Kr. Petrov(1), G. Kobakov(1), M. Manova(2), К. Mitov(2), A. Savova(2) and G. Petrova(2)
(1)Specialized Oncology Hospital for Active Therapy “Dr. Marko Markov”, Varna, Bulgaria
(2)Medical University Sofia, Faculty of Pharmacy, Bulgaria

Summary. The purpose of this study was to evaluate the possible superiority in pharmacological protective effect of sevoflurane compared to isoflurane in patients with liver segmental or lobe resections, through examination of postoperative changes in the liver enzymes ALT and AST and the impact of the choice of anesthetic on surgical hospital charges. It is a prospective study based on the examination of surgical patients. A retrospective cost study analysis after approval of local ethics committee was also performed. Patients with surgical liver resections were divided in two groups according to the main volatile anesthetic used − isoflurane (n = 25) and sevoflurane (n = 17) group. All patients were tested for both liver enzymes AST and ALT before and after the surgery. The health care resources used during the anesthesia were collected. Mean time of operation, minimal alveolar concentration (MAC), average anesthetic quantity used, fresh gas flow, and cost for maintaining anesthesia were calculated. The cost for maintaining anesthesia was compared with the surgical hospital charges. No statistically significant difference has been observed between the two groups according to patients’ age, type of liver resection, as well as hospital stay (р > 0.05). Comparing the postoperative levels of AST and ALT, we found that their levels were higher in the group of patients on isoflurane. Levels of both ALT and AST were significantly lower, and decreased more rapidly in patients receiving sevoflurane than those receiving isoflurane from 1st to 5th postoperative day. The decrease was almost twice faster in the group on sevoflurane and close to normal physiological levels. All hospital costs appear to be equal in both groups except the cost of maintaining anesthesia that represents 1.67 per cent of hospital charges in the group on sevoflurane and 0.41 per cent in the group on isoflurane. In conclusion, for patients that are going to have liver resection, the preferred main anesthetic in the complex of balanced anesthesia should be sevoflurane, which decreases the AST and ALT levels significantly. For both anesthetics the total cost for maintaining anesthesia is an insignificant part of the surgical hospital charges and the choice of anesthetic should be based on clinical results rather than on economical ones.
Key word: anesthesia, sevoflurane, isoflurane, anesthesia cost, liver resections, ALT, AST


M. Manova(1), A. Stoimenova(1), L. Peikova(2), P. Peikov(2) and G. Petrova(1)
Faculty of Pharmacy, Medical University – Sofia
(1)Department of Social Pharmacy and Pharmacoeconomics
(2)Department of Pharmaceutical Chemistry

Summary. The goal of the current study is to analyze the patent protection status of medical products included in the therapeutic class аngiotensin II receptor antagonists or sartans. The analysis covered the period 1995-2008. A three – step internet patent database search methodology was applied in searching EPO, Orange book and Patent watch. Applications were systematised per IPC code, territory, manufacturer and date of patent issuing. The patent activity depends on the time of expiration of the main patent. The highest number of patents granted for IPC class A61K is due to the fact that this class is related with the therapeutic possibility of the formulations. Per territory protection activity is similar in regard to the prefered countries and follows the market dynamics. For some of the products additional factors might play an important role. Our study shows that a variety of factors are influencing the patent protection policy, such as the time of discovery, product application, disease priority, technologies etc. It appears that the therapeutic competition is more important than the generic one related to establishment of patent profile of particular INN. This is in contrast with the beliefs that the patent protection policy affects mainly generic companies.
Key words: Angiotensin II receptor antagonists, patent protection, patent policy


D. Obreshkova(1), D. Tsvetkova(1) and K. Ivanov(2)
(1)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University – Sofia, Bulgaria
(2)Department of Pharmaceutical Sciences, Faculty of Pharmacy, Medical University – Plovdiv, Bulgaria

Summary. L – Arginine is an essential, proteinogenic amino acid and is involved in metabolic pathways, such as protein degradation, synthesis of creatine, citrulline, L – ornithine, L – glutamate, agmatine, proline, polyamines, urea, etc. The aims of the current study were: 1) to collect data for manufactured combined supplements, containing L – Arginine; 2) to analyse the collected data; 3) to estimate the number of multipreparations with L – Arginine, according to their form; 4) to summarize which are the most common combined supplements with L – Arginine. The performed observational study showed that in most cases L – Arginine was combined with: L – Citrulline, L – Glutamic acid, L – Lysine, L – Ornitine and Vitamin B6.
Key words: L – Arginine, HPLC, accuracy, precision, linearity


