Clinical characteristics distinguishing tramadol-using adolescents from other substance-using adolescents in an out-patient treatment setting.

BACKGROUND: Non-medical Prescription Opioid Use (NMPOU) has increased worldwide during the last decades, and specifically, tramadol misuse may represent a novel pattern of substance use among adolescents. The present study aims to analyze characteristics distinguishing tramadol-using adolescents from other substance-using adolescents seeking out-patient treatment. METHODS: This is a cross-sectional study of treatment-seeking patients between 13 and 24 years of age in an out-patient facility for substance use problems in Malmö, Sweden. A total of 526 treatment-seeking adolescents at an out-patient treatment center were included. Data on substance use, treatment history and socio-demographic variables were extracted through a semi-structured interview method aimed specifically for adolescents with alcohol or drug problems (Ung-DOK). Lifetime tramadol users were compared to non-users, and also, primary tramadol users were compared to remaining subjects. RESULTS: Thirty-one percent (n = 162) were tramadol users (lifetime prevalence). In logistic regression, the tramadol group showed a significantly increased risk of tobacco use, problematic lifetime cocaine, benzodiazepine and amphetamine use, and were more likely to report contacts with the judicial system, and less likely to report contacts with child or adult psychiatry, and more likely to have parents born outside the Scandinavian countries. In logistic regression, primary tramadol use was negatively associated with frequent cannabis use. CONCLUSIONS: Tramadol use appears to be a novel pattern among treatment-seeking adolescents. They showed a significantly increased risk of initiation of other illicit drugs and criminal behaviour, despite less contact with psychiatric care. More attention may be needed to this relatively novel pattern of opioid use.

Interactions of the Calcite {10.4} Surface with Organic Compounds: Structure and Behaviour at Mineral - Organic Interfaces.

The structure and the strength of organic compound adsorption on mineral surfaces are of interest for a number of industrial and environmental applications, oil recovery, CO2 storage and contamination remediation. Biomineralised calcite plays an essential role in the function of many organisms that control crystal growth with organic macromolecules. Carbonate rocks, composed almost exclusively of calcite, host drinking water aquifers and oil reservoirs. In this study, we examined the ordering behaviour of several organic compounds and the thickness of the adsorbed layers formed on calcite {10.4} surfaces. We used X-ray reflectivity (XRR) to study calcite {10.4} surfaces that were prepared in three alcohols: methanol, isopropanol and pentanol and one carboxylic acid: octanoic acid. All molecules adsorbed in self-assembled layers, where thickness depended on the density and the length of the molecule. For methanol and isopropanol, molecular dynamic simulations (MD) provided complementary information, which allowed us to develop a surface model. Branching in isopropanol induced slightly less ordering because of the additional degree of freedom. Pentanol and octanoic acid adsorbed as single monolayers. The results of this work indicate that adhered organic compounds from the surrounding environment can affect the surface behaviour, depending on properties of the organic compound.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).

Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons.

BACKGROUND/OBJECTIVES: In studies performed in mice, rose hip powder has been shown to both prevent and reverse high-fat diet-induced obesity and glucose intolerance as well as reduce plasma levels of cholesterol. The aim of this study was to investigate whether daily intake of rose hip powder over 6 weeks exerts beneficial metabolic effects in obese individuals. SUBJECTS/METHODS: A total of 31 obese individuals with normal or impaired glucose tolerance were enrolled in a randomized, double-blind, cross-over study in which metabolic effects of daily intake of a rose hip powder drink over 6 weeks was compared with a control drink. Body weight, glucose tolerance, blood pressure, blood lipids and markers of inflammation were assessed in the subjects. RESULTS: In comparison with the control drink, 6 weeks of daily consumption of the rose hip drink resulted in a significant reduction of systolic blood pressure (-3.4%; P=0.021), total plasma cholesterol (-4.9%; P=0.0018), low-density lipoprotein (LDL) cholesterol (-6.0%; P=0.012) and LDL/HDL ratio (-6.5%; P=0.041). The Reynolds risk assessment score for cardiovascular disease was decreased in the rose hip group compared with the control group (-17%; P=0.007). Body weight, diastolic blood pressure, glucose tolerance, and plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, incretins and markers of inflammation did not differ between the two groups. CONCLUSIONS: Daily consumption of 40 g of rose hip powder for 6 weeks can significantly reduce cardiovascular risk in obese people through lowering of systolic blood pressure and plasma cholesterol levels.

