Influence of hepatitis C virus infection and high virus serum load on biliary complications in liver transplantation.

BACKGROUND: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified. PATIENTS AND METHODS: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded). BCs diagnosed with imaging techniques and abnormal liver enzyme pattern, requiring an intervention, were considered. RESULTS: In a multivariate analysis, HCV serostatus and a high pre-and post-surgery HCV RNA serum load were independent risk factors for anastomotic strictures. HCV positivity and BCs alone did not alter graft loss. HCV-positive patients with BCs, however, had a significantly worse graft outcome (P = 0.02). Non-anastomotic strictures, bile leaks, and the number of interventions needed to treat bile leaks led to worse graft outcome in all patients. CONCLUSION: HCV positivity and a high HCV RNA serum load were risk factors for anastomotic strictures. BCs and HCV had an additive effect on graft loss.

Chronic treatment with a novel γ-secretase modulator, JNJ-40418677, inhibits amyloid plaque formation in a mouse model of Alzheimer's disease.

BACKGROUND AND PURPOSE: γ-Secretase modulators represent a promising therapeutic approach for Alzheimer's disease (AD) because they selectively decrease amyloid ß 42 (Aß42), a particularly neurotoxic Aß species that accumulates in plaques in the brains of patients with AD. In the present study, we describe the in vitro and in vivo pharmacological properties of a potent novel γ-secretase modulator, 2-(S)-(3,5-bis(4-(trifluoromethyl)phenyl)phenyl)-4-methylpentanoic acid (JNJ-40418677). EXPERIMENTAL APPROACH: The potency and selectivity of JNJ-40418677 for Aß reduction was investigated in human neuroblastoma cells, rat primary neurones and after treatment with single oral doses in non-transgenic mouse brains. To evaluate the effect of JNJ-40418677 on plaque formation, Tg2576 mice were treated from 6 until 13 months of age via the diet. KEY RESULTS: JNJ-40418677 selectively reduced Aß42 secretion in human neuroblastoma cells and rat primary neurones, but it did not inhibit Notch processing or formation of other amyloid precursor protein cleavage products. Oral treatment of non-transgenic mice with JNJ-40418677 resulted in an excellent brain penetration of the compound and a dose- and time-dependent decrease of brain Aß42 levels. Chronic treatment of Tg2576 mice with JNJ-40418677 reduced brain Aß levels, the area occupied by plaques and plaque number in a dose-dependent manner compared with transgenic vehicle-treated mice. CONCLUSIONS AND IMPLICATIONS: JNJ-40418677 selectively decreased Aß42 production, showed an excellent brain penetration after oral administration in mice and lowered brain Aß burden in Tg2576 mice after chronic treatment. JNJ-40418677 therefore warrants further investigation as a potentially effective disease-modifying therapy for AD.

[44-year-old woman with elevated liver enzymes and a family history for cholelithiasis]. / 44-jährige Patientin mit unklarer Leberwerterhöhung und familiär gehäuftem Gallensteinleiden.

"Low phospholipid associated cholelithiasis" (LPAC) syndrome is an important differential diagnosis in younger patients with biliary symptoms after cholecystectomy and concomitant elevated serum liver tests. Typical symptoms include recurrence of biliary colics after cholecystectomy, echogenic material in the intrahepatic bile ducts, intrahepatic cholestasis of pregnancy or cholestasis under hormonal contraception and a family history of gallstone disease. Patients with LPAC syndrome can be successfully treated with ursodeoxycholic acid.

The subfornical organ: a central nervous system site for actions of circulating leptin.

