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Biomedical subjects

B Nuttin

Publications and source records attributed to B Nuttin.

At least 19 recordsLinked to original sources
PubMed2005

Effects of peripheral cooling on intention tremor in multiple sclerosis.

OBJECTIVE: To investigate the effect of peripheral sustained cooling on intention tremor in patients with multiple sclerosis (MS). MS induced upper limb intention tremor affects many functional activities and is extremely difficult to treat.Materials/ METHODS: Deep (18 degrees C) and moderate (25 degrees C) cooling interventions were applied for 15 minutes to 23 and 11 tremor arms of patients with MS, respectively. Deep and moderate cooling reduced skin temperature at the elbow by 13.5 degrees C and 7 degrees C, respectively. Evaluations of physiological variables, the finger tapping test, and a wrist step tracking task were performed before and up to 30 minutes after cooling. RESULTS: The heart rate and the central body temperature remained unchanged throughout. Both cooling interventions reduced overall tremor amplitude and frequency proportional to cooling intensity. Tremor reduction persisted during the 30 minute post cooling evaluation period. Nerve conduction velocity was decreased after deep cooling, but this does not fully explain the reduction in tremor amplitude or the effects of moderate cooling. Cooling did not substantially hamper voluntary movement control required for accurate performance of the step tracking task. However, changes in the mechanical properties of muscles may have contributed to the tremor amplitude reduction. CONCLUSIONS: Cooling induced tremor reduction is probably caused by a combination of decreased nerve conduction velocity, changed muscle properties, and reduced muscle spindle activity. Tremor reduction is thought to relate to decreased long loop stretch reflexes, because muscle spindle discharge is temperature dependent. These findings are clinically important because applying peripheral cooling might enable patients to perform functional activities more efficiently.

Activities of Daily Living↗
PubMed2003

Optimized lentiviral vector production and purification procedure prevents immune response after transduction of mouse brain.

HIV-derived lentiviral vectors are efficient vehicula to deliver genes into the brain and hold great promise for future gene therapy of neurodegenerative disorders. However, administration of the current vector preparations in mouse brain was found to induce a systemic immune response to vector proteins and a modest inflammation in the brain. Moreover, serum antibodies from vector-treated animals were capable of partially neutralizing lentiviral vector-mediated transduction in cell culture. To avoid this unexpected immune reaction, we have optimized new vector production and purification protocols. Purification by sucrose gradient ultracentrifugation abolished the immune response, but vector titers also decreased substantially. Lentiviral vector production in the absence of serum in the cell culture medium equally reduced immunogenicity without affecting transduction efficiency. These results have important implications for future clinical use of lentiviral vectors, and for the use of lentiviral vectors to create animal models for neurodegenerative diseases that have an important neuroinflammatory component.

Animals↗
PubMed2003

Intention tremor during manual aiming: a study of eye and hand movements.

Accurate goal-directed movements toward a visual target require a precise coordination of both the oculomotor and limb motor systems. Intention tremor and eye movement deficits are frequently observed in multiple sclerosis (MS). The goal of this study was to examine the characteristics of intention tremor and simultaneously produced eye movements during rapid goal-directed movements. Eye and hand movements were synchronously measured in 16 MS patients with intention tremor and 16 control subjects. Manual performances of the patient group were characterized by a delayed onset, slower execution and aiming inaccuracies. In line with the clinically defined picture of intention tremor differences between patients and control subjects were most pronounced toward the end of the movement. Dependent variables were obviously greater in MS patients compared with control subjects, and correlated well with clinical outcome measures. The application of an inertial load to the limb did not show any effect on intention tremor. In addition to impaired limb coordination, evidence has been found that eye movements, too, were abnormal in patients compared with control subjects. Moreover, eye and hand movement deficits seemed to be closely related, suggesting a common underlying command structure. Inaccurate eye movements were likely to hamper an accurate motor performance of the hand.

Adult↗
PubMed2003

Effect of visual information on step-tracking movements in patients with intention tremor due to multiple sclerosis.

