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Biomedical subjects

A Petrov

Publications and source records attributed to A Petrov.

At least 19 recordsLinked to original sources

[Genetics and epigenetics of facio-scapulohumeral progressive (Landouzy-Dejerine) muscular dystrophy].

Landouzy-Dejerine muscular dystrophy is a rare hereditary disease with prevalence of 0.9 to 1.4 in 100,000. Clinically the disease is characterized by weakness and atrophy of the facial and shoulder girdle muscles. It is caused by partial deletion of the 3.3-kb subtelomeric D4Z4 repeat on chromosome 4 (locus 4q35). This paper presents a critical review of the literature data and hypotheses explaining molecular mechanisms of progressive fascioscapulohumeral muscular dystrophy.

Chromosomes, Human, Pair 4↗

Transmission of 3 keV Ne7+ ions through nanocapillaries etched in polymer foils: evidence for capillary guiding.

We report unprecedented transmission experiments of 3 keV Ne7+ ions through capillaries of 100 nm diameter and 10 microm length produced by etching ion tracks in a polymer foil. We studied foils tilted up to +/-20 degrees for which the incident ions are forced to interact with the capillary surface. Surprisingly, the majority of Ne7+ ions were found to survive the surface scattering events in their initial charge state. The angular distributions of the transmitted particles indicate propagation of the Ne7+ ions along the capillary axis. This capillary guiding of the Ne7+ ion provides evidence that the inner walls of the capillaries become charged and electron capture from the surface is suppressed in a self-organizing process.

Journal Article↗

A study on the basic epidemiological parameters of viral hepatitis a in the region of Plovdiv, Bulgaria.

INTRODUCTION: Infection with hepatitis A virus is of great importance to public health. The disease has a worldwide occurrence due to inadequate sanitation and the variable seroprevalence rates in the community. OBJECTIVE: The present report investigates the epidemiological features of hepatitis A in the region of Plovdiv and outlines the most important epidemiological features of the disease. MATERIALS AND METHODS: In 1999 (a year with a lower hepatitis A prevalence) the basic epidemiological characteristics of the disease were studied: overall morbidity and mortality rates, age, sexual and seasonal distribution, and prevalence in rural and urban areas. The study was carried out in a cohort of 288 patients with hepatitis A admitted to the Clinic of Infectious Disease of the Medical University in Plovdiv. All patients were anti HAV IgM positive. Routine clinical, laboratory, epidemiological and statistical methods were used. Laboratory and serological tests were performed at the Center for Disease Control, Plovdiv and at the University Clinical Laboratory. RESULTS: Of 423 patients with acute viral hepatitis 288 (68.09%) had hepatitis A. In 1999 the morbidity rate for the region of Plovdiv was 49.55 per hundred thousand (intermediate). Disease prevalence was the highest in preschool and early school age as well as in the age groups 20-29 (84.67 per hundred thousand) and 30-39 (71.59 per hundred thousand). Urban residents accounted for 79.85% of the cases. The male/female ratio was 1:1. 82.25% of the preschool children did not attend day-care centers. History of contact with sources of infection was elicited from 17.01% of the patients. Disease rates peaked in October through December (maximum in October). CONCLUSIONS: Accumulated data could contribute to more effective disease control.

Adolescent↗

Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates.

The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5')-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation.

Animals↗

Disulfide cross-linked Fab-aggregates: preparation and biodistribution.

The high-molecular-weight soluble aggregates of Fab fragments of murine antibodies against cardiac myosin were prepared as a potential long-circulating and low immunogenic pharmaceutical carriers by conjugation of thiolated Fab and Fab modified with succinimidyl 3-(2-pyridyldithio)propionate. The clearance time and biodistribution of 111In-radiolabeled aggregates were studied in normal and nude-mice bearing human breast tumor implant and in rabbits with experimental myocardial infarction. The aggregates had a prolonged circulation time (half clearance time ca. 3-5 h) and ability to concentrate in the tumor and in the necrotic area of infarcted myocardium. Similar tumor-to-normal and infarct-to-normal accumulation ratios (ca. 3 h in both cases) suggest that combination of long circulation with impaired filtration in necrotic tissues is responsible for this accumulation rather than a specific interaction. The aggregates prepared may serve as long-circulating drug carriers able to deliver pharmaceuticals into areas with affected and leaky vasculature.

Animals↗

Very early noninvasive detection of acute experimental nonreperfused myocardial infarction with 99mTc-labeled glucarate.