A. Savova, A. Stoimenova, M. Manova and G. Petrova
Department of Social Pharmacy and Pharmacoeconomics,
Faculty of Pharmacy, Medical University

Summary. The objective of the study is to investigate and calculate the direct medical costs of osteoporosis, the indirect ones, as well as the family costs in Bulgaria. A top down retrospective cost study has been developed. Epidemiology data for osteoporosis has been derived from two published reports. The information on the prices of medicines, patient co-payment, level of reimbursement, hospitalization cost and average hospital stay is based on the official national sources. Official information provided by the National Health Insurance Fund is that in 2009 only 2,143,046 BGN for 5,950 treated patients were paid. The annual cost of femoral fractures should be 8 million BGN, and 800,000 BGN for rehabilitation. The rest of the fractures are mild and account for 26,950,000 BGN. The average disability loses account for approximately 23,105,472 BGN. The direct medical cost exhibits the proportion of 2 million for medicines to 36 million BGN for treatment of fractures. The major conclusions from our analysis are that the patients with osteoporosis in Bulgaria are not adequately treated in terms of reimbursement coverage and patients carry the greater part of financial and social burden.
Key words: cost study, pharmacotherapy, osteoporosis, health policy, medicines policy


M. Velizarova(1), D. Popova(2), E. Hadjiev(3), N. Dimitrova(4), I. Dimova(5),
D. Toncheva(5) and K. Tzatchev(1)
(1)Department of Clinical Laboratory and Clinical Immunology, Alexandrovska University Hospital
(2)Department of Clinical Laboratory and Immunology, Military Mediacal Academy
(3)Clinic of Hematology, Alexandrovska University Hospital
(4)National Oncological Hospital, Bulgarian National Cancer Registry
(5)Departments of Medical Genetics, Medical University – Sofia

Summary. Leukemic cells from a significant number of adults with acute lymphoblastic leukemia (ALL) show aberrant co-expression of myeloid-associated markers. We studied the incidence and relations of myeloid-antigen (MyAg) expression to molecular-cytogenetic features of ALL and to outcome. Leukemic blasts from 33 newly diagnosed adults with untreated ALL were examined for myeloid surface antigen expression. The simultaneous expression of lymphoid-associated antigens and myeloid-associated antigen (CD33, CD13, CD15) on leukemic cells was detected by a standard two-color direct immunofluorescent assay. As a result, MyAg(+) ALL was established in 45% of the B-cell lineage. Immunologic subtyping of B-ALLs revealed an association between common B phenotype and coexpression of myeloid antigens – 53% of MyAg(+)ALL (P < 0.05). Various cytogenetic abnormalities, associated with MyAg(+) ALLs, were detected, including t(9;22), 11q23 abnormalities, del 4p, and del 12p. No differences in complete remission rate (p = 0.51) and overall survival (p = 0.75) were observed between MyAg(+) and MyAg(-) patients. In conclusion, a high incidence of poor prognostic chromosomal aberrations was recorded in MyAg (+) cases, but the aberrant myeloid antigen expression was not shown to have an impact on the outcome of B-ALL.
Key words: cytogenetic aberrations, myeloid antigens, adult ALL, survival

St. Sopotensky and Al. Cervenjakov
University hospital “N. I. Pirogov”, 1st Surgery Clinic

