Next generation tau models in Alzheimer's disease research - virus based gene delivery systems.

Alzheimer's disease (AD) the most common form of dementia is characterized by cognitive decline and progressive loss of neurons in the central nervous system. Despite huge scientific progress, there are only few animal models that recapitulate at least majority of the AD pathology and related symptomatology. Therefore, alternative methods to develop animal models for neurodegenerative diseases are constantly explored. Recently, recombinant adeno-associated viruses (AAVs) are widely used viral vectors in development of novel models for neurodegenerative diseases. AAV vectors expressing full length, mutant or truncated forms of tau demonstrate early and robust pathology characterized by AT8 positivity, NFT formation, motor and cognitive deficits. Furthermore, AAVs have been used in expression of tau in amyloid rodent models thus developing both lesions of amyloid and tau therefore recapitulating AD like features. Major advantage of AAV as a delivery system is the site specific expression of tau, mostly in hippocampus and cortex, and thus elimination of unwanted ectopic transgene expression. These novel models may help in better understanding of AD etiopathogenesis and provide a platform for development and testing of disease modifying drugs in preclinical efficacy studies.

Therapeutic hypothermia after out-of-hospital cardiac arrest with the target temperature 34-35 degrees C.

BACKGROUND: The objective of this study was to evaluate the impact of mild hypothermia (34-35 degrees C) on the final neurological outcome in patients after resuscitation from out-of-hospital cardiac arrest. METHODS: Forty three patients, admitted at University Hospital Brno after the out-of-hospital cardiac arrest, were included in the cohort study. The inclusion criteria were out-of-hospital cardiac arrest resulting from ventricular fibrillation or non-perfusing ventricular tachycardia as well as recovery of spontaneous circulation within 60 minutes after first symptoms. Blanketrol II (Cinncinnatti Sub Zero, USA) water mattresses were used for cooling the patients. The temperature was maintained at 34-35 degrees C for 24 hours. Favorable neurological outcome was defined as a Pittsburgh cerebral-performance category 1 (good recovery) or 2 (moderate disability) on five-category scale. RESULTS: The required temperature was reached in all patients; the cooling rate was 0.8 +/- 0.3 degrees C/hour. The time between the restoration of circulation and reaching the temperature of 35 degrees C was 119 +/- 32 minutes. The time induce the hypothermia (with the core body temperature below 35 degrees C) was 26 +/- 2 hours. Good outcome at hospital discharge was achieved in 21 out of 43 (49%) patients. Ten patients died in the hospital and two patients died after the discharge from the hospital, with the overall 6 months mortality being 28%. CONCLUSION: The study confirmed feasibility, safety and possible efficacy of the mild hypothermia (34-35 degrees C) patients after the cardiac arrest. To evaluate whether the target temperature 34-35 degrees C is as beneficial as 32-34 degrees C; a randomised controlled trial design should be used (Tab. 4, Fig. 2, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

[Liver abscesses - one of possible causes of fever of unknown origin]. / Jaterní abscesy - jedna z mozných prícin horecek nejasného puvodu.

Liver abscess is a focal suppurative liver process. According to the etiology liver abscesses are divided into bacterial (pyogenic), and parasiti (amebic). Parasitic cysts (e.g. caused by Echinococcus granulosus) can be secondary bacterial infected and their clinical and laboratory manifestations are like pyogenic abscesses. In clinical manifestation of liver abscesses dominates fever of unknown origin. Authors present two characteristic cases of liver abscesses as a Case reports. The origin of multiple pyogenic abscesses of mixed etiology (Enterococcus faecium, E. coli ESBL, Candida albicans, Candida tropicalis) in 73-years old man was either in secondary infected liver hematomas after his fall and injury or in intrascapular subcutaneous abscess with spreading of microbes by blood stream into liver. Some of liver abscesses were evacuated during surgical laparotomy; the residual ones were puncted by radiologist under CT control. The patient was treated with combination of meropenem, vancomycin, metronidazol (4 weeks), and fluconazole (20 days). Antibiotic treatment with per oral doxycycline was continuing after patient's discharge from the hospital for 3 weeks. Three amebic liver abscesses were diagnosed in 27-years old man of Indian origin. The treatment was based on drainage of abscesses under CT control a long-term metronidazol treatment.

[Peroperative autotransfusion using a cell saver in ruptured aneurysms of the abdominal aorta]. / Vyuzití peroperacní autotransfuze cell saverem u ruptury aneuryzmatu brisní aorty.

The authors present five cases where a cell saver was used in rupture of an aneurysm of the abdominal aorta. During the peroperative collection they obtained 830 +/- 150 ml of autologous red cell concentrate. They assume that this blood is an invaluable source of volume replacement during urgent operations on the abdominal aorta.

[Initial experience with peroperative autotransfusion in spinal surgery]. / První zkusenosti s peroperacní autotransfúzí ve spondylochirurgii.

The authors describe combinations of anaesthesiological methods which enabled them during extensive spondylosurgical operations in 66 patients to reduce the consumption of homologous blood during operation to 90 ml, on the first day after operation to 300 ml and on the second day after operation to 120 ml. In six patients they used preoperative collection of the patient's own blood, in 45 patients acute normovolaemic haemodilution, in all patients controlled hypotension with sodium nitroprusside to a mean arterial pressure of 8-9 kPa and peroperative collection of blood by means of an autotransfusion apparatus Dideco Stat with a standard programme and yield higher than 50%. During and after peroperative collection they did not record any complications. Lower haemoglobin and haematocrit values and a reduced number of erythrocytes, lower than the lower normal range, during and after operation did not threaten the postoperative course in these patients. The authors draw, however, attention to the rise of the number of leucocytes immediately after operation to 19.7 x 10(9). 1(-1) which is due to their shift into the final product. Solution of this phenomenon which can produce ARDS is according to the authors the use of a programme different from the standard one.