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Tumor necrosis factor and soluble interleukin-2 receptor: two immunological biomarkers in female neoplasms.

In this study we have evaluated two new immunological parameters, soluble IL-2 receptor (s IL-2 R) and TNF, in 119 patients with female solid neoplasms (47 ovarian and 72 breast cancer). Our data demonstrate that both these markers have mean serum levels in cancer patients higher than in normal population, particularly in ovarian cases. Also the overall positivities were higher in ovarian (68%) than in breast cancer (51%). Finally we observed no relevant differences according to the status of disease in both groups of cancer patients. These preliminary results could suggest the possible usefulness of an immunological monitoring in cancer patients, above all when an immunotherapy with biological responder modifiers is proposed.

Adult↗

Special control of infection and rejection episodes after four years of cardiac transplantation at the University of Munich.

During the past 4 years, 36 orthotopic heart transplantations and two heart-lung transplantations were performed at Munich University Hospital. Immunosuppressive regimen consisted of cyclosporine A and low dose prednisone. The rejection diagnosis was based on daily cyto-immunological monitoring (CIM) and high frequency electrocardiography. In addition, viral, bacterial, and fungal infections were examined by CIM. The CIM is based on an evaluation of activated lymphocytes, lymphoblasts, and lymphocyte subsets in the mononuclear concentrate isolated from the peripheral blood by Ficoll Hypaque separation. Of the 38 patients, 24 are currently alive from 1 month to 4 years later (including one heart-lung recipient 1.5 years postoperatively). Altogether, 40 rejection episodes occurred among the patients. The diagnosis was based on CIM (sensitivity = 95%) and on endomyocardial biopsies (sensitivity = 95%). Control of rejection therapy was also done by using these methods. When the biopsies showed ongoing acute rejection, additional antithymocyte globulin or antilymphocyte globulin therapy was administered, relative to the CIM results. When using the endomyocardial biopsies for rejection control only, results showed a very low rate of two to three biopsies per patient in the first 3 months postoperatively. In addition, 16 infection periods were detected: five viral, six bacterial, four fungal, and one case of toxoplasmosis. The CIM showed typical hints of these inflammations in 12 cases (sensitivity = 75%) before clinical signs were visible. This immediately led to further diagnostic examinations and specific anti-infectious therapies, which were initiated early.

Journal Article↗

Macrophage-related suppressor cells in human renal transplant recipients.

In this study 66 renal transplant recipients were studied by in vitro immunologic monitoring assays in an attempt to delineate some immune reactivity parameters which migh explain the successful long-term survival of HLA incompatible allografts. Ninety percent of the recipients were found to be responsive to their specific donors in one-way mixed lymphocyte culture assays, indicating the presence of antigen reactive proliferating T cells. In contrast, studies of the in vitro generation of cytotoxic T cells showed that 73% of the long-term recipients demonstrated a marked hyporesponsiveness to the donor in cell-mediated lympholysis (CML) assays. Longitudinal studies indicated that specific CML hyporesponsiveness to the donor developed after transplantion. In the majority of recipients, CML hyporesponsiveness could be related to a suppressor cell phenomenon, since recipient mononuculear cells specifically suppressed the CML reactivity of third-party cells to the donor. Recipient CML hyporesponsiveness to the donor could be abrogated by removal of recipient adherent cells, most of which were monocytes or macrophages. The suppressor cell effect on CML is postulated to be related to macrophages which are either acting independently or under the regulation of suppressor T cells. These studies are among the first to suggest that suppressor cell regulation of relevant effector T cell activity may be important in the facilitation of successful human renal transplantation.

Cell Adhesion↗

[Clinico-metabolic status of fetuses and newborn infants with fetal macrosomia].

A study was made of the development of large fetuses during pregnancy with regard to the clinical picture, ultrasound screening of the placenta and fetuses, biochemical and immunological monitoring of blood of pregnant women, fetuses and neonates. 172 pregnant women were placed under observation. Of these, large fetuses (the main group) were born in 70 cases, whereas in 102 cases, the fetuses were of medium body weight (the control group). The comparison of the data obtained allows a conclusion that macrosomia gives rise to the acceleration of maturation of the fetal organs and systems, to the intensification of metabolism within the system mother--placenta--fetus.

Female↗

Epizootic situation and fox rabies prophylaxis in the territory of Tatarstan.