Summary. The aim of this study is to describe our technique of video-assisted thoracoscopy without fundoplication for surgical treatment of achalasia. The method is developed by surgeons from University hospital “N.I. Pirogov” and applied in 30 patients with achalasia during the years 2002-2010. It is a video-assisted thoracoscopic method applicable for benign processes of the cardia, involving the use of fibrin glue. The technique comprises two main stages: video-assisted thoracotomy (VATS) – cardiomyotomy and application of fibrin glue “TISSUCOL”. The first characteristic of the thoracoscopic approach is that it is not very common for non – invasive techniques. An advantage of its application is that it is associated with improved recovery period and lack of any symptoms of recurrence. We did not have surgical mortality. The frequency of the postoperative heartburn was significantly lower than that in the case of an open procedure and could be managed by medicines relatively easily, which allows the avoidance of the antireflux surgical procedure. This is an advantage in such cases in which preliminary therapeutic approaches had been applied. The third specificity is the application of the fibrin glue as a sealant. To our knowledge this is the first technique in which the glue is applied during the thoracoscopic myotomy. The adapted surgical thoracoscopic Heller’s myotomy in the treatment of achalasia, elaborated by our team, is a safe and efficacious method for surgical treatment of patients with achalasia.
Key words: Achalasia, adapted Hellers’ myotomy, VATS, thoracoscopic surgery

Т. Тurnovska(1), St. Kostianev(2), B. Мarinov(2) and St. Mandadzhieva(2)
(1)Department of Hygiene, Ecology & Epidemiology,
(2)Department of Pathological Physiology, Medical University – Plovdiv, Bulgaria

Summary. The objective of this study was to perform a full functional examination of the external breathing of two cohorts healthy children, living in the same areas, but under the influence of different low levels of air pollution. The following methods were used: First cohort (I) 27 boys at age 10.47 ± 0.49 y and 38 girls at age 10.29 ± 0.46 y were examined in years 1996, 1997, 1998, 1999; Second cohort (II) – 34 boys at age 10.47 ± 0.51 y and 27 girls at age 10.37 ± 0.49 y had lived in conditions of lower level of pollution; they had visited the same schools as the children of the First cohort and were examined in years 2001, 2002, 2003 and 2004. All 8 series of the study were conducted in the Pulmonary Function Testing Laboratory of the Medical University of Plovdiv. The results obtained in the present investigation suggest that the average levels of respiratory indices have significantly lower average values in the first cohort compared to the second one: VC%pred (Vital capacity as a % of predicted value): 94.99 (I) vs. 99.88% (II), P = 0.000; FVC%pred (Forced vital capacity as a % of predicted value): 92.09 (I) vs. 100.94% (II), P = 0.000; FEV1%pred (Forced expiratory volume per 1 s as a % of predicted value): 100.40 (I) vs. 109.09 (II), P = 0.000, etc. The following conclusions were made: 1. The restrictive effect of air pollution on respiratory functions has been established, even when it is below the admissible levels. 2. The pubertal stimulus in development contributes to the compensation of the lower lung function parameters from early childhood, but some unfavorable tendencies continue to persist.
Key words: children, low levels of air pollution, pulmonary functions

Kr. Todorova(1), S. Hayrabedyan(1), J. Dineva(1), I. Vangelov(1), D. Zasheva(1), V. Penchev(2),
G. Nikolov(2), M. Mollova(1) and M. Ivanova(1)
(1)Institute of Biology and Immunlology of Reproduction, Bulgarian Academy of Sciences
(2)Medical Center “REPROBIOMED”

Summary. Selecting oocytes with normal developmental competence is of great importance in assisted reproductive technology. We suspect that the expression of specific genes in cumulus cells would affect the developmental competence of the oocyte and these genes may be used as prognostic indicators for successful in vitro procedure. We investigated cumulus cells samples (n = 39) from women who had a reproductive problem, and were participating in ICSI procedures, as well as cumulus cells samples (n = 9) from women who were from male factor sterility couples. The total number of women been examined was 16. In our study we used quantitative real-time PCR to estimate the differential gene expression levels of sex determining region Y-box (sox9), myb, vascular endothelial growth factor (VEGFA), N-cadherin (CDH2) gene transcripts, normalized to phosphoglycerate kinase (PGK1). We observed increased levels in gene expression of SOX9 transcripts in women with primary sterility compared to women from male factor sterility couples. 2D PAGE showed differential spots, subject to software analysis that revealed putative targets based on spots Mr and pI. Our study suggests that these genes could be putative candidate markers for non-invasive assessment oocyte competence.
Key words: Cumulus oocyte complex, SOX9, MYB, VEGFA, NCDH, 2D PAGE



