Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy

BACKGROUND AND PURPOSE: Proton MR spectroscopy has revealed impaired neuronal integrity in the motor cortex of patients with amyotrophic lateral sclerosis (ALS). We hypothesized that the N-acetylaspartate (NAA)-creatine (Cr) ratios in the motor cortex and adjacent brain could reflect the therapeutic effectiveness of gabapentin (GBP) treatment in ALS. METHODS: Eight patients with ALS underwent MR spectroscopy before and 26.5 days +/- 8.8 after starting GBP. In 10 patients with ALS who were not treated with GBP, paired spectra were obtained 21.4 days +/- 7.2 apart. Fourteen healthy subjects underwent a single MR spectroscopic examination. The NAA/Cr ratio was measured in the precentral gyrus, the postcentral gyrus, the superior parietal lobule, the supplementary motor area, and the premotor cortex. RESULTS: The NAA/Cr ratio was decreased in the precentral and postcentral gyri of patients with ALS compared with healthy controls. In those with ALS, the change in the NAA/Cr ratio was not different between treated patients and untreated patients in any of the regions studied. CONCLUSION: No improvement in neuronal integrity was detected in motor and nonmotor cerebral regions after GBP treatment. This result agrees with that of prior investigations showing the equivocal clinical effectiveness of GBP for ALS and supports the validity of the NAA/Cr ratio as a surrogate of therapeutic effectiveness.     

Injury and fitness outcomes during implementation of physical readiness training

This study examined injury and physical fitness outcomes in Basic Combat Training (BCT) during implementation of Physical Readiness Training (PRT). PRT is the U.S. Army's emerging physical fitness training program. An experimental group (EG, n = 1284), which implemented the PRT program, was compared to a control group (CG, n = 1296), which used a traditional BCT physical training program during the 9-week BCT cycle. Injury cases were obtained from recruit medical records and physical fitness was measured using the U.S. Army Physical Fitness Test (APFT, consisting of push-ups, sit-ups and a two-mile run). Injury rates were examined using Cox regression after controlled for initial group differences in demographics, fitness and other variables. Compared to the EG, the adjusted relative risk of a time-loss overuse injury in the CG was 1.5 (95 % confidence interval [CI] = 1.0 - 2.1, p < 0.01) for men and 1.4 (95 %CI = 1.1 - 1.8, p < 0.01) for women. There were no differences between groups for traumatic injuries. On the first administration of the final APFT, the EG had a greater proportion of recruits passing the test than the CG (men: 85 % vs. 81 %, p = 0.04; women: 80 % vs. 70 %, p < 0.01). After all APFT retakes, the EG had significantly fewer APFT failures than the CG among the women (1.6 % vs. 4.6 %, p < 0.01) but not the men (1.6 % vs. 2.8 %, p = 0.18); the gender-combined EG had a higher pass rate (1.6 % vs. 3.7 %, p < 0.01). Overall, the PRT program reduced overuse injuries and allowed a higher success rate on the APFT.     

Carpal bone postures and motions are abnormal in both wrists of patients with unilateral scapholunate interosseous ligament tears

PURPOSE: The recent ability to measure 3-dimensional in vivo carpal kinematics has facilitated the noninvasive study of complex carpal bone motion. METHODS: In this study we examined the flexion/extension carpal kinematics of both wrists in 8 patients with unilateral scapholunate interosseous ligament (SLIL) tears by using computed tomographic (CT) imaging and a markerless bone registration technique. Carpal bone neutral posture and flexion/extension motion of both wrists of the injured patients were compared with the same parameters in wrists of 10 uninjured male and female volunteers (normals). RESULTS: The neutral posture of the injured scaphoid and lunate were significantly more extended than those of normals. In these patients, however, the postures of the scaphoid and lunate in the contralateral uninjured wrists also were abnormal and were similar to those of the injured wrist. In addition, extension of the lunate and flexion of the scaphoid in both the injured and uninjured wrist were significantly different from normal but not different from each other. CONCLUSIONS: This study was unable to attribute altered carpal posture and motion to SLIL tears because abnormalities were found in both wrists of patients with unilateral injury. The etiology of abnormal wrist kinematics in the asymptomatic wrist of patients with unilateral tears of the scapholunate ligament is not known.     

Pressure-controlled ventilation attenuates lung microvascular injury in a rat model of activated charcoal aspiration

BACKGROUND: Previous animal data suggest that aspiration of activated charcoal is associated with pulmonary microvascular injury that may be related to excessive ventilator-induced airway pressures. The purpose of this study was to test the hypothesis that ventilator-induced airway trauma contributes to the lung vascular injury observed following activated charcoal aspiration. METHODS: Capillary filtration coefficient (Kf,c), a sensitive measure of lung microvascular permeability, was determined isogravimetrically prior to and after intratracheal instillation of 0.4 ml/kg (12% weight/vol. solution, pH 7.4) activated charcoal oran equal volume of sterile water in isolated, perfused rat lungs in which ventilation was either pressure-controlled at 10cm H2O or volume-controlled at 5 ml/kg. RESULTS: There was significant lung injury in both activated charcoal groups regardless of ventilation method compared to control lungs or lungs administered sterile water (p < 0.05 ANOVA). However, injury to pressure-controlled ventilated lungs was significantly less than lungs ventilated with traditional, volume-controlled ventilation. CONCLUSION: The results of this investigation demonstrate that pressure-controlled ventilation reduces the lung microvascular injury observed following aspiration of activated charcoal as compared to traditional volume-controlled ventilation methods.     

