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Biomedical subjects

P Mallmann

Publications and source records attributed to P Mallmann.

At least 73 records · Page 4Linked to original sources
PubMed1991

[The effect of adjuvant combined chemo/immunotherapy on immunological parameters and clinical course in patients with breast carcinoma].

In 61 breast cancer patients the effect of an combined adjuvant chemo-/immunotherapy with thymopentin (Timunox, Cilag) on different parameters of cell-mediated immunity (Leucocyte Migration Inhibition Test, serum level of tumor necrosis factor alpha, IL 2, Interferon alpha and distribution of lymphocyte subsets in the peripheral blood) and the clinical course of disease was evaluated and compared to patients receiving only chemotherapy. In cancer patients additionally treated with thymopentin an increase of the interferon alpha serum level could be observed, whereas the other parameters examined did not change. In the control group the percentage of T helper cells decreased under chemotherapy (p less than 0.05). Due to the short time of observation of 49 months until now no significant changes concerning the disease free interval and the time of survival between both groups could be found. Possibly the additional administration of thymopentin in breast cancer patients at least leads to a reduction of the immunosuppressive side effects of an adjuvant chemotherapy.

Breast Neoplasms↗
PubMed1990

Cellular sensitization against spermatic and seminal plasma antigens in women after intrauterine insemination.

Using an indirect lymphokine-assay, the leucocyte-migration-inhibition-test (LMI-test), the cellular sensitization of fertile and infertile patients before and after homologous and heterologous intrauterine insemination (IUI) was investigated. In this assay several preparations of spermatozoa ("washed"-, "swim-up"- and "pellet"-spermatozoa) in different concentrations (1, 5 and 10 x 10(6) sperms/ml culture medium) and seminal plasma were tested as antigen. In all investigated groups a cellular immune response against spermatic antigen was demonstrable and seemed to be dose dependent. In contrast to fertile women who reacted with an enhancement of the macrophage migration for low concentrations the same concentration of antigen induced an inhibition of macrophage migration in fertile patients. For high concentrations of spermatic antigens there was a difference in the intensity of cell-mediated immune response between fertile and infertile women. Since infertile patients demonstrated an increased level of cell-mediated immune response it is possible that infertility may be caused by this altered immunological reaction. This response changes after multiple IUI-treatment and that change might be caused by the high concentration of spermatic antigens as there was a difference in the intensity of cell-mediated immune response between fertile and infertile women. Since infertile patients demonstrated an increased level of cell-mediated immune response it is possible that infertility may be caused by this altered immunological reaction. This response changes after multiple IUI-treatment and that change might be caused by the high concentration of spermatozoa. The immunological response of infertile patients seems to be similar in those receiving husband and donor IUI.

Adult↗
PubMed1990

Effect of tamoxifen and high-dose medroxyprogesterone acetate (MPA) on cell-mediated immune functions in breast cancer patients.

In 48 postmenopausal patients with non-disseminated breast cancer an adjuvant therapy with tamoxifen, and in 17 breast cancer patients with disseminated disease a therapy with high-dose medroxyprogesterone acetate (MPA) was performed and the results obtained were compared to a control group of 35 postmenopausal patients with non-disseminated disease receiving no further adjuvant treatment and 9 patients with disseminated disease, who were not treated by hormonal therapy or chemotherapy. Before therapy was started and at the end of therapy reactivity in the leukocyte migration inhibition test (LMI-Test) against autologous and homologous tumor tissue, serum levels of TNF alpha, IL-2 and IFN alpha, as well as the differentiation of different lymphocyte subsets in the peripheral blood, were determined. In patients undergoing adjuvant therapy with tamoxifen an increase of reactivity in the LMI test against tumor tissue (14.6% before and 22.9% after tamoxifen therapy) and increase of the percentage of NK cells (13.6% before and 19.8% after therapy) could be observed, whereas with TNF alpha, IL-2 and IFN alpha serum levels, as well as the differentiation of other lymphocyte subsets, no differences were found. In breast cancer patients with disseminated disease treated with high-dose MPA no changes of LMI reactivity and cytokine serum levels could be observed. We only found a decrease of T-helper cells from 38.4% before to 22.7% (p less than 0.05) at the end of therapy. These results indicate that tamoxifen has no severe suppressive side effects on different parameters of cell-mediated immunity and possibly leads to an increase in the number of NK cells. Contrary to this, high-dose MPA must be considered as a depletor of T-helper cells.

Aged↗
PubMed1990

Investigations on cell-mediated immunity in patients with breast and ovarian carcinomas receiving a combination of chemotherapy and immunotherapy with thymopentin.

