Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TB assays with the tuberculin skin test (TST) for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). The Medline, Embase and Cochrane databases were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-γ release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette-Guérin (BCG) vaccinees were evaluated. Specificity of IGRAs varied 98-100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TB and 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA-positive individuals followed for 19-24 months varied 8-15%, exceeding those reported for the TST (2-3%). In multivariate analyses, the odd ratios for TST positivity following BCG vaccination varied 3-25, whereas IGRA results remained uninfluenced and IGRA positivity was clearly associated with exposure to contagious tuberculosis cases. IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion of M. tuberculosis infection with higher reliability.

Cellular and humoral systemic and mucosal immune responses stimulated by an oral polybacterial immunomodulator in patients with chronic urinary tract infections.

An oral polybacterial immunomodulator Urostim (U), composed of killed cells and their lysates from E. coli expressing type 1 and Pili, E. coli Rc mutant, P. mirabilis, K. pneumoniae and E. faecalis was created for immunoprophylaxis and immunotherapy of urinary tract infections (UTIs). In experimental animal models, the stimulating effect of U on lymphocyte functional activity, macrophage phagocytosis and antibody producing cells, was established. In this study the immuno-modulating effects of U on the proliferating capacity and ultrastructural morphologic changes of lymphocytes, cytokine production and specific systemic humoral and mucosal immune responses in patients with UTIs have been evaluated. Patients enrolled in the study, received orally 50 mg U daily for a period of three months. On days 0, 30 and 90 a quantitative analysis was performed on lymphoproliferative responses to polyclonal mitogens, IL-2 and the specific antigen U, the production of specific serum and saliva IgA, IgM and IgG antibodies to all components of U and the concentration of pro-inflammatory cytokines. There was significant improvement of non-specific and specific lymphoproliferative responses on days 30 and 90 after the onset of treatment with U, confirmed by electronmicroscopic studies. The highest concentrations of serum proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 were registered at baseline followed by a decrease until the end of the observation period. This finding correlates with the gradual decrease of immune activation as measured by the spontaneous lymphocyte proliferation. Data from the production of specific antibacterial antibodies in serum and saliva show two types of reactions. The first type was registered in patients with low pre-treatment levels in whom the concentration of specific antibodies increased on days 30 and 90. The second type of reaction was observed in patients with high pre-treatment levels, which dropped on day 30 and were usually followed by an increase at the end of the study. These results provide evidence for the immuno-modulating effect of U. Our data show that the oral administration of the polybacterial immunomodulator Urostim stimulates adequate cellular and humoral systemic and mucosal immune responses in patients with chronic UTIs.

Some parameters of cell-mediated immunity in colon cancer patients.

16 colon cancer patients in the second clinical stage (according to the TNM classification), aged 34 to 71 years were studied before and 14 days after radical surgery. The in vitro cell-mediated immunity was evaluated using the rosette-forming test and blastogenic reactivity of blood lymphocytes to PHA. The percentage of total rosette-forming cells (T-cells) before and after surgery did not alter significantly (p less than 0.1). At the same time there was no significant difference between the number of rosette-forming cells in cancer patients compared to donors (p less than 0.1). Blastogenic reactivity of lymphocytes to PHA expressed as a stimulation index (S. I.) showed a significant decrease of that parameter in patients compared to donors (p less than 0.001). The S. I. was lower in patients 14 days after surgery than prior to treatment (p less than 0.01).

In vitro cell-mediated immune reactivity in colon cancer patients.

147 colon and/or rectum cancer patients in all clinical stages (according to TNM classification) aged 34 to 71 years were studied before radical surgery and 14, 45 and 90 days after it. The in vitro cell-mediated immunity was evaluated using the blastogenic transformation of blood lymphocytes to phytohemagglutinin (PHA), fast and total E rosettes. The immunosuppression observed in all clinical stages in comparison to donors becomes deeper 14 days after operation. 45 and 90 days after operation all three parameters studied increase but only in the clinical stage II (localized disease), the values reach and even surpass their initial level. Based on the obtained data conclusions were made in regard to the correlation of the lymphocyte functions to the clinical stage. In the localized (disseminated) stages a good (bad) ability of the immune system to recover is suggested.

Delayed hypersensitivity reactions in patients with breast cancer.

