Interleukin-2 and interferon-alpha2b as a daily alternating schedule in advanced renal cell cancer

Summary Interferon-alpha (IFN-) and interleukin-2 (Il-2) are effective as single agents in metastatic renal cell cancer (RCC) with response rates of 15–30%. Additionally, IFN- is assumed to act synergistically with Il-2 in the induction of lymphokine-activated killer cells. (LAK cells) in vitro. With the aims of increasing the response rate by combining both cytokines and of reducing side effects, we started a clinical trial with a daily alternating schedule of 10×10⁶ units/m² s.c. rIFN-_2b (Essex, Munich, FRG) and 3×10⁶ Cetus units/m² rIL-2 (EuroCetus, Frankfurt, FRG) in the form of 1 h infusions over a period of 14 days. Patients found to have progressive disease after two cycles of therapy were withdrawn from the study; patients with stable disease or better received two further cycles.Of the 27 patients included in the study, 22 (16 male, 6 female) are evaluable for response. In 1 patient with multiple pulmonary metastases complete remission was achieved, in 5 patients partial remission, and in 2 a minor response. The schedule was practicable; the main side effects were influenza-like symptoms, fatigue and hypotension. Some patients suffered from arthralgias and erythemas up to 3 weeks after finishing the therapy cycle. On the whole, the side effects seem to be less severe than those arising from schedules using continuous Il-2 infusions.This work was supported by Grant No. 01GA8802 of the Bundesministerium für Forschung und Technologie (BMFT)     

Relationship between the high-energy phosphate content and various left ventricular functional parameters of the normal and hypertrophied heart after global ischemia and reperfusion

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the correlation between the high-energy phosphate content and various left ventricular (lv) functional parameters of the hypertrophied heart (spontaneous hypertensive rats lv/body weight ratio 3.6 +/- 0.5 x 10(-3) was determined after normo- (30 min) and hypothermic (25 degrees C, 120 min) cardioplegic arrest and reperfusion, and compared with normal hearts (Wistar rats lv/body weight ratio 2.0 +/- 0.3 x 10(-3). St. Thomas Hospital solution was used as the cardioplegic agent. Before ischemia hypertrophied hearts had a significantly higher developed left ventricular pressure, pressure rate product and dp/dtmax, but a significantly lower ATP and total adenine nucleotide content. Irrespective of the mode and temperature of cardiac arrest there was a strong correlation both for normal and for hypertrophied hearts between the high-energy phosphate content expressed as ATP, total adenine nucleotides or the "energy charge" and the left ventricular functional parameters pressure rate product and dp/dtmax. The correlation coefficient ranged from 0.80 to 0.89 and was highest when the ATP content was plotted against pressure rate product (r = 0.89). There was a different slope for normal and hypertrophied hearts with a steeper decline of the left ventricular function in hypertrophied hearts for any given reduction of the myocardial adenine nucleotide content. Our results indicate that a similar reduction of the ATP or total adenine nucleotide content in both the normal and hypertrophied heart reduces left ventricular function to a greater degree in the hypertrophied heart.     

Sixty-four-MSCT in the characterization of porcine acute and subacute myocardial infarction: determination of transmurality in comparison to magnetic resonance imaging and histopathology

