Post-mortem studies in glioblastoma patients treated with thermotherapy using magnetic nanoparticles.

Patients with glioblastoma multiforme (GBM), the most common primary brain tumor in adults, have still a poor prognosis though new strategies of radio- and chemotherapy have been developed. Recently, our group demonstrated the feasibility, tolerability and anti-tumoral effects of a newly developed therapeutic approach, termed thermotherapy using magnetic nanoparticles or magnetic fluid hyperthermia (MFH), in a murine model of malignant glioma. Currently, the efficacy of MFH is being evaluated in a phase II study. Here, we report on post-mortem neuropathological findings of patients with GBM receiving MFH. In brain autopsies the installed magnetic nanoparticles were dispersed or distributed as aggregates within geographic tumor necroses, restricted in distribution to the sites of instillation. Therefore, our results underscore the need for multiple trajectories of instillation. The typical GBM necrosis with pseudopalisading was free of particles. Dispersed particles and particle aggregates were phagocytosed mainly by macrophages whereas glioblastoma cells showed an uptake to a minor extent. MFH therapy further promotes uptake of nanoparticles in macrophages, likely as a consequence of tumor inherent and therapy induced formation of necrosis with subsequent infiltration and activation of phagocytes. We did not observe bystander effects of MFH such as sarcomatous tumour formation, formation of a sterile abscess or foreign body giant cell reaction. Furthermore, all patients did not present any clinical symptoms related to possible adverse effects of MFH.

Morbidity and quality of life during thermotherapy using magnetic nanoparticles in locally recurrent prostate cancer: results of a prospective phase I trial.

PURPOSE: To investigate the treatment-related morbidity and quality of life (QoL) during thermotherapy using superparamagnetic nanoparticles in patients with locally recurrent prostate cancer. MATERIALS AND METHODS: Ten patients with biopsy-proven locally recurrent prostate cancer following primary therapy with curative intent and no detectable metastases were entered on a prospective phase I trial. Endpoints were feasibility, toxicity and QoL. Following intraprostatic injection of a nanoparticle dispersion, six thermal therapy sessions of 60 min duration were delivered at weekly intervals using an alternating magnetic field. National Cancer Institute (NCI) common toxicity criteria (CTC) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-PR25 questionnaires were used to evaluate toxicity and QoL, respectively. In addition, prostate specific antigen (PSA) measurements were carried out. RESULTS: Maximum temperatures up to 55 degrees C were achieved in the prostates at 25-30% of the available magnetic field strength. Nanoparticle deposits were detectable in the prostates one year after thermal therapy. At a median follow-up of 17.5 months (3-24), no systemic toxicity was observed. Acute urinary retention occurred in four patients with previous history of urethral stricture. Treatment-related morbidity was moderate and QoL was only temporarily impaired. Prostate-specific antigen (PSA) declines were observed in eight patients. CONCLUSIONS: Interstitial heating using magnetic nanoparticles was feasible and well tolerated in patients with locally recurrent prostate cancer. Deposition of nanoparticles in the prostate was highly durable. Further refinement of the technique is necessary to allow application of higher magnetic field strengths.

Persistence of antibodies to meningococcal IgA1 protease versus decay of antibodies to group A polysaccharide and Opc protein.

Sera were taken over a 5 year period from Gambian children vaccinated in 1983, when aged 1-4 years, with A + C meningococcal capsular polysaccharide, ELISA tests were devised to determine the concentrations of immunoglobulin A, G and M reacting with A polysaccharide and of IgG reacting with Opc protein, IgA1 protease and an internal 104 mer peptide derived from IgA1 protease. Vaccination resulted in a brief rise of antibodies to A polysaccharide followed by decline to pre-immunization levels. IgM levels were very high even before vaccination. Antibodies to Opc protein stimulated by natural exposure also declined over the 5 year period. In contrast, antibodies stimulated by natural exposure to IgA1 protease or to the internal peptide remained constant or increased (final geometric mean level of 47 micrograms IgG ml-1). We speculate that healthy carriage of Neisseria meningitidis or Haemophilus influenzae is responsible for this increase in IgG concentration.

[Pasteurella multocida (type D and A) and atrophic rhinitis of swine--hemagglutination, fimbriae and adhesion in vitro in the nasal mucosa of swine fetuses]. / Pasteurella multocida (Typ D und A) und Rhinitis atrophicans des Schweines--Hämagglutination, Fimbrien sowie Adhäsion in vitro an Nasenschleimhaut von Schweinefeten.

79 strains of P. multocida were investigated, mostly isolated from porcine nasal cavities, and a mannose-resistant hemagglutination with guinea pig and human group 0, but not with porcine erythrocytes was found. Fimbriae as adhesins were demonstrated only on 2 strains. A correlation between capsular type, hemagglutination, fimbriation and toxigenicity on the examined P. multocida strains was not observed. Three strains were investigated for the adherence to the nasal mucosa of neonatal pigs; aggregates shown by scanning electron microscopy indicate colonization; a correlation of adherence with surface proteins and slime production of P. multocida is discussed.

Effects of angiographic contrast media on venous endothelium of rabbits.

The effects of ionic and nonionic contrast media on rabbit venous endothelium were examined. In anesthetized animals, caudal mesenteric veins were exposed and perfused with the ionic contrast medium, diatrizoate, and the nonionic contrast media iopromide and iotrolan for 2 minutes at 5 mL/minute. Control animals were similarly perfused with physiologic saline or a 23% sorbitol solution. The specimens were fixed in situ by perfusing 4% glutaraldehyde, and ultrathin stained sections were examined with an electron microscope. The hyperosmolar contrast medium diatrizoate produced shrinkage in cell cytoplasm and in nuclear material. There also were minor structural alterations in endoplasmic reticulum and widening of intercellular junctions. The nonionic contrast media iotrolan and iopromide caused mild to moderate changes in endothelial cells. Sorbitol infusion, however, affected venous endothelium more intensely than the ionic and nonionic contrast media, suggesting hyperosmolality as the causal factor in endothelial damage.