Evaluation of guideline implementation for dispensing driving-impairing medicines by National Pharmacy Organizations.

Background: In 2004, the International Pharmaceutical Federation (FIP) adopted a Statement of Professional Standard on the supply of medicines affecting driving performance, transformed to FIP guidelines in 2014. In 2011, the final report from the European initiative on Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) was published. Both documents provided recommendations for improving dispensing guidelines for driving-impairing medicines for patients who use psychoactive medicines. Objective: This study investigated the extent that European professional organizations of pharmacists (POPs) implemented existing guidelines and DRUID results. Methods: An online questionnaire survey was conducted in April-May 2022. Questionnaires were sent by e-mail to POPs in 46 European countries. The questionnaire addressed the following topics: awareness of FIP guidelines and DRUID outcomes (a), development of dispensing guidelines (b), target groups for information materials (c), evaluations of dispensing practices (d), examples of projects on medicines affecting driving fitness (e), development of ICT (Information and Communication Technology) -support (f), collaboration with organizations of physicians (g), and patients (h). The data were analyzed by indicating implementation initiatives in different countries. Open-ended questions were assessed qualitatively. Results: POPs in 23 European countries responded to the invitation (response rate: 50%). Guidelines for improving dispensing practices were available in 5 countries targeted at professionals, patients, and the general population. Patient and physician organizations were involved in 4 and 3 countries, respectively. Implementation was supported by computerized dispensing systems (5 countries) and public campaigns (5 countries). Conclusions: Twenty years after the introduction of FIP guidelines and ten years after the DRUID outcomes, only 5 European POPs have implemented this knowledge. Different activities were performed to support implementation, resulting in examples of successful use of recommendations for driving-impairing medicines in pharmacy practice. Implementation needs further attention. The successful practices that have been developed are an example for dissemination to other countries.

[Postoperative complications in radically operated patients with non-small cell lung cancer].

SUMMARY: Lung cancer is the leading cause of cancer death. Despite the advances in medicine only 22% of the patients with lung cancer are candidates for radical operative treatment. Postoperative complications and mortality remain relatively high. MATERIAL AND METHODS: We present 320 patients, operated in our clinic for the period 2001-2005. 136 patients underwent lobectomy, 158--pulmonectomy, 22--bilobectomy, and 4--wedge resection. RESULTS: Postoperative complications occurred in 63 (19,61%) patients. Nine deaths (2,81%) occurred within 10 days after the operation. Five patients (1,56%) developed bronchopleural fistula. We observed inflammatory pulmonary complications in 14 (4,37%), atelectasis in 26 (8,12%), postoperative empyema in 6 (1,87%), and wound infection in 3 (0,93%) patients. CONCLUSIONS: The postoperative complications in radically operated patients with lung cancer remain relatively frequent. Precise preoperative evaluation and assessment of the patients are crucial to lower the risk of postoperative complications.

[Remote results for cases of non-small cell lung cancer treated by limited resection].

UNLABELLED: The choice between the limited pulmonary resection and the standard anatomical resection depends on many factors. The most important are the tumor size, age and general condition of the patient. MATERIAL AND METHODS: We present 12 patients with non-small cell lung cancer-IA stage, who underwent limited resection. RESULTS: The 5-year survival rate is 50% (6 patients), the 3-year survival rate is 75% (9 patients), and the 1-year survival rate is 91,6% (11 patients). CONCLUSIONS: We conclude that the limited resection for patients with non-small cell lung cancer-IA stage is associated with a lower 5-year survival, but less complications, which makes it suitable for elderly and compromised patients.

Neuromuscular synaptic function in mice lacking major subsets of gangliosides.

Gangliosides are a family of sialylated glycosphingolipids enriched in the outer leaflet of neuronal membranes, in particular at synapses. Therefore, they have been hypothesized to play a functional role in synaptic transmission. We have measured in detail the electrophysiological parameters of synaptic transmission at the neuromuscular junction (NMJ) ex vivo of a GD3-synthase knockout mouse, expressing only the O- and a-series gangliosides, as well as of a GM2/GD2-synthase*GD3-synthase double-knockout (dKO) mouse, lacking all gangliosides except GM3. No major synaptic deficits were found in either null-mutant. However, some extra degree of rundown of acetylcholine release at high intensity use was present at the dKO NMJ and a temperature-specific increase in acetylcholine release at 35 degrees C was observed in GD3-synthase knockout NMJs, compared with wild-type. These results indicate that synaptic transmission at the NMJ is not crucially dependent on the particular presence of most ganglioside family members and remains largely intact in the sole presence of GM3 ganglioside. Rather, presynaptic gangliosides appear to play a modulating role in temperature- and use-dependent fine-tuning of transmitter output.