Adipose tissue plays a critical role in energy homeostasis, secreting adipokines that control feeding, thermogenesis, and neuroendocrine function. Leptin is the prototypic adipokine that acts centrally to signal long-term energy balance. While hypothalamic and brain stem nuclei are well-established sites of action of leptin, we tested the hypothesis that leptin signaling occurs in the subfornical organ (SFO). The SFO is a circumventricular organ (CVO) that lacks the normal blood-brain barrier, is an important site in central autonomic regulation, and has been suggested to have a role in modulating peripheral signals indicating energy status. We report here the presence of mRNA for the signaling form of the leptin receptor in SFO and leptin receptor localization by immunohistochemistry within this CVO. Central administration of leptin resulted in phosphorylation of STAT3 in neurons of SFO. Whole cell current-clamp recordings from dissociated SFO neurons demonstrated that leptin (10 nM) influenced the excitability of 64% (46/72) of SFO neurons. Leptin was found to depolarize the majority of responsive neurons with a mean change in membrane potential of 7.3 +/- 0.6 mV (39% of all SFO neurons), while the remaining cells that responded to leptin hyperpolarized (-6.9 +/- 0.7 mV, 25% of all SFO neurons). Similar depolarizing and hyperpolarizing effects of leptin were observed in recordings from acutely prepared SFO slice preparations. Leptin was found to influence the same population of SFO neurons influenced by amylin as three of four cells tested for the effects of bath application of both amylin and leptin depolarized to both peptides. These observations identify the SFO as a possible central nervous system location, with direct access to the peripheral circulation, at which leptin may act to influence hypothalamic control of energy homeostasis.

[Revision surgery after implantation of a vertebral disc prosthesis]. / Revisionschirurgie nach Bandscheibenprothesenimplantation.

Assessment of the revisability of surgery after the endoprosthetic replacement of vertebral discs shows that the surgical approach depends on the time of revision surgery and the reason why it is carried out. Our experience is based on nine revision operations out of 152 cervical vertebra prostheses of the Bryan and Prodisc C types implanted from 2003 to 2007 and 312 endoprostheses of the Charité and Prodisc types implanted from 1999 to 2007. Our own results show differing approaches in perioperative or late postoperative revision operations. Operations to exchange implants were not possible, whereas a change of surgical procedure is the rule. The same access route can usually be selected in the cervical spine, but in the lumbar spine this can only be done perioperatively; if revision surgery is carried out at a later date, an alternative access route must be used. Using strict indications for the primary implant is the only way to prevent postoperative revision surgery that is due to an inaccurate primary assessment and not to the vertebral endoprosthesis (e.g. post-discotomy syndrome, facet joint arthropathy, rotation instability, vertebral slip). The next generation of vertebral disc endoprostheses must incorporate reduced load of the zygapophyseal joints and improved revisability.

Proteomics-based strategies in kinase drug discovery.

Studies of drug action classically assess biochemical activity in settings which typically contain the isolated target only. Recent technical advances in mass spectrometry-based analysis of proteins have enabled the quantitative analysis of sub-proteomes and entire proteomes, thus initiating a departure from the traditional single gene--single protein--single target paradigm. Here, we review chemical proteomics-based experimental strategies in kinase drug discovery to analyse quantitatively the interaction of small molecule compounds or drugs with a defined sub-proteome containing hundreds of protein kinases and related proteins. One novel approach is based on 'Kinobeads'--an affinity resin comprised of a cocktail of immobilized broad spectrum kinase inhibitors--to monitor quantitatively the differential binding of kinases and related nucleotide-binding proteins in the presence and absence of varying concentrations of a lead compound or drug of interest. Differential binding is detected by high throughput and sensitive mass spectroscopy techniques utilizing isobaric tagging reagents (iTRAQ), yielding quantitative and detailed target binding profiles. The method can be applied to the screening of compound libraries and to selectivity profiling of lead compounds directly against their endogenously expressed targets in a range of cell types and tissue lysates. In addition, the method can be used to map drug-induced changes in the phosphorylation state of the captured sub-proteome, enabling the analysis of signalling pathways downstream of target kinases.

[Indication, biomechanics and early results of artificial disk replacement]. / Indikation, Biomechanik und Frühergebnisse des künstlichen Bandscheibenersatzes.

AIM: Judgment of factors concerning the indication for the implantation of an artificial disc endoprosthesis, the rating of this operation and biomechanical considerations. METHOD: Presentation of the indication and the value of a new operative concept in comparison to a so-called dynamic stabilization procedure (Dynesys' method). Indications for the operation are: unsuccessful, orthopedic conservative treatment for > 6 months, segmental pain, age < 45 years, evidence of an MRI demonstrable mono- or bisegmental disc degeneration with or without disc prolabation, exclusion of psychogenic disease and positive preoperative, diagnostic measures such as facet joint infiltration and discography. RESULTS: In an earlier investigation the efficacy of the Link method was demonstrated as shown by the reduction of the analgesic use, the angle of the lumbar lordosis (L1-S1) increased from 35.6 degrees to 42.6 degrees (20.2 %), the segmental angle from 19 degrees to 30 degrees (57.5 %). The new investigation using the Aesculap endoprosthesis resulted in a change of the angle of lumbar lordosis from 35.4 degrees to 45.4 degrees (25.4 %) and a change of the segmental angle from 17.3 degrees to 29.1 degrees (57.6 %). This method is a real endoprosthetic instrumentation in the field of spinal surgery. CONCLUSION: In younger patients with mono- or bisegmental disc degeneration there is an indication for the implantation of a disc endoprosthesis. A facet joint arthrosis and an age over 45 years are contraindications for the operation. The indication in patients with a classic failed back surgery syndrome is still unclear, the improvement of the instrumentation and a further adaptation of the systems to the known biomechanics of the lumbar spine are mandatory as is an intensive discussion of the operative procedure in the case of revision operations. The Dynesys method, with the inherent danger of segmental kyphozitation, a published, significant revision quota combined with a reduction of motility, does not fulfill this criterion.

Calcium-dependent maintenance of agrin-induced postsynaptic specializations.

Although much progress has been made in understanding synapse formation, little is known about the mechanisms underlying synaptic maintenance and loss. The formation of agrin-induced AChR clusters on cultured myotubes requires both activation of the receptor tyrosine kinase MuSK and intracellular calcium fluxes. Here, we provide evidence that such AChR clusters are maintained by agrin/MuSK-induced intracellular calcium fluxes. Clamping intracellular calcium fluxes after AChR clusters have formed leads to rapid MuSK and AChR tyrosine dephosphorylation and cluster dispersal, even in the continued presence of agrin. Both the dephosphorylation and the dispersal are inhibited by the tyrosine phosphatase inhibitor pervanadate. In contrast, clamping intracellular calcium at the time of initial agrin stimulation has no effect on agrin-induced MuSK or AChR phosphorylation, but blocks AChR cluster formation. These findings suggest an avenue by which postsynaptic stability can be regulated by modification of intracellular signaling pathways that are distinct from those used during synapse formation.

[Disc replacement with the SB Charité endoposthesis - experience, preliminary results and comments after 35 prospectively performed operations]. / Der Bandscheibenersatz mit der SB Charité-Bandscheibenendoprothese - Erfahrungen, Frühergebnisse und Feststellungen nach 35 prospektiv durchgeführten Operationen.

UNLABELLED: Aim of this prospective study was an investigation concerning the indication for the implantation of an artificial disc endoprosthesis and the rating of this operation. METHOD: 35 patients with 11 bi- and 24 monosegmental implanted disc endoprosthesis were observed over an average follow-up of 14.7 months. Indications for the operation were: unsuccessful, orthopedic conservative treatment > 6 months, segmental pain, age < 45 years, evidence of a radiologic (MRI) demonstrable mono- or bisegmental disc degeneration with or without disc prolabation, exclusion of psychogenic disease and positive preoperative, diagnostic measures. RESULTS: The average stay in the hospital was 16.8 days (preoperative: 4.3 days), the average operation time 85.5 minutes, the average blood loss was 125 ccm. 23 patients were operated in L 5 / S 1, 20 in L 4 / 5 and 2 in L 3 / 4. NSAR was given in 33 patients preoperatively, opiates in 2 further patients, postoperatively NSAR was necessary in 5 patients, opiates in 2 patients. The preoperative angle of lordosis (L 1 - S 1, n = 25) was changed from 35.6 degrees to 42.6 degrees (20,2 %), the segmental angle from 19 degrees to 30 degrees (57.5 %). CONCLUSION: The implantation of the artificial disc was followed by a good pain relief in patients suffering from a mono- or bisegmental disc degeneration. In patients with a facett joint arthrosis and elderly patients > 45 years this method cannot be used, the indication in patients with failed back surgery syndrome cannot be estimated yet. Improvements of the instrumentation and the discussion in the case of revisional operations are mandatory.

[Necessary steps for implementing the Australian DRG system]. / Notwendige Schritte zur Einführung des AR-DRG-Systems.

