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Biomedical subjects

E Keiditsch

Publications and source records attributed to E Keiditsch.

At least 19 recordsLinked to original sources

Key importance of the Helicobacter pylori adherence factor blood group antigen binding adhesin during chronic gastric inflammation.

Helicobacter pylori has been assigned as a class I carcinogen because of its relation to gastric adenocarcinoma. Chronic H. pylori infection may lead to severe gastritis, glandular atrophy (AT), and intestinal metaplasia (IM). Strains secreting the vacuolating toxin VacA and producing the cytotoxin-associated antigen CagA (type 1 strains), as well as the blood group antigen binding adhesin (BabA) targeting Lewis(b) antigens, have been associated previously with distal gastric adenocarcinoma (M. Gerhard et al., Proc. Natl. Acad. Sci. USA, 96: 12778-12783, 1999) and may therefore also be related to lesions preceding gastric cancer. Antral and corpus biopsies were collected from 451 patients; 151 were H. pylori positive, as determined by PCR. Gastric biopsies were histologically evaluated for activity of gastritis (G0-G3, granulocyte infiltration), chronicity of gastritis (L1-L3, lymphocyte infiltration), and the presence of IM and/or AT according to the Sydney classification. Simultaneously, the presence of bacterial genes encoding virulence and adherence factors (racAs1/s2, cagA, and babA2) was determined by PCR. The presence of cagA+ and vacAs1 (alone or combined) both correlated with activity and chronicity of gastritis (P < 0.05); however, the overall prevalence of these genes was 60 or 72%, respectively, and was thus relatively frequent. The babA2 gene, encoding the adhesin BabA, was detected in 38% of infected patients and was correlated with the activity of gastritis in antrum and corpus (P < 0.005). cagA+/vacAs1+ strains (suggesting the presence of type 1 strains) that were also babA2 positive were detected more frequently in patients with severe histological alterations (such as G3, IM, or AT) compared with subjects without these changes (P < 0.01). cagA+/vacAs1+ strains that were babA2 negative, however, lacked a significant correlation with severe histological changes, activity, or chronicity of gastritis in antrum and corpus. Adherence of H. pylori via BabA appears to be of importance for efficient delivery of VacA and CagA and may play a special role in the pathogenesis of severe histological changes.

Adhesins, Bacterial↗

Primary low-grade B cell non-Hodgkin's lymphoma of MALT type simultaneously arising in the colon and in the lung: report of a case.

zone B cell lymphoma of mucosa-associated lymphoid tissue type according to the Revised European American Lymphoma classification). Other mucosa-associated lymphoid tissue-type lymphomas arise in the salivary glands, thyroid gland, and in the lung (bronchus-associated lymphoid tissue). Here, we report the first case of a monoclonal mucosa-associated lymphoid tissue lymphoma with simultaneous manifestation in the colonic and bronchial mucosa in a 62-year-old patient. With mitoxantrone, chlorambucil, and prednisone polychemotherapy, a complete year-long remission was achieved.

Antineoplastic Combined Chemotherapy Protocols↗

Cardiac surgery in patients with previous carcinoma of the breast and mediastinal irradiation: is the internal thoracic artery graft obsolete?

BACKGROUND: The increasing number of patients of more advanced age undergoing cardiac surgery means the number of those with previous curative (relapse free) mastectomy and irradiation of the chest is also increasing. A higher incidence of postoperative complications such as sternal infection in these patients is considered possible. Furthermore the question of whether mediastinal irradiation leads to a relevant internal thoracic artery (ITA) gaft damage remains unclear. In this context the benefit of arterial revascularization (CABG) using one or both ITAs is not sufficiently proven by data available from clinical studies. METHOD: 70 patients (49-85 years) with previous mastectomy or Hodgkin/non-Hodgkin's disease and mediastinal irradiation underwent CABG (n = 59) or an aortic valve replacement (AVR, n = 11). 20 patients received bilateral internal thoracic artery grafts, 34 a single internal thoracic artery graft, and in 16 patients an internal thoracic artery was not used. Perioperative data and data concerning postoperative complications such as mortality, myocardial infarction, and sternal infection or refixation was gathered and compared with all other patients receiving CABG (n = 5102). An histological investigation of ITA segments was done in 12 patients. RESULTS: There was no significant enhancement of the perioperative risk in comparison with other patients of a corresponding age group. Internal thoracic artery damage induced by irradiation was not present. There was no increased incidence of sternal instability requiring refixation observed. CONCLUSION: In the patient cohort investigated there is in general no need for restrictive use of the ITA in CABG.

