[Inherited retinal or optic nerve disorders ­ five steps to diagnosis]. / Erbliche Netzhaut- und Sehbahnerkrankungen ­ 5 Schritte zur Diagnose.

An early diagnosis of inherited retinal or optic nerve disorders is often delayed due to unspecific clinical signs, multiple clinical manifestations and striking genetic heterogeneity of the underlying molecular defects. This study represents a retrospective analysis of findings in 4,021 patients with inherited retinal or optic nerve disorders seen between 1986 and 2014 (1,171 with follow-up). In addition to the basic ophthalmological examination, electrophysiological tests (ERG, n = 2,088, since 1986; EOG, n = 381, since 1986; VEP n = 595, since 1986; mfERG, n = 819, since 1998) and non-invasive retinal imaging (fundus autofluorescence (FAF, n = 1,784, since 2002), near-infrared autofluorescence (NIA, n = 1,091, since 2006), spectral domain OCT (SD-OCT, n = 848, since 2008) and three-wavelengths multicolour spectral reflection imaging (MC, n = 366, since 2013) were performed at least once. Molecular DNA testing was done in 383 patients between 2006 and 2014. Based on these data an efficient diagnostic strategy is suggested: 1) inclusion of inherited retinal and optic nerve disorders into the differential diagnosis of visual loss or visual field defects with undefined causes; 2) non-invasive retinal imaging; 3) electrophysiological tests; 4) DNA testing to confirm the initial clinical diagnosis; 5) examination in specialised centres, therapy and follow-up. In recent years, the spectrum of diagnostic techniques has continuously expanded. Importantly, non-invasive retinal imaging has become the primary diagnostic tool and DNA testing based on state-of-the-art high throughput techniques increases the identification of associated gene mutations. In conclusion, a structured process in the diagnostic procedure of inherited retinal and optic nerve disorders greatly reduces a diagnostic delay, enables an earlier counselling and therapy and avoids further unnecessary diagnostic tests.

Pupillary response to percutaneous auricular vagus nerve stimulation in alcohol withdrawal syndrome: A pilot trial.

BACKGROUND: Autonomic symptoms in alcohol withdrawal syndrome (AWS) are associated with a sympathetic-driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge. METHODS: Thirty patients suffering from alcohol use disorder, undergoing AWS, and stable on medication, were recruited in this open-label, single-arm pilot trial with repeated-measure design. Peripheral VNS (monophasic volt impulses of 1 msec, alternating polarity, frequency 1 Hz, amplitude 4 mV) was administered at the left cymba conchae for 72 h, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as the dependent variable in a repeated-measures ANOVA (rmANOVA). RESULTS: A repeated-measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F(2,116) = 27.97, p < .001, ηp2 > .14). Tukey-adjusted post hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol craving was significantly reduced after pVNS (p < .05, Cohen's d = 1.27). CONCLUSION: Our study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind.

Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy.

The hereditary macular dystrophies are progressive degenerations of the central retina and contribute significantly to irreversible visual loss in developed countries. Among these disorders, Sorsby's fundus dystrophy (SFD), an autosomal dominant condition, provides an excellent mendelian model for the study of the genetically complex age-related macular degeneration (AMD), the most common maculopathy in the elderly. Recently, we mapped the SFD locus to 22q13-qter. This same region contains the gene for tissue inhibitor of metalloproteinases-3 (TIMP3), which is known to play a pivotal role in extracellular matrix remodeling. We have now identified point mutations in the TIMP3 gene in affected members of two SFD pedigrees. These mutations are predicted to disrupt the tertiary structure and thus the functional properties of the mature protein.

[Multimodal diagnostic of CSNB1 with NYX gene mutation]. / Stufendiagnostik einer CSNB1 mit NYX-Genmutation.

This article presents the case of a young male patient with complete congenital stationary night blindness (CSNB1). The informative value of the general medical history and clinical findings for the diagnosis was impaired due to language barriers and low compliance. Full-field electroretinography and optical coherence tomography help to define particular hereditary retinal dystrophies. Molecular genetic analysis by next generation sequencing as a part of multimodal diagnostics finally uncovered a rare, causal missense mutation in the nyctalopin (NYX) gene.

[VMD2 and its role in Best's disease and other retinopathies]. / VMD2 und seine Rolle bei Morbus Best und anderen Retinopathien.

