Correction of intestinal dysbacteriosis in elderly patients with the use of bifidobacterin introduced by different routes

The results of the correction of disturbances in intestinal microflora in elderly patients with the use of bifidumbacterin in the form of powder or suppositories are presented. The effectiveness of the rectal administration of bifidumbacterin (by microinjections through an enema or in suppositories) is shown in comparison with the oral administration of the preparation. The administration of bifidumbacterin in suppositories for 15 days resulted in decreased content of hemolytic Escherichia below the threshold of determination in all examined patients.     

The effect of fermented-milk bifidumbacterin on the intestinal microflora of test pilots]

Bacteriological study of intestinal microflora in test pilots, regularly exposed to excessive physical, as well as nervous and emotional strain, has revealed changes in the composition of their intestinal microflora. Correction of microflora by means of bifidumbacterin, a curative lactic fermentation alimentary product, was carried out. Rapid and effective restoration of intestinal microflora and improvement of the general state of patients were noted, which made it possible to recommend this product as a prophylactic remedy for subjects at risk of development of dysbiotic disturbances.     

Differentiation of myeloid cells in liquid culture. 1. Progenitor cells found in normal peripheral blood

In order to establish a method for studying myeloid differentiation, light density, non-adherent, T-cell depleted mononuclear cells prepared from 26 normal peripheral blood buffy-coats were cultured in McCoy'5A medium supplemented with 15 per cent fetal calf serum (FCS) for three weeks at 37 degrees C in a humidified 5 per cent CO2 atmosphere. The total number of viable cells in the cultures on weeks 1 and 2 represented 73 +/- 10 per cent and 98 +/- 41 per cent of the initial number of viable cells seeded. After one week, blasts represented 26 +/- 10 per cent of the initial number of viable cells while all the initially contaminating mature granulocytes had disappeared. After two weeks, granulocytic differentiation was noted in most cultures and viable myelocytes and more mature cells represented 45 +/- 26 per cent of the initial number of viable cells. The differentiation was independent on the lot of FCS used. The addition of PHA stimulated leukocyte conditioned medium to the cultures did not enhance granulocytic differentiation. The granulocytic differentiation observed in the absence of exogenous CSF persisted after removing the cells adhering to the bottom of the flasks on day 2 of the culture. An endogenous colony stimulating activity was detected in the cultures on week 3 but its intensity did not clearly correlate with the degree of granulocytic differentiation.     

Effectiveness of the intramuscular administration of high doses of penicillin in treating pneumonia]

Clinical tolerance of benzylpenicillin administered intramuscularly in doses of 2000000--3000000 units every 4--6hours (12000000 units a day) was studied in 253 patients with pneumonia. Satisfactory tolerance of sodium benzylpenicillin and pronounced painfulness at the site of injection of potassium benzylpenicillin were noted. General toxic side effects in the form of asthenia, dizziness, pain in the heart region were observed in a part of elderly patients. The benzylpenicillin serum levels after administration of 2000000 units were 6--10 times higher than those after administration of 200000 units. The efficiency of benzylpenicillin elevated doses was studied in 193 patients. In 101 of them the previous treatment with usual doses of benzylpenicillin, i. e. 200000 units every 4 hours was not sufficiently effective. The elevated doses of benzylpenicillin proved to be effective in 78 per cent of the cases, the effect being observed in all the cases with acute pneumonia, in 88.5 per cent of the cases with neglected state and in 83 per cent of the cases with chronic pneumonia. The therapeutic effect was also observed in most of the patients with benzylpenicillin resistant microflora in the sputum. On the basis of high efficiency of penicillin therapy it was concluded that gram-positive cocci played the main role in pneumonia etiology.     

