Phenobarbital induces slow recovery from sodium inactivation at the nodal membrane.

Voltage-clamp experiments were performed on single myelinated nerve fibres of Rana esculenta at 20 degrees C in Ringer's solution and in solutions containing phenobarbital-sodium ([PB] less than or equal to 5 mM). The reduction of the sodium current under phenobarbital could be explained by an increase in the resting sodium inactivation; h infinity (E) was shifted towards more negative membrane potentials. The recovery from sodium inactivation proceeded with two time constants. The fast process could be described with the same time constant as in Ringer's solution, whereas the slow process had a time constant approx. 40 times larger. The slow process was also potential-dependent and could be described by 1/(0.025 alpha h + beta h), where alpha h and beta h denoted the rate constants in Ringer's solution. With the measured blockage of sodium channels by phenobarbital, both the shift of h infinity (E) and the slow recovery from sodium inactivation could be explained.

A three-state model for inactivation of sodium permeability.

The inactivation of Na+ permeability in single myelinated motor nerve fibres of Rana esculenta was investigated under voltage and current clamp conditions at 20 degrees C in Ringer's solution and under blocked K+ currents. Development of inactivation and its recovery was described by two potential-dependent time constants: The smaller time constant followed the usual bell-shaped function of membrane potential, whereas the larger one was monotone-increasing with more negative potentials. Several three-state models for inactivation were investigated. The experiments could best be approximated by a model with two open and one closed state for inactivation following: open in equilibrium closed in equilibrium open. Rate constants were determined for all transitions shown from the voltage clamp experiments. The action potentials computed by means of the proposed model were in good agreement with those measured, both in Ringer's solution and under blocked K+ current conditions.

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.

Influence of Collagenfleece on bone regeneration.

It can be demonstrated that bone regeneration is stimulated by implantation of Collagenfleece a purified, heterologous collagen preparation. Defects were created in rabbit mandibles which were filled with Collagenfleece on the right side, while the defect on the left side served as a control. The progress in bone regeneration was followed by comparative light and electron microscopic investigations. In contrast to the controls, the defects which were treated with Collagenfleece showed quicker ossification.

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.

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.

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.

The effect of epidural application of opioids on spasticity of spinal origin.

The effect of epidural opioids on spinal spasticity is demonstrated in a patient suffering from multiple sclerosis. Flexor reflex spasms are abolished and muscle tone is markedly reduced by the epidural administration of morphine 3 mg or fentanyl 0.1 mg. In contrast, the oligosynaptic motor responses and voluntary movements were unaffected. This is documented by EMG-recordings. Sensory perception thresholds were elevated for pain, but unchanged for touch and vibration sense. Effects on enkephalinergic interneurons on the spinal level are discussed.

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.

[Bilateral hip dislocation in cerebral palsy children: conservative therapy of the less affected hip and adductor tenotomy of the opposite hip]. / Beidseitige Hüftgelenksluxation bei infantiler Zerebralparese: konservative Therapie der weniger betroffenen Seite bei gegenseitiger Adduktorentenotomie.

AIM: In cerebral palsy children with bilateral hip dislocation, a new therapeutic concept was established that treated the less affected hip conservatively and the more affected hip simultaneously with an adductor tenotomy. The current study assessed whether the clinical and radiological outcome was equal to that of established bilateral surgical treatments. We also examined whether this approach leads to an adequate motor function improvement of the affected children. METHOD: In 41 children with cerebral palsy and bilateral hip dislocation, a prospective study assessed the hip abduction, migration percentage (MP) and the motor function (Rancho los Amigos scale). Depending on the pretherapeutic status, all patients were grouped into 3 abduction and 3 MP groups. The less affected hip was treated with a hip abduction splint whereas the more affected hip of the same child was simultaneously treated with a subcutaneous adductor tenotomy. All patients were assessed annually for 4 years. RESULTS: The hip abduction of the conservatively treated hips was pretherapeutically 41.8 +/- 2.6 degrees and improved significantly after 1 year. Patients with a pretherapeutic hip abduction < or = 20 degrees showed the most improvement. After 4 years, a significant deterioration of abduction was avoided in 49%. The pretherapeutic MP of the conservatively treated hips was 31.6 +/- 3.4% and was significantly but only slightly improved. The 4 year MP was significantly improved and the largest improvement was observed when the pretherapeutic MP was larger than 50%. A significant MP improvement after 4 years was achieved in 54%. After 4 years, 34% had undergone a motor function improvement. In 7% a motor function deterioration was observed. Posttherapeutically, the conservatively treated hips showed abduction and MP values that were comparable to those of surgically treated hip joints. CONCLUSION: In cerebral palsy children with bilateral hip dislocation, the conservative treatment of the less affected hip is suitable to achieve clinical and radiological results that are equal to the surgical treatment of the more affected hip. The concept of a combined conservative and surgical treatment of bilateral hip dislocation leads to an adequate motor function improvement that is comparable to established bilateral treatments.

Intrathecal baclofen.

The intrathecal application of the GABA-B agonist baclofen has become more and more popular for severe spinal spasticity. Since it was first introduced in 1984 more than 1000 patients worldwide have been treated by this method, using an implantable drug administration device. Clinical data from 48 patients are presented, as well as further experience from a multicentre trial conducted in Europe, in conjunction with a literature overview. The method is now generally accepted as a powerful treatment for spasticity due to spinal lesions of whatever aetiology; improvement in mobility and function as well as relief of spastic pain are the most obvious benefits for the patient. Bladder function is improved in terms of increased bladder volume and lowered residual volume. In patients with supraspinal lesions causing muscle hypertension, where several mechanisms usually contribute besides hyper-reflexia (spasticity), the response has been less pronounced, but intrathecal baclofen still seems to have clinical effects that are superior to those of any oral drug treatment. The initial technical and methodical problems have been solved and today the procedure is generally assessed as safe.