BACKGROUND: 99mTc glucarate has recently been reported to be an infarct-avid agent. The feasibility of imaging with 99mTc glucarate was evaluated for the early diagnosis of nonreperfused and reperfused myocardial infarction and compared with localization of simultaneously administered 111In anti-myosin. METHODS AND RESULTS: Four groups of six rabbits each were studied. The left anterior descending coronary artery (LAD) was kept persistently occluded (n = 6) or reperfused after 40 minutes (n = 6) in rabbits. After confirmation of LAD occlusion by 201Tl scintigraphy, a mixture of 99mTc glucarate (15.7 +/- 1.6 mCi) and 111In anti-myosin (0.53 +/- 0.03 mCi) was administered intravenously. Another group of rabbits (n = 6) with 5 or 15 minutes of LAD occlusion were used to assess the affinity of 99mTc glucarate for the ischemic myocardium. The remaining 6 rabbits with reperfused myocardial infarction were used for the assessment of subcellular localization of 99mTc glucarate. 99mTc glucarate cleared rapidly from circulation (elimination t1/2, 36 minutes). Infarcts were visualized within 10 minutes in reperfused and within 30 minutes in nonreperfused coronary territories after intravenous administration. 111In anti-myosin delineated reperfused infarcts within 1 to 3 hours, but no uptake was seen in persistently occluded rabbits. 99mTc glucarate uptake in reperfused and nonreperfused infarct centers was 28 and 12 times greater, respectively, than that in normal myocardium (P = .0001). A direct correlation between glucarate and anti-myosin localization (r = .60 for nonreperfused; 0.76 for reperfused; P < .0001) was observed. Ischemic hearts showed no glucarate uptake. Subcellularly, 99mTc glucarate localized predominantly in the nuclear fraction of the infarct, with lesser extents in the mitochondrial and cytoplasmic fractions. CONCLUSIONS: Noninvasive imaging of myocardial infarcts with 99mTc glucarate is possible within minutes in persistently occluded or reperfused myocardial infarcts. Early detectability results from the rapid blood clearance and high avidity of glucarate for the acutely necrotic myocardial tissue.

Animals↗

Noninvasive detection of atherosclerotic lesions by 99mTc-based immunoscintigraphic targeting of proliferating smooth muscle cells.

BACKGROUND: Mouse/human chimeric antibody Z2D3 identifies an antigen produced exclusively by proliferating smooth muscle cells of human atheroma, and also cross reacts with experimentally induced atherosclerotic lesions in rabbits. Fab' fragments of Z2D3 antibody were labeled with (99m)Tc using glucaric acid as a weak transchelator. The potential role of (99m)Tc-labeled Z2D3 scintigraphy was explored for noninvasive imaging of experimental atherosclerotic lesions. METHODS AND RESULTS: (99m)Tc-Z2D3 Fab' was utilized for noninvasive imaging in four rabbits with experimentally induced atherosclerotic lesions and in one control rabbit. In addition, (99m)Tc-labeled nonspecific 103D2 Fab' was used for comparison in four other rabbits with atherosclerotic lesions. The atherosclerotic lesions were induced by balloon de-endothelialization of the infradiaphragmatic abdominal aorta and 12 weeks of hyperlipidemic diet. An aliquot of 15 mCi (550 mBq) of (99m)Tc pertechnetate was incubated with 6.25 mg of glucaric acid for 30 min followed by incubation of (99m)Tc glucarate with 375 microg of Z2D3 Fab' or 103D2 Fab' for an additional 30 min. Instant thin-layer chromatography demonstrated almost complete radiolabeling. (99m)Tc-Z2D3 was administered IV and gamma imaging was performed at the time of injection, 3, 6, 9, and 12 h, followed by ex vivo imaging of the excised aorta, and biodistribution was performed. Unequivocal visualization of atherosclerotic lesions was possible in all four animals at 9 to 12 h with Z2D3 Fab'. Quantitative uptake, as represented by mean lesion-to-liver count density ratio, was 0.6+/-0.05. Imaging with nonspecific 103D2 Fab' did not show any localization in the abdominal aorta (lesion-to-liver ratio, 0.45+/-0.02, p=0.02). Ex vivo lesion-to-normal aortic segment ratio was 4.3+/-0.9 for Z2D3 and 1.04+/-0.08 for nonspecific 103D2 Fab' (p=0.01). Biodistribution studies demonstrated 0.03+/-0.003% injected Z2D3 dose per gram in the atherosclerotic lesions as compared with 0.01+/-0.003% in the nondenuded thoracic aorta of atherosclerotic rabbits (p=0.008). However, only 0.008+/-0.002% of the mean injected dose per gram was obtained in the atherosclerotic lesions (p=0.001) as compared with 0.005+/-0.003% in the normal aortic segments with 103D2. No Z2D3 uptake in normal rabbits was observed on either the in vivo or ex vivo images. CONCLUSIONS: The present study demonstrates that (99m)Tc-based immunoimaging of the vascular lesions may be feasible by the use of smaller antibody fragments. Earlier visualization is possible at the expense of a lower absolute antibody uptake in the lesions as compared to the use of intact antibody or larger fragments with longer circulating time.

