Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An In Vitro and In Vivo Stability Study

Purpose The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted. Methods HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS. Results After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days. Conclusion HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment.Radiation, Radionuclides and ReactorsApplied Science

The Healing Process of Intracorporeally and In Situ Devitalized Distal Femur by Microwave in a Dog Model and Its Mechanical Properties In Vitro

Background: Limb-salvage surgery has been well recognized as a standard treatment and alternative to amputation for patients with malignant bone tumors. Various limb-sparing techniques have been developed including tumor prosthesis, allograft, autograft and graft-prosthesis composite. However, each of these methods has short- and long-term disadvantages such as nonunion, mechanical failures and poor limb function. The technique of intracorporeal devitalization of tumor-bearing bone segment in situ by microwave-induced hyperthermia after separating it from surrounding normal tissues with a safe margin is a promising limb-salvage method, which may avoid some shortcomings encountered by the above-mentioned conventional techniques. The purpose of this study is to assess the healing process and revitalization potential of the devitalized bone segment by this method in a dog model. In addition, the immediate effect of microwave on the biomechanical properties of bone tissue was also explored in an in vitro experiment. Methods: We applied the microwave-induced hyperthermia to devitalize the distal femurs of dogs in situ. Using a monopole microwave antenna, we could produce a necrotic bone of nearly 20 mm in length in distal femur. Radiography, bone scintigraphy, microangiography, histology and functional evaluation were performed at 2 weeks and 1, 2, 3, 6, 9 and 12 months postoperatively to assess the healing process. In a biomechanical study, two kinds of bone specimens, 3 and 6 cm in length, were used for compression and three-point bending test respectively immediately after extracorporeall

Human keratinocytes are vanilloid resistant

BACKGROUND: Use of capsaicin or resiniferatoxin (RTX) as analgesics is an attractive therapeutic option. RTX opens the cation channel inflammatory pain/vanilloid receptor type 1 (TRPV1) permanently and selectively removes nociceptive neurons by Ca(2+)-cytotoxicity. Paradoxically, not only nociceptors, but non-neuronal cells, including keratinocytes express full length TRPV1 mRNA, while patient dogs and experimental animals that underwent topical treatment or anatomically targeted molecular surgery have shown neither obvious behavioral, nor pathological side effects. METHODS: To address this paradox, we assessed the vanilloid sensitivity of the HaCaT human keratinocyte cell line and primary keratinocytes from skin biopsies. RESULTS: Although both cell types express TRPV1 mRNA, neither responded to vanilloids with Ca(2+)-cytotoxicity. Only ectopic overproduction of TRPV1 rendered HaCaT cells sensitive to low doses (1-50 nM) of vanilloids. The TRPV1-mediated and non-receptor specific Ca(2+)-cytotoxicity ([RTX]>15 microM) could clearly be distinguished, thus keratinocytes were indeed resistant to vanilloid-induced, TRPV1-mediated Ca(2+)-entry. Having a wider therapeutic window than capsaicin, RTX was effective in subnanomolar range, but even micromolar concentrations could not kill human keratinocytes. Keratinocytes showed orders of magnitudes lower TRPV1 mRNA level than sensory ganglions, the bona fide therapeutic targets in human pain management. In addition to TRPV1, TRPV1b, a dominant negative splice variant was also noted in keratinocytes. CONCLUSION: TRPV1B expression, together with low TRPV1 expression, may explain the vanilloid paradox: even genuinely TRPV1 mRNA positive cells can be spared with therapeutic (up to micromolar) doses of RTX. This additional safety information might be useful for planning future human clinical trials

Seventh cervical vertebral body solitary osteochondroma. Report of a case and review of the literature

