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Biomedical subjects

G Ochs

Publications and source records attributed to G Ochs.

At least 19 recordsLinked to original sources
PubMed2001

1H spectroscopy in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The authors investigate changes in brain metabolites among patients with amyotrophic lateral sclerosis (ALS). Twelve patients diagnosed with definite ALS (and 2 subgroups with either pronounced upper motoneuron signs or less obvious, probable upper motoneuron involvement) and 10 controls were examined. 1H studies were performed on a 1.5-T Siemens Magnetom Vision with single voxel (SV). A voxel (TR = 1500 ms, TE = 270 ms, 512 acquisitions, VOI = 8 cm3) was placed bilaterally in the precentral gyrus. In addition, chemical shift imaging (CSI) (VOI = 1 x 1 x 1.5 cm, TR = 1500 ms, TE = 135 ms) was performed. Ratios of peak integrals (N-acetyl-aspartate/choline, N-acetyl-aspartate/creatine, and creatine/choline) were determined. A Mann-Whitney U Test and a Wilcoxon Matched Pairs Test were applied. METHODS: The statistical analysis failed to demonstrate any significant differences between the ALS patients and the controls with respect to ratio measures. Using CSI, it was found that patients with clinically pronounced upper motoneuron signs had significantly lower (P = .037) N-acetyl-aspartate/choline ratios in the more affected hemisphere. CONCLUSIONS: The authors conclude that CSI is more effective at detecting lower N-acetyl-aspartate/choline levels among ALS patients than is SV.

Adult↗
PubMed2000

A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis.

BACKGROUND: Brain derived neurotrophic factor (BDNF) is a potent survival factor for motoneurons. This study investigated the safety and tolerability of recombinant methionyl human BDNF (r-metHuBDNF) infused intrathecally by means of an implanted pump in patients with ALS. METHODS: Twenty-five patients with probable or definite ALS were treated with either r-metHuBDNF (25, 60, 150, 400 or 1000 microg/day) or placebo in a 12-week, randomized, double-blinded, sequential, dose-escalation study. Test treatment was interrupted by a washout period from days 11 to 25 to allow the evaluation of laboratory safety measures. In each dose cohort four patients received r-metHuBDNF and one received placebo. On completion of the double-blind period of the study all patients continued to receive r-metHuBDNF in an open-label extension for up to 60 weeks. Lumbar cerebrospinal fluid (CSF) samples were taken periodically from all patients for the measurement of r-metHuBDNF levels and in a minority of patients these were supplemented by cistemal samples. RESULTS: Within days after the initiation of infusion the majority of patients receiving r-metHuBDNF reported mild sensory symptoms, including paraesthesias or a sense of warmth, which were usually confined to the lower limbs and were frequently exacerbated by neck flexion. In most instances these symptoms decreased or even disappeared over several weeks. Sleep disturbance, dry mouth, agitation and other behavioural effects were encountered at higher doses (>150 microg/day) and necessitated dose reductions. The spinal CSF levels of r-metHuBDNF were directly related to dose, with a lumbar to cervical ratio of approximately 4:1. CONCLUSIONS: The intrathecal delivery of r-metHuBDNF in doses of up to 150 microg/day was well tolerated and appears feasible. The reversible CNS effects with higher dose indicate that BDNF can be delivered cranially against CSF flow. The small number of patients and the design of the study did not permit conclusions to be drawn about the efficacy of the treatment.

Adult↗
PubMed1999

Comparison of maximal voluntary isometric contraction and Drachman's hand-held dynamometry in evaluating patients with amyotrophic lateral sclerosis.

Maximal voluntary isometric contraction (MVIC) is a standard tool for assessment of muscle strength in treatment trials for amyotrophic lateral sclerosis (ALS). There is need for more practical bedside techniques especially for severely disabled patients. Hand-held dynamometry (HH-Dyn) is an inexpensive and easy-to-handle device. MVIC was measured in five proximal muscle groups bilaterally and compared with HH-Dyn in 43 ALS patients. After a training period we found good intrarater correlation for HH-Dyn (r = 0.99), with a low coefficient of variation. Measurements tended to become more accurate after repeated testing due to practice effects in examiners and patients. Overall correlation between HH-Dyn and MVIC was good [r = 0.85 (P < 0.01)]. Strength-range-specific analysis showed a significant linear correlation up to 20 kg (44 lbs.) [r = 0.57 (P < 0.01)]. However, we found a tendency to underestimate muscle strength above 10 kg by HH-Dyn as compared with MVIC, but this became meaningful only above a force of 20 kg. HH-Dyn provides a strength estimate with a precision close to MVIC in weak muscle groups (MRC grade 4). With standardization and appropriate training, HH-Dyn is a useful bedside test, providing an alternative to MVIC for follow-up assessment in ALS.