Best's vitelliform macular dystrophy (Best's disease) is an autosomal dominant disease of the central retina and is caused by mutations in the VMD2 gene located on the long arm of chromosome 11. VMD2 encodes bestrophin, a transmembrane protein with putative Ca(2+)-dependent chloride channel activity at the basolateral portion of the retinal pigment epithelium. The N-terminal half of bestrophin reveals high sequence homology to three bestrophin-like proteins in humans but also to protein sequences from evolutionarily distant organisms. Most of the known VMD2 mutations are located within this presumably important functional part of the protein and cause amino acid substitutions and small in-frame deletions of single amino acid residues. The pathogenicity of VMD2 mutations is likely based on a dominant negative effect possibly by oligomerization of normal and mutated bestrophin molecules to form a defective ion channel. Missense mutations in VMD2 were also shown to be associated with vitreoretinochoroidopathy and ocular developmental abnormalities. In this case, the pathogenic sequence changes influence the peptide sequences but simultaneously alter the regulation of mRNA splicing and maturation. Different disease mechanisms may therefore be responsible for the distinct phenotypes associated with VMD2 mutations.

Refined mapping of the gene encoding the p127 kDa UV-damaged DNA-binding protein (DDB1) within 11q12-q13.1 and its exclusion in Best's vitelliform macular dystrophy.

Best's vitelliform macular dystrophy (Best's disease) is an autosomal dominant disorder of unknown causes and is typically characterised by an accumulation of lipofuscin-like material in the subretinal space of the macula. The disease gene has been localised to chromosome 11q12-13.1 within a 1.4 Mbp interval flanked by markers at D11S1765 and uteroglobin (UGB). Here we report the refined mapping of the gene encoding the p127 kDa subunit (DDB1) of a UV damage-specific DNA binding protein within the D11S1765-UGB region. Northern blot analysis demonstrates an abundant expression of the DDB1 transcript in the retina suggesting a functional role for DDB1 in this tissue. These considerations together with the chromosomal localisation have led us to evaluate the possible involvement of DDB1 in the pathogenesis of Best's disease.

Cloning and characterization of the murine Vmd2 RFP-TM gene family.

Mutations in the human vitelliform macular dystrophy type 2 (VMD2) gene are known to cause autosomal dominant Best macular dystrophy (BMD), a degenerative disorder of the central retina. VMD2, together with VMD2L1, VMD2L2 and VMD2L3, belong to a closely related gene family characterized by several transmembrane (TM) spanning helical domains and an invariant arginine, phenylalanine and proline (RFP) tripeptide motif, thus termed VMD2 RFP-TM. The four genes are thought to encode a novel family of anion channels. We now report the cloning and characterization of the murine orthologs by combining biocomputational analyses and molecular genetic approaches. While the murine Vmd2, Vmd2l1 and Vmd2l3 genes are functional, murine Vmd2l2p was found to be a non-transcribed pseudogene. Expression profiling of the murine Vmd2 RFP-TM family members revealed tissue-restricted expression with predominant transcription of Vmd2 in testis, of Vmd2l1 in colon and of Vmd2l3 in heart. Differential splicing was observed for Vmd2l3 in a number of tissues (e.g. in brain, retina/RPE, kidney) although the functional importance of the splice variants remains to be determined.

Inhibition of in vitro clot growth by r-hirudin is more effective and longer sustained than by an analogous peptide.

The specific thrombin inhibitors r-hirudin and a synthetic peptide (I) D-FPRP(G)4-NGDFEEIPEEYL were compared in in vitro tests. r-hirudin proved to be the superior compound with respect to inhibition of amidolytic small substrate turnover that is catalysed by soluble and immobilised thrombin as well as to inhibition of fibrinogen activation. In an in vitro clot model significantly higher molar concentrations of peptide I are needed to achieve fibrin bound thrombin inhibition equivalent to that of r-hirudin. Stable complexes consisting of thrombin and hirudin oppose labile complexes containing the synthetic peptide. The latter leads to a regaining of thrombin activity with subsequent additional fibrin accretion. Analyses of the mixtures of thrombin and peptide I display a time dependent release of amino-terminal D-FPR peptide (III) exhibiting, similar to the residual fragment (peptide II), only weak inhibitory activity. Peptide I and the carboxy-terminal fragment induce, within a certain concentration range, an increase in thrombin activity and clot growth.

Study on the mechanism of action of heparin and related substances on the fibrinolytic system: relationship between plasminogen activators and heparin.

