy) but is not influenced by gonadectomy. The results of this study establish that neurons of Onuf's nucleus and its rat homologues differ from general somatic motor neurons in that they express p75NGFR from early postnatal life (i.e., when all motor neurons express p75NGFR) into the adult (when the former, but not the latter, express the receptor). In view of growing evidence for the role of neurotrophins in the physiology of motor neurons, the above differentiating feature between general somatic and sexually dimorphic motor neurons suggests that p75NGFR may be involved in motor neuron plasticity and may participate in mechanisms by which neurons can protect themselves from degenerative insults.

Androgens↗
PubMed1994

Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons.

The survival of developing motor neurons depends on factors secreted from skeletal muscles and from cells within the central nervous system. Although several members of the nerve growth factor protein family [neurotrophins (NTs)] are able to maintain developing rat motor neurons in vitro, only the brain-derived neurotrophic factor has been shown to have significant effects on the survival of motor neurons in vivo. In the present study, we demonstrate that NT-4/5 also prevents injury-induced death of facial motor neurons in neonatal rats. Furthermore, facial motor neurons express a functional receptor for NT-4/5, whereas mRNA-encoding NT-4/5 can be detected in their environment throughout embryonic and postnatal life. Thus, both NT-4/5 and brain-derived neurotrophic factor may be physiological survival factors for facial motor neurons and may serve as therapeutic agents for motor neuron disease.

Animals↗
PubMed1994

Further characterization of the effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on axotomized neonatal and adult mammalian motor neurons.

Neurotrophins and neural cytokines are two broad classes of neurotrophic factors. It has been reported that ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) prevent the degeneration of axotomized neonatal motor neurons. In addition, BDNF is transported retrogradely to alpha-motor neurons following injection into the muscle, and patterns of BDNF expressed in spinal cord and muscle suggest a physiological role for this factor in motor neurons. In the present study, we characterize the effects of BDNF on axotomized neonatal facial motor neurons and extend these observations to adult models of motor neuron injury (axotomy-induced phenotypic injury of lumbar motor neurons). BDNF reduces axotomy-induced degeneration of neonatal neurons by 55% as determined by Nissl staining (percentage of surviving neurons in vehicle-treated cases, 25%; in BDNF-treated cases, 80%). Rescued neurons have an intact organelle structure but appear smaller and slightly chromatolytic on electron microscopic analysis. As demonstrated by intense retrograde labeling with horseradish peroxidase (HRP) applied to the proximal stump of the facial nerve, neurons rescued by BDNF have intact mechanisms of fast axonal transport. CNTF did not appear to have significant effects on neonatal motor neurons, but the lack of efficacy of this factor may be caused by its rapid degradation at the application site. BDNF is not capable of reversing the axotomy-induced reduction in transmitter markers [i.e., the acetylcholine-synthesizing enzyme choline acetyltransferase (ChAT) or the degrading enzyme acetylcholinesterase (AChE) in neonatal or adult animals or the axotomy-induced up-regulation of the low-affinity neurotrophin receptor p75NGFR (nerve growth factor receptor) in adult motor neurons. However, BDNF appears to promote the expression of p75NGFR in injured neonatal motor neurons. In concert, the findings of the present study suggest that BDNF can significantly prevent cell death in injured motor neurons. However, this neurotrophin may not be a retrograde signal associated with the induction and/or maintenance of some mature features of motor neurons, particularly their transmitter phenotype.

Acetylcholinesterase↗
PubMed1993

Neurotrophic strategies for treating Alzheimer's disease: lessons from basic neurobiology and animal models.

Because neurotrophic factors can prevent natural and experimental cases of neural cell death and induce and maintain differentiation, they are especially attractive agents for the treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). The present report argues for the specific role of particular families of trophic factors, such as neurotrophins (e.g., nerve growth factor [NGF]) and neurokines (e.g., ciliary neurotrophic factor [CNTF]), for the promotion of the survival and phenotype of subsets of central nervous system (CNS) neurons vulnerable in AD, such as basal forebrain cholinergic neurons and cortical projection neurons. Although there is ample evidence for the therapeutic role of NGF in experimental or natural injury of cholinergic neurons, not enough progress has been made on trophic models involving cortical neurons. Further understanding of the mechanisms of cell death in AD and elucidation of the transduction cascades of trophic factors will undoubtedly refine our current concepts of a neurotrophic treatment for AD.

Alzheimer Disease↗
PubMed1993

Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system.

The neurocytokine ciliary neurotrophic factor (CNTF) was described originally as an activity that supports the survival of neurons of the chicken ciliary ganglia in vitro. The widespread expression of CNTF and its principal binding protein, CNTF receptor alpha, in the central and peripheral nervous systems suggests a broader trophic role for this peptide. In the present study, we report that CNTF prevents axotomy-induced cell death of neurons in the anteroventral and anterodorsal thalamic nuclei of the adult rat. Using the polymerase chain reaction, we also demonstrate the presence of CNTF and CNTF receptor alpha mRNA in these same thalamic nuclei. The coincidence of CNTF and its receptor in a population of neurons responding to the factor suggests a paracrine function for CNTF. The present findings establish that CNTF has significant effects on neurons of the central nervous system in vivo and demonstrate that neurocytokines can prevent cell death in the adult central nervous system.

Amino Acid Sequence↗