The introduction of the DRG-System will be followed by severe changes in the German hospitals. From the view of today departments or hospitals are threatened by closing if they do not deal with the new rules. A common implementation of this system by all participants of the health system is necessary before the introduction at 1.1.2003. Only this will guarantee an adequate presentation of the different defaults in the future because the conditions of the implementation of the system are not qualified yet. The hospitals are forced to prepare the introduction of the DRG-System, however. Only the Arrangement of an extensive documentation of all diagnoses and all conservative and operation methods together with a cost--cutting administration will be consequently followed by a financial healthy situation. The most important points to be emphasized are the medical documentation, the controlling, the improvement of the processes and the computer assisted documentation. By an intensive information concerning all further resources the involvement of the employees of the hospital is a necessary part for the success of the introduction.

[Function of back extensor muscles in upright standing position and during sitting with identical back posture--an electromyography study]. / Die Aktivität der Rückenstreckmuskulatur beim aufrechten Stehen und beim Sitzen mit standidentischer Rumpfhaltung--eine elektromyographische Studie.

PROBLEM: There is a controversial discussion about the loading of the spine by the force of the extending muscles of the back in upright sitting with the back curved as in upright standing. Experimental studies investigating this issue are still lacking. METHODS: In the study presented in this paper we measured in 30 subjects the activity of the extending back muscles both in a natural upright standing posture and in sitting with identical posture of the back as recommended in some back training programs. To this end we recorded the electromyographical surface activity of the back muscles at four levels of the spine in both postures. The EMG activities were intraindividually normalized with reference to the respective activity recorded at maximum voluntary isometric contraction (MVC). RESULTS: At three of the four levels of the spine examined, the group averages of the EMG activity in sitting were significantly higher than in standing (p < 0.001). The maximum activity enhancement evaluated was 48% at Th12. The force of the lower back muscles in sitting with a posture of the back as in natural upright standing could be estimated to be at least greater than 30% of the force at MVC. CONCLUSION: The force needed to enforce in sitting a posture of the back identical to the posture at natural standing entails lower back muscle fatigue in a few minutes. The results of our study agree with recent experimental findings about an increased loading of the spine in lordotic sitting.

[Principles of surgical treatment of upper thoracic and cervicothoracic kyphosis]. / Prinzipien der operativen Behandlung hochthorakaler und zervikothorakaler Kyphosen.

Idiopathic upper thoracic and cervicothoracic kyphoses are rare. More frequently they are the consequence of spinal instability as in neurofibromatosis (von Recklinghausen's disease), after laminectomies, in tumors, congenital disorders, spondylodiscitis, and fractures. Neurologic problems with severe pareses complicate these deformities. Anterior bone loss (fracture, tumor, spondylodiscitis), posterior instability (post-laminectomy kyphosis) or a combination of both are responsible for the deformity. The operative treatment of the anatomically unfavorable localization requires great experience in spinal surgery; the procedures often are salvage surgeries. In the absence of a successful conservative treatment, early posterior/anterior or anterior/posterior reconstruction of the sagittal profile with primary stable implants is necessary to minimize the risk of renewed surgery. Transplantation of stable bone grafts such as the fibula is a precondition for postoperative treatment without external support. The indication is restrictive in the presence of malignant primary and secondary tumors with poor prognosis. Restitution of existing neurologic deficits is unpredictable.

[Kyphotic deformation in fractures of the thoracic and lumbar spine]. / Kyphotische Deformierungen bei Frakturen der Brust- und Lendenwirbelsäule.

Kyphosis is the typical deformity of untreated spine fractures. In the majority of all injuries, destruction of the anterior part of the spine occurs. Biomechanical aspects require reconstruction of the anterior column. In 112 patients with a traumatic fracture of the thoracolumbar spine, a loss of correction in the sagittal plane exceeded the intraoperative correction. The cause of deterioration was in the main part the destruction of the intervertebral disk. The results of different surgical techniques are reviewed and discussed based on the literature. The dorsal instrumentation with or without autogenous bone grafting is not sufficient for spinal stabilization and kyphosis is the result. The golden standard for prevention of kyphosis is the combined approach with anterior cortical bone graft and posterior transpedicular screwing. In the case of anterior cage implantation, the risk of graft failure can be avoided. With anterior minimally invasive approaches, traumatization can be reduced by using the same biomechanical principles. In the case of a type A fracture with intact posterior elements, use of an anterior primary stable implant with bone graft represents an alternative method.

