Physiotherapy improves motor function in patients with the Parkinson variant of multiple system atrophy: A prospective trial.

BACKGROUND AND OBJECTIVES: Gait impairment and reduced mobility are disabling symptoms of multiple system atrophy. While physiotherapy is increasingly recognized as a valuable supplement to pharmacotherapy for patients with Parkinson's disease, data on the efficacy of physiotherapy for multiple system atrophy are lacking. This study aimed to explore the feasibility of two consecutive exercise-based interventions in patients with multiple system atrophy. SUBJECTS AND METHODS: We included 10 patients with the parkinsonian variant of multiple system atrophy and 10 patients with Parkinson's disease, matched for gender and Hoehn & Yahr stage (≤3). Interventions consisted of a five-day inpatient physiotherapy program followed by a five-week unsupervised home-based exercise program. Outcomes included instrumented gait analysis, patient questionnaires, clinical rating scales and physical tests. Patients were examined at baseline, after the first inpatient treatment and again after the home-based intervention. Additionally, a structured telephone interview was performed immediately after the second intervention period. RESULTS: Both patient groups exhibited a similar improvement of gait after the interventions, as measured by instrumented gait analysis. These effects reached their maximum level after inpatient physiotherapy and remained stable following the home-based exercise program. Patient questionnaires also showed improvements after the interventions, but motor clinical rating scales did not. CONCLUSION: Our pilot results suggest that a short-term bout of physiotherapy is feasible, safe and improves gait performance in patients with multiple system atrophy. This highlights the potential of physiotherapy for this disabling condition where pharmacotherapy typically achieves poor effects. The present findings warrant a larger controlled study.

Motor output complexity in Parkinson's disease during quiet standing and walking: Analysis of short-term correlations using the entropic half-life.

Parkinson's disease (PD) is associated with alterations in motor outputs such as center of pressure (CoP) adjustments during quiet standing and foot kinematics during walking. Previous research suggests that the complexity of motor outputs reflects the number of control processes stabilizing a specific movement, providing a measure that is linked to the neurological control of the movement. The Entropic Half Life (EnHL) represents a new method for assessing motor output complexity. We hypothesized that there will be a lack of neuromuscular control pathways for PD patients, resulting in a decrease in motor output complexity. We computed the EnHL of CoP adjustments during quiet standing and foot kinematics during walking of 70 PD patients and 33 age-matched controls. Patients with PD showed longer EnHL values compared to controls, suggesting a tighter motor control. Excluding vision led to a decrease of EnHL of CoP in both groups. EnHL was correlated with spatio-temporal gait parameters. We compared EnHL with the pull test and the timed up-and-go test. No significant differences were present in the pull test, yet motor output complexity was correlated with the timed up-and-go test. The results suggest a reduced complexity in motor outputs of PD patients affecting distinct motor functions.

Turbinate reduction with complete preservation of mucosa and submucosa during rhinoplasty.

BACKGROUND: Turbinate surgery is an important adjunct to functional and cosmetic rhinoplasty. Many studies have analyzed the effects of various mucosal-sparing techniques, such as radiofrequency, laser, shaver, and others. These techniques, however, result in the destruction of the submucosal tissue of the turbinate. The goal of this study was to determine whether excellent functional outcome could be achieved with techniques sparing both the mucosa and submucosa from destruction when addressing the turbinates in rhinoplasty surgery. MATERIALS AND METHODS: A prospective single-surgeon clinical study analyzing submucous resection of turbinate bone without destruction of the submucosa or mucosa in patients undergoing functional-esthetic rhinoplasty was performed. In all, 122 patients (47 men, 75 women, average age: 32.1 years, range: 16-69 years) were eligible for the study. The functional outcome was measured prospectively using the Nasal Obstruction Symptom Evaluation (NOSE) score. Occurrence of complications was documented. RESULTS: Of over 1000 surgical patients, 307 candidates fulfilled multiple selection criteria and were entered in a rhinoplasty database. The surveys sufficient for the present study were completed by 122 of 307 patients (39.7%), of whom 91 patients reported improvement, 14 patients reported no subjective change, and 12 patients reported minimal worsening of nasal breathing. Overall, postoperative function was excellent (preoperative vs. postoperative NOSE score 47.5 vs. 20.1, p < 0.001). A large proportion of patients reporting worsening of symptoms (50%) were diagnosed with decongestant nasal spray abuse. Specific complications such as bleeding, foul drainage, dryness, and crusting were not reported. CONCLUSION: All function-bearing structures of the inferior nasal turbinates, mucosa, and submucosa can be fully preserved without impairment of functional outcome during rhinoplasty. The technique of selective submucous bone resection is as an excellent alternative for patients undergoing rhinoplasty for concomitant treatment or prevention of nasal obstruction.

