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| 2. |
- Ahlner, Johan, et al.
(författare)
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Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden
- 2014
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications (UK and US). - 1403-4948 .- 1651-1905. ; 42:2, s. 177-183
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Tidskriftsartikel (refereegranskat)abstract
- Background: Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. Methods: This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. Results: The mean age of all victims (N = 895) was 48 +/- 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (+/- SD) 47 +/- 20 years, than alcohol positive cases (35 +/- 14 years) and illicit drug users (34 +/- 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in similar to 7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. Conclusions: The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.
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| 3. |
- Bastami, Salumeh, et al.
(författare)
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Influence of UGT2B7, OPRM1 and ABCB1 Gene Polymorphisms on Postoperative Morphine Consumption
- 2014
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 115:5, s. 423-431
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic modulation of pain with morphine and other opioids is associated with significant variation in both effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT2B7,OPRM1 and ABCB1 polymorphisms for interindividual variability in morphine-induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsies as morphine is also a very commonly abused drug. Blood samples were collected from 40 patients following abdominal hysterectomy, 24hr after initiation of analgesia through a patient-controlled analgesia (PCA) pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsies found positive for morphine in routine forensic analysis. Patients homozygous for UGT2B7 802C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T, as well as to OPRM1 118A. The dose of morphine in patients included in this study was significantly related to variation in UGT2B7 T802C. Age was significantly related to both dose and concentration of morphine in blood. Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNPs in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients. We conclude that gene polymorphisms contribute significantly to the variation in morphine concentrations observed in individual patients.
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| 4. |
- Bastami, Salumeh, et al.
(författare)
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Inhibitory effect of opiates on LPS mediated release of TNF and IL-8
- 2013
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:5, s. 1022-1033
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with advanced cancer experience severe pain and are often treated with opiates. Cancer patients are especially susceptible to opportunistic infections due to treatment with immunosuppressive and cytostatic drugs. Since opiates have been demonstrated to have immunomodulatory effects, it is of clinical importance to evaluate potential differences between commonly used opiates with regard to their effect on the immune system. The aim of this study was to evaluate the effect of morphine, tramadol, fentanyl and ketobemidone on the functioning of the immune system with special reference to TNF and IL-8 release. Method. U-937 cells were preincubated with different concentrations of opioids followed by stimulation with LPS 100 μg/ml for three hours. The effect of opioids on the levels of cytokine mRNA was studied using RT-PCR. Erk and Akt phosphorylation was also measured by Western blot. Results. All opioids with the exception of fentanyl were capable of inhibiting TNF release from U-937 cells. Morphine had no effect on IL-8 release but the effect of other opiates was almost the same as the effect on TNF. All opioids with the exception of fentanyl were capable of inhibiting production of mRNA for TNF and IL-8. The observed effects of opiates were not always reversible by naloxone, suggesting that the effects might be mediated by other receptors or through a non-receptor mediated direct effect. Although preliminary evidence suggests the involvement of Erk and Akt pathways, further studies are needed to unravel the intracellular pathways involved in mediating the effects of opiates. Our data suggests that the order of potency with regard to inhibition of cytokine release is as follows: tramadol > ketobemidone > morphine > fentanyl. Conclusion. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of tramadol and ketobemidone and to improve opioid treatment strategies in patients with cancer.
