Vertebroplasty, the augmentation of vertebral compression fractures by image-controlled intracorporeal injection of polymethylmethacrylate cement, has shown a steady increase in use. Its chief indication is to palliate pain after a failure of noninvasive therapies. Other benefits include preventing further compression of the treated vertebra and fusing unstable fractures. Controversies include questions regarding its long-term benefit compared with natural history, claims of height restoration, biomechanical compromise of adjacent vertebrae, and its performance compared with kyphoplasty. Complications are uncommon but can be devastating with reported cases of procedural death and paralysis. New operators should be adequately trained and respect the dangers of this procedure.
The hypertriglyceridemia of diabetes is accompanied by decreased lipoprotein lipase (LPL) activity in adipocytes. Although the mechanism for decreased LPL is not known, elevated glucose is known to increase diacylglycerol, which activates protein kinase C (PKC). To determine whether PKC is involved in the regulation of LPL, we studied the effect of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on adipocytes. LPL activity was inhibited when TPA was added to cultures of 3T3-F442A and rat primary adipocytes. The inhibitory effect of TPA on LPL activity was observed after 6 h of treatment, and was observed at a concentration of 6 nM. 100 nM TPA yielded maximal (80%) inhibition of LPL. Long term treatment of cells with TPA is known to down-regulate PKC. To assess the involvement of the different PKC isoforms, Western blotting was performed. TPA treatment of 3T3-F442A adipocytes decreased PKC ␣, , ␦, and ⑀ isoforms, whereas PKC , , , , , and ␥ remained unchanged or decreased minimally. To directly assess the effect of PKC inhibition, PKC inhibitors (calphostin C and staurosporine) were added to cultures. The PKC inhibitors inhibited LPL activity rapidly (within 60 min). Thus, activation of PKC did not increase LPL, but inhibition of PKC resulted in decreased LPL synthesis by inhibition of translation, indicating a constitutive role of PKC in LPL gene expression. Lipoprotein lipase (LPL)1 is a central enzyme in lipid metabolism that is expressed primarily in adipose tissue and muscle (1). The regulation of lipoprotein lipase is complex and regulation may occur at the transcriptional, translational, and posttranslational levels (2). LPL activity is decreased in the adipose tissue of patients with diabetes. After treatment to control hyperglycemia in both type I and type II diabetes, there is an increase in LPL activity (3, 4), along with an increase in LPL synthetic rate with no change in LPL mRNA, suggesting regulation at the level of translation (5). Similar observations have been made in experimental models of insulin-deficient diabetic rats. Whereas short term insulin treatment of insulin-deficient rats increased LPL protein more than LPL mRNA, prolonged insulin treatment increased both LPL protein and LPL mRNA levels (6).Glucose and insulin modulate protein kinase C (PKC) activity in rat adipocytes (7). Hyperglycemia is known to increase cellular diacylglycerol (DAG), which in turn is the natural activator of PKC. Elevated DAG, resulting in PKC activation has been identified in insulin-deficient diabetic adipose tissue (8 -10). The role of hyperinsulinemia and hyperglycemia in the activation of PKC isoforms and involvement in insulin resistance has been studied in various animal models of diabetes (11). PKC is present in the soluble cytoplasmic fraction in cells prior to stimulation, and the treatment of cells with the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) resulted in activation and translocation of PKC to the membrane. TPA activates PKC by interacting with the DAG binding site (12), although the...
UNGAL CONTAMINATION OF METHylprednisolonepreparedbyacompoundingpharmacyresultedinan unprecedented multistate outbreak of meningitis in the fall of 2012. 1-4 Michiganhashadthehigheststate-specific attack rate for fungal infection associated with the contaminated spinal or paraspinal injections. 5,6 Initially, these injections were complicated by meningitis. Within 6 weeks of the outbreak, meningitis becamelessfrequentandlocalizedspinaland paraspinal infections became the principal manifestations of contaminated steroidinjections.Incontrasttotherelatively brief period in which meningitis cases appeared, a steady stream of spinal and paraspinal infections continue to present long aftertheinjectionswerelastadministered. For editorial comment see p 2493.
Background. A nationwide outbreak of fungal infections was traced to injection of Exserohilum-contaminated methylprednisolone. We describe our experience with patients who developed spinal or paraspinal infection after injection of contaminated methylprednisolone.Methods. Data were assembled from the Michigan Department of Community Health, electronic medical records, and magnetic resonance imaging (MRI) reports.Results. Of 544 patients who received an epidural injection from a contaminated lot of methylprednisolone at a pain clinic in southeastern Michigan, 153 (28%) were diagnosed at our institution with probable or confirmed spinal or paraspinal fungal infection at the injection site. Forty-one patients had both meningitis and spinal or paraspinal infection, and 112 had only spinal or paraspinal infection. Magnetic resonance imaging abnormalities included abscess, phlegmon, arachnoiditis, and osteomyelitis. Surgical debridement in 116 patients revealed epidural phlegmon and epidural abscess most often. Among 26 patients with an abnormal MRI but with no increase or change in chronic pain, 19 (73%) had infection identified at surgery. Fungal infection was confirmed in 78 patients (51%) by finding hyphae in tissues, positive polymerase chain reaction, or culture. Initial therapy was voriconazole plus liposomal amphotericin B in 115 patients (75%) and voriconazole alone in 38 patients (25%). As of January 31, 2014, 20 patients remained on an azole agent. Five patients died of infection.Conclusions. We report on 153 patients who had spinal or paraspinal fungal infection at the site of epidural injection of contaminated methylprednisolone. One hundred sixteen (76%) underwent operative debridement in addition to treatment with antifungal agents.
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