Data on the epizootic situation of rabies in the Republic of Tatarstan from 1970-2003 were obtained from epizootological and immunological monitoring. The districts in Tatarstan were divided into four groups according to the intensity of indices and a map of epizootics was developed. A three- to five-year cyclic recurrence of rabies, with peaks in the spring-winter-autumn seasons of the year was established. Foxes are the basic source and spreader of rabid infection in the Republic amounting to 96.5 % of rabies cases among wild animals. The present study gives the results of epizootological analysis of the efficacy of oral immunization of foxes in the republic since 1996.

Animals↗

Monitoring of prostate-specific antigen during external beam radiotherapy for carcinoma of the prostate.

In 35 patients with histologically confirmed carcinoma of the prostate confined to the pelvis, the value of prostate-specific antigen (PSA) was evaluated during external beam radiotherapy to the prostate and draining pelvic lymph nodes. In eleven patients initial prostate-specific antigen levels were more than 10 ng/ml and in twelve patients between 4 and 10 ng/ml. In the remaining twelve, initial prostate-specific antigen levels were less than 4 ng/ml. In the course of radiotherapy we could see a significant decrease of the prostate-specific antigen, even in those with levels between 4 and 10 ng/ml. This decrease seems to follow a logarithmic course but, because only three measurements during radiotherapy were made, this needs further study. With higher levels (more than 20 ng/ml), we rarely saw a value of less than 10 ng/ml at the end of radiotherapy but had to wait for several months for lower values to be reached. In several cases prostate-specific antigen decrease took up to three months after the end of the radiation course. Our results indicate that prostate-specific antigen values actually start decreasing during the radiation course itself and may, therefore, be useful for monitoring response to radiotherapy.

Acid Phosphatase↗

[Transplantation of the heart-lung complex (the first clinical experience)].

The article deals with experience in the first transplantation of a heart-lung complex in the USSR. The recipient was a 34-year-old male with dilation cardiomyopathy. It was decided to perform the transplantation because the terminal stage of cardiac failure and secondary pulmonary hypertension developed (cardiac index 1.3 l/m, pressure in pulmonary artery 80/50 mm Hg, resistance of pulmonary vessels 10.4 units after Wood). The heart and lung were transplanted from a 19-year-old male who died from a craniocerebral injury. Cyclosporine, metipred , imuran, dopamine in small doses, cardiotonics, and antibiotics were given in the postoperative period; the patient was kept on artificial respiration for 48 hours. For up to 10 days the patient's condition was relatively stable and his consciousness was clear. Bilateral pneumonia developed, however, from which he died on the 12th postoperative day. The article discusses organizational problems and some questions of immunosuppressive therapy, immunological monitoring, and the management of patients after transplantation of a heart-lung complex.

Adult↗

Immunological studies of renal allograft recipients treated with total lymphoid irradiation.

It is well known that highly sensitized patients and/or high responders, even under CsA therapy, constitute a risk category for transplantation. Based on this evidence, in 1982, our group initiates a pilot study using total lymphoid irradiation (TLI) as a pre-transplant modulator of patient's immuno-response. TLI has been employed in 30 uremic, non diabetic, patients. During this experience the first protocol, characterized by pre-transplant TLI greater than 2,000 rads (13 pts.) and post-transplant conventional therapy, was abandoned because of the severe TLI side effects. In the second protocol TLI dose never exceeded 2,000 rads and CsA was given, at initial dose of 7-12 mg/Kg/day according to CsA blood through levels. The immunological monitoring was performed during TLI treatment and in the postoperative clinical course by cell markers profile determination and functional assays. The data obtained have demonstrated that TLI treatment causes a prolonged depression in CD4 positive cells, a predominant recovery of T suppressor population, a pronounced impairment of T functions and a development of specific unresponsiveness to donor antigens. Furthermore the TLI plus CsA protocol, showing an additive effect which steadily decreases patient immunoreactivity, a lack of side effects and a stable long term graft function seems to be a more useful method for transplantation in high-risk or in strongly immunoreactive patients.

Antilymphocyte Serum↗

Changes in the T-lymphocyte subpopulation (CD+/CD8+) in the blood of patients following kidney transplant and during the acute rejection episode.

