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Review articles

Volume 41, 2005


Pulmonary hypertension – diagnostic and therapeutic challenge - 41, 2005, № 4, 5-11.
Zl. Iankova
Department of Pulmonology, Medical University – Plovdiv
In the first half of the XX century, the published reports on primary pulmonary hypertension (PPH) were confined to clinical pathological correlations. In 1950s, the physiological epidemiologic studies emerged triggered by an epidemic of PPH, due to the ingestion of an appetite suppressant, аminorex fumarate. Progress in the understanding of PPH catalysed the classification of all pulmonary hypertensive diseases. The etiologic basis of the classification enhances the prospects for a unified approach to diagnosis and therapy.
Key words: primary pulmonary hypertension, secondary pulmonary hypertension, clinical pathological correlations, classification
Address for correspondence:
Assoc. Prof. Zl. Iankova, M. D., Department of Pulmonology, Medical University, 66, Peshtersko shose Str., Bg 4004 Plovdiv, е-mail: zl_yankova


Neoplasms in patients with renal transplantation - 41, 2005, № 4, 12-15.
E. Paskalev
Clinic of Nephrology and Transplantation, University Hospital "Alexandrovska" – Sofia
: Renal transplant recipients need immunosuppressive therapy. The long-term use of immunosuppressive agents increases the risk of neoplasms in patients after renal transplantation. The types of cancers encountered in transplant recipients are different from those found in normal population, with a higher frequency of squa­mous cell carcinomas of the skin, non-Hodgkin lymphomas, in situ carcinomas of the uterine cervix, hepatobiliary carcinomas, and variety of sarcomas. The frequency of tumors in the transplant population is 100 times higher than that in general po­pulation, and the frequency of tumors seen commonly in the general population – lung, breast, prostate, colon, does not increase and may in fact be even lower af­ter transplantation. If all cancers are considered, the average time of their appearance is 61 months after transplantation. The most common post-transplant can­cers are those of the skin and lips, with a frequency of 37%. Of the skin cancers, squamous cell carcinomas are more common than basal cell carcinomas, whereas the reverse is true in the general population. Next to cancers of the skin, lymphoproliferative disorders are among the most serious and potentially fatal, accounting for 21% of all malignant neoplasms in this population. The other neoplasms like hepatobiliary carcinomas, in situ carcinomas of the uterine cervix, and a variety of sarcomas have lower frequency than those of skin and lymphomas. The goal of the review is to show the importance of neoplasms in renal transplant patients.
words: renal transplantation, immunosuppression, neoplasms
Address for correspondence: Assoc. Prof. Emil Paskalev, M. D., Clinic of Nephrology and Transplantation, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg
1431 Sofia, tel. +359 2 923-02-40, e-mail:


Q-fever - basic clinical features- 41, 2005, № 4, 16-21.
M. Tiholova and A. Goceva

Department of Infectious Diseases and Tropical Medicine, Medical University - Sofia
Summary: Q-fever is a zoonosis caused by Coxiella
burnetii. It has been reported from all continents. It occurs in epidemic or sporadic forms. The infection in humans is variable in its clinical manifestation, in its severity and its natural course – acute or chronic. As an acute disease, it can be manifested as fever, pneumonia, hepatitis, cardiac involvement, meningitis or encephalitis. In some patients, acute infection can lead to chronic infection, and in pregnancy, stillbirth or prematurity can be the result. Endocarditis may occur in patients with valve lesions or cancer. Because of the wide spectrum of clinical manifestations, the non specific nature of symptoms and the ignorance of the disease, the diagnosis is usually late and the patients are treated unproperly. This poses the necessity to summarize and to present the clinical symptoms of the still not wellknown disease.
Key words: Q-fever, Coxiella burnetii infection
Address for correspondence:
Assoc. Prof. M. Ticholova, M. D., Department of Infectious Diseases and Tropical Medicine, Medical University, Bg – 1431 Sofia, 17, Acad. Iv. Geshov Str., tel. +359 2 952-26-97, e


Brain renin-angiotensin system in blood pressure regulation and pathogenesis of experimental arterial hypertension - 41, 2005, № 4, 22-28.
E. Lakova
Department of Pathophysiology and General Biology, Medical UniversityPleven
Summary: The local brain renin-angiotensin system (RAS) exists independently of classical circulatory RAS. The brain RAS components have been identified in brain neurons and glial cells by different methods of biochemistry, histochemistry and molecular biology. The brain RAS plays an important role in short- and long-term blood pressure regulation increasing sympathetic activity, blunting baroreflex sensitivity, stimulating pituitary hormone secretion, as well as water and salt intake. Experimental results show that angiotensin and its metabolites are important brain peptidergic mediators in different animal models of hypertension: spontaneous hypertension in rats (SHR), chronic phase of one-clip, two-kidney hypertension, DOCA-salt hypertension, and transgenic models of hypertension. New trends in antihypertensive therapy under experimental and clinical conditions will be derived from our undеrstanding of the brain RAS dysfunction in hypertension.
Key words: brain renin-angiotensin, blood pressure, arterial hypertension
Address for correspondence:
Emilia Lakova, M.D., Ph.D., Medical University, 1, Kl. Ochridski Str., Bg – 5800 Pleven, tel.  + 359 64 884 252, e-mail:


GABA and modulators of GABA-mediated neurotransmission - 41, 2005, № 4,29-33.
R. Nikolov and Kr. Yakimova
Department of Pharmacology, Medical UniversitySofia
Summary: The establishment of gamma-aminobutyric acid (GABA) as an inhibitory neurotransmitter, as well as the discovering of a highly selective process of GABA-reuptake and cloning of specific GABA-ergic receptors can be characterized as a big progress in the pharmacology of GABA. In the present review, there are described the modern conceptions about GABA synthesis and activation of specific GABA-ergic receptors, as well as neuronal and glial reuptake mechanisms and GABA metabolism. The contemporary view of main GABA-ergic receptors (GABA(А), GABA(В) and GABA(С)) is presented, as well as of drugs and other pharmacologically active agents, modulating GABA-ergic neurotransmission.
Key words: gamma-aminobutyric acid, GABA(А) receptors, GABA(В) receptors, GABA(С) receptors
Address for correspondence:
Rumen Nikolov, M. D., Department of Pharmacology, Medical University, 2, Zdrave Str.,  Bg1431 Sofia, tel. +359 2 91-72-622, e-mail:


Insulin resistance in metabolic syndrome and methods for its measurement - 41, 2005, № 4, 34-40.
M. Petkova, N. Petrova and S. Ganeva
Clinic of Endocrinology, University Hospital – Pleven
Summary: In recent years, a new clinical syndrome has been described, that is a major concern of serious clinical researches. It features a cluster of clinical disorders, which are interdependent. It is considered that the insulin resistance is the cause of all the components of the syndrome. This syndrome has been given many names, but its most populare name is the insulin resistance syndrome. This name is justified by the idea that insulin resistance is the major common denominator of the abnormalities involved in the syndrome. The importance of insulin resistance is connected with its role as risk factor for development of glucose intolerance, cardiovascular morbidity and mortality. The early recognition and treatment of insulin resistance seems to have investigational and clinical relevance in screening and prevention subjects at high risk of type 2 diabetes mellitus and cardiovascular disease. Therefore, measurement of insulin resistance is important for identifying of the affected individuals. This article summarizes some of the moleculare mechanisms of insulin resistance and some of the most useful techniques for assessing insulin resistance. It makes a review of the use of HOMA-model and comparison with other well validated methods. HOMA has the advantage of requiring only a single sample assayed for insulin or glucose. The HOMA-model is validated as a rapid, accurate and low-cost method, which can be used in large epidemiological studies.
Key words: metabolic syndrome, insulin resistance, quantitative estimation
Address for correspondence:
Natalia Petrova, M. D., Clinic of Endocrinology, University Hospital, 8A, G. Kochev Str.,  Bg5800 Pleven, tel. +359 64 886 642, +359 887 553856, e-mail:


Contemporary views on the surgical treatment of serous otitis media in childhood - 41, 2005, № 4, - 41, 2005, № 4, 41-43.
D. Vicheva
Department of Otorhinolaringology, Medical UniversityPlovdiv
Summary: Otitis media with effusion is defined as the presence of fluid in the middle ear without symptoms of acute ear infection. In most children and especially following an episode of acute otitis media, otitis media with effusion will resolve for 2 or 3 months. Hearing loss is usually mild, but may impair cognitive and language function in children and result in disturbances in psychosocial adjustment.
Key words: otitis media with effusion, children, surgery
Address for correspondence:
Dilyana Vicheva, M. D., Department of Otorhinolaringology, Medical University, 81A, Il. Makariopolski Str., Bg – 4000 Plovdiv, e-mail:


Orthognatic surgery – helping surgical interventions and mandibular reconstructions - 41, 2005, № 4, 44-51.
A. Djorov
Department of Oral and Maxillofacial Surgery, Faculty of Stomatology, Medical University – Sofia
The paper presents the most used auxiliary surgical interventions (extractions, frenulotomies, germectomies, uncovering and moving of teeth, reductional plastics of the tongue, compactosteotomies) of the complex treatment of dento-maxillo-facial anomalies and deformations. The correct indications help for more effective, faster and stable result. Presented are segmental mandibular osteotomies, reconstructions of the body and ramus mandibulae, and the temporo-mandibular joint, and the mentoplasty. The basic indications of their use are shown. The methods are characterized on the base of literature data and own surgical experience of the author.
Key words: orthognatic surgery, mandibular reconstructions, osteotomies
Address for correspondence
: Anton Djorov, D. D., Department of Oral and Maxillofacial surgery, Faculty of Stomatology, Medical University, 1, Sv. G. Sofiiski Str., Bg – 1431 Sofia, tel. +359 2 9625579, +359 2 8684365, e-mail:



Primary insomnia - 41, 2005, № 3, 5-9
I. Staikov and E. Vavrek

Department of Neurology, University Hospital “Tzaritza Ioanna” – Sofia
Summary: Insomnia is a frequent health problem, which afflicts about one third of the population. Women and elderly people have higher prevalence. Insomnia is usually a symptom of a somatic or psychic disease. The group of primary insomnia merges disorders without another sickness – psychophysiological insomnia, idiopathic insomnia, sleep state misperception. The diagnosis of insomnia includes history, examination and polysomnography. Patients with psychophysiological insomnia demonstrate true sleep difficulties. Excessive worries about not being able to fall asleep maintain the insomnia. Usually an external stress event is necessary to start insomnia. It is characterized by increasing the sleep latency and sleep is more difficult in regular setting. The patients with idiopathic insomnia have organic hyperarousal. The sleep disturbances like increased sleep latency, disturbed sleep activity, increased frequency and duration of awakenings are accompanied by daily symptoms. Subjective complaints of persistent insomnia are typical for sleep state misperception when there is a lack of objective polysomnographic data for sleep disturbance. The treatment of primary insomnia consists of behavioral therapy, sleep hygiene and medical treatment, which is strongly individualized in idiopathic insomnia.
Key words: primary insomnia, psychophysiological insomnia, idiopathic insomnia
Address for correspondence:
Ivan Staikov, M. D., Neurology Clinic, University Hospital “Tzaritza Ioanna”, 8, Bialo more Str., Bg - 1527 Sofia, tel. +359 2 943-25-71, е-mail:


Trends in asthma epidemiology: expenditure of health resources and impairment of quality of life life - 41, 2005, № 3, 10-18.
G. Christoff

Clinic of Allergology, University Hospital “Alexandrovska” – Sofia
Summary: In spite of all efforts that have been exerted to develop, promote and stick to different international guidelines for diagnosis, differential diagnosis and treatment of bronchial asthma, the trends in its epidemiology are permanently negative. The increase in disease’s mortality and morbidity as well as in the level of utilization of health resources is more than clear. Bronchial asthma nowadays is an illness with great social and economic impact on patients’ and their families’ quality of life through the impairment it causes. The author reviews recently published data on the use of health care resources for asthma treatment.
Key words: asthma, epidemiology, health resources, quality of life
Address for correspondence:
George Christoff, M. D., Clinic of Allergology, University Hospital “Alexan­drovska”, Bg - 1431 Sofia, 1, Sv. G. SofiiskiStr., e-mail:

Nasal trauma - 41, 2005, № 3, 19-22.
D. Vitcheva
Department of Otorhinolaryngology, Medical University – Plovdiv
Summary: The diagnosis of nasal trauma begins in various settings, because the population of patients and injuries involved are diverse. Rhinologists may have initial contact with patient who has sustained nasal injuries in the outpatient setting, the emergency room, or the operating room. To diagnose nasal trauma accurately in each of these settings, the history, examination, and ancillary investigations should be performed scrupulously.
Key words: nasal trauma, diagnosis
Address for correspondence:
Dilyana Vicheva, M. D., Department of Otorhinolaryngology, Medical University, 81A, Il. Makariopolski Str., Bg - 4000 Plovdiv, e-mail:

Specific features of renal transplantation in childhood - 41, 2005, № 3, 23-30.
Kirov and E. Jordanov

Clinic of General and Operative Surgery, University Hospital “Sv. Marina”
Summary: Every year 1 of 65 000 children in
USA develops end stage renal failure (ESRF). Till 1955 this disease was incurable. Thanks to progress in surgical techniques and immunosuppression, death rate in children due to ESRF has dramatically decreased. Approximately 1 of 4 children with ESRF is hospitalized for transplantation because of urologic abnormalities. Renal transplantation has become a method of choice in the treatment of ESRF in children population. Because of lack of cadaver organs, a score system for a just distribution of kidneys was developed. Urological complications are the most frequent surgical complications after transplantation. In the past, 70% of transplant patients have developed infection. The incidence of infections now is decreased to 15-44.1%, and the mortality caused by infections is less than 5%.
Кey words: transplantation, donors, recipients, immunosuppression, children, surgery, complications
Address for correspondence:
K. Kirov, M. D., Clinic of General and Operative Surgery, University Hospital "Sv. Marina", 1, Hr. Smirnenski Str., Bg - 9010 Varna


Significance of obesity in renal transplant patients - 41, 2005, № 3, 31-35.
Е. Paskalev
Clinic of Nephrology and Transplantation, University Hospital "Alexandrovska"
Summary: Renal transplantation is currently considered the treatment of choice for most patients with end-stage renal failure. Survival of renal allograft is limited by many factors. Based on previous studies and local data and experience, some centers currently consider obesity as a significant risk factor for renal transplantation. The goal of this review is to make a survey of current literature regarding the relationship between obesity and outcome of renal transplant patients. Data were analyzed with regard to patient morbidity, mortality, graft survival, acute rejection, delayed graft function, and many complications. We established that obesity is important risk factor significantly associated with higher mortality, reduced allograft survival and higher frequency of perioperative complications. Obesity and extremely increase of body weight following transplantation are significant causes of diabetes and cardiac complications. Reductions of body weight by 5-10% in a period of at least six months may reduce the risk related to renal transplantation in obese patients with end-stage renal failure.
Key words: renal transplantation, risk factors, obesity
Address for correspondence:
Assoc. Prof. Emil Paskalev, M. D., Clinic of Nephrology and Transplantation, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, tel. +359 2 923-02-40, e-mail:


Biological agents - a new therapeutic approach to rheumatoid arthritis - 41, 2005, № 3, 36-44.
A. Tontcheva(1) and D. Ianeva(2)

