Changes in the blood immunological indices of newborn infants as affected by T-activin in vitro

T-activin, introduced into the culture of mononuclear cells obtained from the blood of healthy newborn infants, does not induce any essential changes in the levels of E-, Ea- and EAC-rosette-forming cells. An overwhelming majority of healthy infants has shown a decrease in the functional activity of lymphocytes in the blast transformation test in response to the optimal dose of ConA and an increase in their functional activity in response to the suboptimal dose of this mitogen. After stimulation with phytohemagglutinin, both the increase of the stimulation index and its decrease have been observed in an equal number of cases. The introduction of the preparation into the culture of mononuclear blood cells isolated from newborn infants with sepsis leads to a considerable increase in the detection rate of Ea-rosette-forming cells with a tendency to an increase in that of E- and EAC-rosette-forming cells. The final values of the stimulation indexes, no matter what the mitogens used, are in conformity with the values characteristic of the normal parameters for healthy newborns, due to a specific pattern of changes in the T-lymphocyte functional activity in the blast-transformation test.     

The creation of specific immunity to staphylococcal infection in newborn infants by the intranasal administration of adsorbed staphylococcal anatoxin

The possibility of enhancing specific immunity in newborn infants by the intranasal administration of adsorbed staphylococcal toxoid to infants with a high risk of staphylococcal infection in doses of 1 drop (0.05 ml) into each nostril during the first 7-9 years of their life. On days 7-9 the level of anti-alpha-toxin in the blood rose to 3.8 +/- 0.14 I. U./ml and remained sufficiently high 3-6 months later. When this method was used for the simultaneous immunization of mothers, their antitoxic titers were not as high as in newborn infants. No side effects were observed. In the control group, the titers of anti-alpha-toxin were low during the whole period of observation. Infants immunized by the proposed method had no staphylococcal infections both during the newborn period and within the first year of their life. In the control group, 8 cases of minor forms of purulent septic infection were registered during the newborn period, and in 2 infants umbilical staphylococcal sepsis was diagnosed.     

The use of T-activin for the prevention of congenital influenzal infection in mice and the correction of the immune deficiency

Viremia accompanying influenza infection and the possibility of transplacental passage of the virus into the fetus make it expedient to develop measures for the prophylaxis of intrauterine infection of the fetus in case of influenza during pregnancy. The work presents the optimum scheme of administration of T-activin for prophylactic purposes to pregnant mice with acute influenza infection. Besides, the use of T-activin for immunocorrection in case of established congenital influenza infection in mice is proposed.     

An observational cohort study of the kynurenine to tryptophan ratio in sepsis: association with impaired immune and microvascular function

Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-γ activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology. Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase inhibition. We hypothesized that IDO activity in sepsis would be related to plasma interferon-γ, interleukin-10, T cell lymphopenia and impairment of microvascular reactivity, a measure of endothelial nitric oxide bioavailability. In an observational cohort study of 80 sepsis patients (50 severe and 30 non-severe) and 40 hospital controls, we determined the relationship between IDO activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric oxide-dependent microvascular reactivity and lymphocyte subsets in sepsis. Plasma amino acids were measured by high performance liquid chromatography and microvascular reactivity by peripheral arterial tonometry. The plasma KT ratio was increased in sepsis (median 141 [IQR 64–235]) compared to controls (36 [28–52]); p<0.0001), and correlated with plasma interferon-γ and interleukin-10, and inversely with total lymphocyte count, CD8+ and CD4+ T-lymphocytes, systolic blood pressure and microvascular reactivity. In response to treatment of severe sepsis, the median KT ratio decreased from 162 [IQR 100–286] on day 0 to 89 [65–139] by day 7; p = 0.0006) and this decrease in KT ratio correlated with a decrease in the Sequential Organ Failure Assessment score (p<0.0001). IDO-mediated tryptophan catabolism is associated with dysregulated immune responses and impaired microvascular reactivity in sepsis and may link these two fundamental processes in sepsis pathophysiology.     

Magnitude of colonization and sepsis by group B streptococci in newborn infants

Infants admitted to the Neonatal Intensive Care Unit at Tampa General Hospital, Tampa, Florida, were cultured for group B streptococci (GBS). Culture swabs were quantified for GBS to determine the magnitude of colonization in infected infants. Thirty-seven (17%) of the 217 infants cultured were positive for GBS. Six of these colonized infants developed sepsis, with blood cultures positive for GBS. Septic infants generally were colonized by large numbers of GBS (10⁵ bacteria/culture swab) at two or more external skin sites, in comparison to aseptic infants, who were lightly colonized with GBS. The data suggest a possible correlation between magnitude of colonization by GBS at external skin sites and development of GBS sepsis in newborn infants.     

