Surgery versus conservative management of sciatica due to a lumbar herniated disc: a systematic review

The effectiveness of surgery in patients with sciatica due to lumbar disc herniations is not without dispute. The goal of this study was to assess the effects of surgery versus conservative therapy (including epidural injections) for patients with sciatica due to lumbar disc herniation. A comprehensive search was conducted in MEDLINE, EMBASE, CINAHL, CENTRAL, and PEDro up to October 2009. Randomised controlled trials of adults with lumbar radicular pain, which evaluated at least one clinically relevant outcome measure (pain, functional status, perceived recovery, lost days of work) were included. Two authors assessed risk of bias according to Cochrane criteria and extracted the data. In total, five studies were identified, two of which with a low risk of bias. One study compared early surgery with prolonged conservative care followed by surgery if needed; three studies compared surgery with usual conservative care, and one study compared surgery with epidural injections. Data were not pooled because of clinical heterogeneity and poor reporting of data. One large low-risk-of-bias trial demonstrated that early surgery in patients with 6–12 weeks of radicular pain leads to faster pain relief when compared with prolonged conservative treatment, but there were no differences after 1 and 2 years. Another large low-risk-of-bias trial between surgery and usual conservative care found no statistically significant differences on any of the primary outcome measures after 1 and 2 years. Future studies should evaluate who benefits more from surgery and who from conservative care.     

Respiratory Allergy to Trimellitic Anhydride in Rats: Concentration-Response Relationships During Elicitation

The present study investigated whether airway responses of sensitized rats to trimellitic anhydride (TMA) were concentration dependent and whether these were related to irritation by TMA. Groups of BN and Wistar rats were sensitized by two dermal applications of TMA (50% w/v, followed by 25% w/v in vehicle). Controls received vehicle (acetone–olive oil 4:1, v/v). All animals were challenged 3 wk after the first sensitization by inhalation of one of a range of concentrations of TMA (0.2–61 mg/m³ for BN rats, 15–250 mg/m³ for Wistar rats). Breathing pattern, breathing frequency, and tidal volume were measured before, during, and after challenge to assess allergic and irritative airway responses. One day after challenge, nonspecific airway responsiveness to a range of concentrations of methacholine was measured. At necropsy on the same day, blood was withdrawn for measuring total serum immunoglobulin E (IgE) and organs were weighed. Larynx, trachea and lungs were examined histopathologically. In BN rats, TMA sensitization elevated total IgE levels; subsequent inhalation challenge with 2 mg/m³ of TMA and higher caused laryngeal inflammation with squamous epithelial metaplasia, and pulmonary hemorrhages. Concentration-related decreases in breathing frequency and alterations in breathing pattern, which differed from the irritation-induced pattern, were also observed at these levels. Inhalation challenge with TMA concentrations of 12 mg/m³ and higher increased lung weight. Increased nonspecific airway responsiveness was observed at the 2 next higher tested concentrations of 46 and 61 mg/m³. In unsensitized BN rats, only laryngeal squamous metaplasia was observed, albeit at higher challenge concentrations of TMA, and decreased breathing frequency, a typical breathing pattern characteristic of irritation. Identically sensitized Wistar rats showed airway inflammation and pulmonary hemorrhages upon challenge with TMA, but no functional changes, even at distinctly irritating concentrations of TMA up to 250 mg/m³. In conclusion, TMA challenge of sensitized BN rats caused challenge concentration-related allergic airway inflammation, asthmalike changes in breathing pattern, and increased nonspecific airway responsiveness. The lowest no-observed-effect level (NOEL) based on the most sensitive endpoint investigated was 0.2 mg/m³, a value that is well below the irritation concentration. The presence of a NOEL in the sensitized BN rat suggests that assessment of safe human exposure levels is feasible.     

Respiratory Irritation Associated with Inhalation of Boron Trifluoride and Fluorosulfonic Acid

The objectives of this study were to examine the respiratory irritancy of boron trifluoride (BF₃) and fluorosulfonic acid (FSA) following acute inhalation exposure. Testing was conducted using groups of 10 male and 10 female rats (BF₃) or groups of 6 male rats (FSA). Rats were exposed for a single 4-h period (BF₃) or a single 1-h period (FSA) and necropsied 1 or 14 days after exposure (BF₃) or 14 days after exposure (FSA). Measurements consisted of clinical signs, body weight, kidney and lung weight, histopathology (BF₃), and breathing parameters (FSA) and were used to evaluate the possible irritating effects of these compounds. The results indicated treatment-related findings in the larynx and trachea in the rats exposed to 74.4 mg/m³ BF₃, consisting of ventral cartilage necrosis, hemorrhage, and an increase in ventral epithelial hyperplasia and ventral inflammatory cell inflammation 24 h postexposure. In the animals sacrificed 14 days postexposure, the only notable observation was ventral cartilage necrosis, present in 2 animals. The next lower level tested, 24.6 mg/m³ BF, was considered a no-observed-adverse-effects level (NOAEL). A concentration of 4125 mg/m³ FSA resulted in a clearly decreased breathing rate during and shortly after exposure with 67% (4/6) mortality on days 5–9 after exposure. A concentration of 845 mg/m³ FSA resulted in only minor signs of irritation, consisting of slight changes in breathing pattern shorlty after exposure. The results of the present 4-h inhalation study with BF₃ indicated that respiratory irritation was present at a level of 74.4 mg/m³ whereas 24.6 mg/m³ was a NOAEL. A single 1-h exposure to 845 mg/m³ FSA resulted in only minor signs of respiratory irritation, indicating that on a mass basis FSA is no more toxic or irritating than hydrogen fluoride (HF) or sulfuric acid.     

Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives

BACKGROUND: Previous work suggests that impairments in executive function and verbal memory in particular may persist in euthymic bipolar patients and serve as an indicator of genetic risk (endophenotype). METHOD: A systematic review of the literature was undertaken. Effects sizes were extracted from selected papers and pooled using meta-analytical techniques. RESULTS: In bipolar patients, large effect sizes (d>0.8) were noted for executive functions (working memory, executive control, fluency) and verbal memory. Medium effect sizes (0.5相似文献   

Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

Regional variation in ionic membrane currents causes differences in action potential duration (APD) and is proarrhythmic. After several weeks of ventricular pacing, AP morphology and duration are changed due to electrical remodeling of the transient outward potassium current (I _to) and the L-type calcium current (I _Ca,L). It is not clear what mechanism drives electrical remodeling. By modeling the cardiac muscle as a string of segments that are electrically and mechanically coupled, we investigate the hypothesis that electrical remodeling is triggered by changes in mechanical load. Contractile force generated by the sarcomeres depends on the calcium transient and on the sarcomere length. Stroke work is determined for each segment by simulating the cardiac cycle. Electrical remodeling is simulated by adapting I _Ca,L kinetics such that a homogeneous distribution of stroke work is obtained. With electrical remodeling, a more homogeneous shortening of the fiber is obtained, while heterogeneity in APD increases and the repolarization wave reverses. Our results are in agreement with experimentally observed homogeneity in mechanics and heterogeneity in electrophysiology. In conclusion, electrical remodeling is a possible mechanism to reduce heterogeneity in cardiomechanics induced by ventricular pacing.