(1)Clinic of Cardiology and Rheumatology, NMTH “Tzar Boris III” - Sofia
(2)University Hospital "Sv. Anna" - Sofia
Summary: Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease of multifactorial etiology. The proinflammatory cytokines have a pivotal role in the pathogenesis and perpetuation of rheumatoid synovitis. Biological agents are monoclonal antibodies or recombinant forms of natural inhibitory molecules, which selectively interact with molecules or cell receptors affecting immune or inflammatory processes. In RA, etanercept, infliximab and adalimumab are shown to suppress tumour necrosis factor and interleukin-1 receptor antagonist inhibits IL-1 activity. Trials have shown benefits as monotherapy, although the best results for disease control are seen when biological agents are coadministered with methotrexate. The use of these agents in clinical trials and in practice has resulted in dramatic improvements in RA disease control, and in delay and prevention of radiographic damage. The adverse effect profile is evolving and includes, for anti-TNF therapy, an increased risk of infections associated with immune suppression, injection and infusion reactions, and a risk of drug induced autoimmune syndromes such as systemic lupus erythematosus. Where these drugs are affordable, the prognosis of individuals for control of severe RA is better than ever before.
Key words: rheumatoid arthritis, new treatment, biological agents
Address for correspondence:
Assoc. Prof. Antoaneta Tontcheva, M.D., Clinic of Cardiology and Rheumatology, NMTH “Tzar Boris III”, 108 Maria-Luiza Blvd., Bg – 1202 Sofia


Pharmacological treatment of prolactinomas – 41, 2005, № 3, 45-48.
T. Shumkova and N. Boyadjieva

Department of Pharmacology and Toxicology, Medical University – Sofia
Summary: Prolactinoma is the most frequent benign and hormone-secreting tumor of the pituitary gland occuring in women and men. It represents about 40% of the pituitary tumors and the etiology of these tumors is still unknown. The article summarizes basic characteristics of prolactinomas and pharmacological drugs causing hyperprolactinemia. Presented are drugs for medical treatment of prolactinomas that are an appropriate first-line treatment for both micro- and macroprolactinomas.
Key words: prolactinoma, treatment, dopamine agonists
Address for correspondence:
Teodora Shumkova, Department of Pharmacology and Toxicology, Medical University, 2 Zdrave Str., Bg – 1431 Sofia, tel. +359 887-34-92-68, e-mail:


Biphosphonates-induced disorders of the esophagus - 41, 2005, № 3, 49-54.
. Kirkova and S. Janev

Institute of Physiology
, Bulgarian Academy of Science – Sofia
In the organism, alendronate disintegrates to alendronic acid that has tissue-damaging activity. At delayed empting of the esophagus and release of alendronic acid in it, its mucosa could be injured, leading to esophagitis, ulcerations, strictures, and even perforations. In Bulgaria, 2 tablet forms, containing 10 mg alendronate, are registered: Fosamax (Merck) and Lindron (Krka). The results from the performed analysis showed that the tablets Lindron (Krka) are disintegrated 7.6 fold faster. The faster disintegration of these tablets in patients with prolonged esophageal transit is the reason for the increased risk of esophageal injury. The prolonged esophageal transit is occurring rather frequently in senile patients with esophageal motor dysfunctions and/or other accompanying diseases.
Key words: biphosphonates, alendronate, esophagus
Address for correspondence: S. Janev, 23, Acad. G. Bonchev, Str., Bg - 1113 Sofia, tel. +359 2 979-21-07

Nitric oxide, reactive nitrogen species and nitroxidergic processes - clinical application - 41, 2005, № 3, 55-58.
S. Lazarov (1), Е. Ianev
(1) and M. Penev(2)
(1) Department of Pathological Physiology, Medical University - Sofia
(2) Department of Propedeutics of Internal Diseases, Medical University - Sofia
Summary: Nitric oxide (NO) represents a very important inter- and intracellular signal molecule. It is a neurotransmitter and local mediator which is produced by almost all cells in the human organism. NO and its species, called “reactive nitrogen species” (RNS), take part in the regulation of the function of certain tissues and organs. They are important mediators in the pathogenesis of different pathologic processes and diseases. Pharmacological modulation of NO and RNS production and biological effects take a very important place in the modern therapy.
Key words: nitric oxide, reactive nitrogen species, nitric oxide synthase, nitroxidergic processes, pharmacological modulation
Address for correspondence:
Simeon Lazarov, M. D., Department of Pathological Physiology, Medical University, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, tel.+359 2 952-04-61




Differential diagnosis of chronic inflammatory demyelinating polyneuropathy - 41, 2005, № 2, 5-9.
I. Petrov, K. Kostov and R. Ikonomov
Clinic of Neurology, Medical Institute, Ministry of Internal Affairs Sofia
Summary: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired demyelinating disease of the peripheral nervous system with unclear etiology and autoimmune pathogenesis. Its clinical course covers slow development of proximal-distal polyneuropathic syndrome with sensory and motor disorders, electrophysiological and morphological evidence for segment demyelination and axonal degeneration. The diagnosis is defined on the basis of complex clinical, electrophysiological, liquor and biopsy criteria. The disease is relatively well affected after administration of corticosteroids, intravenous immunoglobulin or plasmapheresis. The differential diagnosis (DD) requires the distinction of idiopathic CIDP (I-CIDP) from CIDP syndrome occurring together with some joint diseases and other polyneuropathies. CIDP is found in patients with diabetes mellitus, non-malignant monoclonal gamopathy, hepatitis C, Sjogren’s syndrome, inflammatory bone diseases, HIV-infection. When discussing CIDP diagnosis, other metabolic neuropathies (at uremia, acromegalia, hepatitis, amyloidosis and hypothyroidism), paraneoplastic neuropathies (at lymphoma, myeloma, carcinoma, etc.), polyradiculoneuropathies and polyneuropathies associated with Lyme disease or other infections have to be rejected. The DD of CIDP covers also other acquired demyelinating neuropathies – sensory CIDP, multifocal motor neuropathy, and multifocal acquired sensory and motor neuropathy. The clinical differentiation between CIDP and acute CIDP (syndrome of Guillain-Barre) is important because of the different course, recovery perspectives and therapeutic approach. When discussing DD of CIDP, some inherited demyelinating polyneuropathies should also be considered.
Key words: chronic inflammatory demyelinating polyneuropathy, diagnosis, differential diagnosis
Address for correspondence: Assoc. Prof. Ivan Petrov, M. D., Clinic of Neurology, Medical Institute, Ministry of Internal Affairs, 79A, Skobelev Blvd., Bg1606 Sofia, tel. +359 2 982-15-80


