[The surgical treatment of carcinoma of the extrahepatic bile ducts]. / Operativnoto lechenie na kartsinoma na ekstrakhepatalnite zhluchni putishta.

The authors have carried out a retrospective analysis of 157 patients with Ca in the extrahepatic biliary system, treated at the Clinic for Hepato-Biliary and Pancreatic Surgery within the period 1982-1992. From them 68 patients (43.31%) were with Ca in vesicule biliary and with Ca in the biliary tracts--89 patients (56.69%). The ratio men:women was respectively 1:4.67 and 1.12:1. The medium age of the patients was 63.08 years. In the group of the patients with Ca in biliary tracts the carcinoma was located in the upper third in 20.22% of the cases, in the middle third--in 24.72%, in the distal third--in 55.06%. Radical operations were made in 31.46% of the patients, with lethality 28.57%, whereas the postoperative lethality of the patients with duodeno-hemipancreatectomy was 6.67%, and the average postoperative survival was 32 months. The palliative operated patients constituted 65.17% in the general series, with lethality 15.52% and average postoperative survival 10.4 months. The explorative laparatomies constitute 3.37% from the operated patients. The total operative lethality was 19.1%. In the article the authors discussed the diagnostical methods, stated the preference for echography, computer axial tomography and retrograde cholangio-pancreatography in the mentioned sequence. The endoscopic procedures were discussed as and alternative for the non-resectable carcinomas of the biliary tracts.

[Embryotoxic and teratogenic effect of Pharmachem tetramisole]. / Prouchvaniia za embriotoksichen i teratogenen efekt na tetramizol "Farmakhim".

Studies were carried out to establish the effect of high rates of Tetramizol Pharmachim on the embryonal and fetal development in rats. The preparation was administered orally to pregnant animals under the form of a 1 per cent solution at the rate of 1/5 LD50 (=200 mg/kg), on the fourth and the thirteenth day of gestation. It was found that the amount of the preparation applied on the fourth day after conception took place led to rise of the preimplantation loss of embryos. The rate of the total embryonal mortality also rose. Accordingly, it was concluded that in high doses Tetramizol Pharmachim could produce an embryotoxic effect on rats. The application of the preparation later during pregnacy (the 13th day) did not have an adverse effect on the normal course of gestation. No abnormal effects were demonstrated on the growth and development of fetuses during all stages of investigation, which might point to the teratogenic action of Tetramizol.

[Toxicity of "Farmakhim" tetramisole in laboratory and farm animals]. / Prouchvaniia vurkhu toksichnostta na tetramizol "Farmakhim" pri laboratorni i selskostopanski zhivotni.

Tetramisole produced by ICI, England, and Tetramisole Pharmachim, Bulgaria, were comparatively studied in terms of their acute and subchronic toxicity, and the local and general tolerance and antinematode activity. No differences were found in their acute toxicity (LD50) for albino mice at oral, subcutaneous, and venous application, the index of resorption being 6.3. The same was true so far as the tolerance in calves, sheep, goats, and pigs was concerned. Orally at the rate of 45 mg/kg in sheep and over 30/kg with calves (3, resp., 2 times as high as the therapeutic dose) tetramisole produced nervous and locomotor excitement, tremor, salivation, higher respiration and pulse rate, frequent urination and defecation. Following the tenfold oral administration at intervals, of 3 days at rates of 15 and 45 mg/kg tetramisole Pharmachim did not affect unfavourably the appetite, behaviour, general status, and the clinical and biochemical composition of the blood as well as the structural pattern of the viscera in sheep. Tetramisole Pharmachim was shown to be well tolerated with regard to the conjunctivae at concentrations of up to 5 per cent, the subcutaneous tissues and muscles at conc. of up to 3 per cent, and mucous membranes of the stomach and intestines at conc. of up to 10 per cent.

[Pharmacological studies of Bulgarian gonadotropin preparations]. / Niakoi farmakologichni prouchvaniia vurkhu bulgarski gonadotropni preparati.

Experiments were carried out to prove the influence of SJK gonadotropic preparations (native and lyophilized), gravohormone and luteosiman, on the functional state of the central, the cardio-vascular and the respiratory systems, as well as that of the smooth musculature. It was proved that in doses under 20 MUI/kg t these preparations have no unfavorable effect upon the function of the cardio-vascular system (experiments were carried out on frog's hearts eliminated, on blood vessels of eliminated rabbit's ears and the hind limbs of frogs, on the blood pressure of cats and hens), upon the breathing (experiments on cats), the central nervous system and the muscular tonus (experiments on mice). In high dose SJK decreases blood pressure by slightly increasing in that direction the influence of histamine and acetylcholine. Breathing becomes uneven, stronger and accelerated. The muscular tonus is characterized by depression and decrease. A tonic effect was observed with the uterus, as well as increased contractions of the latter. The gravohormone taken in high doses provoked a decrease in blood pressure, an abatement and a depression of the tonus and motility of the eliminated uterus without any substantial changes of the rhythm and frequency of respiratory movements. In low and high doses (0,2, 20 and 60, 160 UI/kg t) it decreased the blood pressure of the narcotized hens, strengthened and increased the tonus of the motor activity of the uterus, which was probably due to residues of oxytocin.

[Acute and subchronic monensin toxicity for lambs]. / Ostra i subkhronichna toksichnost na monenzina za agneta.

