Free-running cardiac magnetic resonance fingerprinting: Joint T1/T2 map and Cine imaging.

PURPOSE: To develop and evaluate a novel non-ECG triggered 2D magnetic resonance fingerprinting (MRF) sequence allowing for simultaneous myocardial T1 and T2 mapping and cardiac Cine imaging. METHODS: Cardiac MRF (cMRF) has been recently proposed to provide joint T1/T2 myocardial mapping by triggering the acquisition to mid-diastole and relying on a subject-dependent dictionary of MR signal evolutions to generate the maps. In this work, we propose a novel "free-running" (non-ECG triggered) cMRF framework for simultaneous myocardial T1 and T2 mapping and cardiac Cine imaging in a single scan. Free-running cMRF is based on a transient state bSSFP acquisition with tiny golden angle radial readouts, varying flip angle and multiple adiabatic inversion pulses. The acquired data is retrospectively gated into several cardiac phases, which are reconstructed with an approach that combines parallel imaging, low rank modelling and patch-based high-order tensor regularization. Free-running cMRF was evaluated in a standardized phantom and ten healthy subjects. Comparison with reference spin-echo, MOLLI, SASHA, T2-GRASE and Cine was performed. RESULTS: T1 and T2 values obtained with the proposed approach were in good agreement with reference phantom values (ICC(A,1) > 0.99). Reported values for myocardium septum T1 were 1043 ± 48 ms, 1150 ± 100 ms and 1160 ± 79 ms for MOLLI, SASHA and free-running cMRF respectively and for T2 of 51.7 ± 4.1 ms and 44.6 ± 4.1 ms for T2-GRASE and free-running cMRF respectively. Good agreement was observed between free-running cMRF and conventional Cine 2D ejection fraction (bias = -0.83%). CONCLUSION: The proposed free-running cardiac MRF approach allows for simultaneous assessment of myocardial T1 and T2 and Cine imaging in a single scan.

Towards predicting the encoding capability of MR fingerprinting sequences.

Sequence optimization and appropriate sequence selection is still an unmet need in magnetic resonance fingerprinting (MRF). The main challenge in MRF sequence design is the lack of an appropriate measure of the sequence's encoding capability. To find such a measure, three different candidates for judging the encoding capability have been investigated: local and global dot-product-based measures judging dictionary entry similarity as well as a Monte Carlo method that evaluates the noise propagation properties of an MRF sequence. Consistency of these measures for different sequence lengths as well as the capability to predict actual sequence performance in both phantom and in vivo measurements was analyzed. While the dot-product-based measures yielded inconsistent results for different sequence lengths, the Monte Carlo method was in a good agreement with phantom experiments. In particular, the Monte Carlo method could accurately predict the performance of different flip angle patterns in actual measurements. The proposed Monte Carlo method provides an appropriate measure of MRF sequence encoding capability and may be used for sequence optimization.

Regional differences in diabetic patients' pharmacotherapy in Bulgaria.

BACKGROUND: The regional analyses play an important role in understanding a state of diabetes mellitus management and to support informed policy options. They need to be explored in more details in order to ensure an equal patients' access to health care services of the same value and quality. AIM: The aim of this study is to analyze regional differences in a cost of diabetes therapy for insulin users in Bulgaria. MATERIALS AND METHODS: It is a combined prospective and retrospective observational study with duration of 6 months. Diabetic patients on insulin therapy were recruited by 35 endocrinologists. Information about the health care resources used was collected within 3-prospective and 3 retrospective months in 2010 and 2011. The regional cost of illness analysis was performed by calculating the average cost attributable to each individual patient despite the fact that some might not use a particular health care resource. Subgroup analysis was performed for hospitalized patients. RESULTS: A detailed analysis revealed cost differences in the regions, especially with more vulnerable population like Burgas and Pleven regions. Another reason for the cost differences is the type of insulin or type of therapy. Our study confirms the fact that the hospitalizations are the major cost driver. Rising diabetes prevalence and associated costs, including hospitalizations and management of diabetes complications, are a growing concern. The last possible reason for regional differences is the patients' characteristics and therapy differences. We add evidence demonstrating that the patients on insulin and OAD consume more resources including hospitalizations and suffer from more complications of diabetes. CONCLUSIONS: Reasons for regional differences might have different origin as there are various population characteristics, type of therapy, socio economic status and others.

