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Biomedical subjects

J Noth

Publications and source records attributed to J Noth.

At least 55 records · Page 3Linked to original sources

Dynamics of microglial activation in the spinal cord after cerebral infarction are revealed by expression of MHC class II antigen.

Microglial reactivity associated with induction of MHC class II (HLA-DR) antigen is a sensitive indicator for pathological events in the CNS. To assess the response of glial cells after lesions of supraspinal descending tracts, HLA-DR, CD68 and GFAP were studied immunohistochemically on spinal cord tissue of 5 patients who died after unilateral infarction of the middle cerebral artery territory, and 5 control cases. In patients who died shortly after a stroke (4-14 days) increased HLA-DR-immunoreactivity (HLA-DR-IR) could be observed in the intermediate grey matter and in the ventral horn. The CD68-IR was much less intense. After longer survival times (5 weeks to 4 months). HLA-DR-IR in the grey matter was clearly lower than that observed in the spinal cord of short survival times, but very abundant in the dorsolateral funiculus, specifically within the corticospinal tract. In white matter areas, CD68-IR was almost identical to the HLA-DR-IR. Within the grey matter, CD68-IR was similar to the control tissue. A moderate increase of GFAP-positive astrocytes could be seen only in the grey matter after longer survival times. It seems probable, that the dynamics of HLA-DR-positive microglia reflect the early phagocytosis of presynaptic terminals by microglia in target regions of descending fibre tracts. In the white matter, the removal of degenerating axons by phagocytosing microglia expressing HLA-DR and CD68 antigens is a slower process which occurs over a period of months.

Adult↗

Precision grip and Parkinson's disease.

In order to investigate sensorimotor processing and force development in Parkinson's disease, 16 patients, four patients with hemiparkinsonism and 12 age-matched normal subjects were assessed during lifting and holding of an object in a precision grip between thumb and forefinger, or holding the object in this grip at a fixed height above a table. In the former case, object loading could be changed between lifts without warning. In the latter case, unexpected step load changes to the object were applied to the object with a torque motor. All procedures could be applied with or without visual control of the hand and the object. Normal subjects lifted an unpredictable load employing the grip force parameters used in the preceding lift. If a load change was encountered, the parameters became adapted to the new conditions during the lift, modulating grip forces to match the loading. Parkinsonian patients retained this strategy and the ability to regulate grip forces according to load. Under all conditions, however, parkinsonian subjects developed abnormally high grip forces in both the lift and the hold phase, although the ratio of these forces remained normal. Lifting height was normal in parkinsonian subjects, but the duration of the lifting task was significantly prolonged, due to a marked slowing in the rate of grip force development in the lead-up to object lift-off and to prolongation of the movement phase. Forewarning of object loading, with or without visual control, did not reduce timing deficits or improve the rate of grip force development. However, it did allow parkinsonian subjects to reduce the safety margin significantly. Responses to step load changes imposed during holding without visual control showed minor abnormalities in the parkinsonian patients: onset latencies and EMG activity in the first dorsal interosseus and thenar muscles were normal up to 140 ms after displacement. Subsequent EMG activity in the first dorsal interosseus remained largely normal, but activity later in the slip response (140-210 ms), subject to voluntary influence, was reduced in the thenar muscle. Differences were less marked under visual conditions, but remained significant. We concluded that the internal parameter set for lifting an object in a precision grip and the automatic processes adapting precision grip to actual conditions are intact in Parkinson's disease. However, parkinsonian subjects generate abnormally high grip forces and require longer than normal subjects to complete a lift, particularly with lighter loads. This deterioration in performance reflects both reduced effectiveness of sensorimotor processing and impairment in the rate of force development in Parkinson's disease.

Activities of Daily Living↗

Botulinum toxin treatment of synkinesia and hyperlacrimation after facial palsy.