[Necrotizing sarcoid granulomatosis--case report and review of the literature].

The Necrotizing sarcoid granulomatosis is a rarely met angiitis. The disease is predominantly localized in the lung and has a good prognosis. The authors reported about a patient treated in their clinic; the diagnosis is made after histologic examination.

On the influence of soil properties on the transfer of 137Cs from two soils (Chromic Luvisol and Eutric Fluvisol) to wheat and cabbage.

Two types of soils (Eutric Fluvisol and Chromic Luvisol) and two crops (wheat and cabbage) were investigated for determination of the transfer of 137Cs from soil to plant. Measurements were performed using gamma-spectrometry. Results for the soil characteristics, transfer factors of the radionuclides (TF), and conversion factors (CF) (cabbage/wheat) were obtained. The transfer of 137Cs was higher for Chromic Luvisol for both the plants. Statistically significant dependence of TF of 137Cs on its concentration in soil was established for cabbage. Dependence between K content in the soil and the transfer factor of 137Cs was not found due to the high concentrations of available K. Use of bioconcentration factor (BCF) (ratio between the activity concentration of a radionuclide in a reference plant to its concentration in another plant) is demonstrated and proposed for risk assessment studies.

[The therapeutic effect of nitromint retard on patients with stable angina pectoris]. / Lecheben efekt ot nitromint retard pri bolni ot stabilna angina pectoris.

The antianginal [correction of antidiagnose] efficacy of nitromint retard was studied in 62 middle aged patients with angina pectoris in a 4 week treatment with a 24 h dose of 2.6 mg. Bicycle ergometry [correction of A veloergometria] was conducted before the treatment and at the end of the fourth week. The average number of anginal attacks decreased from 4.0 +/- 1.9 to 1.6 +/- 1.3 during the first week and to 0.0 +/- 0.7 at the end of the 3rd week. The average threshold power increased at the end of the 4th week. Nitromint retard increased considerably the tolerance to physical load and did not increase the consumption of oxygen. The desired effect was achieved in 66.13% of the patients.

[Mechanisms of the lactogenic action of thyroid hormones and nonspecific resistance in ruminants]. / Mekhanizmi na laktogennoto deistvie na tireoidnite khormoni i nespetsifichnata ustoichivost pri prezhivnite zhivotni.

Studied was the effect of thyroid hormones on the nonspecific resistance and the milk productivity of ruminant animals in the conditions of hypodynamia and in various functional conditions of the thyroid gland. Both the removal of the thyroid gland (thyroidectomy) and the hypofunction of the gland (as induced by ammonium perchlorate at 10 mg/kg body mass) were accompanied by the drop of the indices characterizing the nonspecific resistance of the animals as well as their milk productivity. The immobilization of lactating ruminant animals (hypodynamia) had a negative impact on the milk producing process, enhanced the incretion of ACTH, lowered the release of thyroid hormones (T3, T4, FT4) and decreased milk productivity, deteriorating the biologic properties of colostrum. The thyroid gland and its hormones (T4, T3) were shown to have a positive effect on milk secretion, raising the activity of the enzyme adenylate cyclase and the amount of the cyclic 3.5 cyclic adenosine monophosphate (cAMP) in the parenchymal tissue of the mammary gland.

[Effect of a chromatographically purified bile secretion on the blood protein levels in hens]. / Efekt na khromatografski prechisten zhluchen sekret vurkhu nivoto na kruvnite beltutsi na kokoshki.

The injection of chromatographically purified biliary fraction from broiler birds, rich in bile acids, led to a dependable drop of serum proteins in chickens. Treatment of the latter with a bile sample from swine, obtained in a similar way (the reaction for bile acids being negative) did not lead to essential changes in the content of plasma colloids. Results showed that bile acids were of definite importance as regards the blood level of proteins and the redistribution of proteins in the body with the individual species of animals.