Adult↗
PubMed1999

[Clenbuterol in amyotrophic lateral sclerosis. No indication for a positive effect].

The anabolic effects of clenbuterol have been recognized for a long time. Clenbuterol augments the expression of specific muscle proteins with a differential effect on type I and type II fibres. Furthermore, clenbuterol induces the synthesis of endogenous nerve growth factor (NGF) and may itself be a myotrophic factor released by neuron endings. Side effects include tremor and headache and dose dependent abnormalities of laboratory values (hypokalemia, hypoglycemia). After long-term medication increasing fatigue of muscles has been observed. Decreased expression of beta 2-adrenergic receptors may limit the expected functional improvement. The efficacy of clenbuterol as symptomatic treatment of amyotrophic lateral sclerosis has not been proved. Controlled treatment trials are warranted to assess this question.

Adrenergic beta-Agonists↗
PubMed1999

Epi-arachnoidal drug deposit: a rare complication of intrathecal drug therapy.

Intrathecal (i.t.) drug application is accepted as a highly effective treatment option for various neurological conditions. Technical risks and potentially dangerous complications require appreciation. We present the case of a patient treated with i.t. recombinant, human brain-derived neurotrophic factor (rhBDNF) as an experimental therapy for amyotrophic lateral sclerosis (ALS). Five days after starting the i.t. drug infusion, she complained of severe headache and nausea. Radiological studies suggested the catheter was located within the epi-arachnoidal space. A deposit of more than 10 ml secluded from the subarachnoidal space was found within this space. I.t. contained a high concentration of the applied drug. Revision of the catheter resulted in complete recovery from symptoms and i.t. infusion could be continued. The epi-arachnoidal positioning of a spinal catheter is a potential cause for treatment failure. If the membrane around the fluid deposit ruptures, the drug could be released into the subarachnoidal space, with the consequence of a potentially life-threatening complication.

Amyotrophic Lateral Sclerosis↗
PubMed1999

Complexity and expression of the glutamine synthetase multigene family in the amphidiploid crop Brassica napus.

In the amphidiploid genome of oilseed rape (Brassica napus) the diploid ancestral genomes of B. campestris and B. oleracea have been merged. As a result of this crossing event, all gene loci, gene families, or multigene families of the A and C genome types encoding a certain protein are now combined in one plant genome. In the case of the multigene family for glutamine synthetase, the key enzyme of nitrogen assimilation, six different cDNA sequences were isolated from leaf and root specific libraries. One sequence pair (BnGSL1/BnGSL2) was characterized by the presence of amino-terminal transit peptides, a typical feature of all nuclear encoded chloroplast proteins. Two other cDNA pairs (BnGSR1-1/BnGSR1-2 and BnGSR2-1/BnGSR2-2) with very high homology between each other were found in a root specific cDNA library and represent protein subunits for cytosolic glutamine synthetase isoforms. Comparative PCR amplifications of genomic DNA isolated from B. napus, B. campestris and B. oleracea followed by sequence-specific restriction analyses of the PCR products permitted the assignment of the cDNA sequences to either the A genome type (BnGSL1/BnGSR1-1/BnGSR2-1) or the C genome type (BnGSL2/BnGSR1-2/BnGSR2-2). Consequently, the ancestral GS genes of B. campestris and B. oleracea are expressed simultaneously in oilseed rape. This result was also confirmed by RFLP (restriction fragment length polymorphism) analysis of RT-PCR products. In addition, the different GS genes showed tissue specific expression patterns which are correlated with the state of development of the plant material. Especially for the GS genes encoding the cytosolic GS isoform BnGSR2, a marked increase of expression could be observed after the onset of leaf senescence.

Blotting, Northern↗
PubMed1998

Potential implications of a ciliary neurotrophic factor gene mutation in a German population of patients with motor neuron disease.