A study was made of changes in the ratio of CD4+/CD8+ in patients who had received cadaverous kidneys and who were under treatment with a combination of cyclosporin A + azathioprine + cor ticosteroids. The results showed that one month after the transparent there was a significant drop (P less than 0.05) in the immunoregulation index compared with the pretransplantation values. Throughout the whole period a correlation (r = -0.65, P less than 0.05) was found between the CD4+/CD8+ ratio and serum, creatinine. In recipients with acute rejection episode no significant difference was found between the CD4+/CD8+ values before the rejection episode (7 +/- 1 days and 3 +/- 1 days) and after it was diagnosed. The introduction of monoclonal antibodies specific for determinants in T-lymphocyte transplantation. Many authors have investigated changes in the CD4+ (helper inducer) to subpopulations (1) made possible immunological monitoring following the organ CDB+ (cytotoxic suppressor) ratio following the organ transplant (2, 3, 4, 5). Some reports (6, 7) have indicated that during rejection of a transplanted kidney there is a rise in the immunoregulation index (CD4+/CD8+), while other works (8, 9) failed to confirm this. Our work presents the dynamics of changes in the CD4+/CD8+ ratio in peripheral blood of recipients of cadaverous kidney transplants, and points to changes in the immunoregulation index before and during acute rejection episodes.

Acute Disease↗

[Sandoglobulin immunocorrection in trauma].

Twenty one patients with the long-term compression syndrome (LCS) and 12 patients with burns treated with sandoglobulin in combination with antibacterial therapy were followed up. The control groups included 14 and 18 patients, respectively. All the patients had wound infections. Increased or lowered respiratory burst of peripheral blood neutrophils and lowered contents of active T-lymphocytes were detected in the majority of the patients. The patients had also an increased respiratory burst of tissue homogenate in the primary focus. Sandoglobulin decreased the periods of normalization of the immunological indices, body temperature and leukogram shifts to the right. The most pronounced effect of the drug was recorded before radical operations, i.e. in the presence of acute microbial toxemia or in patients with severe and extended burns. The procedure of immunological monitoring developed by the authors rapidly estimates the indications to the use of sandoglobulin alone or in combination with other immunomodulators.

Bacterial Infections↗

[Initial results of a controlled study of small cell and squamous epithelial bronchial cancer: polychemotherapy and interferons].

We investigated a combination of polychemotherapy with beta- and gamma-interferon in patients with small cell and squamous cell bronchial carcinoma. Immunological monitoring was designed to detect systemic and local immunomodulatory effects of interferon therapy. Small cell carcinoma was treated every three weeks with adriamycin, cyclophosphamide and vincristine, squamous cell carcinoma was treated every three weeks with mitomycin, vindesine and ifosfamide. In one group of patients polychemotherapy was combined with beta- and gamma-interferon. In the event of no change or tumour progression cisplatin and etoposide were administered. In the case of PR and CR the initial schedule was continued. Treatment was stopped on achieving CR after 6 cycles, or in the case of no response. To date, 40 patients have been evaluated. Results indicate a slight increase in the response rate in patients with small cell carcinoma, extensive disease, in the interferon group, and an unchanged response rate in patients with squamous cell carcinoma. Besides the common "flu-like" symptoms there was considerable myelosuppression in patients under additional interferon therapy. In the interferon group we found measurable gamma-interferon serum levels, an increase in the spontaneous production of IL 2 by peripheral lymphocytes, and an increase in the spontaneous production of IL 1 and an in the phagocytic capacity of monocytes. In contrast, alveolar macrophages as part of local immunity show a decrease in the spontaneous and LPS-induced production of IL-1.

Antineoplastic Combined Chemotherapy Protocols↗

[Intraarterial combination immunotherapy in hepatocellular carcinoma].

Unresectable hepatocellular carcinoma (HCC) has a poor prognosis and little sensitivity to anticancer agents. We planned a combination immunotherapy, associating with rIL-2 continuous injection. Combination immunotherapy consists of 5 different biological response modifiers (BRM), i.e., rIL-2, OK-432, adriamycin (ADR), cyclophosphamide (Cy), and famotidine (Fa). rIL-2, OK-432 and ADR were administered from implantable infuser port connecting to a catheter which was injected into the hepatic artery via the gastroduodenal artery under laparotomy. OK-432, Cy, and Fa were also administered systemically. From 1988 to 1990, seven patients with unresectable HCC and two patients who underwent curative resection were treated by this therapy. The objective responses were evaluated by CT and angiography. This combination immunotherapy produced 3 cases of complete response and 2 of minor response. Immunological monitoring of lymphocyte subsets and NK activity of peripheral blood mononuclear cells was also performed. NK activity was significantly augmented and the percentage of Leu 7(-) NCD 16(+) cells increased during this therapy. Serious toxicity, but transient high fever and hypotension, was not observed during this therapy. All of these patients left the hospital within two weeks and returned to their previous job or similar life activity. These results suggest that this combination immunotherapy is worth performing in further clinical trials for hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical significance of Su-polysaccharide (Su-PS) skin test in patients with primary lung cancer treated with chemotherapy and administration of OK-432, with special reference to the therapeutic effect and prognosis].

