Determination of TNF alpha, interferon alpha, interleukin 2 and reactivity in the leucocyte migration inhibition test in breast cancer patients.

To date, the results concerning the prognostic importance of parameters of cell-mediated immunity in breast cancer patients are very contradictory; moreover, in most of them the results are hardly comparable due to methodological differences and heterogeneous groups of patients. In 123 patients with nonmetastatic breast carcinoma TNF alpha, INF alpha, IL 2 and reactivity in the leucocyte migration inhibition test (LMI-Test) against autologous tumor tissue were determined and the results correlated with the clinical course of the disease up to a maximum of 108 months. In breast cancer patients TNF alpha-serum levels were significantly (p less than 0.05) elevated compared to healthy controls. We also found that patients with progressive disease had higher levels than patients without recurrences. There were no differences concerning the IL-2 and IFN alpha serum levels between cancer patients and controls, nor did we find a correlation with the clinical course of the disease. In 38% of all breast cancer patients examined, a MIF production against tumor tissue could be demonstrated in the LMI-test. There was no difference concerning the LMI-reactivity between the groups of lymph-node negative and positive patients, but the observation that those patients with an unfavourable clinical course respond more frequently with an enhanced macrophage migration and rarely with migration inhibition was considered of notable prognostic significance. According to these results, it is possible that determination of TNF alpha and delayed type hypersensitivity reaction against tumor tissue in the LMI-test is of clinical value for the determination of risk groups.

[Comparison of tumor-associated cellular and nonspecific humoral immune parameters in immunologic monitoring of breast cancer]. / Vergleich tumorassoziierter zellulärer und unspezifischer humoraler Immunparameter beim immunologischen Monitoring des Mammakarzinoms.

In 119 patients with breast cancer states pT1-4 N0-3 M0 the following parameters of tumor-associated cellular and unspecific humoral immunity were determined: (1) leukocyte-migration-inhibition test against preparations of the autologous and homologous tumor tissue; (2) determination of the immunosuppressive activity of the serum on the PHA-, Con A- and PWM-induced lymphocyte transformation; and (3) determination of the alpha-2 pregnancy-associated globulin (alpha-2-PAG) serum level. In both groups of lymph node negative and positive breast cancer patients, half of the patients showed a significant reaction in the LMI test in the form of a reduced or enhanced migration of the macrophages (enhancement). In lymph node negative breast cancer patients the immunosuppressive activity of the serum on the PHA- and CON A-induced lymphocyte reactivity was decreased, whereby we found a positive correlation between the immunosuppressive activity of the serum and the LMI reactivity against autologous tumor tissue. We found no differences in the alpha-2-PAG serum level between lymph node negative and positive breast cancer patients, but there were greatly increased alpha-2-PAG levels in LMI-reactive patients compared to those showing an enhancement in the LMI test. A tumor-associated cellular immunity could be shown in the LMI test in breast cancer patients, which can be correlated with other humoral immune parameters. Especially the demonstration of an immunological enhancement in the LMI test could possibly be used for the definition of high-risk groups.

Differences in lymphocyte mitogenic stimulation pattern depending on anaesthesia and operative trauma: I. Halothane-nitrous oxide anaesthesia.

Cell-mediated immunity (investigated by in vitro mitogen/antigen induced lymphocyte proliferation) is known to be depressed in the post-operative period. In the present investigation, performed with halothane/nitrous oxide inhalational anaesthesia in healthy patients without trauma (eye surgery) and with operative tissue trauma (gynaecological operations), only the combination of major surgery with halothane/nitrous oxide anaesthesia was associated with a depression of lymphocyte reactivity to phytohaemagglutin (PHA-P), Concanavalin A (Con A) and pokeweed mitogen (PWM). This lasted for 3-10 days post-operatively.

Differences in lymphocyte mitogenic stimulation pattern depending on anaesthesia and operative trauma: II. Combined neuroleptanaesthesia.

In this study, neuroleptanaesthesia reduced the reactivity of lymphocytes to phytohaemagglutin (PHA-P) and pokeweed mitogen (PWM) in patients in a manner similar to that seen with halothane/nitrous oxide and enflurane/nitrous oxide inhalational anaesthesia. These findings began 4 h post-operatively, lasted throughout the first post-operative day and were similar in both operative trauma groups (eye surgery/gynaecological surgery). However, unlike the situation with the inhalational agent, Concanavalin A (Con A)-induced proliferation did not alter. It was also noted that, on the third post-operative day in both trauma groups, PHA-P- and PWM-induced proliferation ratios were significantly higher than were the pre-operative values. These findings could be the result of a specific effect of neuroleptanaesthesia.

Occurrence and characterization of different types of cytotoxic antibodies in pregnant women in relation to parity and gestational age.

