Osteonecrosis of the jaws associated with use of risedronate: report of 2 new cases.

Use of various bisphosphonates has been associated with the development of osteonecrosis of the jaws (ONJ). At least 865 cases of ONJ attributed to these agents have been reported in the English-language literature. Approximately 96% of these published cases were seen with administration of the intravenous agents pamidronate and zoledronate, whereas only 26 cases have been associated with oral bisphosphonates, 25 of them with alendronate. Only a single case of ONJ associated with the oral bisphosphonate risedronate has been previously cited. We report 2 cases of ONJ attributed to risedronate administration. The patients developed osteonecrosis 15 and 24 months after treatment for osteopenia. A regimen of antibiotics and chlorhexidine mouthrinse resolved the osseous defect in the mandible caused by complete exfoliation of a lingual torus in 1 patient. The other patient required sequestrectomy, repeated courses of antibiotics, surgical debridement, and steroids to promote closure of an oroantral fistula and management of sinusitis after bone grafting and implant placement in the posterior maxilla. A demographic profile of reported oral bisphosphonate users affected by ONJ is also provided. With the millions of patients receiving various oral bisphosphonates for osteopenia and osteoporosis, health care practitioners should be aware of the potential for the onset of osteonecrosis and familiar with its management.     

Assigning the source of human campylobacteriosis in New Zealand: A comparative genetic and epidemiological approach

Integrated surveillance of infectious multi-source diseases using a combination of epidemiology, ecology, genetics and evolution can provide a valuable risk-based approach for the control of important human pathogens. This includes a better understanding of transmission routes and the impact of human activities on the emergence of zoonoses. Until recently New Zealand had extraordinarily high and increasing rates of notified human campylobacteriosis, and our limited understanding of the source of these infections was hindering efforts to control this disease. Genetic and epidemiological modeling of a 3-year dataset comprising multilocus sequence typed isolates from human clinical cases, coupled with concurrent data on food and environmental sources, enabled us to estimate the relative importance of different sources of human disease. Our studies provided evidence that poultry was the leading cause of human campylobacteriosis in New Zealand, causing an estimated 58–76% of cases with widely varying contributions by individual poultry suppliers. These findings influenced national policy and, after the implementation of poultry industry-specific interventions, a dramatic decline in human notified cases was observed in 2008. The comparative-modeling and molecular sentinel surveillance approach proposed in this study provides new opportunities for the management of zoonotic diseases.     

Spread of local anaesthetic solution in epidural space visualisation with ultrasound in single shot caudals

Background: Ultrasonography is becoming an important adjunct in paediatric neuraxial blockade. Ultrasound guidance helps in visualisation of relevant neuraxial structures, predicting depth of epidural space from skin, reduction in bony contact and faster epidural placement. The visibility of neuraxial structures declines in patients as age increases. To date, there are no studies looking at the extent of spread of local anaesthetic solution in the epidural space and its correlation to the volume used, under ultrasound guidance. We report the results of our audit on spread of local anaesthetic solution in the epidural space in single shot caudal blocks. This abstract is based on the first 17 patients, the presentation will be based on all 50 patients. Methods: This audit was approved by the local audit committee. We aimed to follow the extent of the spread of local anaesthetic within the epidural space with real time ultrasonography. Patients were selected when the planned anaesthetic included a single shot caudal block. The anaesthetists performing the anaesthetic and the caudal block consented to our ultrasound visualisation. All patients were below 5 years of age. No attempt was made to standardise the technique, the dose, or the speed of injection. After the placement of the caudal cannula by the primary anaesthetist involved in patient care, a separate anaesthetist, experienced in using ultrasound, visualised the neuraxial structures and subsequent spread of the local anaesthetic solution with real time ultrasound. The spread was followed during the injection and for 10 s after the completion of the injection. A 5 cm 7.5–12 MHz linear array was used longitudinally with either midline or paramedian approach. Results: We are reporting the preliminary results from 17 patients. Patients were aged between 1 day and 1 year 10 months. They weighed between 3.3 kg and 14.6 kg. Either 22 gauge Jelco or Abbocath were used to perform the procedure; 0.25% or 0.20% L‐bupivacaine was used on all occasions. The volume administered per kg ranged between 0.33 and 1.27 ml. The visibility of neuraxial structures was good on all occasions. On calculating the Spearmans correlation coefficient, the extent of spread of local anaesthetic in the epidural space was positively correlated with the volume used by a correlation coefficient of 0.64, with a P value of 0.008. The postoperative pain score in recovery was 0 in 16 out of the 17 cases. The one failure occurred when the observed spread would not have been expected to provide analgesia for the performed operation. Conclusions: Among children below 5 years of age, there seems to be a positive correlation between the volume of local anaesthetic injected into the epidural space and the extent of its spread. This needs to be further investigated by a prospective randomised control trial. The utility of real time ultrasound to allow a reliable achievement of a desired level of sensory block, should be investigated i.e, whether the volume used in achieving a desired level of local anaesthetic spread, as guided by ultrasound, provides superior analgesia and fewer adverse effects compared with the volume calculated using the Armitage regimen. References 1 Rapp HJ, Folger A, Grau T. Ultrasound guided epidural catheter insertion in children. Anesth Analg 2005; 101 : 333–339. 2 Willschke H, Marhofer P, Bosenberg A, et al. Epidural catheter placement in children: comparing a novel approach using ultrasound guidance and a standard loss of resistance technique. Br J Anaesth 2006; 97 : 200–207. 3 Marhofer P, Bosenberg A, Sitzwohl C et al. Pilot study of neuraxial imaging by ultrasound in infants and children. Pediatr Anesth 2005; 15 : 671–676.     