[Biopharmaceutical and clinico-pharmacological research on the intramammary preparation Cephamasten]. / Biofarmatsevtichni i klinikofarmakologichni prouchvaniia na intramamarniia preparat tsefamasten.

An animal drug formula, Cephamasten, for intramammary application in the treatment of mastitis-affected cows, ewes, and goats in the lactation period was worked out on the base of microbiologic, technologic, biopharmaceutic, and clinico-pharmacologic studies. Its active ingredient was the Pharmachim cephalexin-monohydrate. The consistence of Cephamasten has proved suitable for intracisternal introduction. It is tolerated well within the udder of cows, and it rapidly releases the antibiotic incorporated in it. The milk of the treated quarters has proved free from cephalexin after the 72nd hour of the last infusion. Cephamasten has shown high effectiveness in the treatment both of the preclinical and of the acute clinical mastitis. In the first case best results were obtained with the twofold treatment at a 24-hour interval, and in the second case--with the sixfold treatment at 12-hour intervals (intracisternal introduction of the preparation). In the case of generalized mastitis, in dependence on the severity of the process Cephamasten is to be applied at 4-6-12 intervals along with frequent milking and the parenteral application of other agents.

[Trials using drugs in diseases of the silkworm (Bombyx mori L.)]. / Opiti za prilozhenie na lekarstveni sredstva pri bolestite po koprinenata buba (Bombyx mori L.).

Studied was the pharmacokinetic of chloramphenicol, tylosine, ampicillin, and penicillin in silkworm moths. The antibiotics were applied only once in the form of water solutions in concentrations of 0.062 to 1 per cent for chloramphenicol, 50 to 1500 IU/cm3 for tylosine, 0.03 to 0.5 per cent for ampicillin, and 300 to 2500 IU/cm3 for benzilpenicillin at the rate of 25 cm3/cm2 of a mulberry tree leaf. It was found that chloramphenicol in conc. 0.25 to 0.5 per cent was absorbed in the alimentary canal of the silkworm and was found in the haemolymph in bacteriostatic levels up to the 96th hour following treatment. Tylosine was also absorbed, and in concentrations of 500 to 1500 IU/cm3 was shown to maintain bacteriostatic levels in the haemolymph of the moths for a period of 24-32 hours. Ampicillin and penicillin were absorbed to a slight extent, and were eliminated from the haemolymph up to the eighth hour. It is suggested to use chloramphenicol and tylosine in the concentrations referred to for the control of the spontaneous nuclear polyhedria and flasheria in silkworm moths.

[Blood concentrations and anti-Borrelia anserina activity of erythromycin salts in birds]. / Kruvni kontsentratsii i aktivnost sreshtu Borrelia anserina na eritromitsinovi soli pri ptitsi.

Tested was comparatively the antispirochaetal activity of erythromycin asparaginate (EA), thiocyanate (ET), and lactate (EL) in a total of 314 chickens, pullets and cockerels artificially infected with Borrelia anserina (strains Surnevo and Pamoukchii). The antibiotics were applied via the crop, with the drinking water, and subcutaneously. The general status of the birds mortality rate, spirocheataemia, and the blood level of antibiotics were followed up along with the effect of EA and ET on the post vaccinal immunity against spirochaetosis. The crop application of EA, ET, and EL at rates of 25000 and 50000 IU/kg from the day of infection for 3 days produced a good prophylactic effect (with single birds only there was transient spirochaetaemia without death cases). At 15000 UI/kg the prophylactic effect was very weak. EA, ET, EL at 120, 180, 250, and 300 IU/kg with the drinking water, and at 150000 and 350000 UI/kg with the feed in the course of 3 to 7 days from the day of infection did not have satisfactory antispirochaetal effect because the birds did not readily accept the medicated water and feed. A comparatively better antispirochaetal effect was established with EA and ET. These antibiotics were found not to inhibit the conference of post vaccinal immunity. Highest blood levels and longest retention were by EA. Very good results were obtained with the subcutaneous application of EA at 25000, 18000, and 15000 IU/kg, once daily in the course of 3 days from the day of infection.

