The release of tumor necrosis factor-alpha is associated with ischemic tolerance in human stroke

Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF-alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p < 0.0001) and IL-6 levels were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF-alpha in the presence of reduced concentrations of IL-6.     

Treatment of thoracic pseudarthrosis in the adult: is combined surgery necessary?

In deformity surgery in adults, pseudarthrosis remains an important cause of progressive deformity and postoperative pain. Revision surgery for pseudarthrosis in the lumbar spine is a difficult challenge with failure rates of as much as 50% using posterior surgery alone. Treatment of pseudarthrosis of the thoracic spine has not been well-described. The purpose of the current study was to review the long-term clinical and radiographic results of posterior-only surgery for the treatment of pseudarthrosis in the thoracic spine. Using a posterior extension osteotomy through the identified pseudarthrosis with reinstrumentation and autogenous bone grafting, an improvement of regional sagittal balance was shown and reliable clinical outcomes were obtained. A single-stage posterior revision surgery with extension osteotomies through the regions of pseudarthrosis coupled with rigid internal fixation and autogenous bone grafting is an effective technique for treatment of pseudarthrosis of the thoracic spine. This technique improves regional sagittal deformity and leads to reliable arthrodesis. Combined anterior and posterior surgery was not necessary for effective treatment of thoracic pseudarthrosis in this series.     

Support for the resumption of sexual activity in the postpartum woman, a subject devoid of interest

This study reports the results of an Italian sampling survey carried out in 1999 on the evaluation of the support and the information activities offered to women who delivered, with specific regard to sexual resumption and postpartum contraception. 1986 women have been interviewed. The response rate was 95%. Sixty-three percent of the women reported they would use a contraceptive method at sexual resumption, but only 21 and 25% had the opportunity to receive adequate information on sexual resumption and family planning during post-delivery hospital stay.     

Rye bread in the diet of pigs enhances the formation of enterolactone and increases its levels in plasma,urine and feces

To obtain new insight into the quantitative and qualitative metabolism of rye and wheat lignans, we performed three series of experiments with catheterized pigs. Two diets with similar levels of dietary fiber and macronutrients but with contrasting levels of plant lignans (isolariciresinol, lariciresinol, matairesinol, pinoresinol, secoisolariciresinol and syringaresinol) were prepared from rye (high in lignans) and wheat (low in lignans) soft and crisp breads. In two series of experiments we quantified the uptake from the gut of enterolactone in four pigs fitted with catheters in the portal vein and mesenteric artery and with an ultrasonic flow probe attached to the portal vein to monitor the blood flow. In a third study with six pigs, we quantified the bioavailability of the plant lignans that can be converted to enterolactone (lariciresinol, matairesinol, pinoresinol, secoisolariciresinol and syringaresinol) and the concentration in the peripheral blood. Plant and mammalian lignans in diets and stool were analyzed by isotope dilution gas chromatography-mass spectrometry and enterolactone in plasma and urine determined by time-resolved fluoroimmunoassay. There was a significantly higher formation of enterolactone in pigs fed the rye diet, and higher fecal and urinary excretion and circulating levels of mammalian lignans than in pigs fed the wheat diet. The conversion of mammalian lignan precursors to enterolactone was 48% with the wheat diet and 60% with the rye diet. Mammalian lignans are absorbed by passive diffusion from the large intestine and a substantial fraction of the absorbed mammalian lignans undergoes enterohepatic circulation, resulting in low diurnal variation in plasma levels of enterolactone.     

Biomechanically derived guideline equations for burst fracture risk prediction in the metastatically involved spine

Methods to quantify burst fracture risk and neurologic deficit for patients with spinal metastases have not been well defined. This study aims to develop objective biomechanically based guidelines to quantify metastatic burst fracture risk. An experimentally validated finite element model of a human lumbar motion segment was used to simulate burst fracture. Through parametric analysis, the behavior of metastatically involved vertebrae was quantified and a formula to relate patient-specific variables to burst fracture risk defined. The equation-based guidelines were able to describe the mechanical behavior of the metastatically involved vertebral model (R2 = 0.97) reflecting the risk and mechanism of fracture. Vertebral density was found to influence the mechanism of burst fracture with respect to endplate failure. These analyses provide clinically feasible equation-based guidelines for burst fracture risk assessment in the metastatically involved spine.     

