Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Minimal-invasive Adrenalektomie beim Phäochromozytom

ZusammenfassungHintergrund Bedingt durch die intraoperative Katecholaminsekretion mit hämodynamischen Veränderungen, einem größeren Tumordurchmesser und einer deutlichen Neovaskularisation ist die Adrenalektomie beim Phäochromozytom im Vergleich zu anderen Nebennierenerkrankungen schwieriger und potenziell komplikationsträchtiger. Ziel unserer Studie war die Frage, ob das Risiko intraoperativer kardiovaskulärer Komplikationen durch das minimal-invasive Vorgehen potenziert wird.Patienten und Methodik Im Zeitraum zwischen Februar 1992 und Mai 2005 wurden in unserer Klinik 82 Eingriffe wegen eines Phäochromozytoms bei 71 Patienten durchgeführt. Davon wurden 8 (1) Patient(en) bi-(tri-)lateral adrenalektomiert und bei 2 Patienten erfolgte eine ipsilaterale Rezidivoperation. Eingeschlossen sind 5 weitere Patienten mit Rezidiv nach Erstoperation vor 1992. Sechsunddreißig Eingriffe erfolgten konventionell (transperitoneal n=35, retroperitoneal n=1) und 46 Operationen endoskopisch (transperitoneal n=28, retroperitoneal n=18), davon keine Konversion zum offenen Vorgehen.Ergebnisse Das mediane Alter zum Zeitpunkt der Operation betrug 45 (24–75) Jahre bei einer Anamnesedauer von 12 (0–180) Monaten. Die offen operierten Phäochromozytome waren mit 5,5 (1–19) cm vs. 3,5 (0,5–8) cm (endoskopisch) signifikant größer (p=0,0011). Patienten mit endoskopischer, insbesondere mit retroperitoneoskopischer Adrenalektomie hatten im Vergleich zum konventionellen Vorgehen intraoperativ höhere systolische und diastolische maximale Blutdruckwerte sowie Spitzen über 200 mmHg (statistisch nicht signifikant). Faktoren mit möglichem Einfluss auf intraoperative hämodynamische Veränderungen waren in der multivariaten Analyse das Geschlecht (p=0,0107), der operative Zugangsweg (p=0,0153), das Patientenalter (p=0,0364) und die Tumorgröße (p=0,0484). Die postoperative stationäre Verweildauer war nach endoskopischer Operation signifikant kürzer (p<0,0001).Schlussfolgerung Die endoskopische Adrenalektomie beim Phäochromozytom ist in der Routine ohne vermehrtes Risiko kardiovaskulärer Komplikationen die Methode der Wahl. Das offene Vorgehen sollte extraadrenalen Befunden oder sehr großen Tumoren mit Malignitätsverdacht vorbehalten bleiben.      

Energy cost of activity and exercise in children and adolescents with cystic fibrosis.

In cystic fibrosis (CF), perturbations of total daily energy expenditure (TDEE) may be a major determinant of altered nutrition and growth. Measurement of TDEE is problematic, though the flex-heart rate method (FHRM) provides a close estimation of TDEE, as compared to the cost-prohibitive, gold standard, the double-labeled water method, and permits estimates of the energy cost of daily activities (ECA) above resting energy expenditure (REE). We hypothesize that alterations in ECA affects TDEE in CF. PURPOSE: To measure components of TDEE in adolescents with CF and normal lung function compared with controls, and to determine whether ECA can be improved by diet and exercise. METHODS: Clinically stable CF subjects (aged 9-13, n=12) and age- and gender-matched controls (n=13) had repeated measurements of TDEE by FHRM, REE, and maximal cardiopulmonary exercise testing (CPET) during a 6-week exercise and diet program. RESULTS: While the mean REE was similar in both groups, ECA was significantly lower in CF adolescents as compared to controls (p=0.02). During CPET, maximal exercise in CF was characterized by hyperventilation, which was unrelated to ventilation-perfusion mismatching. There were no changes in REE after dietary intervention. CONCLUSION: ECA in CF adolescents with normal lung function is lower when compared to healthy controls. These findings support the hypothesis that clinically stable patients with CF have inefficient energy metabolism or alternatively conserve energy during activities of daily living.     

Hippocampal damage and cytoskeletal disruption resulting from impaired energy metabolism

To determine if impaired energy metabolism might contribute to some aspects of Alzheimer disease (AD), including the vulnerability of the CA1 region of the hippocampal formation and the altered cytoskeleton evident in neurofibrillary tangles, we examined the effects of metabolic poisons on neuronal damage and cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death, particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but sparing of axonal τ. MK-801 (a noncompetitive NMDA receptor antagonist) did not atenuate the lesions produced by intrahippocampal injection of malonate. MK-801, however, was effective against intrastriatal malonate. Acute systemic 3-NP resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but sparing of τ. The neuronal loss in CA1 was delayed as compared to striatum. Chronic intraventricular infusion of 3-NP produced a different pattern of neuronal damage. Loss of τ-1 immuno-reactivity was observed in CA3 and CA1 s. oriens, whereas MAP2 immunostaining was preserved. These results demonstrate that chronic and acute administration of metabolic inhibitors produce distinct patterns of neuronal damage and cytoskeletal disruption. The results further suggest a differential involvement of the NMDA receptor in malonate-induced neuronal damage in striatum as compared to the hippocampus. The pattern of neuronal damage and cytoskeletal disruption observed following acute metabolic impairment resembled some aspects of neurofibrillary pathology in AD, but did not result in τ hyperphosphorylation.     

Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.

Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg x m(-2), primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.     

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK(-/-) mice.

Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.