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| 5. |
- Bastami, Salumeh, 1967-
(författare)
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Practical and clinical use of opioids
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pain is a common symptom of a number of conditions including cancer and one of the most frequent reasons for seeking healthcare. Acute and chronic pain result in considerable discomfort with a detrimental impact on the quality of life. Opioids are the mainstay of pain management for many patients with severe pain. Opioids are, unfortunately, also commonly abused drugs, and are well-represented in forensic toxicology investigations.Side effects related to the central nervous system are the major reasons fordiscontinuation of opioid treatment. In this thesis, we tested the hypothesis that local analgesic treatment by opioids, without the usual opioid-related side effects, could be a potential alternative to systemic opioid treatment. We examined the analgesic effect of topically applied morphine in a randomized, double blind, cross over study in patients with painful leg ulcers. Significant reduction of pain was obtained after application of both morphine and placebo gel. Morphine reduced pain more than placebo but the difference was not statistically significant. However, morphine could reduce pain considerably more than placebo in those cases where VAS (Visual analog scale) was higher initially.Another issue with opioid therapy is the substantial individual variability in response to opioids including morphine and tramadol. We investigated the significance of UGT2B7, CYP2D6, OPRM1 and ABCB1 polymorphisms for pharmacokinetic and pharmacodynamic properties of morphine and tramadol. We showed that genetic variants in CYP2D6 and UGT2B7 have an important role in the metabolism of tramadol and morphine respectively. While the role of SNPs in ABCB1 remained unclear, genetic variants in OPRM1 gene were correlated with the required dose of morphine. Taken together, these findings suggest that genotypes should be taken into consideration when interpreting clinical pharmacology and forensic toxicology results.Opioids, besides their analgesic properties, have other pharmacological effects including effects on immune system. We evaluated potential differences between commonly used opiates with regard to their effect on the immune system. We found an inhibition of cytokine release, in the order of potency as follows: tramadol > ketobemidone >morphine >fentanyl. All opioids with the exception of fentanyl were capable of inhibiting production of mRNAs for TNF-alpha and IL-8. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of opioids and to improve opioid treatment strategies in patients with cancer.Here, we have found that individual genotype matters and affects the individual response. Further research is warranted to tailor individualized treatment. Personalized medicine has increased in importance and will hopefully in the near future become standard procedure to improve and predict the outcome of treatment by opioids.
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| 6. |
- Bastami, Salumeh, et al.
(författare)
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Topical morphine gel in the treatment of painful leg ulcers, a double-blind, placebo-controlled clinical trial : a pilot study
- 2012
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Ingår i: International Wound Journal. - : Blackwell Publishing. - 1742-4801 .- 1742-481X. ; 9:4, s. 419-427
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Tidskriftsartikel (refereegranskat)abstract
- Chronic painful wounds, a major health problem, have a detrimental impact on the quality of life due to associated pain. Some clinical reports have suggested that local administration of morphine could be beneficial. The aim of this study was to evaluate the analgesic effect of topically applied morphine on chronic painful leg ulcers. Twenty-one patients were randomly assigned to receive either morphine or placebo in a randomised, placebo-controlled, crossover pilot study. Each patient was treated four times in total. Pain was measured by the visual analogue score (VAS) before application of gel, directly after and after 2, 6, 12 and 24 hours. Although an overall, clinically relevant, reduction of pain was observed upon treatment with morphine, the difference was not statistically significant. Morphine reduced pain scores more than placebo on treatment occasions 1 and 2. The difference was statistically significant only 2 hours after dressing on the first treatment occasion. Thus, our study did not demonstrate a consistent and globally significant difference in nociception in patients treated with morphine. However, the relatively small number of patients included in our study and other methodological limitations makes it difficult for us to draw general conclusions regarding efficacy of topically applied morphine as an effective treatment for some painful ulcers. Further studies are warranted to evaluate the value of topically applied morphine in the treatment of patients with chronic painful leg ulcers.
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| 7. |
- Boiso, Samuel, et al.
(författare)
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ABCB1 gene polymorphisms are associated with suicide in forensic autopsies
- 2013
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Ingår i: Pharmacogenetics & Genomics. - : Lippincott, Williams and Wilkins. - 1744-6872 .- 1744-6880. ; 23:9, s. 463-469
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Tidskriftsartikel (refereegranskat)abstract
- Background Polymorphisms in ABCB1 have the ability to affect both the function and the expression of the transporter protein P-glycoprotein and may lead to an altered response for many drugs including some antidepressants and antipsychotics.Objective The aim of this study was to examine the impact of the ABCB1 polymorphisms 1199Gandgt;A, 1236Candgt;T, 2677Gandgt;T/A, and 3435Candgt;T in deaths by suicide.Patients and methods A total of 998 consecutive Swedish forensic autopsies performed in 2008 in individuals 18 years of age or older, where femoral blood was available and a toxicological screening had been performed, were investigated. Genotypes were assessed with pyrosequencing and information on the cause and manner of each death was obtained from the forensic pathology and toxicology databases.Results There was a significantly higher frequency of the T allele at positions 1236, 2677, and 3435 among the suicide cases compared with the nonsuicide cases.Conclusion Our result from forensic cases suggests that ABCB1 polymorphisms are associated with an increased risk for completed suicides. The biological mechanisms involved and the clinical implications for these findings are largely unknown and need to be examined further.
