[Pregnancy in paroxysmal nocturnal hemoglobinuria: from survival to life].

BACKGROUND: Pregnancy in paroxysmal nocturnal hemoglobinuria (PNH) patients has historically been a high-risk situation. The combination of chronic complement-mediated hemolysis caused by the disease and physiological activation of the complement system during pregnancy, significantly worsened the prognosis for the life. For a long time, there were no effective methods for the PNH treatment, and pregnancy in patients seemed to be extremely risky, as it significantly increased the risk of life-threatening complications. The advent of targeted therapy with eculizumab turned the prognosis of this disease upside down: patients began not only to survive, but also to live comparable to healthy people. A comparative analysis of the course and outcomes of pregnancy in patients with PNH treated with eculizumab and in patients without targeted therapy was carried out. AIM: The study was to evaluate the course and outcomes of pregnancy in patients with PNH, depending on the therapeutic approach. MATERIALS AND METHODS: We analyzed data from 57 pregnancies in 49 women (31 used eculizumab, 26 with supportive care only) observed at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology or with remote consultation (23 clinics from 19 cities of Russia). RESULTS: The high probability of pregnancy complications and its adverse outcomes outside of targeted therapy indicates the vital need for its use: all observations were accompanied by complications of varying severity. The course of pregnancy with the eculizumab is generally more favorable: an apparently higher rate of live births and a lower likelihood of complications are registered. Without increasing the incidence of complications, eculizumab significantly improves pregnancy outcomes for both mother and fetus, and does not adversely affect the health of newborns. CONCLUSION: Thus, eculizumab allows not only to increase the survival rate of patients with PNH, but also to comprehensively improve their quality of life, including the possibility of safe childbirth.

[Impaired expression of genes regulating homeostasis of stem hemopoietic cells in stromal cells of patients with aplastic anemia].

AIM: To evaluate expression of genes participating in regulation of hemopoietic stem cells (HSC) in the cells of stromal sublayer of bone marrow long-term cultures in patients with aplastic anemia (AA); to determine effects of parathyroid hormone (PTH) on stromal microenvironment and on its ability to maintain HSC homeostasis. MATERIAL AND METHODS: Gene expression in the sublayer of the adherent cells (SAC) was examined with RT-PCt. SAC was for a long time treated with PTH, then their ability to secure survival of early hemopoietic precursors was tested. Changes in the function of stromal cells and expression of some genes were compared in 9 AA patients and 14 donors. RESULTS: Stromal sublayer of AA patients is characterized by low expression of Ang-1 and VCAM-1 genes and high VEGF expression compared to mean level of healthy donors. PTH stimulates expression of different genes participating in HSC regulation in stromal cells of some patients and improves survival of early hemopoietic hemopoietic precursors on such sublayers. CONCLUSION: AA patients have severe defects in SAC interaction with stroma. In some cases the defects can be partially compensated with application of PTH.

[Splenectomy in programmed therapy of aplastic anemia].

AIM: To define efficacy of splenectomy (SE) in current programmed therapy of aplastic anemia (AA). MATERIALS AND METHODS: SE efficacy was analysed in 2 stages: a retrospective study of efficacy of surgery as monotherapy (1986-1996) (74 AA patients) and of SE in programs of immunosuppressive therapy (IST) (1991-2002). Program treatment of AA patients was conducted on the base of IST algorithm developed in Hematological Research Center after many year investigations. RESULTS: SE as monotherapy improved AA course in 73.3% patients with non-severe AA (NAA) and 18.2% patients with severe AA (SAA). Three and five year survival in NAA postsplenectomy patients was 80%. One-year survivors after surgery were likely to survive long. Overall survival of SAA after SE was significantly less (p < 0.0001): 3-year survival - 6%. SE efficacy in programs including antilymphocytic globulin (ALG) and cyclosporin A (CsA) was studied in 69 AA patients. A 85.5% response was registered to program treatment including ALG, CsA and SE, being 81% in SAA and 1% in NAA patients. Efficacy of SE in combination with CsA at the first stage NAA treatment (a 30% positive response) was much inferior to ALG+CsA (68% response). At stage two treatment SE improved treatment results in most of SAA patients. Long-term survival in SAA patients after program treatment with SE is 60%. CONCLUSION: SE in the program of combined therapy in adult AA patients including CsA is an alternative to ALG in NAA patients. In SAA, SE can be included in the program at the first stage in ALG intolerance or in the absence of the drug, at the second stage--to overcome resistance to conducted therapy.

[Effectiveness of cefotetan in clinical practice]. / Effektivnost' tsefotetana v klinicheskoi praktike.

Forty five patients at the age of 15 to 84 years with signs of infection requiring active antibacterial therapy were treated with cefotetan. In the majority of the patients pulmonary affections such as double pneumonia, pleurisy or bronchopneumonia were stated. In some patients bronchopulmonary pathological processes were associated with pancreatitis, cholecystitis or other diseases of the gastrointestinal tract. A separate group included patients with diseases of the small pelvis organs (pelvioperitonitis, metroendometritis or prostatitis) and diseases of the urogenital system (pyelonephritis) arachnoiditis. In all the patients except for one with bronchopneumonia at the background of chronic myeloleukemia and agranulocytosis the results of the treatment were good and satisfactory. Cefotetan proved to be efficient in the treatment of purulent affections of the skin and subcutaneous fat (abscesses and phlegmona), trophic disturbances at the background of pathological processes in the vessels and pyoseptic condition. Cefotetan practically had no side effects. Only in 2 patients insignificant nausea during the first 2 days of the treatment was recorded. In some patients the antibiotic intramuscular injections were painful with formation of cold infiltrates. After intravenous administration of cefotetan no adverse reactions were observed.

[Age-related features of inflammatory and immune responses of the gastric mucosa in women with chronic gastritis]. / Vozrastnye osobennosti vospalitel'noi i immunnoi reaktsii slizistoi obolochki zheludka pri khronicheskom gastrite u zhenshchin.

The paper presents the results of studies of the specific features of an inflammatory reaction of the mucosa in the gastric body and antrum in chronic gastritis associated with Helicobacter pylori (HP) in females of reproductive age and in menopause. In the gastric body, there were prevalent chronic inflammatory processes with developed mononuclear infiltration in reproductive females whereas there were predominant elements of exudative and destructive inflammation in older females. The antral mucosa of young females showed predominantly destructive changes. The magnitude of HP seeding in the superficial and fossular mucosa was much higher both in the fundum and antrum in menopausal than reproductive females. There was great differences in the nature of inflammatory and immune reactions in either females with HP-associated chronic gastritis.

[The age-related characteristics of the immune reaction of the mucosa of the gastric antrum in chronic gastritis]. / Vozrastnye osobennosti immunnoi reaktsii slizistoi obolochki antral'nogo otdela zheludka pri khronicheskom gastrite.

Stomach biopsies from 16 adult patients at the age from 18 to 55 years, 16 adults of 56-68 years and 23 children were studied histologically, immunohistochemically and morphometrically. The frequency of Helicobacter pylori findings was dependent on the age. Local production of IgM and IgG was higher in the adults of young and mature age. Number of IgA producing cells decreased and that of IgG producing cells sharply increased in the aged persons; in this category also was increased the number of intraepithelial lymphocytes and of T-lymphocytes relating to the subpopulation of suppressor cytotoxic cells.