Dynorphin and prodynorphin mRNA changes in the striatum during nicotine withdrawal

Nicotine withdrawal causes somatic and negative affective symptoms that contribute to relapse and continued tobacco smoking. So far, the neuronal substrates involved are not fully understood, and an opioid role has been suggested. In this regard, the opioid dynorphin (Dyn) is of interest as it produces aversive states and has been speculated to play a role in the nicotine behavioral syndrome. These studies explore whether Dyn metabolism is altered during withdrawal following chronic administration of nicotine. Mice were administered nicotine, 2 mg/kg, s.c., four times daily for 14 days, and Dyn and prodynorphin (PD) mRNA estimated in selective brain regions at various times (30 min to 96 h) following drug discontinuation. The content of Dyn, estimated by RIA, was decreased in the striatum for a protracted time, from 30 min to over 72 h. In contrast, the mRNA for PD, evaluated by Northern blot, was elevated, appearing by 8 h and lasting over 96 h. Dyn was decreased in both ventral and dorsal striatum, and PD mRNA was differentially increased in the two striatal compartments as demonstrated by in situ hybridization. PD message was predominantly augmented in the nucleus accumbens, rostral pole, core, and shell, and the medial aspects of caudate/putamen. We interpret these data to indicate increased activity of striatal, particularly accumbal, dynorphinergic neurons during nicotine withdrawal resulting in enhanced peptide release and compensatory synthesis. Heightened dynorphinergic tone might be responsible, in part, for the emergence of the negative affective states observed during nicotine withdrawal.     

Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties

Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.     

Race/ethnicity,acculturation, and psychological distress: Fatalism and religiosity as cultural resources

Data from a community sample of 1,784 Anglo, African-American, and Mexican-American adults were examined to assess: (1) the nature and magnitude of observed racial/ethnic and acculturation level differences in depression, (2) the relative contribution of sociodemographic and psychosocial factors (fatalism and religiosity) to observed differences, and (3) the joint effects of fatalism and religiosity as sociocultural resources with regard to depression in differing racial/ethnic and acculturation level subgroups. Analyses indicate the most dramatic differences in depression among males—African Americans were roughly similar to Anglos and levels of depression were significantly higher among the least acculturated Mexican Americans relative to Anglos, even after statistical controls. Acculturation level differences among Mexican-American females were explained by statistical controls. Lower levels of depression among more highly acculturated than among less acculturated Mexican Americans provide little support for a simplistic stress formulation of acculturation. Rather, the interplay of acculturation, fatalism, and religiosity supports a more complex cultural marginality model, emphasizing the consistency of attitudinal elements and language use as facilitators or inhibitors of assimilation into Anglo culture. Both those who successfully acculturate and those who are most insulated in traditional culture appear least depressed from this perspective.     

Impact of Anesthesia on the Outcome of Acute Ischemic Stroke after Endovascular Treatment with the Solitaire Stent Retriever

BACKGROUND AND PURPOSE:General anesthesia during endovascular treatment of acute ischemic stroke may have an adverse effect on outcome compared with conscious sedation. The aim of this study was to examine the impact of the type of anesthesia on the outcome of patients with acute ischemic stroke treated with the Solitaire stent retriever, accounting for confounding factors.MATERIALS AND METHODS:Four-hundred one patients with consecutive acute anterior circulation stroke treated with a Solitaire stent retriever were included in this prospective analysis. Outcome was assessed after 3 months by the modified Rankin Scale.RESULTS:One-hundred thirty-five patients (31%) underwent endovascular treatment with conscious sedation, and 266 patients (69%), with general anesthesia. Patients under general anesthesia had higher NIHSS scores on admission (17 versus 13, P < .001) and more internal carotid artery occlusions (44.6% versus 14.8%, P < .001) than patients under conscious sedation. Other baseline characteristics such as time from symptom onset to the start of endovascular treatment did not differ. Favorable outcome (mRS 0–2) was more frequent with conscious sedation (47.4% versus 32%; OR, 0.773; 95% CI, 0.646–0.925; P = .002) in univariable but not multivariable logistic regression analysis (P = .629). Mortality did not differ (P = .077). Independent predictors of outcome were age (OR, 0.95; 95% CI, 0.933–0.969; P < .001), NIHSS score (OR, 0.894; 95% CI, 0.855–0.933; P < .001), time from symptom onset to the start of endovascular treatment (OR, 0.998; 95% CI, 0.996–0.999; P = .011), diabetes mellitus (OR, 0.544; 95% CI, 0.305–0.927; P = .04), and symptomatic intracerebral hemorrhage (OR, 0.109; 95% CI, 0.028–0.428; P = .002).CONCLUSIONS:In this single-center study, the anesthetic management during stent retriever thrombectomy with general anesthesia or conscious sedation had no impact on the outcome of patients with large-vessel occlusion in the anterior circulation.