Study of the action of immunomodulator T-activin on electric properties of plasma membranes of thymus cells by the use of fluorescent probes

T-activin alters the electric properties of plasmatic membranes of the T-activin treated suspension of mouse (CBAX X057B1) F1 thymic cells. These alterations were registered by means of negative charged fluorescent probe l-anilino-naphthalene-8-sulfonate (ANS) and positive charged 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM) by measurement of their fluorescence in the individual thymic cell. Apparently, T-activin leads to depolarization of transmembrane potential on plasmatic membrane of thymic cells. It seems that action of T-activin is similar to the effect of polycations, which alter cells ionic streams during lymphocyte activation. However, there is a version, that T-activin acts like neuraminidase, but it is activity less expressed.     

Cell proliferation in mouse tissues after thymectomy and the administration of T-activin

The epithelium of mouse cornea and lymph nodes was examined for DNA-synthetic and mitotic activity at different times after thymectomy and administration of T-activin, an active factor of the thymus. Thymectomy entails retardation of the rate of corneal epithelium regeneration, diminution in both tissues under study of the amplitude of oscillations in cell proliferation throughout the day. Administration to the animals of the immunoactive thymic factor T-activin makes the circadian rhythm of cell proliferation return to normal. It is assumed that T-activin raises the capacity of lymphocytes to interact with epithelial cells, which manifests itself in the enhancement of their mitotic activity.     

A Systematic Review of Risk Factors Associated with Surgical Site Infections among Surgical Patients

Importance

Surgical site infection (SSI) complicates 2-5% of surgeries in the United States. Severity of SSI ranges from superficial skin infection to life-threatening conditions such as severe sepsis, and SSIs are responsible for increased morbidity, mortality, and economic burden associated with surgery. Staphylococcus aureus (S. aureus) is a commonly-isolated organism for SSI, and methicillin-resistant S. aureus SSI incidence is increasing globally.

Objective

The objective of this systematic review was to characterize risk factors for SSI within observational studies describing incidence of SSI in a real-world setting.

Evidence Review

An initial search identified 328 titles published in 2002-2012; 57 were identified as relevant for data extraction. Extracted information included study design and methodology, reported cumulative incidence and post-surgical time until onset of SSI, and odds ratios and associated variability for all factors considered in univariate and/or multivariable analyses.

Findings

Median SSI incidence was 3.7%, ranging from 0.1% to 50.4%. Incidence of overall SSI and S. aureus SSI were both highest in tumor-related and transplant surgeries. Median time until SSI onset was 17.0 days, with longer time-to-onset for orthopedic and transplant surgeries. Risk factors consistently identified as associated with SSI included co-morbidities, advanced age, risk indices, patient frailty, and surgery complexity. Thirteen studies considered diabetes as a risk factor in multivariable analysis; 85% found a significant association with SSI, with odds ratios ranging from 1.5-24.3. Longer surgeries were associated with increased SSI risk, with a median odds ratio of 2.3 across 11 studies reporting significant results.

Conclusions and Relevance

In a broad review of published literature, risk factors for SSI were characterized as describing reduced fitness, patient frailty, surgery duration, and complexity. Recognition of risk factors frequently associated with SSI allows for identification of such patients with the greatest need for optimal preventive measures to be identified and pre-treatment prior to surgery.     

Effect of T-activin on the production of immune interferon

A study was made of the effect of T-activin on the biosynthesis of immune gamma-interferon. It was shown that in 27% of patients with chronic nonspecific pulmonary diseases, production of gamma-interferon by lymphocytes was substantially reduced during exacerbation of inflammatory process in the lungs. It was discovered that T-activin was not an interferon inductor but enhanced its synthesis in patients with a low capacity of producing immune interferon even at small doses of interferon inductor. The preparation does not produce any effect on this process in normal subjects and in patients showing the normal level of gamma-interferon. Thus T-activin can be used for stimulation of interferonogenesis.     

Modeling sepsis in the laboratory: merging sound science with animal well-being

Despite impressive advances in biomedical research, few noteworthy breakthroughs have been made in the treatment of sepsis during the past several decades. This stalemate is primarily due to the intricate and heterogenic nature of the systemic immune responses characterized as the sepsis syndrome. In general, such complexity must be approached with in vivo models. Several animal models have been described, suggesting that none adequately address all of the pressing needs in sepsis research. The most clinically applicable models involve a localized infection, such as surgically induced polymicrobial sepsis, that gradually propagates a systemic immune response. Because relevant models must mimic a severe and chronic syndrome, animal well-being is often a concern in sepsis research. A balance between the needs of sepsis research and animal welfare can only be achieved through knowledge of the strengths and weaknesses of and alternatives to in vivo sepsis models.     

