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Biomedical subjects

J Noth

Publications and source records attributed to J Noth.

At least 19 recordsLinked to original sources
PubMed2003

[Rhabdomyolysis following cerivastatin monotherapy--implications for therapy with HMG-CoA reductase inhibitors].

Cerivastatine was administered as a reversible HMG-CoA reductase inhibitor (statine) to treat hypercholesterolemia until its withdrawal from the market following 52 reports of death due to drug-related rhabdomyolysis and acute renal failure. In most cases, cerivastatine was applied in combination with drugs which influenced the liver metabolism of cerivastatine via cytochromeoxidase P 450 isoenzymes. We report a well-documented case of acute rhabdomyolysis following cerivastatine monotherapy. The diagnosis was confirmed additionally by muscle biopsy.Finally,we give an overview of the current knowledge concerning therapy with HMG-CoA reductase inhibitors,1 year after the withdrawal of cerivastatine from the market.

Acute Disease↗
PubMed2002

Hypertrophic nerve roots in a case of Roussy-Lévy syndrome.

Hypertrophic radiculopathy is a rare feature of neuropathies. Single cases of enlarged nerve roots have been described in hereditary motor sensory neuropathies (HMSN) and chronic inflammatory demyelinating diseases (CIDP). This is the first description of hypertrophied nerve roots in a patient with Roussy-Lévy syndrome. MRI did not show contrast enhancement of the enlarged nerve roots or nodular lesions.

Charcot-Marie-Tooth Disease↗
PubMed2002

Increased expression of the putative axon growth-repulsive extracellular matrix molecule, keratan sulphate proteoglycan, following traumatic injury of the adult rat spinal cord.

Keratan sulphate proteoglycan (KSPG) is a developmentally regulated barrier molecule, directing axonal growth during central nervous system (CNS) formation. The possible re-expression and functional significance of KSPG in preventing axon regeneration following spinal cord injury (SCI) is poorly understood. In the present investigation, the spatio-temporal expression of KSPG was studied following experimental SCI. There was no indication of sparing of axons at the lesion epicentre following severe compression injury. By 7 days post operation (p.o.) a diffuse increase of KSPG immunoreactivity (KSPG-IR) was observed in the parenchyma surrounding the lesion. This was followed by a delayed (21-28 days p.o.) and largely heterogeneous increase of KSPG-IR in the lesion epicentre, which revealed both cellular and extracellular matrix-like distribution patterns. Although no re-growth of anterogradely labelled corticospinal axons was observed, many 200-kDa neurofilament (NF)-positive axons could be detected growing into the connective tissue scar. This phase of spontaneous axonal re-growth was closely associated with a framework of glial cells (including Schwann cells from damaged local spinal nerve roots) that had migrated into the lesion site. The spontaneous nerve fibre re-growth could be detected in both KSPG-rich and KSPG-poor territories. The present data suggest that the lesion-induced up-regulation of KSPG-IR may have contributed to the lack of corticospinal axon re-growth. However, the lack of any direct spatio-temporal correlation between the distribution of raised KSPG-IR and spontaneous NF-positive axonal regeneration suggests that at least some populations of axons can resist the putative inhibitory effects of this extracellular matrix molecule.

Animals↗
PubMed2001

Deficits in sensorimotor control during precise hand movements in Huntington's disease.

OBJECTIVES: To investigate the performance of patients with Huntington's disease (HD) while manipulating objects using a precision grip. METHODS: The grip forces developed by the fingers were studied while subjects lifted an object of unpredictable weight in the hand. The ability to stabilize grip force after externally imposed weight change was also studied. RESULTS: Patients used higher grip forces than the normal subjects in both the lifting and holding phases, particularly with a lighter weight. Lift timing was slowed in the patients, most markedly with a lighter weight. Increased levels of inter-trial variation were observed only with a light weight. This indicates that the slowing in HD differs from that in Parkinson's disease, which remains constant regardless of object load, and that the slowing in HD is not due to involuntary antagonist muscle activity resulting from an underlying chorea. The grip force response to sudden weight change was normal, but appeared after a delay which increased at lower rates of weight change. CONCLUSIONS: Disturbances in precision grip timing and magnitude in HD may result from a reduced ability to process relevant tactile afferent input. The delay in the adaptive response suggests an increased threshold for detection of weight change in HD. Alternatively, this delay may arise from mediation of the response over an additional cerebellar pathway to compensate for damage to the basal ganglia.