Animals↗

Feasibility for evaluation of the efficacy of conventional ventilatory support in very low birth weight infants.

Morbidity and mortality analysis in prematurely born low birth weight (LBW) neonates, very low birth weight (VLBW) neonates and extremely low birth weight (ELBW) neonates forms the cornerstone in current pediatric decision-making from both medical and socioeconomic point of view. The successful introduction of artificial ventilation for neonatal respiratory failure treatment has changed tremendously the prognosis of many diseases with a fatal outcome. This retrospective observational longitudinal study was designed to evaluate the changes in the following main indices: mean airway pressure (MAP), oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2), alveolar-arterial oxygen gradient (A-a)DO2, ventilation index and VEI in VLBW infants treated with conventional ventilatory support (CV), assess the information yield of these indices as indicators of gas exchange at each and every one moment of CV, and to analyze their feasibility, accuracy and real-time convenience as indicators of the adequacy of inhalation therapy and their role as an indispensable tool in constructing the optimal treatment regimen in VLBW infants. Forty-seven VLBW infants requiring ventilatory support within 24 hours of birth were enrolled in the study. Four of the infants survived and the remaining 43 died. The data collected were entered into a high-yield Neonatal Intensive Computer File and the indices were followed up sequentially and thoroughly analyzed as the primary outcome measures of the study. Our results show that: 1. The combination of indices we propose is a useful high-yield discriminating method for evaluating the efficacy of neonatal ventilatory support, arterial blood gas exchange and clinical status. 2. These indices allow early diagnosis of the changes in pulmonary mechanics, hemodynamics and blood saturation. 3. Using the combination of indices improves the diagnostic reliability and information yield of each one of them. 4. The twofold pattern of change of the indices in VLBW infants is well-recognized:--whereas a/A and OI change rapidly in the group of non-survivors reflecting the delicate balance in optimal gas-exchange using conventional methods in the survivors group there is a sustained tendency towards an increase in a/A values with a concomitant decrease in OI values. The airway pressure is constant in the presence of great fluctuations in OI values reflecting the breakdown in oxygenation at the high price paid for its sustenance in the nonsurvivors group whereas the mean airway pressure showed a gradual decrease in the survivors group and allowed early weaning from mechanical ventilation. (A-a)DO2 remained high in the non-survivors group thus reflecting a high-degree, practically constant shunting whereas the same index showed a tendency towards decrease in the survivors group. 5. These indices allow optimal management of neonatal ventilation and oxygenation and timely correction or a change of the ventilatory or/and oxygenation strategy. 6. This information forms the basis for prognostic conclusions regarding the current status or the survival of the neonates.

Humans↗

Unusual chromosome aberration, t(13;14)(q32;q32.3), in a case of essential thrombocythemia with extreme thrombocytosis.

A case of essential thrombocythemia (ET) with extreme thrombocytosis in a 70-year-old male patient is described. The cytogenetic analysis revealed a pathologic clone with the following previously unreported, unusual karyotype: 46,XY,t(13;14)(q32:q32.3) and pericentric inversion of chromosome 9. The possible association of t(13;14) with the high platelet count is discussed.

Aged↗

Noninvasive localization of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab')2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments.

