Biomedical subjects

K Wohlfarth

Publications and source records attributed to K Wohlfarth.

At least 19 recordsLinked to original sources

PubMed2004

Introductory experience with the continuous glucose monitoring system (CGMS; Medtronic Minimed) in detecting hyperglycemia by comparing the self-monitoring of blood glucose (SMBG) in non-pregnant women and in pregnant women with impaired glucose tolerance and gestational diabetes.

OBJECTIVE: To assess the detection rate of hyperglycemia with a continuous glucose monitoring system compared to a self-monitoring blood glucose profile in non-pregnant, non-diabetic pregnant women, and patients with impaired glucose tolerance or gestational diabetes.. METHODS: Eight non-pregnant (NP) and 56 pregnant women (17 dietary-treated gestational diabetics (GDM), 15 women with impaired glucose tolerance (IGT), and 24 non-diabetic pregnant women (NDP)) underwent a 72-hour measurement with the CGMS (Medtronic Minimed, Northridge, CA, USA). Self-monitored blood glucose measurements, performed 30 minutes before and 120 minutes after each meal, were compared to the duration of hyperglycemia monitored by the continuous glucose monitoring system. RESULTS: No clinically observable infection was found at the subcutaneous tissue where the electrode was placed. A statistically significant difference was found between the groups in body mass index, HbA1c, and in gestational age, but not in age or parity. Using the self-monitored blood glucose (SMBG), 88 % (7/8) of the NP and 54 % (13/24) of the NDP had no measurement above 6.7 mmol/l. However, 17 % (4/24) of the NDP and 40 % (6/15) of the IGT showed more than two measurements above 6.7 mmol/l compared to 24 % (4/17) of the dietary-treated GDM. The differences between these groups were not significant (p = 0.21). The mean durations (+/- SD) of hyperglycemia above 6.7 mmol/l/24 h were: NP 111 +/- 120 min, NDP 138 +/- 120 min, IGT 381.8 +/- 295 min, and GDM 190 +/- 155 min, p = 0.017; above 7.8 mmol/l/24 h NP 24 +/- 49 min, NDP 38 +/- 47 min, IGT 170.7 +/- 190 min, and GDM 64 +/- 88 min, p = 0.016; and above 8.9 mmol/l/24 h NP 9.3 +/- 25 min, NDP 7.5 +/- 14 min, IGT 59 +/- 77 min, and GDM 14 +/- 21 min, p = 0.026. There was no significant difference in the fetal outcome or rate of birth percentiles using the sensor data. CONCLUSIONS: The use of the sensor in pregnant women is unproblematic. a) The CGMS detected more frequent and longer durations of hyperglycemia in GDM compared to non-diabetic pregnant women than the SMBG. b) Women with an IGT exhibited higher glucose levels than patients with gestational diabetes. c) The clinical importance of these hyperglycemic intervals, e.g. with respect to the risk for macrosomia, must be assessed in larger trials.

Blood Glucose Self-Monitoring↗

PubMed2001

Botulinum A toxin: Dysport improvement of biological availability.

We investigated the efficacy and potency of Dysport, a botulinum neurotoxin type A complex approved for therapy, under various conditions. Conditions for maximal expression of biological activity were explored in vitro in the phrenic nerve-hemidiaphragm preparation, while conditions for optimal distribution of the toxin were tested in vivo in a double blind trial involving volunteers, using the foot Muscles extensor digitorum brevis. In contrast to the recommendations of the manufacturer, the biological availability of Dysport could be enhanced by (1) lowering its concentration, (2) supplementing with albumin, and (3) increasing the injection volume. On the basis of these experimental findings Dysport was diluted to a final concentration of 50 U/ml for therapeutic purposes. In a blind, single crossover study patients suffering from various forms of dystonia were treated with Dysport, first diluted and dosed as suggested by the manufacturer and then with doses cut by approximately 70% in accordance with the experimental findings. The low-dose treatment was as effective as the treatment with the recommended higher doses, but side effects were considerably less apparent. The benefits to be derived from these adjustments include a low risk of antibody formation, which could preclude continued or future treatment and substantial cost savings.

Action Potentials↗

PubMed2001

Remote F-wave changes after local botulinum toxin application.