It is now generally well accepted that heparin and related substances increase the fibrinolytic activity in vivo. The stimulation of the amidolytic, plasminogenolytic and fibrinogenolytic activity of tissue plasminogen activator and urinary plasminogen activator through heparin was investigated in vitro. A concentration-dependent stimulation of the plasminogenolytic and fibrinogenolytic activity of both urinary and tissue-type plasminogen activators was observed in the presence of heparin. No heparin dependence was observed in the amidolytic assay. Heparin stimulates the plasminogenolytic activity of tissue plasminogen activators in the same manner as fibrin. Both activators form complexes with heparin; the heparin-binding-site seems to be identical or related with the fibrin-binding-site of tissue plasminogen activator. The physiological role of these interactions is discussed.

Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular degeneration.

BACKGROUND: A long term project was initiated to identify and to characterise genes that are expressed exclusively or preferentially in the retina as candidates for a genetic susceptibility to age related macular degeneration (AMD). A transcript represented by a cluster of five human expressed sequence tags (ESTs) derived exclusively from retinal cDNA libraries was identified. METHODS: Northern blot and RT-PCR analyses confirmed preferential retinal expression of the gene, which encodes a G protein coupled receptor, GPR75. Following isolation of the full length cDNA and determination of the genomic organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD patients and 252 controls from Germany, the United States, and Italy. Employed methods included single stranded conformational polymorphism (SSCP) analysis, denaturing high performance liquid chromatography (DHPLC), and direct sequencing. RESULTS: Nine different sequence variations were identified in patients and control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P, and Q234X) were found once in single AMD patients and were considered variants that could affect the protein function and potentially cause retinal pathology. CONCLUSION: The presence of six potential pathogenic variants in a cohort of 535 AMD patients alone does not provide statistically significant evidence for the association of sequence variation in GPR75 with genetic predisposition to AMD. However, a possible connection between the variants and age related retinal pathology cannot be discarded. Functional studies are needed to clarify the role of GPR75 in retinal physiology.

Quantitation of the factor VII- and single-chain plasminogen activator-activating protease in plasmas of healthy subjects.

Plasma samples of 189 healthy subjects were investigated for antigen levels of the recently reported factor VII- and single-chain plasminogen activator-activating protease (FSAP) and the corresponding pro-urokinase activating potencies. While the age of donors had no significant effect on the investigated parameters, female plasmas revealed a trend to higher antigen contents and activity levels. Surprisingly, as much as 9% of all samples contained significantly reduced single-chain urinary plasminogen activator activating potential, whereas antigen concentrations were normal. Additionally, 1% of the plasmas was found to decrease in both FSAP antigen and activity contents. FSAP of three subjects displaying reduced activities throughout a follow-up period of 6 months were purified from plasmas and were characterized. As compared with pool plasma derived FSAP, investigation of the individual preparations confirmed their reduced potency to activate pro-urokinase. However, factor VII activation was not affected. It is speculated that the FSAP binding site for single-chain plasminogen activators is affected, potentially by as yet unknown polymorphism(s) or mutation(s).

A protease isolated from human plasma activating factor VII independent of tissue factor.

An activity detected in a prothrombin complex concentrate, termed 'thrombin-like' due to its amidolytic properties, was recently reported by another working group. This serine-protease revealed partial structural homology with a 'hepatocyte growth factor activator'. An impact of this protease on coagulation has not yet been described. The protease was isolated from plasma fractions by ion exchange chromatography and adsorption to immobilized heparin and/or aprotinin. Clotting tests including the FVIIa-rTF assay were performed employing coagulometry. A monoclonal antibody-derived F(ab')2 to FVIII was used to investigate the FVIII bypassing activity (FEIBA). The identity of the-protease with the so-called 'thrombin-like' protease was supported by sequencing of the amino-termini. Its amidolytic activity was significantly enhanced in the presence of calcium and/or heparin. Incubation with purified FVII revealed the generation of FVIIa, but was prevented by pre-incubation of the protease with aprotinin. In contrast, purified FV and FVIII were inactivated. Studying coagulation parameters, clotting times like plasma recalcification times and the prothrombin times were found to be shortened by addition of the protease. Employing a FVIII-inhibitory F(ab')2 and enhancing clotting times significantly, FEIBA of the protease was found. We demonstrated that the isolated protease activates FVII independent of tissue factor. Net acceleration of coagulation was found in several global clotting assays resulting in an in vitro FEIBA. The physiological relevance of these findings deserves further investigation.

