University of Lausanne

About: University of Lausanne is a education organization based out in Lausanne, Switzerland. It is known for research contribution in the topics: Population & Poison control. The organization has 20508 authors who have published 46458 publications receiving 1996655 citations. The organization is also known as: Université de Lausanne & UNIL.

Intravenous Administration of Human γ‐Globulin*

Abstract: Summary Intravenous administration of standard human γ-globulin can lead to untoward reactions. This is due to at least one endogenous and an exogenous factor. The “endogenous” factor is revealed by the finding that certain subjects only - especially patients with an antibody deficiency syndrome - react to intravenous infusions of γ-globulin administered under standard conditions. The “exogenous” factor resides in the γ-globulin preparation itself and is related to its anticomplementary activity. The “endogenous” factor can be temporarily eliminated by “desensitizing” the patient; the “exogenous” factor may be eliminated by ultracentrifugation, enzymatic breakdown of the γ-globulin, or other treatment involving exposure to low pH values. Upon clinical trial, the preparations obtained by enzymatic degradation or by exposure to pH 4 at 37 °C displayed the best tolerance after intravenous application. Enzymatically degraded γ-globulin is partially eliminated by the kidney and has no desensitizing effect. On the other hand, pH 4 exposed γ-globulin does not pass through the kidney and is still capable of desensitizing “sensitive” individuals. Resume L'administration intraveineuse de γ-globuline bumaine peut provoquer chez l'homme des reactions serieuses. Ces phenomenes d'intolerance sont dus a l'existence au moins d'un facteur endogene et d'un facteur exogene. Le facteur “endogene” se manifeste en ce sens que seul certains malades - specialement ceux souffrant d'un syndrome par carence d'anticorps - tolerent mal l'injection intraveineuse de γ-globuline. Le facteur “exogene” est associe a la γ-globuline meme et est en relation directe avec son action anticomplementaire. Le facteur “endogene” peut etre elimine temporairement par une desensibilisation du malade; le facteur “exogene” peut etre elimine par ultracentrifugation, par degradation enzymatique de la γ-globuline ou par d'autres traitements tels qu'une exposition prolongee a des acides tres dilues. Ce sont les preparation obtenues par degradation enzymatique ou par l'action d'acides dilues qui sont le mieux tolerees lors de l'injection intraveineuse. La γ-globuline digeree sous l'action d'un enzyme est eliminee partiellement par les reins et n'exerce aucune action desensibilisante. Par contre, la γ-globuline exposee a un pH de 4 ne passe pas le seuil renal, et sa capacite de desensibiliser des individus sensibles, persiste. Zusammenfassung Die intravenose Applikation von menschlichem Standard-γ-Globulin kann zu schweren Zwischenfallen Anlas geben. Diese Unvertraglichkeit beruht zumindest auf einem exogenen und einem endogenen (individuellen) Faktor. Der “endogene” (individuelle) Faktor ausert sich darin, das nur gewisse Individuen—in der Regel handelt es sich dabei um Patienten mit einem Antikorpermangelsyndrom - auf eine i.v. γ-Globulingabe mit Unvertraglichkeitserscheinungen reagieren. Der “exogene” Faktor liegt im γ-Globulinpraparat; er steht mit dessen anti-komplementarer Wirkung in direkter Beziehung. Es ist moglich, den “endogenen” Faktor vorubergehend durch “Desensibilisierung” des Patienten (rnit Standard-γ-Globulin) auszuschalten. Der “exogene” Faktor kann entweder durch Ultrazentrifugierung, durch enzymatische Verdauung, oder durch blose Ansauerung (pH 4) eliminiert werden. Bei der klinischen Prufung erwiesen sich diejenigen Praparate als gut vertraglich, die durch enzymatische Verdauung oder durch Ansauern gewonnen wurden. Enzymatisch abgebaute γ-Globuline gehen teilweise durch die Niere verloren; sie besitzen auserdem keine desensibilisierende Wirkung. Demgegenuber erscheint das durch Aneauern gewonnene Praparat nicht im Urin des Patienten. Es verhalt sich auch in bezug auf seinen desensibilisierenden Effekt wie Standard-γ-Globulin.

Changing Paradigms—An Update on the Multidisciplinary Management of Malignant Glioma

Abstract: Treatment of malignant glioma requires a multidisciplinary team. Treatment includes surgery, radiotherapy, and chemotherapy. Recently developed agents have demonstrated activity against recurrent malignant glioma and efficacy if given concurrently with radiotherapy in the upfront setting. Oligodendroglioma with 1p/19q deletions has been recognized as a distinct pathologic entity with particular sensitivity to radiotherapy and chemotherapy. Randomized trials have shown that early neoadjuvant or adjuvant administration of procarbazine, lomustine, and vincristine chemotherapy prolongs disease-free survival; however, it has no impact on overall survival. Temozolomide, a novel alkylating agent, has shown modest activity against recurrent glioma. In combination with radiotherapy in newly diagnosed patients with glioblastoma, temozolomide significantly prolongs survival. Molecular studies have demonstrated that the benefit is mainly observed in patients whose tumors have a methylated methylguanine methyltransferase gene promoter and are thus unable to repair some of the chemotherapy-induced DNA damage. For lower-grade glioma, the use of chemotherapy remains limited to recurrent disease, and first-line administration is the subject of ongoing clinical trials. Irinotecan and agents like gefitinib, erlotinib, and imatinib targeting the epidermal growth factor receptor and platelet-derived growth factor receptor have shown some promise in recurrent malignant glioma. This review summarizes recent developments, focusing on the clinical management of patients in daily neuro-oncology practice.

Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis.

Abstract: Rationale: Lung injury leads to pulmonary inflammation and fibrosis through myeloid differentiation primary response gene 88 (MyD88) and the IL-1 receptor 1 (IL-1R1) signaling pathway. The molecular mechanisms by which lung injury triggers IL-1β production, inflammation, and fibrosis remain poorly understood.Objectives: To determine if lung injury depends on the NALP3 inflammasome and if bleomycin (BLM)-induced lung injury triggers local production of uric acid, thereby activating the NALP3 inflammasome in the lung.Methods: Inflammation upon BLM administration was evaluated in vivo in inflammasome-deficient mice. Pulmonary uric acid accumulation, inflammation, and fibrosis were analyzed in mice treated with the inhibitor of uric acid synthesis or with uricase, which degrades uric acid.Measurements and Main Results: Lung injury depends on the NALP3 inflammasome, which is triggered by uric acid locally produced in the lung upon BLM-induced DNA damage and degradation. Reduction of uric acid levels using the ...