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Biomedical subjects

M Jakob

Publications and source records attributed to M Jakob.

At least 19 recordsLinked to original sources
PubMed2006

Differential cartilaginous tissue formation by human synovial membrane, fat pad, meniscus cells and articular chondrocytes.

OBJECTIVE: To identify an appropriate cell source for the generation of meniscus substitutes, among those which would be available by arthroscopy of injured knee joints. METHODS: Human inner meniscus cells, fat pad cells (FPC), synovial membrane cells (SMC) and articular chondrocytes (AC) were expanded with or without specific growth factors (Transforming growth factor-beta1, Fibroblast growth factor-2 and Platelet-derived growth factor bb, TFP) and then induced to form three-dimensional cartilaginous tissues in pellet cultures, or using a hyaluronan-based scaffold (Hyaff-11), in culture or in nude mice. Human native menisci were assessed as reference. RESULTS: Cell expansion with TFP enhanced glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold) following pellet culture. In all models, tissues generated by AC contained the highest fractions of GAG (up to 1.9% of wet weight) and were positively stained for collagen type II (specific of the inner avascular region of meniscus), type IV (mainly present in the outer vascularized region of meniscus) and types I, III and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC developed tissues containing negligible GAG and no detectable collagen type II protein. Tissues generated by AC remained biochemically and phenotypically stable upon ectopic implantation. CONCLUSIONS: Under our experimental conditions, only AC generated tissues containing relevant amounts of GAG and with cell phenotypes compatible with those of the inner and outer meniscus regions. Instead, the other investigated cell sources formed tissues resembling only the outer region of meniscus. It remains to be determined whether grafts based on AC will have the ability to reach the complex structural and functional organization typical of meniscus tissue.

Adipose Tissue↗
PubMed2006

A less invasive anterior intrapelvic approach for the treatment of acetabular fractures and pelvic ring injuries.

BACKGROUND: The ilioinguinal approach by Letournel has fundamentally contributed to the successful treatment of acetabular fractures. Since most of the present complications arise from soft tissue structures in the inguinal part, it would be desirable to avoid the surgical dissection of this region. We have therefore developed a less invasive anterior intrapelvic approach consisting of a suprapubic access combined with the lateral window of the ilioinguinal approach. METHODS: Between January 2000 and October 2002, 14 patients with acetabular fractures and 6 patients with pelvic ring injuries were consecutively operated using our technique. The patients were prospectively followed up clinically and by standard X-rays for 1 year. RESULTS: In 19 patients the technique was successful and only one patient was converted to an ilioinguinal approach due to difficulties in reducing the fracture. Our access allowed good visibility but reduction manoeuvres were sometimes difficult and the development of a new reduction forceps became necessary. Anatomical and satisfactory reduction was achieved in 13 acetabular fractures and 4 pelvic ring injuries. One cutaneous femoris neurapraxy and one superficial infection occurred related to the approach and both resolved with conservative treatment. Clinical outcome at one year was good to excellent in 17 patients (modified Merle d'Aubigné/Postel score). In 3 patients the result was fair to poor for reasons unrelated to the approach. CONCLUSIONS: Our approach permits visualisation of the entire anterior column and pelvic ring without the necessity to dissect the inguinal neurovascular structures. Our preliminary results demonstrate that safe reduction and stable fixation of selected acetabular- and pelvic ring fractures are possible.

Acetabulum↗
PubMed2005

Structural characterization and reliable biomechanical assessment of integrative cartilage repair.

Structural and functional characterization of integrative cartilage repair in controlled model systems can play a key role in the development of innovative strategies to improve the long-term outcome of many cartilage repair procedures. In this work, we first developed a method to reproducibly generate geometrically defined disk/ring cartilage composites and to remove outgrown fibrous layers which can encapsulate cartilaginous tissues during culture. We then used the model system to test the hypothesis that such fibrous layers lead to an overestimation of biomechanical parameters of integration at the disk/ring interface. Transmission electron microscopy images of the composites after 6 weeks of culture indicated that collagen fibrils in the fibrous tissue layer were well integrated into the collagen network of the cartilage disk and ring, whereas molecular bridging between opposing disk/ring cartilage surfaces was less pronounced and restricted to regions with narrow interfacial regions (< 2 microm). Stress-strain profiles generated from mechanical push-out tests for composites with the layers removed displayed a single and distinct peak, whereas profiles for composites with the layers left intact consisted of multiple superimposed peaks. As compared to composites with removed layers, composites with intact layers had significantly higher adhesive strengths (161+/-9 vs. 71+/-11 kPa) and adhesion energies (15.0+/-0.7 vs. 2.7+/-0.4 mJ/mm2). By combining structural and functional analyses, we demonstrated that the outgrowing tissue formed during in vitro culture of cartilaginous specimens should be eliminated in order to reliably quantify biomechanical parameters related to integrative cartilage repair.