Endovascular treatment of acute ischemic stroke due to large-vessel occlusion in the anterior circulation is safe and effective for improving functional outcome.¹ However, there is an ongoing debate about the type of anesthesia to be used, general anesthesia (GA) or conscious sedation (CS). No patient movements, better airway control, and perceived procedural safety and efficacy are regarded as potential advantages of GA, but more recent data of nonrandomized studies including 1 meta-analysis of 9 studies suggest that CS during endovascular stroke treatment might improve outcome.^2–5 This finding might be explained by a shorter time to start the intervention, less blood pressure dip, and easier neurologic monitoring during and after CS. However, many confounding factors such as stroke severity, occlusion site, pretreatment with IV rtPA, age, endovascular treatment techniques, and recanalization rates, might influence outcome.^3,6–11 Recently, the results of the first randomized study, Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA), were published, which showed no differences between GA and CS for the primary end point defined as early neurologic improvement on the NIHSS after 24 hours.¹²The aim of this study was to examine the impact of the type of anesthesia (GA versus CS) on the outcome of patients with acute ischemic stroke with large-vessel occlusion in the anterior circulation who were treated with the Solitaire stent retriever (Covidien, Irvine, California), while accounting for confounding factors.     

Comparison of three bone ultrasounds for the discrimination of subjects with and without osteoporotic fractures among 7562 elderly women.

Bone ultrasound measures (QUSs) can assess fracture risk in the elderly. We compared three QUSs and their association with nonvertebral fracture history in 7562 Swiss women 70-80 years of age. The association between nonvertebral fracture was higher for heel than phalangeal QUS. INTRODUCTION: Because of the high morbidity and mortality associated with osteoporotic fractures, it is essential to detect subjects at risk for such fractures with screening methods. Because quantitative bone ultrasound (QUS) discriminated subjects with osteoporotic fractures from controls in several cross-sectional studies and predicted fractures in prospective studies, QUS could be more practical than DXA for screening. MATERIAL AND METHODS: This cross-sectional and retrospective multicenter (10 centers) study was performed to compare three QUSs (two heel ultrasounds: Achilles+ [GE-Lunar] and Sahara [Hologic]; the phalanges: ultrasound DBM sonic 1200 [IGEA]) for determining by logistic regression nonvertebral fracture odds ratio (OR) in a sample of 7562 Swiss women, 75.3 +/- 3.1 years of age. The two heel QUSs measured the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). In addition, Achilles+ calculated the stiffness index (SI) and the Sahara calculated the quantitative ultrasound index (QUI) from BUA and SOS. The DBM sonic 1200 measured the amplitude-dependent SOS (AD-SOS). RESULTS: Eighty-six women had a history of a traumatic hip fracture after the age of 50, 1594 had a history of forearm fracture, and 2016 had other nonvertebral fractures. No fracture history was reported by 3866 women. Discrimination for hip fracture was higher than for the other nonvertebral fractures. The two heel QUSs had a significantly higher discrimination power than the QUSs of the phalanges, with standardized ORs, adjusted for age and body mass index, ranging from 2.1 to 2.7 (95% CI = 1.6, 3.5) compared with 1.4 (95% CI = 1.1, 1.7) for the AD-SOS of DBM sonic 1200. CONCLUSION: This study showed a high association between heel QUS and hip fracture history in elderly Swiss women. This could justify integration of QUS among screening strategies for identifying elderly women at risk for osteoporotic fractures.     

Analgesic efficacy of equimolar 50% nitrous oxide/oxygen gas premix (Kalinox®) as compared with a 5% eutectic mixture of lidocaine/prilocaine (EMLA®) in chronic leg ulcer debridement

Chronic foot and leg ulcers are a common health problem worldwide. A mainstay of chronic ulcer therapy is sharp mechanical wound debridement requiring potent analgesia. In this prospective, controlled, single‐centre, crossover design study, patients were assigned to either the administration of topical analgesia with 5% lidocaine/prilocaine cream or the inhalation of an analgesic 50% N₂O/O₂ gas premix. Primary outcome parameter was level of pain at maximum wound depth during debridement as measured by a visual analogue scale. Secondary outcomes included level of pain after debridement, overall duration of treatment session, duration and completeness of debridement, and the patient's subjective perception of analgesic quality during debridement. Pain level increased from 0·60/0·94 (first/second debridement; baseline) to 1·76/2·50 (debridement) with 5% lidocaine/prilocaine and from 1·00/1·35 (baseline) to 3·95/3·29 (debridement) with 50% N₂O/O₂ gas premix. Patient satisfaction was 90·48%/94·44% (first/second debridement) with topical 5% lidocaine/prilocaine analgesia and 90·48%/76·47% with the inhalation of 50% N₂O/O₂ gas premix. Debridement was completed in a significantly higher percentage of 85·71%/88·89% (first/second debridement) with 5% lidocaine/prilocaine than with 50% N₂O/O₂ gas premix (42·86%/58·82%) (odds ratio 6·7; P = 0·001). This study provides sound evidence that analgesia with topically administered 5% lidocaine/prilocaine cream is superior to the use of inhaled 50% N₂O/O₂ gas premix in chronic leg ulcer debridement.     