Encephalotropic and psychotropic effects of intravenous buflomedil in the elderly: double-blind, placebo-controlled pharmaco-EEG and psychometric studies.

In a double-blind placebo-controlled study, the encephalotropic and psychotropic properties of intravenously administered buflomedil--a new vasoactive drug--were studied in 10 elderly volunteers in their 60s by means of quantitative EEG and psychometric analyses. At weekly intervals the patients received randomized (latin square design), single, intravenous doses of placebo, 50 mg, 100 mg and 200 mg buflomedil as well as 2000 mg piracetam as reference substance. EEG recordings and the monitoring of blood pressure, heart rate and side-effects were carried out at hours 0, 1, 2, 4, 6 and 8. Psychometric tests were performed at hours 0, 2, 4, 6 and 8. Computer-assisted spectral analysis of the EEG demonstrated that buflomedil exerted a significant effect on the central nervous system (CNS) as compared with placebo, characterized by a decrease of delta and theta, increase of alpha and alpha-adjacent beta activity as well as by an acceleration of the centroid of the alpha activity and also of the total activity. 2 g piracetam induced the same type of changes only at the end of the recording day. These quantitative EEG changes have been previously observed after several antihypoxidotic/nootropic drugs and indicate an improvement in vigilance in the sense of Head. Treatment-efficacy calculations demonstrated that 200 mg buflomedil was the most CNS-effective substance followed by 100 mg and 50 mg buflomedil and 2 g piracetam. Time-efficacy calculations showed that the encephalotropic effects were already marked in the 1st hour after i.v. application, decreased to a low in the 4th hour and subsequently increased again to reach a maximum in the 8th hour. In contrast, 2 g piracetam induced CNS changes which increased from the 1st throughout the 6th hour to show only a slight decline thereafter. The hysteresis between pharmacodynamic and pharmacokinetic findings is discussed. Psychometric investigations demonstrated that after 50 mg buflomedil i.v. there was a significant improvement as compared with placebo in cognitive function based on the Pauli test as well as an increase in correct reactions in the alphabetical reaction test. Doses of 100 mg buflomedil also produced an improvement in the Pauli test, attenuated errors in the reaction time task, improved complex reaction on the Vinnese Determinationsgerät, increased CFF but also errors in the concentration test.(ABSTRACT TRUNCATED AT 400 WORDS)

Objective measures in determining the central effectiveness of a new antihypoxidotic SL-76188: pharmaco-EEG, psychometric and pharmacokinetic analyses in the elderly.

In a double-blind, placebo-controlled, cross-over study, the blood levels as well as the encephalotropic and psychotropic properties of SL-76188 - a new molecule of the hexahydrocanthinone series - were studied in 10 elderly subjects by means of quantitative EEG and psychometric analysis. They received randomized and in weekly intervals single oral doses of 100, 175 and 250 mg SL-76188, placebo and 20 mg D-amphetamine as the reference substance. Blood sampling, EEG recordings and the monitoring of blood pressure, heart rate and side effects were done at 0, 1, 2, 4, 6 and 8 h. Psychometric tests were performed at 0, 2, 4, 6 and 8 h. HPLC demonstrated that the drug was rapidly absorbed as the peak plasma levels were found within the first 2 h. A dose-dependent kinetic profile was observed based on exponential correlations between dose and peak plasma levels and AUC. Computer-assisted spectral analysis of the EEG showed a significant CNS effect as compared with placebo. The attenuation of delta and theta activity, increase of alpha and certain beta activities and the acceleration of dominant frequency suggested an improvement in vigilance. This was reflected behaviorally by an improvement in concentration, attention variability, complex reaction and mood, especially in the higher dosage range. The reference substance 20 mg D-amphetamine exhibited more psychostimulatory properties, which were also observed in regard to the side effects. Blood pressure and heart rate increased only with D-amphetamine as compared to placebo. Finally, the relationship between kinetic and dynamic data was explored. An increase in pharmacodynamic changes on the descending slope of the kinetic curve resulted in a so-called 'hysteresis loop', the implication of which is discussed.

[Classification and determination of the pharmacodynamics of a new tetracyclic antidepressive agent, pirlindol, using pharmaco-EEG and psychometry]. / Klassifikation und Bestimmung der Pharmakodynamik eines neuen tetrazyklischen Antidepressivums, Pirlindol, mittels Pharmako-EEG und Psychometrie.