Hyperbaric oxygen therapy improves health-related quality of life in patients with diabetes and chronic foot ulcer.

AIMS: Adjunctive treatment with hyperbaric oxygen therapy has recently been shown to improve ulcer healing in patients with chronic diabetic foot ulcer. The aim of the present study is to evaluate whether hyperbaric oxygen therapy improves the health related quality of life in these patients. METHODS: Prospective randomized placebo-controlled double-blinded study setting using SF-36. RESULTS: A total of 75 patients were included in the study; 38 were randomized to hyperbaric oxygen therapy and 37 to placebo (hyperbaric air). The overall mean physical and mental summary scores for the entire study population at baseline were 29.6 ± 8.8 and 47.5 ± 12.4, respectively. There was a significant difference between baseline and 1 year follow-up responses to the mental summary score and two of the eight (SF-36) (?) domains in the -hyperbaric oxygen group, whereas no significant improvement of health related quality of life was seen in the placebo group. Comparing quality of life in patients who healed their ulcer (healers) with those who did not (non-healers), post-treatment levels of the mental health summary score, social functioning and role limitations due to physical and emotional health were significantly improved in healers. No differences were seen in any SF-36 (?) domain in non-healers. CONCLUSIONS: Hyperbaric oxygen therapy improves long-term health related quality of life in patients with chronic diabetic foot ulcers, possibly attributable to better ulcer healing.

Relationship between ulcer healing after hyperbaric oxygen therapy and transcutaneous oximetry, toe blood pressure and ankle-brachial index in patients with diabetes and chronic foot ulcers.

AIMS/HYPOTHESIS: The randomised, double-blind, placebo-controlled Hyperbaric Oxygen Therapy (HBOT) in Diabetic Patients with Chronic Foot Ulcers (HODFU) study showed beneficial effect of HBOT. As this treatment is expensive and time-consuming, being able to select patients for therapy would be very useful. The aim of this study was to evaluate whether circulatory variables could help in predicting outcome of HBOT. METHODS: All HODFU study participants who completed therapy, predefined as receiving at least 36 out of 40 scheduled HBOT/placebo sessions, were included in this study (n = 75). Baseline transcutaneous oximetry (TcPO2), toe blood pressure (TBP) and ankle-brachial index (ABI) were measured. Ulcer healing rate was registered at the 9-month follow-up visit. An ulcer was considered healed when it was completely epithelialised and remained so at the 12-month follow-up. RESULTS: In the HBOT group TcPO2 were significantly lower for patients whose ulcer did not heal as compared with those whose ulcers healed. A significantly increased healing frequency was seen with increasing TcPO(2) levels in the HBOT group (TcPO2/healing rate: <25 mmHg/0%; 26-50 mmHg/50%; 51-75 mmHg/73%; and >75 mmHg/100%). No statistically significant relation between the level of TBP or ABI and healing frequency was seen. CONCLUSIONS/INTERPRETATION: Our results indicate that TcPO2 in contrast to ABI and TBP correlates to ulcer healing following HBOT. We suggest HBOT as a feasible adjunctive treatment modality in diabetic patients with chronic non-healing foot ulcers when basal TcPO2 at the dorsum of the foot is above 25 mmHg. TRIAL REGISTRATION: NCT00953186 FUNDING: Mrs Thelma Zoegas Foundation and Faculty of Medicine, Lund University.

Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families.

The main genetic predisposition to type 1 diabetes (T1D) is known to be conferred by the HLA-DRB1, -DQA1 and -DQB1 genes in the major histocompatibility complex (MHC). Other genetic factors within this complex are known to contribute, but their identity has often been controversial. This picture is shared with several other autoimmune diseases (AIDs). Moreover, as common genetic factors are known to exist between AIDs, associations reported with other AIDs may also be involved in T1D. In this study, we have used these observations in a candidate gene approach to look for additional MHC risk factors in T1D. Using complementary conditional methods (involving conditional logistic regression and family-based haplotype tests) and analyses of linkage disequilibrium (LD) patterns, we confirmed association for alleles of the HLA-A and HLA-B genes and found preliminary evidence for a novel association of a single-nucleotide polymorphism (rs2259571) in the AIF1 gene, independent of the DRB1-DQA1-DQB1 genes and of each other. However, no evidence of independent associations for a number of previously suggested candidate polymorphisms was detected. Our results illustrate the importance of a comprehensive adjustment for LD effects when performing association studies in this complex.

Implicit testing of odor memory: instances of positive and negative repetition priming.