[Injection of Lipotransplants for Wound Healing Complications after Radiotherapy]. / Injektion von Bauchfett bei radiogenen Wundheilungsstörungen.

Wound healing complications in irradiated tissues represent a major clinical challenge. Fistula or even major vessel rupture may occur. The injection of adipose tissue derived stem cells seem to be a promising therapeutical strategy. The article describes the clinical case of a patient suffering from a pharyngo-cutaneous fistula after laryngectomy and radiotherapy. The patient was successfully treated by the injection of fat tissue.

Platelet-rich plasma stimulates dermal microvascular endothelial cells and adipose derived stem cells after external radiation.

BACKGROUND: Platelet-rich plasma (PRP) products are currently suggested in the treatment of chronic wounds due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of PRP on irradiated cells of the cutaneous wound healing process are still poorly understood. MATERIAL AND METHODS: Human dermal microvascular endothelial cells (HDMEC) and human adipose derived stem cells (hASC) were cultured and irradiated with doses of 2 to 12 Gy. PRP was activated, characterized and added to the incubation media in different concentrations after external radiation. Cell count was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in the supernatants of HDMEC and hASC co-cultures were determined by enzyme-linked immunosorbent assay (ELISA). Non-irradiated hASC and HDMEC served as controls. RESULTS: The employed PRP preparations were characterized and contained platelet derived growth factor (PDGF-AB), vascular endothelial growth factor (VEGF), bFGF and high levels of sICAM-1. Addition of PRP to irradiated cultures of HDMEC and hASC prevented profound radiation-induced decline in cell numbers. 10% PRP restored cell numbers to levels of untreated, non-irradiated cultures. Basic FGF expression was decreased significantly in hASC monocultures treated with 10% PRP without external radiation and after irradiation with 6 and 12 Gy. These inhibitory effects of PRP were also observed in HDMEC. In contrast, co-cultures of HDMEC-ASC showed a dose-dependent increase in bFGF expression when treated with 5 or 10% PRP. Doses of 6 and 12 Gy increased IL-6 expression in cultures stimulated with 5% PRP. CONCLUSIONS: Use of PRP in co-cultures of hASC and HDMEC restores proliferative defects caused by external radiation probably by induction of bFGF. Under irradiated conditions, PRP might induce pro-inflammatory stimuli which could be beneficial in treatment of chronic wounds where healing processes are defective. Combined use of hASC and PRP products might be helpful in the treatment of radiogenic wounds.

[Minimally invasive surgery of the anterior skull base: transorbital approaches]. / Minimal-invasive Chirurgie der vorderen Schädelbasis: Transorbitale Zugänge.

Minimally invasive approaches are becoming increasingly popular to access the anterior skull base. With interdisciplanary cooperation, endonasal endoscopic in particular approaches have seen an impressive expansion of indications over the past decades. The more recently described transorbital approaches represent minimally invasive alternatives with a differing spectrum of access corridors. The purpose of the present paper is to discuss transorbital approaches to the anterior skull base in the light of the current literature.The transorbital approaches allow excellent exposure of difficult to reach areas like the the anterior and posterior wall of the frontal sinus; working angles may be more favorable and the paranasal sinus system can be preserved while exposing the base of skull. Because of their minimal morbidity and the cosmetically excellent results, the transorbital approaches represent an important addition to established endonasal endoscopic and open approaches to the anterior skull base. Their execution requires an interdisciplinary team approach.