Fifty six patients with metastatic cancer of the breast (stage IV) were treated with Cyclophosphamide, 5-Fluorouracil and Cyclophosphamide + 5-Fluorouracil. Tests for delayed hypersensitivity to homologous tumor antigen before treatment were positive in 83.9% and negative in 16.1%. Response to DNCB was positive before treatment in 51.8% and negative in 48.2%. Following chemotherapy the skin reaction, to homologous tumor antigen remained positive, only in 12.6% and negative in 87.4%. The reaction of DNCB remained positive after treatment only in 17.8%. In the remaining 82.2% suppression of the reaction occurred. These data show that chemotherapy may suppress, to a certain excent, immune responses. It is established that among patients who have shown a positive reaction to homologous tumor antigen 55.3% of all cases have displayed objective response to the treatment, and among these with negative skin reactions objective responses were observed in 22.22% of all cases. In patients with positive DNCB reactions objective responses were observed in 79.3% and among the negative ones--in 37.4%.

[The treatment of vaginal mycosis with Orungal]. / Lechenie na vaginalnata mikoza s Orungal.

UNLABELLED: The authors report their results of the treatment of the vaginal mycosis with Orungal (Janssen-Cilag). Twenty two sexually active women are included in the study, all with clinical signs of fungal vaginitis. Microscopic examination of vaginal secretions and fungal cultures are performed for all of the patients. Twenty cultures show C.albicans as causing agent and 2-non-C.albicans. One-day treatment with Orungal 2 x 200 mg is prescribed. Control examination and mycologic cultures are performed on day 7-10 and 30 after treatment. In 20 patients (91%) there is not clinical signs and the cultures remains negatives. In 2 (9%) the signs of fungal vaginitis persists which evoke the giving of the same dose once again. Adverse reaction (nausea) has been notify by one woman. CONCLUSION: The treatment with Orungal of the vaginal mycosis is highly effective, with minimal adverse reactions and very good acceptance by women.

[Hysterectomy--a time for reappraisal]. / Khisterektomiiata--vreme za preotsenka.

Hysterectomy is the most common non-pregnancy-related surgical procedure performed worlwide. The objective of our study was to investigate the hysterectomy by age, indication and surgical method employed during 1994-1998 in Department of Obstetrics and gynecology of Higher Medical Institute-Plovdiv, Bulgaria. During the period 1352 hysterectomies are performed. The most common indication was uterine myoma--50.3%. The most frequently the removal of the uterus is made at the age of 45-49. The low percentage of vaginal hysterectomies has been noticed--4.6%, as well as the comparatively frequent removal of the ovaries along with hysterectomy for benign diseases. A thorough analysis has been made in order to reduce the unnecessary hysterectomies, to choose the right approach and extend of the operation.

[Perforation of duodenal ulcer in the puerperium--a case report]. / Perforatsiia na duodenalna iazva v puerperiuma--s prinos na edin sluchai.

The authors present a case of perforated duodenal ulcer in the puerperium at a patient who underwent Ceaserian section. Urgently 12 hours after the perforation relaparotomy was made. The exit of the illness depends on the precise and early diagnosis and subsequent surgical treatment.

Correlation between the degree of immune activation, production of IL-2 and FOXP3 expression in CD4+CD25+ T regulatory cells in HIV-1 infected persons under HAART.

Chronic immune activation is the leading event in the pathogenesis of HIV-1 infection and is associated with depletion of CD4+ T cells and Th1/Th2 imbalance. The role of Tregs in HIV infection is still controversial as these cells may control both immune activation and HIV-specific T cell responses. Aim of the present study was to correlate the degree of immune activation with FOXP3 expression and production of IL-2 and IL-10. Peripheral blood was obtained from 10 HIV-1-infected subjects with sustained response to HAART. Four cellular fractions were purified and simultaneously used in further experiments: PBMCs, CD4+CD45RO+, CD4+CD45RO+CD25- and CD4+CD45RO+CD25+. The level of immune activation was measured both by flow cytometry and radiometry as short-term 1-hour spontaneous lymphocyte proliferation; IL-2 and IL-10 production were determined by ELISA in supernatants of cultures non-stimulated or stimulated with PHA and p24 antigen. FOXP3 mRNA expression was detected by RT-PCR. A group of healthy subjects was used as control. Statistical analysis was performed by SPSS. The level of immune activation (total CD25 expression) was found correlated to both CD4+ and Tregs (CD4+CD25high+; FOXP3mRNA) and it was found higher in HIV-1 infected subjects in comparison to the healthy control group. The highest SLP-1 h was measured in the CD4+CD4+CD45RO+ CD25- population (T reg depleted), suggesting a role of Tregs in controlling immune activation during HIV-1 infection. In addition, CD4+ cells from HIV-infected individuals remained responsive to the negative regulation by Tregs (measured as IL-10 production) both spontaneously and upon stimulation. It is worth noting, however, that total PBMCs of these patients also responded well to specific antigen (p24) stimulation even though IL-2 release was impaired. The results obtained suggest that Tregs significantly influence the level of immune activation. At the same time, their function appears to be dependent on IL-2 production by the remaining T cells. These findings suggest that the control of Th1/Th2 balance could be an approach to immune-based therapy for HIV infection.