Adhesiveness↗
PubMed2004

Chondrogenesis of expanded adult human articular chondrocytes is enhanced by specific prostaglandins.

OBJECTIVE: To investigate the effects of the cyclooxygenase-2 (cox-2)-dependent prostaglandins D(2) (PGD(2)), E(2) (PGE(2)) and F(2)alpha (PGF(2)alpha) on the redifferentiation and cartilage matrix production of dedifferentiated articular chondrocytes. METHODS: Human articular chondrocytes from three adult donors were dedifferentiated by monolayer expansion and induced to redifferentiate by culture as 3D pellets in a defined serum-free medium containing TGF-beta(1) and dexamethasone, without or with further supplementation with PGD(2), PGE(2) or PGF(2)alpha. After 2 weeks, pellets were assessed histologically, immunohistochemically, biochemically and by real-time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: All three PGs, but predominantly PGE(2), reduced the staining intensity of pellets for collagen type I, whereas PGD(2) and PGF(2)alpha increased the staining intensity of pellets for collagen type II and glycosaminoglycans (GAG). The GAG/DNA content of pellets was not affected by PGE(2) but was increased 1.5- and 2.1-fold by PGD(2) and PGF(2)alpha respectively. PGE(2) reduced the expression of collagen type I mRNA (9.0-fold), whereas PGD(2) and PGF(2)alpha increased the mRNA expression of collagen type II (6.2- and 4.1-fold respectively) and aggrecan (29.8- and 10.7-fold respectively). CONCLUSION: In contrast to PGE(2), PGD(2) and PGF(2)alpha enhanced chondrogenic differentiation and hyaline cartilage matrix deposition by expanded human articular chondrocytes, and could thus be used to improve in vitro or in vivo cartilage regeneration approaches based on these cells.

Adult↗
PubMed2004

Heparin-binding epidermal growth factor-like growth factor: a component in chromaffin granules which promotes the survival of nigrostriatal dopaminergic neurones in vitro and in vivo.

Chromaffin cells can restore function to the damaged nigrostriatal dopaminergic system in animal models of Parkinson's disease. It has been reported that a protein which is released from chromaffin granules can promote the survival of dopaminergic neurones in vitro and protect them against N-methylpyridinium ion toxicity. This neurotrophic effect has been found to be mediated by astroglial cells and blocked by inhibitors of the epidermal growth factor (EGF) receptor signal transduction pathway. Here we report the identification of bovine heparin-binding EGF-like growth factor (HB-EGF) in chromaffin granules and the cloning of the respective cDNA from bovine-derived adrenal gland. Protein extracts from bovine chromaffin granules were found to promote the survival of embryonic dopaminergic neurones in culture, to the same extent as recombinant human HB-EGF. Furthermore, the neurotrophic action of the chromaffin granule extract could be abolished by antiserum to recombinant human HB-EGF. We also show that intracerebral injection of recombinant human HB-EGF protected the nigrostriatal dopaminergic system in an in vivo adult rat model of Parkinson's disease. Intracerebral administration of this protein at the same time as a 6-hydroxydopamine lesion of the medial forebrain bundle was found to spare dopamine levels in the striatum and tyrosine hydroxylase-immunopositive neurones in the midbrain. This study has found that the main component in chromaffin granules responsible for their neurotrophic effect on dopaminergic neurones is HB-EGF. Furthermore, HB-EGF has significant protective effects on nigrostriatal dopaminergic neurones in vivo, making it a potential candidate for use in the treatment of Parkinson's disease.

Amino Acid Sequence↗
PubMed2004

Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation.