In 78 patients with breast and 37 patients with ovarian cancer the effect of combined chemo- and immunotherapy with thymopentin (Timunox, Cilag) on different parameters of cell-mediated immunity (leukocyte migration inhibition test, serum level of TNF-alpha, IL-1, interferon-alpha, distribution of lymphocyte subsets) and the clinical course of disease was evaluated and compared to patients receiving only chemotherapy. In cancer patients additionally treated with thymopentin an increase in reactivity in the LMI test and an increase of IFN-alpha serum levels could be observed, whereas serum levels of TNF-alpha and IL-2 and the distribution of T-helper, T-suppressor, total T and natural killer cells did not change. Concerning the clinical course of disease, no significant differences could be observed in patients with disseminated spread of disease, whereas in patients receiving combined chemo-immunotherapy in the course of an adjuvant treatment a benefit was found compared to those receiving only chemotherapy. Thus, it seems that the additional administration of thymopentin in breast and ovarian cancer patients under chemotherapy results in a reduction of immunosuppressive side effects of chemotherapy and a positive effect of the survival time in patients with limited spread of disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Comparison of tumor-associated cellular and nonspecific humoral immune parameters in immunologic monitoring of breast cancer].

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.

Breast Neoplasms↗
PubMed1989

[The effect of immunotherapy with thymopentin on the parameters of cellular immunity and the clinical course of gynecologic tumor patients].

In 25 patients with cervical, uterine and ovarian cancer with a depletion of T-helper cells and a lack of reactivity in the LMI-Test a course of immunotherapy with thymopentin (Timunox, Cilag Biotech) at a dosage of 100 mg/die for 2 weeks and subsequently 100 mg 3 x/week for 4 weeks was performed and a comparison was made with a control group of 59 patients receiving no immunotherapy. The following parameters of cell-mediated immunity were determined: (1) leucocyte-migration-inhibition-test (LMI-test) against the tumor and varidase, and (2) number of T-helper/inducer-, T-suppressor/cytotoxic-, total T-, and natural killer cells in the peripheral blood. After a course of immunotherapy no changes in the mean value of the percentage of the cell-subpopulations could be observed, but in a quarter of all patients a reaction in the LMI-test could be shown. In the control group, under chemotherapy, the percentage of T-helper-, T-suppressor- and total T-cells decreased strongly, whereas in the immunotherapy group the percentage of these populations remained unchanged. Under the restriction of a mean observation time of only 18 (5-32) months no differences concerning the survival time between both groups could be observed; only in advanced ovarian cancer patients could a slight positive effect of immunotherapy be shown. These results support the indication of a course of immunotherapy with thymopentin in combination with chemotherapy, especially in advanced cancer patients.

Adjuvants, Immunologic↗
PubMed1989

[Circadian rhythm of cellular and humoral immunologic parameters].

From 8 o'clock AM to 6 o'clock PM every two hours in 22 healthy volunteers the following examinations were done: 1. lymphocyte transformation test using the mitogens PHA, Con A and PWM, 2. immunosuppressive activity of the serum on the mitogen-induced lymphocyte transformation, 3. determination of the serum levels of cortisol and human growth hormone (hgH). In the morning the mitogenic lymphocyte transformation was on the lowest and at 4 o'clock PM on the highest level. In opposite to this the immunosuppressive activity of the serum an the serum level of cortisol reached the highest level in the morning and decreased to the minimum at 4 resp. 6 o'clock PM. These findings can be interpreted at least for these parameters in the meaning of a reduced cellular and humoral immunity in the first part of the day, which is confirmed from further results in the literature.

Circadian Rhythm↗
PubMed1989

[In vitro studies of the effect of flunitrazepam on cellular immune parameters].

We investigated in vitro the influence of flunitrazepam concentrations ranged between 10 and 140 ng/ml on immunological parameters by using the rosette-inhibition-test and the lymphocyte-transformation-test. After addition of 30 ng/ml flunitrazepam, which is in accordance with a threshold concentration of 1 mg flunitrazepam after intravenous injection, we saw a significant decrease of the positive cells in the rosette-inhibition-test. In higher concentrations no significant changes could be observed. By the lymphocyte-transformation-test no significant evidence of immunodepression could be demonstrated in concentration usually achieved during anaesthesia or possibly after long term application in intensive care unit, independent of the used mitogenes. Thus, flunitrazepam demonstrates no immunosuppressive effect in concentrations achieved during anaesthesia or in intensive care unit as could be observed by tests of cellular immune competence. However, one has to take into consideration that only parts of the immunesystem could be examined with these tests and in vivo-investigations have to verify these results.

