Persistent Hypotension Associated with Hypermedullipinemia: A New Syndrome

A new syndrome is described in a patient with advanced renal insufficiency. This consists of severe and persistent hypotension causing weakness but associated with a clear mental status. Also present is evidence for decreased vascular reactivity. The hypotension was not orthostatic. The hypotension was associated with a circulating vasodepressor substance having the characteristics of medullipin I. The medullipin appears to have been derived from the remaining right kidney. Hypotension existed despite the presence of major prohypertensive mechanisms, including an endstage kidney, hyperreninemia and hyperaldosteronemia. It is likely that hypotension due to hypermedullipinemia is an entity occurring in the human being.     

db/db mice exhibit severe wound-healing impairments compared with other murine diabetic strains in a silicone-splinted excisional wound model

The pathophysiology of diabetic wound healing and the identification of new agents to improve clinical outcomes continue to be areas of intense research. There currently exist more than 10 different murine models of diabetes. The degree to which wound healing is impaired in these different mouse models has never been directly compared. We determined whether differences in wound impairment exist between diabetic models in order to elucidate which model would be the best to evaluate new treatment strategies. Three well-accepted mouse models of diabetes were used in this study: db/db, Akita, and streptozocin (STZ)-induced C57BL/6J. Using an excisional model of wound healing, we demonstrated that db/db mice exhibit severe impairments in wound healing compared with STZ and Akita mice. Excisional wounds in db/db mice show a statistically significant delay in wound closure, decreased granulation tissue formation, decreased wound bed vascularity, and markedly diminished proliferation compared with STZ, Akita, and control mice. There was no difference in the rate of epithelialization of the full-thickness wounds between the diabetic or control mice. Our results suggest that splinted db/db mice may be the most appropriate model for studying diabetic wound-healing interventions as they demonstrate the most significant impairment in wound healing. This study utilized a novel model of wound healing developed in our laboratory that stents wounds open using silicone splints to minimize the effects of wound contraction. As such, it was not possible to directly compare the results of this study with other studies that did not use this wound model.     

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.     

Reference and target region modeling of [11C]-(R)-PK11195 brain studies.

PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain.