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Biomedical subjects

M Betzler

Publications and source records attributed to M Betzler.

At least 55 records · Page 3Linked to original sources

Depression of nonadaptive immunity after surgical stress: influence on metastatic spread.

The question of increased tumor cell dissemination after surgical stress was addressed in the model system of the spontaneously metastasizing rat adenocarcinoma BSp73ASML, wherein amputation of the hind leg 7 days after intrafootpad implantation of tumor cells cured the animals, while surgical stress by laparotomy 2 days prior to amputation resulted in lung metastases in 80% of rats. A detailed in vitro analysis of natural killer (NK) and macrophage (Mo) activity in different lymphatic compartments revealed the following impacts of surgery: splenic NK cells displayed unaltered activity. Yet, there was a considerable decrease in the number of lymphoid cells during the first 4 days after surgery, being followed by an overshooting repopulation. In the peripheral blood, activity levels of NK cells dropped significantly during the first 24 h after surgery; later on, NK cells appeared activated with an over 2-fold increase in lytic units (LU), 4 days after surgery, NK activity had returned towards normal levels. Most dramatic changes were observed in the peritoneal cavity, being directly involved in the surgical intervention. Six hours after surgery the peritoneal cavity was nearly depleted of NK cells and Mo, the few remaining cells being highly activated. Within 2 days the peritoneal cavity was repopulated with a 3-4 fold excess of lymphoid cells and Mo, but the repopulating cells were extremely low in lytic activity. It is concluded that depression of nonadaptive immunity after surgical stress is mainly due to traffic and repopulation with immature cells, i.e. there was no indication of suppressor cell activity. This was confirmed by a combined treatment consisting in a systemic application of Corynebacterium parvum 2 days before surgery and a local application of C. parvum after surgery, which counter-balanced the stress-induced depression of NK and Mo activity. Accelerated and increased metastatic spread could be prevented concomitantly.

Animals↗

Plasma glutamate concentration and lymphocyte activity.

Elevated glutamate concentrations are commonly observed in tumor patients, and glutamate was recently found to competitively inhibit the membrane transport of cystine. We therefore investigated the possibility that elevated plasma glutamate levels may damage the immune system. The experiments in this report demonstrate a link between the individual plasma glutamate level and the individual immunological reactivity as measured by mitogenic responses. This correlation has been analyzed in 39 colorectal carcinoma patients, 40 oat cell carcinoma patients, 24 large cell lung carcinoma patients, and 31 apparently healthy persons (blood donors). Blood cells from all three groups of tumor patients in comparison with cells from healthy persons produced markedly reduced mitogenic responses against PWM, and all three groups of tumor patients had on average significantly elevated plasma glutamic acid concentrations. Our analysis revealed a linear regression of the logarithm of the individual plasma glutamate levels (before therapeutic treatment) on the logarithm of the corresponding mitogenic reactivity against PWM for the entire population of 134 persons tested (correlation coefficient -0.80; level of significance P less than 0.00001). A statistically significant linear correlation with a similar regression equation was also observed in the group of the healthy blood donors (n = 31; correlation coefficient -0.56; P less than 0.01), indicating that this correlation is universal and not dependent on the presence of a tumor. Mitogenically stimulated murine lymphocyte cultures revealed an inverse correlation between glutamate concentration and cell proliferation in response to the mitogens PHA and PWM.

Adult↗

[Preoperative diagnosis, pathologic anatomy and clinical significance of mucoceles of the appendix from the gynecologic viewpoint].

Owing to their proximity to the true pelvis and their topography, mucoceles of the appendix frequently cause clinical symptoms which call a gynecologic condition to mind. Sonographically, the structures of mucoceles are often similar to those of ovarian tumors. Within 12 months four patients with mucoceles underwent surgery at Heidelberg University Gynecological Clinic following diagnosis of a gynecologic disease (two tentative diagnoses of ovarian carcinoma, one of advanced ovarian carcinoma, one chance finding during Wertheim's operation). The problems of this rare condition are discussed with reference to the clinical findings, the intraoperative site, and the different morphology and maturity. Pathoanatomically and biologically, however, the clinical picture is not uniform. In mucoceles there is an accumulation of mucus with cystic dilatation of the lumen of the appendix. This is usually due to a tumor, which may be anything from a simple mucous membrane hyperplasia with extreme mucous formation, or an adenoma, to a mucilaginous adenocarcinoma. The rupture of a mucocele or metastasization of a carcinoma often lead to peritoneal mucous spread or peritoneal metastasization: in their patterns of distribution these are similar to a pseudomyxoma peritonei or a metastasizing ovarian carcinoma.

Aged↗

[Carcinoid tumor of the ampulla of Vater. Morphology, diagnosis and therapy of a rare papilla tumor].