OBJECTIVE: Although the therapeutic effects of botulinum toxin A can be explained by its action at the neuromuscular junction, central or more proximal effects have also been discussed. METHODS: Eleven patients with torticollis spasmodicus and 3 patients with writer's cramp were studied before and 1 and 5 weeks after the first treatment with botulinum toxin. We measured compound muscle action potentials (CMAPs), motor conduction velocities (MCVs), the shortest (SFL) and the mean F-wave latencies (MFL) and F-wave persistence (30 trials) of untreated muscles for each side (ulnar nerve-abductor digiti minimi muscle, peroneal nerve-tibialis anterior muscle). RESULTS: CMAPs and MCVs showed no significant changes. For both nerves, however, SFL and MFL were prolonged slightly 1 week after treatment and returned to about baseline after 5 weeks (t test). The F-wave persistence was reduced 1 week after treatment for the right ulnar and both peroneal nerves (t test). CONCLUSIONS: These results are not likely due to an impairment of neuromuscular transmission. Instead, we propose a decreased excitability of alpha-motoneurons supplying non-treated muscles. A reduction of muscle spindle activity or changes of the recurrent inhibition are discussed as possible causes.

Action Potentials↗

PubMed2001

Neutralizing botulinum toxin type a antibodies: clinical observations in patients with cervical dystonia.

Neutralization of antibodies poses a problem for a substantial number of cervical dystonia (CD) patients treated with botulinum toxin type A (BoNT/A). Presence of these antibodies may lead to a secondary nonresponse to BoNT/A treatment. In this study, we compared 6 antibody-positive (Ab+) with 12 antibody- negative (Ab-) CD patients treated with BoNT/A (Dysport) and matched for du- ration of treatment, number of BoNT/A injections, and severity of clinical symptoms. The two groups differed in cumulative BoNT/A dose (Ab+, 5984 mouse units [MU ], SD = 3151 MU; Ab-, 3143 MU, SD =1294 MU; P <.05), in addition, ab+ patients were significantly younger (ab+ mean age = 41.3 y, sd =5.9 y; ab - mean age = 56.8 y, sd = 15.3 y; p <.05), in or- der to avoid formation of neutralizing antibodies, doses of bont/a should be kept as low as possible, the risk of antibody formation seems to be higher in younger patients.

Adult↗

PubMed2000

Botulinum toxin treatment of cocontractions after birth-related brachial plexus lesions.

The authors studied botulinum toxin type A therapy of severe biceps-triceps cocontractions after nerve regeneration following birth-related brachial plexus lesions. Six children (age, 2 to 4 years) were treated two to three times over a period of 8 to 12 months with 40 mouse units of botulinum toxin at two sites of the triceps muscle. Elbow range of motion improved from 0 to 25 to 50 deg to 0 to 25 to 100 deg (p < 0.05), and muscle force of elbow flexion increased from a mean of Medical Research Council classification 1.7 to 3.7 (p < 0.05). After a 1-year follow-up, there was no clinical recurrence.

Birth Injuries↗

PubMed2000

Effects of somatosensory input on central fatigue: a pilot study.

OBJECTIVE: Depression of motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) may be a sign of central motor fatigue. As a pilot study, we have examined whether post-exercise MEP depression can be compensated by application of sensory stimuli prior to TMS. METHODS: We studied 15 healthy volunteers (aged 21-28 years) who were required to perform an exercise protocol of ankle dorsiflexion until force fell below 66% of maximum force. MEPs were recorded from the right tibialis anterior muscle. Prior to TMS, electrical stimuli were applied to the ipsilateral sural nerve with an individual interstimulus interval between 50 and 80 ms. RESULTS: MEP areas decreased after exercise. When a sensory stimulus was administered MEPs did not change. CONCLUSION: We conclude that the effects of central fatigue may be influenced by application of sensory stimuli.

Adult↗

PubMed2000

Low-dose treatment of cervical dystonia, blepharospasm and facial hemispasm with albumin-diluted botulinum toxin type A under EMG guidance. An open label study.