[Effect of dissolved heterologous collagen on human platelet aggregation]. / Einfluss von gelöstem heterologem Kollagen auf die Aggregation menschlicher Thrombozyten.

Our in vitro experiments showed the positive effect of a solution containing collagen fleece on aggregation in platelet-rich plasma of healthy subjects and of patients with thrombocytic coagulation disturbances. The added collagen directly affects the adhesion and aggregation of the platelets. The platelets then complete the process of primary hemostasis by forming a thrombus and the plasmatic "intrinsic system" is started. These results have already been implemented at the practical level.

[Heterologous collagen as crystallization germ for bone mineralization]. / Heterologes Kollagen als Kristallisationskeim für die Knochenmineralisation.

In vitro and in vivo experiments with animals showed that heterologous, implanted collagen fleece accelerates the mineralization of bony tissue and intensifies the synthesis of the osteocytes. Healing of the bony defects therefore is accelerated.

Glutamine synthetases of green and etiolated leaves ofSinapis alba : Evidence of the identity of the respective enzyme proteins.

Studies on the glutamine synthetases (GS, EC 6.3.1.2) of green (GS2) and etiolated leaves (GSet) ofSinapis alba L. (cv. Steinacher) revealed striking similarities between the respective enzyme proteins. The enzymes showed corresponding chromatographic properties, both on dimethylaminoethyl-Sephacel and on hydroxylapatite columns. The purified GS proteins were also identical with regard to the molecular weight of their subunits. Isoelectrofocusing of pure GSet yielded two distinct polypeptide bands in the pH 5.6 region of the gels. This pattern corresponded to the two strong bands of GS2. Two charge variants of GS polypeptides could be detected by Western-blot analysis of the soluble protein of green leaves using antibodies against mustard GS2. In immunoprecipitation experiments, the holoenzymes of GS2 and GSet were recognized with identical affinities by this antiserum. We conclude that strong similarities exist between the proteins of the GS enzymes in green and etiolated leaves of mustard. Most probably only one GS form, namely the plastidic enzyme, can be found in the epigeal organs ofSinapis. The polypeptides of the GS2 subunits showed no differences in the hydrophobicity of the polypeptide chains. Neither glucosyl nor mannosyl residues could be detected.

Fine calibration of large-aperture optical scintillometers and an optical estimate of inner scale of turbulence.

Large-aperture optical scintillometers [Ting-i Wang et al., J. Opt. Soc. Am. 68, 334 (1978)] lose their calibration if they are sensitive to portions of the spatial spectrum of temperature fluctuations where (K)(-11/3) fails to hold. The model temperature spectrum having the bump [R. J. Hill, J. Fluid Mech. 88, 541 (1978); R. J. Hill and S. F. Clifford, J. Opt. Soc. Am. 68, 892 (1978)] is used to find conditions under which the scintillometers maintain their calibration. We find that the aperture size D should be at least twenty times the inner scale l(0) if the contribution of the spectral bump is to be ignored. For application in the surface layer, one needs the height above ground of the optical path to be much greater than three times the aperture size if outer-scale effects are to be negligible. It is shown that the inner scale dependence of a scintillometer having D/l(0) approximately 2.0 and the lack of such dependence for a scintillometer having D/l(0) approximately 20.0 can be used to estimate both l(0) and C(2)(n) if the two systems are used simultaneously on the same path. A preliminary experiment was performed in the atmospheric surface layer with scintillometers having aperture sizes of 2.0 cm, 5.0 cm, and 15.0 cm; the results are consistent with the existence of the spectral bump. The inner scale is estimated by comparing data from the 2.0-cm and 15.0-cm systems. Using this inner scale, the C(2)(n) values from the 5.0-cm and 15.0-cm scintillometers are corrected for the spectral bump; the corrected values are in agreement. Other turbulence parameters are not deduced from the l(0) and C(2)(n) estimates because the l(0) values have been found to be insufficiently accurate.

Finite aperture optical scintillometer for profiling wind and C(2)(n).

A new optical technique is described for measuring the path profiles of crosswind and of a refractive-index structure parameter C(2)(n) along a line-of-sight path. Different sizes of transmitters and receivers are used to control the path-weighting function so that it will peak at different path locations. Various linear combinations of these measurements yield the path profile of crosswind and C(2)(n). A prototype instrument has been built and tested. Experimental results show good agreement with the theoretical predictions.

Effects of saturation on the optical scintillometer.

Measurements of the level of turbulence C(2)(n) have been successfully performed with the optical scintillometer. The success of this instrument is based on the observed fact that the variance of aperture averaged scintillation is described by weak scattering theory even for conditions in which strong scintillation is observed for point detectors. However, for sufficiently long propagation paths, the aperture averaged variance is affected by strong scattering. The effects of strong scattering are calculated theoretically and compared to experimental results. The physics of this regime are discussed and the important parameters investigated. The new range of validity of the optical scintillometer is discussed.

Optical-scintillation method of measuring turbulence inner scale.

An optical technique is described that uses coherent and incoherent optical scintillation to measure the path-averaged value of the turbulence inner scale. The technique is verified by comparison with an in situ measurement, and inner scale values obtained 1.5 m above the ground over a 24-h period are shown.

Wind measurements by the temporal cross-correlation of the optical scintillations.

Various methods of correlation analysis that have been used to deduce crosswind from a drifting scintillation pattern are briefly described and then compared with regard to their immunity to noise and their accuracy when faced with nonuniformities along the propagation path or changes in the characteristics of the turbulence. Of the techniques considered, none is ideal; but a new technique, using complete knowledge of the cross-covariance function, proves to be advantageous in a wide variety of situations.