OBJECTIVES: To investigate the effects of injection of botulinum toxin type A (BTX A) into the orbicularis oculi muscle and lacrimal gland in patients with aberrant regeneration after facial palsy (facial synkinesias and hyperlacrimation). METHODS: The effect of the toxin injection (on average 75 mouse units of BTX A) into the orbicularis oculi muscle on facial synkinesias was assessed on a five point (0 to 4) scale in 10 patients with aberrant regeneration of facial nerve fibres after a peripheral facial nerve palsy. Six patients underwent a videographic control, which was assessed by a blinded independent investigator. In two patients with hyperlacrimation an extra dose of botulinum toxin (on average 20 mouse units BTX A) was injected into the lacrimal gland and the effect was assessed using the Schirmer test and on a three point scale. RESULTS: Botulinum toxin type A had a good to excellent (grades 3 and 4) effect over an average of six months after 91% of injections. In 9% the injections had a moderate (grade 2) effect. Patients with hyperlacrimation showed a nearly complete recovery. There were no systemic side effects but focal side effects due to a temporary weakness of the orbicularis oculi muscle were not uncommon. CONCLUSIONS: Botulinum toxin type A is the treatment of choice in motor and autonomic effects of aberrant regeneration of facial nerve after a peripheral palsy. The required dose is similar to or slightly lower than the dose usually recommended for hemifacial spasm.

Adult↗

The effect of propranolol versus placebo on resident surgical performance.

PURPOSE: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome.

Adrenergic beta-Antagonists↗

Effects of sustained low-level elevations of carbon dioxide on cerebral blood flow and autoregulation of the intracerebral arteries in humans.

Cerebral blood flow velocity (CBFv) was measured by insonating the middle cerebral arteries of four subjects using a 2 Mhz transcranial Doppler. Ambient CO2 was elevated to 0.7% for 23 d in the first study and to 1.2% for 23 d in the same subjects in the second study. By non-parametric testing CBFv was elevated significantly by +35% above pre-exposure levels during the first 1-3 d at both exposure levels, after which CBFv progressively readjusted to pre-exposure levels. Despite similar CBFv responses, headache was only reported during the initial phase of exposure to 1.2% CO2. Vascular reactivity to CO2 assessed by rebreathing showed a similar pattern with the CBFv increases early in the exposures being greater than those elicited later. An increase in metabolic rate of the visual cortex was evoked by having the subjects open and close their eyes during a visual stimulus. Evoked CBFv responses measured in the posterior cerebral artery were also elevated in the first 1-3 d of both studies returning to pre-exposure levels as hypercapnia continued. Cerebral vascular autoregulation assessed by raising head pressure during 10 degrees head-down tilt both during the low-level exposures and during rebreathing was unaltered. There were no changes in the retinal microcirculation during serial fundoscopy studies. The time-dependent changes in CO2 vascular reactivity might be due either to retention of bicarbonate in brain extracellular fluid or to progressive increases in ventilation, or both. Cerebral vascular autoregulation appears preserved during chronic exposure to these low levels of ambient CO2.

Adult↗

Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack.

To evaluate the additional value of transesophageal (TEE) compared with transthoracic (TTE) echocardiography and the role of patent foramen ovale (PFO) and deep vein thrombosis in the work-up of embolic events, patients with presumed cardiac embolic stroke or transient ischemic attack (neurovascular etiology was excluded) were prospectively studied by transthoracic and transesophageal contrast echocardiography. If PFO was detected echocardiographically, PFO size was assessed semiquantitatively and phlebography of both legs was performed. Two hundred forty-two consecutive patients (153 men, 60 +/- 15 years) were studied. In 197 patients, neuroimaging showed evidence of embolic infarction. TEE identified 138 potential cardiac sources of embolism in 111 patients, compared with 69 by TTE (p <0.01) in 59 patients. TEE detected potential cardiac sources in 52 patients with negative TTE examination and was significantly superior compared with TTE for identifying left atrial thrombi, spontaneous echo contrast, PFO, atrial septal aneurysm, and atheroma of the ascending aorta. In patients with a positive TTE, additional diagnostic information by TEE was found in only 6 patients and did not change therapy. Phlebography was performed in 53 patients with PFO and revealed deep vein thrombosis in 5 patients (9.5%); all had medium or large PFOs. Thus, in patients with cerebral ischemia of suspected cardiogenic origin and a normal TTE examination, TEE detects potential causes of embolism in 31% of patients and is therefore of diagnostic relevance. Conversely, in the presence of a diagnostic TTE an additional TEE confers only marginal diagnostic benefit. Deep venous thrombosis was detected in nearly 10% of patients with PFO as the sole identifiable cardiac risk factor. Given that in 4 of 5 patients deep vein thrombosis was clinically silent, phlebography should be performed in patients with medium or large interatrial shunts if paradoxical embolism is suspected.

Adult↗

Disturbances of precision grip in Huntington's disease.