The frequency of a recently described point mutation of the ciliary neurotrophic factor (CNTF) gene was investigated in a population of 154 German patients with motor neuron disease (MND). Twenty-two percent of the patients were heterozygous, 2% homozygous for the CNTF mutation. Since the gene defect is per se not linked to MND, the identification of additional gene defects occurring simultaneously with this mutation could be informative for the understanding of pathogenic mechanisms of MND.

Adolescent↗
PubMed1998

The corticospinal tract in amyotrophic lateral sclerosis: an MRI study.

Cortical motor neurone loss and corticospinal tract (CST) degeneration are typical of amyotrophic lateral sclerosis (ALS). It is a matter of debate whether qualitative assessment of the CST by MRI is useful in the diagnosis. It is also an open question whether quantitative determination of the T2 relaxation times can improve its value. Signal intensity along the CST on 14 consecutive slices was assessed using arbitrary visual rating on double-echo T2-weighted and proton-density spin-echo images of 21 patients with ALS and 21 age- and sex-matched controls. T2 was determined quantitatively. On the T2-weighted images the patients' ratings did not differ from that of controls. The T2 of patients and controls showed no statistical difference in any slice. There was no correlation between T2 and patient age, duration of the disease, or predominant bulbar, lower or upper motor neurone signs. The only correlation between MRI findings and disease was on the proton-density images: all cases in which the CST was poorly seen were controls; a clearly high-signal CST was seen only in the patients. High conspicuity of the CST was thus specific but not sensitive for the diagnosis of ALS. T2-weighted images and measurement of T2 were not useful for diagnosis.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Distribution, tolerability and tissue compatibility of intrathecal tizanidine in the sheep.

BACKGROUND: Tizanidine (TZD) is an alpha-2-adrenergic drug with potential spinal analgesic action and could be a substitute or additive for intrathecal (i.t.) opiates in chronic pain treatment. However, long-term tolerability and tissue compatibility are not yet established. METHODS: Three sheep were infused intrathecally with TZD up to 4000 micrograms/d over a time period of up to 440 d using implantable drug administration devices; one control animal was infused with vehicle only; standard values were collected from untreated sheep. CSF samples and blood samples were analyzed to determine pharmacokinetics and systemic redistribution. Behavioral effects were studied. The spinal cord tissue was investigated using standard laboratory histology. RESULTS: Bolus kinetics after i.t. injection of TZD are best described by a two-phase model. Elimination half-lives of TZD in CSF were 15 min and 152 min, respectively. Clearance of TZD from lumbar CSF was 0.48 ml/min. Doses higher than 500 microgram i.t. caused dose-dependent motor inactivity and sleepiness. Continuous i.t. TZD up to 4 micrograms/d was well tolerated regarding behavioral, physical activity, heart rate, muscle counts and total protein were detected both in saline and TZD-treated animals, presumably due to local irritation by the catheter and repeated sampling procedures. Histological evaluation of the spinal cord and adjacent tissues showed no abnormalities. CONCLUSION: The long-term intrathecal infusion of TZD is well tolerated and non-toxic in the sheep. The data favor clinical trials in patients with chronic pain.

Adrenergic alpha-Agonists↗
PubMed1996

Pharmacokinetics of intrathecally applied BDNF and effects on spinal motoneurons.

Brain-derived neurotrophic factor (BDNF) is a potential drug for treatment of amyotrophic lateral sclerosis. Previous studies have demonstrated little or no penetration of the blood-brain barrier by BDNF, hence systemic application does not result in significant penetration into the spinal cord to produce direct action on motoneurons. Intrathecal (i.th) application of BDNF to sheep was investigated as a mean of topical administration. After continuous infusion a caudalcranial gradient of BDNF concentration in cerebrospinal fluid (CSF) and at the meninges was observed. BDNF did not penetrate spinal parenchyma but accumulated in spinal motoneurons probably due to axonal uptake in ventral roots and subsequent retrograde transport. Spinal motoneurons showed reduced levels of tropomyosin receptor kinase (trk) B and increased levels of c-fos at high BDNF doses in comparison to treatment with saline, even after treatment periods of several months. After bolus injection and cessation of continuous delivery multiphasic reduction of the BDNF concentration in CSF was detected. Our study demonstrates that i.th. application of BDNF is feasible, setting the stage for future clinical trials.