Acidic noncaspase proteases-like cathepsins have been introduced as novel mediators of apoptosis. A clear role for these proteases and the acidic endolysosomal compartment in apoptotic signalling is not yet defined. To understand the role and significance of noncaspases in promoting and mediating cell death, it is important to determine whether an intersection of these proteases and the caspase pathway exists. We recently identified the endolysosomal aspartate protease cathepsin D (CTSD) as a target for the proapoptotic lipid ceramide. Here, we show that tumor necrosis factor (TNF)-induced CTSD activation depends on functional acid sphingomyelinase (A-SMase) expression. Ectopic expression of CTSD in CTSD-deficient fibroblasts results in an enhanced TNF-mediated apoptotic response. Intracellular colocalization of CTSD with the proapoptotic bcl-2 protein family member Bid in HeLa cells, and the ability of CTSD to cleave directly Bid in vitro as well as the lack of Bid activation in cathepsin-deficient fibroblasts indicate that Bid represents a direct downstream target of CTSD. Costaining of CTSD and Bid with Rab5 suggests that the endosomal compartments are the common 'meeting point'. Caspase-9 and -3 activation also was in part dependent on A-SMase and CTSD expression as revealed in the respective deficiency models. Our results link as novel endosomal intermediates the A-SMase and the acid aspartate protease CTSD to the mitochondrial apoptotic TNF pathway.

Animals↗
PubMed2003

Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity.

We developed a bioreactor for automated cell seeding of three-dimensional scaffolds by continuous perfusion of a cell suspension through the scaffold pores in oscillating directions. Using quantitative biochemical and image analysis techniques, we then evaluated the efficiency and uniformity of perfusion seeding of Polyactive foams as compared to conventional static and spinner flask methods. Finally, we assessed the efficacy of the perfusion seeding technique for different scaffolds and cell types. Perfusion seeding of chondrocytes into Polyactive foams resulted in "viable cell seeding efficiencies," defined as the percentages of initially loaded cells that were seeded and remained viable, that were significantly higher (75 +/- 6%) than those by static (57% +/- 5%) and spinner flask seeding (55% +/- 8%). In addition, as compared to static and spinner flask methods, cells seeded by perfusion were respectively 2.6-fold and 3.8-fold more uniformly distributed and formed more homogeneously sized cell clusters. Chondrocytes seeded by perfusion into Hyaff-11 nonwoven meshes were 26% and 63%, respectively, more uniformly distributed than following static and spinner flask seeding. Bone marrow stromal cells seeded by perfusion into ChronOS porous ceramics were homogeneously distributed throughout the scaffold volume, while following the static method, cells were found only near the top surface of the ceramic. In summary, we demonstrated that our cell seeding perfusion bioreactor generated constructs with remarkably uniform cell distributions at high efficiencies, and was effective for a variety of scaffolds and different mesenchymal cell types.

Animals↗
PubMed2003

Dynamic compression of cartilage constructs engineered from expanded human articular chondrocytes.

Recent works have shown that mechanical loading can alter the metabolic activity of chondrocytes cultured in 3D scaffolds. In this study we determined whether the stage of development of engineered cartilaginous constructs (expanded adult human articular chondrocytes/Polyactive foams) regulates the effect of dynamic compression on glycosaminoglycan (GAG) metabolism. Construct maturation depended on the culture time (3-14 days) and the donor (4 individuals). When dynamic compression was subsequently applied for 3 days, changes in GAG synthesized, accumulated, and released were significantly positively correlated to the GAG content of the constructs prior to loading, and resulted in stimulation of GAG formation only in the most developed tissues. Conversely, none of these changes were correlated with the expression of collagen type II mRNA, indicating that the response of chondrocytes to dynamic compression does not depend directly upon the stage of cell differentiation, but rather on the extracellular matrix surrounding the cells.

Cartilage, Articular↗
PubMed2003

Development and validation of a bioreactor for physical stimulation of engineered cartilage.

A bioreactor has been developed to apply different regimes of physical stimulation to tissue specimens under highly controlled conditions. The computer-controlled device exposes specimens to compressive deformation at various strains and frequencies, measures the load applied to each sample and allows simultaneous medium stirring at different velocities. Validation tests confirmed the accuracy of the system in (i) its displacement (errors averaged 0.072+/-0.051 microm), and in (ii) setting the contact with the samples utilizing micrometer screws coupled to plungers (errors averaged 1.74+/-0.36% for samples of 1.60-3.18 mm thickness), thus ensuring accurate compressive deformation. The developed bioreactor, which represents an advance in the technology for physical stimulation of tissue specimens, is currently used to apply compressive deformation and hydrodynamic forces to human chondrocytes cultured in biodegradable polymer scaffolds, with the goals of (i) engineering functional grafts for the repair of cartilage defects (ii).