Rat subchronic inhalation study of smoke from cigarettes containing flue-cured tobacco cured either by direct-fired or heat-exchanger curing processes

A subchronic, nose-only inhalation study compared the effects of mainstream smoke from a cigarette containing 100% flue-cured tobacco cured by a direct-fired process to that of a cigarette containing 100% flue-cured tobacco cured by a heat exchanger process. The tobaccos and mainstream smoke from tobaccos cured by the heat exchanger process have been shown to have significantly lower levels of tobacco-specific nitrosamines than tobaccos cured by a direct-fired process. Male and female rats were exposed for 1 h/day, 5 days/wk, for 13 wk to mainstream smoke at 0, 0.06, 0.20, or 0.80 mg wet total particulate matter per liter of air. Clinical signs, body and organ weights, clinical chemistry, hematology, carboxyhemoglobin, serum nicotine, plethysmography, gross pathology, and histopathology were determined. When histologic changes resulting from exposure to smoke from the two types of cigarettes were compared, the only significant difference was increased epithelial hyperplasia of the anterior nasal cavity in males in the high-exposure group for the heat-exchanger cigarette. At the end of the exposure period, subsets of rats from each group were maintained without smoke exposures for an additional 13 wk (recovery period). At the end of the recovery period, there were no statistically significant differences in histopathological findings observed between the heat-exchanger-cured tobacco cigarette when compared to the direct-fired cured tobacco cigarette. The complete toxicological assessment in this study of heat exchanger and direct-fired tobaccos suggests no overall biologically significant differences between the two cigarettes.     

Personality conflicts and objectivity in appraising performance

A daunting challenge for any health care manager is to be involved in a personality conflict with an employee and then maintain objectivity in appraising that employee's performance. This article explores the relationship between personality conflicts and performance appraisal. Types of perceptual problems, such as recent behavior bias and horn effect, are discussed. Methods for involving input from appropriate individuals other than the manager and ways managers can improve objectivity in appraising performance are covered.     

Randomized,double-blind,placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain

This randomized, controlled trial compared the analgesic efficacy and safety of the new oxycodone 10-mg/acetaminophen 325-mg formulation (Percocet) for the treatment of acute pain following oral surgery with double the dose of oxycodone alone (controlled-release [CR] oxycodone 20 mg [OxyContin]). A total of 150 male and female patients with > or = 2 full or partial bone-impacted mandibular molars, at least moderate persistent pain, and moderate trauma received a single dose of combination agent, CR oxycodone, or placebo following oral surgery and rated pain intensity and pain relief over the next 6 hours. The intent-to-treat population comprised 141 patients (55 on combination agent, 56 on oxycodone, and 30 on placebo). Combination agent and CR oxycodone were significantly superior to placebo for all efficacy measures. Combination agent was statistically superior to CR oxycodone in four of five outcome measures of pain intensity and pain relief (PPID, PPAR, SPID, and SPRID). It also provided a faster onset and 24% reduction in the number of patients reporting treatment-related adverse events compared with twice the dose of opioid alone. This new formulation offers the combination of two analgesic drugs with complementary mechanisms of action, which results in enhanced analgesia, an "opioid-sparing" effect, and an improved side effect and safety profile.     

Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: a review of the literature

The safety, tolerability, and efficacy of the lidocaine patch 5% (Lidoderm), a targeted peripheral analgesic with an FDA-approved indication for the treatment of postherpetic neuralgia, has been well established. Recent case reports and studies have suggested potential efficacy in other neuropathic and nonneuropathic pain conditions. Several pharmacokinetic studies have demonstrated minimal systemic absorption with 12-, 18-, and 24-hour/day dosing. Mean maximum plasma concentrations have shown the lidocaine patch to possess a minimal risk for systemic toxicities or drug-drug interactions. The most common adverse events generally involve mild skin reactions. There have been no drug-drug interactions noted in clinical trials. Recent evidence suggests that extended application does not result in A-beta-mediated sensory loss at the application site, which is particularly important in patients who already have a degree of sensory loss due to their underlying condition. The lidocaine patch provides a treatment option that carries a relatively low systemic adverse event and drug-drug interaction risk burden, even with continuous application of up to four patches per day.     

Nitric oxide donor molsidomine favors features of atherosclerotic plaque stability during cholesterol lowering in rabbits

Rupture-prone atherosclerotic plaques are characterized by a thin fibrous cap containing numerous macrophage-derived foam cells and few smooth muscle cells (SMC). Decreasing the ratio between macrophages and SMC might favor plaque stabilization. Macrophages expressing inducible nitric oxide (NO) synthase become hypersensitive to killing by exogenous NO donors. Therefore, we investigated in cholesterol-fed rabbits (20 weeks 0.3% cholesterol) the effect of 4 weeks cholesterol withdrawal alone and in combination with the NO donor molsidomine on plaque size, cell composition, superoxide production and extracellular superoxide dismutase (ecSOD) mRNA expression in the atherosclerotic plaques in the aorta. Cholesterol withdrawal alone did not alter atherosclerotic plaque size, the increased superoxide production or the decreased ecSOD mRNA, but led to the formation of a thin subendothelial macrophage-free layer and reduced both vascular cell adhesion molecule-1 expression and cell replication in the luminal part of the plaques. Treatment with molsidomine (1 mg/kg/day) during cholesterol withdrawal did not affect plaque size but increased the thickness of the subendothelial macrophage-free layer consisting of SMC, and normalized both superoxide production and ecSOD mRNA expression. The latter findings demonstrate that molsidomine, when combined with cholesterol lowering, decreases signs of oxidative stress and increases features of stable atherosclerotic plaques.