OBJECTIVE: The aim of this study was to assess the accuracy of MSCT in characterizing myocardial infarction (MI) and, thereby, determine the extent of early perfusion defect (ED), microvascular obstruction (MO) and transmural depth of late enhancement (LE) in comparison to MRI and histology. MATERIALS AND METHODS: Seven pigs were studied with MSCT (Somatom Sensation 64) and MRI (Magnetom Sonata) a median 1 and 21 days following temporary occlusion of a diagonal branch and creation of small reperfused infarction. For depiction of ED, CT images were acquired in the early arterial phase and following 35 s; LE and MO were evaluated on images obtained at 3, 5, 10 and 15 min. Thereby, a bolus/low-flow contrast injection protocol was used. Triphenyltetrazolium-chloride (TTC) stain and histology were obtained. Volumes of enhancement patterns were assessed as percentage of the ventricle and compared by Bland-Altman analysis. Segmental co-localization and graded transmurality was evaluated with weighted-kappa-test. RESULTS: Close spatial agreement was observed for MRI-MO and MSCT-MO (bias=0.55; CI=-1.49 to 2.60 at 5 min MSCT), TTC and MSCT-LE (bias=-1.28; CI=-3.76 to 1.19) or MRI-LE and MSCT-LE (bias=-0.79; CI=-4.19 to 2.60). There was good segmental co-localization for MO (weighted kappa=0.93) and high agreement for transmural extent of TTC, MRI-LE and MSCT-LE (weighted kappa=0.84 TTC versus MSCT; 0.86 MRI versus MSCT). Arterial and 35s ED significantly underestimated infarct size and showed poor segmental or transmural agreement (weighted kappa=0.33; 0.44). CONCLUSIONS: MSCT late-scans not only reliably depict size of MO and LE in acute or subacute infarct phases but, moreover, allow for accurate determination of LE transmurality.     

Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia

BACKGROUND:: Fludarabine monophosphate is a new adenine nucleoside analoguewith a promising efficacy in B-cell chronic lymphocytic leukemia(B-CLL) with response rates, including hematological completeremissions, of 50%–60% in previously treated and 75%–80%in previously untreated patients. PATIENTS AND METHODS:: Here, the clinical experience with and side effects of fludarabineare reported in 19 patients with refractory CLL (17 B-CLL, 2T-CLL). All patients were pretreated with one to four differentregimens and had progressive disease. Fludarabine was administeredat a dosage of 25 mg/m² daily for 5 days as a 30-minute intravenousinfusion. This course was repeated every fifth week. Dosageand time course were adapted to toxicity. RESULTS:: 12/18 (67%) evaluable patients achieved partial remissions (PR),1/18 (6%) had stable disease (SD) and 5/18 (28%) were progressive.The median duration of partial remission until relapse or deathwas 6 months. Most responses to fludarabine occurred withintwo treatment courses. Major toxic effects included infectionsin 11 patients and nausea in 8 (mainly grade 1). Meanwhile,three patients died of progressive disease and 8 of pneumoniasor other infections. Two patients had pneumocystis carinii pneumoniasand one an aspergillus pneumonia. The high infection rate maybe due not only to hypogammaglobulinaemia or fludarabine-inducedgranulocytopenia but also to a remarkable decrease of CD4⁺-cellsduring fludarabine therapy. In one case a tumor lysis syndromewas observed. No CNS toxicity was noted. CONCLUSION:: It is concluded that fludarabine is effective even in patientswith advanced chronic lymphocytic leukemia refractory to multiplechemotherapy regimens. However, fludarabine has a remarkablesuppressive effect on T-lymphocytes, predominantly CD4⁺-lymphocytes.Long-term antibiotic prophylaxis is recommended. fludarabine, chronic lymphocytic leukemia, immunosuppression, infection rate     

Fast whole-body assessment of metastatic disease using a novel magnetic resonance imaging system: initial experiences

OBJECTIVE: The objective of this study was to investigate the clinical use of a novel whole-body magnetic resonance imaging (MRI) system for comprehensive assessment of tumor spread in clinical routine. MATERIAL AND METHODS: Sixty-five patients with different tumors with known metastatic disease and 6 healthy volunteers were included. High-resolution MRI from head to toe was performed using multiple phased-array surface coil elements, 24 independent receiver channels, and an integrated parallel acquisition technique (iPAT). A total room time of less than 60 minutes was required. Whole-body MRI and conventional spiral computed tomography (CT) were independently evaluated and compared in terms of feasibility, location/number of detected metastases, and therapeutic relevance. RESULTS: Whole-body MRI was successfully performed in 68 of 71 subjects. Compared with CT, more metastases were detected by MRI in 11 of 63 patients (17%), particularly in brain, liver, spleen, lymph nodes, bone marrow, muscle, and subcutaneous fat tissue. According to these findings, therapy had to be modified in 6 of 63 patients (10%). CONCLUSIONS: High-resolution whole-body MRI is feasible in clinical routine within 1 single examination and offers great potential for fast assessment of individual tumor spread and total tumor burden.     