A case of trisomy 22 with a probable Robertsonian translocation 21/22.

A 2-year-old girl with a prabable trisomy-22 translocation is described. The principal clinical symptoms described by the authors who have reported cases with proved trisomy 22 are presented. A probable 46,XX,-21,+t(21q;22q) karyotype was established in the patient. The proband's clinical picture is compared with other trisomy 22 cases described in the literature. The incidence of this trisomy among the human population is discussed.

Experimental investigations on the immunomodulating activity of polybacterial preparation for peroral immunotherapy and immunoprophylaxis of uroinfections.

The immunomodulating effect of a polybacterial immunostimulator Urostim in experimental animal models was investigated. The preparation was created for immunotherapy and immunoprophylaxis of uroinfections. It consists of killed bacterial cells and their lysates of four microbial species: Escherichia coli expressing type 1 pili, Rc mutant of E. coli, Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis, BALB/c mice and guinea-pigs were treated orally with Urostim for 5 or 10 days, respectively. A stimulatory effect of Urostim on phagocytosis (increased phagocytic index and phagocytic number) of mice peritoneal exudate cells was observed. An increased number of plaque-forming cells and elevated titres of haemagglutinating antibodies in mice demonstrated activation of humoral immunity. Lymphoproliferative studies showed a significant response to phytohaemagglutinin (PHA) and Urostim, especially after the second application of the preparation. At the same time no changes in the absolute number of peripheral blood lymphocytes were found. An active protection of mice against a systemic infection and of guinea-pigs against uroinfection caused by Gram-negative bacteria was obtained. In conclusion, the results obtained characterize Urostim as an effective immunostimulator. Its peroral application leads to the activation of innate resistance, cell-mediated, humoral and local immunity.

Immunostimulating and protective effects of an oral polybacterial immunomodulator 'Dentavax' in a rabbit experimental model.

The immunostimulating and protective effects of an oral polybacterial immunomodulator, Dentavax (D), composed of killed cells from Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Candida albicans and Lactobacillus acidophilus and their lysates, have been investigated on an experimental rabbit model. In this model, mixed suspensions of the above bacterial wild strains have been injected in six sides of oral mucosa. A long-lasting inflammation with the development of infiltrates and confluating abscesses has been observed. The influence of orally given Dentavax on the course of the model infection as well as on the dynamics of the immune response has been studied. A two-fold decrease in the duration and severity of inflammatory reaction, confirmed by the histological findings, has been registered. In immunised animals, an activation of polymorphonuclear phagocytosis, together with stimulation of humoral systemic and mucosal immunity with synthesis of specific serum (predominantly, IgG) and coproantibodies (predominantly, S-IgA) determined by ELISA, has been found. The results obtained proved the strong immunostimulating and protective effects of the preparation D, which is meant for the prophylaxis and treatment of inflammatory periodontal diseases.

Stimulating effect of an oral polybacterial immunomodulator on the proliferative activity of guinea pig lymphocytes.

A preparation for the prophylaxis and treatment of inflammations of oral mucosa and parodont Dentavax (D) was investigated in guinea pigs. Animals were given orally D for 5 consecutive days and a month later the procedure was repeated. On day 3, 10, 21, and 28 after immunization and reimmunization lymphoproliferative responses to PHA, rIL-2, LPS and D were measured by the radiometric blast transformation assay in peripheral blood, spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP). The percentage of cells entering S and G2/M-phases of cell cycle was assessed by the flow cytometric DNA analysis. A correlation in proliferative activity of cells after in vitro stimulation with PHA and LPS has been established by both methods. Peak values of lymphocyte stimulation were found on day 10, especially after the second administration of D in all organs tested, mainly in MLNs and spleen. Electron-microscopic studies demonstrated an extensive development of the endoplasmatic reticulum in plasmatic cells from spleen, PPs, mesenteric, bronchial and inguinal lymph nodes. The results obtained may be considered a proof of the immunostimulating effect of Dentavax.