Epidemiological surveillance

A case of Campylobacter infection in a 2-day old infant is described. The possibility for a newborn infant to get infected with Campylobacter jejuni directly from the infected mother in the process of parturition is considered. The methods of the laboratory diagnosis of Campylobacter infection, including the main principles of the identification of Campylobacter species, are presented. The possibility of using the enzyme immunoassay for the serological diagnosis of Campylobacter infection is shown. The possible ways and factors of the transfer of this infection to newborn infants are discussed.     

Change in immunological and biochemical parameters in germ-free animals in response to T-activin

The influence of immunoregulating humoral thymus factor T-activin (fraction AFT-6) on the activity of xenobiotic metabolism enzymes (EMX) and cellular-dependent cytotoxicity was investigated in germ-free guinea-pigs. Germ-free and conventional animals were injected 5 micrograms of T-activin intraperitoneally, on 3 successive days. The control animals were injected a physiologic saline. A day after the last injection the animals were killed, and EMX and K cell activity was measured. It was found that EMX activity in germ-free animals was decreased. T-activin stimulated cytochrome P-450, NADP-cytochrome-C-reductase, glutathione-S-transferase, benzopyrene hydroxylase and epoxyhydrase activity. In conventional animals the activity of these enzymes remained unchanged under the influence of T-activin. K-cell activity in germ-free animals was decreased, as compared to conventional guinea-pigs. Under the influence of T-activin the parameter increased and stood at about 70% of normal values.     

Effects of T-activin on the morphology of the thymus gland in experimental injury of the lower limbs in mice (anti-stress effect of T-activin)

The effect of T-activin on thymic involution under the experimental trauma of femur was studied. T-activin in a dose of 1.0 micrograms/mouse was injected into young male (CBA X C57BL)F1 mice weighing 17.5-19.0 g before (I injection) or immediately after the fracture of the femur during 3 days. Morphometric analysis of the thymus was made 1, 5, 10 and 15 days after the trauma. It was found that T-activin suppressed the involution of the thymus, induced by the trauma, during the first 5 days and accelerate the process of its regeneration. It is suggested, that T-activin displays protective anti-stress effect on the mouse thymic involution.     

联合检测PCT、hs-CRP在新生儿脓毒症诊疗中的应用价值

目的探讨联合检测血浆降钙素原(PCT)及超敏C反应蛋白(hs-CRP)在新生儿脓毒症诊疗中的应用价值。方法选取2015年2月至2016年2月大连市妇幼保健院新生儿科88例住院感染患儿作为感染组,同期出生的21例正常足月产儿作为对照组,采用免疫荧光干式定量法进行血浆PCT及hs-CRP的检测。结果感染组患儿PCT、hs-CRP水平均明显高于对照组,差异有统计学意义(P0.01);2组患儿WBC水平差异无统计学意义(P0.05)。轻度脓毒症组、中度脓毒症组、重度脓毒症组各患儿治疗前血浆PCT、hs-CRP水平依次升高,各组间比较差异有统计学意义(P0.01);而各组患儿全血WBC水平比较差异无统计学意义(P0.05)。轻度脓毒症组、中度脓毒症组、重度脓毒症组各患儿治疗后血浆PCT、hs-CRP水平较治疗前显著降低(P0.01);而各组患儿全血WBC治疗前后水平比较差异无统计学意义(P0.05)。结论 PCT及hs-CRP能反映脓毒症的病情严重程度,联合检测PCT及hsCRP、并对其动态监测对新生儿脓毒症的早期诊断、疗效评价和预后判断具有重要的应用价值。     

Virologic and serologic studies on an outbreak of echovirus type 11 infection in a hospital maternity unit.

An outbreak of echovirus type 11 (E-11) infection occurred among newborn babies in a hospital maternity unit in the summer of 1971. The results of studies are as follows: 1) Forty-one of 188 infants developed febrile illness with stomatitis during one and a half months from July to September. E-11 was isolated from stool specimens of 14 infants and two throat swabs. Antibody response to the virus was shown in all the 19 cases examined. Some of their mothers were suffering from subclinical infection. 2) The isolates were identified as a variant of E-11 which is not neutralized with antiserum against prototype E-11. Antiserum against the current virus neutralized both current and prototype viruses. 3) Sucrose gradient centrifugation of sera from infants revealed that the neutralizing antibody activity resided more predominantly in 19S than in 7S fractions. These antibodies reacted more specifically with the current strain than with the prototype Gregory strain.     