Microbial ecology of the intestines in health and in pathology

Bifidoflora constitute 85--95 per cent of the large intestine microbiocenosis in children under 1 year of age. Bacteroides are not specific of children under 6 months of age. Lactobacilli, lactic acid streptococci, colon bacilli, enterococci and staphylococci (saprophytic, epidermal) constitute not more than 15 per cent. The predominating group peculiar of eubiosis in adults includes bifidobacteria and bacteroides. Changes in human autoflora are often induced by such factors as impaired ecology, stress, uncontrolled use of antibacterial drugs, radio- and chemotherapy, etc. Dysbacteriosis (first of all lower quantitative contents of bifidoflora) has an unfavourable effect on the intestine secretory function, absorption and certain indices of protein, lipid and mineral metabolism, vitamin synthesizing and fermentative functions and leads to disfunction of the gastrointestinal tract. It is a cause of persisting and relapsing infections in children and adults. High and optimal levels of bifidoflora in the intestine usually prevent the pathogenic action of pathogens. Lysozyme of digestive secretion and secretory immunity with immunoglobulin A prevalence also play an important role in the complicated mechanism of the protective barrier. The use of bacterial preparations such as bifidumbacterin, lactobacterin or bifilact for stabilization and recovery of high bifidoflora levels is indicated in all the cases with impaired microbiocenosis of the intestine.     

Efficacy of penicillin therapy of meningococcal infection in children undergoing different regimes of pathogenetic therapy

The course of meningococcal infection and nonspecific and specific immunity in children subjected to different regimens of pathogenetic therapy were studied. It was shown that the clinico-immunological indices were more favourable in children treated with lasix as a diuretic agent. Recovery with defects was observed in 6.8 per cent of the children of this group, while in patients subjected to routine treatment the respective value amounted to 14.6 per cent. The use of lasix in combination with penicillin increased the efficacy of penicillin therapy and shortened the recovery period by 8.4 +/- 0.2 days as compared to that of routine treatment. No unfavourable effect of elevated penicillin concentrations on the lysozyme activity, blood bactericidal characteristics and composition of immunoglobulins A, M and G in the children was recorded.     

Sodium nucleinate increase of nonspecific macroorganism resistance to conditionally pathogenic and pathogenic microorganisms

Sodium nucleinate significantly increased the non-specific resistance of mice to E. coli O26, Ps. vulgaris, Ser. marcesens, Ps. aeruginosa, Kl. ozaenae and their associations and total resistance also accompanied by a significant decrease in the number of the bacteria in the spleen and blood, the total number of the cells in the peritoneal exudate and the number of the cells adhering to the glass (macrophages). The preparation is a low molecular RNA consisting mainly of fraction 3S and a small amount of fraction 4S. It contains 1.5 per cent of protein and 2 per cent of DNA and does not contain any polysaccharides. Repeated purification of sodium nucleinate lowering the levels of the admixtures 5 times did not change its efficacy. The low molecular RNA of the rat liver (4S) had a pronounced stimulating activity. On infection of the host stimulated with sodium nucleinate, formation of the post-infection immunity was not decreased.     

The clinical laboratory assessment of vancomycin (Edicin) efficacy in treating suppurative wounds of the skin and soft tissues, burn wounds and the infectious complications of burns]

Clinical and bacteriological efficacies of vancomycin (Edicin, LEK) in the treatment of 17 patients with wound infection and 13 patients with thermal affections were studied. The clinical efficacy in the group of the patients with purulent wounds of the soft tissues amounted to 94.1 per cent and that in the patients with thermal affections was 92.3 per cent. The bacteriological effect was recorded in 86.6 per cent of the patients with purulent wounds of the soft tissues and in 69.3 per cent of the patients with burn infections. The drug intolerability was observed in two cases.     

Ascites Bacterial Burden and Immune Cell Profile Are Associated with Poor Clinical Outcomes in the Absence of Overt Infection