Rheumatoid arthritis and cardiovascular risk - 41, 2005, № 2, 10-17.
А. Toncheva and S. Torbova

Clinic of Cardiology and Rheumatology, MNTH “Tzar Boris III”
Summary: During the last few years, there has been data for the increased risk of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA), as well as increased mortality from cardiovascular events. It is considered that the inflammation of the vessel wall is a common pathogenetic mechanism both for atherosclerosis and rheumatoid arthritis. Along with the usual risk factors for CVD, in patients with RA there is a statistically reliable reduced insulin sensitivity as well as predisposition to low HDL cholesterol. It is suggested that RA is considered a separate risk factor for CVD, and more aggressive treatment and control of cholesterol levels, blood glucose, C-reactive protein, blood pressure and other risk factors are needed.
Key words: rheumatoid arthritis, atherosclerosis, cardiovascular risk factors, endothelial disfunction, treatment
Address for correspondence:
Ass. Prof. Antoaneta Toncheva, M.D., Clinic of Cardiology and Rheumatology, MNTH “Tzar Boris III”, 108 Maria-Luiza Blvd., Bg – 1202 Sofia


Trends in asthma epidemiology: mortality and morbidity - 41, 2005, № 2, 18-25.
G. Christoff
Clinic of Allergology, University Hospital “AlexandrovskaSofia
Summary: In spite of all efforts that have been exerted to develop, promote and stick to different international guidelines for diagnosis, differential diagnosis and treatment of bronchial asthma, the trends in its epidemiology are permanently negative. The increase in disease’s mortality and morbidity as well as in the level of utilization of health resources is more than clear. Bronchial asthma nowadays is an illness with great social and economic impact on patients’ and their families’ quality of life through the impairment it causes. The author reviews the data on asthma epidemiology trends published recently.
Key words: asthma, epidemiology, mortality, prevalence, incidence
Address for correspondence:
Georgi Christoff, M. D., Clinic of Allergology, University HospitalAlexandrovska”, 1431 Sofia, 1, Sv. G. Sofiiski Str.,


Alpha-1 antitrypsin deficiency in patients with pulmonary diseases- 41, 2005, № 2, 26-32.
M. Mircheva and М. Baleva
Department of Allergology and Clinical Immunology,
University HospitalAlexandrovska”  Sofia
Summary: Alpha
-1 antitrypsin (ААТ) deficiency is one of the commonest genetic deficiencies in Caucasian (white) populations. Оver 100 different genetic variants of alpha-1 antitrypsin have been identified. Normal alpha-1 antitrypsin is labelled M and the two most important abnormal variants are called S and Z. Both are result from mutations of the alpha-1 antitrypsin gene. Аlpha-1 antitrypsin deficiency most frequently causes emphysema. Alsо, there is an association between AAT deficiency and bronchiectasis. Тhis deficiency is the most common genetic or inherited cause of hepatitis and cirrhosis in infants and children. S type of the mutation has the highest frequency in the Iberian Peninsula, North America, Australia and New Zealand and Z type has the highest frequency in Northern and Western Europe, New Zealand, Thailand, Afghanistan.
Key words: a
lpha-1 antitrypsin deficiency, genetics, emphysema, bronchiectasis, asthma
Address for correspondence: Mariana Mircheva, M.D., Department of Allergology and Clinical Immunology, University Hospital Alexandrovska, 1, Sv. G. Sofiiski Str., Bg 1431 Sofia, e-mail:


T-regulatory lymphocytes and bronchial asthma - a new look at “hygiene hypothesis” - 41, 2005, № 2, 33-38.
I. Tzоtcheva
Pediatric Clinic, University Hospital “Alexandrovska”; Sofia
Summary: T helper type 2 immune responses against harmless antigens (allergens) are critical in the pathogenesis of allergy and asthma. A number of epidemiological studies have suggested that the increase in the prevalence of allergic disorders that occurred over the past few decades is attributable to a reduced microbial burden during childhood (the “hygiene hypothesis”). However, the immunological mechanisms that regulate and protect against the development of these disorders are poorly understood. The initial interpretation proposed a missing immune deviation of allergen-specific responses from a Th2 to a Th1 profile, as a result of the reduced production of interleukin-12 and interferons by natural immunity cells, stimulated by bacterial products via their Toll-like receptors. More recently, the role of reduced activity of the T regulatory
cells has been emphasized. The T regulatory cells include four groups of CD4+ T cells: Th3 cells, Tr1 cells, CD4+ CD25+ cells and NKT cells. A better understanding of the role of the regulatory cells in allergic diseases and bronchial asthma is important not only from a theoretical point of view, but also may lead to the identification of novel therapies.
Key words: asthma, hygiene hypothesis, Th2 immune response, T
regulatory cells
Address for correspondence: Iren Tzotcheva, M.D., Pediatric Clinic, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski str., Bg
1431 Sofia, tel. +359 2 923-03-73, GSM +359 887-20-70-28, e-mail:


Antimicrobial resistance of etiologically significant bacteria opportunities of antimicrobial resistance surveillance systems - 41, 2005, № 2, 39-44.
M. Petrov
National Reference Laboratory “Control and Monitoring of Antimicrobial Resistance”, Microbiology Department, National Center of Infectious and Parasitic Diseases, Sofia.

Summary: In the last few years, the rising tide of ever-increasing antimicrobial resistance among clinically important microorganisms has become one of the most serious concerns and disputed problems in the healthcare systems worldwide. Surveillance of antimicrobial resistance has proven to be an essential tool in the strategy to contain and reduce resistance. The article describes and compares The Bulgarian Surveillance Tracking Antimicrobial Resistance  BulSTAR and some of the main national and international longitudinal surveillance systems. Some universal limitations and difficulties of monitoring process are pointed and special emphasize is given to specific local BulSTAR impediments. Comments and conclusions on the advantages and shortcomings of the Bulgarian surveillance system are made. Finally, some proposals for future improvements of the system are given and analyzed.
Key words: BulSTAR, surveillance, antimicrobial resistance, antibiotics, Bulgarian Association of Microbiologists
Address for correspondence: Mihail Petrov, M. D., National Reference Laboratory “Control and Monitoring of Antimicrobial Resistance”, Microbiology Department, National Center of Infectious and Parasitic Diseases, 26, Yanko Sakazov Blvd., Bg 1504 Sofia, tel. +359 2944-69-99/312, e-mail:


Free radicals, neurodegenerative and psychiatric diseases and antioxidants - 41, 2005, № 2, 45-51
M. Varadinova, D. Drenska, G. Dimitrov and N. Boyadjieva

Department of Pharmacology and Toxicology, Medical University; Sofia.
In our modern world there are too many environmental factors, e.g. ecological imbalance, tension, fear, terrorism, wars, that act aggressively on the human organism. On the cellular level, these stressors lead to oxidative stress. There is a growing body of data indicating that free radicals generated by oxidative stress take substantial part in the pathogenesis of many diseases, including neurodegenerative and psychiatric diseases. The harmful environmental factors added to the genetic base may be the main reason for the high frequency of these diseases. The antioxidants are substances which act as scavengers for the free radicals and support the physiological antioxidant system. We believe that if we add antioxidants to conventional therapy of neurodegenerative and psychiatric diseases we will improve their treatment and will help the patient to lead a better life.
Kеy words: free radicals
, neurodegenerative and psychiatric diseases, antioxidants
Address for correspondence:
Diana Docheva-Drenska, M.D., Department of Pharmacology and Toxicology, Medical University, 2, Zdrave Str., Bg – 1431 Sofia, tel. +359 2 917-26-15, e-mail:

Historical development of radical hysterectomy- 41, 2005, № 2, 52-54.
Gynecology Clinic, MHAT “Sveta Anna”; Varna
Summary: The present review traces the stages of development of radical hysterectomy from its introduction in practice in the end of XIX century to the middle of XX century. During this period, many investigators had used their own knowledge, experience and failures to improve the technique of radical hysterectomy, to decrease the complication rate and to increase the survival rate of the operated patients. These investigators had laid the basis of the pelvic surgery and the modern surgical treatment of gynecological malignancies.
Key words: radical hysterectomy, history
Address for correspondence: Yavor Dimitrov Kornovski, M. D., 39 Chaika, apt. 51, Bg 9010 Varna, GSM
+359 887-62-47-50, fax +359 52 31-24-15


Practical clinical aspects of microbiological examination in pre-analytical stage - 41, 2005, № 2, 55-61
R. Komitova(1) and M. Murdjeva(2)
(1)Department of Infectious Diseases, University Hospital “Sv. Anna“ Sofia
(2)Department of Microbiology and Immunology, Medical University – Plovdiv
Summary: The pre-analytical stage of clinical microbiological testing requires competence from the time of collection through all stages of transport, storage and processing of the patient’s specimen. Based on information in guidelines, instructions and Medical Standard of Clinical Microbiology, the present review aims to help the general practitioners and specialists in the pre-analytical stage of the microbiological diagnosis. The practical approach is presented for collection, transport and storage of the most frequently examined specimens – nasal and throat swabs, sputum, feces, urine, blood, cerebrospinal fluid.
words: clinical microbiology, pathological specimen, collection, transport, storage, procedure
Address for correspondence: R. Komitova, M. D., Department of Infectious Diseases, University Hospital „Sv. Anna”, 309, Slivnica Blvd., Bg1202 Sofia, е-mail:


Clinical manifestations, risks and trends regarding human Parvovirus B19 infection– 41, 2005, No 1, 5-14.
Z. Mihneva
Department of Virology, NCIPD - Sofia
Summary: The review presents information about Parvovirus B19 – the only human representative of Parvoviridae family, which became known for the first time during 80’s of 20th century. The etiological role of this pathogen is accentuated in wide area of diseases, syndromes and pathological states running acutely and chronically. Viral tropism and persistence, variable transmission, clinical polymorphism as well as treatment, contingents at risk and future trends in application of molecular and viral mechanisms for therapeutic purposes are discussed.
Key words: parvovirus B19, viral tropism, persistent-infection, clinical polymorphism
Address for correspondence:
Zefira Mihneva, M. D., Department of Virology, NCIPD, 44A Stoletov Blvd., Bg - 1233 Sofia, tel. +359 2 931-07-13/254, e-mail:


Poliomyelitis will be defeated– 41, 2005, No 1, 15-20– 41, 2005, No 1, 15-20.
National Center of Infectious and Parasitic Diseases - Sofia
Summary: Significant progress is being made towards the global eradication of poliomyelitis since this initiative was launched by the General Assembly of the World Health Organization in 1988. By the end of 2003, poliomyelitis had been eliminated from all but 6 contries in the world. Although endemic polio transmission is now geographically restricted, wild poliovirus importation continues to paralyse children in polio-free areas. Poliomyelitis remains a real threat. The current report reviews the actual problems regarding pathogenesis, clinical manifestations, epidemiology, vaccine strategy, diagnosis and control of poliomyelitis. Data of the latest epidemic outbreak of poliomyelitis in Bulgaria in 2001 are presented.
Key words: poliomyelitis, polioviruses, acute flaccid paralyses, eradication, vaccines
Address for correspondence:
Assoc. Prof. Neli Korsun, M. D., National Referent Enterovirus Laboratory, National Center of Infectious and Parasitic Diseases, 44A Stoletov Blvd., Bg - 1233 Sofia, tel. +359 2 931-07-13/247, e-mail:


Sarcoma of the uterus– 41, 2005, No 1, 21-25.
Iа. Kornovski(1) and V. Ivanova(2)
(1)Gynecology Clinic, MHAT “Sveta Anna” - Varna
(2)Department of General and Clinical Pathology, Medical University - Pleven
Summary: This review presents clinical classification, histologic subtypes and treatment strategies for one of the rare but with extremely malignant nature uterine tumors. The low incidence rate of this disease leads to inconclusive survival rates reported by different centers, using one or another type of management. This urges the need to perform meta-analysis and reviews including large numbers of patients in order to determine the appropriate treatment strategy.
Key words: sarcoma uteri, chemotherapy, radiotherapy
Address for correspondence: Iavor
Dimitrov Kornovski, M. D., 39 Chaika, apt. 51, Bg - 9010 Varna, GSM +359 887-62-47-50, fax +359 52 31-24-15


Restless legs syndrome – 41, 2005, No 1, 26-30.
I. Staikov(1) and J. J. Petrova(2)
(1)Clinic of Neurology, University Hospital “Tzaritza Ioanna” - Sofia
(2)Clinic of Neurology, University Hospital “Alexandrovska” - Sofia
Summary: Restless legs syndrome is one of the most common neurological disorders, with a prevalence of 5 to 15%. RLS manifestations are unpleasant sensations in the lower extremities that are accompanied by an urge to move. Symptoms predominantly occur at rest, are more pronounced in the evening and/or at night, are relieved by movement and may lead to severe sleep disturbances. Characteristically, RLS patients have nocturnal periodic movement during sleep and while being awake. Typical history and normal neurological examination lead to the clinical diagnosis. Additional laboratory and neurophysiological investigations are necessary to rule out associated diseases. Polysomnography is needed to record periodic limb movements in sleep. After differential diagnosis, pharmacotherapy should be started if RLS symptoms restrict the patient’s well being and if sleep disturbances are present. Treatment strategies are recommended individually according to the disease severity. In the article, an overview of the etiology, clinical symptomatology, diagnosis and treatment of restless legs syndrome is presented.
Key words: restless legs syndrome, sleep disorders, periodic limb movements
Address for correspondence: Ivan Staikov, M. D., Clinic of Neurology, University Hospital “Tzaritza Ioanna”, 8, Bialo more Str., Bg - 1504 Sofia, tel. +359 2 943-25-71, е-mail:


Arterial hypertension – a powerful risk factor for stroke. Pathogenetic mechanisms and possibility for therapeutic modification – 41, 2005, No 1, 31-36.
Sv. Torbova

Clinic of Cardiorheumatology, NMTH “Tzar Boris III” - Sofia
Summary: Arterial hypertension is the most powerful and significant independent risk factor for stroke. The stroke risk rises progressively with the level of blood pressure – systolic, as well as diastolic. Systolic blood pressure is directly related to risk of stroke, particularly after 65 years of age. Isolated systolic hypertension has twice the risk of stroke in men and 1.5 times increased risk in women. Analyses of a large number of clinical trials suggest that the blood pressure should be < 125/85 mm Hg to reduce the risk of stroke. Hypertension contributes directly to the occurrence of stroke in at last 3 major ways and indirectly by exacerbating several other degenerative processes. There are several proposed mechanisms relating renin-angiotensin system with stroke. Diroton (Lisinopril) has many well established vasoprotective effects. Diroton has more than class effects and must be proposed for successful prevention of stroke.
Key words: hypertension, stroke, ACE inhibitors, lisinopril, cerebrovascular risk factors
Address for correspondence:
Prof. Svetla Torbova, Clinic of Cardiorheumatology, NMTH “Tzar Boris III”, 104, Maria-Luiza Blvd., Bg - 1202 Sofia, tel. + 359 2 932-21-34