[Potential of adipose-derived stem cells concerning the treatment of wound healing complications after radiotherapy]. / Potenzial adipogener Stammzellen bei radiogenen Wundheilungsstörungen.

BACKGROUND: Compromised wound healing in irradiated tissues is a common and challenging clinical problem. The pathophysiology and underlying cellular mechanisms including the complex interaction of cytokines and growth factors are still incompletely understood. OBJECTIVES: In this article, the potential of adipose-derived stem cells concerning the treatment of wound healing complications after radiotherapy is discussed. METHODS: Human dermal fibroblasts (NHF), microvascular endothelial cells (HDMEC) and human adipose-derived stem cells (ASC) were cultured in a co-culture setting and irradiated with doses of 2-12Gy. Cell count was determined and levels of cytokines and growth factors relevant for wound healing were measured using enzyme-linked immunosorbent assays (ELISA) and qPCR techniques. Irradiated NHF, HDMEC and ASC as well as non-irradiated mono and co-cultures, NHF, HDMEC or ASC respectively were used as controls. RESULTS: Cell count was significantly reduced in irradiated co-cultures of NHF, HDMEC and ASC compared to non-irradiated controls. Levels of IL-6, bFGF, ICAM-1 and VCAM-1 in the supernatants of the co-cultures were significantly less affected by external radiation in comparison to HDMEC. Levels of IL-6 and VEGF in the supernatants of co-cultures were significantly less affected by external radiation in comparison to NHF. DISCUSSION: The increased expression of cytokines and adhesion molecules by NHF and HDMEC after external radiation is mitigated in the co-culture setting with ASC. These in vitro changes seem to support the clinical observation that ASC may have a stabilizing effect when injected into irradiated wounds.

Fish length exclusively determines sexual maturation in the European whitefish Coregonus lavaretus species complex.

The probability that a fish matures at a certain age and length (the so-called probabilistic maturation reaction norm, PMRN) was analysed for a European whitefish Coregonus lavaretus species complex population living in the Austrian pre-alpine Lake Irrsee. Fish length was found to be the only relevant determinant of maturation probability, and females matured at slightly smaller sizes than males.

Effects of radiation on the expression of adhesion molecules and cytokines in a static model of human dermal microvascular endothelial cells.

BACKGROUND: Radiation-induced wound healing complications represent an important clinical problem. Microvascular compromise is an important component of its pathogenesis and the microvascular endothelial cell is the key representative affected at the cellular level. MATERIAL AND METHODS: Human dermal microvascular endothelial cells (HDMEC) were cultured and irradiated with doses of 2 to 12 Gy. Cell density was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the supernatants of HDMEC were determined by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Non irradiated HDMEC were used as controls. RESULTS: Cell density was significantly impaired in irradiated cells compared to non irradiated controls. Radiation resulted in significant elevation of levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of HDMEC in a dose dependent manner. CONCLUSION: The inflammatory response observed clinically after radiation seems to correlate with elevated expression of cytokines and adhesion molecules by microvascula endothelial cells. The model of HDMEC documents the impairment of microcirculation. These in vitro changes may enhance our understanding of the pathomechanisms leading to radiation-induced vasculitis and associated wound healing problems.

[Rare malignant tumor of the parotid gland. Myoepithelial carcinoma]. / Seltener maligner Tumor der Gl. parotis. Myoepitheliales Karzinom.

A parotid mass in a 62-year-old woman presented intraoperatively as a highly malignant tumor with facial nerve infiltration. Classification by means of rapid section histology was not possible. Immunohistochemical studies were necessary to diagnose this rare case of myoepithelial carcinoma of the parotid gland. We performed a total parotidectomy including partial nerve resection and neck dissection on the tumor side. The patient was referred to radiotherapy postoperatively.

[Structural grafts and suture techniques in functional and aesthetic rhinoplasty surgery]. / Struktur-Transplantate und Nahttechniken in der funktionell-ästhetischen Rhinochirurgie.

Rhinoplasty has undergone important changes. With the advent of the open structure approach, requirements for structural grafting and suture techniques have increased substantially. The present review analyzes the current literature on frequently referenced structural grafts and suture techniques. Individual techniques are described and their utility is discussed and critically reviewed in light of available data.