Bioreactors↗
PubMed2001

Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro.

Adult human articular chondrocytes were expanded in a medium with 10% serum (CTR) or further supplemented with different mitogens (i.e., EGF, PDGFbb, FGF-2, TGF beta 1, or FGF-2/TGF beta 1). Cells were then induced to redifferentiate in 3D pellets using serum-supplemented medium (SSM), serum-free medium (SFM), or SFM supplemented with factors inducing differentiation of chondroprogenitor cells (i.e., TGF beta 1 and/or dexamethasone). All factors tested during expansion enhanced chondrocyte proliferation and dedifferentiation, as assessed by the mRNA ratios of collagen type II to type I (CII/CI) and aggrecan to versican (Agg/Ver), using real-time PCR. FGF-2/TGF beta 1-expanded chondrocytes displayed the lowest doubling times, CII/CI and Agg/Ver ratios, averaging, respectively, 50, 0.2 and 15% of CTR-expanded cells. Redifferentiation in pellets was more efficient in SFM than SSM only for EGF-, PDGFbb- or FGF-2-expanded chondrocytes. Upon supplementation of SFM with TGF beta and dexamethasone (SFM TD), CII/CI ratios decreased 4.4-fold for EGF- and PDGFbb-expanded chondrocytes, but increased 96-fold for FGF-2/TGF beta 1-expanded cells. Chondrocytes expanded with FGF-2/TGF beta 1 and redifferentiated in SFM TD expressed the largest mRNA amounts of CII and aggrecan and generated cartilaginous tissues with the highest accumulation of glycosaminoglycans and collagen type II. Our results provide evidence that growth factors during chondrocyte expansion not only influence cell proliferation and differentiation, but also the cell potential to redifferentiate and respond to regulatory molecules upon transfer into a 3D environment.

Adult↗
PubMed2001

Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints.

OBJECTIVE: To quantify the expression of genes encoding extracellular matrix (ECM) proteins in human cartilage from normal and osteoarthritic (OA) joints. DESIGN: Human cartilage samples were classified as control (CTR) or OA according to clinical evaluation and assessed histologically and biochemically to confirm the diagnosis. mRNAs encoding collagen types I, II and X, aggrecan, versican, osteopontin and osteocalcin were quantified by real-time reverse transcription-PCR assays and normalized to a reference mRNA (GAPDH). RESULTS: RNA from native cartilage could be reproducibly and efficiently amplified by real-time PCR only if isolated using purification membranes. Primers and fluorescent probes for real-time PCR, endowed with comparable (<6% difference from GAPDH) and high (>91%) amplification efficiencies, were designed and validated for the selected ECM genes. The expression of most genes under investigation displayed large variations and was not significantly different in CTR and OA cartilage. Only osteopontin mRNA levels were significantly higher in OA than CTR specimens. mRNA ratios of collagen type II to I and of aggrecan to versican, defined as indexes of chondrocyte differentiation, were less variable within each population than the single genes and markedly higher (27.0 and 7.6-fold, respectively) in CTR than OA cartilage, with high statistical significance (P = 0.00013 and P = 0.00007, respectively). CONCLUSIONS: Our results provide evidence that gene patterns related to chondrocyte differentiation discriminate between CTR and OA human cartilage with higher sensitivity than single ECM genes. The method described here has the potential to improve understanding of the progression of OA and could become a valuable diagnostic tool.

Adult↗
PubMed2000

Efficacy of single lead VDD pacing in patients with impaired and normal left ventricular function.

