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Review articles

Volume 40, 2004




Tick-borne infections - challenges and problems – 40, 2004, No 4, 5-12.
R. Komitova(1), E. Alexandrov(2) and I. Hristova(3)
Clinic of Infectious, Parasitic and Tropical Diseases, University hospital "Sv. I. Rilski” - Sofia
(2)National Referent Laboratory of Ricketsiosis, Military Medical Academy - Sofia
(3)National Center of Contagious and Parasitic Diseases - Sofia
Summary: Tick-borne zoonoses as a cause of human diseases have been known for many years but the major impact on public health in Europe and in the USA was first recognized by identification of Borrelia burgdorferi as the cause of Lyme disease in early 1980s. Some of tick-transmitted diseases such as Mediterranean spotted fever and human ehrlichiosis can be life-threatening but they are also eminently treatable when recognized early. This article reviews the clinical and epidemiological features of Mediterranean spotted fever and Lyme borreliosis, the prevailing tick-borne diseases in Bulgaria, as well as Crimean-Congo hemorrhagic fever and ehrlichiosеs. Current therapeutic and preventive strategy are summarized.
Key words: tick-borne zoonoses, Mediterranean spotted fever, Lyme borreliosis, Crimean-Congo hemorrhagic fever, ehrlichiosеs, therapy, prevention
Address for correspondence:
  Radka Komitova, M. D., Clinic of Infectious, Parasitic and Tropical Diseases, University Hospital "Sv. I. Rilski", 15 Acad. I. Geshov Blvd., Bg - 1431 Sofia, e-mail:

Cryoglobulinemia and cryoglobulinemic nephritis – 40, 2004, No 4, 13-17.
M. Nikolova

Clinic of Nephrology, University Hospital “Alexandrovskd” - Sofia
Summary: Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 centigrade C and redissolve when warmed. The presence in the serum of such immunoglobulins is referred as cryoglobulinemia. This review discusses the etiology, pathogenesis, clinical manifestations and treatment of cryoglobulinemia and cryoglobulinemic nephritis.
Key words:  cryoglobulinemia, hepatitis C, hepatitis B, glomerulonephritis
Address for correspondence:
Milena Nikolova, M. D., Clinic of Nephrology, University Hospital Alexandrovska, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, PB 45, tel. +359 2 92-30-299, e-mail:

Aspirin-induced asthma – 40, 2004, No 4, 18-22.
S. Filtchev
Clinic of Pediatric Pulmonology, University HospitalAlexandrovska” - Sofia
Summary: Aspirin-induced asthma (AIA) is a distinct clinical syndrome affecting some asthmatic patients. In these patients, aspirin may exacerbate asthma and prоvoke life-threatening reactions. Persistent rhinusinusitis precedes development of nasal polyposis, aspirin hypersensitivity and asthma. Although the name of the disease relates to aspirin, it is well established that 93-100% of affected patients are cross sensitive to all non-steroidal anti-inflammatory drugs (NSAIDs), that inhibit cyclo-oxygenase (COX) enzymes. Paracetamol (ace­ta­mi­nophen) however, is seldom associated with cross sensitivity in patients with AIA. Less than 2% of asthmatic patients are sensitive to both aspirin and paracetamol and reactions to paracetamol tend to be less severe. Patients with AIA should avoid all products that contain aspirin or NSAIDs indefinitely; paracetamol should be recommended, unless contraindicated.
Key words: aspirin, asthma, paracetamol, nonsteroidal anti-inflammatory drugs
Address for correspondence:
 Slavi Filtchev, M. D., Chair of Pediatrics, University Hospital “Alexandrovska”, Medical University, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, tel. +359 2 923-03-73; GSM 0887 3000 74

Methods for the measurement of body composition – 40, 2004, No 4, 23-27.
Zh. Boneva(1), Vl. Christov(2), P. Popivanov(2), M. Boyanov(2) and N. Temelkova(2)
Department of Endocrinology, Medical Institute, Ministry of Internal Affairs - Sofia
(2)Clinic of Endocrinology, University Hospital Alexandrovska” - Sofia
Summary:  The aim of this article is to compare the current methods for assessment of body composition. Body composition measurements can be useful in laboratory and epidemiological studies, as well as in clinical situations. Many diseases and disorders are accompanied by changes or abnormalities in body composition and the most common problem may be obesity. Body fat can be determined in vivo in different ways, using rather accurate laboratory techniques or using simple estimation techniques that can also be applied in clinical conditions. The choice of particular technique should be based on a balance of practical and financial considerations and the aim of the study.
Key words:
 obesity, body composition, body fat, fat-free mass
Address for correspondence: Zhivka Boneva, M. D., Department of Endocrinology, Medical Institute, Ministry of Internal Affairs, 79, Skobelev Blvd., Bg - 1606 Sofia,
tel. +359 2