Nitric oxide synthase (NOS-1) coclustered with agrin-induced AChR-specializations on cultured skeletal myotubes.

Previously we reported that neuronal nitric oxide synthase type-1 (NOS-1) is expressed in skeletal myotubes in vitro. In the present paper we sought to determine whether agrin-induced membrane specializations known to include the nicotinic acetylcholine receptor (AChR) on cultured myotubes may also contain NOS-1 and related molecules. After treatment with various agrin constructs containing the full C-terminally AChR-clustering domain (fragments N2, N4), but not with fragment C2 (truncated), NOS-1 expressed in the cytosol of mouse C2C12 skeletal myotubes coclustered with AChR, 43K rapsyn, MuSK, and the dystrophin/utrophin glycoprotein-complex (DUGC). Agrin-induced specializations also included coaggregates of N-methyl-d-aspartic acid (NMDA)-receptor, alpha-sodium (NaCh), or Shaker-type K+ channel (KCh)/PSD-95 complexes, and NOS-1. We conclude that agrin is crucial for recruitment of preassembled multimolecular membrane clusters, including AChR, NMDAR, and ion channels linked to NOS-1. Coassembly of NOS-1 to postsynaptic molecules may reflect site-specific NO-signaling pathways in neuromuscular junction formation and functions.

[Criteria for treatment of idiopathic scoliosis between 40 degrees and 50 degrees. Surgical vs. conservative therapy]. / Kriterien zur Behandlung idiopathischer Skoliosen zwischen 40 degrees und 50 degrees. Operative vs. konservative Therapie.

The treatment of idiopathic scoliosis over 40 degrees (Cobb) during the growth period is under discussion concerning the indication for conservative or surgical treatment. Curve progression depends on the degree of the frontal and sagittal deformity, vertebral rotation, rigidity of the curve, the skeletal age, the age and sex of the patient, the familial frequency of scoliosis and the location of the curve. In scoliosis over 40 degrees progression is fast and the possibilities for successful conservative brace treatment are reduced during the growth period. Progression occurs more frequently in thoracic and double major scolioses, especially in young patients (Risser sign 0 and 1). Predictive factors of a successful brace treatment are the correction of scoliosis and rotation; deterioration of both during the brace treatment leads to poor results. Evaluating the flexibility of the sagittal profile is important, as is primary correction of 30-50% in the brace during the 3 months. Operative correction of small primary curves reduces the fusion length, operation time, and blood loss and is followed by a reduction in loading on the adjacent vertebral segments in comparison to the long fusions necessary in more structural and double major scolioses. So far it is not possible to make an equivalent judgment of the frequency of the "crankshaft" phenomenon and the treatment necessary in young patients (Rissersign 0 and 1) treated by dorsal instrumentation alone, but temporary brace treatment may be considered in those cases.

[Scoliosis and hip flexion contracture in Duchenne muscular dystrophy]. / Skoliose und Hüftbeugekontraktur bei Duchennescher Muskeldystrophie.

UNLABELLED: Spinal deformity is common in muscular dystrophy and usually occurs after loss of walking ability. Unlike in idiopathic and other scoliosis forms, there seems to be no side preference of the convexity. Aim of the study was to analyse, if there is any relation between incidence and extent of walking ability, lower limb contractures and development of scoliosis. METHODS: In a retrospective study, 45 patients with Duchenne muscular dystrophy who underwent surgery were analysed, concerning walking ability, contractures of lower extremities and scoliosis. RESULTS: 1: No scoliosis was observed in ambulatory patients. 2: 96% of the wheelchair bound patients suffered from scoliosis. 3: 96% of the scoliosis patients had hip flexion or abduction contractures. 4: In 12 of 15 cases with side-different contractures, scoliosis tended to the side with the greater contracture. CONCLUSIONS: The influence of hip contracture and pelvic obliquity on scoliosis is discussed controversially. Concerning muscular dystrophy, there seems to be a positive correlation between convexity and hip contracture. If this is a causal relation or if there is a faster progression of structural alteration of the muscles on one side has to be further investigated.

One-stage versus two-stage spinal fusion in neuromuscular scolioses.

