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In dieser randomisierten, kontrollierten, multizentrischen Studie wurde die Nichtunterlegenheit einer transdermalen Applikation einer Nanocarrier-Thiamazolsalbe gegenüber der oralen Gabe von Thiamazoltabletten zur Behandlung der felinen Hyperthyreose untersucht. Im Studienzeitraum von Dezember 2016 bis April 2018 wurden Katzen mit einem Serum-T4-Wert > 4,5 µg/dl (58 nmol/l) eingeschlossen, die zufällig der dermalen oder oralen Behandlungsgruppe zugewiesen wurden. Katzen der dermalen Gruppe erhielten abhängig vom anfänglichen T4-Wert eine Dosierung von 3,6 mg (T4-Wert > 4,5–10 µg/dl resp. > 58–129 nmol/l) bzw. 7,2 mg (T4-Wert > 10 µg/dl resp. > 129 nmol/l) täglich und die der oralen Gruppe unabhängig vom T4-Wert 5,0 mg täglich. Primärer Endpunkt war die Bestimmung des Anteils euthyreoter Katzen (T4-Wert 0,8–4,0 µg/dl resp. 10–51 nmol/l) in der Per-Protocol-Population nach 120 Tagen Behandlungsdauer in Bezug auf die Nichtunterlegenheit der dermalen gegenüber der oralen Behandlungsgruppe. Als Nichtunterlegenheitsgrenze wurde a priori ein Unterschied der Erfolgsraten zwischen beiden Gruppen von 10 % festgelegt. Nichtunterlegenheit der dermalen Gruppe war gegeben, wenn das untere 95 %-Konfidenzintervall größer -10 % war. Für weitere Analysen auf Überlegenheit wurde eine Grenze von 0 % definiert. Insgesamt wurden 88 Katzen (dermale Gruppe53, orale Gruppe 35 Katzen) in die Per-Protocol-Analyse eingeschlossen. Nach 21, 42, 63 und 120 Tagen waren 72 %, 77 %, 83 % und 83 % der dermalen Gruppe sowie 46 %, 63 %, 65 % und 54 % der oralen Gruppe euthyreot. Zu allen Kontrollpunkten konnte die Nichtunterlegenheit der dermalen Gruppe gegenüber der oralen Gruppe nachgewiesen werden (Konfidenzintervall zu Tag 21, 42, 63 bzw. 120: 6–47 %; -5–34 %; -1–38 %; 9–48 %). Die Studie zeigt, dass eine transdermale Formulierung von Thiamazol, die auf Kern-Multischalen-Nanocarriern basiert, in ihrer Wirksamkeit zu keinem Studienzeitpunkt der oralen Behandlung gegenüber unterlegen war und als sicher bewertet werden kann.

Introduction: The oral treatment of feline hyperthyroidism with antithyroid drugs often results in gastrointestinal side effects (10-20%). To date only oral formulations are approved although the oral application is not tolerated by all cats. Transdermal therapy can be an alternative. Nanocarriers could be used to ensure adequate transport of active agents through the skin. The present pilot study investigated the efficacy and safety of a novel dermal formulation of thiamazole for the treatment of feline hyperthyroidism. For the first time, amphiphilic dendritic core-multishell-nanocarriers were used. Cats with T4 values ≥ 4.0 µg/dl or a T4 value from 3.0-4.0 µg/dl and defined clinical findings were recruited. The euthyroid range for the T4 value was defined from ≥ 0.8 and ≤ 4.0 µg/dl. A total of 24 hyperthyroid cats were included and treated with thiamazole ointment for three weeks (24 cats) up to eight weeks (12 cats). The treatment success was 50% after three weeks and 41,7% after eight weeks. Cats that were within the euthyroid range required after three weeks a mean total dose of 1,09 mg/kg/d (0,68-1,7 mg/kg/d, 12/24) and after eight weeks 1,65 mg/kg/d (1,49-2,04 mg/kg/d, 5/12). No side effects were observed during the three resp. eight-week study period. Variations of the T4 value in companion cats in the same household were comparable to those of an independent control group. Thiamazole ointment based on nanocarriers is suitable for the treatment of feline hyperthyroidism.

Background: p53 gene aberrations are the most common genetic changes seen in human carcinogenesis. Frequently, single point mutations are detected, resulting in increased levels of (an aberrant) p53 protein in tumor cells. The cellular protein produced appears to become immunogenic during tumor development, inducing the production of circulating antibodies against p53., Methods: For this study, sera from 126 patients with oral squamous cell carcinomas (102 primary tumours and 24 recurrent/secondary tumours) were examined for p53 autoantibodies and their further clinical course was followed up for more than 5 years. 80 sera from internal medicine patients without known or suspected neoplasm served as control. A sandwich ELISA (enzyme linked immuno sorbent assay) designed by Dianova, Hamburg was used to detect p53 autoantibodies., Results: In 18.6 % of the patients with primary oral squamous cell carcinomas, p53 autoantibodies were detected, and also in 50 % of the patients with recurrent or local secondary carcinomas. None of the sera of the control group was positive. Patients with anti-p53 have noticeably poorer prognosis (Log Rank Test, p < 0.005). After a period of 5 years, the overall survival rate of the p53-positive group was 24 % - less than half of that of the p53-negative group with a survival rate of 51 %., Conclusions: : The detection of p53 autoantibodies definitely permits a clearer prognostic assessment, which in turn influences clinical procedures. If p53 autoantibodies are detected in a patient during therapy, the applied therapeutic method should be reconsidered and the patient be more closely observed than other, p53 negative patients.

Intraoperative fat embolism associated with cemented total hip arthroplasty is a well recognized complication. In a new sheep model allowing for standardized bilateral, simultaneous cement pressurization we studied the effectiveness of both pulsatile and syringe lavage of equal volume with regard to their cleansing capabilities as measured by fat and bone marrow intravasation. The operative procedure involved bilateral placement of intravenous catheters into the external iliac veins via retroperitoneal approach. After femoral neck osteotomies both femoral cavities were prepared for retrograde cement application. After randomization one side was lavaged with 250 ml irrigation using a bladder syringe, the contralateral femur with the identical volume but using a pulsatile lavage. A specially designed apparatus was used to allow for bilateral simultaneous cement pressurization. Venous blood from both iliac catheters was then collected, anticoagulated and a quantitative and qualitative fat analysis was performed. Despite equal volume manual lavage produced significantly higher fat and bone marrow intravasation (P < 0.001) than pulsatile lavage thus suggesting that not only the volume but also the quality of bone lavage is an essential factor influencing the risk of fat embolism and adverse cardiorespiratory effects. Our findings further emphasize the important role of pulsatile lavage in preventing fat and bone marrow embolisation during cemented total hip arthroplasty.