Mechanisms of opioid-induced tolerance and hyperalgesia.

Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.     

Longitudinal study on potential neurotoxic effects of aluminium: II. Assessment of exposure and neurobehavioral performance of Al welders in the automobile industry over 4 years

Objectives  

This is the second of two parallel longitudinal studies investigating Al exposure and neurobehavioral health of Al welders over 4 years. While the first published study in the trail and truck construction industry examined the neurobehavioral development of Al welders from age 41–45 in the group mean (Kiesswetter et al. in Int Arch Occup Environ Health 81:41–67, 2007), the present study in the automobile industry followed the development from 35 to 39. Although no conspicuous neurobehavioral developments were detected in the first study, which furthermore exhibited the higher exposure, it cannot be excluded that exposure effects appear in earlier life and exposure stages.     

Bromodeoxyuridine Labeling Index as an Indicator of Early Tumor Response to Preoperative Radiotherapy in Patients with Rectal Cancer

Purpose Assessment of tumor proliferation rate using Bromodeoxyuridine labeling index (BrdUrdLI) as a possible predictor of rectal cancer response to preoperative radiotherapy (RT). Methods and material Ninety-two patients were qualified either to short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I), or to short RT and 4–5 weeks interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. The samples were incubated with BrdUrd for 1 h at 37°C, and the BrdUrdLI was calculated as a percentage of BrdUrd-labeled cells. Results Thirty-eight patients were treated according to schedule I and 54 patients according to schedule II. Mean BrdUrdLI before RT was 8.5% and its value did not differ between the patients in the two compared groups. After RT tumors showed statistically significant growth inhibition (reduction of BrdUrdLI). As the pretreatment BrdUrd LI was not predictive for early clinical and pathologic tumor response, prognostic role of the ratio of BrdUrdLI after to BrdUrdLI before RT was considered. The ratios were calculated separately for fast (BrdUrd LI > 8.5%) and slowly (BrdUrd LI ≤ 8.5%) proliferating tumors and correlated with overall treatment time (OTT, i.e., time from the first day of RT to surgery). One month after RT, accelerated proliferation was observed only in slowly proliferating tumors. Conclusions Pretreatment BrdUrdLI was not predictive for early clinical and pathologic tumor response. The ratio after/before RT BrdUrdLI was correlated to inhibition of proliferation in responsive tumors. The paper was presented at ECCO 13, October 30 to November 03, 2005 in Paris, France     

Broncho-alveolar Lavage Matrix Metalloproteases as a Sensitive Measure of Bronchiolitis Obliterans

Bronchiolitis obliterans (BO) is a survival-limiting factor in lung transplantation. There are no common BO markers in use. Since BO is associated with extracellular matrix remodeling, we asked whether matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) could serve as BO markers. In 72 lung transplant patients (34 BO syndrome (BOS) 0, 15 BOS 0-p, and 23 BOS 1) serum and broncho-alveolar lavage (BAL) MMP and TIMP levels were examined by ELISA. The BAL cell counts were additionally analyzed. The serum MMP-2, MMP-8, MMP-9 and TIMP-2 levels were not different in all groups. In contrast, the BAL MMP-8, -9 and TIMP-1 levels were significantly elevated in BOS 0-p (p = 0.003; p = 0.007; p = 0.0003, respectively) and BOS 1 (p = 0.003; p = 0.001; p = 0.0004, respectively) as compared to BOS 0 patients. The BAL MMP-8, -9 and TIMP-1 levels were significant predictors of BOS 0-p (p = 0.01; p = 0.01; p = 0.01, respectively) and BOS-1 (p = 0.007; p = 0.01; p = 0.006, respectively) in receiver operating characteristic analysis. Except for BAL macrophages that were significantly decreased in BOS 0-p versus BOS 0 patients; other cell counts were not different between the groups. BAL MMP-8, -9 and TIMP-1 might be useful markers to detect BO in lung transplant patients.     

Long-term results of laryngotracheal resection for benign stenosis.