BACKGROUND: A murine monoclonal antibody designated Z2D3 (IgM) generated against homogenized human atherosclerotic plaques was demonstrated to be highly specific for proliferating smooth muscle cells. The primary clone subsequently was genetically engineered to provide a mouse/human chimeric antibody with human IgG1 constant region expressed in a rat myeloma cell line. The resulting Z2D3-73.30 chimeric retained the immunoreactivity relative to the parent Z2D3-IgM and was pepsin-digested to yield F(ab')2. 111In-labeled chimeric Z2D3 F(ab')2 was then used for noninvasive imaging of experimental atherosclerotic lesions. To improve the imaging characteristics, we modified chimeric Z2D3 F(ab')2 fragments to carry a high negative charge. Improved visualization of targets with 111In-labeled, negatively charged, polymer-modified antibodies most probably is the result of faster blood clearance and a decrease in nontarget background activity. METHODS AND RESULTS: Experimental atherosclerotic lesions were induced in rabbits by deendothelialization of the infradiaphragmatic aorta followed by a 6% peanut oil-2% cholesterol diet. After 12 weeks, localization of the conventionally labeled 111In-Z2D3 F(ab')2 (24 Mbq [650 microCi]/500 to 750 micrograms) (n = 4) was compared with 111In-labeled, negatively charged, polymer-modified Z2D3 F(ab')2 (24 Mbq [650 microCi]/25 to 50 micrograms) in eight atherosclerotic rabbits. Three control rabbits also received radiolabeled polymer-modified Z2D3. Ten rabbits with atherosclerotic lesions received 111In-labeled nonspecific human IgG1 F(ab')2 with (n = 6) or without (n = 4) negative charge modification. Atherosclerotic lesions were visualized in all rabbits with the conventional Z2D3 F(ab')2 at 48 hours. However, unequivocal lesion visualization was possible at 24 hours only with negatively charged, polymer-modified Z2D3 F(ab')2. Quantitative uptake of F(ab')2 fragments was essentially determined by the presence of atherosclerotic lesions (F1.37 = 69.8; P < .0001) and the specificity of the antibody (F1.37 = 36.6; P < .0001). Uptake of the conventional Z2D3 in atherosclerotic lesions (mean +/- SEM percent injected dose per gram, 0.112 +/- 0.024%) was six times higher than background activity in the normal aortic segments (nondenuded thoracic aorta; mean percent injected dose per gram, 0.019 +/- 0.003%). Uptake of the conventional Z2D3 was also significantly higher than that of nonspecific human IgG1 F(ab')2 (0.027 +/- 0.004%). Specific uptake of the conventional Z2D3 in the lesions was comparable to the charge-modified Z2D3 uptake (0.084 +/- 0.017; P = .20). Uptake of negative charge-modified Z2D3 in the lesions was significantly higher than in the corresponding background activity in normal thoracic aorta (0.021 +/- 0.002). Uptake of negative charge-modified Z2D3 F(ab')2 in the lesions was higher than the uptake of negative charge-modified nonspecific IgG1 F(ab')2 (0.020 +/- 0.002) in the lesions. Uptake of charge-modified Z2D3 in the atherosclerotic lesions was also significantly higher than the corresponding regions of the aorta of the control rabbits (0.017 +/- 0.002; F1.18 = 27.9; P = .0001). There was, however, no difference in the specific lesion uptake of negative charge-modified Z2D3 at 24 hours (0.079 +/- 0.014) and 48 hours (0.084 +/- 0.0017; P = .99) after intravenous administration. Nontarget organ activities were lower with negative charge-modified 111In-labeled Z2D3 F(ab')2 than with the conventional Z2D3 F(ab')2. Mean kidney activity was fourfold less with the modified (0.45 +/- 0.06) than with the conventionally radiolabeled (1.67 +/- 0.264; P = .001) Z2D3 F(ab')2.

Animals↗

[Changes in the clinico-functional and immunological indices of patients with chronic obstructive lung disease, the allergic form, following combined climatotherapy at Sandanski health resort].

20 patients with chronic obstructive pulmonary disease who were treated in the resort of Sandanski, Bulgaria, during the autumn of 1988 were investigated for changes of some clinical, functional and immunologic indices--secretory immunoglobulins, lysozyme, serum bactericidal activity. The results revealed an improvement of the clinical indices mean in 50% of the patients, of the expiratory spirometric indices in mean 47% of the patients. Other findings were a distinct tendency towards a decrease of IgG and albumin in the saliva and an increase of the secretory IgA together with a statistically significant increase of the indices characterizing the nonspecific defence mechanisms of the lung.

Balneology↗

Inactivation of O6-alkylguanine-DNA alkyltransferase in the rat liver due to an intraperitoneal administration of methylated DNA.

Intraperitoneal administration of 6.5 mg of in vitro methylated DNA (meDNA) containing 1.5 x 10(-4) mM of O6-methylguanine (6MG) to male outbred rats weighing 150 g led to a considerable decrease in the activity of liver O6-alkylguanine-DNA alkyltransferase (AT). One hour after treatment there occurred a 4- to 5-fold decrease in the AT activity followed by its slow recovery. However, after 48 h, AT activity considerably exceeded control levels. A 5-fold decrease in the amount of administered meDNA resulted in the absence of its effect, whereas administration of higher amounts produced a further AT inactivation. A similar treatment with non-methylated DNA did not change AT activity. The possibility of AT exhaustion under in vivo conditions and thereby inhibition of repair of O6-alkylguanine in DNA, playing a key role in mutagenic, carcinogenic and antineoplastic effects of certain alkylating agents, might be helpful in increasing susceptibility of animals to such compounds.

Animals↗

[Complications in the cardiovascular system from neuroleptic treatment].

The arterial pressure fell abruptly in 23.38% of 124 psychic patients during the first days of treatment with neuroleptics. About two weeks later it gradually rose to its initial values. The patients who do not feel well with the low arterial pressure need peripheral stimulants such as Effortil, Mephentermin, etc. Other complications of the neuroleptic therapy are the rhythm and conduction cardiac disorders (19.96% of the patients over 60 years of age showed rhythm and conduction disorders--polytopic and multiple extrasystoles, ventricular paroxysmal tachycardia, atrioventricular block III degree). These patients need active surveillance and emergency treatment with antiarrhythmic drugs. The modern treatment of psychic diseases with larger doses of neuroleptics requires regular clinical and ECC control, especially in older patients.

Adult↗