Biomedical subjects
S Melchior
Publications and source records attributed to S Melchior.
A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma.
PURPOSE: WX-G250 is a chimeric monoclonal antibody that binds to carbonic anhydrase IX(G250/MN), which is present on greater than 95% of RCCs of the clear cell subtype. The suggested working mechanism of WX-G250 is by ADCC. Because the number of activated ADCC effector cells can be increased by a low dose interleukin-2 pulsing schedule, a multicenter study was initiated to investigate whether WX-G250 combined with LD-IL-2 could lead to an improved clinical outcome in patients with progressive RCC. MATERIALS AND METHODS: A total of 35 patients with progressive clear cell RCC received weekly infusions of WX-G250 for 11 weeks combined with a daily LD-IL-2 regimen. Patients were monitored longitudinally for ADCC capacity. Radiological assessment of metastatic lesions was performed at week 16 and regularly until disease progression. RESULTS: A durable clinical benefit was achieved in 8 of 35 patients (23%), including 3 with a partial response and 5 with stabilization at 24 weeks or greater. Mean survival was 22 months. In general treatment was well tolerated with little toxicity. The number of effector cells increased during treatment but lytic capacity per cell did not increase. ADCC and clinical outcome did not appear to correlate. CONCLUSIONS: WX-G250 combined with LD-IL-2 in patients with metastatic RCC is safe and well tolerated. With a substantial clinical benefit and a median survival of 22 months in patients with metastatic RCC who have progressive disease at study entry combination therapy showed increased overall survival compared to WX-G250 monotherapy. Survival was at least similar to that of currently used cytokine regimens but with a favorable toxicity profile.
A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients.
Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on >90% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials.
[Plexiform testicular schwannoma. Rare differential diagnosis of a testicular tumor].
In this report we describe the case of a testicular schwannoma in a human. Histologically, the tumor presented as a plexiform schwannoma. This rare benign peripheral nerve sheath tumor is an uncommon nodular variant of schwannoma, which mimics plexiform neurofibroma by its multinodular growth.
[Diabetes mellitus and bladder function. What should be considered?].
Increasing prevalence of diabetes mellitus and rising patient life expectancy are causing an accumulation of urologic late complications-despite or due to steadily improving medical health care. The prevalence of diabetic cystopathy (impaired bladder sensation, increased bladder capacity, sometimes accompanied by voiding difficulties and residual urine) is 25% in non-insulin-dependent diabetics and 48% in insulin-dependent diabetics. Autonomic and peripheral neuropathy lead to detrusor hyposensitivity, and chronic overstretching of the bladder causes myogenic detrusor hypocontractility. Since diabetic cystopathy often develops insidiously and asymptomatically, prevention of secondary complications such as recurrent urinary tract infections, vesicorenal reflux, nephrolithiasis, and pyelonephritis requires the urologist's full attention as well as early and repeated urodynamic diagnostics. Comorbidities can lead to a variety of urodynamic findings. Therapeutic options are generally conservative (timed voiding, micturition training, CIC, pharmacotherapy) and should be part of an integrated interdisciplinary health care approach since undiscovered complications involving non-urologic organ systems create a higher long-term socioeconomic burden than preventive support provided by other specialists.
[Does vasectomy increase risk of prostate carcinoma?].
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Variations of components of the plasminogen activation system with the cell cycle in benign prostate tissue and prostate cancer.
BACKGROUND: Components of the fibrinolytic system are involved in tumor cell invasion and metastasis. Previous investigations suggested a cell cycle-dependent expression of urokinase-type plasminogen activator (u-PA) in epithelial cells. In order to determine a correlation of cell cycle phases with the fibrinolytic system, we investigated the expression of u-PA, tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1) in normal and tumor-containing prostate extracts and analyzed a possible relationship with flow cytometry-determined proliferative activity of the samples. Cell cycle phases were correlated with fibrinolytic parameters in prostate tissue. METHODS: Samples were obtained from patients undergoing radical prostatectomy for prostate cancer and separated into two portions for DNA analysis and the detection of u-PA, t-PA, and PAI-1. Flow cytometric analysis was performed according to the Vindelov technique. The concentrations of u-PA, t-PA, and PAI-1 were determined from tissue extracts after homogenization by an enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Correlations of u-PA and t-PA expression with the frequency of G0/G1, S, G2M, S-phase fraction (SPF), and proliferation index (PI) for normal prostate and prostate cancer revealed no significant correlation. The only significant finding was observed in normal tissue revealing a positive correlation between PAI-1 expression and G0/G1 and a negative correlation with S-phase, SPF, and PI. No dependence of PAI-1 expression on different cell phases was found in prostate cancer. Furthermore, no significant correlation of u-PA, t-PA, and PAI-1 with cell cycles in organ-confined ( or = pT3a) tumors was found. No significant correlation in prostate cancer of components of the fibrinolytic system differentiated according to tumor grade or perineural tumor infiltration and cell cycle analysis was found. Only in highly differentiated G1 (Gleason 2-4) cancer, u-PA had a significant positive correlation with G2M-phase. CONCLUSION: Absence of a correlation between levels of components of the fibrinolytic system and cell cycle phases suggests that the reported association between increases of some of these components and aggressive biological behavior of prostate cancer is secondary to non-cell cycle-related mechanisms.
[Sling-plasty in therapy of female urinary incontinence].
Traditionally, women with type III stress incontinence (intrinsic sphincter deficiency) are treated with sling procedures, which have undergone multiple modifications during the last 90 years regarding surgical approach, sling course, and materials. The latest variation of the established sling concept is the tension-free vaginal tape (TVT) procedure. The choice of sling material influences the postoperative complication rate and reveals a conflict between unrestricted availability (alloplastic material) and optimal tissue compatibility (autologous material). Although valid information about the surgical outcome of sling procedures is rare, at least some evidence-based conclusions may be drawn from the meta-analysis of the published data: sling procedures and colposuspensions are more efficient and more durable than needle suspensions or anterior repairs in the treatment of female stress incontinence. The complication profile does not show a significant difference between slings and colposuspensions. The lack of long-term results for the TVT procedure precludes any definite assessment of this innovation. In any case, to meet the patient's interests, no surgical approach for correction of stress incontinence should be undertaken without complete diagnostic evaluation of the problem.
The value of a reverse transcriptase polymerase chain reaction assay in preoperative staging and followup of patients with prostate cancer.
PURPOSE: The reverse transcriptase polymerase chain reaction (RT-PCR) assay is an extremely sensitive technique of detecting cells expressing prostate specific antigen (PSA). Controversy exists regarding the ability of peripheral blood PSA RT-PCR testing to reflect pathological staging or treatment outcome. We examine the phenomenology of RT-PCR results in patients with prostate cancer, with particular emphasis on the RT-PCR test before and after radical prostatectomy, and correlations with pathological staging and treatment outcome. MATERIALS AND METHODS: Peripheral blood was obtained from a wide variety of patients with and without prostate cancer, including before and after radical prostatectomy. After ribonucleic acid isolation, complementary deoxyribonucleic acid was generated and amplified with a hot-start technique. RT-PCR results were compared with pathological stage, Gleason score, tumor volume and disease-free status. Correlations between preoperative and postoperative RT-PCR tests were also made. RESULTS: The RT-PCR test was positive in 1 of 56 controls (1.8%) without suspicion of prostate cancer. A positive test was obtained in 12 of 65 men (18.5%) with a suspicion of prostate cancer but a negative biopsy. Before radical prostatectomy a positive test was obtained in 13 of 75 men (17.3%) with pT2 disease versus 10 of 46 (21.7%) with pT3 disease. There was no significant difference in serum PSA, Gleason score or tumor volume between the men with positive or negative results. With repetitive testing an increasing percentage of men had at least 1 positive test preoperatively. With a median followup of 8 months 6 of the 7 patients in whom radical prostatectomy failed had had negative RT-PCR before treatment. Of patients with known metastatic disease or failed primary treatment a positive test was obtained in 32 to 75%. Radical prostatectomy and prostate needle biopsy appeared to have a negligible effect on RT-PCR tests immediately following these procedures. Following radical prostatectomy results were variable but many men who are RT-PCR positive preoperatively become RT-PCR negative postoperatively. CONCLUSIONS: The PSA RT-PCR test in our laboratory cannot be used preoperatively to predict pathological stage of prostate cancer or treatment failure. Most cases that are positive preoperatively become negative postoperatively. While increasing tumor burden increases the likelihood of positive tests, there appears to be significant sampling error associated with the use of this test in the peripheral blood.
[MR tomography in testicular processes. The significance of Gd-DTPA enhanced sequences in comparison with plain T2-weighted sequences].
The value of T1-weighted sequences after intravenous administration of Gd-DTPA and of T2-weighted sequences was compared in 43 patients suspected of having scrotal abnormalities. T2-weighted sequences gave better demonstration of the tunica albuginea and better contrast between tumor and parenchyma. The two techniques were equally sensitive for demonstrating testicular tumors but orchitis was better demonstrated on the contrast enhanced sequences. Motion artifacts were less marked in the T1-weighted sequences with contrast enhancement. In selected cases, contrast enhancement may be a valuable addition to native protocols. Our experience has indicated that MRI provides specific findings in cases of orchitis which are clinically atypical; this facilitates the decision to conservative treatment and prevents unnecessary exploration of the testes.
[Achalasia of the esophagus in children].
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Transient infantile hypermethioninaemia and liver dysfunction.
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Transient hyperammonaemia in a preterm neonate.
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Eosinophilic infiltration of the oesophagus in an infant.
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Myasthenia gravis, clinical findings before and after thymectomy.
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Exantherma in sepsis neonatorum.
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Gastro-oesophageal reflux in infancy and childhood: a retrospective study of 27 patients.
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