P. Nenoff(1), M. Peter(2), G. Tchernev(3), G. Mulyowa(2), E. Amerson(4), U. Paasch(5) and J. Ananiev(6)
(1)Laboratory for Medical Microbiology, Mölbis, Germany
(2)Skin Clinic, Department of Dermatology, Mbarara University of Science and Technology, Mbarara, Uganda, Africa
(3)Policlinic of Dermatology and Venerology, University Hospital Lozenetz, Academic
Educational Hospital of the Saint Kliment Ohridski University, Medical Faculty, Sofia, Bulgaria
(4)Department of Dermatology and Venerology, University of California, San Francisco, USA
(5)Department. of Dermatology, Venerology and Allergology, University of Leipzig, Leipzig, Germany
(6)Department of General and Clinical Pathology, Medical Faculty, Trakia University, Stara Zagora, Bulgaria

Summary. Lichen striatus is a rare, benign, self-limited, mostly asymptomatic, inflammatory condition of unknown etiology, typically occurring in childhood. It is rare in adults. The unilateral papular lesions have a linear morphology following the lines of Blaschko. The most commonly involved sites of the lichenoid lesions are the limbs. Differential diagnosis should consider other blaschkoid and papular dermatoses, such as linear psoriasis, linear atopic dermatitis, linear lichen planus, inflammatory linear verrucous epidermal nevus (ILVEN), and, in particular, the so-called “Blaschkitis”. A 30-year old HIV-negative patient from Uganda suffered from lichen striatus of his left arm, chest, and palm. Diagnosis was made based on the characteristic clinical picture and medical history of the disorder. A 13-year old Ugandan boy showed strand-like papular hyperpigmented and hypopigmented lesions of his right arm. This is the first description of lichen striatus in Sub-Saharan-Africa, in particular in Uganda. It is suggested that lichen striatus could be found much more frequent in tropical and subtropical countries however not published.
Key words: Lichen striatus; linear papular dermatosis; Blaschkitis; Uganda; Sub-Saharan Africa, tropical dermatosis



Ju. Ananiev(1), X. Baraliakos(2) and G. Tchernev(3)
(1)Department of General аnd Clinical Pathology, Medical Faculty, Stara Zagora, Bulgaria
(2)Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany
(3)Policlinic of Dermatology and Venerology, Saint Kliment Ohridski University, University
Hospital Lozenetz-Academic Teachning Hospital of the Saint Kliment Ohridski University, Medical Faculty, Sofia, Bulgaria

Summary. A patient is presented with a history of subacute cutaneous lupus erythematodes (SCLE), appearing immediately after an intensive exposure to UVA rays. The relapse of the diseases was established in the form of the so-called “Rowell syndrome”. Literature data relating to the pathogenesis and the existence of this rare clinical variant of SCLE is contradictory to date. The paper emphasizes critical key points relating to the diagnostics of the Rowell syndrome and its precise restriction by Erythema Exudativum Multiforme (EEM) as well as the possibility for a parallel manifestation of both conditions.
Key words: Rowell syndrome, subacute cutaneous Lupus erythematodes, target lesions, EEM, SSA


E. Boteva(1) and D. Iovchev(2)
(1)Department of Conservative Dentistry, (2)Department of Oral Rentgenology and
Oral Diagnostics, Faculty of Dental Medicine, Sofia, Bulgaria

Summary. The macromorphology of pulp chambers has been studied in the last few decades, but there is a lack of knowledge on the sizes of the pulp chambers of molars. The aim of the present study was to measure the size of the pulp chambers of upper and lower molars with different root curvatures and to compare them with the same dimensions in molars without root curvatures. Seventy-seven upper and lower molars, matured, fully mineralized and sound were selected in the following groups: two groups, including upper and lower teeth, respectively and three groups, divided as follows: with straight roots up to 25-30º, with severe curvatures up to 45º and with abnormalities 45º-90º from the axial axis. Three dimensions of the crowns were measured for each tooth in mm: one mesio-distal and two bucco-lingual dimensions, one of then being measured from the top of buccal cusp to the top of the mesio-lingual (palatal) cusp. All teeth were submitted to X-rays and were photographed after opening the pulp chambers. Measurements of the pulp chambers were made after opening with horizontal cuts, made 1 mm apically from the equator with a diamond blend. The two buccolingual dimensions were refered to as L1 and L2, the mean value – as L and the mesio-distal – as MD, sizes were measured in the widest part of the pulp chamber with an endodontic file and endoblock in mm. A careful approach to these sizes of the pulp chambers of the molars with severe curvatures can safe hard dental tissues during endocavity and pulp chamber preparation .These findings are important for the prevention of crown and root fractures, and teeth loses and for lowering the use of posts and pins and the use of crowns and bridges in young age groups.
Key words: endodontics, curved root canals, pulp anathomy