Cells, Cultured↗
PubMed1988

[The immune system and benzodiazepines].

Alterations of the immune-system by benzodiazepines are of minor degree in dependence of their central or peripheral activity. Regarding their central effects a modulation may be assumed via the endocrine system. In vitro and in vivo studies lead to the assumption, that benzodiazepines have a mutagenic effect, even though this hypothesis could not be confirmed by in vitro investigations. In vivo a possible mutagenic action could only be found in two patients after long term therapy. A more mitosis-inhibiting effect of diazepam was shown in in vitro studies. In animal experiments this observation could not be confirmed for the thymus. With regard to specific immunity, diazepam seems to have a stimulating effect on the T-helper cells. Locomotion and chemotaxis of human polymorphonuclear granulocytes is not influenced by anaesthetic doses of benzodiazepines. It is questionable whether benzodiazepines are of clinical importance for the immune-system of patients receiving anaesthetic doses. However, the presently generous use of benzodiazepines, e.g. on intensive care units, should be reconsidered in respect to immunological consequences.

Animals↗
PubMed1988

[Changes in immunological parameters in vitro and in vivo due to midazolam].

We investigated in vitro the influence of midazolam concentrations ranged between 0.2 and 1.6 microgram/ml on immunological parameters by using the rosette-inhibition-test and the lymphocyte-transformation-test. Additionally, in vivo studies using the lymphocyte-transformation-test and the immunomodulatory activity of serum were performed in young volunteers during experimental determination of hypnotic threshold concentration of midazolam. In vitro, no significant evidence of immunodepression could be demonstrated in a concentration range usually achieved during anaesthesia. In vivo, midazolam concentrations between 0.4-0.8 microgram/ml more likely increased than decreased the reagibility of lymphocytes. This was determined by the lymphocyte-transformation-test, especially for T-lymphocytes stimulated by the mitogens phytohemagglutinin and concanavalin A. Thus, midazolam demonstrates no immunosuppressive effect in concentrations achieved during anaesthesia as could be observed by tests of cellular immune competence. However, one has to take into consideration that only parts of the immunesystem could be examined with these tests.

Humans↗
PubMedDate not supplied

Immunologic features of tumor-infiltrating lymphocytes and peripheral blood lymphocytes in ovarian cancer patients.

OBJECTIVE: To determine the immunologic characteristics of tumor infiltrating lymphocytes (TILs) in comparison with the corresponding peripheral blood lymphocytes (PBLs) of patients with ovarian cancer in order to detect specific antitumor-reactive-immunocompetent cells. METHODS: Tumor infiltrating lymphocytes and PBLs were phenotyped by their surface markers, cytokine pattern, proliferation rate, and cytotoxic ability. RESULTS: The phenotypes of both lymphocyte populations were very heterogeneous. Peripheral blood lymphocytes had a higher proliferative activity and cytotoxicity against natural killer-sensitive tumor cells than the corresponding TILs. Furthermore TILs showed increased interleukin-4 expression whereas in PBLs, interferon-gamma production predominated. CONCLUSION: Peripheral blood lymphocytes showed more potentially valuable behavioral characteristics than TILs. In the future we need to combine several methods in order to define immune cells with antitumor activity. These cells should be expanded ex vivo and stimulated specifically for use in the immunotherapy of ovarian cancer.

Aged↗
PubMedDate not supplied

[Endometriosis and malignoma].

Malignant tumors arising from endometriosis are rare. A frequency of about 1% has been reported with in 80% the ovary, and in 20% extragonadal sites being affected. The most common extragonadal manifestations are the rectosigmoid and the rectovaginal septum. For extragonadal malignant tumors arising from endometriosis, complete resection followed by post-operative radiotherapy, possibly plus adjuvant progestin therapy, is the treatment of choice. Endometriosis-associated ovarian carcinomas are likely to present with lower stage disease and predominantly lower grade tumors. While their treatment follows that of common ovarian cancer, a poorer response to chemotherapy must be considered. As unopposed estrogen replacement therapy has been identified as a risk factor for the development of endometriosis-associated cancer, it is not recommended for hormone replacement therapy in women with a history of endometriosis. Loss of heterozygosity and mutations of the PTEN tumor suppressor gene may be early events of tumorigenesis. Endometriosis and its malignant transformation, perhaps, may serve as a suitable model in this regard. According to recent studies, endometriosis is associated with an increased relative risk of non-Hodgkin lymphoma.

Endometriosis↗
PubMedDate not supplied

Cellular sensitization against sperm and seminal antigens in women.

