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Biomedical subjects

H Heynemann

Publications and source records attributed to H Heynemann.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

Adult↗
PubMed2006

[Ultrasound differential diagnosis in renal parenchymal disease].

Ultrasound examination is an integral part of nephrologic differential diagnosis in renal parenchymal disease. A systematic recognition of kidney position, size, shape, contour, structural design and renal perfusion lead together with clinical findings in correct direction of differential diagnosis. Unspecific findings exist in many acute renal diseases (large kidney with prominent pyramids and echogenic cortex). In chronic renal diseases the sonomorphology of chronic glomerulonephritis, pyelonephritis or analgesic nephropathy are more specific. Diagnosis of renal arterial stenosis is almost possible with duplex ultrasonography. Disturbances of kidney perfusion (infection, infarction) are diagnosed with echocontrast-ultrasonography.

Acute Disease↗
PubMed2006

[Renal ultrasound. Urologic and nephrologic viewpoint].

Renal ultrasound examination is an integral part of urologic and nephrologic clinical examination. It brings very useful information about kidney morphology (B-mode) and haemoperfusion (renal color coded duplex ultrasonography). Standard examination technique is required for recognition of normal findings, urinary transport disturbances of diverse causes (stones, intrinsic or extrinsic compression), kidney tumours and kidney injury. Typical ultrasound findings of these abnormalities were demonstrated. Renal ultrasound with new techniques (sono-CT, harmonic tissue imaging, power mode etc.) is for urology and nephrology an indispensable diagnostic method. In combination with patient history, clinical and laboratory examination takes important part in accomplishing the diagnosis.

Angiomyolipoma↗
PubMed2006

[Diagnostics and treatment of prostate cancer after kidney transplantation].

The number of patients with prostate cancer and end-stage renal disease or prostate cancer following kidney transplantation has continuously increased in industrialized countries. According to the data generated by Penn et al. a higher incidence of prostate cancer following kidney transplantation can be seen but is probably due to a more intense screening of the recipients. It is rather a common opinion that no elevated risk of prostate cancer following kidney transplantation exists. In patients with strictly localized prostate cancer curative treatment should be the aim also after kidney transplantation. Kidney transplantation does not interfere with surgical access to the prostate gland (retropubic or perineal). Nonlocal tumors of the prostate should also be treated following the general recommendations regarding prostate cancer. Looking at the current literature, a reduction or change of immunosuppression seems reasonable. It is necessary to establish a nationwide (or even European) cancer register, especially for patients before and after transplantation.

Adolescent↗
PubMed2005

Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We conducted a prospectively randomised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma. In total, 203 renal carcinoma patients' status post radical tumour nephrectomy were stratified into three risk groups: patients with tumour extending into renal vein/vena cava or invading beyond Gerota's fascia (pT3b/c pN0 or pT4pN0), patients with locoregional lymph node infiltration (pN+), and patients after complete resection of tumour relapse or solitary metastasis (R0). Patients were randomised to undergo either (A) 8 weeks of outpatient subcutaneous interleukin-2 (sc-rIL-2), subcutaneous interferon-alpha2a (sc-rIFN-alpha2a), and intravenous 5-fluorouracil (iv-5-FU) according to the standard Atzpodien regimen (Atzpodien et al, 2004) or (B) observation. Two-, 5-, and 8-year survival rates were 81, 58, and 58% in the treatment arm, and 91, 76, and 66% in the observation arm (log rank P=0.0278), with a median follow-up of 4.3 years. Two, 5-, and 8-year relapse-free survival rates were calculated at 54, 42, and 39% in the treatment arm, and at 62, 49, and 49% in the observation arm (log rank P=0.2398). Stage-adapted subanalyses revealed no survival advantages of treatment over observation, as well. Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-alpha2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy.

Adult↗
PubMed2004

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.

Adult↗
PubMed2004

[New techniques in uro-sonography].

New sonographic techniques in urology, together with their principles of operation, will be presented. Together with the utilization of broadband ultrasound scanners and digital beam formers, leading to better spatial resolution and increased line density in ultrasound imaging, panorama sonography enables the outline of wide lateral regions independent of the width of the scanner. Spatial compound sonography achieves a comparatively better visualization of details in the b-mode image than has yet been available. The continuously improved 3-D, now leading to 4-D, techniques, which means real time capabilities, make the visualization of unrestricted imaging planes, which are not seen in conventional 2-D techniques, possible. The second harmonic imaging technique, including the special applications tissue harmonic imaging (THI) and contrast harmonic imaging (CHI), uses special ultrasound signal processing procedures for capturing and evaluating tissue hemoperfusion-here in combination with ultrasound contrast agents (UCA). Furthermore, microvascular imaging (MVI) enables the visualization of perfusion in tissues reaching the microcirculation regions. This leads to new possibilities for the assessment of pathological perfusion patterns, e.g. in andrology (perfusion of testicles) and uro-oncology (hyperperfusion of malignant regions).