[Intramammary drug forms of neotil in treating mastitis during lactation]. / Prouchvaniia vurkhu intramamarnata lekarstvena forma "neotil" za lekuvane na mastiti po vreme na laktatsiia.

Technological, biopharmaceutical, and clinico-pharmacological studies were carried out on the varying composition of drug formulas that included a tylosin base and neomycin sulfate, intended for the treatment of mastitis-affected cows during the lactation period. A base was developed of suitable viscosity and physico-chemical properties, that rapidly released the active ingredients included in it and made them penetrate in depth in the udder glandular tissue. Both the base and the drug formula Neotil were shown to be well tolerated. Following the single intracisternal infusion tylosin was excreted with the milk up to fifth milking (the 60th hour), and neomycin--up to the 4th milking (the 48th hour). When applied therapeutically in the case of clinical and subclinical mastitis Neotil led to the clinical and bacteriological recovery of 92.5 per cent of the affected quarters. Developed was a microbiological method for the analysis of the active ingredients contained in the drug formula and the milk secretion.

[Pharmacokinetic and microbiological studies of Pharmachem erythromycin asparate]. / Niakoi farmakokinetichni i mikrobiologichni prouchvaniia na eritromitsinov aspartat.

Anti-microbial activity and pharmokinetics of erythromycin aspartate "Pharmachim" (EA) in chickens was studied. The investigations included erythromycin thiocyanat (ET) of the company Abbott-USA (the preparation Gallimycin poultry formula). The studies revealed that EA has an effect on Gram-positive microorganisms mainly. It is quickly resorbed by the digestive tract and following the administration of 50 and 100 mg/kg body weight (applied by tube) in doses of 0.14 to 0.8 meg/cm3 it can be detected in the blood serum of chickens after 10 min only have elapsed. Maximal concentrations (from 0.35 to 0.95 meg/cm3) are discovered at about the 30-60th min and after that EA levels are gradually reduced to traces or 0.125 mcg/cm3 by 24th h. Application via drinking water in a dose of 115 mg/l results in EA quantities of 0.11 to 0.2 meg/cm3 detected in the blood during the entire course of treatment with therapeutic water. The use of equal ET doses results in 20 to 39% lower antibiotic levels. The same is true for EA and ET content in organs and tissues. Both preparations are eliminated by the bile secretion untill the 96th h post treatment's end. Resorption of EA is quick and high grade following muscular injection and at a dose of 20 mg/kg body weight the antibiotic persists in bacteriostatic concentrations in the blood up to the 15th, while at a dose of 40 mg/kg body weight-up to the 24th h post its single application.

[Antimicrobial and antispirochetal activity of Pharmachem's tylosin]. / Prouchvaniia vurkhu antimikrobnata i antispirokhetnata aktivnost na tilozin "Farmakhim".

Studies are the following preparations, produced by "PHARMACHIM": tylosine-base (Tylosine-50), tylosine tartarate (Tylosine pulvis) and tylosine phosphate (substance and granules) and their analogues: tylosine-base (Tylan-50), tylosine tartarate (Tylan soluble) and tylosine phosphate (Tylan AF 99), produced by the "Elanco" Company. The biological activity of the preparation was determined by means of the microbiological method of diffusion in agar. In the case of all experimental treatments, the preparations were compared in conformity with their biological activity expressed in IU/mg of the preparations. The minimum inhibition concentrations of the preparations were determined by the method of serial dilutions in liquid nutritive media on 19 different pathogenic strains. The antispirochetal activity of the preparations compared was tested on 130 cockerels and pullets, experimentally infected with Borrelia anserina of the Surnevo and Pamoukchii serotypes. The application of the preparations started simultaneously with the infection or 24 and 48 hrs after it and continued for days. No significant differences are found in the antibacterial and antispirochetal activities of the Bulgarian tylosine preparations and those manufactured by the "Elanko" Company. The tylosine base does not differ significantly in its antimicrobial and antispirochetal activities from the tylosine phosphate and the tylosine tartarate when equal in IU concentrations and doses are applied.