Adult↗
PubMed2001

Precision grip deficits in cerebellar disorders in man.

OBJECTIVE: To investigate the effect of a variety of cerebellar pathologies on a functional motor task (lifting an object in a precision grip). METHODS: The study involved 8 patients with unilateral damage in the region of the posterior inferior cerebellar artery (PICA), 6 with damage in the region of the superior cerebellar artery (SUPCA), 12 patients with familiar or idiopathic cortical cerebellar degeneration, and 45 age-matched normal subjects. Subjects lifted an object of unpredictable load (internally guided task) or responded to a sudden load increase while holding the object steadily (externally guided task). RESULTS: Damage to the dentate nucleus (SUPCA) or its afferent input (cerebellar atrophy) resulted in disruption of the close coordination normally seen between proximal muscles (lifting the object) and the fingers (gripping the object) during a self-paced lift. Both the SUPCA group and, more markedly, the atrophy group, showed exaggerated levels of grip force. All patients showed a normal rate of grip force development. Damage in the PICA region had no significant effect on any of the measured lifting parameters. All patient groups retained the ability to scale grip force to different object loads. The automatic grip force response to unexpected load increase of a hand held object showed normal latency and time course in all patient groups. The response was modulated by the rate of the load change. Response magnitude was exaggerated in the atrophy patients at all 3 rates tested. CONCLUSIONS: Disturbances associated with cerebellar disorders differed from those seen following damage to the basal ganglia, with no evidence of slowed rates of grip force development. Disruption of temporal coordination between the proximal muscles (lifting) and the fingers (gripping) in a lift was apparent, supporting the role of the cerebellum in coordinating the timing of multi-joint movement sequences. Exaggeration of grip force levels was found in association with damage to the dentate nucleus or, in particular, to its afferent input. This could support a role or the cerebellum in sensorimotor processing, but might also represent a failure to time correctly the duration of grip force generation.

Action Potentials↗
PubMed2001

Long-term follow-up of patients after intraarterial thrombolytic therapy of acute vertebrobasilar artery occlusion.

Local thrombolysis may reduce mortality after acute vertebrobasilar artery occlusion. We focused on variables affecting recanalization, outcome and long-term prognosis. Thirty-six patients with vertebrobasilar artery occlusion were treated with local intraarterial thrombolytic therapy. Four of the survivors were among the 16 patients without recanalization. Recanalization was associated with a higher survival rate. Top-of-the-basilar-type occlusions have the highest recanalization rate. The thrombolytic medication used did not influence the recanalization frequency. One patient died due to an intracerebral bleed after thrombolysis. There was no association between the time interval (greater or less than 6 h) between the onset of symptoms and therapy initiation and survival. Relapses during follow-up (mean follow-up 3.7 years) did not occur. MRI/MRA and ultrasound studies during follow-up showed unchanged results in these patients. All survivors at the time of follow-up lived at home.

Acute Disease↗
PubMed2000

Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response.

Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4-14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1-4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.

Aged↗
PubMed2000

Detection of stenoses in the anterior circulation using frequency-based transcranial color-coded sonography.