In a double-blind placebo-controlled study the encephalotropic and psychotropic properties of a new tetracyclic pyrazino-indole derivative were studied in 10 normal volunteers. They received, randomized at weekly intervals, single oral doses of placebo, 75 mg, 150 mg and 225 mg pirlindol, as well as 75 mg imipramine, 20 mg tranylcypromine and 150 mg nomifensine as reference drugs. Pharmaco-EEG, psychometric and physiological data were obtained at the hours 0, 1, 2, 4, 6 and 8 after oral administration. Digital computer period analysis of the EEG demonstrated moderate CNS effects with pirlindol as compared with placebo. Its pharmaco-EEG profile, especially after higher dosage (150 and 225 mg), was characterized by a decrease in delta and theta activity, an increase in alpha activity and a delta and theta activity, an increase in alpha activity and a decrease in beta activity, as well as by an attenuation of the average frequency and frequency deviation and a trend towards an augmentation of the amplitude and amplitude variability. This profile is typical for antidepressants of the desipramine type and was also observed in our present study after 150 mg nomifensine and (although less markedly) and 20 mg tranylcypromine. 75 mg pirlindol induced, however, changes characterized by a concomitant increase in slow and superimposed fast activities and by a decrease in alpha activity. These alterations were described previously as typical for antidepressants of the imipramine type, and were also noted after 75 mg imipramine in the present study. Time-efficacy calculations showed the maximal pharmacodynamic effect of pirlindol in the 4th to 6th hour, of 75 mg imipramine in the 2nd hour, of 20 mg tranylcypromine in the 4th hour and of 150 mg nomifensine in the 6th hour. Dose/treatment-efficacy calculations identified in the 1st and 2nd hour post drug 75 mg imipramine as the most CNS-effective drug, in the 4th and 6th hour 150 mg pirlindol and in the 8th hour 225 mg pirlindol. Psychometric investigations showed only slight changes after pirlindol, reaching only rarely the level of statistical significance (improvement in attention after 225 mg pirlindol, decrease in tapping after 75 and 150 mg pirlindol, as well as attenuation of the complex reaction after all 3 doses of pirlindol). Concentration, attention-variability, psychomotor activity, CFF, after effect (Archimedean spiral), reaction time, mood and affectivity were not significantly altered as compared with placebo. Pulse, systolic and diastolic blood pressure did not show any clinical relevant changes either.(ABSTRACT TRUNCATED AT 400 WORDS)

[Central nervous system activation in opioid dependent patients, evaluation with Fourier analysis of pupillary oscillations]. / Zentralnervöse Aktiviertheit bei opioidabhängigen Patienten, evaluiert durch Fourieranalyse der Pupillenoszillationen.

The aim of the present investigation was to determine whether Fourier analysis of pupillary oscillations permits detection of differences in the activation of the central nervous system of opioid-addicted patients. We analysed pupillary oscillations during the recording period of static pupillometry, which lasted 25.6 s. Using Fourier analysis, the spectrum was divided into five frequency bands (0.0-0.20, 0.21-0.40, 0.41-0.60, 0.61-0.80, 0.81-1.0 Hz); the total spectrum (0-1 Hz) was also assessed. Three groups of patients were selected: the group addicted to heroin (consuming exclusively heroin) consisted of 26 patients with a mean age of 25.0 +/- 6.3 years, the methadone substitution group of 20 patients with a mean age of 30.9 +/- 8.2 years, and the morphine substitution group of 20 patients with a mean age of 33.2 +/- 4.6 years. The 3 patient groups were compared with normal controls of similar age (25.1 +/- 4.6 years). In the frequency band of 0.0-0.20 Hz the morphine group showed significantly lower amplitudes than the heroin group. Also in the frequency band of 0.41-0.60 Hz the morphine group differed significantly from the other groups concerning lower amplitudes, reflecting deactivation. In the total spectrum of 0 to 1 Hz the differences between these two groups were significant. Comparison with normal controls also showed significant differences. The groups were further divided according to dose (high/low): Patients of the heroin group as well as those of the methadone and morphine groups who had consumed higher doses showed greater activation of the central nervous system. In conclusion the morphine group was more deactivated than the methadone and heroin group and patients who received higher doses of the substances showed greater central nervous activation. Thus, the measurement of central nervous activation by means of Fourier analysis of pupillary oscillations might be useful in monitoring substitution therapy.

