Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Biomechanical comparison of a new technique of mandibular angle fractures: biplanar and bicortical superior proximal 3 holes and bicortical inferior plate fixation

Miniplates have been used for mandibular angle fractures during the past 2 decades. The technique of placing single miniplate at the upper border based on the tension lines of the fracture was proposed by Michelet and Champy. The need for a second miniplate to be applied to the lower mandible has been discussed recently. Biomechanical comparison of biplanar and monoplanar dual-miniplate fixation techniques was investigated by Haug. Our hypothesis is in dual-miniplate fixation; the proximal 3 holes of superior border miniplate could be fixated by bicortical screws. The first 2 are at the proximal bone segment and are not related to the tooth and also superior to the alveolar nerve. Generally, the third molar tooth is extracted because it is at the fracture site. Hence, the proximal third hole could also be fixated by bicortical screws. We define a biplanar dual-miniplate technique in which the lower plate and the proximal 3 holes of the upper plate are fixated by bicortical screws. We have designed a study for biomechanical comparison of our method and popular types of mandibular fixation methods.     

Patients’ postures during migraine attacks

Abstract The aim of this study was to determine postures adopted by patients during migraine attack. A total of 199 migraine patients were questioned about their postures during the migraine attack. Of these, 92 patients did not choose a specific lying position, 22 could not lie down during the attack because of the increase in pain, while 6 avoided lying due to scalp tenderness. During the attack, 19 patients preferred holding their heads up (compared to painless period) with a few pillows and 41 applied pressure on the aching side; 15 lay with their necks extended and 15 lay face downward. Various combinations of these postures were also reported. Pain may arise from extracranial muscles as well as vessels during a migraine attack. The posture chosen during attack is a reflection of vascular and muscle pains that provoke symptoms. The postures that patients chose were aimed to lessen the severity of symptoms of their migraine attacks. Patients know the position they adopt and do not need to be told by a doctor, but they come to consultations to be understood, to learn that others behave in the same way, and in some, to obtain reasons for their posture. The existence of a specific lying posture can be an advantage for the physician in terms of approaching the patient and selecting an appropriate therapy.     

Clinical review of grayanotoxin/mad honey poisoning past and present

Grayanotoxin is a naturally occurring sodium channel toxin which enters the human food supply by honey made from the pollen and nectar of the plant family Ericaceae in which rhododendron is a genus. Grayanotoxin/mad honey poisoning is a little known, but well studied, cholinergic toxidrome resulting in incapacitating and, sometimes, life-threatening bradycardia, hypotension, and altered mental status. Complete heart blocks occur in a significant fraction of patients. Asystole has been reported. Treatment with saline infusion and atropine alone is almost always successful. A pooled analysis of the dysrhythmias occurring in 69 patients from 11 different studies and reports is presented. The pathophysiology, signs, symptoms, clinical course, and treatment of grayanotoxin/mad honey poisoning are discussed. In the nineteenth century grayanotoxin/mad honey poisoning was reported in Europe and North America. Currently, documented poisoning from locally produced honey in Europe or North America would be reportable. Possible reasons for this epidemiologic change are discussed.     

Comparison of Adhesive Properties of Five Different Prosthetic Materials Used in Hernioplasty

This experimental study was designed to assess and to compare intra-abdominal adhesions following the use of five commercially available prosthetic mesh grafts in the repair if abdominal wall defects. Sixty Wistar albino rats were randomly divided into six groups (n = 10). A 2 × 1 cm defect at abdominal wall was created and defects were closed either primarily or with one of the following prosthetic mesh grafts: monofilament polypropylene, polytetrafluoroethylene, sodium hyaluronate/carboxymethylcellulose-coated polypropylene, polypropylene/polyglactin 910 composite, or resorbable hydrophilic collagen-coated multifiber polyester. The severity of adhesions was graded, tensile strengths of adhesions were measured, and histopathological grades of inflammation and fibrosis were evaluated. Polypropylene mesh resulted in more adhesion formation in comparison to primary repair and other grafts used in this study, except polypropylene/polyglactin 910 composite mesh. In addition, the highest tensile strength of omental adhesions was detected in the polypropylene group (χ² = 26.249; p =. 0001). Polyester composite mesh caused the least adhesion formation among the groups. Sodium hyaluronate/carboxymethylcellulose-coated polypropylene and polyester composite meshes revealed the highest fibrosis scores (χ² = 50.776; p =. 0001). The highest inflammatory activity was detected in the polytetrafluoroethylene mesh group (χ² = 16.564; p =. 005). Thus, sodium hyaluronate/carboxymethylcellulose-coated polypropylene and polytetrafluoroethylene meshes following polyester composite mesh were the minimal adhesion-forming grafts in this study. Disadvantages of the polytetrafluoroethylene mesh were lower fibrotic activity and higher inflammatory reaction to the graft.     

Giant left atrial myxoma in an elderly patient: natural history over a 7-year period

We present the case of a 71-year-old woman with a 7-year history of a giant left atrial myxoma. The myxoma was attached to the atrial septum and occupied almost the entire left atrial cavity. The patient was hospitalized 4 times because of dyspnea on exertion, palpitations, fatigue, general asthenia, and weight loss. During prior hospitalizations, the patient had refused cardiac surgery. She developed several complications, including atrial fibrillation, mitral and tricuspid regurgitation, mesenteric embolism, pulmonary edema, and thrombotic stroke. We herein describe the natural history of left atrial myxoma in an elderly patient over a 7-year period.     

Combined gracilis tendon autograft reconstruction and discus repair of a chronic anterior–superior sternoclavicular joint dislocation

A case of an 18-year-old gardener who sustained an anterior–superior dislocation of the sternoclavicular joint while playing handball and falling on his right shoulder is presented. Non-surgical treatment failed, and the patient could willingly dislocate the right clavicle while abduction and external rotation of the arm. This painful condition was finally treated with surgical reconstruction of the sternoclavicular joint using gracilis tendon autograft and repair of the discus. Level of evidence Therapeutic study, case report and technical note, Level IV.     

Incidence and management of epithelial loosening after LASIK

To determine the incidence of recurrent epithelial loosening (REL) following laser in situ keratomileusis (LASIK) and evaluate the efficacy of anterior stromal micropuncture (ASP) and the application of bandage contact lenses (BCLs) in the management of REL after LASIK. A retrospective study including all individuals who underwent LASIK with a microkeratome between January 2006 and January 2007. Medical records were reviewed to identify patients who were diagnosed as having epithelial loosening with or without epithelial defects. Data were collected on 5,566 eyes that underwent LASIK with a microkeratome. Eight eyes (0.14 % or one in 696 eyes) of seven patients had REL with or without epithelial defects. Frequent lubrication, BCL application, and ASP were needed for four eyes (50 %) in the management of REL, respectively. All patients remained free of symptoms after completion of ASP. REL following LASIK is uncommon. Follow-up of patients showed that BCL application and ASP were effective in the management of REL following LASIK.