The aim of this study is to determine the predictive values of laboratory indicators of pyogenic vertebral osteomyelitis (PVO) and a potential cure if the microorganism cannot be identified. Forty-five consecutive patients with PVO were enrolled. Antibiotic therapy with or without surgery was performed according to microorganism. In the negative-culture (NC) group, cefazolin was administered in cases of hematogenous PVO, and vancomycin was administered in cases of postoperative or procedure-related PVO. The clinical, laboratory, and radiological findings were followed up with regard to an appropriate response to antimicrobial therapy. Nine patients were treated with antibiotics alone. We were able to identify the microorganism in 34 cases (75.6%). Ten cases in NC group were cured without recurrence, but one was not. Identification of the microorganisms did not have any significant influence on the treatment outcome, duration of antibiotic administration or normalization of laboratory profiles. For erythrocyte sedimentation rate (ESR) values over 55 mm/h and C-reactive protein (CRP) values of 2.75 mg/dL at fourth week after antibiotic administration by means of ROC curve analysis, we expect significantly high rates of treatment failure by Pearson chi(2) test (chi(2) = 4.344, Odds ratio = 5.15, p = 0.037, 95% CI 1.004-26.597). Even in patients with negative culture findings, it is expected that a good outcome will be achieved by the administration of cefazolin or vancomycin for about 6 weeks. It is concluded that antibiotics selected according to the etiological setting can be initiated without the need to start empirical antibiotics. In every instance at fourth week after the initiation of antibiotic therapy, the values of CRP and ESR can provide meaningful information regarding whether clinicians need to reevaluate the effectiveness of antibiotics by performing follow-up imaging studies and monitoring the patient's clinical manifestations.
Paragangliomas of the cauda equina are rare neuroendocrine tumors. Four cases of nonsecreting paraganglioma of the cauda equina, preoperatively misdiagnosed as neurinoma, are presented with an emphasis on the correlation between magnetic resonance imaging findings and pathological features. Although it is difficult to correctly diagnose paraganglioma preoperatively for intradural extramedullary tumors, especially in the cauda equina, paraganglioma should be included in differential diagnoses.
The systemic treatment with angiogenesis inhibitor has been shown to result in weight reduction and adipose tissue loss in various models of obesity. To verify the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732's peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.) in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates. Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion (CTA) was performed using lithium chloride (LiCl) as a positive control agent in Long-Evans Tokushima Otsuka and Otsuka Long-Evans Tokushima fatty (OLETF) rats. As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake and the body weight significantly in both treated obese (e.g. 114 . 8G13 . 4 g vs 170 . 7G20 . 6 g, 7 . 9G0 . 5% decrease vs 0 . 3G2 . 2% decrease; in treated OLETF rat versus control OLETF rat, P!0 . 01 respectively) and non-obese models. Epididymal and mesenteric fat pads, and the size of adipocytes were significantly decreased in treated rats. A single i.c.v. injection decreased food intake and body weight in ARC lesion mice and ob/ob mice but not in normal littermates. Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl injection, which is a commonly used agent to produce a CTA. In conclusion, CKD-732 causes significant body weight and appetite reduction, possibly by decreasing adiposity directly and inducing central anorexia, which is partly explained by a CTA. These results should be carefully verified to assess the utility of CKD-732 as an anti-obesity drug.
The development of heterotopic ossification (HO) is considered one of the major complications following cervical total disc replacement (TDR). Even though previous studies have identified clinical and biomechanical conditions that may stimulate HO, the mechanism of HO formation has not been fully elucidated. The objective of this study is to investigate whether mechanical loading is a biomechanical condition that plays a substantial role to decide the HO formation. A finite element model of TDR on the C5-C6 was developed, and HO formation was predicted by simulating a bone adaptation process under various physiological mechanical loadings. The distributions of strain energy on vertebrae were assessed after HO formation. For the compressive force, most of the HO formation occurred on the vertebral endplates uncovered by the implant footplate which was similar to the Type 1 HO. For the anteriorly directed shear force, the HO was predominantly formed in the anterior parts of both the upper and lower vertebrae as the Type 2 HO. For both the flexion and extension moments, the HO shapes were similar to those for the shear force. The total strain energy was reduced after HO formation for all loading conditions. Two distinct types of HO were predicted based on mechanically induced bone adaptation processes, and our findings were consistent with those of previous clinical studies. HO formation might have a role in compensating for the non-uniform strain energy distribution which is one of the mechanical parameters related to the bone remodeling after cervical TDR.