Disturbed motor control of the fingers, as revealed by the response to unexpected loading of an object held in a precision grip, or to finger perturbation during isometric holding, has been studied in patients with Huntington's disease (HD) and in normal subjects. In normal subjects unexpected loading elicited a reflex response (mean latency 73 ms) in the first dorsal interosseus muscle (FDI). This was accompanied by a clear increase in grip force, reaching a maximum at 200 ms, which stabilised block position. Index finger perturbation led to a long-latency reflex response in the FDI of all normal subjects. No such response was seen in the HD patients. The response to object loading, in contrast, was present, but significantly delayed (mean onset 95 ms; P = 0.0135). The response was qualitatively normal, with grip force reaching a maximum at 220-230 ms. It is suggested that the absence of the long-latency stretch reflex and the delay in the response to loading in HD patients may represent a reduction in somatosensory input to the cortex caused by disruption of basal ganglia structures.

Adult↗

Differential distribution of immunoreactivity in the adult rat spinal cord revealed by the monoclonal antibody, Py: a light and electron microscopic study.

The monoclonal antibody Py has previously been shown to be a useful marker for subpopulations of neurons in the rat brain. However, the distribution of Py immunoreactivity in other regions of the CNS and PNS is not known. Here, we present a light and electron microscopic investigation into the distribution of Py immunoreactivity in the adult rat spinal cord, dorsal root ganglia, and peripheral nerves. Py immunoreactivity was associated with cytoskeletal elements in the cell body and dendrites of large-diameter neurons (particularly motoneurons, Clarke's nucleus neurons, and some dorsal root ganglion cells). Small-diameter neurons of lamina II (substantia gelatinosa) were Py negative. Py immunoreactivity was also detected in some populations of nerve fibers, notably axons located in the corticospinal tract, axons in the region of the white matter bordering the gray matter (presumably propriospinal axons), and also motor axons of the ventral root, but not in peripheral nerve. Dorsal roots were largely unstained. The present observations suggest a possible involvement of the Py antigen in the function or maintenance of the cytoskeleton of some populations of neurons and that the antibody may be a potentially useful tool for studying lesion-induced cytoskeletal alterations, particularly in alpha-motoneurons and Clarke's nucleus neurons.

Animals↗

Axotomy-induced alterations in the red nucleus revealed by monoclonal antibody, Py, following a low thoracic spinal cord lesion in the adult rat.

The monoclonal antibody Py was previously developed as a tool for the identification of subpopulations of hippocampal neurons. Here, the differential distribution of Py immunoreactivity in the mid-brain is described showing that Py also serves as a useful marker for other populations of neurons. Medium to strong immunoreactivity was observed in the cell body and dendrites of neurons of the oculomotor nucleus, superior colliculus and substantia gelatinosa reticulata. However, particularly intense Py-immunoreactivity was identified in the magnocellular neurons in the caudal pole of the red nucleus. Unilateral transection of the rubrospinal tract at Th9-10 induced a marked reduction of Py immunoreactivity in the ventrolateral territory of the caudal pole of the axotomised red nucleus. A small but statistically significant reduction of Py-immunoreactivity was first seen at 7 days after surgery and a maximal loss of immunoreactivity (reduced to 66% of control levels) was observed by 21 days after surgery. Immunoreactivity in the axotomised red nucleus was reduced for the duration of the experiment but at the longer survival times studied (3 and 6 months) a small degrees of recovery of staining was observed in small-medium diameter atrophic neurons. These results indicate that monoclonal antibody Py, may be a useful novel and sensitive tool for investigating the cell body reaction of particular populations of axotomised CNS neurons following spinal cord injury.

Animals↗

Prevalence and time course of microembolic signals in patients with acute stroke. A prospective study.