News in the treatment of atopic dermatitis – 40, 2004, No 4, 28-32.
S. Valkova
Clinic of Dermatology and Venereology, Higher Medical Institute - Pleven
Summary: Atopic dermatitis (AD) is a chronically-relapsing disease with increasing prevalence and serious impact on the quality of life of the patients and their families. The most common methods for treatment of AD include antihistamines, topical or systemic corticosteroids, emollients and physiotherapy. The introduction of the local immunosuppressors (tacrolimus, pimecrolimus) marks the beginning of a new era in the therapy of the disease in children and adults. Their main advantage compared with the topical corticosteroids is the lack of serious side effects. The initial investigations over the role of some saprophytic microorganisms (L. rhamnosus, M. vaccae) in the treatment and prevention of AD also give encouraging results. The most recalcitrant forms of the disease often require the use of systemic immunosuppressors (mycophenolate mophetil). A new approach in the treatment of AD is the application of antileukotriens and some of the methods of the Chinese medicine.
Key words:  atopic dermatitis, treatment
Address for correspondence:
Sonia Valkova, M. D., Clinic of Dermatology and Venereology, Higher Medical Institute, 130, Doiran Str., Bg - 5800 Pleven, e-mail:

Hormone replacement therapy for cardiovascular disease prevention - a myth or reality?
Part II: Evidence from clinical trials – 40, 2004, No 4, 33-42.
Y. Yotov

Department of Internal Medicine, Medical University – Varna
Summary:  The importance of the cardio-vascular diseases (CVD) in the modern developed society proves the interest in the peculiarities in their development in the female gender and the possibilities for their prevention. The hormone replacement therapy (HRT) is a good candidate for the well-known beneficial effects of estrogens on the atherosclerosis process, on the lipid and carbohydrate metabolism, and the vascular dilation. These protective on the cardio-vascular system biological effects of the estrogens are confirmed in numerous observational epidemiologic studies and meta-anаlyses which show on the average 25-30% lower risk from CVD in women taking HRT. The large randomized, placebo-controlled trials have to confirm whether these benefits from the HRT in the prevention of CVD would be proven in the clinical practice. Unfortunately, all available trials failed to find a significant difference between the HRT and the placebo groups, moreover, some have shown a higher risk especially during the first months or year of treatment. All studies proved higher incidence of deep venous and pulmonary thromboembolic events, of breast cancer, and of genital bleeding, the last being the most important reason for withdrawal from participation. The lack of any evident benefit from HRT in decreasing CVD and the presence of increased additional risk of other diseases do not give reason nowadays to propose HRT for the primary and secondary prevention of the CVD.
Key words: cardiovascular diseases, hormone replacement therapy, clinical trials
Address for correspondence:
Yoto Yotov, M. D., First Cardiology Clinic, University Hospital “Sv. Marina”, Medical University, 1, Hristo Smirnenski Blvd., Bg - 9010 Varna, tel. + 359 52-30-28-51/286, fax + 359 52-30-29-33, е-mail:

Substitution of cyclosporine microemulsion (Neoral) by new generic formulations in renal transplant patients – 40, 2004, No 4, 43-47.
E. Paskalev and P. Simeonov
Clinic of Nephrology and Transplantation, University Hospital "Alexandrovska” - Sofia
Summary: Neoral microemulsion formulation is a main immunosuppressant in organ transplantation nowadays. It is a critical-dose drug because a small change in its dose or concentration results in a clinically significant change in efficacy or toxicity. Generic formulations of cyclosporine A (CyA) are becoming more widely available, but standard criteria for bioequivalence in healthy volunteers demonstrate that mean pharmacokinetic parameters fall within 80-125% of the mean values for Neoral. The limited available clinical evidence has shown that stable renal transplant patients receiving Neoral have a significant reduction in mean CyA level after conversion to the Cicloral formulation. Mean pharmacokinetic values have been reported as equivalent following conversion to Gengraf in one study, but mean CyA level fell and mean serum creatinine rose significantly. The only clinical outcome data available are from retrospective study of de novo renal transplant patients, which reported a significantly higher incidence of biopsy proven acute rejection in patients receiving Gengraf versus Neoral (39% versus 25%, p < 0.05). Bioequivalence does not equal clinical equivalence and clinical equivalency requires extensive comparative testing in clinical practice. It is well known that CyA pharmacokinetics affects clinical outcome and formulation choice is a key factor affecting clinical outcome. In conclusion, the use of CyA generic formulations affects survival of renal graft - a main characteristic of good clinical practice.
Key words: renal transplantation, cyclosporine A, cyclosporine A generic formulation, clinical outcome
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:

Regarding medical information given to parents and patients – 40, 2004, No 4, 48-52.
L. Despotova-Toleva
Medical University - Plovdiv
Summary: The parents, the patients and particularly the children have the right to be informed and to receive clear, comprehensive and unambiguous answer of their questions correspondingly to the limits of current medical knowledge and practice. Achieving full-bodied and free of conflicts contacts between the parents/patients/children and medical staff depends on proper targeted education of the teams. They need good knowledge and skills to deal with parents, patients, relatives and non-medical members of the team, properly convey the good and the bad news, to facilitate obtaining informed consent, to give additional information and/or to suggest suitable information sources. The physicians in our country still do not have enough experience and skills in this field. They rely on personal quality and experience. The aims of this study are presented as followеs. To define, describe and characterize the main groups of individuals, searching for medical and related information; to evaluate the main information sources used by parents, patients and relatives; to study the uses and abuses of information excess. Following problems are discussed: 1) Different medical and related information sources for parents and patients; 2) Assessment of the information gained from different sources; 3) The impact of the information; 4) Problems related to lack of information; 5) Problems related to information excess. Searching for information, the parents and the patients may become victims of persons or criminal groups, their private information might be misused etc. Both the lack and the excess of information may be complicated by misunderstanding, misuse or incorrect comments, making the dialog between parents/patients and physicians substantially difficult. These problems are not well known and developed in our country, the physicians are not properly trained to solve them. Large multicenter studies in accordance to medical low and ethics are lying ahead.
Key words: medical information, information sources, misinformation, parents/children/physician interrelations
Address for correspondence:
Ljubima Despotova-Toleva, M. D., International Collaboration, Medical University, 15-a Vasil Aprilov Str., Bg - 4002 Plovdiv, е-mail:,

Supplement 1

Biological Properties of Coumarins - Review. 40, 2004, Suppl. 1, pp. 1-26.
I. Kostova (1), I. Manolov (2) and P. Atanasov (3)

(1) Department of Chemistry, Faculty of Pharmacy, Medical University - Sofia
(2) Department of Organic Chemistry, Faculty of Pharmacy, Medical University - Sofia
(3) Section Of Emergency Internal Diseases and Cardiology, Institute of Emergency Medicine "N. I. Pirogov"
The review contains data on the most pronounced biological activities of coumarins, including anticoagulant, antimicrobial, spasmolitic, antineoplastic, antioxidant ones etc. The most active compounds of this class and their mechanism of action are shown. The pharmacological and biochemical effects, as well as the therapeutic application of the compounds depend on the substituents in the coumarin structure. Researches of the structure-activity relationship are shown in order to determine the most important groups of substituents.

Address for correspondence:
Irena Kostova, Department of Chemistry, Faculty of Pharmacy, Medical University, 2, Dunav Str., Bulgaria, 1000 Sofia, tel +359 2 923 65 69.



