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Biomedical subjects

M Kriegmair

Publications and source records attributed to M Kriegmair.

50 records · Page 3Linked to original sources

Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines.

Metastatic renal cell carcinoma (RCC), like melanoma, belongs to the small group of human tumors in which partial or complete remission has been observed in some patients after treatment with various forms of immunotherapy. In contrast to melanoma, CTL showing MHC-restricted lysis of RCC have not been easily found among tumor-infiltrating lymphocytes (TIL). This has led to the suggestion by some that responses to immunotherapy are mediated predominantly by non-MHC-restricted effector cells. We have characterized an MHC-restricted, CD8+ CTL line obtained from an uncloned TIL population of a primary RCC using a low concentration of rIL-2; in fact, these CTL represented a majority of the short-term cultured TIL population. The CTL lysed autologous tumor cells but not normal kidney cells or target cells sensitive to non-MHC-restricted effector cells. In contrast, lymphokine-activated killer (LAK) cells grown in a high concentration of rIL-2 from the patient's PBL lysed autologous tumor and normal kidney cells in addition to several allogeneic tumors. The TIL could be expanded optimally using an autologous tumor line retrovirally transduced with the human cDNA encoding IL-2. TIL were 20-fold more potent than LAK cells in eliminating the IL-2 expressing tumor cells in vitro. The cultured TIL utilized a restricted number of V alpha gene families, suggesting that they may recognize only a limited number of MHC-peptide complexes presented by autologous tumor cells. HLA-A2 was identified as an MHC restriction molecule for presentation of one tumor-derived peptide to these CTL. Only some allogeneic HLA-A2 RCC tumors were lysed. Sequencing of the second and third exons of the HLA-A2 alleles of these cells revealed that both heterogeneity in MHC and peptide availability influenced CTL recognition. These studies demonstrate that some RCC express common antigenic determinants that can be recognized by MHC-restricted CTL and open the possibility of defining the nature of RCC-derived peptides, which, combined with HLA-A2, can generate specific immune responses.

Antibodies, Monoclonal↗

[Treatment of ureteral colic with glycerol trinitrate].

METHOD: In an open randomized clinical trial, the efficacy of 2.4 mg glycerol trinitrate (GTN) administered in a variety of forms (2 x 1.2 mg capsules; 6 x 0.4 mg puffs of an atomizer; 2.4 ml of an 0.1% infusion solution) in comparison with 20 mg of butylscopolamine bromide i.v. (BSB) in 80 patients suffering from acute ureteral colic. RESULTS: Some 30 minutes following medication, the effect was adjudged by the physician to be good (no pain) moderate (some pain still present) or non-existent (alternative treatment within 30 minutes). CONCLUSION: GTN was effective in 40% of the cases, BSB in 26.3%. A moderate effect was seen in 46.7% and 62.3%, respectively, while no response was elicited in 13.3 and 10.5%, respectively. In addition, recurrence within 24 hours, blood pressure, pulse rate and laboratory tests were recorded. Side effects occurred in 13 patients (12 in the GTN and 1 in the BSB group), but, with one exception (GTN i.v.), were all mild in nature.

Administration, Inhalation↗

Immunocytochemical double staining of cytokeratin and prostate specific antigen in individual prostatic tumour cells.

Early dissemination of malignant cells is the main cause for metastatic relapse in patients with solid tumours. By use of monoclonal antibodies (mAbs) specific for cytokeratins, disseminated individual epithelial tumour cells can now be identified in mesenchymal organs such as bone marrow. Further to characterize such cells in patients with prostate cancer, an immunocytochemical procedure was developed for simultaneous labelling of cytokeratin component no. 18 (CK18) and prostate specific antigen (PSA). In a first step, cells were incubated with mAb ER-PR8 against PSA and secondary gold-conjugated goat anti-mouse antibodies. In a second step, biotinylated mAb CK2 to CK18 was applied as primary antibody and subsequently incubated with complexes of streptavidin-conjugated alkaline phosphatase, which were developed with the Newfuchsin substrate. The binding of gold-labelled antibodies was visualized by silver enhancement. The sensitivity and specificity of the technique was demonstrated on cryostat sections of hyperplastic prostatic tissue, and cytological preparations of LNCaP prostatic tumour cells. Double staining was restricted to cells derived from the secretory epithelium of the prostate. Cross-reactivity between both detection systems was excluded by several controls, including the use of unrelated antibodies of the same isotype and the staining of CK18+/PSA- HT29 colon carcinoma cells. CK18+ cells co-expressing PSA were found in bone marrow aspirates from 5 out of 13 patients with carcinomas of the prostate, a finding that is consistent with the relative fraction of double-positive LNCaP cells. The specificity of CK18 for epithelial tumour cells in bone marrow was supported by negative staining of 12 control aspirates from patients with benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Concepts in surgical therapy of kidney cancer].

Three new aspects of the operative treatment of renal cell carcinoma can be made out: 1. for the removal of tumor thrombus extending to the right atrium, the surgical technique of choice involves whole-body hypothermia and extra-corporeal circulation. Only in this way can these tumors be removed completely under good vision. 2. Provided the patient's contralateral kidney is healthy, even small peripheral renal tumors should be submitted to radical nephrectomy. The rate of concomitant small tumors is reported to be as high as 20, while the recurrent rate associated with local incision is just on 7%, and the risk of carcinomas developing in the contralateral kidney is only 1.8-3.8%. 3. Radical nephrectomy for tumor should continue to include the ipsilateral adrenal gland. Although in our own patients the incidence of simultaneous adrenal metastasis was only 1.4%, if the adrenal gland is left in situ, part of the renal capsule also has to be left behind, and the upper pole of the kidney dissected free, with the associated risk of disseminating tumor cells.

Adrenal Gland Neoplasms↗

[Laser lithotripsy with automatic shut-off on tissue contact].

A group of 88 patients with 89 ureteral calculi were treated with the pulsed dye-laser. Visual control was carried out through 8.5-F or 9.5-F ureteroscopes. The laser has automatic shut-off via spectrum analysis of back-scatter laser light. Effective laser pulses can therefore only be induced in the case of contact with the stone. Of the 89 stones 58 (65.2%) were completely fragmented by laser lithotripsy, 15 (16.8%) by laser lithotripsy in combination with ESWL and 9 (10.1%) by other ureteroscopic techniques. Ureterolithotomy was necessary only in 1 case (1%). There were 5 calculi (5.6%) that were too hard for fragmentation. The pulsed dye-laser is a safe and effective treatment modality for ureteral calculi that are not accessible for ESWL or in which ESWL has been unsuccessful. Further experimental and clinical trials will have to show whether miniature probes for electrohydraulic lithotripsy, dye-laser with automatic shut-off, or alexandrite laser will be the method of choice for lithotripsy of ureteral calculi.

Endoscopes↗

[Diverticular calculi of the kidney calices--extracorporeal shockwave lithotripsy, percutaneous extraction or open surgery].

The incidence of caliceal diverticula, mostly found on routine excretory urography, is very low. The indications for treatment include chronic or recurrent pyelonephritis, pain, gross hematuria and renal damage. There is controversy as to which treatment is best: extracorporeal shock-wave lithotripsy (ESWL), percutaneous techniques, or traditional open surgery. Since 1984, 27 patients with 28 caliceal diverticula calculi have been treated. Ten patients underwent ESWL, 13 patients percutaneous treatment, and 4 patients open surgery. The success rates as far as a stone-free status is concerned were: 1 patient (ESWL), 10 (percutaneous), and 4 (open surgery). There were no complications due to ESWL or open surgical treatment. Direct traumata such as severe bleeding in two and hydrothorax in one patient occurred during the training phase of the percutaneous techniques. Due to the low complication rate, non-invasive ESWL treatment should be tried first. The indications for percutaneous removal of calculi in caliceal diverticula depend on two aspects: it should be possible to puncture the caliceal diverticula via by a short parenchymal route coaxial to the axis of the calix and, if the intercostal approach is used, a pleural lesion must be excluded. If these requirements cannot be fulfilled, open surgical treatment should be performed, especially if the diverticula are located in the upper and anterior part of the kidney.

Adolescent↗

[Intracorporeal shockwave lithotripsy using the neodymium YAG laser].

The problem of suitable energy transfer and conversion for intraureteral lithotripsy has not yet been solved satisfactorily. Laser-induced shockwave lithotripsy (LISL) appears to be a very promising solution to this problem. We report on initial clinical experience using a Q-switched Nd:YAG laser generating a shockwave on the metallic surface of an optomechanic coupler. This leads to the fine fragmentation of a urinary calculus situated close to or in contact with the coupler. Only minimal side effects occur in biological tissue. Further development of the coupler resulted in considerable increase of its fragmentation capability with no increase in side-effects. As a result, application under fluoroscopic control alone became possible, which appears adequate in approximately half of the cases. In the other half visual inspection via ureteroscopy is required. Laser-induced lithotripsy is the only technique that uses a flexible transmission system, results in the fine fragmentation of calculi, and is free of serious side effects on tissue, i.e. does not lead to perforation of the wall of the ureter.

Humans↗

[Interferon therapy in urology].

Interferons are the first type of a new generation of substances, called lymphokines, which allow regulatory manipulation of the immune system and thus offer new treatment options. Since recombinant production became possible, interferons have been available in sufficient quantities for clinical trials. Up to now, in urology interferons have been investigated mostly in the treatment of metastatic renal cell carcinoma. The response rate (complete and partial) found in 19 clinical reviews was 16% (139 of 881 patients). Comparable results had previously only been achieved with vinblastine. The in vitro synergistic effect of the two drugs seems to be confirmed by the first clinical trials. Further preliminary results with have been reported interferons in the treatment of superficial bladder cancer, advanced prostatic cancer and condyloma acuminata.

Carcinoma, Renal Cell↗

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↗

BTA-TRAK--a useful diagnostic tool in urinary bladder cancer?

During recent years the BTA-TRAK-assay (Bard Diagnostics, Redmont, USA) has been described in several investigations to be of clinical utility for patients suffering from bladder cancer. In a prospective study we investigated over four months the voided urine samples of all consecutive patients undergoing cystoscopy independent of their clinical background (n = 244) with the BTA-TRAK-assay. With a specificity of 95% for benign urological diseases (cut off: 1300 U/mL) we found a sensitivity of 13% for active bladder tumours. Using healthy individuals as a reference group (cut off: 40 U/mL) we found a sensitivity of 56% (specificity 67%). Using the cut off value recommended by the manufacturer (14 U/mL) a specificity of 54% and a sensitivity of 62% was found. For patients without relapse (NED) versus patients with active bladder tumours we got a specificity of 55% and a sensitivity of 62%. Due to an insufficient specificity and sensitivity the BTA-TRAK-test is not able to replace cystoscopy nor to improve existing diagnostic strategies in bladder cancer.

Cystoscopy↗