[The research programme "Artificial Heart" at the 2nd Department of Surgery, University of Vienna: a ten year review (author's transl)]. / Das Forschungsprojekt "Künstliches Herz" an der II. Chirurgischen Universitätsklinik Wien. Ein 10-Jahres-Bericht.

The experimental and clinical results are presented of the research programme "Artificial Heart" carried out by the 2nd Department of Surgery, University of Vienna. In particular, an assessment of the clinical experience in 177 patients with the intra-aortic balloon pump is documented and it is concluded that only limited cardiac support is possible by this pump. In view of this fact more efficient methods of mechanical circulatory support, such as the interaortic auxilliary ventricle, the aortic "Windkessel" ventricle with guiding balloon, and two types of ventriculo-aortic bypass ventricle were tested with regard to their haemodynamic and long-time efficacy. The transatrio-aortic auxilliary ventricle (E-LVAD) was also clinically tested in 11 patients. In conclusion the problems of total mechanical heart replacement are discussed.

Functional electrostimulation of paraplegics: experimental investigations and first clinical experience with an implantable stimulation device.

A method of functional electrostimulation with an implantable 16-channel device and direct nerve stimulation for mobilization of paraplegic patients is presented. The experimental investigations to develop suitable electrode and stimulation devices, to find out optimal pulse parameters, and to study nerve and muscle alterations during FES are presented and discussed. The first clinical application in two cases and the results after one year are demonstrated.

[Effect of transplant length on functional and morphologic outcome of nerve transplantation--an experimental study]. / Der Einfluss der Transplantatlänge auf das funktionelle und morphologische Ergebnis der Nerventransplantation--Eine experimentelle Studie.

BACKGROUND: The present study was done in order to clarify whether the sometimes poor results after the use of long grafts for nerve reconstruction are due to the length of the graft itself or due to the concomitant big defect in the soft tissues necessitating the use of long grafts. METHODS: In 22 rabbits, the saphenous nerve was used as a nerve graft. Animals were separated into three groups with different lengths of the grafts, namely 3 cm (group 1), 5 cm (group 2) and 7 cm (group 3). In one hindlimb, the proximal end of the graft was coapted to the motor nerve branch of vastus medialis. In a second step, the distal end of the graft was coapted to the nerve branch of rectus femoris. After a total period of 15 months the maximum tetanic tensions in the reinnervated rectus femoris and in the contralateral untreated muscle were determined. Biopsies of the graft and the motor branch distal to the graft were taken in order to count the number of regenerated myelinated nerve fibers. RESULTS: The average maximum tetanic tension in the rectus femoris muscle reinnervated by the 3 cm long graft was 27.2 N; in group 2 the force amounted to 20.4 N. In group 3, the maximum force was 17.6 N, which meant an average loss of 29% compared to the contralateral untreated muscle. In accordance with the functional results, the mean number of regenerated myelinated fibres in the rectus femoris motor branch decreased from 1683 in group 1 to 1136 in group 3. CONCLUSIONS: The results show that the length of the graft influences the results after nerve grafting to a certain extent, but a combination of other factors like concomitant soft tissue injury and destroyed target organs may also be responsible for some of the poor results after the clinical use of long nerve grafts.

[Circulatory support by an electrically stimulated muscle flap. Experimental experiences]. / Kreislaufunterstützung durch elektrisch stimulierte Muskellappen. Experimentelle Erfahrungen.

Functional electrical stimulation of the latissimus dorsi muscle flap for circulatory assistance extends the traditional concept of using this flap for reconstructive procedures into the field of cardiac surgery. It requires a transformed muscle which is able to contract for long periods of time without fatigue. Two main groups of experiments have been carried out in sheep. In six sheep the latissimus dorsi muscle (MLD) was transformed into a fatigue-resistant muscle by the means of multichannel stimulation of the supplying motor nerve. After that, stimulation of MLD at a frequency of 70 contractions per minute could be performed continuously without significant muscle fatigue. The loss of maximal force caused by the conditioning procedure was about one third of the initial force. In a second series of acute experiments the MLD was used for cardiomyoplasty. The muscle was divided into two parts which were wrapped around the heart in two different forms. The resting tension of the muscle was preserved. EKG-synchronous stimulation resulted in an increase in left ventricular pressure between 12 and 53%. The increase in arterial pressure was between 10,6 and 58%.