The study provides a test and evaluation of a new repetition priming procedure designed to solve problems in investigating olfactory-specific priming. Although the results did not reveal any overall priming effect, a post-hoc analysis showed that incorrectly identified odors were more quickly processed than control odors, whereas correctly identified odors were processed more slowly These results are discussed and interpreted as instances of positive and negative repetition priming respectively.

Region-specific migration of embryonic glia grafted to the neonatal brain.

Cell fate determination and region-specific migration among neurons from the developing brain have been widely studied. Because similar attributes have been mostly unexplored in reference to glia, the present study has characterized the migratory responses of glia from diverse regions of the embryonic mouse brain after their transplantation to the brains of early postnatal (still developing) rats. Through the use of the mouse-specific, glial-specific marker M2, immunocytochemical processing of host tissues three to four weeks after transplantation revealed notable difference in the migratory patterns of phylogenetically diverse populations of glia. While glia from the ventral mesencephalon, cerebral cortex, and cerebellar neuroepithelium all showed a similar affinity for the nigropallidal tract after grafting to the internal capsule, only ventral mesencephalon-derived glia showed restricted migration toward and into the substantia nigra after transplantation to the thalamus or pontine tegmentum. These results suggest the presence of a highly favourable substrate for glial migration along developing fibre tracts, but, more importantly, indicates the potential for certain glia to respond to particular (region-specific) distal cues within the developing brain.

Functional neuroanatomical correlates of electrodermal activity: a positron emission tomographic study.

To reveal areas in the central nervous system of importance for electrodermal control, regional cerebral blood flow (rCBF) was correlated to nonspecific skin conductance fluctuations (NSF) during aversive and nonaversive conditions. Participants viewed a TV screen displaying white noise or snake videotapes presented both with and without electric shocks given to the right hand. H2 15 O positron emission tomography was used to measure rCBF, and the constant voltage technique was used to measure NSF from the left hand. Electrodermal activity was positively related to rCBF in the left primary motor cortex (MI, Brodmann's Area 4) and bilaterally in the anterior (Areas 24 and 32) and posterior cingulate cortex (Area 23). Negative relations were observed bilaterally in the secondary visual cortex (Areas 18 and 19) and the right inferior parietal cortex (Area 39), with a tendency also for the right insular cortex (Areas 13, 15, and 16). Because results from lesion and stimulation studies in humans converge with the present imaging results, we conclude that the cingulum and the motor cortex, in addition to the parietal and possibly the insular cortex, form part of one or several distributed neural network(s) involved in electrodermal control. Because these areas also support anticipation, affect, and locomotion, electrodermal responses seem to reflect cognitively or emotionally mediated motor preparation.

Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure.

The aim of this 2-year study was to test the hypothesis that folic acid, vitamin B12 and sun exposure could be helpful in treating vitiligo. One hundred patients with vitiligo were treated with oral folic acid and vitamin B12 after being informed that sun exposure might enhance repigmentation. They were requested to keep a record of sun exposure in summer and UVB irradiation in winter. The minimal treatment time suggested was 3-6 months but should be longer if improvement was achieved. Clear repigmentation occurred in 52 patients, including 37 who exposed their skin to summer sun and 6 who used UVB lamps in winter. Repigmentation was most evident on sun-exposed areas, where 38% of the patients had previously noted repigmentation during summer months. Total repigmentation was seen in 6 patients. The spread of vitiligo stopped in 64% of the patients after treatment. Folic acid and vitamin B12 supplementation combined with sun exposure can induce repigmentation better than either the vitamins or sun exposure alone. Treatment should continue as long as the white areas continue to repigment. Further studies are needed to determine ideal minimal dosages of vitamins and UV exposure, as well as treatment time.

Influence of dolichol on microsomal membrane functions.

Microsomal membranes from rat liver were extracted with n-pentane in order to remove the lipid products of the mevalonate pathway, dolichol, ubiquinone and cholesterol. Dolichol and cholesterol were subsequently reincorporated into these extracted membranes. Electron microscopic examination demonstrated that extraction did not alter the vesicular membrane structure of the microsomes. The extracted vesicles were permeable to uncharged molecules in the same manner as control microsomes but had an increased permeability for charged molecules. Enzyme denaturation was not observed. The contraction of extracted vesicles was greatly increased when the incubation medium was supplemented with non-penetrating compounds such as polyethylene glycol and was much greater than that of control microsomes. When extracted membranes were reconstituted with dolichol or cholesterol, the original lower degree of contraction was reestablished. The effects of dolichol reincorporation on a number of microsomal enzyme activities were investigated and some limited changes were observed. These results demonstrate that extraction of microsomes with n-pentane and subsequent reincorporation of dolichol is an effective approach for investigating the functions of this lipid. Dolichol and cholesterol both affect microsomal membrane fluidity, but only cholesterol modifies the activities of certain integral microsomal membrane enzymes to a larger extent.

