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A Savov

Publications and source records attributed to A Savov.

At least 19 recordsLinked to original sources
PubMed2005

[Impact of inherited thrombophilia on the development of some pregnancy complications].

AIM: To assess the clinical significance of inherited thrombophilia [IT] for the development of some pregnancy complications. MATERIAL AND METHODS: The incidence of the following factors was studied in 97 pregnant women with pregnancy complications and in 103 controls: R506Q mutation encoding Factor V Leiden [FVL] synthesis, Prothrombin G20210A mutation, T677 methylenetetrahydropholate reductase mutation [MTHFR], 4G/4G polymorphism of the plasminogen activator inhibitor [PAI 4G/4G]. Among 97 patients in the group studied 39 had early onset severe preeclampsia [PE], 14--placental abruption [AP] without PE, 18--intrauterine growth restriction [IUGR] without PE, 12--stillbirth [SB] without PE, 14--habitual spontaneous abortions [HSA]. The control group included 103 clinically healthy pregnant women with at least one previous uneventful pregnancy, without history of thromboembolic disorders. In addition, patients with severe PE with and without IT were compared regarding g. a. and birthweight at delivery and intrauterine fetal loss rate. DNA analysis was performed according to internationally accepted standards. Pregnancy outcomes were ascertained from hospital records. Statistical significance (p < 0.05) was assessed by means of Student's t-test. RESULTS: FVL mutation was found in 23.7% (23/97) of the patients from the studied group and in 5.8% (6/103) of the controls. Prothrombin G20210A carriers were 11% (11/97) of the studied and 3.8% (4/103) of the controls, while with PAI 4G/4G polymorphism they were 30.9% (30/97) and 14.5% (15/103) respectively. MTHFR T677 was not more frequent in the studied group (8.2%) compared to the control one (29%). Eight of the patients (9.6%) were carriers of more than one mutation. In 22 cases with early onset severe PE and IT gestational age and birthweight at delivery were lower than in the cases with severe PE without IT while intrauterine fetal loss rate did not differ significantly between the two groups. CONCLUSIONS: Inherited thrombophilia is found more frequently in women with pregnancy complications like PE, IUGR, AP, SB, HSA. The incidence of homozygous MTHFR T677 is not higher in these cases. IT worsens the prognosis of severe PE. The diagnosis of IT is important since anithrombotic therapy has to be considered to protect the mother and the fetus.

Abortion, Habitual↗
PubMed2004

[Sucessful pregnancy outcome following three severe placental abruptions and intrauterine fetal death in the patient--heterozygous carrier of R506Q mutation of factor V (Leiden)].

A case of successful pregnancy outcome is reported in a patient with 3 preceding severe placental abruptions with intrauterine fetal death and caesarean deliveries. In the course of the current pregnancy heterozygosity for R506Q mutation of factor V (Leiden) was diagnosed in 26 weeks of gestation [w.g.] and low molecular weight heparin [LMWH] therapy initiated. Maternal condition was stable until delivery and all laboratory findings were within normal range. The fetus was followed up by ultrasound biometry and Doppler blood flow studies. From 28 w.g. on NST and biophysical profile were included. An emergency caesarean section was performed in 34 w.g. because of contractions not responding to tocolysis. The newborn was in good condition with weight and length corresponding to the 10th centile for gestational age [g.a]. Histologic study of the placenta showed anemic infarctions and recent haemorrhages in the basal and the chorionic plate. The initiation of LMWH therapy in the case reported was late (26 w.g.). By that moment there was already evidence of impaired fetal growth with fetal biometry corresponding to the 10th centile for g.a. After LMWH therapy was started no further slow down of fetal growth was registered. Successful pregnancy outcome may be related not only to LMWH therapy but also to other factors like active fetal monitoring after 28 w.g. and the emergency caesarian delivery immediately after the onset of uterine contractions. Patients with past obstetric history of severe preeclampsia, placental abruption or fetal growth restriction have to be screened for hereditary or acquired thrombophilia. If a thrombophillic state is present early LMWH therapy has to be considered. It is aimed to prevent anaemic placental infarctions and thrombotic complications.

Abruptio Placentae↗
PubMed2000

Hereditary motor and sensory neuropathy--Lom (HMSNL): refined genetic mapping in Romani (Gypsy) families from several European countries.

Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb.

Adolescent↗
PubMed2000

Audiological problems in patients with tinnitus exposed to noise and vibrations.