The acute and subchronic toxicity of monenzine (preparation Elancoban -- 100 of Elanco Co., USA) to male lambs for fattening aged 3-4 months and weighing 16-28.5 kg was studied. It was established that the single per oral dose of 5 mg/kg weight of the natrium monoenzine salt causes a temporary lack of appetitie but no changes in the behavior and the general state of the animals. The use of a 10 and 30 mg/kg weight dose of the preparation led to death of the lambs on the 72nd-120th hour. The toxicity was clinically manifested by anurexia, arumination, ataxia, paresis, and paralysis of the limbs, tachicardia, taxipnea, hypothermia and showed down and weakened rumen movements. Erosive rumitis and abomasis, catharrhalhemorrhagis duodenitis, hemorrhages on the epicardis, hyperremia and parenchymal organ oedema, 3-4 times increased gall-bladder with numerous nodes having a sunken center on its walls were observed pathologo-anatomically, while microscopically blood vessel disturbances (hyperremia, hemorrhages and oedema) of the lungs, heart, spleen, endocrinal glands (thyroid, adrenal and hypophysis), the brain, and the leptomeninges, liver distrophy, distrophic nephrosis and necrotic holecystitis were obvious. Following a long term (30 days) application to the fodder in 10 and 50 g/t doses, monenzine-natrium does not have a negative effect on the behaviour, general condition, clinical and biochemical blood composition and the structural build up of the inner organs, but in the first 5-10 days of the treatment it causes loss of appetite. Additional specific investigations are needed to elucidate the effect of the preparation on body gain.

[Toxicological studies of the technical phosphate of Pharmachem tylosin]. / Toksikologichni prouchvaniia vurkhu tekhnicheskiia tilozinov fosfat "Farmakhim".

Studies on the acute, subchronic and chronic toxicity of technical tylosine phosphate (TTP) with 50 UI/mg activity, produced by Pharmachim were carried out. It was established that TTP does not cause lethality in white rats following application of 20, in white mice--of 40, in chickens--of 30 and in pigs--of 2 g/kg body weight. Long term application to the rations--of chickens for 40 days, in doses of 20, 40 and 60 g/kg fodder (=1.3 and 5 ED100) and of pigs for 32 days in doses of 2.6 and 10 g/kg fodder (=1.3 and 5 ED100) stimulates gain in weight of both species by 2-11.5% and improves the utilization of nutrition by 4.5-12.5% without any unfavourable effect on the clinical-biochemical composition of the blood and the structure and development of inner organs.

[Anaphylactogenic properties of Bulgarian gonadotropic preparations]. / Prouchvaniia vurkhu anafilaktogennite svoistva na bulgarski gonadotropni preparati.

Laboratory and clinical studies were carried out to elucidate the anaphylactogenic qualities of the Bulgarian goinadotropic preparations PMS (an untreated and a freeze-dried formula), gravohormone, and luteoziman. Comparatively was assessed the sensitivity of three methods employed in the routine determination of drug anaphylactogenicity. One of them is the author's personal modification of a pharmacopeia method (U. S. P. XVII)--sensibilizing doses were introduced in guinea pigs subcutaneously, once daily, in the course of three days at 3-day intervals. The resolution dose was applied intraperitoneally on the 10th day following the last sensibilizing dose. The manifestation of anaphylaxia were recorded immediately after the introduction of the resolution dose or two hours later (at the very latest). Studies revealed that the preparations tested had no equal anaphylactic properties. In guinea pigs, sheep, and cattle PMS induced allergic reactions in 50 per cent of the examined series. In these animals both gravohormone and luteoziman did not generate such response. Suggested is the use of a U. S. P. XVII modified method (as cited above) to determine the anaphylactogenicity of gonadotropic preparations; it makes it possible to qualify such preparations for a shorter time. The new modification is readily applicable at a production control basis.

[Several pharmacokinetic studies on "Farmakhim" tylosin phosphate]. / Niakoi farmakokinetichni prouchvaniia vurkhu tilozinoviia fosfat "Farmakhim".

Studies were carried out on the resorption in the digestive tract the binding with the tissue elements, the dissemination within the body, and the residual amounts of tylosine "Pharmachim" phosphate and its pelleted drug formulation tylosine-200. It was found that tylosine-200 was well resorbed by the intestinal mucosa of pigs and birds, and was weakly and variably utilized by calves. The blood concentrations of tylosine-200 in pigs and birds in the first hours following treatment surpassed by 1 to 5 times those resulting from the administering of the analogous therapeutic formula Tylan AF 99 of the Elanco Firm. The tylosine phosphate was found to combine reversely with the tissue in birds and pigs. The quantitative indices of this process were used to specify the actual content of the antibiotic in the body. Experiments with birds and pigs revealed that the tylosine phosphate released from tylosine 220 pellets invaded to a virious extent organs, tissues, and fluids and passed through seroses, and the blood-brain and blood-ocular barriers. It was excreted in substantial amounts with the urine and the bile. It was established that on the 5th day after the administration of the drug was discontinued the body of mammals and birds was practically free from the preparation. No differences in the distribution within the body and the retention were found between tylosine-200 and Tylan AF 99.

[Long-term follow-up of mitral commissurotomy patients from Razgrad District]. / Produlzhitelno proslediavane na bolni s mitralna komisurotomiia ot Razgradski okrug.

The authors observed 51 patients after mitral commisurotomy was performed for 1 to 12 years. After the operation the number of the decompensations and the rhythm disturbances had decreased. Twenty six subjects are back at the same work place, 23 retired on pension or changed their work, two died. The mitral commisurotomy appears the only ailing method in advanced cases of mitral stenosis. The active dispensary treatment is an important stage prior to the operation as well as after it.