[Total LDH activity and isoenzyme spectrum in experimental Cysticercus ovis infestation of lambs and kids]. / Obshta aktivnost i izoenzimen spektur na LDKh pri eksperimentalno invazirani s Cysticercus ovis agneta i kozleta.

Investigations were carried out with 10 lambs and 4 kids at the age of two months, divided into three groups. The test animals of the first group (5 lambs) were infected with 7,000 T. ovis eggs each, and those of the second group (5 lambs) and those of the third group (4 kids)--with 20,000 T. ovis eggs each. It was found that following infection the total activity of lactate dehydrogenase (LDH) rose, reaching its peak values on the 12th and 15th day. On the 12th day the strongly enhanced enzyme activity was due to the rise of LDH1, while on the 15th day the enhancement was associated with the rise of LDH5 that was characteristic of the skeletal muscles. In the period of forming the connective tissue capsule around the cysticerci the changes in the total activity and the isoenzyme spectrum were more slightly manifested. After the 30th day both the activity and the spectrum of LDH steadily came back to normal. With a C. ovis infection there was also a strongly expressed response on the part of hemopoietic organs, with a pronounced LDH3 activity.

[Biochemical and ultrastructural changes in the liver of rats with a severe form of acute radiation sickness]. / Biokhimichni i ultrastrukturni izmeneniia vurkhu cherniia drob na plukhove pri tezhka forma na ostra lucheva bolest.

Biochemical and ultrastructural studies were carried out on the liver of male rats with a severe form of acute radiation disease. The animals were treated only once with a total dose of 6.7 Gy by means of a gamma-unit Rokus at the rate of 0.9 Gy per min. It was found that with the acute and severe form of radiation disease thus produced the activity of liver enzymes with cytoplasmic localization such as SDG, GPT, and GOT strongly rose in the blood plasma over the first 24 hours following treatment. The activity of ChE as an enzyme that was specific of the endoplasmic reticulum also rose. The normal ultrastructure of hepatocytes was unaffected over the first 24 hours after irradiation. Within the period of the clinical manifestation of the disease, however, there set in strongly expressed destructive changes in the mitochondria (from the eighth to the fifteenth day). It was concluded that the changes in the liver that were characteristic of the severe form of radiation disease set in early.

[Enzymatic and morphological study of the liver in acute radiation sickness]. / Enzimno i morfologichno izsledvane na cherniia drob pri ostra lucheva bolest.

The morphologic changes in the liver were investigated along with those in the activity of the specific liver enzymes in the blood plasma of rats in the case of the severe form of acute radiation disease. The rats were treated with 670 Rad at the rate of 90 Rad/min. The studies were carried out on the 1st, 8th , 15th, 22nd, and 30th day following irradiation. It was found that under the conditions of the experiment the activity of the cytoplasmic enzymes sorbitoldehydrogenase , cholinesterase, and leucinaminopeptidase strongly rose on the 1st day after treatment (the activity of sorbitoldehydrogenase increased 11 times). The activity of acid phosphatase and glutamate dehydrogenase also increased strongly, whereupon there was deterioration of the mitochondrial and lysosomal structures. Seen were well expressed processes of fatty and parenchymal dystrophy. The studies on the changes in the activity of these enzymes can be used as an adjunct, resp., an auxiliary test to the haematologic indices in the evaluation of the severity of radiation disease.

[Leukocyte enzyme activity in the gamma-ray irradiation of lambs]. / Aktivnost na levkotsitni enzimi pri oblucheni s gama-luchi agneta.

Investigated was the activity of lactatedehydrogenase (LDH) and alkaline phosphatase (AP) of leukocytes obtained by means of urographic gradient in the clinical course of acute radiation sickness of small ruminants. The lambs were irradiated with 3.2 Gy (320 rad). It was found that the activity of AP and LDH rose in the first 20 hours following treatment, the processes of aerobic glycolysis becoming more intense in the leukocytes. The study on the activity of AP and LDH in the leukocytes could be used as an adjunct along with the use of the hematologic indices in the determination of the severity of the disease.

[Experimental mastitis in cows caused by Staphylococci, Streptococci and Corynebacteria]. / Eksperimentalni mastiti na kravi, predizvikani ot stafilokoki, streptokoki in korinebakterii.