Tinnitus is a hearing sensation appearing without available sound fluctuations in the external environment. It is one of the major, constant and earliest symptoms suggesting different pathology of the hearing analyser. It must be considered, though, that it is evidenced also at disturbed functions of other organs and systems of the organism. The aim of the present study is to elucidate the state of the hearing analyser in patients with tinnitus occupationally exposed to noise and vibrations in relation to therapy. The study was performed on 67 miners, aged 34-55, mean age 44.5 years. The workers with subjective tinnitus (29 persons--43% of the studied group) are the object of this investigation. They were subjected to the following tests of the hearing analyser: pure tone audiometry; above-threshold audiometry (Carhardt's adaptation test, Lusher's differential threshold, SISI test, Kietz test. The evidence reveals that the studied group of workers occupationally exposed to noise, vibrations, dust, toxic substances etc. complain predominantly of tinnitus. It is accompanied by vertigo, headache and disturbed balance. Changes in the hearing function are observed; manifested by different degree of hypacusia concerning air and bone conductivity in the pure tone audiometry. The above-threshold tests also evidence deviations suggesting disturbed hearing function. These changes can be explained by mechanical-toxic pathogenic mechanisms leading to cerebral and vestibular dysfunction most probably of vascular-circulatory type manifested by the above stated deviations. The results are the basis for the following conclusions: 1. The anamnestic profile of workers with tinnitus exposed to noise and vibrations shows a prevalent percentage of vertigo, followed by headache and disturbed balance. 2. The otoneurological profile shows changes in the air and bone conductivity manifested by different degree of hypacusia. 3. The evaluation of the above-threshold tests also confirms the evidence of disturbed hearing function. 4. The relevant therapeutical approach has to be elaborated, having in mind the existing suggestion about the mechanical-toxic etiopathogenesis of the developed process of vascular-circulatory type.

Adult↗
PubMed1999

A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies).

Galactokinase deficiency is an inborn error in the first step of galactose metabolism. Its major clinical manifestation is the development of cataracts in the first weeks of life. It has also been suggested that carriers of the deficiency are predisposed to presenile cataracts developing at age 20-50 years. Newborn screening data suggest that the gene frequency is very low worldwide but is higher among the Roma in Europe. Since the cloning of the galactokinase gene (GK1) in 1995, only two disease-causing mutations, both confined to single families, have been identified. Here we present the results of a study of six affected Romani families from Bulgaria, where index patients with galactokinase deficiency have been detected by the mass screening. Genetic linkage mapping placed the disease locus on 17q, and haplotype analysis revealed a small conserved region of homozygosity. Using radiation hybrid mapping, we have shown that GK1 is located in this region. The founder Romani mutation identified in this study is a single nucleotide substitution in GK1 resulting in the replacement of the conserved proline residue at amino acid position 28 with threonine (P28T). The P28T carrier rate in this endogamous population is approximately 5%, suggesting that the mutation may be an important cause of early childhood blindness in countries with a sizeable Roma minority.

Adolescent↗
PubMed1999

Tinnitus, heart rate variability, and some biochemical indicators.

Twenty-three tinnitus patients between the ages of 25 and 66 years (mean age, 47.6) were examined completely in the neurootological clinic of the Medical University, Sofia. Heart rate variability measurements were obtained to reveal the relationship between tinnitus and the autonomic equilibrium. Some biochemical indicators (serotonin and the colored sedimentary uric reaction of Kimbarovski [CSURK]) also were followed up. For 19 patients with transitional disturbances in the vertebrobasilar blood circulation, the sympathetic portion of the autonomic nervous system predominates, and heart rate variability is suppressed. The higher suppression of heart rate variability and higher values of the health risk in four occupationally exposed patients are attributable to the higher expressed level of stress connected with the adverse work conditions. Changes in the health risk, CSURK, and serotonin blood values in four tinnitus patients also are discussed.

Adult↗
PubMed1997

SSCP analysis: a blind sensitivity trial.

Studies of the sensitivity of SSCP analysis usually have been performed under conditions contrary to the rules of quality control trials and have produced widely different results. We have performed a blind trial of the sensitivity of SSCP analysis for the detection of mutations in fragments up to 500 bp in length under a fixed single set of electrophoretic conditions. The mutation detection rate was 84%. In addition, we have identified a second mutation in nine samples. All these mutations are polymorphisms, including a novel polymorphism 1248 + 52T/C first reported in the present work.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed1997

Cystic fibrosis mutations and associated haplotypes in Bulgaria - a comparative population genetic study.