The aim of this study was to analyze the clinical characteristics of thoracic ossified ligamentum flavum (OLF) and to elucidate prognostic factors as well as effective surgical treatment modality. The authors analyzed 106 thoracic OLF cases retrospectively from January 1999 to December 2008. The operative (n = 40) and the non-operative group (n = 66) were diagnosed by magnetic resonance imaging (MRI) and/or computed tomography (CT) imaging. We excluded cases exhibiting ventral compressive lesions causing subarachnoid space effacement in thoracic vertebrae as well as those with a coexisting cervical compressive myelopathy. Those in the operative group were treated with decompressive laminectomy as well as resection of OLF. The preoperative neurologic status and postoperative outcomes of patients, as indicated by their modified Japanese Orthopedic Association (mJOA) scores and recovery rate (RR), Modic changes, the axial (fused or non-fused) and sagittal (omega or beak) configurations of OLF, and the ratios of the cross-sectional area (CSA) and anteroposterior diameter (APD) of the most compressed level were studied. The most commonly affected segment was the T10-11 vertebral body level (n = 49, 27.1%) and the least affected segment was the T7-8 level (n = 1, 0.6%). The ratios of the CSA in non-fused and fused types were 77.3 and 59.3% (p < 0.001). When Modic changes were present with OLF, initial mJOA score was found to be significantly lower than those without Modic change (7.62 vs. 9.09, p = 0.033). Neurological status improved after decompressive laminectomy without fusion (preoperative vs. last mJOA; 7.1 ± 2.01 vs. 8.57 ± 1.91, p < 0.001). However, one patient exhibited transient deterioration of her neurological status after surgery. In the axial configuration, fused-type OLF revealed a significant risk for a decreased postoperative mJOA score (0-7, severe and moderate) (Odds ratio: 5.54, χ (2) = 4.41, p = 0.036, 95% CI: 1.014-30.256). The results indicated that the new categorization of axial-type of OLF is a helpful predictor of postoperative patient outcome and fused type was related with poor prognosis. In OLF cases free from ventral lesions compressing the spinal cord, decompressive laminectomy is enough for successful surgical outcome. Therefore, early surgical treatment will be considered in cases with fused-type OLF compressing spinal cord even though they do not have myelopathic symptoms.
In vitro treatment with a pharmacological dose of simvastatin, a potent pro-drug of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, stimulates bone formation. In our study, simvastatin stimulated differentiation of osteoblasts remarkably in a dose-dependent manner, with minimal effect on proliferation. To identify the mediators of the anabolic effects of simvastatin on osteoblasts, we tried to identify and characterize simvastatin-induced proteins by using proteomic analysis. Calcyclin was significantly up-regulated by more than 10 times, and annexin I was also up-regulated by simvastatin. However, annexin III, vimentin, and tropomyosin were down-regulated. Up-regulated calcyclin mRNA by simvastatin was validated by reverse transcription in mouse calvarial cells. In confocal microscope analysis, green fluorescence protein-calcyclin fusion protein was ubiquitously observed in the of MC3T3-E1 cells transfected with green fluorescence protein-calcyclin cDNA containing plasmid and was quickly concentrated in the nucleus 20 min after simvastatin treatment. Overexpression of calcyclin cDNA stimulated both the proliferation and expression of alkaline phosphatase mRNA significantly, without exposure to simvastatin in MC3T3-E1 cells. However, both the rate of proliferation of the osteoblasts and the expression of alkaline phosphatase mRNA were suppressed significantly 1 day after treatment with the calcyclin-specific small interference RNA, and furthermore, simvastatin did not overcome this suppression in the small interference RNApretreated MC3T3-E1 cells. In conclusion, calcyclin is one of the candidate proteins that plays a role in osteoblastogenesis in response to simvastatin, although the precise functions of calcyclin in osteoblast remain to be verified.
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