Aged↗

Intrarenal distribution of organic osmolytes in human kidney.

The distribution pattern of renal organic osmolytes in surgically explanted human kidneys was investigated and compared with that of untreated Sprague-Dawley rats (Uosmo = 1186 mosmol/kg H2O). Sorbitol, myo-inositol, glycerophosphorylcholine and betaine were measured by liquid chromatography (HPLC) in homogenates of five different kidney zones from the cortex towards the papillary tip. All four organic osmolytes were detected as in human as in rat kidney. The expected increase from the inner medulla to the papillary tip for sorbitol and betaine, and from the outer medulla to the papilla for glycerophosphorylcholine, was observed in rats, but not in explanted human kidney. An inverse distribution pattern was observed with decreasing tissue contents from the inner and outer medulla to the papillary tip for all organic osmolytes and urea. This intrarenal osmolyte profile is in accordance with that observed during water and lithium diuresis in rats. Therefore it can be assumed that a loss of renal medullary osmolytes during the intra-operative treatment of patients led to the observed osmolyte pattern. We conclude that organic osmolytes are involved in renal medullary osmoadaptation of humans.

Animals↗

[Interstitial laser coagulation of benign prostatic hyperplasia].

We report on the new method of interstitial laser coagulation for the treatment of benign prostatic hyperplasia (BPH). The procedure is based on the interstitial application of Nd:YAG laser irradiation, delivered through a new light guide system. Such light applicators coagulate constant tissue volumes in a homogeneous manner, as proven by in vitro studies in different tissues, including surgically removed prostate adenoma. The extent of the coagulation is determined by laser power and irradiation time. At 5 W, for example, and during a 10-min period, this zone reached a diameter of up to 20 mm. Temperatures generated in the process were over 100 degrees C, as measured by time/space resolution. These results were confirmed by in vivo studies in canine prostates. In the course of 7 weeks, the coagulated areas formed scars with degeneration and fibrosis, accompanied by marked shrinking. Neighbouring organs were not affected. The method was successfully transferred to clinical practice. The application of the light guides to the lateral lobes was performed percutaneously from the perineum under transrectal ultrasound guidance. The median lobe was punctured transurethrally under direct vision. Twenty-seven patients with an average age of 67.7 years were treated between July 1991 and March 1992. At the time of evaluation 15 patients had a follow-up of more than 2 months. They experienced a mean increase of peak flow rate from 6.6 to 15.2 ml/s and a mean decrease of residual volume from 206 to 38 ml. This was accompanied by a marked lessening of symptoms. The average prostate weight decreased from 63 to 44 g. Sexually active patients did not experience retrograde ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Morphological, immunocytochemical and growth characteristics of three human glioblastomas established in vitro.

The human glioblastoma-derived cell lines 86HG-39, 87HG-28 and 87HG-31, used for the production of monoclonal antibodies (mAbs) against glioma-associated antigens (GAA), were characterized in terms of morphology, growth behaviour, chromosomes and antigen expression. In the primary tumours, differential expression of glial fibrillary acidic protein, S100 protein, Leu-7 and GAA as defined by mAbs MUC 2-39, MUC 2-63 and MUC 8-22 was demonstrated. Receptors for epidermal growth factor (EGFr) and nerve growth factor (NGFr) were found in many cells in short-term cultures, but the transferrin receptor (Tr) was found in only a few cells of 87HG-28. In permanent cell lines, differentiation antigens and EGFr decreased and Tr increased markedly. NGFr and GAA remained stable. Transplantation tumours of 86HG-39 were partly positive for Tr and GAA. Chromosomal analysis revealed that the 86HG-39 and 87HG-28 cell lines had a hypodiploid or diploid stem line with lines in the hypotetraploid to tetraploid region for 50 in vitro passages. The 87HG-31 cell line had chromosomal patterns in the hypotriploid to triploid region. A gain of chromosomes was seen in the groups C7, C8, C10, D14, F19, F20, G21, G22. The variability of antigens in these tumours and especially during long-term cultivation probably reveals an ability to influence the growth of malignant glioma cells via the respective effector molecules.