Animals↗
PubMed1991

Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course.

In order to evaluate the efficacy, time-course of action and predictors of response to topical capsaicin, 39 patients with chronic post-herpetic neuralgia (PHN), median duration 24 months, were treated with 0.025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow-up investigation was performed 10-12 months after study onset on the patients who had improved. Nineteen patients (48.7%) substantially improved after the 8-week trial; 5 (12.8%) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations (4) or mastitis (1); 15 (38.5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72.2% were still improved at the follow-up; only one-third of them had continued application irregularly. Treatment effect was not dependent on patient's age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time-course or severity of capsaicin-induced burning. If confirmed in controlled trials, the long-term results of this open, non-randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents.

Administration, Cutaneous↗
PubMed1989

Painful dysaesthesias following peripheral nerve injury: a clinical and electrophysiological study.

Thirty-three patients with complete median, ulnar or digital nerve transections were studied 4 months to 13 years subsequent to suture or nerve grafting. In all cases, sensory disturbances, in terms of paraesthesia or hypaesthesia, were encountered. Painful or unpleasant symptoms, allodynia or hyperpathia, were observed most frequently in patients with poor recovery. The clinical findings and the patients' subjective complaints were correlated to microneurographic single fibre recordings of regenerated cutaneous mechanoreceptors. In more than 80% of the recordings, discharge properties of regenerated receptors, thresholds and a variety of other electrophysiological data were similar or equal to normal controls. Less than 20% of the receptors exhibited atypical properties suggesting defective steady-state regeneration. The ratio of rapidly adapting (RA-units) to slowly adapting mechanoreceptors (SA-units) was inverse in relation to normals. The density of regenerated RA-receptors was higher in the proximal than in the distal part of the reinnervated area. This paralleled the clinical finding of reduced sensory discrimination in these cases and suggests that SA-units may regenerate preferentially. In painful conditions no single fibres could be recorded, reflecting the relative paucity of fibres and probably the atrophy of the nerve. The results of the microstimulation experiments, although less reliable, revealed some evidence that the central processing of regenerated units is abnormal. Clinical and electrophysiological data supported this concept of central changes underlying some of the phenomena observed during peripheral nerve regeneration.

Adolescent↗
PubMed1989

Intrathecal baclofen for long-term treatment of spasticity: a multi-centre study.

Twenty eight patients with severe, intractable spasticity have been treated by chronic intrathecal administration of baclofen. An implantable programmable drug-administration-device (DAD) was used with a permanent intrathecal catheter. Infusion of 50 to 800 micrograms/day of baclofen completely abolished spasticity. Follow-up was up to two years. Therapeutic effect was documented by clinical assessment of tone, spasms and reflexes and by electrophysiological recordings of mono- and polysynaptic reflex activity. Complications and untoward side-effects of the procedure were few. This procedure is recommended for spasticity of spinal origin refractory to physiotherapy and oral medication. It is a preferable alternative to ablative surgical intervention.

Adult↗
PubMed1988

CSF somatostatin is elevated in patients with postzoster neuralgia.

We evaluated the concentration of the neuropeptide somatostatin (SOM) in the CSF of patients with several neurologic diseases. Since SOM is localized in high concentrations in primary sensory pathways, such as the dorsal root ganglia and dorsal horn of the spinal cord, it might be involved in conditions of chronic pain due to functional alterations of nociceptive neurons, such as postinfectious zoster neuralgia. Our study indicated a marked elevation of SOM in patients suffering from postzoster neuralgia compared with controls. Comparison with other neurologic diseases revealed decreased CSF SOM levels in Parkinson's and Alzheimer's disease, unchanged values in patients with amyotrophic lateral sclerosis, and increased concentrations in patients with brain tumors. In neurodegenerative disorders, SOM levels in CSF seemed to reflect the anatomic distribution as well as a reduction or preservation of the peptide in certain brain areas affected by the disease process. In postzoster patients, postinfectious degeneration of dorsal root ganglia cells might cause deafferentation of dorsal horn neurons and activation of SOM-containing systems with increased release either locally from neurons in the dorsal horn of the spinal cord or from descending fiber projections. The results suggested that SOM may take part in the modulation of nociceptive responses.

Herpes Zoster↗