The effect of visual information on step-tracking movements was studied in 18 patients with intention tremor due to multiple sclerosis (MS) and 15 healthy controls. Parricipants performed a slow wrist step-tracking task with stationary targets under five visual feedback conditions. The display of the target and movement cues was selectively withdrawn to examine the effects of visual information on intention tremor and movement accuracy. Results showed that intention tremor was most pronounced when visual display of both target and movement cues was available. Withdrawing visual information of the limb movement reduced tremor more than withdrawing the visual display of the target cues. Both the patient and control group was less accurate when the display of limb movement was occluded. Patients, however, were more dependent on visual information of the limb movement for accurate motor performance than healthy controls. When the visual display of the limb movement was partially occluded between or near to the targets, tremor decreased without deterioration of movement accuracy.

Adult↗
PubMed2003

Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases.

OBJECTIVE: Investigation of deep brain stimulation (DBS) as a last-resort treatment alternative to capsulotomy in treatment-refractory obsessive-compulsive disorder (OCD). METHOD: Prospective single-case based design with evaluation of DBS impact on emotions, behaviour, personality traits and executive function in three patients with OCD. RESULTS: Two patients experienced sustained improvement of OCD symptoms with DBS. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) dropped 12 points and 23 points to baseline and Y-BOCS self-rating scale (Y-BOCS-SRS) and Profile of Mood States (POMS) for depression and tension decreased with increasing stimulation amplitude. Total Maladjustment Score on the Brief Psychiatric Rating Scale reduced with 44 and 59% to baseline. Reduction in psychopathology was sustained under continuous stimulation. No deleterious impact of DBS on neuropsychological testing or personality traits measured on a self-rated personality inventory was detected. CONCLUSION: These preliminary findings demonstrate that DBS may have important therapeutic benefits on psychopathology in OCD. No harmful side-effects were detected during follow-up (33/33/39 months, respectively).

Adult↗
PubMed2003

Deep brain stimulation in treatment refractory obsessive compulsive disorder.

Obsessive-compulsive disorder is a worldwide psychiatric disorder with a lifetime prevalence of 2% and mainly characterized by obsessional ideas and compulsive behaviors and rituals. Many patients show improvement under cognitive behavioral and/or pharmacological treatment. A minority of patients is refractory to all available therapy and may benefit from capsulotomy. This study aims to investigate deep brain stimulation (DBS) as a last resort treatment alternative to capsulotomy in treatment refractory obsessive-compulsive disorder. Eight patients have been implanted bilaterally in the anterior limbs of the internal capsules with a quadripolar electrode. This paper presents the results of the first 4 operated patients. Acute deep brain stimulation displays an immediate improvement of the speech, mood, eye contact and motor function. Chronic deep brain stimulation improves significantly the obsessional and compulsive symptomatology in three out of the four patients. This study definitely needs replication, but the results are promising. Reversible deep brain stimulation may improve the symptomatology of treatment refractory OCD patients, without significant side effects.

Adult↗
PubMed2001

Effect of the serotonin agonist 8-OH-DPAT on the sensorimotor system of the rat.

8-Hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT, 2 mg/kg) is used to induce perseverative behavior in rats in a T-maze as a model for obsessive-compulsive disorder (OCD). Using the open-field test, radiant heat test, and the test with von Frey filaments, we examined whether alterations in sensorimotor functioning could contribute to the perseverative tendencies in this model by measuring differences in left versus right hind paw reactions after 8-OH-DPAT administration (2 mg/kg, sc). Also, the effect of repeated 8-OH-DPAT administration on sensorimotor functioning was tested every third day. 8-OH-DPAT administration induced a significantly decreased sensorimotor performance in the open-field test, an increased threshold for noxious thermal stimulation (increased withdrawal latency, WL, and decreased elevation time, ET) in the radiant heat test, and a decreased nociceptive threshold for mechanical stimulation in the test with von Frey filaments. All changes in sensorimotor functioning were similar for left and right hind paws suggesting that, these changes as measured with the tests in the present study, are not likely to contribute to the perseverative behavior of rats in a T-maze. Further, repeated administration of 8-OH-DPAT had no effect in the radiant heat test and the test with the Frey filaments, but produced a tolerance effect in the open-field test.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Chronaxie calculated from current-duration and voltage-duration data.

