Safety and efficacy of atorvastatin in patients with severe renal dysfunction.

OBJECTIVE: To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. MATERIAL AND METHODS: This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. RESULTS: The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. CONCLUSION: Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Motorneuron protection by N-acetyl-cysteine after ventral root avulsion and ventral rhizotomy.

Motor recovery after proximal nerve injury remains extremely poor, despite advances in surgical care. Several neurobiological hurdles are implicated, the most fundamental being extensive cell death within the motorneuron pool. N-acetyl-cysteine almost completely protects sensory neurons after peripheral axotomy, hence its efficacy in protecting motorneurons after ventral root avulsion/rhizotomy was investigated. In adult rats, the motorneurons supplying medial gastrocnemius were unilaterally pre-labelled with retrograde tracer (true-blue/fluoro-gold), prior to L5 and 6 ventral root avulsion, or rhizotomy. Groups received either intraperitoneal N-acetyl-cysteine (ip, 150 or 750 mg/kg/day), immediate or delayed intrathecal N-acetyl-cysteine treatment (it, 2.4 mg/day), or saline; untreated animals served as controls. Either 4 (avulsion model) or 8 (rhizotomy model) weeks later, the pre-labelled motorneurons' mean soma area and survival were quantified. Untreated controls possessed markedly fewer motorneurons than normal due to cell death (avulsion 53% death; rhizotomy 26% death, P<0.01 vs. normal). Motorneurons were significantly protected by N-acetyl-cysteine after avulsion (ip 150 mg/kg/day 40% death; it 30% death, P<0.01 vs. no treatment), but particularly after rhizotomy (ip 150 mg/kg/day 17% death; ip 750 mg/kg/day 7% death; it 5% death, P<0.05 vs. no treatment). Delaying intrathecal treatment for 1 week after avulsion did not impair neuroprotection, but a 2-week delay was deleterious (42% death, P<0.05 vs. 1-week delay, 32% death). Treatment prevented the decrease in soma area usually found after both types of injury. N-acetyl-cysteine has considerable clinical potential for adjuvant treatment of major proximal nerve injuries, including brachial plexus injury, in order that motorneurons may survive until surgical repair facilitates regeneration.

Instantaneous axis of rotation as a function of the three columns of the spine.

A knowledge of the rotatory motion of the vertebral bodies is needed to understand the normal biomechanical behavior of the spine. The aims of this investigation were 1) to define the instantaneous axis of rotation of the lumbar spine in rotation; and 2) to study the effect of the loss of the anulus, facet joints, and ligamentous structures on the location of the instantaneous axis of rotation. The instantaneous axis of rotation was found in 10 human cadaver thoracolumbar spines by the method of Reuleaux from superimposed serial photographs. Long-segment specimens were tested to minimize the effect of the imposed axis of the testing device. The instantaneous axis of rotation was consistently posterior to the anulus in the intact spine. With isolated destruction of the columns of the spine, the instantaneous axis of rotation migrated to the remaining intact structures. Anterior releases enhance derotation by removing the primary rotatory stabilizer. Ultimate control of a rotatory deformity or instability lies in the recognition that the anterior structures have a mechanical advantage in resisting torsion.

The effect of the three columns of the spine on the instantaneous axis of rotation in flexion and extension.

Instrumentation designed for stabilization and correction of spinal deformities must limit the amount of motion in flexion and extension. In flexion or extension, the vertebral bodies move about a specific point called the instantaneous axis of rotation. The ability of the implant to limit this motion is a function of its relation to the axis of rotation of the spine. The goal of this study was threefold: 1) to define the instantaneous axis of rotation of the spine in flexion and extension; 2) to study the effect of the loss of the three columns of the spine on the location of the instantaneous axis of rotation; and 3) to determine how the above parameters relate to the choice of anterior or posterior instrumentation. Ten human cadaver spines were subjected to compressive loads in flexion and extension. The columns of the spine were then destroyed in sequence at L3. The instantaneous axis of rotation for each vertebral body was found by the method of Reuleaux, and the effect of the compromise of the columns on the location of the instantaneous axis of rotation was noted. Understanding the exact location of the instantaneous axis of rotation after a specific injury would allow the clinician to objectively choose the best surgical approach and the appropriate instrumentation.

The contribution of the three columns of the spine to rotational stability. A biomechanical model.

A function of the spine as a structural column is its ability to resist torsion. The goal of this study was to evaluate the contribution of the columns of the spine to torsional rigidity. Ten human cadaver spines were harvested and frozen. The specimens, consisting of segments from T11 to S1, were subjected to torsional loads of up to 20 N-m. Rotation was recorded throughout the loading cycle. The columns of the spine were destroyed at the L2-3 interspace in a predetermined fashion and loading was repeated. The data were plotted as torsion versus rotation in degrees. The curves of each loading cycle were compared and the ratios of the intact and compromised specimens were calculated. The contribution of each column of the spine to torsional rigidity was determined. In an intact lumbar spine, the anulus was the most effective structure in resisting torsion. Experience gained in this study supports the following conclusion: Flexion-distraction injuries of the thoracolumbar and lumbar spine involving soft tissue destruction of the anterior column and anulus result in rotational instability.