Bacterial infections, most commonly spontaneous bacterial peritonitis in patients with ascites, occur in one third of admitted patients with cirrhosis, and account for a 4-fold increase in mortality. Bacteria are isolated from less than 40% of ascites infections by culture, necessitating empirical antibiotic treatment, but culture-independent studies suggest bacteria are commonly present, even in the absence of overt infection. Widespread detection of low levels of bacteria in ascites, in the absence of peritonitis, suggests immune impairment may contribute to higher susceptibility to infection in cirrhotic patients. However, little is known about the role of ascites leukocyte composition and function in this context. We determined ascites bacterial composition by quantitative PCR and 16S rRNA gene sequencing in 25 patients with culture-negative, non-neutrocytic ascites, and compared microbiological data with ascites and peripheral blood leukocyte composition and phenotype. Bacterial DNA was detected in ascitic fluid from 23 of 25 patients, with significant positive correlations between bacterial DNA levels and poor 6-month clinical outcomes (death, readmission). Ascites leukocyte composition was variable, but dominated by macrophages or T lymphocytes, with lower numbers of B lymphocytes and natural killer cells. Consistent with the hypothesis that impaired innate immunity contributes to susceptibility to infection, high bacterial DNA burden was associated with reduced major histocompatibility complex class II expression on ascites (but not peripheral blood) monocytes/macrophages. These data indicate an association between the presence of ascites bacterial DNA and early death and readmission in patients with decompensated cirrhosis. They further suggest that impairment of innate immunity contributes to increased bacterial translocation, risk of peritonitis, or both.     

Incomplete protection, but suppression of virus burden, elicited by subunit simian immunodeficiency virus vaccines.

We compared the efficacy of immunization with either simian immunodeficiency virus (SIV) Env glycoprotein (Env), Env plus Gag proteins (Gag-Env), or whole inactivated virus (WIV), with or without recombinant live vaccinia vector (VV) priming, in protecting 23 rhesus macaques (six vaccine and two control groups) from challenge with SIVmac251 clone BK28. Vaccination elicited high titers of syncytium-inhibiting and anti-Env (gp120/gp160) antibodies in all vaccinated macaques and anti-Gag (p27) antibodies in groups immunized with WIV or Gag-Env. Only WIV-immunized macaques developed anticell (HuT78) antibodies. After homologous low-dose intravenous virus challenge, we used frequency of virus isolation, provirus burden, and change in antibody titers to define four levels of resistance to SIV infection as follows. (i) No infection ("sterilizing" immunity) was induced only in WIV-immunized animals. (ii) Abortive infection (strong immunity) was defined when virus or provirus were detected early in the postchallenge period but not thereafter and no evidence of virus or provirus was detected in terminal tissues. This response was observed in two animals (one VV-Env and one Gag-Env). (iii) Suppression of infection (incomplete or partial immunity) described a gradient of virus suppression manifested by termination of viremia, declining postchallenge antibody titers, and low levels (composite mean = 9.1 copies per 10(6) cells) of provirus detectable in peripheral blood mononuclear cells or lymphoid tissues at termination (40 weeks postchallenge). This response occurred in the majority (8 of 12) of subunit-vaccinated animals. (iv) Active infection (no immunity) was characterized by persistent virus isolation from blood mononuclear cells, increasing viral antibody titers postchallenge, and high levels (composite mean = 198 copies per 10(6) cells) of provirus in terminal tissues and blood. Active infection developed in all controls and two of three VV-Gag-Env-immunized animals. The results of this study restate the protective effect of inactivated whole virus vaccines produced in heterologous cells but more importantly demonstrate that a gradient of suppression of challenge virus growth, reflecting partial resistance to SIV infection, is induced by subunit vaccination. The latter finding may be pertinent to studies with human immunodeficiency virus vaccines, in which it is plausible that vaccination may elicit significant suppression of virus infection and pathogenicity rather than sterilizing immunity.     

The antibiotic prophylaxis of postoperative complications in breast cancer patients

The studies showed that infectious complications in patients operated for breast cancer (BC) most frequently developed after removal of the drainage tube resulting in poorer discharge favourable for development of infections. The causative agents in such cases are usually exogenous bacteria differing from endogenous ones (Staphylococcus epidermidis) inhabiting the human skin and sometimes contaminating the operative field. The endogenous bacteria are detectable bacteriologically in 60 per cent of the cases. Still, since the operation wound contains humoral and tissue immunity factors (specifically active against the host microflora) such bacteria rarely grow on artificial media (18 per cent) and even more rarely cause infections. Therefore, to prevent postoperative infections in patients with BC it should be recognized rational to use broad-spectrum antibacterial drugs such as ampiox, ampicillin, doxycycline, cephalosporins of the 2nd and 3rd generations, etc. for 5 to 6 days after the drainage removal. If an infection develops the preventive therapy should be replaced by an adequate therapy in accordance with the pathogen sensitivity.     