To determine the rheobase and the chronaxie of excitable cells from strength-duration curves both constant-current pulses and constant-voltage pulses are applied. Since the complex impedance of the electrode-tissue interface varies with both the pulsewidth and the stimulation voltage, chronaxie values estimated from voltage-duration measurements will differ from the proper values as determined from current-duration measurements. To allow a comparison of chronaxie values obtained by the two stimulation methods, voltage-duration curves were measured in human subjects with a deep brain stimulation electrode implanted, while the current and the load impedance of the stimulation circuit were determined in vitro as a function of both stimulation voltage and pulsewidth. Chronaxie values calculated from voltage-duration data were shown to be 30-40% below those estimated from current-duration data. It was also shown that in the normal range of stimulation amplitudes (up to 7 V) the load impedance increases almost linearly with the pulsewidth. This result led us to present a simple method to convert voltage-duration data into current-duration data, thereby reducing the error in the calculated chronaxie values to approximately 6%. For this purpose voltage-duration data have to be measured for pulses up to 10-20 times the expected chronaxie.

Brain↗
PubMed2000

Intrathecal baclofen for intractable cerebral spasticity: a prospective placebo-controlled, double-blind study.

OBJECTIVE: To conduct a placebo-controlled prospective study of the effectiveness of intrathecal bolus injections and continuous administration of baclofen on functional parameters in patients with severe spasticity of cerebral origin. To compare this functional evaluation with spasticity scores in different muscle groups. METHODS: In 11 patients with spasticity of cerebral origin (mainly cerebral palsy), double-blind scoring of spasticity (Ashworth scale score and visual analog score), spasms, pain, and functional abilities was performed during tests with bolus injections including a placebo control. Eight patients were considered good responders and received a subcutaneous device for intrathecal drug delivery. Six of these patients were followed up for 2 years, during which they underwent the same scoring procedures as after their bolus injections. These patients were subjected to a blinded dose reduction test. RESULTS: There was a noticeable placebo effect on spasticity scores during tests with bolus injections. Eight patients demonstrated a significant beneficial effect of intrathecal bolus injections compared with this placebo effect. Functional improvements were noted in most patients. During continuous infusion, Ashworth scale scores were less favorable but still significantly lower than at baseline. Subjective evaluation (visual analog scores) remained positive, functional improvements were maintained, and patient comfort was invariably and significantly improved. CONCLUSION: Intrathecal administration of baclofen is a safe and effective treatment for spasticity of cerebral origin. Functional improvement was demonstrated. The presence of a placebo effect on the spasticity scores suggests the need for double-blind screening in each patient.

Adolescent↗
PubMed2000

DNA-Dependent protein kinase is not required for efficient lentivirus integration.

How DNA is repaired after retrovirus integration is not well understood. DNA-dependent protein kinase (DNA-PK) is known to play a central role in the repair of double-stranded DNA breaks. Recently, a role for DNA-PK in retroviral DNA integration has been proposed (R. Daniel, R. A. Katz, and A. M. Skalka, Science 284:644-647, 1999). Reduced transduction efficiency and increased cell death by apoptosis were observed upon retrovirus infection of cultured scid cells. We have used a human immunodeficiency virus (HIV) type 1 (HIV-1)-derived lentivirus vector system to further investigate the role of DNA-PK during integration. We measured lentivirus transduction of scid mouse embryonic fibroblasts (MEF) and xrs-5 or xrs-6 cells. These cells are deficient in the catalytic subunit of DNA-PK and in Ku, the DNA-binding subunit of DNA-PK, respectively. At low vector titers, efficient and stable lentivirus transduction was obtained, excluding an essential role for DNA-PK in lentivirus integration. Likewise, the efficiency of transduction of HIV-derived vectors in scid mouse brain was as efficient as that in control mice, without evidence of apoptosis. We observed increased cell death in scid MEF and xrs-5 or xrs-6 cells, but only after transduction with high vector titers (multiplicity of infection [MOI], >1 transducing unit [TU]/cell) and subsequent passage of the transduced cells. At an MOI of <1 TU/cell, however, transduction efficiency was even higher in DNA-PK-deficient cells than in control cells. Taken together, the data suggest a protective role of DNA-PK against cellular toxicity induced by high levels of retrovirus integrase or integration. Another candidate cellular enzyme that has been claimed to play an important role during retrovirus integration is poly(ADP-ribose) polymerase (PARP). However, no inhibition of lentivirus vector-mediated transduction or HIV-1 replication by 3-methoxybenzamide, a known PARP inhibitor, was observed. In conclusion, DNA-PK and PARP are not essential for lentivirus integration.