1.000.000 Fu?ballfans in einer Stadt mit 120.000 Einwohnern �C ein notfallmedizinischer Albtraum?

The 2008 European Football Championship 2008 (Euro 08) is the largest sporting event ever organized in Switzerland. One million visitors came to the city of Berne during the event and the local airport in Bern/Belp registered 261 extra flights. For each football game there were 33,000 fans in the stadium and 100,000 fans in the public viewing zones.The ambulance corps and the Department of Emergency Medicine (ED) at Inselspital, University Hospital Berne, were responsible for basic medical care and emergency medical management. Injuries and illnesses were analyzed by a standardized score (NACA score). The preparation strategy as well as costs and patient numbers are presented in detail.A total of 30 additional ambulance vehicles were used, 4,723 additional working days (one-third medical professionals) were accumulated, 662 ambulance calls were registered and 240 persons needed medical care (62% Swiss, 28% Dutch and 10% other nationalities). Among those needing treatment 51 were treated in 1 of the 4 city hospitals. No injuries with NACA grades VI and VII occurred (NACA I: 4, NACA II: 17, NACA III: 16, NACA IV: 10 and NACA V: 4 patients). The city of Berne compensated the Inselspital Bern with a total of 112,603 Euros for extra medical care costs. The largest amount was spent on security measures (50,300 Euros) and medical staff (medical doctors 22,600 Euros, nurses 29,000 Euros). Because of the poor weather and the exemplary behavior of the fans, the course of events was rather peaceful.     

Acquired immune hemolytic anemia associated with IgA erythrocyte coating: investigation of hemolytic mechanisms

We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.     

Comparison of 16-slice MSCT and MRI in the assessment of squamous cell carcinoma of the oral cavity

The goal of this retrospective study was to assess the accuracy of 16-slice multislice CT (MSCT) and MRI in staging of patients with primary squamous cell carcinoma (SCC) of the oral cavity. Fifty-two patients with histologically proven primary SCC were examined with contrast enhanced MSCT and MRI at 1.5 T with a combined head and surface neck coil. Image modalities were evaluated in a blinded fashion by two radiologists and an oral-maxillofacial surgeon in consensus concerning tumour depiction, local tumour infiltration and cervical lymph node metastases. Results of the radiological assessment were correlated with the intraoperative and histopathological findings in all patients. 36 of 52 primary tumours (69.2%) were depicted by MSCT while 44 were localized by MRI (84.6%). Regarding muscle infiltration MRI versus MSCT had a sensitivity of 81.8% versus 72.7%, but a low specificity and an accuracy of 63.4% versus 61% and 67.3% versus 63.5%, respectively, were found. There was a trend towards a better detection of bony infiltration by MRI than MSCT with a sensitivity of 100% versus 71.4%, a specificity of 93.3% versus 95.5% and an accuracy 94.2% versus 92.3%, respectively. Detection of cervical lymph node involvement was similar for MRI and MSCT with a sensitivity of 84.2% and 78.9%, a specificity of 63.6% and 75.7% and an accuracy of 71.1% and 76.9%, respectively. For N-staging both methods failed to detect small metastasis. For T-staging MRI was superior to MSCT, because there was a tendency to underestimate the tumour size by MSCT more often (19.4% versus 6.8% by MRI). Therefore, pre-operative MRI is recommended as the basic imaging modality of choice for treatment planning of oral SCC. MSCT is a valid alternative imaging method especially in cases with low patient compliance.     

Fetale Magnetresonanztomographie

Ultrasonography is the primary imaging modality for the evaluation of fetal or maternal anomalies. This method is safe, relatively inexpensive, easily accessible, and allows real-time imaging. Continuous technical improvements in ultrasonography in the last 10-15 years have led to improved diagnostic accuracy for fetal malformations. In cases of complex anomalies magnetic resonance imaging (MRI) can provide additional information. MRI has evolved as a valuable diagnostic method for evaluating fetal pathology. Particularly with regard to similarity of liver and lung parenchyma in ultrasonography, diagnosis of congenital diaphragmatic hernia (CDH) can be difficult. Beside morphological aspects, e.g., herniation of abdominal contents into the chest, small amounts of compressed lung can be visualized on MRI. The feasibility of using volumetric measurement on MRI may be helpful to predict high-risk fetuses and facilitate decisions to assure adequate prenatal and postnatal management to improve postnatal outcome.