Several studies support the hypothesis that low-dose botulinum toxin treatment may be as beneficial as high-dose regimen. Therefore, we studied 115 patients (aged 27-84; mean 58.0, SD = 12.9 years; 68% females, 32% males) suffering from cervical dystonia (n = 66), blepharospasm (n = 28), and facial hemispasm (n = 21) over a period of 2 years in an open label, non-controlled pilot study. Patients received low-dose treatment with botulinum toxin type A (Dysport((R))). The toxin was diluted in 20 ml of 0.1% albumin solution to arrive at a concentration of 25 MU/ml and injected under EMG control. Patients responded to the treatment about 1 week after injection (mean 7.3 days, SD = 4.6). The mean duration of beneficial effects was 11.7 weeks (SD = 5.6). Patients evaluated the clinical global improvement on a scale ranging from 0 to 4. For the whole population, the mean was 2.7 points (SD = 1.1). In none of the subjects could antibodies to botulinum toxin type A be detected, and only a few side effects were observed. In conclusion, low-dose therapy with botulinum toxin A merits further controlled studies.

Adult↗

PubMed2000

Acamprosate reduces motor cortex excitability determined by transcranial magnetic stimulation.

Acamprosate is effective in reducing alcohol intake in weaned alcoholics. We were interested if acamprosate had an effect on the excitability of cortical motoneurons determined by transcranial magnetic stimulation (TMS). We studied 12 male healthy volunteers (mean age 29.5 years, SD = 4.8) who were either treated with 6 tablets of acamprosate (each containing 333 mg verum) per day or placebo (randomized cross-over design) for 1 week. TMS was performed after each treatment session including a paired stimulation paradigm. Motor evoked potentials (MEPs) of the placebo and verum group did not differ with respect to paired stimulation. However, motor threshold increased in the acamprosate group (verum: 61.5% (SD = 7.9) vs. placebo: 58.9% (SD = 8.8), p = 0.036). We conclude that acamprosate leads to a hypoexcitability of the motor cortex. This might be due to subcortical mechanisms, e.g. thalamocortical pathways since intracortical inhibition and facilitation was not affected.

Acamprosate↗

PubMed1999

Muscle vibration: different effects on transcranial magnetic and electrical stimulation.

Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) were applied before and 3 s after onset of vibration (0.5 mm, 80 Hz) of the right extensor carpi radialis muscle in 5 healthy subjects. Vibration induced significant augmentation and latency shortening of motor evoked potentials elicited by TMS, but not TES. This provides evidence for an involvement of cortical mechanisms by muscle vibration in the augmentation of MEPs following TMS.

Adult↗

PubMed1999

Effects of acamprosate on memory in healthy young subjects.

OBJECTIVE: Several studies have shown acamprosate (calciumacetylhomotaurinate) to increase abstinence rates in weaned alcoholics. Chronic alcoholics often suffer from cognitive deficits. Since acamprosate appears to interact with N-methyl-D-aspartate (NMDA) receptors, a subclass of glutamate receptors playing an important role in learning and memory processes, this study was performed in order to investigate different cognitive functions during administration of acamprosate. METHOD: A randomized, double-blind, cross-over, placebo-controlled design, involving 12 healthy male volunteers was used. Acamprosate 2 g daily per os or placebo were administered for 7 days respectively, with a wash-out interval of 21 days between phases. Mood and different memory functions (i.e., working memory, delayed recall, recognition tasks) were assessed. RESULTS: It was shown that a dose of acamprosate 2 g/day for 7 days may produce an impairment in delayed free recall. Recognition tasks, short term working memory and mood were not altered. CONCLUSIONS: The present study supports the hypothesis that acamprosate impairs memory functions. This is in keeping with the concept of acamprosate acting as NMDA receptor antagonist. The limitations of the study are discussed.

Acamprosate↗

PubMed1998

Walking and fatigue in multiple sclerosis: the role of the corticospinal system.

Transcranial magnetic stimulation was used to study motor evoked potentials (MEPs) of leg muscles in controls and patients with multiple sclerosis (MS) before and after walking. In controls, MEP areas were significantly reduced after walking. A similar or greater reduction was seen in most patients, although there was a wide range of values. The M waves were unchanged. We conclude that walking induces functional changes of the corticospinal system and/or connected neurons contributing to central fatigue, especially in patients with MS.

Adult↗

PubMed1998

Supraglottal injection of botulinum toxin type A in adductor type spasmodic dysphonia with both intrinsic and extrinsic hyperfunction.