Atherosclerotic stenoses of the intracranial vessels are less frequent than those of the extracranial vessels, but they are associated with a considerable annual stroke rate. The aim of the present study was to investigate the usefulness of frequency-based transcranial color-coded sonography (TCCS), transcranial Doppler sonography (TCD) and digital subtraction angiography (DSA) in patients with middle cerebral artery (MCA) and intracranial internal carotid artery (ICA) stenosis. Forty patients presenting with 48 intracranial stenoses of the anterior circulation were involved in the study. The stenoses were detected in the neurovascular laboratory during routine TCD examinations. All patients underwent an additional frequency-based TCCS examination. Both the axial and coronal planes were obtained to allow the exact localization of MCA stenosis and differentiation from intracranial ICA stenosis. Angle-corrected flow velocity measurements were performed if straight vessel compartments were 20 mm or more in length. A total of 18 stenoses (44%) were investigated additionally with DSA. According to the investigation with TCD, 20 (42%) stenoses were low-grade, 12 (25%) were moderate, and the remaining 16 (33%) were severe. Angle-corrected flow velocity measurements obtained with the integrated pulse-wave Doppler device of the TCCS machine were highly correlated (0.912, p < 0.001) with those obtained with TCD. TCCS achieved a reliable differentiation of MCA main stem stenosis vs. intracranial ICA stenosis in 7 patients and vs. MCA branch stenosis in 4 patients, but TCD failed in these two subgroups. The agreement between DSA and TCCS to evaluate semiquantitatively 18 intracranial stenoses resulted in a weighted-kappa value of 0.764. The major clinically relevant advantages of TCCS over TCD in MCA stenosis are its ability to differentiate MCA trunk stenosis from terminal ICA or MCA branch stenosis reliably and to perform angle-corrected flow velocity measurements.

Angiography, Digital Subtraction↗
PubMed2000

Attempted endogenous tissue repair following experimental spinal cord injury in the rat: involvement of cell adhesion molecules L1 and NCAM?

It is widely accepted that the devastating consequences of spinal cord injury are due to the failure of lesioned CNS axons to regenerate. The current study of the spontaneous tissue repair processes following dorsal hemisection of the adult rat spinal cord demonstrates a phase of rapid and substantial nerve fibre in-growth into the lesion that was derived largely from both rostral and caudal spinal tissues. The response was characterized by increasing numbers of axons traversing the clearly defined interface between the lesion and the adjacent intact spinal cord, beginning by 5 days post operation (p.o.). Having penetrated the lesion, axons became associated with a framework of NGFr-positive non-neuronal cells (Schwann cells and leptomeningeal cells). Surprisingly few of these axons were derived from CGRP- or SP-immunoreactive dorsal root ganglion neurons. At the longest survival time (56 days p.o.), there was a marked shift in the overall orientation of fibres from a largely rostro-caudal to a dorso-ventral axis. Attempts to identify which recognition molecules may be important for these re-organizational processes during attempted tissue repair demonstrated the widespread and intense expression of the cell adhesion molecules (CAM) L1 and N-CAM. Double immunofluorescence suggested that both Schwann cells and leptomeningeal cells contributed to the pattern of CAM expression associated with the cellular framework within the lesion.

Animals↗
PubMed1999

Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunt in patients with cerebral embolic events.