Atrial synchronous ventricular pacing seems to be the best pacing mode for patients with advanced AV block and impaired LV function. The long-term follow-up of single lead VDD pacing was studied in 33 patients with impaired LV function and compared to 42 patients with normal LV function. All patients received the same VDD lead and VDDR pacemaker. The lead model with 13-cm AV spacing between the atrial and ventricular electrode was implanted in 89% of the patients. Follow-ups were 1, 3, 6, and 12 months after implantation. The percentage of atrial sensing and the P wave amplitude were determined at each follow-up. Minimal P wave amplitude at implantation was 2.0 +/- 1.4 mV in patients with impaired and 1.7 +/- 0.9 mV with normal LV function (not significant). At the 12-month follow-up, 33 patients with normal and 23 patients with depressed LV function remained paced in the VDD mode. The remaining patients died in five (impaired LV function) and seven cases (normal LV function) or their pacemakers were programmed to the VVI/VVIR pacing mode in four (impaired LV function) and three cases (normal LV function). P wave amplitude did not differ in the two groups (e.g., at month 12: impaired: 1.17 +/- 0.42 mV; normal: 1.09 +/- 0.49 mV). The atrial sensitivity was programmed in most patients to sensitive settings with no differences between the two groups (e.g., at month 12: impaired: 0.13 +/- 0.06 mV; normal: 0.13 +/- 0.05 mV). The diagnostic counters indicated nearly permanent atrial sensing (e.g., at month 12: impaired: 99.3 +/- 2.2%; normal: 99.0 +/- 1.0 mV). In conclusions, single lead VDD pacing restored AV synchronous ventricular pacing in patients with normal and with impaired LV function indicating that it could be an alternative to DDD pacemakers, but not to dual-chamber pacing.

Aged↗
PubMed2000

Fractures of the distal radius treated by internal fixation and early function. A prospective study of 73 consecutive patients.

Stable fixation of fractures of the distal radius can be achieved by using two 2.0 mm titanium plates placed on the radial and intermediate columns angled 50 degrees to 70 degrees apart. We describe our results with this method in a prospective series of 74 fractures (58 severely comminuted) in 73 consecutive patients. Early postoperative mobilisation was possible in all except four wrists. All of the 73 patients, except two with other injuries, returned to work and daily activities with no limitations. The anatomical results were excellent or good in 72 patients and fair in one. Our discussion includes details of important technical considerations based on an analysis of the specific complications which were seen early in the series.

Adult↗
PubMed1999

Focal sensory nerve abnormalities in patients with amyotrophic lateral sclerosis.

Slowing of sensory nerve conduction is an unexplained finding in patients with sporadic amyotrophic lateral sclerosis (ALS). To study the frequency of these abnormalities and to study if a predisposition to the development of entrapment neuropathies is causal, 23 patients with definite ALS and 23 age-matched healthy volunteers were investigated prospectively. Antidromic sensory and motor nerve conduction velocities (NCVs) were measured in ulnar and median nerves. Median sensory NCV was abnormally low in three patients if compared with the lower limit of the control group; and median sensory NCV was abnormally low in nine patients (six right, eight left hands) if compared with ipsilateral ulnar sensory NCV. Sensory nerve conduction data did not correlate with clinical findings, such as forearm weakness or usage of canes. Motor nerve conduction data did not correlate with sensory nerve conduction data, with the exception of distal motor latency of right median nerves, which correlated with right median sensory NCV. Our findings show how affection of sensory fibers of distal segments of median nerves can be detected in individual patients with ALS. Nerve entrapment may contribute to this affection, but it is not the only cause. This should be considered in discussions about diagnostic criteria for ALS.

Adult↗
PubMed1999

Comparison of primary angioplasty with conservative therapy in patients with acute myocardial infarction and contraindications for thrombolytic therapy. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

The benefit of primary angioplasty in patients with acute myocardial infarction (AMI) and contraindications for thrombolysis compared to a conservative regimen is still unclear. Out of 5,869 patients with AMI registered by the MITRA trial, 337 (5.7%) patients had at least one strong contraindication for thrombolytic therapy. Out of these 337 patients 46 (13.6%) were treated with primary angioplasty and 276 (86.4%) were treated conservatively. Patients treated conservatively were older (70 years vs. 60 years; P=0.001), had a higher rate of a history with chronic heart failure (14.8% vs. 4.4%; P=0.053), a higher heart rate at admission (86 beats/min vs. 74 beats/min; P=0.001), and a higher prevalence of diabetes mellitus (27.1% vs. 12.8%; P=0.056). Patients treated with primary angioplasty received more often aspirin (91.3% vs. 74.6%; P=0.012), beta-blockers (60.9% vs. 46.1%; P = 0.062), angiotensin converting enzyme (ACE) inhibitors (71.7% vs. 44%; P=0.001), and the so-called optimal adjunctive medication (54.4% vs. 32.3%; P=0.004). Hospital mortality was significantly lower in patients who received primary angioplasty (univariate: 2.2% vs. 24.7%; P=0.001; multivariate: OR=0.46; P=0.0230). In patients with AMI and contraindications for thrombolytic therapy, primary angioplasty was associated with a significantly lower mortality compared to conservative treatment. Therefore, hospitals without the facilities to perform primary angioplasty should try to refer such patients to centers with the facilities for such a service, if this is possible in an acceptable time.