Patients with adductor type spasmodic dysphonia (SD) often exhibit both glottal and supraglottal hyperfunction. Based on the hypothesis that a "ventricular muscle" may contribute to the hyperfunction in these cases, eight patients with adductor type SD were treated with bilateral injection of botulinum toxin type A into the ventricular folds. Four weeks after injection, ventricular fold hyperfunction was absent in all cases. Number of voice breaks, standard deviation of fundamental frequency, and shimmer were significantly improved. Voice range profiles of the speaking voice were significantly extended in dynamic and frequency range. Side effects were a breathy phonation and mild swallowing difficulties without aspiration for about 1 week. Patients' self-rating concerning strangled and breathy voicing demonstrated an interval of acceptable voice quality between 1 week and 4 months after injection in all cases. Results suggest that supraglottal injection in patients with SD of both glottal and supraglottal hyperfunction, as a new approach, can normalize supraglottal activity and improve glottal voicing. Based on our experience with other patients with adductor type of SD, this injection technique is as efficient as injection into the thyroarytenoid muscle. Nevertheless, it remains to be proved that a pathologic ventricular muscle activity is addressed by this technique or if it is based on spreading to the thyroarytenoid muscle.

Acoustics↗

PubMed1997

Botulinum A toxin therapy: neutralizing and nonneutralizing antibodies--therapeutic consequences.

Although muscle-relaxant doses of botulinum A toxin (BoNT/A) are generally lower than doses stimulating the immune system, specific antibodies are raised in a substantial number of patients. As a rule, this necessitates the termination of treatment. Therefore, a reliable determination of specific anti-BoNT/A antibodies is helpful and we introduced, for this purpose, a novel in vitro toxin-neutralizing assay based on a nerve-muscle preparation. We measured the antibody titers in four groups of subjects: Group 1 comprised 75 randomly selected patients of a total of 295 who responded to treatment with Dysport in our local clinic. Five patients, in group 2, were nonresponders. Group 3 consisted of 32 untreated volunteers and group 4 of 8 subjects immunized with a toxoid more than 10 years ago. Two of the responders had marginal titers of neutralizing antibodies, while they were present in all nonresponders. The sera of all responders were also tested for nonneutralizing antibodies by ELISA. Their occurrence, however, was of no consequence to the therapeutic success. The blood samples of volunteers were free from specific antibodies, whereas antibodies persisted in the immunized subjects for longer than a decade. Patients from various clinics who had been treated unsuccessfully with the toxin-14 patients had received BOTOX, 7 had been treated with Dysport, and 7 with both products-all had neutralizing antibodies. Whether there was an antibody response depended on the amount of toxin administered. We believe, however, the effective toxin dose can be reduced by so much as to make antibody production highly improbable.

Animals↗

PubMed1997

Botulinum A toxins: units versus units.

We investigated the efficacies and potencies of two commercial preparations of botulinum neurotoxin type A (BoNt/A) reputed to differ in potency. Tests were conducted in vitro using the mouse phrenic nerve-hemidiaphragm which is an approved tool for measuring clostridial toxicity. In addition, in a double-blind trial on volunteers, varying amounts of one product were injected into the Musculus extensor digitorum brevis of the left foot, while equal amounts, i.e. units, of the other preparation were injected into the same muscle of the right foot. Compound muscle action potentials (CMAPs) were recorded before and at various points in time after the injections. As opposed to wide-spread anecdotal reports, no difference in effectiveness was found. The dose-response curves obtained from the mouse organ preparation with both commercial products equalled one another in potency (number of units) and corresponded to previous toxicity tests in mice conducted elsewhere. Dose-response curves from volunteers were also identical for both commercial preparations. The time course of paralysis and recovery of muscle function did not differ either. At lower concentrations of toxin, however, restoration of muscle function was more rapid than at higher concentrations. Since the results obtained from man and the animal organ preparation are in excellent accord, we conclude that 1 unit of Botox corresponds to 1 unit of Dysport.

Action Potentials↗

PubMed1996

Muscle fatigue, lactate, and pyruvate in mitochondrial myopathy with progressive external ophthalmoplegia.