Pokeweed mitogen-induced immunoglobulin secretion by peripheral blood lymphocytes from patients with primary intracranial tumors. Characterization of T helper and B cell function

We have previously demonstrated that patients with primary malignant brain tumors have impaired in vivo and in vitro cell-mediated immunity. The purpose of the present research was to employ pokeweed mitogen (PWM)-induced secretion of immunoglobulin (Ig) by peripheral blood lymphocytes (PBL) to further investigate impaired lymphocyte function in these patients. The PWM response of PBL from normal individuals averaged 8384 plaque-forming cells (PFC) per 10(6) cells, whereas the response of PBL from patients averaged 1590 PFC/10(6). The decreased PWM response of PBL patients could not be improved by varying the number of PBL placed in culture or employing different concentrations of PWM. Co-culture experiments to detect the presence of suppressor cells in PBL and purified T cell preparations from patients demonstrated that enhanced suppressor cell activity was not evident. Next, experiments were performed to assess the T-helper cell activity present in purified T cell preparations obtained from patients. The results demonstrated that T cells from patients lacked the ability to provide adequate helper activity in the PWM response. Moreover, studies with monoclonal antibodies directed against T cell subsets revealed that PBL from patients have a reduced percentage of T-helper cells (40%) as compared with normal values (55%). In concert with T-helper cell anomalies, B cell function in these patients also is diminished. Thus, these observations indicate that a combined T-helper and B cell defect may contribute to the broad impairment of host immunocompetence observed in patients with primary gliomas.     

Course and outcomes of infectious endocarditis in HIV-infected patients

39 patients with acute infectious endocarditis were observed; of these, 28 patients had HIV infection at different stages of the disease. The specific features of the course of acute infectious endocarditis in HIV-infected patients were established. The severe course of acute septic endocarditis was observed in those patients whose parameters of the cell-mediated immune system (cells CD4+) were in the state of compensation or subcompensation. At different stages of HIV infection different clinical syndromes of infectious endocarditis prevailed. In patients with HIV infection the combined lesions of the heart valve apparatus were observed and mixed microflora was isolated from the blood more frequently. The development of acute septic endocarditis negatively affected the course of HIV infection and was manifested by a rapid decrease in the amount of CD4 lymphocytes.     

Nippostrongylus brasiliensis: effects of immunity on the pre-intestinal and intestinal larval stages of the parasite

Nippostrongylus brasiliensis: effects of immunity on the pre-intestinal and intestinal larval stages of the parasite. International journal for Parasitology4: 183–191. Migration of the pre-intestinal larval stages of N. brasiliensis was studied in rats undergoing either primary or challenge infections. In rats undergoing a primary infection, more than 67 percent of larvae successfully migrated from the skin to the oesophagus by 70 h after infection, and subsequently over 90 per cent of these larvae became established in the small intestine as sexually mature adults. In immune rats undergoing a second infection, 46 per cent of larvae completed migration to the oesophagus by 70 h and of these, only 1·6 per cent became established in the intestine to produce eggs. These inhibitory effects on the pre-intestinal and intestinal larval stages were even more pronounced in immune rats undergoing a third or fourth infection and in addition, there was a prolonged sojourn and substantial retention of larvae in their lungs. There was no evidence that the immune response had an adverse effect on oesophageal fourth stags larvae as these organisms (obtained from immune donors) were able to establish and develop to maturity when transferred per os to normal animals.Syngeneic transfer of immune mesenteric lymph node cells to normal recipients, caused expulsion of parasites from the intestine but failed to effect migration of pre-intestinal larval stages. The implications of these findings are discussed in the context of current knowledge of the mechanisms of immunity to helminths.     