Aged↗
PubMed1999

[Use of coronary angiography after acute myocardial infarction in Germany: a comparison of daily clinical practice with international guidelines. MITRA Study].

OBJECTIVES: Two third of patients with acute myocardial infarction are admitted to hospitals without cardiac catheterization facilities. Whether a postinfarction patient will undergo cardiac catheterization or not is more often decided by general physicians than by cardiologists. The purpose of this presentation is to investigate the determinants for decision making to use cardiac catheterization in patients after myocardial infarction. METHODS: MITRA is a prospective, multicenter registry, which enrolls all consecutive patients with acute Q wave infarction admitted to 54 hospitals in Southwestern Germany. During the pilot phase 949 consecutive survivors of acute myocardial infarction were included, and inhospital outcome as well as therapeutic strategies were registered. RESULTS: Only half of the patients underwent cardiac catheterization regardless of whether a catheterization facility was available or not. In 63% of the patients under 65 years of age coronary angiography was performed; however, every fourth patient with age above 70 years was transferred to an invasive therapeutic strategy. The percentage of male patients was twice a high in the invasive group, whereas patients with prior infarction, clinical signs of congestive heart failure, patients with moderately or severely impaired left ventricular function, and finally patients with a prehospital delay of more than 4 hours were more frequent in the conservative group. The following three parameters were calculated to be independent determinants of an invasive strategy: pathological stress ECG (OR: 2.8; CI: 1.80-4.60), patients < 70 years without stress ECG (OR: 2.18; CI: 1.5-3.18), and male gender (OR: 1.45: CI: 1.10-2.00). Independent factors of a conservative strategy were primary PTCA (OR: 0.2; CI: 0.09-0.46), prehospital delay > 4 hours (OR: 0.71; CI: 0.51-0.97), and the combination of age > 70 years and the absence of a stress ECG (OR: 0.78; CI: 0.55-1.11). CONCLUSIONS: In Germany, patients with acute myocardial infarction are less likely to undergo cardiac catheterization compared to patients in other Western countries (e.g. , the United States). Despite recommended guidelines, invasive strategies are more frequent in low risk groups (younger patients, male gender) than in postinfarction patients at high risk (severely impaired left ventricular function, clinical signs of congestive heart failure, the elderly).

Adult↗
PubMed1999

Assessment of temporal dispersion in motor nerves with normal conduction velocity.

Demyelinated nerves attenuate high-frequency components of propagating action potentials. In order to study if there is diagnostic use of this in motor nerves, the spectral energy above 49 Hz, amplitude, area, and duration of the compound muscle action potentials were measured; values after distal and proximal stimulation of posterior tibial nerves were compared. Normative data were collected in 48 control subjects. The same measurements were made in 20 patients with polyneuropathy and reduced motor nerve conduction velocity, in 21 patients with mild polyneuropathy but normal motor nerve conduction velocity, and in 8 patients with myasthenia gravis. Overall, high-frequency attenuation was closely correlated with amplitude decay (r = 0.63, P<10(-19)) and with increase of action potential duration (r = 0.34, P = 10(-5)). In the group of patients with normal NCV, high-frequency attenuation was abnormal in 9 (43%), amplitude decay was abnormal in two (10%), and area decay was abnormal in one (5%) patient. The action potential duration was normal in all of these patients. High-frequency attenuation was not influenced by stimulus intensity, thus it is not changed by conduction block, and it was not influenced by impaired neuromuscular transmission. Hence, high-frequency attenuation, both sensitively and specifically does indicate abnormal temporal dispersion. In conclusion, the simple measurement of high-frequency attenuation markedly improves detection and characterization of demyelination of human motor fibers.

Action Potentials↗