OBJECTIVES: We sought to evaluate whether transthoracic contrast echocardiography using second harmonic imaging (SHI) is a diagnostic alternative to transesophageal contrast echocardiography (TEE) for the detection of atrial right to left shunt. BACKGROUND: Paradoxic embolism is considered to be the major cause of cerebral ischemic events in young patients. Contrast echocardiography using TEE has proven to be superior to transthoracic echocardiography (TTE) for the detection of atrial shunting, SHI is a new imaging modality that enhances the visualization of echocardiographic contrast agents. METHODS: We evaluated 111 patients with an ischemic cerebral embolic event for the presence of atrial right to left shunt using an intravenous (IV) contrast agent in combination with three different echocardiographic imaging modalities: 1) TTE using fundamental imaging (FI); 2) TTE using SHI; and 3) TEE. The severity of atrial shunting and the duration of contrast visibility within the left heart chambers were evaluated for each imaging modality. Image quality was assessed separately for each modality by semiquantitative scoring (0 = poor to 3 = excellent). Presence of atrial right to left shunt was defined as detection of contrast bubbles in the left atrium within the first three cardiac cycles after contrast appearance in the right atrium either spontaneously or after the Valsalva maneuver. RESULTS: A total of 57 patients showed evidence of atrial right to left shunt with either imaging modality. Fifty-one studies were positive with TEE, 52 studies were positive with SHI, and 32 were positive with FI (p<0.001 for FI vs. SHI and TEE). The severity of contrast passage was significantly larger using SHI (61.6+/-80.2 bubbles) compared to FI (53.7+/-69.6 bubbles; p<0.005 vs. SHI) but was not different compared to TEE (43.9+/-54.3 bubbles; p = NS vs. SHI). The duration of contrast visibility was significantly longer for SHI (17.4+/-12.4 s) compared to FI (13.1+/-9.7 s; p<0.001) and TEE (11.9+/-9.6 s; p<0.02). Mean image quality improved significantly from FI (1.5+/-0.8) to SHI (2.0+/-0.8; p<0.001 vs. FI) and TEE (2.5+/-0.7; p<0.001 vs. SHI). CONCLUSIONS: In combination with IV contrast injections, TEE and SHI have a comparable yield for the detection of atrial right to left shunt. Both modalities may miss patients with atrial shunting. In young patients with an unexplained cerebrovascular event and no clinical evidence of cardiac disease, a positive SHI study may obviate the need to perform a TEE study to search for cardiac sources of emboli.

Adult↗
PubMed1999

Differential distribution of immunoreactivity in the developing rat spinal cord revealed by the monoclonal antibody Py.

Monoclonal antibody Py was developed as a useful tool for the identification of large diameter neurons of the adult rat central nervous system [Woodhams et al., J. Neurosci., 9 (1989) 2170-2181]. Here, we present a detailed light-microscopic study of the distribution of Py-immunoreactivity in the developing rat spinal cord. The first cells which demonstrated Py-immunoreactivity were the motoneurons in layer IX of the gray matter at embryonic day 15. These cells, including their axons and dendrites, remained Py-immunoreactive throughout subsequent developmental stages into adulthood and were the most intensely stained cells in the adult rat spinal cord. Other cell populations which became Py-immunoreactive during development were neurons in layers III-VIII, and large-to-medium diameter neurons of the dorsal root ganglion (DRG). Transient Py-immunoreactivity was observed in the distal portions of DRG axons as well as in the ascending fibers in the dorsal funiculus. Py-immunoreactive fibers could be detected in the ventral most part of the dorsal funiculus (corticospinal tract area), even at embryonic ages prior to the arrival of corticospinal fibers. The localization and transient expression of the antigen recognized by the Py-antibody in developing rat spinal cord strongly suggests an important role of this molecule in stabilization and/or plasticity of the neuronal cytoskeleton. The results presented here form the foundation for the use of Py-immunocytochemistry to study well-defined cell populations under a range of experimental and pathological conditions.

Animals↗
PubMed1999

Astrocytes re-express nestin in deafferented target territories of the adult rat hippocampus.

Up-regulation of the intermediate filament protein, nestin, is a sensitive indicator for the extent of astrocytic activation in regions of CNS close to the point of injury. However, it remains unclear whether activated astrocytes in distant, deafferented CNS territories are also capable of nestin re-expression. Here, we demonstrate that traumatic injury to the dentate gyrus is followed by the rapid but transient expression of nestin in astrocytes located in the stratum lucidum of field CA3. Up-regulation of nestin was first detected at 1 day, was still visible at 14 days, and returned to close to control levels by 28 days post-injury. The present investigation clearly demonstrates the sensitivity of nestin expression as a indicator of astroglial activation in hippocampal target territories undergoing deafferentation-related changes.

Afferent Pathways↗