Antibodies, Monoclonal↗

Legionella infection of the colon presenting as acute attack of ulcerative colitis.

A 42-yr-old woman with long-standing ulcerative colitis of the descending colon, sigmoid, and rectum presented with bloody diarrhea, tenesmus, and high fever. Endoscopic findings were compatible with an acute attack of ulcerative colitis, which proved to be resistant to systemic corticosteroid treatment. In the presence of an acute abdomen with ascites and double-contoured colonic wall, hemicolectomy was performed. Postoperatively, high temperature, hyponatremia, and elevated liver enzyme levels persisted. Pleural effusions developed. Antibodies to Legionella pneumophila serogroup 3 were detected in the serum. Erythromycin therapy induced rapid improvement. In a massive submucosal edema of the affected colon, L. pneumophila of the same serogroup was demonstrated by direct immunofluorescence staining.

Acute Disease↗

Simultaneous demonstration of glia- and glioma-associated antigens in human astrocytomas.

Glial fibrillary acidic protein (GFAP) and glioma-associated antigens (GAA) defined by monoclonal antibodies (MAbs) were demonstrated simultaneously in human astrocytoma tissue. GFAP was stained by PAP-method, GAA were visualized by avidin-biotin-technique using alkaline phosphatase. In primary and secondary tumors as well as in tissue culture heterogeneity of GFAP- and GAA-expression is obvious. GFAP is mostly restricted to cell processes and less marked in the perinuclear space. Depending on the individual antibody, MAbs-positive material is located either in the tumor cell plasma (MUC 8-22) or on cell surface membranes (MUC 2-63). There is remarkable expression of GAA in cell clusters which fail to express GFAP. At higher magnification, 3 types of cellular reactivity are detectable: (a) cells which react only with anti-GFAP, (b) cells which react only with anti-GAA and (c) cells which express both, GFAP and GAA, especially those of protoplasmic astrocyte type. These cells also occur in subcutaneous tumor grafts, and may thus represent not only a reactive event, but be part of tumor cell populations.

Animals↗

Comparative investigations of the effects of the neodymium:YAG laser at 1.06 microns and 1.32 microns on tissue.

The beneficial deep homogeneous coagulation of neodymium (Nd):YAG laser radiation at 1.06 microns owing to low absorption and high scattering in tissue has been documented widely. For another Nd:YAG laser wavelength at 1.32 microns the absorption coefficient of water and saline is approximately ten times higher than at 1.06 microns. This results in more efficient energy conversion into heat in tissue at 1.32 microns. The extinction coefficient in blood at 1.32 microns is only one-third of that at 1.06 microns. We would expect this to result in less heat dissipation by blood and deeper penetration in tissue at 1.32 microns. Nevertheless, at this wavelength scattering also contributes to an effective, uniform distribution of the laser light in the tissue. Animal experiments have been done to examine the effect of wavelength, irradiation time, and beam geometry on tissue damage and to assess its possible clinical uses. The results imply that the 1.32 microns wavelength will produce further indications for the use of the Nd:YAG laser in surgery.

Animals↗

Regulated high frequency diathermy for bipolar electrocoagulation--a new method for the treatment of carcinoma of the bladder.

In the endoscopic treatment of bladder cancer, especially for stages beyond T2, transurethral resection does not seem to be sufficient. The risk of bladder wall perforation, the possibility of incomplete resection, seeding of tumor cells and high recurrence rates support the former statement [6]. Results of a multicentre prospective randomised study have exemplified that irradiation with the Neodymium-YAG Laser has been a reasonable alternative in the therapeutic approach to bladder cancer [2]. Diathermy coagulation must produce a sufficiently deep, homogeneous and well demarcated tissue necrosis. The coagulation depth has to be adjustable and heat production during coagulation should not lead to bladder wall perforation and consequent damage to the bowel. These criteria were investigated using regulated bipolar high frequency diathermy. The innovation in this method is, that thermal side effects on the tissue, e.g. vaporisation and carbonisation are prevented by a protective relay with constant current flow. Animal experimental studies have shown that this method meets all postulated requirements and therefore clinical trials can proceed.

Animals↗

Monoclonal antibodies against human astrocytomas and their reactivity pattern.

The establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from BALB/c mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 X 10(6) chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner.

Animals↗

Growth inhibition of experimental glioma grafts by monoclonal antibody treatment.

The effects of 14AC1 monoclonal antibody (McAb) on 79FR-G-41 rat glioma cells in vitro, on the formation of metastases in lung by antibody coated glioma cells, and on the growth of glioma grafts in BALB/c-nu/nu mice were investigated. The 14AC1 antibodies - isotyped as IgG2a - were obtained from a hybridoma clone established after fusion of X63-Ag8.653 myeloma cells and spleen cells of BALB/c mice hyperimmunized with 79FR-G-41 glioma cells. Antibody treatment of glioma cells in vitro caused evident cell surface alterations and pronounced growth depression of most cells. However, a few tumor cells remained unchanged in morphology and continued to proliferate. Moreover, 14AC1 antibodies drastically reduced lung metastasis by pretreated and i.v. delivered glioma cells. Additionally, 14AC1 antibodies suppressed the growth of transplanted rat gliomas in nude mice as evidenced by a longer latency period and a smaller volume of glioma grafts in treated than in control tumor bearers. Nevertheless, glioma grafts showed accelerated growth after termination of antibody treatment. Further experimental investigation is required in order to identify the precise mechanisms of the effects of McAbs on tumor cells in vitro and in vivo.

Animals↗

Morphological fundamentals in the treatment of tumors with the neodymium-YAG laser.

On the basis of experimental animal research regarding type, distribution, and depth of necrosis in urinary bladder under neodymium-YAG (Nd:YAG) laser irradiation, identical results have been confirmed in human tissue. Bladder tumors indicated for cystectomy have first been treated with the Nd:YAG laser and histologically examined. Destruction of tumor tissue is demonstrated. Particular attention was paid to the temporary closing of the lymphatic drainage system due to the deep coagulation capability of the Nd:YAG laser irradiation. Nd:YAG laser irradiation is especially suitable for tumor coagulation, since simultaneous interception of lymphatic drainage will inhibit the spreading of tumor cells.

Animals↗

Use of the neodymium-YAG laser in the treatment of ureteral tumors and urethral condylomata acuminata. Clinical experience.

The further development of endoscopic instruments has made neodymium-YAG laser irradiation of ureteral tumors possible. To date a total of 13 ureteral tumors in 10 patients have been photocoagulated. Over a mean follow-up period of 23 months, only 1 heterotopic recurrence was found after 14 months. In view of the results achieved so far, nephroureterectomy as the first therapeutic step appears to have been made obsolete. Since 1979 we have treated 48 patients with the neodymium-YAG laser. Seven patients with excessive condyloma involvement were followed postoperatively. Our experience indicates that, in view of its low complication and recurrence rates, endoscopic laser coagulation of urethral condylomata is the method of choice. A short-term ureteroscopic follow-up examination, however, is required to detect any condylomata that might have been overlooked.

Adult↗

Experimental investigation of neodymium-YAG laser induced shock waves for lithotripsy.

Experiments on the endoscopic destruction of kidney stones by neodymium-YAG laser, either thermically or mechanically, are being carried out with various results. The thermal destruction is clinically not feasible, and the risk of damaging neighboring tissue is inevitable. The direct generation of shock waves with pulsed Q-switch systems seems to represent the only feasible endoscopic method subject to further development of suitable devices for clinical tests.

Humans↗

Localization of experimental glioma grafts by means of iodinated monoclonal antibodies and radionuclide imaging.

Purified McAbs (14AC1) of IgG2a isotype raised against an experimental rat glioma (79FR-G-41) were labeled with Na131I and used for in vivo imaging of glioma grafts by external body scintigraphy. Normal mouse 131I-IgG was applied as control for non-specific uptake of proteins in the tumor. Nude mice bearing glioma grafts were injected i.v. with 15 micrograms of the 131I-McAb or 131I-IgG with an activity of approximately 150 microCi. Scans obtained 30 min, 24, 48, 72, and 96 h after injecting the intact 131I-14AC1 antibody demonstrated enrichment of radioactivity in the tumors. The tumors were clearly visible 48 h after injection of 131I-labeled antibody. The time course experiments showed that the uptake of 131I-14AC1 antibody in the glioma grafts was the result of specific antigen binding. Intact antibody provided adequate tumor visualization in the scintigrams without background subtraction. Therefore, this technique appears promising for in vivo tumor detection and may offer the possibility of improvement in the evaluation of diagnostic and therapeutic approaches to human gliomas.

Animals↗