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Biomedical subjects

N I Kapranov

Publications and source records attributed to N I Kapranov.

At least 19 recordsLinked to original sources

[Dynamics of markers of blood inflammation against the background of antibacterial therapy in children with mucoviscidosis, with the various regimens of intake of pancreatic enzymes].

The results of the studies show that patients with mucoviscidosis diagnosed for the first time who do not receive any adequate replacement pancreatic therapy should not be prescribed high doses of pancreatic enzymes along with antibacterial therapy when they are hospitalized on account of exacerbation of the bronchopulmonary process. Sharply increased lipid absorption can cause an aggravation of oxidative stress and impair the patient's state instead of improving it. In our opinion, such patients should be prescribed delayed adequate pancreatic therapy with immediate introduction of high doses of antioxidants (vitamins E, A, C, beta-carotene, etc.). There is no doubt that it is necessary to conduct further research into the problem for a greater number of patients.

Adolescent↗

Improvement of nutrient absorption may enhance systemic oxidative stress in cystic fibrosis patients.

BACKGROUND: The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the pulmonary disease severity and progress. Malnutrition may be an important complicating factor in active and chronic lung disease. AIMS: The focus of this study was to investigate several inflammatory markers in pancreatic-insufficient CF patients with different enzyme treatment regimens. METHODS: CF patients with pancreatic insufficiency were examined at a time of symptomatic exacerbation of their lung disease. Group A (n = 11) regularly received microspheric enzymes. Group B (n = 8) were treated with enzymes during the hospitalization period only and demonstrated the presence of malnutrition. Inflammatory markers in the sputa (neutrophil elastase activity, interleukin-8 and tumour necrosis factor-alpha levels) and in the peripheral blood (plasma malondialdehyde (MDA), lymphocyte response to PHA, and the cell sensitivity to steroid suppression) have been investigated. RESULTS: During acute lung exacerbation, group B demonstrated reduced levels of lymphocyte proliferation. This parameter was normalized after combined antibiotic and pancreatic enzyme therapy. Simultaneously, plasma MDA in group B markedly increased following treatment. For this group, a significant positive linear association between values of plasma MDA and lymphocyte proliferation has been observed. For group A, neither the same correlation nor changes in MDA levels and lymphocyte proliferation have been found. CONCLUSIONS: Our data indicate that acute lung exacerbation in malnourished CF patients may be associated with alteration in T-lymphocyte activity. Adequate therapy normalizes lymphocyte function but results in systemic oxidative stress.

Absorption↗

Tumor necrosis factor-alpha/interleukin-10 balance in normal and cystic fibrosis children.

BACKGROUND: The balance between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-alpha contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-alpha is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators. AIMS: In the present study, the relationships between TNF-alpha and IL-10 in the plasma of healthy school-children and cystic fibrosis (CF) patients have been investigated. METHODS: Blood samples were obtained from 12 CF patients with chronic pulmonary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-alpha were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-alpha over anti-inflammatory IL-10 (TNF-alpha/IL-10 > 1). In these subjects, a significant positive linear association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-alpha/IL-10 ratios. In addition, a disappearance of correlation between the cytokine values was observed. Such disturbance was related to exuberant elevation of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma cytokine values remained in strong linear association independently of TNF-alpha or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients during a 6-month observation period have been revealed. CONCLUSIONS: There were no fundamental differences between CF and healthy children in the regulation of TNF-alpha and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-alpha, whereas immune disturbance was characterized by IL-10 superiority. The only abnormality that was found in CF patients consisted of their inability to produce unlimitedly IL-10 in response to antigen stimuli.

Adolescent↗

[Outcomes of the long-term treatment with a novel mucolytic drug pulmozin in mucoviscidosis patients].

AIM: To study clinical effectiveness and safety of a new mucolytic drug pulmozim (Switzerland) adjuvant to basic therapy in mucoviscidosis patients of different age in Russia. MATERIAL AND METHODS: 15 patients with mucoviscidosis aged 5-36 years, functional lung capacity and FEV-1 at least 40% received pulmozim for 30 days. The drug was given in a single daily dose 2.5 mg in inhalations. The study included three stages: initial 14 days--discontinuation of all mucolytic drugs, 30-day course of pulmozim, 14-day follow-up without pulmozim and other mucolytics. RESULTS: Pulmozim in the above regimen was effective in patients with mixed and moderate mucoviscidosis. The drug facilitates respiration, improves sputum rheology, normalizes general condition of the patient, is simple for use, has good organoleptic properties. CONCLUSION: Pulmozim is an effective mucolytic drug in combined treatment of mucoviscidosis.

Adolescent↗

[Antibiotic therapy of cystic fibrosis in children].

It is postulated that P. aeruginosa in monoculture or in association with Staphylococcus aureus keeps its leading position in chronic bacterial inflammatory broncho-pulmonary processes in children with cystic fibrosis. Antibiotic resistant strains of Burkholderia cepacia, Stenotrophomonas maltophila, Alcaligenes xylosoxidans were revealed (7.1% of the strains). P. aeruginosa strains were susceptible to aminoglycosides, ciprofloxacin, and polymixin B. Susceptibility of smooth and mucoid forms of P. aeruginosa to ceftazidime stayed at the level of 49.6-57.1%. Such microbial associations as P. aeruginosa sm. + S. aureus, P. aeruginosa sm. + P. aeruginosa muc. + S. aureus were mainly susceptible to ciprofloxacin, aminoglycosides and resistant to ceftasidime. Meropenem, cefepim and ciprofloxacin are highly effective antibiotics for the treatment of broncho-pulmonary processes exacerbations at children with chronic P. aeruginosa cystic fibrosis. Intravenous use of antibiotics out of hospital for the treatment of the children with cystic fibrosis is clinically effective, and is economically and psychologically reasonable. It should be used more widely in medical practice.

Anti-Bacterial Agents↗

[Comparative yearly growth rate of children with mucoviscidosis treated and not treated with ciprofloxacin:clinicomorphological comparisons].

The results of the prospective and comparative investigation of the linear growth of children at the age of 4 to 16 years with mucoviscidosis treated with ciprofloxacin in combination with a cephalosporin or an aminoglycoside in the main group and a cephalosporin or an aminoglycoside alone in the control group are presented. The children were observed for 3 and 5 years. It was shown that in spite of the treatment term with ciprofloxacin the yearly growth rate in the children in the main and control groups did not significantly differ. The morphological investigation did not reveal any injury of the armicular cartilage and growth zone. The hyperplastic reaction in the tegmental cartilage was states and considered as a physiological one in response to the presence of ciprofloxacin and therefore reversible. No chondrotoxicity of the fluoroquinolones and ciprofloxacin, particularly in the children, is explained.

Adolescent↗

[The efficacy and safety of ciprofloxacin in treating children with mucoviscidosis].

Ciprofloxacin clinical and bacteriological efficacies, as well as tolerability mainly with respect to chondrotoxicity were evaluated in the treatment of children with mucoviscidosis. The drug was shown to have high clinical and moderate bacteriological efficacies. As for its tolerability, adverse reactions chiefly associated with affection of the gastrointestinal tract, i.e. nausea, stomach pain, diarrhea, increased transaminase levels were recorded. The arthrotoxicity episode was single and transitory. The use of ciprofloxacin had no negative effect on the children growth. No chondrotoxic effect of ciprofloxacin in the treatment of children was observed which is explained in the paper. It is concluded that ciprofloxacin is in general an efficient and safe antibiotic useful for the treatment of children.

Adolescent↗

[Immunologic monitoring of patients with cystic fibrosis: value of different laboratory findings].