Vascular and cardiac renin-angiotensin systems under normal and pathological conditions  – 41, 2005, No 1, 37-42.
E. Lakova

Department of Pathophysiology, Medical University - Pleven
Summary: All components of renin-angiotensin system (RAS) - angiotensinogen, renin, angiotensin-converting enzyme, angiotensins and angiotensin receptors are identified in vascular wall and cardiomyocytes. Expression of these components in vasculature depends on gene polymorphism, sodium intake, steroid hormones, while in myocardium it depends on mechanical stretch, and neurohumoral influences. Vascular angiotensin is not only a potent vasoconstrictor, but also inflammatory mediator, inductor of oxidative stress, and regulator of cell growth apoptosis and migration of vascular smooth muscles. It participates in pathogenesis of hypertension, atherosclerosis and their complications. Cardiac RAS regulates heart contractility and impulse propagation, stimulates myocyte growth, triggers apoptosis and is involved in myocardial hypertrophy, development of heart failure, and cardiac remodeling after myocardial infarction. Blocking of angiotensin actions rather than hemodynamic changes may account for the beneficial effects of angiotensin antagonists and ACE-inhibitors in cardiovascular disease.
Key words: vascular renin, cardiac renin, angiotensin, cardiovascular disorders
Address for correspondence: Emilia Lakova, M.D., Department of Pathophysiology, Medical University,1, Kl. Ochridski Str., Bg - 5800 Pleven, tel. +359 64 88-42-52, e-mail:


Antiphospholipid syndrome and pregnancy  – 41, 2005, No 1, 43-47.
M. Pantchovska

Clinic of Rheumatology, Medical University - Plovdiv
Summary: Antiphospholipid syndrome (APS) is a specific clinical-laboratory complex of symptoms, manifested by recurrent arterial and venous thromboses, habitual abortions and thrombocytopenia. A wide spectrum of autoantibodies associated with the disease besides classic antiphospholipid antibodies – lupus anticoagulant and anticardiolipin antibodies were established during the last years. Obstetric pathology in APS includes premature birth, intrauterine fetal death, pre-eclampsia and eclampsia, HELLP syndrome, postpartal thrombosis. The frequency of these complications may be reduced by adequate prophylaxis and treatment. The review presents basic manifestations of APS in pregnant women and a therapeutic algorithm.
Key words: antiphospholiid syndrome, manifestations, pregnancy, treatment
Address for correspondence:
Assoc. prof. Maria Pantchovska, M. D., Clinic of Rheumatology, Medical University - Plovdiv, tel. +359 32 60-23-61, e-mail:


Therapy with Cyclosporin A of nephrotic syndrome  – 41, 2005, No 1, 48-55.
E. Paskalev

Clinic of Nephrology and Kidney Transplantation, University Hospital “Alexandrovska” - Sofia
Summary: Cyclosporin A (CA) is used in the therapy of many immune diseases including the renal ones. Limit factor of that is its nephrotoxicity. CA leads to a dose-dependent reduction of glomerular filtration rate and renal plasma flow (functional toxicity). Superimposed on functional toxicity morphological changes in the vascular-interstitial space (small vessels) and tubules may also occur. The present knowledge on the pathogenesis of cyclosporine nephrotoxicity suggests that glomerular filtration rate is mainly reduced due to a preglomerular vasoconstriction. The goal of the study is to show the efficacy, the dosage and administration, and the limits of CA in glomerular diseases associated with nephrоtic syndrome.
Key words: cyclosporin A, nephrоtic syndrome, treatment, nephrotoxicity
Address for correspondence:
Ass. Prof. Emil Paskalev, M. D., Clinic of Nephrology and Transplantation, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, tel. +359 2 923-02-40, e-mail:

Strontium ranelate – the contemporary application of an old principle in the treatment of osteoporosis  – 41, 2005, No 1, 55-59.
D. Bakalov and M. Boyanov

Endocrinology Clinic, Department of Internal Medicine, Medical University – Sofia
Summary: This review article displays the use of strontium salts of the raneleic acid in the treatment of osteoporosis. The main biological actions of strontium ranelate are listed. Data are shown on the in vivo and in vitro experiments in animal models. The results of the two largest up-to-date studies on the treatment of osteoporosis with strontium ranelate are commented. The Spinal Osteoporosis Therapeutic Intervention assesses the effect of strontium ranelate on the risk of vertebral fractures, whereas The Treatment of Peripheral Osteoporosis Study assesses its effect on the risk of peripheral (non-vertebral) fractures. Strontium ranelate showed significant anti-fracture efficacy in both studies. The relative risk reduction of new fractures was about 40%. Strontium ranelate seems to be a promising agent for the treatment and prevention of osteoporosis.
Key words: osteoporosis, bone-building and antiresorptive agents, strontium ranelate
Address for correspondence:
D. Bakalov, M. D. Endocrinology Clinic, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, tel. + 359 2 923-03-46

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