Six hunting dogs were investigated after showing signs of diffuse back pain. In three of the dogs, prodromal signs included coughing. Swelling in the dorsal lumbar region was noted in four of the dogs, but in two there was no visible or palpable swelling. Initial radiographs of the lumbar region were normal in two of the dogs and showed mild to moderate ventral periosteal reactions in the L1 to L4 region in the remaining four. On ultrasonography and magnetic resonance imaging, changes were seen in the sublumbar muscles (e.g., abnormal echogenicity and increased signal intensity) in five dogs examined. Exploratory surgery revealed plant material foreign bodies in the sublumbar muscles in the L1 to L4 region in five of the six dogs. The concurrent infections were caused predominantly by anaerobic bacteria common to the mucous membranes of the oropharyngeal and respiratory tracts. All dogs recovered, with restored hunting ability. The mean follow-up period was five years (range 1.3 to 7.8 years). It is proposed that the plant parts were inhaled, and then migrated along either diaphragmatic crus to lodge in the sublumbar muscles.
BackgroundAccumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn’t require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs.MethodsTwelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5–20 × 106 DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care.ResultsNo INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy.ConclusionsOur findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.Trial registrationClinicaltrials.gov identifier: NCT01525017.
Non-biodegradable superparamagnetic particles were used as an oral contrast medium in different concentrations, and evaluated in 25 human volunteers. The aim of the study was to determine the most appropriate concentration of the contrast medium, and to evaluate the effect, distribution, safety and tolerance. With the concentration of 1.0 g/l a substantial reduction of the signal intensity in the bowel was achieved in both T1 and T2 weighted images. The intraabdominal structures were well differentiated from the bowels containing contrast medium. 'Metal' artifacts and bluning of adjacent structures, probably due to an increased local concentration, were observed at higher dosages. The distribution of the preparation in the gastrointestinal tract varied between individuals. As a rule a good contrast effect was achieved in the small bowel with the exception of the duodenum. The contrast medium was well accepted and did not cause any side effects of clinical importance. The results suggest that the preparation is well tolerated by humans and may be a useful contrast medium for abdominal MR imaging.
• More bladder tumours are detected during the corticomedullary phase than during other phases. • Sensitivity and NPV for bladder cancer detection were highest in corticomedullary phase. • The corticomedullary phase in CT urography should be used for bladder assessment.
The detection rate of bladder tumours for the CTU protocol including an enhancement-triggered scan was high and comparable to flexible cystoscopy. Hence, this protocol could be used to assess the bladder as the primary investigation and direct further investigation of the patient.
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