We studied muscle fatigue and serum lactate and pyruvate levels in 20 patients with mitochondrial myopathy with progressive external ophthalmoplegia (PEO). Fatigue was assessed in the adductor pollicis muscle (AP) using a low-intensity exercise protocol (20 min). Forces (TFs) and relaxation times of ulnar nerve evoked twitches, compound muscle action potentials (CMAPs), and maximal voluntary contractions (MVCs) were monitored. Serum lactate and pyruvate levels were independently measured at rest and after exercise on a bicycle (15 min, 30 W). Most patients showed abnormal fatigue of the AP with a reduction of TFs and MVCs and normal CMAPs. The reduced TFs were significantly correlated with lactate levels at rest (r= - 0.60, P<0.05) and less so with those after exercise (r=- 0.47,P<0.05). Pyruvate levels revealed a similar correlation although they were widely scattered. We conclude that abnormal fatigue in PEO is metabolic, is localized beyond the muscle fiber membrane, and involves the electrome-chanical coupling and the contractile apparatus. Serum lactate levels at rest are good predictors of fatigue in PEO.

Action Potentials↗

PubMed1994

Assessment of human motor unit twitches--a comparison of spike-triggered averaging and intramuscular microstimulation.

We recorded twitches of single motor units (MUs) in the human first dorsal interosseus muscle using either spike-triggered averaging (STA; 236 MUs in 12 normal subjects) or low-rate intramuscular microstimulation of motor axons (IMS; 200 MUs in 20 normal subjects). We analysed twitch force (TF), maximal rate of rise of force (MRRF), contraction time (CT) and half-relaxation time (HRT). MRRF, CT and HRT were significantly smaller with STA than with IMS whereas TFs were fairly similar. Higher stimulus rates (up to 14 Hz) in IMS resembling the voluntary MU firing rates in STA were associated with a decrease of all twitch parameters because of partial fusion of the twitches (20 MUs). Concerning MRRF, CT and HRT, the reduced values matched those obtained by STA, suggesting that the underestimation of these parameters in STA can be mainly attributed to partial fusion. The reduction of TF with high rate IMS but not with STA reveals that other factors such as MU synchronization and non-linear force summation of MU contractions must counteract the effects of partial fusion in STA. We conclude that both STA and IMS are appropriate for assessing TFs in man while the time-dependent parameters MRRF, CT and HRT will be underestimated with STA.

Adult↗

PubMed1993

Activation of high-threshold motor units in man by transcranial magnetic stimulation.

Motor units (MUs) with low voluntary recruitment thresholds are the first to be activated by transcranial magnetic stimulation. It is not clear, however, if high-threshold MUs can also be activated and if they contribute to motor evoked potentials (MEPs). We therefore studied 11 high-threshold motor units in the first dorsal interosseous muscle of 11 healthy subjects. Voluntary recruitment thresholds ranged from 22 to 41% (29.5 +/- 5.6%; mean +/- S.D.) of maximal muscle force. When MUs were driven at their recruitment thresholds, transcranial magnetic stimuli were applied to the vertex. Peri-stimulus time histograms of MU discharges were constructed. All MUs studied revealed a period of increased firing probability at 19-27 ms after the stimulus (primary peak). Stimulus intensities were lower by 10-57% of the maximal stimulator output than required to produce near maximal MEPs in conventional surface EMG recordings in the same subjects. We conclude that high-threshold MUs can be activated by transcranial magnetic stimulation and that they contribute to conventionally recorded MEPs.

Adult↗

PubMed1992

Local botulinum toxin in the treatment of spastic drop foot.

Ten patients with spastic drop foot were treated by local injections of botulinum toxin A (botulinum toxin A haemagglutinin complex). The purpose was to improve stance and gait and/or to facilitate physiotherapy and patient care. Various calf muscles were injected using EMG guidance. The average dose used was 23 ng. Prior to and 4 weeks after treatment, positions of the upper and lower ankle joint at rest and the corresponding end positions of passive and active movement were determined. In addition, changes of spasticity and pain, the transmission phenomenon and stance and gait were evaluated. Most patients showed improvement of some aspects of the spastic drop foot. Positions of the upper and lower ankle joint were improved in most of the patients, as were the other parameters examined. Except for weakness of the injected muscles no side-effects were observed. The results appear promising and may be optimized in further trials by using higher doses of the toxin.

Adolescent↗