Animals↗
PubMed2000

Identification of the target neuronal elements in electrical deep brain stimulation.

The aim of this study is to identify the primary neuronal target elements in electrical deep-brain stimulation, taking advantage of the difference in strength-duration time constant (tau(sd)) of large myelinated axons ( approximately 30-200 micros), small axons ( approximately 200-700 micros) and cell bodies and dendrites ( approximately 1-10 ms). Strength-duration data were measured in patients suffering from Parkinson's disease or essential tremor and treated by high-frequency stimulation in the ventral intermediate thalamic nucleus or the internal pallidum. Threshold voltages for the elimination of tremor were determined at various pulsewidths and a pulse rate of 130 pulses per second. The tau(sd) was calculated using Weiss's linear approximation. Its mean value was 64.6+/-25.4 micros (SD) for the thalamic nucleus and 75.3+/-25.5 micros for the internal pallidum. Corrections to the mean values were made because the tau(sd) values were based on voltage-duration measurements using polarizable electrodes. Apart from this systematic error, a resolution error, due to the relatively large increment steps of the pulse amplitude, was taken into account, resulting in mean tau(sd) estimates of 129 and 151 micros for the thalamic nucleus and the internal pallidum, respectively. It is concluded that the primary targets of stimulation in both nuclei are most probably large myelinated axons.

Axons↗
PubMed2000

Targeting the basal ganglia for deep brain stimulation in Parkinson's disease.

The revitalization of surgery for Parkinson's disease (PD) has fueled discussion about the best methodology to define the target. Placement of electrodes for deep brain stimulation (DBS) requires the usual stereotactic technique but the argument is mainly centered on whether or not microrecording neuronal activity is necessary. We compared the accuracy of calculating the coordinates X (medio-lateral) and Y (rostro-caudal) considered by the classic stereotactic method, i.e., definition of the AC-PC intercomissural line by MRI and a digitized version of the Schaltenbrand's atlas, with final electrode placement according with microrecording and microstimulation in 21 patients. For both the globus pallidum internum (GPi) (n = 21) and the subthalamic nucleus (STN) (n = 36) there was, respectively, a 43% and 45% mismatching of more than 3 mm between the theoretic coordinates and the final site of electrode location. This applies to both the X and Y planes. Accuracy was not improved in patients (n = 11) in whom the bilateral procedure was undertaken in a single day. We conclude that proper electrode positioning of the STN and GPi requires fine electrophysiologic assessment.

Adult↗
PubMed2000

Gene therapeutic strategies for neurodegenerative diseases.

Gene transfer into the central nervous system by ex vivo or in vivo techniques is a rapidly emerging field in neuroscience. Potential applications of gene therapy for the nervous system include not only congenital single gene disorders, but also brain tumors and acquired chronic diseases. Considerable progress has been made in the understanding of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. As a result, gene therapy for Parkinson's, and possibly Alzheimer's disease could be regarded as a realistic alternative to the limited treatment options currently available. In this review, we highlight the most important developments in gene transfer techniques as well as the newest insights in the mechanisms of some neurodegenerative disorders and put these into the perspective of gene therapeutic strategies for the central nervous system.

Adenoviridae↗
PubMed1998

Purification of toxic compounds from larvae of the gray fleshfly: the identification of paralysins.

Larval haemolymph of Neobellieria bullata (Insecta, Diptera) is highly toxic to adults of the same species: injection causes instant paralysis to death. Referring to their dramatic effect in adult insects the responsible compounds were designated paralysins. Two paralysins, soluble in organic solvents and heat stable, were chromatographically purified to homogeneity. They were identified by use of mass spectrometry and nuclear magnetic resonance respectively as beta-alanine-tyrosine (beta-Ala-Tyr) and as 3-hydroxy-kynurenine (3-HK). The quantities of beta-Ala-Tyr and 3-HK in the insect appear to increase steadily during larval development, with peak values prior to the pupal stage. These findings may contribute to a better understanding of some aspects of the process of insect metamorphosis. Orienting experiments in mammals suggest that both compounds, when injected intraspinally, are also neurotoxic to rats. In addition, cytotoxicity tests revealed that 3-HK, but not beta-Ala-Tyr is toxic to human neuroblastoma cells, rat primary cortex neurons as well as to rat glial cells.