'Global worming': first record of an epidemic of Triaenophorus crassus in a population of Arctic charr Salvelinus umbla.

In May 2005, an epidemic of the cestode Triaenophorus crassus occurred in the Salvelinus umbla population of Lake Grundlsee, an oligotrophic Austrian Alpine Lake. Based on catches with a standardized multi-mesh gillnet survey 53% of S. umbla were infected with up to 17 cysts of T. crassus per fish. This is the first documented record of an epidemic of this tapeworm in S. umbla.

Quantitative study of nasal tip support and the effect of reconstructive rhinoplasty.

OBJECTIVES: To develop a method to quantify nasal tissue resilience, to establish the normal range for persons without nasal obstruction, and to measure the changes in tissue resilience resulting from standard open rhinoplastic techniques. METHODS: A new device is described that determines nasal tissue resilience. Measurements on the nasal tip were obtained in triplicate at 5 distinct anatomical sites. Normal values (N = 60) were stratified for both sexes into 3 different age groups. Preoperative and postoperative measurements were also obtained in 6 patients who underwent open rhinoplasty for airway obstruction. One patient who underwent intranasal valve repair was included for comparison. All operative patients underwent preoperative and postoperative rhinomanometric measurements. RESULTS: Across all age and sex groups the anterior septal angle is the firmest area of the nasal tip. The mean tissue resilience over the interdomal area and the midcolumella is significantly greater in men than in women. The resilience of the interdomal area exhibits an age effect, with decreasing stiffness over time. The postoperative changes seen correlate well with the placement of structural grafts during rhinoplasty. CONCLUSIONS: Nasal tip support can be quantified. Normative values have been established, which allow one to identify areas of inadequate tip support in persons with nasal obstruction. Alterations in tip support resulting from surgical intervention can be quantified. Open rhinoplasty techniques are an excellent tool to restore deficiencies in nasal tip support.

Addition of an anesthetic agent to enhance the predictability of the effects of botulinum toxin type A injections: a randomized controlled study.

OBJECTIVE: To determine whether the paralyzing effect of botulinum toxin type A reconstituted in a solution of lidocaine with epinephrine is as effective as that of the same toxin reconstituted in saline and to determine whether the addition of lidocaine with epinephrine enhances the predictability of outcomes of botulinum toxin injections. SUBJECTS AND METHODS: This double-blind, within-subject, randomized controlled study was conducted in 10 volunteer subjects. Lidocaine was added to botulinum toxin type A to achieve an immediate paralyzing effect on the injected muscle, and epinephrine was added to minimize diffusion of the injected toxin to adjacent muscles. This combination of agents was injected to temporarily paralyze the frontalis, corrugator supercilii, and procerus muscles on 1 side of the forehead of the 10 volunteers. The contralateral side was injected with the same dosage of the toxin, reconstituted in an equal volume of saline, to serve as control. Photographic and video documentation of the drugs' effects was obtained before injection and at 5 to 10 minutes, 1 week, and 3 months after the injections. RESULTS: Immediate paralysis ensued on the experimental side (botulinum toxin type A + lidocaine + epinephrine) in all 10 volunteers. As assessed by 3 blinded evaluators, the extent of immediate paralysis resulting from the anesthetic agent was predictive of the extent of delayed paralysis resulting from the botulinum toxin. The botulinum toxin-induced paralysis wore off symmetrically in all subjects. CONCLUSION: The injection of botulinum toxin reconstituted in lidocaine with epinephrine provided the physician immediate feedback on the extent of paralysis to be expected from the chemodenervating action of the botulinum toxin. This may enhance the safety and predictability of botulinum toxin injections in many applications.

Treatment of facial wounds with botulinum toxin A improves cosmetic outcome in primates.