Mastitis was experimentally induced in seven cows of the Black-and-white breed through the intramammary or i/v application of bacterial cultures of the encapsulated variant of Staph. epidermidis as well as of Str. agalactiae and Cor. pyogenes. The disease ran a course with high body temperature, strongly manifested inflammatory changes in the mammary gland, and altered phagocytic activity. It was found that the introduction into the mammary gland of a 'stable-specific' bovine blood serum in combination with the preparation nitrofuridine (a Shiff base of the 5-nitrofurfurol with sulfaguanidine) which boosts the phagocytic activity, had produced a therapeutic effect.

[Enzyme activity in the blood plasma of lambs with acute radiation sickness]. / Enzimna aktivnost v kruvna plazma na agneta pri ostra lucheva bolest.

The activity was determined of sorbitol-dehydrogenase (SDH), cholinesterase (CE), leucine-aminopeptidase (LAP), acid phosphatase (AP), and glutamate-dehydrogenase (GDH) in blood plasma of lambs irradiated with 200, 320, and 450 Rad. Results showed that with the mild form of acute radiation sickness (treatment with 200 Rad) the activity of the blood enzymes did not change. With the severe (320 Rad) and the peracute (450 Rad) forms of the disease within the first 24 hours the activity of SDH and CE rose 3 to 5 times, and that of GDH and AP--twice within a period of 1 to 3 days following irradiation. In the case of a threefold increased activity of SDH and CE within 15 to 24 hours of treatment the diseased animals died. Parallel hematologic investigations revealed that well manifested leukopenia with these two forms of the sickness took place after the 24th hour. Activity determination of the investigated plasma enzymes within the first 15-24 hours following irradiation could be used as an adjunct test to the study of the hematologic indices for the early diagnosis of the severe and peracute forms of irradiation sickness as well as for the exit of the disease.

[Aspects of the large divergence in the sialic acid level of the blood serum of poultry]. / Niakoi aspekti otnosno goliamoto razlichie v nivoto na sialovata kiselina v kruvniia seum na ptitsi.

Scanning electron microscopy made it possible to establish that there were no echocytic forms of the erythrocytes in chickens in which the blood serum level of sialic acid was below 35 and over 60 mg%. The amount of the total protein and the individual protein fractions did not correlate with the level of sialic acid. On the other hand, the high level of sialic acid could be accompanied by both low and high blood sugar content. Contrary to mammals the blood serum level of sialic acid in chickens was found to vary within a wide range. This could be explained by the amount and composition of the gall secretion which had an impact on the aging of erythrocytes and the enzyme activity of their membrane. Stated is the part played by the occasional mechanism in the 'decialization' process with regard to glucoproteins in vivo and the opinion is set forth that the mechanism of triggering the proteolytic activity of the membrane of aging erythrocytes could be associated with certain components of the bile.

Processing and migration of ribosomal ribonculeic acids in the nucleolus and nucleoplasm of rat liver nuclei.

Kinetic studies on the labelling in vivo with [14C]orotate of rat liver nucleolar and nucleoplasmic pre-rRNA (precursor of rRNA) and rRNA, isolated from detergent-purified nuclei, were carried out. The mathematical methods used for the computer analysis of specific-radioactivity curves are described. Evaluation of the experimental data permitted the selection of the most probable models for the processing of pre-rRNA and the nucleo-cytoplasmic transfer of rRNA. It was shown that considerable flexibility exists in the sequence of endonuclease attacks at critical sites of 45 and 41 S pre-rRNA chains, resulting in the simultaneous occurrence of several processing pathways. However, the phosphodiester bonds involved in the formation of mature 28 and 18 S rRNA appear to be protected until the generation of their immediate pre-rRNA. The turnover rates and half-lives of all pre-rRNA and rRNA pools were determined. The turnover rate of 45 S pre-rRNA corresponds to the formation of 1100 ribosomes/min per nucleus. The model for the nucleolus-nucleoplasm-cytoplasm migration of rRNA includes a 'nucleoplasm' compartment in which the small ribosomal subparticle is in rapid equilibrium with the respective cytoplasmic pool. At equimolar amounts of nuclear 28 and 18 S rRNA this model explains the faster appearance of labelled small ribosomal subparticles in the cytoplasm simultaneous with a lower labelling of nuclear 18 S rRNA as compared with 28 S rRNA.