Lymphocytotoxic antibodies in sera from 55 pregnant women (of whom 23 were in their first, 21 were in their second, and 11 were in their third pregnancy), as detected by four different microcytotoxicity tests, were predominantly cold reactive and of the IgM class. During pregnancy, there is an increase in lymphocytotoxic antibody formation which is most pronounced after delivery. It is impressive that during first and second pregnancies antibody frequency is similar in the first and second trimesters, whereas in a third pregnancy there is a decrease intermittently. The behavior of antibody frequency in the second trimester may suggest a possible absorption by fetal and/or placental structures. The antibodies seem to be part of a natural immunization process and may play a protective role in pregnancy.

Serum interferon levels in patients having radiotherapy for cervical carcinoma.

The well-known stimulation of interferon (IFN) both by non-specific and immune-specific stimulants, the effect of IFN on tumor therapy and against radiation damage gave us reason to examine cervical cancer patients undergoing radiation therapy for the presence of IFN. IFN was found in several serum samples of only two out of 47 patients.

[The technic of "open pelviscopy". A new method for increased safety in laparoscopy]. / Technik der "Offenen Pelviskopie" Eine neue Methode zur Erhöhung der Sicherheit bei der Bauchspiegelung.

The method of "open pelviscopy" is described and compared with the common performance of gynecological pelviscopy. The "open pelviscopy" combines the advantages of laparotomy--preparation of anatomical layers under view of the operator--with those of pelviscopy--minimal traumatization and optimal view at the intraabdominal organs. This method avoids blind puncture of the abdominal cavity, which otherwise is necessary to perform the pneumoperitoneum and to use the optic instruments. Apart from the well established indications for diagnostic and therapeutic gynecological pelviscopy we prefer this method especially in obese patients and in those who formerly had several laparotomies.

[Lymphocytotoxic antibodies in cervical cancer]. / Lymphozytotoxische Antikörper bei Patientinnen mit einem Zervixkarzinom.

Sera of 120 patients, suffering from cervical cancer (CCa) of different clinical stages (stage 0: n = 27; stage I: n = 29; stage II--IV: n = 64) as well as the sera of 116 healthy individuals as control group were examined for lymphocytoxic antibodies by microlymphocytotoxicity tests, variated in incubation temperatures (15 degress -- 22 degrees -- 37 degrees C) and incubation times (30--180 minutes). At an incubation temperature of 15 degrees C cold reacting lymphocytotoxic antibodies were detected in 26 patients' sera (21.7%) and in 13 control sera (11.2%). At an incubation temperature of 22 degrees C 36 CCa-sera (30%) were positive in comparison to 11 sera of the control group (9.5%). At an incubation 37 degrees C 40 CCa-sera (33.3%) and 7 control sera (6%) were positive. Relating these results to the clinical stages of the carcinoma, the highest percentage of lymphocytotoxicity was found in the sera of patients with an early stage of the disease. Increased evidence of lymphocytotoxic antibodies in the sera of patients with cervical carcinoma supports the assumption, that various immune reactions may be involved in this disease.

[Cell mediated immunity in cervical cancer patients: evaluation by in vitro leukocyte-migration-inhibition-assay (author's transl)]. / Zellulär vermittelte Immunreaktionen bei Patientinnen mit einem Zervixkarzinom: In vitro-Untersuchungen mit dem Leukozyten-Migration-Inhibitions-Test.

Cellular mediated immune reactions (CMI) against tumour associated antigens are the demonstration of an interrelationship between tumour and tumour host. They are related to the stage and prognosis of the disease. 41 patients with cervical cancer were tested by leukocyte-migration-inhibition test. Cryostat sections of 10 micron of the tumour-tissue, gained by excision or curettage and histologically defined, were taken as tumour antigens. The test was performed in Sykes-Moore-Chamber as so-called one-way-test with the lymphocytes/leukocytes and macrophagen of the tumour patient. Reactions against autologous and homologous tumour tissue and against recall antigens (tuberculin and varidase) were tested. There was no overall diminution of cellular mediated immune reactions. CMI was demonstrated in 69.7% (inhibition in 30.3%, stimulation in 39.4%) in the autologous and in 51.3% in the homologous system (21.6% inhibition, 29.7% stimulation).

[Anaesthesia and immunology (author's transl)]. / Anästhesie und Immunologie: Eine Ubersicht.

There is evidence of immunosuppressive influence of trauma/operation and anesthesia. The human immunological system is outlined as a complex functioning apparatus with humoral and cellular factors. The influence of operation and/or anesthesia on immunocompetence has been demonstrated by animal studies, in vitro examinations and clinical investigations. The analysis of these results and their significance for an impairment of the immunological surveillance of the patient is tried to be elucidated. There should be payed attention to the clinical consequences, especially in patients on high risk.