We present data on the population genetics of cystic fibrosis (CF) in Bulgaria, obtained by comprehensive mutation analysis and the construction of intragenic microsatellite haplotypes. The sample of 262 CF alleles analysed is representative of the patients diagnosed during the period of referral and of the three main ethnic groups in the country. deltaF508 accounted for 100% of Gypsy CF alleles, which thus differed significantly from both Bulgarians and ethnic Turks. In Bulgarian and Turkish CF patients, 92% of the mutant alleles were identified, yielding a total of 25 different mutations, of which only 7 occurred at frequencies higher than 1%. The findings were compared to other European populations and to the distribution of phenylketonuria mutations. Genetic distances and population trees demonstrated that in the south-eastern tip of Europe, the overall distribution of CF mutations and polymorphic haplotypes is very close to that of Mediterranean populations, with a high frequency of N1303K and G542X, a large number of rare mutations and a prevalence of the 23 31 13 haplotype in association with deltaF508. These findings are consistent with a main role for the Neolithic expansion in the shaping of the CF mutation spectrum in Bulgaria and southern Europe.

Bulgaria↗
PubMed1997

[Occupational sensitization to methylene diphenyl diisocyanate during the manufacture of polyurethane products].

A complex occupational hygienic and clinical allergologic investigation in a methylene-diphenyl diizocyanate (MDI)-based polyurethane products manufacture was carried out for the first time in this country. The average MDI concentrations for a shift are within the limits of TWA, but during short operations exceed STEL and reach 0.072-0.181 mg/m3. By clinical and immuno-allergologic methods, applied on 46 MDI-exposed workers and 42 controls, the sensibilizing effect on the respiratory system, skin and eyes was detected. The allergic reactions take the course of bronchial asthma (6.5%), rhinitis and rhinopharyngitis (37%), rhinosinusitis (13%), conjunctivitis (13%), and urticaria and dermatitis (17.4%), as in 12 cases (12%) the allergic illnesses are combined. The specific occupational sensibilization, proved by positive dermal allergy tests with MDI in 24 (52%) exposed workers, and increased MDI-IgE antibodies in 4 workers, is of high statistical reliability in comparison with the control group and supposes immune reactions of quick type (IgE) and mainly retarded type--cell mediated. Various prophylactic measures against the proven occupational sensibilization risk are proposed.

Adult↗
PubMed1997

Optimization of single-strand conformation polymorphism analysis in the presence of polyethylene glycol.

We report optimization of single-strand conformation polymorphism (SSCP) analysis in the presence of polyethylene glycol. The protocol developed separates single-strand conformers in a much shorter time (1-3 h) than conventional SSCP protocols and broadens the applicability of SSCP analysis from 150 to as much as 500 bp of DNA by different percentages of GC content present. We conclude that addition of polyethylene glycol helps improve the differential separation of conformers and, in combination with high-resolution polyacrylamide gel electrophoresis, offers an alternative to previous SSCP analysis protocols. This protocol should be very useful for clinical applications in routine detection of mutations as well as for research purposes.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed1996

Gene mapping in Gypsies identifies a novel demyelinating neuropathy on chromosome 8q24.

Founder effect and linkage disequilibrium have been successfully exploited to map single gene disorders, and the study of isolated populations is emerging as a major approach to the investigation of genetically complex diseases. In the search for genetic isolates ranging from Pacific islands to Middle East deserts, the 10 million Gypsies resident in Europe have largely escaped the attention of geneticists. Because of their geographical ubiquity, lack of written history and the presumed social and cultural nature of their isolation, Gypsies are construed as not meeting the criteria for a well defined founder population. Gypsy society has a complex structure with subdivisions and stratifications that are incomprehensible to the surrounding populations. Marginalization by the health care systems in most countries results in a lack of information on causes of morbidity and mortality and little is known about hereditary disorders or the population genetic characteristics of Gypsies. This study is the first example of mapping a disease gene in endogamous Gypsy groups. Using lod score analysis and linkage disequilibrium, we have located a novel demyelinating neuropathy to a narrow interval on chromosome 8q24. We show that the disease, occurring in Gypsy groups of different identity and history of migrations, is caused by a single mutation whose origin predates the divergence of these groups.

Adolescent↗
PubMed1995

Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation.

Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) that codes for a cAMP-regulated chloride channel. The R347P is a missense mutation located within the first membrane spanning domain (MSD1) of the CFTR protein. This mutation occurs with an overall worldwide frequency of about 0.2%. The patients, originally described with this mutation were compound heterozygotes with the delta F508 mutation and had a very mild course of CF, suggesting that R347P, similar to other missense mutations affecting the MSD1 domain, causes a mild phenotype. We report here a group of 19 CF patients with the R347P mutation of German, Bulgarian, Czech, and Slovak origin, including two homozygotes. Most patients presented with early disease onset, pancreas insufficiency (PI), and early pulmonary involvement, suggesting that this mutation can lead to a severe course of CF. Most R347P alleles in the group studied share a common polymorphic haplotype. In addition, these analyses gave evidence for recurrence of the mutation in two CF patients of German and Czech origin.

Cystic Fibrosis↗