Low back pain - 40, 2004, No 3, 5-9.
M. Pantchovska
(1) and Y. Sheitanov(2)
(1)Clinic of Rheumatology, Medical University - Plovdiv
(2)Clinic of Rheumatology, Medical University - Sofia
Summary: Low back pain (lumbalgia) is often registered by general practitioners and other specialists - rheumatologists, neurologists, orthopedists, neurosurgeons. Up to 80% of the adults report of lumbalgia in different periods of their life. The article presents the causes of low back pain, the differential diagnostic approach and the algorithm of conduct in acute and chronic pain. The possibilities of various imaging methods are analysed. Directions for conservative and surgical treatment according to the etiology of the syndrome are presented.
Key words:  low back pain, etiology, diagnosis, treatment
Address for correspondence: Ass. Prof. Maria Pantchovska, M. D., P. B. 136, Bg - 4023 Plovdiv, tel. 0888-60-23-81,e-mail:

Respiratory syncytial virus and its role in child pathology. Diagnosis and prophylaxis – 40, 2004, No 3, 10-14.
Sl. Pavlova
(1), T. Hadzhiolova(1), R. Kotseva(1) and S. Filtchev(2)

(1)Laboratory of Influenza and Acute Respiratory Diseases, Department of Virology, National Center of Infectious and Parasitic Diseases - Sofia
(2)Clinic of Pediatric Pulmonology, UMHAT “Alexandrovska” - Sofia
Summary: Respiratory syncytial virus (RSV) is one of the most common pathogens of the lower respiratory tract in infants and young children and about 40% of the infected patients develop bronchiolitis or pneumonia. The current report summarizes the role of RSV in some groups at high risk (prematurely born infants, infants with bronchopulmonary dysplasia, congenital heart diseases and immunodeficient patients). Subjects regarding the symptoms and complications, contemporary diagnosis, treatment and possible immunoprophylaxis of infections etiologically connected with RSV are discussed. The purpose of this review is to present recent data with regard to this agent and associated infections.
Key words:   respiratory syncytial virus, high risk groups, diagnosis, prophylaxis
Address for correspondence: Slava Pavlova, M. D., Department of Virology, National Center of Infectious and Parasitic Diseases, 44A, Stoletov Blvd., Bg - 1233 Sofia, tel. + 359 2 931-07-13/207

Monkeypox: an emerging zoonosis – 40, 2004, No 3, 15-19.
R. Komitova

Clinic of Infectious, Parasitic and Tropical Diseases, University Hospital “Sv. Iv. Rilski” - Sofiа
Summary: Human monkeypox is a rare viral zoonosis endemic to Central and Western Africa that has recently emerged in the USA. Laboratory diagnosis is important because the virus can cause disease that is clinically indistinguishable from other pox-like illnesses, particularly smallpox and chickenpox. Although the natural animal reservoir of the monkeypox is unknown, rodents are the probable sourse of its introduction into the USA. A clear understanding of the virulence and transmissibility of human monkeypox has been limited by inconsistencies in epidemiological investigations. Monkeypox is the most important orthopoxvirus infection in human beings since the eradication of smallpox in the 1970s. There is currently no proven treatment for human monkeypox and questions about its potential as an agent of bioterrorism persist.
Key words: monkeypox, smallpox vaccination, bioterrorism
Address for correspondence: Radka Komitova, M. D., Clinic of Infectious, Parasitic and Tropical Diseases, University Hospital, “Sv. Iv. Rilski”, 15 Acad. Iv. Geshov Blvd., Bg - 1431 Sofia

Reactive oxygen species, endogenic antioxidants and acute gastric injury – 40, 2004, No 3, 20-26.
B. Galunska
(1), D. Paskalev(2), H. Divanyan(3) and T. Yankova(1)
(1)Department of Preclinical, Clinical Pharmacology and Biochemistry, Medical University – Varna
(2)Clinic of Nephrology and Dialysis, University Hospital “Sv. Marina” – Varna
(3)Department of Medical Physics, Chemistry and Biology, Medical University – Varna
Summary: Recent evidences indicated that oxidative stress plays a significant role in the pathogenesis of acute gastric mucosal injury. Reactive oxygen species (ROS) are implicated in the mucosal damage induced by ischemia-reperfusion, Helicobacter pylori infection, stress, ethanol and non-steroidal anti-inflammatory drugs. Recent studies on experimental models and clinical trials demonstrated that ROS are involved in the impairment of the protective mechanisms of the mucosa and the mucosal damage. The main cellular sources of ROS production in mucosal injury are xanthine oxidase, activated in local ischemia-reperfusion, lipid peroxidation, activated phagocytic cells etc. Oxidative stress can become an injuring factor due to decreased cellular antioxidant defence systems (reduced glutathione and glutathione-related enzymes, superoxide dismutase, catalase etc.), thus contributing to mucosal damage. Therefore, antioxidants combined with the conventional therapy may be a more successful approach in the treatment of acute mucosal injury.
Key words: reactive oxygen species, antioxidants, ulcerogenesis
Address for correspondence: Bistra Galunska, M. D., Department of Preclinical, Clinical Pharmacology and Biochemistry, Medical University, 55, Marin Drinov Blvd., Bg - 9002 Varna, tel. + 359 052/60-67-86/251, e-mail:

Hormone replacement therapy for cardiovascular disease prevention – a myth or reality? Part I: Biological plausibility and epidemiologic evidence  – 40, 2004, No 3, 27-35.
Y. Yotov

Department of Internal Medicine, Medical University – Varna
Summary: Cardio-vascular diseases (CVD) in women are a substantial scientific, medical, and social problem because of their importance and because of the biological and clinical differences in the course of the diseases in the female gender. CVD are the major cause of death in females, and acount for two thirds of the fatal cases in Bulgaria. The incidence of CVD increases after menopause, which implies that hormone replacement therapy (HRT) as a substitution of the natural hormone activity could have a beneficial effect on the morbidity and mortality from CVD. The biological effects of the estrogens on the cardio-vascular system are presented in the first part of the proposed reviews as well as the results from animal experiments, studies on the potential risk factors of atherosclerosis and from the large descriptive epidemiological studies. All of them show an extensive cardiovascular protective effect of the estrogens, which results in decrease of LDL-cholesterol and increase of HDL-cholesterol, beneficial effect on the vascular reactivity, inflammation processes and coagulation, as well as antioxidant effects. All large observational studies and meta-analyses of the results describe a significant risk reduction of CVD between 16% and 50%, especially in the high-risk groups. But in the era of the evidence-based medicine, large clinical trials are needed to prove in practice these potential benefits of HRT for the CVD protection in females.
Key words: cardiovascular diseases, hormone replacement therapy, prevention
Address for correspondence: Yoto Yotov, M. D., First Cardiology Clinic, University Hospital “Sv. Marina”, Medical University, 1, Hristo Smirnenski Blvd., Bg - 9010 Varna, tel. + 359 052-30-28-51/286, fax + 359 052-30-29-33, е-mail:



Rare diseases as a clinical and public health problem - 40, 2004, № 2, 5-8.
. Stefanov
(1, 2) and E. Daina (2)
(1)Department of Social Medicine and Health Management, Medical University - Plovdiv, Bulgaria
(2)Clinical Research Centre for Rare Diseases "Aldo e Cele Dacco"
Mario Negri Institute for Pharmacological Research, Italy
Summary: Generally, rare diseases could be defined as pathological conditions with low prevalence and incidence. Each disease affects comparatively small part of the population, but summed as a total, because of the huge number of nosological units, rare diseases emerge as a serious public health problem for the health systems worldwide. The aim of the article is to introduce to the Bulgarian scientific and medical community the most important contemporary problems of patients with rare diseases and their doctors. The necessity of establishment of a national policy in Bulgaria towards the rare diseases is discussed.
Key words: rare diseases, orphan drugs, public health
Address for correspondence: Rumen Stefanov, M. D., Department of Social Medicine and Health Management, Medical University, 15а, Vasil Aprilov Blvd., Bg - 4000 Plovdiv, e-mail:;