OBJECTIVE: We report the long-term results of our 16-year experience with laryngotracheal resection for benign stenosis. METHODS: Between 1991 and 2006, 35 consecutive patients (19 males, 16 females) underwent laryngotracheal resection for subglottic postintubation (32) or idiopathic (3) stenosis. Mean age was 43 years (range 14-71). At the time of surgery 13 patients presented with tracheostomy and 7 with a Dumon stent. The upper limit of the stenosis was from 0.6 to 1.5 cm below the vocal cords. The length of airway resection ranged between 1.5 and 6 cm. Suprahyoid release was performed in two patients and pericardial release in one. Nine patients had psychiatric and/or neurological post-coma disorders. Mean follow-up is over 5 years (61 months; range 3-194). RESULTS: There was no perioperative mortality. Thirty patients (85.7%) had excellent or good anatomic and functional results. Four patients (11.4%) presented restenosis at a distance of 25-110 days from the operation. Restenosis was successfully treated by endoscopic procedures in all four patients. One patient (2.9%) presented anastomotic dehiscence that required temporary tracheostomy closed after 1 year with no sequelae. Three patients (8.4%) had wound infection. Long-term follow-up was uneventful also in patients who had early complications. CONCLUSIONS: Long-term follow-up confirms that laryngotracheal resection is the definitive curative treatment for benign subglottic stenosis. Surgical complications can be successfully managed by non-operative procedures. Despite the occurrence of early complications, excellent and stable results can still be obtained at long term.     

The effect of single and repeated UVB radiation on rabbit cornea

Background Cumulative effect of ultraviolet radiation (UVR) is an important aspect of UV corneal damage. The purpose of this study was to apply high resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS ¹H NMR) spectroscopy to evaluate the effect of single and repeated UV radiation exposure of the same overall dose on the rabbit cornea.Methods Corneal surfaces of 24 normal rabbit eyes were examined for the effects of UVB exposure (312 nm). In the first group (UVB1), animals were irradiated with a single dose (3.12 J/cm²; 21 min) of UVB radiation. The animals in the second group (UVB2) were irradiated three times for 7 min every other day (dose of 1.04 J/cm²; days 1, 3, 5) to give the same overall dose (3.12 J/cm²). The third group served as an untreated control group. One day after the last irradiation, the animals were sacrificed, and the corneas were removed and frozen. HR-MAS ¹H NMR spectra from intact corneas were obtained. Special grouping patterns among the tissue samples and the relative percentage changes in particular metabolite concentrations were evaluated using modern statistical methods (multivariate analysis, one-way ANOVA).Results The metabolic profile of both groups of UVB-irradiated samples was significantly different from the control corneas. Substantial decreases in taurine, hypo-taurine and choline-derivatives concentrations and substantial elevation in glucose and betaine levels were observed following the UVR exposure. There was no significant difference between the effect of a single and repeated UVB irradiation of the same overall dose.Conclusions For the first time, the effects of single and repeated UVR doses on the metabolic profile of the rabbit cornea were analysed and compared. The combination of HR-MAS ¹H NMR spectroscopy and modern statistical methods (multivariate analysis, one-way ANOVA) proved suitable to assess the overall view of the metabolic alterations in the rabbit corneal tissue following UVB radiation exposure.     

Evaluation of 188 consecutive homografts implanted in pulmonary position after 20 years.

OBJECTIVE: Homografts are considered the gold standard for right ventricular outflow tract reconstruction. Their long-term durability is limited, and alternatives became available. We evaluate their long-term hemodynamic performance to permit comparisons with alternative devices. METHODS: Between 1985 and 2004, 188 homografts were implanted in pulmonary position at our institution. Mean patient age was 24.8 years (range 2 days-75 years); 56 were female and 132 male. Total follow-up time was 1073 years. Fifty-eight percent were Ross procedures (mean age 31.5 years) and 42% were different procedures (mean age 15.6 years); main diagnoses were tetralogy of Fallot (48%), truncus arteriosus (14%), transposition of the great arteries (11%). Twenty-six percent were redo implantations. We evaluated freedom from death, explantation, insufficiency, relevant gradient, degeneration, and the interval between diagnosis of degeneration and therapeutic procedure (therapeutic gap). Results were stratified by indication, age, history, homograft size, and origin. RESULTS: Ten-year-freedom-from explantation was 82% in homografts >19 mm and 45% in smaller ones. Ten-year freedom from degeneration was 68% after Ross procedure and 25% after other operations; it was 83% in patients older than 10 years at implantation and 51% in younger ones. 'Non-Ross-procedure' and 'implantation age below 10 years' were the only independent risk factors for degeneration. The observed trend towards therapeutical gap reduction was not statistically significant. CONCLUSIONS: Homograft implantation in the pulmonary position can be performed with good long-term freedom from explantation. However, freedom from degeneration is a matter of concern. Therefore, alternative valved conduits are required especially for pediatric patients.     

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

Racial trends in syphilis among men with same-sex partners in Atlanta, Georgia.

Early syphilis cases attributable to homosexual transmission declined in DeKalb County, Georgia, from 191 in 1981 to 97 in 1985. This decline occurred only among White men with same sex partners (SSP); early syphilis among Black men with same sex partners has risen. This pattern is consistent with the hypothesis that changes in sexual behavior instituted by White men at risk of acquiring HTLV-III/LAV infection may have resulted in decreased incidence of early syphilis among those men.