In 13 healthy women and 6 virgins the cellular sensitization against sperm and seminal plasma antigens was demonstrated by an indirect lymphokin assay, the leucocyte migration inhibition test (LMI-test) using the following preparations: "washed" spermatozoa, seminal plasma and spermatozoa of the supernatant prepared with the "swim-up" technique. In both groups of women a cellular sensitization against sperm and seminal plasma antigens could be observed. Further, a dose dependent correlation was found in that way, that increasing concentrations of spermatozoa lead to an increased inhibition of macrophage migration. In virgins cellular sensitization against seminal plasma proteins did not differ from non-virgins, only the percentage of significant reactions in the LMI-Test was reduced. As low sperm concentrations (1 million ml-1), which represent best the physiological situation in the uterus, induced an enhanced migrations of macrophages the enhancement of macrophage migration is considered as physiological cellular sensitization of females against sperm-associated antigens.

Adult↗
PubMedDate not supplied

Lack of correlation between P53 expression, BCL-2 expression, apoptosis and ex vivo chemosensitivity in advanced human breast cancer.

The relationship between apoptosis and chemosensitivity remains complex. We tested the chemosensitivity of 45 patients with advanced breast cancer (BC) ex vivo against anthracyclines (A: doxorubicin, epirubicin), taxanes (T: paclitaxel, docetaxel), cisplatin (DDP) and CMF and any correlation with the expression of p53, Bcl-2 and apoptosis. Viable cells were processed for ex vivo ATP Tumor Chemosensitivity Assay (ATP-TCA). Immunohistochemistry was performed in corresponding tumor samples. Apoptosis prior to chemotherapy was assayed using a TUNEL Test. Of 45 BC tested, 18 (40%) were p53+ and 37 (82%) showed high Bcl-2 expression. Apoptosis was detected in 29 (64.4%) specimens. The Ex vivo Response Rate (EVRR) for T was 75.6% in all cases. This was the highest rate among the 4 drugs tested followed by CMF (66.7%). For A and DDP the positive rates were lower (27.6% and 10.6%, respectively). A significant correlation (r = 0.589, p < or = 0.01) was found between tumors which were sensitive to A and DDP. There was no association between chemosensitivity and apoptosis. Moreover tests for p53 and Bcl-2 did not show a correlation to ex vivo chemosensitivity. Pretreatment apoptotic parameters are unlikely to predict the individual response of breast cancer to antineoplastic agents.

Antineoplastic Agents↗
PubMedDate not supplied

Vitrification of human spermatozoa without cryoprotectants.

The aim of our study was to investigate the effects of vitrification (cooling rate approximately 10000(C/min) without cryoprotectants on swim-up prepared human spermatozoa in comparison to standard conventional freezing with cryoprotectants. Motility, morphology, rate of viability and acrosome reaction of spermatozoa were evaluated. The described method of cryopreservation of human spermatozoa by direct plunging into liquid nitrogen slush without cryoprotectants was effective and could be recommended for routine IVF.

Cell Survival↗
PubMedDate not supplied

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.

Biomarkers, Tumor↗
PubMedDate not supplied

[A possible "immunologic" origin of idiopathic non-immunologic hydrops fetalis and initial results of preventive immunotherapy of subsequent pregnancies].

The cause of the nonimmune hydrops fetalis remains unsettled in spite of greatest efforts. Under an immunologic point of view of pregnancy as a successful course of an allograft it seems possible, that the idiopathic NIHF can be caused by an immunologic disorder in the meaning of a host-versus-graft-reaction. From 300 cases with prenatal diagnosed NIHF 37 (12.4%) could be classified after exclusion of all other causes as idiopathic and in 25 patients, as well as in 25 age- and parity-paired controls a differentiation of HLA-antigens and a determination of lymphocytotoxic antibodies using the NIH-, Prolonged incubation- and Cold-Complement Dependent-Cytotoxicity-Test (CoCoCy-Test) were performed. In cases with idiopathic NIHF the percentage of parents sharing 4 or 5 HLA-antigens was increased with 4/25 to 2/25 compared to the control group. In women with idiopathic NIHF the incidence of lymphocytotoxic antibodies was decreased, in dependence of the test-system used between 28 and 68% in the NIHF group and 24 and 80% in the control group. The percentage of women without lymphocytotoxic antibodies was increased in the NIHF group with 72% to 52%, in opposite to the control group in none of the patients a higher cytotoxicity with a lysing rate of more than 75% could be detected. In 4 cases with idiopathic NIHF, an increased paternal histocompatibility and a decreased incidence and percentage of lymphocytotoxic antibodies an immunotherapy was performed, in order to induce maternal blocking antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antilymphocyte Serum↗