Animals↗
PubMed1998

Functional MRI of the brain: localisation of eloquent cortex in focal brain lesion therapy.

The aim of this study was to assess the feasibility of functional MRI (fMRI) in a clinical environment on a large patient group, and to evaluate the pretherapeutic value of localisation of eloquent cortex. Forty patients with focal brain lesions of different origin were studied using fMRI. Functional information was obtained using motor, somatosensory, auditory and phonological stimuli depending on the localisation of the lesions. To obtain information about the spatial accuracy of fMRI, the results were compared with postoperative electrocortical stimulation. Two patients with secondary trigeminal neuralgia were scanned using a motor protocol and were implanted with an extradural plate electrode. Imaging was successful in 40 of 42 patients (including the 2 with trigeminal neuralgia). These patients were analysed for strength of activation, the relation of the lesion to activation sites and the presence of mass effect. The correlation between these data and surgical findings provided significant additional clinical information. Functional MRI can be accurately performed in patients with focal brain lesions using a dedicated approach. Functional MRI offers important clinical information as a contribution to a decrease in posttherapeutic morbidity. The accuracy of the technique can be confirmed by other modalities, including invasive cortical electrostimulation.

Adolescent↗
PubMed1998

Clinical evaluation of paresthesia steering with a new system for spinal cord stimulation.

OBJECTIVE: The goal was to evaluate, in a clinical study, the predicted performance of the transverse tripolar system for spinal cord stimulation, particularly the steering of paresthesia, paresthesia coverage, and the therapeutic range of stimulation. METHODS: Six transverse tripolar electrodes were implanted in the lower thoracic region in four patients experiencing chronic neuropathic pain. Electrode positions, relative to the spinal cord, were estimated from computed tomographic scans. A dual-channel stimulator was used for initial percutaneous tests, and an implanted single-channel stimulator was used for follow-up test sessions. Nine "balance" settings and several cathode-anode combinations were used with the dual-channel and single-channel stimulator, respectively. In each test, the increase of paresthesia coverage from the perception threshold to the discomfort threshold was registered on a body map and the corresponding voltages were recorded. RESULTS: Paresthesia steering occurred in all but one patient. The normalized steering score, enabling quantitative comparisons of paresthesia steering among tests and patients, showed that maximum paresthesia steering occurred when the electrode was at least 3 mm dorsal to the spinal cord and centered <2 mm from its midline. Paresthesia coverage included 70 to 100% of the body up to the electrode level, unless the electrode migrated or had broken wires. The therapeutic range, defined as the discomfort/perception of paresthesia threshold ratio, varied from 1.6 to 4.0. CONCLUSION: The clinical performance of transverse tripolar stimulation is in accordance with the characteristics predicted by computer modeling. It enables finer control of paresthesia than that achieved by polarity changes in conventional spinal cord stimulation systems.

Adult↗
PubMed1998

Estimation of fiber diameters in the spinal dorsal columns from clinical data.

Lack of human morphometric data regarding the largest nerve fibers in the dorsal columns (DC's) of the spinal cord has lead to the estimation of the diameters of these fibers from clinical data retrieved from patients with a new spinal cord stimulation (SCS) system. These patients indicated the perception threshold of stimulation induced paresthesia in various body segments, while the stimulation amplitude was increased. The fiber diameters were calculated with a computer model, developed to calculate the effects of SCS on spinal nerve fibers. This computer model consists of two parts: 1) a three-dimensional (3-D) volume conductor model of a spinal cord segment in which the potential distribution due to electrical stimulation is calculated and 2) an electrical equivalent cable model of myelinated nerve fiber, which uses the calculated potential field to determine the threshold stimulus needed for activation. It is shown that the largest fibers in the medial DC's are significantly smaller than the largest fibers in the lateral parts. This finding is in accordance with the fiber distribution in cat, derived from the corresponding propagation velocities. Moreover, it is shown that the mediolateral increase in fiber diameter is mainly confined to the lateral parts of the DC's. Implementation of this mediolateral fiber diameter distribution of the DC's in the computer model enables the prediction of the recruitment order of dermatomal paresthesias following increasing electrical stimulation amplitude.

Electric Conductivity↗