We report on a patient with a carcinoid tumour of the ampulla of Vater and review the 33 known cases of the literature with regard to clinical presentation, morphology and therapy. As it is apparent from the location of the tumour, obstructive jaundice, pancreatitis and nonspecific upper abdominal complaints are the most frequent symptoms. The ampullary carcinoid belongs histogenetically to the APUD cell system with the ability of multiple endocrine activity. The expression of somatostatin peptide and neuron-specific enolase are the most common histopathological findings. A systemic function of these hormones, however, has not yet been shown. For diagnostic purposes in surgical pathology we found synaptophysin and chromogranin A to be important markers. For surgical treatment, partial duodenopancreatectomy remains the current therapy of choise, if the tumour exceeds two centimeters in diameter.

Ampulla of Vater↗

Reversal of defective lymphoproliferation in postoperative patients with colon cancer.

To establish a method for evaluation of immunological parameters in small blood samples, a whole blood technique was developed for the estimation of mitogen- or antigen-induced proliferation. Studies regarding cellular immunity in patients with colon cancer were done with 108 patients in all tumor stages, aged 32 to 80 years. They were studied before surgery and 10 days after operation. A group of 35 patients were further tested 3 months after surgical treatment. In patients with colon cancer the proliferative responses of peripheral blood lymphocytes to mitogens were significantly lower in comparison to healthy controls. These results were found when the response to concanavalin A, phytohemagglutinin, OKT 3, and pokeweed mitogen were analyzed preoperatively and 10 days postoperatively. There was no relation to the stage of disease. The marked reduction of mitogen responses was followed by a gradual return toward normal values 3 months after surgical resection of neoplastic growth in 80% of the patients. Our studies indicate that the defects were largely restored when testing was performed 3 months after operation. Using this result, it will be possible to perform long-term studies in order to establish if there is a correlation between the return to normal immune reactivity and the survival of individual patients.

Adult↗

Elevated plasma glutamate levels in colorectal carcinoma patients and in patients with acquired immunodeficiency syndrome (AIDS).

Amino acid concentrations were analyzed in the sera of HIV (LAV/HTLV-III) positive persons and in the plasma of colorectal carcinoma patients. Both groups of persons showed significantly elevated glutamate concentrations when compared with healthy control persons. Glutamate concentrations were found to be strongly elevated in all groups of HIV-positive persons including patients with acquired immunodeficiency syndrome (AIDS) or lymphadenopathy as well as HIV-positive persons without overt symptoms, indicating that increased plasma glutamate levels may be among the earliest consequences of the HIV infection. Moreover, the increased plasma glutamate concentrations in the colorectal carcinoma patients were correlated with a decreased immunological reactivity (mitogenic responses against concanavalin A). This suggests the possibility that the increased plasma glutamate concentrations may be causally responsible for the decreased immunological reactivity in colorectal carcinoma patients as well as in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Relationship of an unstable argG gene to a 5.7-kilobase amplifiable DNA sequence in Streptomyces lividans 66.

The relationship between an unstable argG gene and a 5.7-kilobase (kb) amplifiable DNA sequence in Streptomyces lividans 66 was investigated. Spontaneous, high-frequency Arg mutants deleted for this gene typically contain 200 to 300 copies of the tandemly reiterated sequence. A library of S. lividans 66 (strain 1326) wild-type genomic DNA was prepared in the vector lambda Charon 35. Chromosome walking over 44 kb established that argG is located 25 kb distant from a duplicated amplifiable DNA structure. A sequence was characterized, located farther distal from the amplifiable structure, containing strong homology with an internal sequence of the amplifiable DNA, which may have a role in the deletion of argG. Genetic mapping showed that argG and the 5.7-kb amplifiable sequence are linked to another unstable gene, determining chloramphenicol resistance (Camr) and that together these genes may be located in a silent chromosomal arc.

Argininosuccinate Synthase↗

T cell and OKM1-positive monocyte populations in the intestinal lamina propria mucosae and in the peripheral venous blood in Crohn's disease.

Nineteen patients with Crohn's disease were examined prior to operation. Peripherally circulating mononuclear cells were examined for the presence of the cell surface markers recognized by monoclonal antibodies OKT3, OKT4, OKT8 and OKM1. After surgical treatment samples of the mucosal lesions were obtained from the resected bowel segments of these patients. The inflammatory infiltrate in the lamina propria mucosae was examined immunohistologically for the presence and distribution of the cell surface markers recognized by Dako T11, OKT4, OKT8 and OKM1. In comparison to normal controls, the patients with Crohn's disease had a relative peripheral lymphocytopenia with a relative monocytosis. The intestines afflicted by active Crohn's disease showed a significant increase in macrophages and T cells in the lamina propria mucosae; both T helper and T suppressor cell populations had equally increased without a significant change in the T helper/suppressor ratio. These findings suggest a change in the equilibrium state between intravascular and intestinal mucosal lymphocytes and monocytes in the active phase of the disease. The new equilibrium can be characterized as an intestinal lymphomonocytosis with a relative lymphocytopenia and monocytosis in the peripheral blood.