BACKGROUND AND PURPOSE: Cerebral emboli can be identified by the presence of typical microembolic signals (MES) in transcranial Doppler (TCD) spectral curves. The usefulness of this technique was studied by evaluating the prevalence and time course of MES in patients with acute stroke. In addition, we examined the influence of anticoagulation therapy on the occurrence of MES. Another study objective was to identify the value of MES in elucidation of the underlying pathology of cerebral ischemia in patients with acute stroke. METHODS: We used bilateral TCD monitoring of the middle cerebral artery to search for microemboli in 100 patients with acute nonhemorrhagic stroke in the anterior circulation. Monitoring time was for 30 minutes at admission (examination I), after 24 hours (examination II), and again after 48 hours (examination III). RESULTS: Twenty-two of the 100 patients had to be excluded from the study after examination 1 because retrospectively they did not fulfill the inclusion criterion or because they had an insufficient bone window. Forty of the patients (51%) showed MES during at least one of the three TCD examinations. In 9 of the 47 patients without MES during examination I (19%), MES could be recorded subsequently during examinations II and III. A statistically significant decrease in the prevalence of MES occurred between examinations I and III (P = .01). The frequency of MES in a single patient decreased between examinations I and II but increased again in examination III, although it did not reach the initial level. Prevalence of MES was the highest during the period up to 6 hours after the onset of symptoms. However, even at > 72 hours after the onset of symptoms, a substantial number of MES could be recorded. In 18 of the 21 patients with carotid artery stenosis or occlusion who showed MES (86%), these signals occurred ipsilateral to the affected carotid artery. In 5 of the 13 patients with MES and a potential cardiac source of embolism (38%), MES were observed bilaterally. Forty-one patients were without anticoagulation treatment at the time of examination: 19 of these patients (46%) presented with MES. In contrast, of the 37 patients receiving anticoagulation treatment at the time of the first examination, MES could be recorded in only 12 (32%). CONCLUSIONS: Microemboli are a frequent phenomenon in patients with acute stroke arising from a variety of causes, both in the very early stages and several days after the onset of symptoms. The prevalence of MES decreases significantly over time. MES occur more frequently in patients with carotid artery disease than in patients with a potential cardiac source of embolism. Ipsilateral MES are frequent in patients with carotid artery disease, whereas bilateral MES are suggestive of a cardioembolic origin. Anticoagulation treatment appears to decrease the prevalence of MES, but microemboli still occur in patients receiving intravenous therapy with heparin. Because MES occur intermittently, TCD examinations should be repeated several times, even in patients without MES in the first examination, and long-term monitoring equipment is necessary.

Acute Disease↗

Do chronic middle cerebral artery stenoses represent an embolic focus? A multirange transcranial Doppler study.

BACKGROUND AND PURPOSE: It remains uncertain whether the annual stroke risk of 7% to 8% in middle cerebral artery (MCA) stenosis is of embolic or hemodynamic origin. Preliminary reports provide evidence of emboli exiting from acute MCA stenoses, detected by transcranial Doppler (TCD) sonography. With multirange monitoring before and after the stenosis, TCD monitoring may help for the first time to differentiate microemboli exiting from the MCA stenosis from those with a source proximal to the MCA stenosis. We searched for microembolic signals (MES) using multigated monitoring in patients with chronic MCA stenoses. METHODS: Fifty-eight patients with 78 chronic stenoses of the MCA were enrolled in the study. Additional sources of embolism were ruled out by extensive clinical workup. Twenty-four patients were treated with coumarin, whereas 28 patients received aspirin. The remaining 6 patients discontinued their medication after a few weeks. The sample volume of the multirange probe was placed on either side of the stenotic area of the MCA. RESULTS: Twenty-three (29.5%) of the stenoses were low grade, 18 (23%) were moderate, and 37 (47.5%) were severe. Thirty-seven (47%) of the stenoses were symptomatic and 41 (53%) were asymptomatic before study entry. During follow-up, 2 strokes and 7 transient ischemic attacks occurred. Computer tomography revealed two watershed-type infarcts. Sufficient insonation of the prestenotic and poststenotic segments of the MCA was possible in 70 stenoses (90%). No MES could be detected during a total of 1740 minutes' monitoring time distal to the MCA stenoses, regardless of the patients' medication. MES were also absent in the contralateral MCA. CONCLUSIONS: MES are not detectable in patients with chronic MCA stenoses of different degrees. No MES were found in either symptomatic or asymptomatic stenoses, regardless of the patients' medication. These results indicate that chronic MCA stenoses do not represent a significant embolic source. The absence of MES in the prestenotic Doppler sample volume, the watershed-type infarcts during follow-up, and the absence of small-vessel disease on computed tomography suggests that hemodynamic mechanisms are responsible for recurrent cerebral ischemia.

Aged↗

Transient decrease of acetylcholinesterase in ventral horn neurons caudal to a low thoracic spinal cord hemisection in the adult rat.

Light microscopic enzyme histochemistry was employed to study the alterations of acetylcholinesterase (AChE) within lumbosacral ventral horn neurons at survival times of 1, 4, 7, 14, 28, 60, and 90 days after low thoracic spinal cord hemisection in adult rats. The intensity of histochemical staining was quantified using densitometric techniques. Virtually all ventral horn neurons of sham-operated and unoperated animals, which served as controls, displayed intense AChE staining. Hemisection of the spinal cord induced a transient ipsilateral decrease of AChE staining in most neuronal cell bodies and in the neuropil of lamina IX at all segmental levels caudal to the lesion. Quantitative analysis of representative segments revealed a reduction of AChE in the ventral horn during a postoperative (p.o.) period of 1 to 28 days followed by a phase of recovery over the next two months. AChE activity still remained slightly reduced, even at 90 days p.o. The transient decrease in AChE is a well-known metabolic response of axotomized motoneurons. However, the observed changes of AChE reactivity in intact motoneurons ipsilateral and caudal to the hemisection are presumably induced by the interruption of supraspinal descending pathways. These metabolic changes may functionally affect the whole motor unit and be involved in the disturbances of motor function following spinal cord injury.

Acetylcholinesterase↗

An increased frequency of patent foramen ovale in patients with transient global amnesia. Analysis of 53 consecutive patients.

OBJECTIVE: Alerted by the number of patients with transient global amnesia (TGA) in whom Valsalvalike activities immediately preceded the onset of TGA, we have investigated the frequency of patent foramen ovale (PFO) as the prerequisite for paradoxical embolism. DESIGN: Case series with comparison to a control group. SETTING: Hospitalized and ambulatory patients at the neurological departments of the Alfried Krupp Hospital, Essen, Germany, and the Rheinisch-Westfälische-Technische Hochschule, Aachen, Germany. PATIENTS: Fifty-three consecutive patients with TGA were evaluated by the 2 centers between 1988 and 1995. RESULTS: Using contrast transcranial Doppler sonography we have observed a PFO in 55% of the patients with TGA, compared with 27% of a control group of 100 patients. This difference was statistically significant (P < .01). Twenty-five patients with TGA (47%), 15 of them with a proven PFO, reported a precipitating activity, such as the lifting of heavy weights, immediately before the TGA occurred. CONCLUSIONS: In addition to other pathological mechanisms, paradoxical embolism with temporobasal ischemia could possibly play a role in the clinical syndrome of TGA. This hypothesis could explain the frequent observation of preceding Valsalvalike activities in patients with TGA.

Adult↗

Stretch reflexes of the proximal arm in a patient with mirror movements: absence of bilateral long-latency components.

The stretch reflex responses evoked by unilateral limb displacement in distal (first dorsal interosseus (FDI)) and in proximal (biceps brachii (Bb)) arm muscles were studied during matched bilateral contractions in a patient with congenital mirror movements. In this patient unilateral transcortical magnetic stimulation (TMS) elicited not only the normal contralateral EMG response but also a clear ipsilateral component in the EMG of both proximal and distal arm muscles. As expected from previous studies, the ipsilateral FDI muscle responded to stretch of the index finger with short- (M1) and long-latency (M2) reflex components. In addition, the FDI contralateral to displacement exhibited an abnormal mirrored response corresponding to the M2 interval. In contrast, whereas the ipsilateral Bb responded to imposed elbow extension with a marked M1/M2 reflex response, no mirroring of either reflex component was apparent in the contralateral Bb EMG. If the mirroring of the M2 in the FDI is accepted as evidence for the transcortical nature of the M2 reflex response, then it follows that the absence of such mirroring in the Bb indicates that a transcortical mechanism cannot play a major role in the generation of long-latency stretch reflex responses in proximal arm muscles.

Adult↗

B-50 (GAP-43) in the rat spinal cord caudal to hemisection: lack of intraspinal sprouting by dorsal root axons.

The controversial hypothesis that intraspinal sprouting by dorsal root axons promotes reinnervation of partially denervated neurons caudal to a low thoracic cord hemisection was re-investigated in rats using quantitative immunohistochemical analysis of the neural specific growth-associated protein B-50 (GAP-43) at postoperative survival times of 3, 10, 21, 42, and 90 days. The lack of increase in B-50-immunoreactivity in all segments below the hemisection at all survival times does not support the concept of intraspinal sprouting following the removal of supraspinal descending pathways.

Animals↗

Recovery from Wernicke's aphasia: a positron emission tomographic study.

Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right-handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke.

Aged↗