E. Boteva(1) and D. Yovchev(2)
(1)Department of Conservative Dentistry
(2)Department of Imaging and Oral Diagnostics, Faculty of Dental Medicine, Sofia, Bulgaria

Summary. Curved root canals are a challenge for instrumentation, preparation, irrigation and obturation. The aim of the present study was to find the working length and irrigation efficiency in root canals with curvatures 30º-45º and in root canals with anatomical abnormalities 45º-90º. Sixty-eight human, matured, extracted molars with 201 root canals were included in the study. Molars were placed in three groups in relation to the angle between the root and the axis. The first group of molars – straight – 25º-30º, was the control group, n = 14 teeth – 45 root canals; second group – 25-30º to 45º, n = 22 teeth with 66 root canals; third group – 45º to 90º (n = 31 teeth with 96 root canals). Measurements: mesio-distal buccal size of the chamber in its largest part and both bucco-lingual sizes – the mesio dimension was refered to as L1 and the distal one – as L2. Root canal preparation: extraction of the root pulp with K endofiles number 6, 8, 10, with Step Down and Balance force techniques. Canals length was measured rentgenologically using intraoral radiography, preparation continued after X-ray analysis of the level of penetration of irrigants with contrast solution of diluted Urograffin 66%. Regime of active irrigation: same for all groups with 2 % H2O2 and 1% NaOCl and paper points drying. To follow up the results a fourth radiography was used and a second one with Urograffin. The applied criteria for working length and for penetration of the irrigant were as follows: 3 – whole working length, 2-1 mm shorter than the working length, 1-2 mm shorter than the working length and 0 – more than 2 mm shorter than the working length. X-ray – working length detection of molars with root canal curvatures was more accurate, compared with straight roots, due to curved canals in straight roots and inadequate instrumentation. The active irrigation was more efficient in curved root canals, because in straight canals most of the irrigant was lost back in the mouth or periapically. In straight root canals only moisturizing (Miller pins) the canal could be more effective and less dangerous.
Key words: endodontics, working length, curved root canals


N. Dimitrov, P. Tsekov and B. Matev
Clinic of Surgery of the upper limb
USHATO – “Prof. B. Boychev”

Summary. The shoulder joint is most vulnerable to dislocation. Anterior dislocation is common, while the posterior one is very rare – about 4% of all dislocations of the shoulder. Because of this, the diagnosis is frequently missed at the initial examination – McLaughlin called the situation a “diagnostic trap”. The surgical treatment of posterior dislocations initially aimed at reduction of the joint. However, this is not sufficient for aging dislocations. Stability is to be provided. In recent years, the promotion of arthroscopic treatment is becoming increasingly important, especially given for its indisputable advantages. In the Department of Surgery of the Upper Limb in the University Specialized Hospital for Active Treatment in Orthopedics USHATO – “Prof. B. Boychev” for the period 2005-2011, were operated 12 patients (8 men and 4 women – a total of 12 shoulders). All had persistent posterior dislocation of the shoulder as a result of injury, after a lapse of between 3 and 8 months – an average of 4.5 months. In all cases an osteohondral defect from 25 to 45% (average 30%) located on the front surface of the head of the humerus was set. Surgery: Seven patients were first operated through arthroscopic reduction and then stability was restored by transposition of m.subscapularis in the osteohondral defect. Five patients were operated without prior arthroscopic reduction – only through open surgery. Follow-up period was from 6 months to 6 years (3 years averagely). The reported results indicate that abduction, flexion and internal rotation increased much more rapidly and to a larger volume in patients in which first arthroscopic reduction was made, compared with those where it was held via conventional surgery, due to its larger volume and greater operational trauma. These results were also confirmed using two post-operative function of the shoulder joint scoring systems: Murley Constant Score and UCLA.
Key words: posterior locked luxation of the shoulder, arthroscopic-assisted reduction, stability

  © 2009