Surgeons have constantly sought to achieve the most aesthetic scar. A major factor determining the final cosmetic appearance of a cutaneous scar is the tension acting on the wound edges during the healing phase. Since Theodor Kocher pioneered the alignment of skin incisions with Langer's lines in 1892, surgical techniques that attempt to overcome closing tension have become standard. Yet, no treatment has been available to minimize underlying muscle contractions, which are the major cause of this tension. Botulinum toxin A is a potent drug that produces temporary muscular paralysis when injected locally. It has proven to be safe and effective in the treatment of a variety of disorders, including hyperkinetic facial lines. The objective of this randomized, double-blind, placebo-controlled primate study was to investigate the efficacy of a single injection of botulinum toxin A to improve the cosmetic appearance of cutaneous scars. Symmetric pairs of standardized excisions were performed on either side of the forehead of six primates. The half foreheads were randomized to the botulinum toxin A treatment side versus the placebo injection side. A panel of three blinded facial surgeons assessed the cosmetic appearance of the mature scars 3 months postoperatively. The wounds that had been immobilized with botulinum toxin A were rated as significantly better in appearance than the control wounds (p < 0.01). Histologic examination confirmed that all scars were mature. Blinded, randomized, placebo-controlled human clinical trials are presently under way at the Mayo Clinic.

CSF rhinorrhea: 95 consecutive surgical cases with long term follow-up at the Mayo Clinic.

A persistent cerebrospinal fluid (CSF) leak is potentially lethal, and surgical treatment is often required. CSF leak repair is an infrequently performed procedure, and only limited information is available on the long term success of the surgical techniques that are used. This retrospective chart review includes 95 patients who underwent various types of repair surgery for CSF rhinorrhea at the Mayo Clinic. The purpose of this study was to extract factors such as the choice of sealing material, etiology, location of defect(s), surgical approach, and previous procedures, and to analyze their association with the long term success and failure of surgical repair. The mean time interval in this study between unsuccessful surgery and recurrence was 50.8 months, and the mean follow-up 109 months. Among the various approaches, defects repaired endonasally had the lowest recurrence rate. Local nasal mucosa advancement flaps failed more frequently (83.3% failure) than other types of graft material (p = 0.023). These failures took place in a delayed fashion (mean interval until failure: 80 months). Local osteo-mucoperiosteal or chondro-mucoperichondrial flaps (22.2% recurrence rate) and free graft material (15.6% recurrence rate) had the best outcome. The use of fibrin glue to fixate free grafts did not improve the result in this series. Transcranial procedures were associated with a higher complication rate than extracranial procedures (12.9% versus 3.2%). Overall, successful repair was achieved in 91.6% of the patients. We discourage the use of mucosa advancement flaps and advocate free grafts or pedicled osteomucoperiosteal or chondro-mucoperichondrial flaps as sealing material of choice in the majority of cases. The occurrence of delayed failure has to be considered when evaluating reports of CSF rhinorrhea after surgical repair.

Differential effects of transforming growth factors on localization of adhesion complex proteins following corneal epithelial cell wounding.

PURPOSE: The differential effects of transforming growth factor (TGF) alpha, beta 1 and beta 2 on the de novo localization of heparan sulfate proteoglycan, collagen type VII and laminin-1 to the adhesion complex were analyzed using an in vitro model of corneal epithelial cell wound healing. METHODS: Bovine corneal explants were maintained in culture media containing either no growth factor or 1, 5, or 10 ng/ml TGF alpha, TGF beta 1 or TGF beta 2. After 24 or 48 hours in culture, cryostat sections of explants were processed for immunofluorescence microscopy using antibodies directed against heparan sulfate proteoglycan, collagen type VII or laminin-1. RESULTS: A comparison of antibody labeling patterns and relative fluorescence intensity of antibody labeling to controls suggested that TGF alpha inhibits the spatial polarization of proteins into the reforming adhesion complex during early stages of wound healing. Both TGF beta 1 and beta 2 enhanced the linear localization of the three proteins to the site of the reforming adhesion complex. However, in our model TGF beta isoforms did not have identical functions. TGF beta 2 accelerated the temporal localization of collagen type VII to the adhesion complex, an effect which was not observed with TGF beta 1. CONCLUSIONS: TGF beta, but not TGF alpha, may play an important role in corneal epithelial cell wound healing by accelerating the reformation of the adhesion complex and subsequent epithelial cell-extracellular matrix adhesion.