Ca(2+)-induced Ca2+ oscillations in parathyroid cells.

Parathyroid cells from patients with hyperparathyroidism were first cultured in a growth cocktail supplemented version of Dulbecco's MEM/F12 medium and then used for measurements of the cytoplasmic Ca2+ concentration ([Ca2+]i). Elevation of extracellular Ca2+ from 0.5 to 1.5-3 mM often triggered rhythmic oscillations of [Ca2+]i. Whereas the amplitude of the oscillations remained constant their frequency (0.4-2.6 /min) increased with the Ca2+ concentration and there was sometimes transformation into sustained increase of [Ca2+]i at the highest extracellular Ca2+ concentration. The oscillations were abolished by the inorganic Ca2+ channel blocker Ce3+ and by K+ depolarisation, which lowered [Ca2+]i, as well as by thapsigargin, an inhibitor of the intracellular Ca(2+)-pumping ATPase. The data indicate that extracellular Ca2+ can trigger [Ca2+]i oscillations in parathyroid cells, dependent on mobilisation of the ion from intracellular Ca2+ stores and on influx through non-voltage dependent channels.

[PCB methyl sulphone: comparison of tissue levels in Baltic grey seals and a Yusho patient].

Methyl sulphone metabolites of PCB and DDE were isolated from different tissues of a Baltic grey seal (Halichoerus grypus). Main components in the seal blubber were identified as 3-MeSO2-2,2',4',5,5'-pentaCB, 4-MeSO2-2,2',4',5,5'-pentaCB, 3-MeSO2-p,p'-DDE, 4-MeSO2-2,2',3',4',5-pentaCB and 4-MeSO2-2,2',3,4',5',6-hexaCB. Liver and lung in the seal contained different MeSO2-PCB pattern compared to all other tissues. These levels in the both tissues were estimated to be 28 and 15 ppm (lipid basis) which corresponded to the same level as the PCB. Concentrations of MeSO2-PCB in any tissues of a Yusho patient were low compared to those in the seal.

Blood glutathione-peroxidase levels in skin diseases: effect of selenium and vitamin E treatment.

Blood glutathione-peroxidase (GSH-Px) was determined in 61 healthy subjects and 506 patients with various skin disorders. Depressed levels were observed in patients with psoriasis, eczema, atopic dermatitis, vasculitis, mycosis fungoides and dermatitis herpetiformis. Low values of GSH-Px were also found in some patients with pemphigoid, acne conglobata, polymyositis, rheumatoid arthritis, scleroderma and systemic lupus erythematodes. Vegetarian diet, malnutrition and alcohol abuse could possibly account for the low values in some patients. Fifty patients with low GSH-Px levels were treated with tablets containing 0.2 mg selenium as Na2SeO3 and 10 mg tocopheryl succinate. The GSH-Px levels increased slowly within 6-8 weeks of treatment. The clinical effect was encouraging and calls for controlled studies.

Plasma amino acid response to single test meals in humans. III. Supplementary effect of dried skim milk and L-methionine on a vegetable protein mixture.

The plasma amino acid response to single test meals in young adults was used for human biological evaluation of the supplementary effect of dried skim milk powder (DSM) and synthetic L-methionine on a vegetable protein mixture. The protein sources in the vegetable mixture were wheat flour, defatted soya bean flour and pea flour. The plasma amino acid responses were evaluated both as PAA ratios (a modification of the Longenecker and Hause method), and as delta MR% (percentage change in the postprandial essential amino acid molar ratios according to Graham and Placko). Both evaluation methods indicated that there was an adequate supply of all the essential amino acids in the basic vegetable mixture, except for a small deficit of methionine. Supplementation (5% and 10%) with DSM did not significantly improve the low plasma amino acid response of methionine. The addition of synthetic L-methionine proved to be very effective in this respect. 1 g of L-methionine per 100 g of proteins from the vegetable mixture gave a plasma methionine response similar to that of the other essential amino acids. This implies that the deficit of methionine in the basic wheat/soya bean/pea mixture was about 30%.