Adult↗

[Effect of intestinal resection on the behavior of mononuclear subpopulations in Crohn disease].

The literature data about the distribution of mononuclear cells in Crohn's disease are still contradictory. In 50 surgical C.D. patients, clinically classified corresponding to the Crohn's Disease Activity Index (CDAI), the T-lymphocytes and their subsets helper-T- and suppressor-T-lymphocytes (TH/TS) were therefore determined by use of monoclonal antisera, the B-lymphocytes by F(a b)-anti human Ig and the macrophages by uptake of latex microparticles. 37 C.D. patients underwent diseased bowel removal. Blood was drawn from the Crohn-draining mesenteric vein for analysis. Further investigations were performed at the 10th p. op. day as well as after an average period of 7 months (2-18). In comparison the mononuclear cell distribution was examined in 14 patients suffering from chronic osteitis and in 14 patients without any inflammatory disease as controls. C.D. patients showed preoperatively a significantly decreased TH/TS-ratio as well as a significantly increased proportion of macrophages. There was a lymphocytopenia in the peripheral differential blood count. Whereas the distribution of mononuclear subpopulations in the mesenteric blood was identical to the peripheral blood, significant lymphocytosis in the differential blood count of mesenteric blood was found. On the 10th p. op. day the TH/TS-ratio rose almost up to normal, which continued during the follow-up period. The macrophages remained constantly increased in all stages of investigation although during the follow-up none of the patients had signs of disease recurrence. Osteitis patients showed a similar distribution as C.D. patients, even if the changes compared to controls were not as distinct. The proportion of B-lymphocytes was the same in all groups examined. The individual TH/TS-ratios and proportions of macrophages of C.D. patients did not correlate to their clinical data. The changes within the T-cell-subpopulations seem to reflect less M. Crohn's disease itself than its inflammatory complications. Further studies have to be undertaken concerning the impact of the constant increase in macrophages, even after resection of the Crohn bearing bowel segment.

Adolescent↗

The predictive role of delayed cutaneous hypersensitivity testing in postoperative complications.

Ten parameters, including delayed cutaneous hypersensitivity testing (DCH), were evaluated with regard to their predictive value in instances of postoperative septic complications. In 302 patients undergoing surgical treatment, 45 complications, including wound infection, abscess, pneumonia and sepsis, were seen postoperatively in 42 patients. When these patients were compared with 260 patients without complications, hemoglobin, leukocyte count, serum albumin, total protein, blood sedimentation rate, age and sex were found not to contribute to the prediction of postoperative complications. In DCH testing, the complication rate increased from 7.5 per cent in normergic patients to 20.6 per cent in anergic patients. With increasing length and severity of operation, the complication rate increased from 6.5 to 26.4 per cent and from 6.5 to 31.8 per cent, respectively. Only in severe, long lasting operations could DCH testing differentiate the complication risk. Normergic patients had a 8.6 per cent complication rate; hypoergic patients, 36.6 per cent, and anergic patients, 37.5 per cent. The results of DCH testing did not correlate with the complication rate in any of the other operative groups. In conclusion, the predictive value of DCH testing is clearly greater in groups of patients highly affected by the operative trauma. The results of this study show that it is important to consider both host defense mechanisms and environmental factors in the assessment of operative risks.

Adult↗

[Melanoma of the anorectum].

The therapy of choice in cases with the prognostically poor (mean 5-year-survival rate maximal 12%) and rare anorectal melanoma is the surgical removal. Primary local excision should be done if technically feasible. On the basis of an exact pathohistological examination with special respect to tumor thickness a radical exstirpation or resection should be performed in cases with lesions more than 2 mm thick. In patients with tumors less than 2 mm a clinically and endoscopically follow-up in short intervals (3 months) after local excision can be recommended. At present, no effective radiotherapy nor systemic treatment exist.

Adult↗

Adjuvant chemo(immuno-)-therapy of primary breast cancer with adriamycin-cyclophosphamide (and levamisole)--six-year evaluation.

In a phase II-type study 52 patients with no signs of metastases but with a high risk of recurrence were treated with 6 courses of adriamycin-cyclophosphamide as adjuvant systemic therapy following modified radical mastectomy of primary breast cancer. Half of the patients were randomized to receive additional immunotherapy with levamisole for 2 yr. The scheduled dose and time regimen could be achieved in over 90% of patients. A comparison of the actuarial disease-free and overall survival with data reported in the literature indicates a similar positive effect of adjuvant systemic therapy as described in adjuvant studies using polychemotherapy regimens. Immunotherapy with levamisole has no effect on disease-free and overall survival but added to general toxicity. Particular attention was paid to psychological consequences of adjuvant systemic therapy; consistent attention by one specifically trained physician during the whole therapy and follow-up period was effective in coping with the emotional problems. The difficulties in treating recurrences after adjuvant therapy became apparent. A high rate of loco-regional recurrences and of cerebral metastases was noted.

Breast Neoplasms↗