The severe acute respiratory syndrome (SARS) outbreak - one year later- 40, 2004, № 2, 9-17.
. Filtchev
Clinic of Pediatric Pulmonology, UMHAT “Alexanrovska”
Summary: Severe Acute Respiratory Syndrome (SARS) is an acute respiratory illness caused by infection with the SARS Co-V virus. Fever followed by a rapidly progressive respiratory compromise is the key complex of signs and symptoms, which also include chills, muscular aches, head-ache and loss of appetite. The mortality of SARS ranges from 0% to 50% depending on the age group affected: less than 1% in persons aged 24 years or younger and greater than 50% in persons aged 65 years and older. The etiologic agent of SARS, a specific coronavirus, is predominantly spread by droplets or by direct and indirect contact. Shedding in feces and urine also occurs. Medical personnel, physicians, nurses, and hospital workers are among those commonly infected. Control of this disease relies on the rapid identification of cases and their appropriate management, including the isolation of suspect and probable cases and the management of their close contacts. At present, the most efficacious treatment regimen for SARS is still subject to debate. For patients with progressive deterioration, intensive and supportive care is of primary importance. Immunomodulation by steroid treatment may be important. The signs and symptoms of SARS are nonspecific, and there is no early diagnostic test, no specific treatment, and no vaccine. Although the recent outbreak of SARS appears to have waned, most experts believe SARS is here to stay. This will be true especially if there is an animal reservoir that cannot be eradicated.
Key words: severe acute respiratory syndrome (SARS), SARS coronavirus, epidemic, respiratory distress
Address for correspondence:
Slavi Filtchev, M. D., Chair of Pediatrics, University Hospital “Alexandrovska”, Medical University, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, tel. +359 923-03-73; GSM 0887-30-00-74

Subsyndromal schizophrenia spectrum: schizotaxia and prodromes - 40, 2004, № 2, 18-23.
G. Onchev

Department of Psychiatry, Medical University - Sofia
Summary: Apart from the syndromal schizophrenia spectrum, attenuated cognitive and behavioral disturbances in individuals without manifest psychopathology are encountered. There is undoubtful evidence, especially from neurogenetics, functional morphometrics and neuro-psychological research, demonstrating links between these disturbances and arrest in the maturation process of the CNS. These disturbances are conceptualized in the framework of a broader endophenotype with underlying schizotaxia. A detailed review of its phenomenology demonstrates huge variety and relatively low specificity. Core features of the subsyndromal spectrum are discrete changes in self-experience, e.g. in bodily self-perception, authorship of inner experience, and intuitive attunement to common sense aspects of reality. Epistemology of such subjective phenomena is a challenge to general psychopathology that is still – despite Jaspers’ legacy – more oriented to recognition of observed and clearly verbalized signs and symptoms. Not unexpectedly, the contemporary diagnostic criteria of schizophrenia are twisted towards positive psychotic symptoms at the expense of features like autism and formal thought disorder. Subsyndromal phenomena may persist over the life cycle as “formes frustes” of schizophrenia, or may escalate to psychosis. Their role as prodromes, in the latter case, still being assessed mainly in a retrospective way, is at the background of one of the most promising developments in psychiatry aiming at early recognition and interventions in the pre-psychotic stage. Some of the perspectives and ethical problems ahead of this new development are presented.
Key words: schizophrenia spectrum, schizotypy, schizotaxia, endophenotype, prodromes, early diagnosis, early interventions
Address for correspondence: Georgi Onchev, Department of Psychiatry, Medical University, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia

Risk factors for development of vascular calcifications in hemodialysis patients - 40, 2004, № 2, 24-27.
D. Yonova
Dialysis Clinic, University Hospital “Alexandrovska” - Sofia
Summary: Patients with advanced renal failure on conservative or dialysis treatment are in a status of disturbed mineral, protein, lipid and other kinds metabolism, that predispose development of several types of soft tissue calcifications, between them especially significant cardiovascular calcifications. The mechanisms of appearance and enlargement of these calcifications is not clearly defined up to now, but a multi-factor genesis was recently proved and a key role was designated to hyperphosphatemia, high calcium body burden and lower levels of some protective proteins. A strict control of the above mentioned factors would reduce the risk of cardiovascular calcifications and would decrease cardiovascular morbidity and mortality in uremic patients on conservative or dialysis treatment.
Key words: chronic renal failure, dialysis, mineral metabolism, hyperphosphatemia, vascular calcifications
Address for correspondence: Diana
Ionova, M. D., Clinic of Dialysis, University Hospital “Alexandrovska”, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia, tel. + 359 923-04-63, 923-05-15, e-mail:

The intima-media thickness assessment - a possiblity for early diagnosis of atherosclerosis - 40, 2004, № 2, 28-33.
J. J.
Petrova (1), A. Marintchev (2) and I. Staikov (3)
Clinic of Neurology, University Hospital "Alexandrovska" - Sofia
(2)SHATENG “Acad. I. Pentchev” - Sofia
(3)Clinic of Neurology, University Hospital “Tzaritza Ioanna” - Sofia
Summary: The atherogenic risk can be evaluated by non invasive methods by measuring the intima-media thickness of the blood vessel wall. The intima-media thickness is considered to be an early marker of atherosclerosis. Its measuring by ultrasound is possible due to the different histological characteristics of the tissues of the blood vessel wall. One of the recent methods in use is the measuring of the a. carotis interna at a distance of 1-2 cm from the bifurcation. A correlation between the intima-media thickness and the development of atherosclerotic plaque has been found. The evaluation of the intima-media thickness can be usefull in early diagnosis and prophylaxis of patients with brain circulatory disease.
Кey words: intima-media thickness, atherosclerosis, risk factors, ultrasound
Address for correspondence: J. J. Petrova, M. D., Clinic of Neurology, University Hospital “Alexandrovska”, Medical University - Sofia, 1, Sv. G. Sofiiski Str., Bg - 1431 Sofia

The role of Notch receptors in the intercellular signaling in different biological events - 40, 2004, № 2, 34-42.
Trifonova and M. Stamenova
Department of Immunochemistry, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences - Sofia
Summary: Notch are evolutionarily conserved cell surface receptors that initiate signaling events between neighbouring cells in multicellular organisms. Notch signaling plays a crucial role in cell fate determination through the regulation of cell proliferation, differentiation and apoptosis. The review presents the molecular mechanisms of the Notch signaling events, mediated by the interaction between Notch receptors and their putative ligands. The role of Notch during the embryogenesis and postembryonic development is discussed. This review presents also data about the association of aberrant Notch signaling with different pathological conditions in humans.
Key words: Notch receptors, Delta ligand, Jagged ligand
Address for correspondence: Ass. Prof. M. Stamenova, Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 73, Tzarigradsko schosse Blvd., Bg - 1113 Sofia, tel. +359 2 870-72-85, e-mail:



What is the news in the pathophysiology of acne? - 40, 2004, № 1, 5-9.
S. Valkova
Department of Dermatology, Higher Medical Institute – Pleven
Summary: Acne is a common inflammatory skin disease affecting the pilo-sebaceous unit. The four basic pathophysiologic mechanisms of the disease are: hyperandrogenemia, hyperseborrhoea, infundibular hyperkeratosis and inflammation. Latest scientific investigations establish that hyperseborrhoea develops due to an increased expression of androgen receptors, hyperactivity of the enzyme 5*-reductase and the secretion of an insulin-like growth factor. Different cytokines which potentiate inflammation and infundibular hyperkeratinization are also of significant importance. One of the main inflammatory factors in acne is Propionibacterium acnes. It produces a number of chemotactic factors, enzymes and proinflammatory molecules. Genetic predisposition and stress are also considered to play an important role in the development of the disease. Despite the latest scientific achievements, in the pathophysiology of acne still exist a lot of questions. Their solution in future would greatly facilitate the introduction of new, causative methods for treatment of the disease.
Key words: acne, pathophysiology
Address for correspondence: Sonia Valkova, M. D., Department of Dermatology, Higher Medical Institute, 130, Doiran Str., Bg - 5800 Pleven, e-mail:

Kidney transplantation and cardiovascular diseases - 40, 2004, № 1, 10-14.
E. Paskalev
Clinic of Nephrology and Transplantation, University Hospital "Alexandrovska" – Sofia
Summary: It is now well established that patients with chronic renal failure are at increased risk of cardiovascular disease. Many studies suggest that this problem is attenuated, but is not corrected by successful renal transplantation. Cardiovascular disease has now emerged along with infection as the leading cause of mortality in renal transplant recipients, particularly after the first year. Since many of these patients die with functioning graft, these deaths represent an increasingly important cause of graft loss. More grafts were lost by patients mortality than rejection during the 2-5 year post-transplant period (49% vs 41%). Ischaemic heart disease and other vascular events collectively accounted for 63% of these deaths. Improvement of cardiovascular status in renal transplant patients is of significant importance in attaining better results for survival of graft, rather than further advances in immunosuppressive or antimicrobial therapy. The goal of the survey is to summarize real clinical possibilities for assessment of the risk of ischaemic heart disease and its minimizing in renal transplant patients.
Key words: kidney transplantation, risk factors, ischaemic heart disease
for correspondence: 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:

Diagnosis and treatment of nasal polyps - 40, 2004, № 1, 15-17.
D. Vicheva
Department of Otorhinolaryngology, Medical University – Plovdiv
Summary: Nasal polyps are а common disorder and a significant burden on society. Individuals with associated sinusitis have a significantly impaired quality of life. Many cells of the immune system and their mediators have a crucial role in the pathogenesis of nasal polyps. There are different methods for treatment.
Key words: nasal polyps, diagnosis, treatment
Address for correspondence: D. Vicheva, M. D., Department of Otorhinolaryngology, Medical University, 81A, Il. Makariopolski Str., Bg - 4000, Plovdiv; e-mail:

Epidemiology and classification of eye injuries - 40, 2004, № 1, 18-21.
I. Kuneva
Clinic of Ophthalmology, University Hospital "Tzaritza Ioanna"
Summary: Ocular traumatism has always been and unfortunately still is a main problem in ophthalmology. There are many classifications of eye injuries, according to different criteria. According to the mechanism and the conditions of occurance, they are divided into domestic, professional, transport, sport, criminal and military trauma. Another classification of ocular trauma is according to the type of the eye trauma. The distribution of ocular trauma according to sex, age and socioeconomical status is an important characteristic in the study of traumatism. The purpose of this review is to pay attention to this very important problem in ophthalmology and its wide distribution in society.
Key words: eye injury, epidemiology, classification
Address for correspondence: Irina Kuneva, M. D., Clinic of Ophthalmology, University Hospital "Tzaritza Ioanna", 8, Bialo more Str., Bg - 1527 Sofia, tel. + 359 2 943-22-25

Mutations in the hepatitis B virus genome and their significance - 40, 2004, № 1, 22-32.
A. Sakarev and P. Teocharov
National Center of Infectious and Parasitic Diseases - Sofia
Summary: Hepatitis B virus infection remains a major public health problem worldwide with more than 300 million chronic carriers. Under the influence of different factors, changes can occur in genome of the hepatitis B virus and mutated variants of the virus with changed characteristics appear. There are different factors that may lead to such changes. From viral side, the unusual way of replication with reverse transcriptase involved in it is the main reason for such "mistakes". Other important reasons are the contact of the virus with the host immune system, ongoing treatment with different medicines and a large immunization programs carried out worldwide. Recent evidence suggests a possible association of some hepatitis B virus mutants with the development of severe liver diseases, including hepatocellular carcinoma and could lead to unreliable diagnostics procedure. They also lead to drug resistance. The main problem is the appearance of "escape" mutants which are undetectable for the immunity after vaccination. So far such mutants are rare but they should be monitored very closely because of the possibility of domination over the wild type hepatitis B virus population. The problems caused by the changes in the viral genome apply for the development of new diagnostic methods, new drugs and even modification of the existing vaccines.
Key words: hepatitis, hepatitis B virus, mutation, HBV DNA
for correspondence: A. Sakarev, M. D., National Center of Infectious and Parasitic Diseases, 44A, Stoletov Blvd., Bg - 1233 Sofia, tel. +359 2 931-07-13

Erythropoietin and erythropoietin therapy. Part II. Erythropoietin in surgical patients. Erythropoietin treatment of anemia in congestive heart failure, HIV-infection, anemia of prematurity and other states of hypoxia- 40, 2004, № 1, 33-37.
M. Nikolova
Clinic of Nephrology, University Hospital Alexandrovska - Sofia
Summary: After the introduction of recombinant human erythropoietin (rhEPO) in the clinical practice for the treatment of anemia in chronic renal disease and malignancy, a wide range of new clinical indications for the use of rhEPO has been published in the medical literature. Among these new indications are: erythropoietin treatment before major elective surgery (for autologous transfusion of red blood cells); when the patient is reluctant or contraindicated to receive blood transfusions; anemia in HIV-infection; cardio- and neuroprotection; in critically-ill patients; blood-doping etc. This review focuses on these new indications for EPO treatment.
Key words: erythropoietin, anemia in chronic congestive heart failure, anemia in HIV-infection, anemia of prematurity, neuroprotection, treatment
Address for correspondence: Milena Nikolova, M. D., Clinic of Nephrology, University Hospital Alexandrovska, PB 45, 1431 Sofia, e-mail:


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