Effect of first-line treatment on second primary malignancies and Richter's transformation in patients with CLL.

This study aimed to assess the frequency of and the contributing factors for second primary malignancies (SPMs) and Richter's transformations (RTs) following first-line treatment of chronic lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine (F) vs F+cyclophosphamide (FC), chlorambucil vs F, FC without or with rituximab, and bendamustine+R (BR). Among 1458 patients, 239 (16.4%) experienced either an SPM (N=191) or a RT (N=75). Solid tumors (N=115; 43.2% of all second neoplasias) appeared most frequently, followed by RTs (N=75; 28.2%). Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry. Age>65 (hazard ratio (HR) 2.1; P<0.001), male sex (HR 1.7; P=0.01), co-morbidities (HR 1.6; P=0.01) and number of subsequent treatments⩾1 (HR 12.1; P<0.001) showed an independent adverse prognostic impact on SPM-free survival. Serum thymidine kinase>10 U/l at trial enrollment (HR 3.9; P=0.02), non-response to first-line treatment (HR 3.6; P<0.001) and number of subsequent treatments⩾1 (HR 30.2; P<0.001) were independently associated with increased risk for RT.

Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards CD28 engagement.

Human lamina propria T lymphocytes (LPT) possess functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). While they are characterized by a low proliferative response to T cell receptor (TCR)/CD3 stimulation in vitro their responsiveness to activation through the 'co-stimulatory' CD2-receptor is enhanced when compared to PBT. In this study, we demonstrate that engagement of another co-stimulatory receptor on both LPT and PBT, namely CD28, by a single monoclonal antibody (mAb), respectively, strongly activates the former but not the latter through a PI3-kinase dependent signalling pathway leading to the production of inflammatory cytokines such as interleukin (IL)-2, tumour necrosis factor (TNF)-α, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition to the high sensitivity of LPT to CD2 stimulation, this finding supports the notion that 'non-specific/innate' mechanisms to activate T lymphocytes play a predominant role vis-à-vis'TCR driven/adaptive' responses in the intestinal mucosa. Furthermore, it suggests that results from preclinical tests for therapeutic antibodies performed with human blood derived T cells are probably insufficient to predict reactivities of tissue-resident immune cells, which--given their quantitative predominance--may critically determine the in-vivo response to such compounds.

Measurement of fluid volume shifts during hemodialysis by A-mode ultrasonography.

BACKGROUND: The rate of intercompartmental fluid volume changes during hemodialysis (HD) is a major determinant of dialysis-induced hypotension and lacks direct monitoring. The aim of the study was to evaluate the feasibility of tissue thickness (TT) measurement in monitoring the mobilization of interstitial fluids during HD. METHODS: We studied the intradialytic changes in forehead TT and inferior vena cava diameter (IVCD) in 20 patients. Plasma refilling was calculated from changes in hematocrit (Hct) and ultrafiltration rates. RESULTS: During ultrafiltration of 2,437 +/- 117 ml (mean +/- SEM), Hct increased significantly from 27.9 +/- 0.7 to 30.0 +/- 0.9%. IVCD decreased significantly from 9.7 +/- 0.2 to 6.1 +/- 0.4 mm/m(2). We found a simultaneously pronounced reduction in TT from 4. 46 +/- 0.12 to 3.78 +/- 0.12 mm (> or =15.3%) with a significant correlation to plasma refilling (0.613). CONCLUSION: Volume changes in the peripheral shell tissues during HD can be monitored directly and noninvasively by A-mode ultrasound.

Internet-based physician's workbench as user interface for a central medical case repository.

Two World Health Organization Radiation Medical Emergency Preparedness and Assistance Network centers have constructed a standardized central repository of acute radiation syndrome case histories. The case histories are stored on a database server. Radiation protection centers can remotely access the database by user-friendly client software over the Internet. Physicians can use the medical information system to retrieve similar case histories for decision support, to improve their medical knowledge by inspecting real case histories, and for research on the acute radiation syndrome. The system architecture is presented and it is shown in detail how the information system can be employed to deliver medical decision support. Dialogue-response times over narrow-bandwidth Internet connections are better than when using conventional World-Wide-Web technology. However, the latter does not require the installation of client software other than a browser. A Java applet as client could combine the advantages of the two approaches.

Measurement of peripheral tissue thickness by ultrasound during the perioperative period.