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| 8. |
- D Cherma, Maria, et al.
(författare)
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Antidepressant Drugs in Children and Adolescents Analytical and Demographic Data in a Naturalistic, Clinical Study
- 2011
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Ingår i: JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY. - : Williams andamp; Wilkins. - 0271-0749. ; 31:1, s. 98-102
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacokinetics of antidepressant drugs (ATDs), in terms of steady-state and trough values, in patients from Child and Adolescent Psychiatry centers in the midsouth-eastern part of Sweden, were evaluated, and the use of ATDs in this population were described. Patients to be prescribed an ATD were studied between 2002 and 2004. Two hundred eleven children, 64% girls and 36% boys (ages 8-20 years) were evaluated. The primary indication for the antidepressant treatment was depression in 69% of subjects. The median body mass index was 20.2 kg/m(2) (range, 12.4-38.6 kg/m(2)). Suspected adverse drug reactions were spontaneously reported in 31% (no serious). Monotherapy was indicated in 49% of request forms. The most common drug combination with the ATD was oral contraceptives. The concentrations of drugs in the patient evaluated population to referenced data for adults from the dose administered were as expected in 63%, higher than expected in 26% and lower than expected in 11%. The most prescribed ATD was sertraline (SERT). Dose-concentration relationships for SERT and metabolite desmethylsertraline (DSERT) were seen, r(s) = 0.48 and r(s) = 0.5, respectively. No relationship was found between dose and ratio DSERT/SERT. The median daily dose was 50 mg (range, 12.5-150 mg), SERT concentration 16 ng/mL (range, 3-88 ng/mL), and DSERT 33 ng/mL (range, 0-253 ng/mL). CYP2D6*4 was the most common poor metabolizer allele. Therapeutic drug monitoring may provide support to prescribing physicians to individual dose optimizing and to assess drug compliance, above all when ATDs are not well studied in pediatric patients before approval for general prescription.
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| 9. |
- Hedlund, Jonatan, et al.
(författare)
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A population-based study on toxicological findings in Swedish homicide victims and offenders from 2007 to 2009
- 2014
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 244, s. 25-29
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Previous research on the toxicology of homicide has shown that about half of offenders and victims have psychoactive substances in their blood. The purpose of this study was to examine this topic in a Swedish setting. Methods: Toxicological data were sought in a database for all victims (n = 273) and perpetrators (n = 257) of homicide in Sweden from 2007 to 2009. Sufficient tests were identified for 97.1% of all victims (n = 265) and 46.7% of all offenders (n = 120). Additional information was obtained from court records and police reports. Results: A majority of individuals involved in homicides displayed positive toxicology (57.0% of victims and 62.5% of offenders). The most commonly detected substances, in both victims and offenders, were ethanol (44.9% vs. 40.8%) and benzodiazepines (8.3% vs. 19.2%). The difference between offenders and victims concerning benzodiazepines was statistically significant (OR 2.6; p = 0.002). Perpetrators of homicide-suicide had a lower prevalence of positive toxicology (30.8%) than other homicide offenders (66.4%; p = 0.04) and victims in unsolved cases more often exhibited positive drug toxicology compared to victims in solved cases (36.1% vs. 8.3%; p less than 0.001). Conclusions: The results of the study support the notion that substance abuse is firmly linked to committing homicide and to becoming a victim thereof.
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