In order to evaluate the significance as a parameter for monitoring immunological status and for predicting therapeutic effect and prognosis, Su-PS skin test was performed in 68 cases of primary lung cancer treated with chemotherapy and administration of OK-432. In 16 of 68 cases, lymphocyte subsets of peripheral blood using Leu monoclonal antibodies were analyzed to investigate the immunological status. Su-PS skin test was performed at the time of before treatment, 1 week after administration of OK-432, 4 weeks after chemotherapy and intervals during treatment. The reactions to Su-PS skin test in these patients were divided into 3 groups according to the maximum size during the treatment as follows; less than 20 mm, 20 mm to 50 mm and over 50 mm. As compared with the reaction to Su-PS skin test and the survival, there was a significant difference between each group. The analysis of the lymphocyte subsets also indicated that immunological status tended to be activated more in strong responders to the Su-PS skin test than in weak responders. Therefore, Su-PS skin test is considered to be an useful immunological parameter of cancer patients under treatment.

Adult↗

[Tumor-induced immunosuppression in breast cancer patients].

A comparative study of immunological reactivity of healthy volunteers and cancer patients with different stages of the disease was carried out. The study of 8 types of suppressor cells, chemoreceptor sensitivity and blast transformation of lymphocytes, natural killer cells, the level of immunoglobulins, regulatory subpopulation of lymphocytes, etc., has revealed several alterations in regulatory and effector links of immunity in the patients with late stages of the disease. The detailed immunological monitoring in the course of varying schemes of treatment is emphasized.

B-Lymphocytes↗

[Cancerogenic effect of long-term benzene exposure. Occurrence at the same work place of a plasmacytoma and two solid carcinomas ].

A report is given on three different malignomas appearing after high inhalative exposure to benzene for many years at the same working place in a cable plant. The exposure to benzene amounted to 22 years in a 50 year old man with oesophagus carcinoma, 17 years in a 61 year old man with plasmocytoma and 10 years in a 45 year old man with embryonal carcinoma of the testicles. The malignomas appeared 5-7 years after the end of the exposure. The carcinogenity of benzene is discussed on the basis of a survey of medical literature on epidemiological studies, casuistic contributions and experimental investigations in animals. A direct and indirect mechanism of benzene inducing carcinogenity is discussed: Activation of normal cellular oncogenes in DNA molecules by changes directly caused by benzene and; Damage of the lymphatic cell particularly susceptible to benzene followed by a disturbance of immunological monitoring and defence reactions against tumour cells.

Air Pollutants, Occupational↗

[Cell-mediated immunity in calves immunized against or infected with the bovine rhinotracheitis virus].

Simple and expeditious methods--leucocyte adherence inhibition LAI and leucocyte migration inhibition LMI--are described in the present paper; these methods enable to investigate cell-mediated immunity of animals. The two tests, along with serological and virological methods, were used to study changes in the immunity of calves after experimental infection by IBRV and after immunization by inactivated oil vaccine against IBRV. The results have indicated that the changes in cell-mediated immunity after experimental infection and vaccination of calves assumed courses independent of the changes in humoral reaction. Total cell-mediated immunity reaction started earlier in experimentally infected calves than in vaccinated ones. In some vaccinated calves a modified course of cellular immunity reactions was observed, characterized also by elimination of IBR virus on the nasal mucous membrane after challenge infection. The LAI and LMI test can be recommended for immunological monitoring in clinical laboratories and in research.

Animals↗

[Analysis of T-cell subpopulations and expression patterns of lymphocytic activation markers in patients in the early phase following kidney transplantation using laser flow cytometry].

In 10 patients after kidney transplantation the T cell subpopulations (CD4, CD8) and the number of activated lymphocytes (IL-2R and transferrin receptor+, 4F2+, HLA-DR+, CD3+) in the peripheral blood were determined. In 9 out of 9 cases with rejection a clear immune activation could observed. In patients with CMV-associated rejection crisis the CD4/CD8 ratio was significantly higher compared with patients with rejection crisis but without CMV infection. In all patients with CMV infection (n = 5) an increase of activated lymphocytes was observed. In a clinical-immunological monitoring the dynamics of the CD4/CD8 ratio, the expression of activation marker (especially CD3+, HLA-DR+ and 4F2+) and the absolute number of lymphocyte subpopulations should included.

Adult↗