Myocardial perfusion after angioplasty in patients suspected of having single-vessel coronary artery disease: improvement detected at rest-stress first-pass perfusion MR imaging--initial experience

PURPOSE: To prospectively assess myocardial perfusion before and after successful intervention in patients suspected of having single-vessel coronary artery disease by using a steady-state free precession (SSFP) perfusion magnetic resonance (MR) imaging sequence. MATERIALS AND METHODS: Local ethics committee approval and informed consent were obtained. Rest-stress perfusion MR imaging studies were performed in 18 patients with coronary artery disease (12 men, six women; mean age, 58.6 years +/- 13.6 [standard deviation]; range, 30-79 years) at 1.5 T with a multisection saturation-recovery SSFP sequence and 0.025 mmol gadopentetate dimeglumine per kilogram of body weight. MR studies were performed before (n = 18), several days after (n = 18), and 8 months after (n = 10) coronary intervention. Nine patients underwent percutaneous transluminal coronary angioplasty (PTCA) alone, and nine patients underwent PTCA with stent placement. Myocardial perfusion reserve index (MPRI) was calculated by dividing results of myocardial perfusion at maximal vasodilation by results at rest. The standard for myocardial perfusion was technetium 99m tetrofosmin single photon emission computed tomography. Statistical significance was tested with univariate variance analysis and Student t tests. RESULTS: In the area of the stenosed vessel, MPRI was 1.04 +/- 0.24 before treatment and 2.18 +/- 0.57 several days afterward (P < .001). In remote areas, MPRI was 2.42 +/- 0.44. In the stent group, MPRI increased by 156%, from 0.99 +/- 0.20 before stent placement to 2.53 +/- 0.53 after (P < .001). Similarly, in the PTCA only group, MPRI increased by 72%, from 1.08 +/- 0.27 before PTCA to 1.87 +/- 0.39 after (P < .001). At follow-up in patients without recurring chest pain, MPRI was 2.14 +/- 0.37 in the area of the treated artery and 2.29 +/- 0.47 in remote areas (P = .06). CONCLUSION: The MPRI, derived from rest-stress examinations, can provide information on success of interventional procedures in stenosed coronary arteries.     

Scimitar syndrome: morphological diagnosis and assessment of hemodynamic significance by magnetic resonance imaging

Scimitar syndrome has a variable presentation depending on the age at which the diagnosis is made. We report a case of a young woman (age 18 years) with suspected right pulmonary hypoplasia in whom a scimitar syndrome was diagnosed. Using MRI morphological findings and hemodynamic significance of the syndrome were assessed. Left-to-right shunt was calculated from blood flow measurements performed in the ascending aorta, the main pulmonary artery, and the aberrant scimitar vein.     

Epithelioid sarcoma of the penis--a rare differential diagnosis of Peyronie's disease

We report on a case of penile epithelioid sarcoma in a 29-year-old man presenting with a dorsal penile plaque that primarily was misdiagnosed as Peyronie's disease. Although the initial clinical findings of these two different entities appear similar, the consequence for the patient is severe. The only way of differentiating these disorders are histological findings. The principal microscopic characteristics of epithelioid sarcoma are the distinctive nodular arrangement, central degeneration and necrosis of the tumor cells with epithelioid appearance and eosinophilia. Immunohistochemical data (cytokeratin, epithelial membrane antigen, vimentin, CD 34, desmin) confirm the diagnosis. We conclude that in cases with slightest doubts on the diagnosis of Peyronie's disease, especially in younger men suffering from a fast-growing penile induration, a bioptic clarification of the entity should be performed to exclude a high malignant disease that can be only treated as far as it is localized by radical surgery.