Animals↗
PubMed2003

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Administration, Inhalation↗
PubMed2002

[Transrectal ultrasound of the prostate. Current status and prospects].

In recent years the role of ultrasound in the diagnosis of prostate carcinoma has increased in importance. In view of the increasing incidence of prostate cancer, which is the most frequent malignant neoplasm in men, TRUS (transrectal ultrasound) is an important imaging method in the diagnosis of various prostate diseases. This paper provides a basic overview of physical and technical bases of TRUS investigation of the prostate. It concerns technical developments and modern techniques designed to improve its value in diagnosis. Impressive innovations in ultrasound equipment, particularly in the area of colour-coded Doppler sonography in association with microbubble-enhanced colour Doppler ultrasound, have given rise to justifiable hope of improvements in the early diagnosis of prostate cancer.

Diagnosis, Differential↗
PubMed2002

[Determination of acoustic parameters from ultrasound raw and HF data--a comparison].

Different methods for determination of acoustical tissue parameters based on rf data acquisition as well as the analysis of B-mode image data are well established. Because of limitations of the dynamic range and the restricted control of the tgc and focus settings the analysis of image data is not achievable in clinical practice. On the other side rf data are not available in most of the clinical scanners. So the analysis of raw data can be used as an compromise. Raw- and rf-data of complete B-mode scans obtained form a set of test phantoms by a clinical ultrasound device (HDI 5000, Philips) in connection with the applied gain settings were analyzed. For different system settings the estimated parameters showed a good agreement with the acoustical properties of the phantoms.

Acoustics↗
PubMed2001

Differential diagnostic use of interleukin patterns in patients being monitored after transplantation.

BACKGROUND AND AIM: We investigated how far the determination of selected interleukins in bodily fluids of patients who had received kidney allografts can help to confirm the diagnosis of complications after transplantations. MATERIALS AND METHODS: Levels of soluble interleukin-2-receptor, interleukin 6 and interleukin 8 were determined in serum and urine of 79 patients. According to the type of diagnosis obtained with histological, serological and microbiological methods and to the clinical course, the groups "stable graft function without complication", "allograft rejection", "cytomegalovirus infection", "systemic extrarenal bacterial infection", "urinary tract infection" and "pyelonephritis" were created. RESULTS AND CONCLUSIONS: The activation of the immune system in different ways depending on the trigger substance (alloantigen, virus, bacterium) and the possibility to differentiate systemic and local processes cause typical patterns of interleukin levels in serum and urine in conjunction with the above mentioned complications after kidney transplantation. Cytomegalovirus infections and systemic extrarenal bacterial infections differ from rejection by the unchanged urine interleukins IL 6 and IL 8, the local urinary tract infections differ from rejection by the unchanged serum interleukins. Acute pyelonephritis differs from rejection by the significantly higher serum IL 6 level. During our daily clinical work, the practical interleukin determinations were proven to be an important tool for early and differential diagnosis of complications after kidney transplantation.

Diagnosis, Differential↗
PubMed2001

Detection and enrichment of disseminated renal carcinoma cells from peripheral blood by immunomagnetic cell separation.

We have established an immunomagnetic separation procedure for the detection of circulating tumor cells in the peripheral blood based on the magnetic cell sorting (MACS) technique. In previous in vitro experiments, renal-cell carcinoma (RCC) cells were mixed with peripheral blood. In dilutions of 1:200 to 1:107 tumor cells per mononuclear blood cells, an average recovery rate of 84% of tumor cells was determined. In our study, 104 peripheral blood samples from 59 renal carcinoma patients were analyzed. MACS resulted in significant depletion of leukocytes, permitting a search for tumor cells on just 1 slide. Analyzing 8 ml of peripheral blood per patient, 19/59 RCC patients carried disseminated tumor cells (32%) in the range of 1 to 38 cells (median 8). Interestingly, for the cytokeratin-positive (CK+) patient group, we found a correlation between tumor cell number and grading (G2 vs. G3) and an increased number of CK+ patients with advanced tumor stage. MACS appears to be an efficient technique to detect disseminated tumor cells in peripheral blood.

Adult↗
PubMed2000

Lipid peroxidation and the expressional regulation of the heat-shock response during ischemia-reperfusion of rat kidney.