We have studied changes in peripheral tissue thickness with a novel hand-held ultrasound device during the perioperative course of 60 healthy surgical patients in three different intraoperative body positions. The nil-by-mouth period led to a significant decrease in forehead tissue thickness. Standardized infusion therapy with Ringer's solution at a rate of 8 ml kg-1 h-1 resulted in a gradual increase in tissue thickness, which was significantly different from preoperative baseline values after 90 min. Packed cell volume decreased significantly after the start of infusion and remained low over the rest of the observation time. Different body positions did not influence changes in tissue thickness. We conclude that changes in perioperative tissue thickness in healthy patients can be detected easily by ultrasound, independent of body position. This method may prove useful for the non-invasive assessment of fluid balance state.

[Ultrasonography of the inner stifle joint in dogs with rupture of the cruciate ligaments]. / Die Ultraschalluntersuchung des inneren Kniegelenkes bei Hunden mit Kreuzbandriss.

This paper gives an overview of the sonographic possibilities to examine the canine stifle joint with rupture of the cruciate ligament. Sonographic examination was performed in 100 surgical patients because of a lesion of the joint. Ultrasound sections are presented with corresponding sonographical findings and pathological changes. For stifle joint, a linear transducer with 7.5 Mhz proved to be useful. Both the lateral and medial meniscus could be inspected, as well as injuries of the menisci. As an indirect sign to a lesion, effusions of the joint were demonstrable quite sensitively. The cruciate ligaments could not be investigated correctly with ultrasound. Ultrasonography is used to investigate the soft tissue structures as a completion of the radiological examination. The scanning diagnostic technique is practicable with a low technical expenditure, it is not stressful for the patient and can be repeated for therapy controls. Disadvantageous is that ultrasound is prone to artefacts, caused by the thinness of the structures examined.

[Ultrasonography of the stifle joint in dogs]. / Die Ultraschalluntersuchung des Kniegelenkes des Hundes.

This paper gives an overview of the sonographic possibilities to examine the canine stifle joint. Sonographic examination was performed in stifle joints of 30 dogs without any pathologic changes in the hind leg. The sonographic examination is presented with corresponding sonographical findings. For this indication a linear- and sector transducer with 7.5 Mhz was proved to be useful. The patellar ligament could be scanned very well by a linear transducer in a longitudinal section using a standoff pad. Both the lateral and medial meniscus could be inspected, as well as injuries of the menisci. As an indirect sign to a lesion, effusions of the joint were proved quite sensitively. The cruciate ligaments could not be demonstrated correctly with ultrasound. The ultrasonography is used for the investigation of the soft tissue structures as the completion of the radiology. The scanning diagnostic technique is practicable with a low technical expenditure, is not stressful for the patient and can be repeated for therapy controls: Disadvantageous is that ultrasound is prone to artifacts, caused by the thinness of the structures examined.

[Bone scintigraphy and arthroscopy--diagnostic methods for the detection of lameness in dogs]. / Skelettszintigraphie und Arthroskopie--diagnostische Verfahren zur Abklärung einer Lahmheitsursache beim Hund.

For the detection of lameness in the dog two additional diagnostic methods-bone scintigraphy and arthroscopy-are available. The cooperation of these techniques in the clinical diagnosis is presented by case examples. The techniques and the applicabilities of bone scintigraphy and arthroscopy are shown and discussed.

[Pharmacokinetics and tolerance of an orally administered combination preparation containing phenylbutazone and prednisolone in the dog]. / Pharmakokinetik und Verträglichkeit eines oral verabreichten Kombinationspräparates mit den Inhaltsstoffen Phenylbutazon und Prednisolon beim Hund.

Tolerance and pharmacokinetics of a combination of phenylbutazone and prednisolone (tablets) were studied in Beagle dogs. For two weeks, the drug was administered orally (3.33 mg/kg phenylbutazone combined with 0.1 mg/kg prednisolone and 6.66 mg/kg phenylbutazone combined with 0.3 mg/kg prednisolone twice daily). The dosage was reduced to 50 per cent after one week. No signs of intolerance were found. After treatment with 3.33 mg/kg phenylbutazone, a plasma concentration of 10 micrograms/ml was reached within 1 to 2 hours. No prednisolone concentration above 2 ng/kg was measured. Additionally, a synergistic antiinflammatory effect of the two ingredients was obvious (hind paw dextran edema in rats). In addition to results of ENGELKE et al. (1995) who studied the clinical efficacy of the combination, the presented data demonstrate a good tolerance.