The principles of the operative treatment of neuromuscular scolioses differ from those of idiopathic scolioses. Depending upon the deformity in the frontal and sagittal plane, the amount of pelvic obliquity and especially the etiology of the curve, consideration of a posterior, an anterior or a combined anterior-posterior procedure is necessary. Statistics demonstrate a higher preoperative angle and a higher rate of complications combined with worse corrections in comparison with idiopathic scolioses. The existing deterioration of vital capacity in patients with Duchenne muscular dystrophy, as in patients with spinal muscle atrophy, makes an anterior approach impossible. The correction of a severe pelvic obliquity combined with a rigid lumbar or thoracolumbar scoliosis requires a combined approach in most patients suffering from myelomeningcele (MMC) and cerebral palsy. In neurofibromatosis Recklinghausen associated with an angulated kyphotic curve the anterior approach is mandatory to avoid further deterioration. Multisegmental primary-stable anterior or posterior instrumentations allow postoperative care without external support.

Outcome after palliative posterior surgery for metastatic disease of the spine--evaluation of 106 consecutive patients after decompression and stabilisation with the Cotrel-Dubousset instrumentation.

From 1987 to 1996, 106 consecutive patients with metastatic disease of the spine who underwent palliative decompression from a dorsal approach and subsequent stabilisation with Cotrel-Dubousset instrumentation (CDI) were followed prospectively, and independent of the surgeons. Parameters evaluated were neurological function, perioperative complications, survival and rehabilitation. Following the Frankel system for the assessment of neurological disorder, 33 patients had a major deficit (grade A, B or C), 23 a minor deficit (grade D) and 50 no deficit. If there was no neurological dysfunction, the only patients who underwent operation were those graded as class IV according to Harrington. Our surgical strategy combined posterior decompression of the spinal cord followed by CD stabilisation without bone grafting. Of 56 patients who had a neurological deficit preoperatively, 35 enjoyed complete or partial recovery within the first 3 months after the operation. Of the 50 patients without neurological dysfunction, 3 developed an incomplete transient paresis. The rate of survival was 72% (76 of 106) at 6 months and 50% (53 of 106) at 12 months. At 12 months 42 of the 53 patients who were alive were still able to walk. All but 13 patients were able to return home. Overall survival time was 19.2 months, with 5 patients still alive. Six patients required re-operation for tumour recurrence at the same or at a new level. The results of this study show that neurological function, pain level and mobility can be enhanced by decompression and stabilisation through a posterior approach.

Orthopedic and neurosurgical treatment of severe kyphosis in myelomeningocele.

Kyphosis in myelomeningocele is characterized by a complex pattern of problems during development and therapy. On the one hand, decompensation of upright posture leads to loss of sitting ability and social integration; on the other hand, accompanying malformations and trophic alterations threaten the physical integrity and performance. Neurologic function, cerebrospinal fluid (CSF) circulation, skeletal deformity and the urinary transport system need to be kept in mind and need to be treated with cooperation between the different specialties. Especially during serious surgical interventions such as spinal surgery, neither the nervous system nor the kidneys must be ignored. Sixteen patients underwent kyphectomy in the Orthopedic Department of the University of Mainz between 1993 and 1997, all of them supervised by the Neurosurgical Department. In 13 cases, transversal myelotomy was performed. No insufficiency of CSF circulation was seen; neither were there any CSF fistulae. Particular problems arose from the skin and soft tissue above the gibbus, the lack of muscles and the regeneration deficiency caused by trophic disorders. Therefore, a significantly higher complication rate was found than with other correctional operations.

Shock-wave therapy for tennis and golfer's elbow--1 year follow-up.

Thirty patients with chronic medial epicondylitis were treated with low-energy shock waves. They received 500 impulses of 0.08 mJ/mm2 three times at weekly intervals. At 1 year follow-up examinations were performed. According to the Verhaar criteria, only seven patients reached excellent or good results. In eight cases a fair outcome was recorded, and in 14 patients the outcome was poor. Only six patients were satisfied with the treatment. The average relief of pain was 32%. These data were significantly worse than for identically treated patients with chronic tennis elbow. Thus, the question arises as to whether extracorporal shock-wave therapy is indicated in medial epicondylitis.