Nonspecific immunomodulation influences resistance of mice to experimental infection with Mesocestoides corti and Ascaris suum

The influence of nonspecific immunomodulation on the course of experimental infection was examined in larval cestodosis (Mesocestoides corti) and ascaridosis (Ascaris suum) in mice. Immunosuppressive treatment (with azathioprine or hydrocortisone) resulted in a decrease of resistance in both models. The subsequent administration of T-activin to immunosuppressed mice led to the restoration of resistance to a level equal to that of untreated control mice. The administration of different immunomodulators partially protected mice against M. corti (T-activin, thymomodulin) or A. suum (T-activin, thymomodulin, thymosin fr.5, bursa-activin) infection. The protective effect of different treatments did not correlate with the level of specific antibody in the sera of infected mice. These results, which confirmed the decisive role of T-cell immunity in the resistance to the helminth infections, raise the possibility of the use of immunomodulators (thymic preparations) in the immunoprophylaxis of helminthoses.     

The Microbial Spectrum of Neonatal Sepsis in Uganda: Recovery of Culturable Bacteria in Mother-Infant Pairs

Neonatal sepsis in the developing world is incompletely characterized. We seek to characterize the microbial spectrum involved in sepsis and determine the role of maternal transmission by comparing organisms that can be cultured from septic newborn infants and their mothers. From 80 consecutive mother-infant pairs meeting clinical criteria for neonatal sepsis, we collected infant blood and spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal fluid cultures, for a total of 35% recoverable putative causative agents. Bacteria recovered from vaginal specimens were not concordant with those recovered from infants. Similarly there was no concordance of bacteria recovered from blood and cerebrospinal fluid. We conclude that relying on traditional bacterial culture techniques does not adequately delineate the role of maternal versus environmental sources of neonatal sepsis in this setting. More sensitive molecular approaches will be needed to properly characterize the maternal and environmental microbial community involved in neonatal sepsis in such developing countries.     

Direct Antiglobulin Reaction in ABO-Haemolytic Disease of the Newborn

The minimum number of IgG anti-A (or anti-B) molecules detectable on A or B red cells by the antiglobulin reaction was found to be the same—that is, about 150 molecules per red cell—with newborn as with adult cells. Furthermore, the ratio of anti-IgG bound to IgG anti-A (or anti-B) molecules was the same whether the anti-A (or anti-B) molecules were present on newborn or on adult cells and was similar to that found for anti-IgG bound to IgG anti-Rh.In 15 infants (11 group A, 4 group B) with haemolytic disease of the newborn due to ABO-incompatibility the amount of anti-A or anti-B on the red cells ranged from 0·25 to 3·5 μg antibody per ml red cells, corresponding to 90-1,320 antibody molecules per cell; only five infants had more than 0·55 μg antibody per ml of red cells. These amounts are far smaller than those found in most moderate or severe cases of Rh-haemolytic disease.It is concluded that the weak direct antiglobulin reactions observed in ABO-haemolytic disease are due simply to the fact that the number of anti-A (or anti-B) molecules on the infant''s red cells is at the lower limit of sensitivity of the test. Since ABO-haemolytic disease can be quite a severe process it seems probable that IgG anti-A and anti-B molecules are more effective than anti-Rh molecules in bringing about red cell destruction.     

Interaction of T-activin with peritoneal macrophages

The action of T-activin on peritoneal macrophages of CBA mice after its introduction into the animals has been studied. In intact mice the phagocytic activity of macrophages and their resistance to the cytopathogenic action of Salmonella typhimurium live cells remains unchanged. The injection of corpuscular pertussis vaccine into mice leads to a decrease in the resistance of macrophages to the action of salmonellae. The simultaneous injection of T-activin into mice in doses of 0.1 and 1.0 microgram per animal abolishes the damaging action of the vaccine. The analysis of the in vitro action of T-activin on macrophages of intact mice revealed that the preliminary incubation of cells with the preparation sharply increases their resistance to the action of salmonellae, while its introduction simultaneously with bacteria or after them rapidly leads to the death of macrophages. The action of T-activin is supposed to be linked with triggering the biosynthetic processes mediating the resistance of macrophages to the cytopathogenic action of salmonellae.     

Enhancement of antitoxic immunity in newborn infants by peroral administration of donor antistaphylococcal immunoglobulin

The possibility of enhancing specific immunity by the oral administration of homologous antistaphylococcal immunoglobulin in a dose of 50 I. U./kg b. w. before the first feeding was shown in 75 newborn infants with a high risk of staphylococcal infection. 24 hours after the first administration of Ig the titer of staphylococcal anti-alpha toxin in the blood rose from 0.68 +/- 0.05 I. U./ml to 2.9 +/- 0.14 I. U/ml, on day 7 this titer persisted at the level of 2.86 +/- 0.12 I. U./ml, and 3 months later the titer was 1.5 +/- 0.05 I. U./ml. No side effects were observed. In the reference group (50 infants) antitoxic titers remained low. No suppurative-septic diseases were observed in the test group within 3 months, while in the controls, focal forms of staphylococcal infection (12 cases) and sepsis (1 case) were registered.