Differentiation of myeloid cells in liquid culture: 2. Acute myelocytic leukemia cells

In a companion paper we demonstrated that normal peripheral blood granulocytic precursor cells differentiate after 2-3 weeks in suspension culture. In the studies described here leukemic blast cells obtained from 14 patients with acute myelocytic leukemia (AML) and two patients with chronic myelocytic leukemia in blastic crisis were cultured in McCoy's 5A medium containing 15 per cent fetal bovine serum for 2-3 weeks at 37 degrees C in an atmosphere of 5 per cent CO2-95 per cent room air. 'Spontaneous' myeloid differentiation (20 x 10(4) viable mature myeloid cells ml-1) occurred in the cultures of cells obtained from 8 pts. The differentiation was granulocytic in three cases, monocytic in four cases and of mixed type in one case. Differentiation was independent of the growth of the cells in culture and occurred in four cases after the first week. Monocytic differentiation was seen only in AML of the FAB M4 type whereas granulocytic or mixed differentiation were seen only in AML of the FAB M1 or M2 types. When PHA leucocyte conditioned medium (PHA-LCM) was added to the cultures monocytic/macrophage differentiation was favoured. Inducers of the differentiation of the HL-60 cell line (N-methylacetamide, cytosine arabinoside, or retinoic acid) had no consistent effect on the differentiation and were at times inhibitory. Three patients received therapy with low dose cytosine arabinoside and no correlation was observed between the outcome of the treatment and leukemic cell differentiation in culture in the presence of the drug.     

CD4+ T cells, including Th17 and cycling subsets, are intact in the gut mucosa of HIV-1-infected long-term nonprogressors

During acute human immunodeficiency virus (HIV) infection, there is a massive depletion of CD4(+) T cells in the gut mucosa that can be reversed to various degrees with antiretroviral therapy. Th17 cells have been implicated in mucosal immunity to extracellular bacteria, and preservation of this subset may support gut mucosal immune recovery. However, this possibility has not yet been evaluated in HIV-1-infected long-term nonprogressors (LTNPs), who maintain high CD4(+) T cell counts and suppress viral replication in the absence of antiretroviral therapy. In this study, we evaluated the immunophenotype and function of CD4(+) T cells in peripheral blood and gut mucosa of HIV-uninfected controls, LTNPs, and HIV-1-infected individuals treated with prolonged antiretroviral therapy (ART) (VL [viral load]<50). We found that LTNPs have intact CD4(+) T cell populations, including Th17 and cycling subsets, in the gut mucosa and a preserved T cell population expressing gut homing molecules in the peripheral blood. In addition, we observed no evidence of higher monocyte activation in LTNPs than in HIV-infected (HIV(-)) controls. These data suggest that, similar to nonpathogenic simian immunodeficiency virus (SIV) infection, LTNPs preserve the balance of CD4(+) T cell populations in blood and gut mucosa, which may contribute to the lack of disease progression observed in these patients.     

Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria

The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.     

Olemorphocycline treatment of calculous and noncalculous pyelonephritis]

40 patients suffering from calculous and non-calculous pyelonephrits were treated with olemorphocycline administered intravenously in a dose of 250 00 Units 2 times a day for 5--7 days. The clinical effect was observed in 62.5 per cent of the cases. In 54.7 per cent of the cases the isolates were resistant to oleandomycin and morphocycline. The kidney tissue and urine from the kidney pelvis taken during surgical operations of 20 patients were plated out. Staphylocci were most often detected in the platings of the kidney tissue. The microflora of the urinary bladder before the treatment and that of the urine from the kidney pelvis and the kidney tissue taken during the surgical operation was mainly ident     

Efficacy of meropenem in the treatment of severe complicated urinary tract infections]

The clinical and bacteriological efficacies of meropenem in the treatment of 12 patients with urinary tract infection were studied. In 8 patients the drug was administered intravenously in a dose of 1 g every 8 hours and in 4 patients with the creatinine clearance below 50 ml/min it was administered in a dose of 1 g every 12 hours (the treatment course of 7 to 10 days). Meropenem was used in the monotherapy. Severe complicated urinary tract infections were mainly observed in the patients with long-term urolithiasis, subjected to repeated surgical interventions and isolating as a rule polyresistant strains of Pseudomonas aeruginosa and E.agglomerans as the pyelonephritis pathogens at a titre of 5 x 10(5)-5 x 10(8) microbial cells per 1 ml of the urine susceptible to meropenem in 80 to 96 per cent of the cases. The clinical efficacy of the drug was stated in all the patients while the bacteriological efficacy amounted to 88.9 per cent.