Assessing the Stiffness of Spinal Fusion in Animal Models

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines. We hypothesized that this method would be more sensitive than manual palpation and would be able to distinguish unilateral vs bilateral fusion. Spines from four mixed breed dogs and four New Zealand white rabbits were used to simulate posterolateral fusion with polymethyl methacrylate as the fusion mass. We performed manual palpation and nondestructive mechanical testing in four-point bending in four planes of motion: flexion, extension, and right and left bending. This testing protocol was used for each specimen in three fusion modes: intact, unilateral, and bilateral fusion. Under manual palpation, all intact spines were rated as not fused, and all unilateral and bilateral simulated fusions were rated as fused. In four-point bending, dog spines were significantly stiffer after unilateral fusion compared with intact in all directions. Additionally, rabbit spines were stiffer in flexion and left bending after unilateral fusion. All specimens exhibited significant differences between intact and bilateral fusion except the rabbit in extension. For unilateral vs bilateral fusion, significant differences were present for right bending in the dog model and for flexion in the rabbit. Unilateral fusion can provide enough stability to constitute a fused grade by manual palpation but may not provide structural stiffness comparable to bilateral fusion.     

Risperidone and falls in ambulatory nursing home residents with dementia and psychosis or agitation: secondary analysis of a double-blind, placebo-controlled trial.

OBJECTIVE: Authors evaluated the association between use/dosage of risperidone (RIS) and falls in a residential-care dementia population. METHODS: Authors performed secondary analysis of data from ambulatory patients in a randomized, double-blind, placebo-controlled, 12-week trial of three RIS dosages (0.5 mg/day, 1 mg/day, 2 mg/day). Outcomes included number of fallers, rate of falls, and time until the first fall after randomization. Additional analyses evaluated wandering as a potential moderating or mediating variable. RESULTS: The ambulatory sample included 537 subjects. Of those, 22.3% on placebo, 18.0% on RIS 0.5 mg/day, 12.7% on 1 mg/day, and 27.3% on 2 mg/day, respectively, fell during the trial. The difference between the RIS 1 mg/day group and placebo was significant, with a significantly lower hazard ratio in the RIS 1-mg/day group than placebo. Wandering was associated with an increased risk of falls. Among 205 patients with the highest levels of wandering at baseline, RIS 1 mg/day was associated with approximately a 70% reduction in risk for falls versus placebo condition. However, in those with the lowest levels of wandering at baseline, RIS 2 mg/day may have increased the risk of falls. CONCLUSIONS: Evaluating the benefits versus risks of risperidone in patients with dementia is complex and must consider multiple outcomes as a function of dose. At 1 mg/day, RIS was associated with decreased falls, especially in patients who exhibit wandering. However, at 2 mg/day, it may increase the risk of falls in ambulatory individuals with low levels of wandering.     

Increased response of renal perfusion to the antioxidant vitamin C in type 2 diabetes.

BACKGROUND: Reactive oxygen species play a major role in the development of endothelial dysfunction. It is as yet unspecified whether increased oxidative stress contributes to endothelial dysfunction of the renal vasculature in patients with type 2 diabetes. METHODS: Renal haemodynamics were studied in 20 patients with type 2 diabetes and arterial hypertension (age 62 +/- 5 years) and 20 non-diabetic hypertensive patients at baseline and following infusions of the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg); the substrate of nitric oxide synthase, L-arginine (100 mg/kg); and the antioxidant, vitamin C (3 g, co-infused with L-arginine 100 mg/kg). RESULTS: The response of renal plasma flow (RPF) to L-NMMA (-54 +/- 62 and -45 +/- 42 ml/min/1.73 m(2); P = NS) and L-arginine (+46 +/- 36 and +49 +/- 25 ml/min/1.73 m(2); P = NS) was not different between diabetic and non-diabetic patients. In contrast, vitamin C induced a more pronounced increase in RPF in diabetic than in non-diabetic patients when co-infused with L-arginine (+71+/-47 and +43+/-33 ml/min/1.73 m(2); P<0.05). CONCLUSIONS: The difference in the response of renal perfusion to an antioxidant suggests increased formation of reactive oxygen species and thereby reduced nitric oxide bioavailability in the renal vasculature of patients with type 2 diabetes.