Because of the continuing shortage of donor organs, 'marginal kidneys' are increasingly being used. The purpose of our experiments was to characterize the extent of lipid peroxidation after ischemia-reperfusion (IR) injury in rat kidney, to analyze the expressional regulation of the heat-shock response and now to discuss the clinical application of these results. After ischemia, xanthine oxidase (XO) is thought to be the main oxygen radical-generating system and malondialdehyde (MDA) is considered to be a marker of LPO. In young rats (10 weeks) a unilateral warm ischemia of 40 and 60 min duration with subsequent reperfusion up to 1 h was conducted. Beside the 'footprints' of oxidative stress, the cytosolic antioxidative capacity, expressed as superoxide anion (SOA) scavenging capacity, was investigated. There was only a moderate and transient increase of renal MDA 5 and 10 min after the onset of reoxygenation (133.57/70.67 and 97.84/91.57 vs. 49.47 nmol/g wet weight (ww) in preischemic controls). ATP breakdown (to 83/65 from 2,947 nmol/g ww) with consecutive accumulation of hypoxanthine (up to 1,105 nmol/g ww) at the end of the ischemic period and the subsequent rapid decline of hypoxanthine by XO during reperfusion were used for an assessment of the SOA-generating capacity of these kidneys. Only 1/25-1/50 of the kidney cytosol was able to scavenge the whole amount of SOA generated by the total XO activity of rat kidney. Thus, it could be analytically and stoichiometrically shown that after IR there is only a moderate oxidative stress in kidneys of young rats; this is due to their high SOA-scavenging capacity compared to their SOA-generating ability. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in renal cortex after different periods of unilateral warm renal ischemia (10-60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats, since IR is known to cause induction of both genes. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA - generally being expressed on a far lower level than HSP70-1 mRNA - was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped down to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period thus showing a good relation to the heat-shock (protein) gene expression. We conclude that the HSP70-2 is the more sensitive gene with a lower threshold activation by mild injury, while the HSP70-1 gene mediates the big response of HSP induction after severe injury. Thus, the measurement of the cytosolic antioxidative capacity and the differential expression of HSP70-1 and -2 mRNA could be promising clinical tools to assess the donor viability.

Adenosine Triphosphate↗
PubMed1999

Preliminary results of simultaneous radiochemotherapy with paclitaxel for urinary bladder cancer.

BACKGROUND: Paclitaxel (Taxol) has been shown to be effective in metastatic bladder cancer as single agent and in combination with other cytotoxic drugs. Its efficacy seems to be comparable to cisplatin. We have used paclitaxel as alternative to cisplatin in selected patients with simultaneous radiochemotherapy. The objective of this article is to summarize the preliminary results with regard to feasibility and toxicity. PATIENTS AND METHODS: From 10/97 through 10/98 7 patients with locally advanced or recurrent urothelial bladder cancer were treated with radiotherapy and simultaneous paclitaxel + cisplatin. All patients had macroscopic irresectable residual tumor after transurethral surgery or cystectomy. Paclitaxel was given twice weekly in a daily dosage of 25 through 35 mg/m2 as 1-hour-infusion. Cisplatin was given in a dosage of 25 mg/m2 daily on days 1 to 5. RESULTS: All patients completed the scheduled therapy regimen. The acute toxicity consisted mainly of enteritis (Grade I to II CTC). As severe toxicity, 1 severe skin reaction in the groins (Grade III) after 20 Gy and 1 Grade-III enteritis were noted. Both patients with severe complications recovered within 4 weeks after treatment. Hematological toxicity was mild to moderate in all cases. CONCLUSIONS: This report suggests that paclitaxel is a promising agent for simultaneous radiochemotherapy protocols. The clinical value remains to be better defined especially the question whether paclitaxel may improve the results if used as alternative to standard cisplatin. At the moment paclitaxel offers at least an attractive alternative to cisplatin in patients with impaired renal function.

Adult↗
PubMed1999

Evidence for only a moderate lipid peroxidation during ischemia-reperfusion of rat kidney due to its high antioxidative capacity.

The extent of lipid peroxidation after ischemia-reperfusion (I-R) injury in rat kidney has been controversial. After I, xanthine oxidase (XO) is thought to be the main oxygen radical-generating system and malondialdehyde (MDA) is considered to be a marker of lipid peroxidation (LPO). In young rats (10 weeks old) a unilateral warm I of 40 and 60 min duration with subsequent R up to 1 h was conducted. Beside the "footprints" of oxidative stress, the cytosolic antioxidative capacity, expressed as superoxide anion (SOA) scavenging capacity, and the renal catalase were also investigated. There was only a moderate and transient increase of renal MDA 5 and 10 min after the onset of reoxygenation (133.57/70. 67 and 97.84/91.57 vs. 49.47 nmol/g ww in preischemic controls). ATP breakdown (to 83/65 from 2947 nmol/g ww) with consecutive accumulation of hypoxanthine (up to 1105 nmol/g ww) at the end of ischemic period and the subsequent rapid decline of hypoxanthine by XO during reperfusion were used for an assessment of the SOA-generating capacity of these kidneys. Superoxide dismutase (SOD) activity, glutathione (GSH) and the high activity of catalase (18000 U/g ww) remained nearly unchanged during R. Only 1/25-1/50 of the kidney cytosol was able to scavenge the whole amount of SOA generated by the total XO activity of rat kidney. Thus, it could be analytically and stoichiometrically shown that after IR there is only a moderate oxidative stress in kidneys of young rats; this is due to their high SOA-scavenging capacity compared with their SOA-generating ability.

Adenosine Triphosphate↗