Pharmacokinetic characterization in xenografted mice of a series of first-generation mimics for HLA-DR antibody, Lym-1, as carrier molecules to image and treat lymphoma.

Despite their large size, antibodies (Abs) are suitable carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. Lym-1 Ab has proven to be an effective radioisotope carrier, even in small amounts, for targeting human leukocyte antigen DR (HLA-DR), a surface membrane protein overexpressed on B-cell lymphoma. Pairs of molecules (referred to as ligands), shown by computational and experimental methods to bind to each of 2 sites within the Lym-1 epitopic region, have been linked to generate small (<2 kDa) molecules (referred to as selective high-affinity ligands [SHALs]) to mimic the targeting properties of Lym-1 Ab. METHODS: A lysine-polyethylene glycol (PEG) backbone was used to synthetically link 2 of the following ligands: deoxycholate, 5-leuenkephalin, triiodothyronine, thyronine, dabsyl-L-valine, and N-benzoyl-L-arginyl-4-amino-benzoic acid to generate a series of 13 bidentate SHALs with a biotin or 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid (DOTA) chelate attached to the linker. These SHALs have been assessed for their selectivity in binding to HLA-DR10-expressing cells and for their pharmacokinetics and tissue biodistribution in mice. Biotinylated versions of these SHALs discriminated cell lines positive for HLA-DR10 expression with near-nanomolar affinity. The DOTA versions of 4 SHALs were labeled with (111)In for pharmacokinetic studies in mice with HLA-DR10-expressing malignant Raji xenografts. RESULTS: The bidentate, biotinylated, and DOTA-SHALs were synthesized in high-purity, multimilligram amounts. Mean radiochemical and product yields and purities were 90%, 75%, and 90% at mean specific activities of 3.9 MBq/microg (105 microCi/microg) for the (111)In-labeled SHALs. As expected, rapid blood clearance and tumor targeting were observed. The pharmacokinetics of the SHALs was influenced by the component ligands. Biliary clearance, kidney localization, and serum receptor binding contributed to less favorable tumor targeting. CONCLUSION: A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.     

Analysis of three-dimensional sinter shrinkage of copings made from alumina in an innovative direct shaping process.

The three-dimensional (3D) evaluation and comparison of free-form-surfaces is a complex problem [Dent. Mater. 8 (1992) 49; J. Dent. Res. 76 (1997) 1799; Dent. Mater. 16 (2000) 145; J. Prosthet. Dent. 70 (1993) 457; Dent. Mater. 19 (2003) 19]. However, it is essential in order to analyze the sinter shrinkage of dental ceramic-restorations where isotropic and linear shrinkage is desired for accurate fit on the prepared teeth. In this article, we examine the 3D sinter shrinkage in general and for nine copings from alumina in particular. Using various scaled CAD-models in an iteration scheme, each model was compared to the filtered point cloud of the coping, determining the surface-cloud difference. The magnitude of deviations from linear sinter shrinkage was investigated. Furthermore, a new fabrication process for ceramic-restorations is introduced.