Brief,repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors

1. Ischemic preconditioning in the brain consists of reducing the sensitivity of neuronal tissue to further, more severe, ischemic insults. We recorded field epsps (fepsps) extracellularly from hippocampal slices to develop a model of in vitro ischemic preconditioning and to evaluate the role of A1, A2A and A3 adenosine receptors in this phenomenon. 2. The application of an ischemic insult, obtained by glucose and oxygen deprivation for 7 min, produced an irreversible depression of synaptic transmission. Ischemic preconditioning was induced by four ischemic insults (2 min each) separated by 13 min of normoxic conditions. After 30 min, an ischemic insult of 7 min was applied. This protocol substantially protected the tissue from the irreversible depression of synaptic activity. 3. The selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nm), completely prevented the protective effect of preconditioning. The selective adenosine A2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 100 nm) did not modify the magnitude of fepsp recovery compared to control slices. The selective A3 adenosine receptor antagonists, 3-propyl-6-ethyl-5[ethyl(thio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523, 100 nm) significantly improved the recovery of fepsps after 7 min of ischemia. 4. Our results show that in vitro ischemic preconditioning allows CA1 hippocampal neurons to become resistant to prolonged exposure to ischemia. Adenosine, by stimulating A1 receptors, plays a crucial role in eliciting the cell mechanisms underlying preconditioning; A2A receptors are not involved in this phenomenon, whereas A3 receptor activation is harmful to ischemic preconditioning.     

2-pyrrolidinone moiety is not critical for the cognition-enhancing activity of piracetam-like drugs

Following the indications of previous work, 2-pyrrolidinone moiety of piracetam and piracetam-like compounds has been opened to the corresponding amide derivatives. As found previously in the case of 1,4-diazabicyclo[4.3.0]nonan-9-one compounds, the cognition-enhancing activity of 2-pyrrolidinone compounds is maintained in most cases, suggesting that this moiety is not crucial for activity.     

The implementation of occupational health guidelines principles for reducing sickness absence due to musculoskeletal disorders

BACKGROUND: Occupational health guidelines recommend a biopsychosocial approach to manage sickness absence due to musculoskeletal disorders (MSDs), with a primary focus on early intervention through provision of a supportive network. AIMS: To investigate the implementation of a guidelines-based intervention (early contact of absentees; addressing psychosocial obstacles; offering temporary modified work; communicating among the players), and to determine whether this is effective for reducing return-to-work times and duration of future absence. METHODS: A non-randomized controlled trial was conducted within a UK company. Occupational health nurses at two experimental sites (1,435 workers) were trained to deliver the intervention to workers taking absence due to MSDs (low back and upper limb disorders), while usual care was delivered at three control sites (1,483 workers). Company-recorded absence data were collected over a 12-month follow-up period. RESULTS: The implementation of the experimental intervention was impeded by unforeseen organizational obstacles at one site (policies, procedures and individual approaches) which had a detrimental effect on uptake and delivery. At the site where the intervention was delivered per protocol, absence was significantly less compared with controls; 6.5 and 10.8 days, respectively. However, the duration of future absence was not significantly different (13.0 and 25.1 days, respectively). CONCLUSIONS: An early intervention addressing psychosocial obstacles to recovery can be effective for reducing absence due to MSDs. Successful implementation, where the key players are onside and organizational obstacles are overcome, is difficult to achieve.     

The regulation of renal ammoniagenesis in the rat by extracellular factors. III. Effects of various fuels on in vitro ammoniagenesis

The addition of many oxidizable substrates to the medium of incubating rat renal slices decreases ammoniagenesis from glutamine and glutamate. Interestingly, lactate and β-hydroxybutyrate depress ammoniagenesis less in renal slices from acidotic rats compared with normal-control rats. In this study, the effects of an expanded panel of substrates on ammoniagenesis in kidney slices from control and acidotic rats were followed to discern patterns of inhibition. In addition to lactate and β-hydroxybutyrate, acetate, pyruvate, and perhaps acetoacetate caused relatively less depression of ammoniagenesis in acidotic slices. Citrate, succinate, fumarate, octanoate, and α-ketoglutarate decreased ammoniagenesis to the same extent or more in acidotic slices compared with that in normal-control slices. Glycerol had little effect on ammoniagenesis under either condition. From the substrates tested, it can be generalized that those outside the TCA cycle (with exception of octanoate) depress ammoniagenesis less during acidosis, while those in the TCA cycle depress ammoniagenesis equally or even more during acidosis. We hypothesize from the pattern of our results that changes in renal intermediary metabolism at or before citrate formation occur during acidosis and are important regulatory mechanisms for ammoniagenesis.