Cystic fibrosis (CF) is a common, serious, and frequently fatal autosomal recessive genetic disorder associated with the poor function of chloride channels. Chronic endobronchial inflammation and bacterial infection are main causes of morbidity and mortality due to CF. The study dealt with a relationship between progression and inflammation markers. Twenty one CF children with acute pulmonary exacerbation were examined. The signs of peripheral blood inflammation (responses of lymphocytes to PHA and their sensitivity to the antiproliferative effect of glucocorticoids) and in situ inflammation markers (sputum elastase activity, IL-8 and TNF-alpha, and protein concentrations in the same sputum specimens). These laboratory findings were used to calculate a "laboratory index" (LI). The clinical status of each patient was evaluated with a "clinical index" (CI), a parameter that includes respiratory secretion cultures, pulmonary function test results, nutritional status, and the presence of disease-related complications. There was a positive linear correlation between LI and CI. The presence of P. aeruginosa was strongly associated with the changes of inflammatory markers. CF patients with prolonged P. aeruginosa infection demonstrated extremely enhanced elastase activity and elevated amounts of sputum IL-8 and TNF-alpha as compared to uninfected subjects. The lung elastase activities, sputum protein contents, and TNF-alpha levels in individuals with short-term colonization were at or below those without P. aeruginosa infection. In patients with or without short-term colonization, the normalization of laboratory parameters was strongly related to evident clinical improvement. At the same time, antibiotic treatment failed to suppress an excessive inflammatory response in the lungs of patients with prolonged P. aeruginosa infection. The importance of individual inflammation markers is discussed in the paper.

Adolescent↗

[Evaluation of tolerance and efficacy of pefloxacin in the treatment and prevention of severe infections in children with mucoviscidosis and aplastic anemia].

Pefloxacin (Abaktal) efficacy and safety were investigated at 21 children (7-16 years old) randomized in 2 groups: children with mucoviscidosis and children with aplastic anemia. The drug was used at the dose 15-20 mg/kg per day bid for 14-28 days. Pefloxacin was used in combination with ceftazidime and amikacin. Combined therapy demonstrated good clinical efficacy. Bacteriological efficacy was not uniform: staphylococci were not isolated from sputum since the 7th day of treatment, but pseudomonads were cultured even on the 14th day of the treatment (the sensitivity to pefloxacin remained). The only but frequent side-effect was arthropathy. The background and some peculiarities of arthropathy development were analyzed. This phenomenon is called quinolone-induced synovitis. The risk group for quinolone-induced synovitis was estimated--children elder than 10 years with allergic anamnesis. Good clinical efficacy and tolerability of pefloxacin at the children with mucoviscidosis or aplastic anemia is a reason and base to cancel the limits to its use in pediatrics.

Adolescent↗

[Comparative morphological analysis of the articular cartilage, epiphyseal plate, spongy bone, and synovial membrane of the knee joint in children treated and not treated with ciprofloxacin].

Comparative data on he postmortem morphological examination of the knee joint in children treated and not treated with ciprofloxacin while alive are presented. Nine children were ill with mucoviscidosis and 8 children were ill with aplastic anemia. The patients were ill with mucoviscidosis and 8 children were ill with aplastic anemia. The patients were treated with ciprofloxacin in a daily dose of 20 to 40 mg/kg body weight at the average for 148 days. The condition of the articular cartilage, growth area, spongy bone and synovial membrane of the knee joint was examined visually, histologically and morphologically. It was revealed that ciprofloxacin had no chondrotoxic effect. The structure affected in some cases by the ciprofloxacin treatment was the synovial membrane which developed subacute synovitis not clinically manifested (latent) in life. The phenomenon is explained.

Adolescent↗

[Fluorine level in the bone and cartilage in children treated with ciprofloxacin (data obtained from the femur distal part].

Comparative data on the content of fluorine in various sections of the left femur distal part, i.e. spongy bone, process zone and articular cartilage are presented. The examination was performed on postmortem sections from 10 pediatric cases (the average age of 9.5 years) with mucoviscidosis or aplastic anemia treated before the death for up to 12 months with ciprofloxacin in a dose of 20 to 40 mg/kg body weight. The control postmortem sections were from 10 practically healthy children (the average age of 10.4 years) killed in a car accident. The sections were subjected to 2-stage dry ashing with ionometric determination of the fluorine ions. The results were treated according to the V.Yu. Urbach procedure. It was shown that the content of fluorine in the sponge bone and process zone in both the groups did not significantly differ. A comparatively high content of fluorine was detected only in the postmortem sections of the articular cartilage from the children of the main group who however had no chondrotoxic symptoms while alive. That means that the difference is statistically and clinically insignificant.

Adolescent↗

Inflammatory markers in cystic fibrosis patients with lung Pseudomonas aeruginosa infection.

Chronic endobronchial inflammation and bacterial infection are the main causes of morbidity and mortality in cystic fibrosis (CF), an autosomal recessive genetic disorder associated with improper function of chloride channels. Inflammation in CF lung is greatly amplified after Pseudomonas aeruginosa infection. In this study the relationship between P. aeruginosa status and inflammatory markers has been investigated. Seventeen CF children in acute lung exacerbation were examined. CF patients without P. aeruginosa infection were characterized by elevated activity of sputum elastase, reduced response of peripheral blood lymphocytes to PHA and significant resistance to the antiproliferative action of glucocorticoids. These parameters were normalized after antibiotic treatment. The patients with prolonged P. aeruginosa infection demonstrated extremely high levels of elastase activity and elevated amounts of sputum IL-8 and TNF-alpha. Although antibiotic treatment resulted in clinical improvement, it failed to suppress excessive immune response in the lung. The data indicate that CF patients with prolonged P. aeruginosa need the modified treatment, which should include immunomodulating drugs and protease inhibitors as well as antibacterial therapy.

Anti-Bacterial Agents↗

[The safety of ofloxacin].

The data on a comparative study of ofloxacin arthrotoxicity in pediatric and adult patients are presented. The tolerability of ofloxacin used in various doses and treatment terms (acute and cumulative effects) was investigated in children. The impact of the patient pubertal age, sex, ofloxacin concentrations (Cmax above 4 micrograms/ml) and arthrological diseases (in adult patients) on the risk of the quinolone arthropathy was evaluated. Good tolerability of the various ofloxacin dosing regimens in both the adult and pediatric patients was shown.

Adolescent↗

[Detection of frequent mutations of the CFTR gene in cystic fibrosis patients from Central Russia].

About 100 patients with cystic fibrosis (CF) from the European part of Russia were screened for mutations 2143delT, 2184insA, S1196X, 3732delA, and W1282X. The patients had one or two mutations (other than delta F508) in CF chromosomes. The frequency of these mutations were estimated in CF chromosomes without the delta F508 mutation. The frequencies of mutations 2143delT, 2184insA, S1196X, and W1282X were 2.9, 7.4, 2.2, and 4.8%, respectively. Linkage was found between allele 6 of the variable site (a tetranucleotide repeat in intron 6 of the gene for CF) and mutations G542X and 2143delT, as well as between allele 7 and mutations R334W, 2184insA, S1196X, and W1282X. Except for delta F508, the most common mutations were 2184insA, 2143delT, and W1282X.

Alleles↗

[TUB9 polymorphism in the CFTR gene of cystic fibrosis patients, carriers, and healthy donors from the Moscow region. SSCP and restriction analyses].

Data on the screening of 266 non-delta F508 chromosomes (42 cystic fibrosis patients, 43 carriers, and 48 healthy donors from the Moscow region) for the presence of structural abnormalities within the tenth exon of the CFTR gene conducted by means of the single-stranded conformation polymorphism (SSCP) technique in nonisotope modification are presented. The method used made it possible to detect three SSCP variants, one of which was present in cystic fibrosis patients (23.8%) and carriers (9.3%), but not in healthy donors. Sequencing of the 5 amplified DNA fragments carrying this SSCP variant revealed an A-->G substitution in the 1525-61 position, which indicated the presence of TUB9 polymorphism with allele 1 in the homozygous state in all cases tested. The three SSCP variants described corresponded to the three allelic variants of TUB9 polymorphism as judged by MnlI restriction analysis of the amplified tenth exon sequence. The modified SSCP technique is also suitable for routine screening for the G542X, G55ID, and W1282X point mutations within the CFTR gene. The frequency distribution of polymorphic TUB9 marker alleles across the non-delta F508 chromosomes in the three studied groups were estimated. Homozygotes for the TUB9 allele 1 were shown to have identical GATT-TUB9-M470V haplotypes.

Case-Control Studies↗

[Use of ciprofloxacin in children with mucoviscidosis].

The efficacy of ciprofloxacin was estimated for the last 3 years in the treatment of 139 children with mucoviscidosis. The drug was mainly used under hospital conditions. In 119 cases ciprofloxacin was administered orally in a daily dose of 25 to 50 mg/kg divided into 2 portions. The treatment course was 14-42 days. In 20 cases ciprofloxacin was used intravenously in a daily dose of 10 to 23 mg/kg injected twice a day with an interval of 12 hours. The treatment course was 14-18 days. Ciprofloxacin was used either alone (exclusively in outpatients) or in combination with the 2nd or 3rd generation cephalosporins or aminoglycosides. The positive effect was practically stated in all the patients in 10-14 days from the therapy start. The clinical remission at the background of the ciprofloxacin therapy in the inpatients was observed 3 days earlier than that in the inpatients treated without the use of ciprofloxacin. The remission period in the outpatients averaged 62 days while in the cases treated with gentamicin it was 35 days and in the cases treated with azlocillin it was 30 days. The adverse reactions were recorded in 8 per cent of the patients.

Administration, Oral↗

[Molecular genetic analysis of TUB18 and TUB20 intragenic polymorphism and various mutations of the CFTR gene in the Moscow region].

Allelic frequencies of two intron polymorphisms in the cystic fibrosis transmembrane regulator (CFTR) gene, TUB18 and TUB20, were estimated on chromosomes of 67 cystic fibrosis patients and on that of 37 healthy donors from Moscow and the Moscow oblast. Allele 2 of the TUB 18, and allele 1 of the TUB20 were 2.1 and 1.5 times more frequent on the non-delta F508 chromosomes of the cystic fibrosis patients than on chromosomes of healthy donors, i.e. these alleles were in linkage disequilibrium with the CFTR gene. Allele 1 of the TUB18 marker and allele 2 of the TUB20 marker demonstrated absolute linkage disequilibrium with the delta F508 mutation of the CFTR gene. The degree of association between the TUB18 and TUB20 intron polymorphisms and the GATT and T854T intragenic polymorphisms was analyzed. Of all 62 delta F508 chromosomes tested, 98.3% shared the 2-1-1-2 GATT- T854T-TUB18-TUB20 haplotype. Eight major (more frequent) GATT-T854T-TUB18-TUB20 haplotypes were found in 89.5% of normal, and in 97.9% of non-delta F508 chromosomes of cystic fibrosis patients from the Moscow region. Three of these major haplotypes, 2-1-1-2, 1-2-2-1, and 2-2-1-2, were respectively 2.5, 2, and 1.5 times more frequent on non-delta F508 cystic fibrosis chromosomes than on normal chromosomes. Data on screening for the G542X, N1303K, and 394delTT mutations of the CFTR gene, carried out on 134 chromosomes of cystic fibrosis patients from the Moscow region are presented. The frequencies of the G542X and 394delTT mutations were estimated as 1.5%, while the frequency of the N1303K mutation was 2.2%.

Alleles↗

Complete screening of mutations in the coding sequence of the CFTR gene in a sample of CF patients from Russia: identification of three novel alleles.

To date, a large number of mutations causing the disease, cystic fibrosis, have been reported worldwide. Having analysed the coding sequence of a sample of cystic fibrosis (CF) patients from Russia, we have identified three novel CF mutations. Two of them, 175 del C in exon 1 and 624 del T in exon 5, are frameshift mutations, predicted to result in premature termination of the CFTR transcript. The third mutation is missense and occurs in exon 12 (D572N). The profile of mutations in this sample of Russian CF patients is particular, with two mutations in exon 13 (2143 del T and 2184 ins A), accounting for 12% of the non-delta F508 alleles.

Alleles↗