[Methodological recommendations for surgical care in patients with hemophilia A receiving prophylactic therapy with emicizumab]. / Metodicheskie rekomendatsii po okazaniyu khirurgicheskoi pomoshchi u patsientov s gemofiliei A, poluchayushchikh profilakticheskuyu terapiyu emitsizumabom.

Methodological recommendations for surgical care in patients with hemophilia A receiving prophylactic therapy with emicizumab. Recommendations of the expert group. Moscow, 2024.

Recombinant B-domain-deleted porcine sequence factor VIII (r-pFVIII) for the treatment of bleeding in patients with congenital haemophilia A and inhibitors.

INTRODUCTION: Development of inhibitors to human FVIII (hFVIII) significantly complicates the control of bleeding events in patients with haemophilia A. AIM: This prospective, multicentre, open-label, non-comparative, Phase II study evaluated the haemostatic activity of a recombinant B-domain-deleted porcine FVIII (r-pFVIII), in the treatment of non-life/non-limb-threatening bleeding in individuals with haemophilia A and FVIII inhibitors. METHODS: Acute bleeding episodes in patients with pFVIII inhibitor titres <0.8 BU mL-1 were treated with 50 U kg-1 body weight r-pFVIII. Those with pFVIII inhibitor titres of >0.8 BU mL-1 received an initial calculated r-pFVIII loading dose followed by 50 U kg-1 treatment dose. Treatment continued at 6-hourly intervals until bleeding was determined, controlled or till a maximum of eight doses was reached. RESULTS: All 25 bleeding episodes in nine patients (mean age: 23.7 years; range: 14-34 years) were controlled successfully with eight or fewer injections of r-pFVIII. The median time from bleeding onset to the administration of r-pFVIII was 5.7 h (range: 1.5-20.0 h). Twenty of the bleeding episodes (80%) were controlled with one treatment dose of r-pFVIII (with or without a loading dose, median dose: 200.8 U kg-1 ; range: 50-576 U kg-1 ) regardless of pFVIII level. r-pFVIII was well tolerated and no treatment-emergent serious adverse events were considered by the investigator to be related to r-pFVIII administration. CONCLUSION: The results suggest that FVIII replacement therapy with r-pFVIII could be a viable alternative to bypassing agents for the treatment of bleeding episodes in individuals with haemophilia A and FVIII inhibitors.

[Non-Hodgkin lymphoma (a case of simultaneous ocular and orbital involvement)].

The paper presents an integrated analysis of clinical, instrumental, and morphological data on a very rare pathological condition-- simultaneous ocular and orbital involvement in a lymphoproliferative disorder.

[Effects of mercazolyl and L-thyroxine on the antiedematous activity of immunotropic preparations during development of toxic brain edema and swelling].

Dysfunction of thyroid gland plays an important role in the pathogenesis of brain edema and swelling. Toxic brain edema and swelling was modeled under condition of hypo- and hyperfunction of thyroid gland. Mercazolyl and L-thyroxine ambiguously influence the development of toxic brain edema and swelling in rats. L-thyroxin (35.7 microg/kg) favors increase in the water content in brain tissue, which can be considered as synergism with the edematous factor and the formation of brain tissue susceptibility to the development of brain edema and swelling. The administration of mercazolyl (5 mg/kg) and L-thyroxin (35.7 microg/kg) with thymogen (10 microg/kg), thymalin (1.2 mg/kg), cycloferon (0.5 mg/kg) results in decreasing brain tissue density as compared to intact animals. Dysfunction of the thyroid gland leads to changes in pharmacodynamics of immune preparations, which results in a decrease of their antiedematous activity.

[On the taxonomic rank of ciscaucasicus and its relationships with the pygmy wood mouse Sylvaemus uralensis inferred from the mtDNA cytochrome b gene sequence].

To specify the taxonomic rank of form ciscaucasoides (independent species Sylvaemus ciscaucasoides, or intraspecific form of pygmy wood mouse, S. uralensis), a 402-bp the mtDNA cytochrome b gene fragment (402 bp) was examined in S. ciscaucasoides individuals from six geographic localities of the Caucasus and Ciscaucasus, (Krasnodar krai and Adygeya Republic) and 17 S. uralensis individuals from seven localities of the Russian Plai (Saratov oblast, Smolensk oblast, Voronezh oblast, Tula oblast, Moscow oblast, and Tver' oblast). For comparison, the cytochrome b gene was partly sequenced in the samples of yellow necked, S. flavicollis (n = 2, Samara oblast), and Caucasian, S. ponticus (n = 6, Krasnodar krai), wood mice. One Mus musculus specimen from Western Europe, whose nucleotide sequences were deposed in the GenBank, was used as intergeneric outgroup. Phylogenetic trees for the forms examined were constructed based on the mtDNA sequence variation and using the neighbor joining and maximum parsimony methods. The network of the cytochrome b haplotypes was also constructed. The level of genetic divergence was evaluated using Kimura's two-parameter algorithm. Based on the data on the sequence variation in a 402-bp mtDNA cytochrome b gene fragment, the hypothesis on the species status of the ciscaucasicus form was. The mean intergroup distances (d) between the geographic groups of S. uralensis varied from 0.0036 to 0.0152. At the same time, the distances between the pygmy wood mice and the group of S.flavicollis-S. ponticus varies in the range from 0.0860 to 0.0935, and the level of intergeneric genetic differentiation (Sylvaemus-Mus) is higher than the latter index (d = 0.142). Ciscaucasoides should be considered as geographic substitution form of S. uralensis. Furthermore, the Caucasian populations of S. uralensis (= ciscaucasoides) were characterized by a threefold lower value of intergroup genetic divergence (d = 0.0062) than the East European populations (d= 0.0179). This finding pointed to some isolation of Caucasian populations of pygmy wood mouse and depletion of their gene pool. However other molecular genetic data (similarity of nucleotide composition and consistence of the levels of intra- and intergroup distances) suggest the absence of geographic subdivision between Caucasian and East European populations ofS. uralensis relative to the molecular marker examined.

[Effect of a levopromazine-thymalin combination on the development of toxic edema and swelling in the brain]. / Vliianie kombinatsii levomepromazina i timalina na razvitie toksicheskogo oteka-nabukhaniia golovnogo mozga.

The development of toxic edematous brain swelling in rats is accompanied by disproteinemia of the blood plasma and buildup of the gamma-globulin fraction. The administration of levopromazine (5 mg/kg), thymalin (1.2 mg/kg), or their combination reduces this disorder in the blood protein fractions. The antiedematous effect of the levopromazine--thymalin combination has an additive synergistic interaction.

[The effect of tactivin and levamisole on the development of toxic brain edema-swelling]. / Vliianie taktivina i levamizola na razvitie toksicheskogo oteka-nabukhaniia golovnogo mozga.

Edema-swelling of the brain (ESB) is among the urgent problems of modern medicine. The purpose of the research was the study of the effect of immunotropic agents on formation of the pathologic process. It was demonstrated on a model of toxic ESB that taktivin and levamisole possess antiedemic activity. The effect is dose-dependent and is determined by the structural characteristics of the drugs under study. Unlike taktivin, large doses of levamisole demonstrate synergism with the effect of the edematous factor.

[The diagnostic characteristics of von Willebrand's disease]. / Osobennosti diagnostiki bolezni Villebranda.

70 patients from 48 families were examined. Of them, 59 (84%) patients had type I Willebrand's disease (WD), 9 (13%) type II, 2 (3%) type III WD. Hemostasis was assessed by functional tests: APTT, FVIII activity, bleeding time, ristocetin-cofactor activity of plasma Willebrand factor (WF). The WF levels in plasma and platelets were measured on a Reader-210 Microwell system by enzyme immunoassay with 380 F2 monoclonal antibodies to human WF. The functional parameters in 65 patients in remission were within normal range in half the patients. The only objective diagnostic criterion of the patients inclusion into WB group was the level of WF in plasma, especially when patients with type I WD were examined. The level of WF was always low in patients of this group even in the presence of normal values of functional tests. The severity of WD course and definition of laboratory signs of the disease depended mainly on the involvement of platelet WF in pathological process. In patients with a decrease of both plasma and platelet WF the course of the diseases was most serious and laboratory data most shifted from normal.

[The effect of specific transfusion therapy on the level of circulating immune complexes in hemophilia patients]. / Vliianie transfuzionnoi spetsificheskoi terapii na uroven' tsirkuliruiushchikh immunnykh kompleksov u bol'nykh gemofiliei.

The level of circulating immune complexes (CIC) was measured in 108 hemophilic patients registered at the Republican Center for Hemophilia Treatment. High levels of CIC were detected in hemophilic patients of different age. The concentrations of CIC were higher in adult patients than in children. Formation of immune complexes in the test groups did not go beyond the framework of the physiological process, for the signs of vasculitis, which is an indispensable component of immunocomplex pathology, could not be identified. Higher levels of CIC in adults were related to a greater number of transfusions made throughout the life, particularly if the annual dose of the preparations infused exceeded 10,000 Units of factor VIII or IX. No significant correlation was established between the rise of CIC levels in the patients' serum and the biochemical alterations in liver function, detected in these patients. Therefore, CIC detected by the authors are not specific and lesions of the liver parenchyma in hemophilic patients are not determined by their presence.

[Detection of carriers of hemophilia A by testing for HindIII polymorphism in the factor VIII gene by PCR]. / Vyiavlenie nositelei gemofilii A pri pomoshchi testirovaniia polimorfnogo saita HindIII v gene faktora VIII metodom PCR.

Representatives of 62 families from Moscow and Leningrad with haemophilia A observed in the pedigree were tested for HindIII polymorphism in the factor VIII gene. The proposed scheme of investigation was based on intron 19 of the FVIII gene amplification by the PCR technique followed by restriction analysis with the inner control of hydrolysis. 207 unrelated X-chromosomes were analysed, the frequency of the incidence of the polymorphic HindIII site in the given population found to be 0.29. The frequency of incidence of the HindIII heterozygotes calculated according to Hardy-Weinberg equation was 0.41. This value evidences for relatively high informativity of this polymorphism for carrier detection and prenatal diagnosis of haemophilia A. 23 families (37%) out of 62 examined in the study were informative for this criteria. The new scheme proved to be effective in testing HindIII polymorphism for haemophilia A carrier detection and prenatal diagnosis. The whole procedure takes one day, the radiolabelled probes are not used. The scheme described was inculcated in the All-Union Research Center for Haematology, Ministry of Health, USSR, Moscow, Research Institute for Obstetrics and Gynecology, Leningrad, Institute of Medical Genetics, Greifswald, DDR.

[Detection of the heterozygote carrier state and prenatal diagnosis of hemophilia A using DNA probes]. / Vyiavlenie geterozigotnogo nositel'stva i prenatal'naia diagnostika gemofilii A pri pomoshchi DNK-zondov.

Southern blot analysis of DNA samples from 110 persons related to 30 high risk hemophilia A families was carried out using intergenic probe St-14 and intergenic probes p 51-61 and p 1.8. Thirty-five hemophilia A patients, 24--their mothers--obligatory carriers and 51 close proband relatives were studied altogether. 16 female proband relatives were diagnosed as hemophilia A carriers, hemophilia A heterozygosity was rejected in three persons. Twenty five families were found to be at risk for prenatal hemophilia A diagnosis. One case of hemophilia A diagnosis in a 10-week fetus has been presented.

[Use of ultrasound in the quantitative estimation of soil and rhizospheric microorganisms]. / O primenenii ul'trazvuka pri kolichestvennom uchete pochvennykh i rizosfernykh mikroorganizmov

Ultrasonic treatment of soil, though being very effective for desorption of cells and deaggregation of microcolonies, may damage and kill microorganisms. Possible application and effectiveness of ultrasonic treatment was studied in this work with chernozem (dry and wet samples), rhizosphere and rhizoplane of pea. An ultrasonic disintegrator of low frequency is recommended for dry soils. Ultrasound cannot be recommended for treating rhizosphere and rhizoplane of plants without checking its effectiveness in each case.