Solitary osteochondroma of the cervical spine is a rare manifestation of a common bony tumour. It can create symptoms, depending on the adjacent compressed structures. In this report, a patient suffering solitary osteochondroma on the anterolateral aspect of the C7 vertebral body is presented and the literature is reviewed. A 46-year-old female presented with dysphagia and pain at the anterolateral surface of her neck during cervical movements or application of local pressure. The clinical and imaging assessment ascertained that the above complaints were due to a local tumour in the neck firmly attached to the spine at the anterolateral aspect of the C7 and which resembled an osteochondroma. Surgical treatment was chosen due to the persistence of the symptoms. The lump was resected using an anterolateral cervical approach and it was sent to the pathology department for confirmation of the lesion’s histological character. The patient was completely relieved of her symptoms. Resection of the osteochondroma seems to be the only reliable solution for definitive relief from the clinical complaints. This surgical treatment, as it is reported, has no major complications and gives good functional results. One to four per cent of the osteochondromas are located at the spine. At the cervical spine, they can cause neurological symptoms and more rarely, dysphagia. Reviewing the literature, no case of solitary osteochondroma located in the anterior aspect of the C7 body was found. Two cases suffering from dysphagia were reported due to external compression by anterior hyperostosis of the cervical spine, but not due to osteochondroma

Otitis and respiratory distress episodes following a respiratory syncytial virus infection

Objective To document, over two consecutive respiratory syncytial virus (RSV) seasons, the occurrence of acute otitis media (AOM) and recurrence of respiratory distress in children <2 years of age hospitalized for respiratory distress. Methods Patients were examined during hospitalization and at 6 weeks and 6 months after discharge. RSV testing was performed on all patients, and hospitalized patients were evaluated daily for the occurrence of AOM. Results In total, 347 children were enrolled; 54.8% were RSV positive, and 45.2% were RSV negative. Children were most frequently diagnosed as having bronchiolitis (71.9%) or asthmatic bronchitis (17.9%); other diagnoses included pneumonia, laryngitis, and rhinitis. During hospitalization, AOM was diagnosed in 16.8% of RSV-positive versus 8.3% of RSV-negative children (P < 0.05). Six weeks after discharge, AOM was reported in 10.4% of RSV-positive as compared with 5.8% of RSV-negative patients. Six months later, AOM was reported in 2.9% of the RSV-positive and 7.6% of the RSV-negative patients. A second episode of acute respiratory distress, which either required (9) or did not require (35) hospitalization, occurred in 18.4% of the total population, with similar proportions of RSV-positive and RSV-negative children (17% versus 18.6%). Conclusion We conclude that RSV appears to be an important contributing factor for the occurrence of AOM in young children hospitalized with respiratory distress. The occurrence of a second episode of acute respiratory distress did not appear to correlate with the previous RSV infection, but longer-term follow-up is required

Markers of hepatitis viruses and human T-lymphotropic virus types I/II in patients who have undergone open-heart surgery: Evidence of increased risk for exposure to HBV and HEV

Background: Open-heart procedure is characterized by a high-risk for contracting blood-borne infections. We evaluated the prevalence of several markers of hepatitis viruses (B-E) and human T-cell lymphotropic virus types I/II (HTLV-I/II) in a consecutive series of patients who had undergone open-heart surgery. Methods: 204 patients and 158 selected age- and sex-matched healthy volunteers were investigated. Samples were collected at least 6-12 months postoperatively. Commercial enzyme immunoassays and confirmatory immunoblot assays for HCV, HEV and HTLV-I/II were used. Results: None of the subjects tested positive for antibodies to HTLV-I/II. Prevalence of markers of past HBV infection and antibodies to HEV (anti-HEV) were higher in patients than in healthy controls (anti-HBc: 45.1% vs. 31%, p = 0.009; anti-HBs: 31.9% vs. 22.2%, p = 0.02; anti-HBe: 32.4% vs. 10.1%, p = 0.000; anti-HEV: 5.4% vs. 0%, p = 0.008). HBsAg and antibodies to HCV did not differ between the groups. Conclusions: HTLV, HBsAg and HCV infection markers did not differ between patients and healthy controls. However, patients had significantly increased prevalence of markers of previous HBV infection suggesting that an intensive vaccination schedule against HBV preoperatively might be helpful in minimizing the risk. The increased prevalence of anti-HEV in cardiac patients requires further investigation. Prospective studies are needed in order to definitely address whether the high prevalence of exposure to HBV and HEV infections in patients who had undergone open-heart surgery is procedure-related or not and whether it has any impact on morbidity of these patients. © 2005 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved