Design and validation of an advanced entrained flow reactor system for studies of rapid solid biomass fuel particle conversion and ash formation reactions.

The design and validation of a newly commissioned entrained flow reactor is described in the present paper. The reactor was designed for advanced studies of fuel conversion and ash formation in powder flames, and the capabilities of the reactor were experimentally validated using two different solid biomass fuels. The drop tube geometry was equipped with a flat flame burner to heat and support the powder flame, optical access ports, a particle image velocimetry (PIV) system for in situ conversion monitoring, and probes for extraction of gases and particulate matter. A detailed description of the system is provided based on simulations and measurements, establishing the detailed temperature distribution and gas flow profiles. Mass balance closures of approximately 98% were achieved by combining gas analysis and particle extraction. Biomass fuel particles were successfully tracked using shadow imaging PIV, and the resulting data were used to determine the size, shape, velocity, and residence time of converting particles. Successful extractive sampling of coarse and fine particles during combustion while retaining their morphology was demonstrated, and it opens up for detailed time resolved studies of rapid ash transformation reactions; in the validation experiments, clear and systematic fractionation trends for K, Cl, S, and Si were observed for the two fuels tested. The combination of in situ access, accurate residence time estimations, and precise particle sampling for subsequent chemical analysis allows for a wide range of future studies, with implications and possibilities discussed in the paper.

Real-time PCR-assay in the delivery suite for determination of group B streptococcal colonization in a setting with risk-based antibiotic prophylaxis.

OBJECTIVE: Intrapartum antibiotic prophylaxis (IAP) reduces the incidence of neonatal early onset group B streptococcal infections. The present study investigated if an automated PCR-assay, used bedside by the labor ward personnel was manageable and could decrease the use of IAP in a setting with a risk-based IAP strategy. METHODS: The study comprises two phases. Phase 1 was a multicenter, randomized, controlled trial. Women with selected risk-factors were allocated either to PCR-IAP (prophylaxis given if positive or indeterminate) or IAP. A vaginal/rectal swab and superficial swabs from the neonate for conventional culture were also obtained. Phase 2 was non-randomized, assessing an improved version of the assay. RESULTS: Phase 1 included 112 women in the PCR-IAP group and 117 in the IAP group. Excluding indeterminate results, the assay showed a sensitivity of 89% and a specificity of 90%. In 44 % of the PCR assays the result was indeterminate. The use of IAP was lower in the PCR group (53 versus 92%). Phase 2 included 94 women. The proportion of indeterminate results was reduced (15%). The GBS colonization rate was 31%. CONCLUSION: The PCR assay, in the hands of labor ward personnel, can be useful for selection of women to which IAP should be offered.

High re-arrest rates among drug-impaired drivers despite zero-tolerance legislation.

BACKGROUND: A zero-tolerance law for driving under the influence of drugs (DUID) in Sweden led to a 10-fold increase in the number of cases submitted by the police for toxicological analysis. The statutory blood-alcohol concentration (BAC) limit for driving is 0.2 mg/g ( approximately 0.02 g%). METHODS: An in-house database (TOXBASE) was used to investigate re-arrests for impaired driving over 4 years (2001-2004), which comprised 36,799 cases. The age, gender, re-arrest rate of the offenders and the concentrations of ethanol and amphetamine in blood samples were evaluated. RESULTS: We found that 44% of individuals (N=16,277) re-offended 3.2 times on average (range 1-23 arrests). Between 85 and 89% of first-time offenders were men and there was also a male dominance among the recidivists (88-93%). The mean age of drunken drivers was approximately 40 years compared with approximately 35 years for driving under the influence of amphetamine, which was the drug identified in 50-60% of DUID cases, either alone or together with other licit or illicit drugs. The median BAC was 1.5mg/g ( approximately 0.15 g%), which suggests a dominance of heavy drinkers. The median BAC was even higher in recidivists (1.6-1.7 mg/g). The median concentration of amphetamine in blood was 1.0 mg/L in recidivists compared with 0.5mg/L in the first-time offenders. About 14% of drunken drivers re-offended 1-10 times compared with 68% of DUID suspects, who were re-arrested 1-23 times. People with only a scheduled prescription drug in blood were re-arrested much less frequently ( approximately 17%) compared with those taking illicit drugs (68%). CONCLUSIONS: The appreciable increase in number of arrests for DUID after a zero-tolerance law might reflect a heightened enthusiasm by the police authorities armed with knowledge that a prosecution is easier to obtain. Zero-tolerance laws do not deter people from impaired driving judging by the high re-arrest rates. During the sentencing of hardcore offenders, the courts should give more consideration to the underlying substance abuse problem.

Predominance of illicit drugs and poly-drug use among drug-impaired drivers in Sweden.

OBJECTIVE: After Sweden's zero-tolerance law came into force (1 July 1999), the number of cases of driving under the influence of drugs (DUID) submitted by the police for toxicological analysis increased more than 10-fold. This prompted an in-depth investigation into the kinds of drugs used by DUID offenders, whether licit or illicit, and the frequency of their occurrence. METHODS: All blood samples from DUID suspects sent by the police for toxicological analysis over a 4-year period (2001-2004) were investigated (N = 22,777 cases). Specimens of blood or urine were subjected to a broad screening analysis by immunoassay methods aimed at detecting amphetamines, cannabis, opiates, cocaine metabolite, and the major benzodiazepines. All positive results from the screening stage were verified by use of more specific analytical methods (e.g., GC-MS, LC-MS, GC-FID, and GC-NPD). RESULTS: Between 80 and 85% of all the blood samples contained at least one banned substance and many contained two or more therapeutic and/or illicit drugs. About 15% of cases were negative for drugs, although these frequently (30-50%) contained ethanol above the legal limit for driving in Sweden, which is 0.20 mg/g (0.02 g%). Amphetamine was the most prominent illicit drug seen in 55-60% of cases either alone or together with other drugs of abuse. Stimulants like cocaine and/or its metabolite were infrequently encountered ( approximately 1.2% of cases). The next most prevalent illicit drug was cannabis, with positive results for tetrahydrocannabinol (THC) in blood either alone ( approximately 4%) or together with other psychoactive substances ( approximately 20%). Morphine, codeine, and/or 6-acetyl morphine were identified in approximately 2% of all DUID suspects, being indicative of heroin abuse. The major prescription drugs identified in blood were benzodiazepines (10%) as exemplified by diazepam, alprazolam, nitrazepam, and flunitrazepam. Drugs for treating insomnia, zolpidem and zopiclone, were also identified in blood samples from DUID suspects over the study period. Other therapeutic agents were encountered in only 1-2% of all cases. CONCLUSIONS: The dramatic increase in DUID after the zero-tolerance law came into force probably reflects enhanced police activity and more enthusiasm to apprehend and charge individuals for this offence. Illicit drugs, particularly amphetamine and cannabis, and poly-drug use were predominant compared with use of scheduled prescription drugs. The typical DUID offender in Sweden abuses central stimulants, particularly amphetamine, and has probably done so over many years. Options for treating offenders for their underlying substance abuse problem should be considered instead of the more conventional penalties for drug-impaired driving.

Cause of death and drug use pattern in deceased drug addicts in Sweden, 2002-2003.

Compared with their contemporaries, individuals abusing illicit drugs suffer a higher risk of premature death. In Sweden, a simple protocol for registration of fatalities among abusers of alcohol, pharmaceuticals, illicit drugs, or other substances, has been used by the forensic pathologists since 2001. This routine was introduced to allow for an evaluation of the cause and manner of death, and patterns of abuse among different groups of abusers. We explored the data on drug abusers (i.e. abusers of illicit drugs) subjected to a forensic autopsy 2002-2003. The Swedish forensic pathologists examined 10,273 dead victims during the study period and 7% (743/10,273) of the cases were classified as drug abusers. Toxicological analyses were carried out in 99% (736/743) and illicit drugs were detected in 70% (514/736) of these. On average, 3.8 substances (legal or illegal) were found per case. The most common substances were ethanol and morphine, detected in 43 and 35% of the cases, respectively. When exploring the importance of the different substances for the cause of death, we found that the detection of some substances, such as fentanyl and morphine, strongly indicated a poisoning, whereas certain other substances, such as benzodiazepines more often were incidental findings. In total, 50% (372/743) died of poisoning, whereas only 22% (161/743) died of natural causes. Death was considered to be directly or indirectly due to drug abuse in 47% (346/743), whereas evidence of drug abuse was an incidental finding in 21% (153/743) or based on case history alone in 33% (244/743). We believe that this strategy to prospectively categorize deaths among drug addicts constitutes a simple means of standardizing the surveillance of the death toll among drug addicts that could allow for comparisons over time and between countries.

Toxicological findings and manner of death in autopsied users of anabolic androgenic steroids.

With the aim to characterize patterns in toxicological profile and manner of death in deceased users of anabolic androgenic steroids (AAS), a retrospective autopsy protocol study of 52 deceased users of AAS was undertaken. The AAS users were compared to 68 deceased users of amphetamine and/or heroin who were consecutively tested and found to be negative for AAS. Use of AAS was in the majority of cases (79%) associated with concomitant use of psychotropic substances. AAS-related deaths differed in several respects from deaths among users of heroin or amphetamine, most strikingly with regard to: (a) the median age at death, which was significantly lower for AAS users (24.5 years) than for users of heroin and/or amphetamine (34 and 40 years, respectively); (b) the manner of death, with AAS users dying significantly more often from homicide or suicide than users of other drugs; and (c) the body mass index (BMI), with AAS users exhibiting significantly higher BMI than users of other drugs. These results support the earlier reported association between use of AAS and use of other psychoactive substances. In addition, the data suggest that AAS users are more likely to become involved in incidents leading to violent death and have a higher risk of dying at a younger age than users of other drugs.

Application of direct urine LC-MS-MS analysis for screening of novel substances in drug abusers.

A newly developed liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was used to study 3000 human urine samples from 3 different populations for 23 analytes covering phenylethylamines, benzylpiperazine, and non-benzodiazepine hypnotics. Direct injection of urine and LC-MS-MS with rapid chromatography and atmospheric pressure chemical ionization was used in the screening step. The cutoff levels were chosen to be at the limit of detection for most analytes to identify as many positive samples as possible. Typically one ion transition was monitored from the pseudo-molecular ions in the multiple reaction monitoring mode. Of the 797 positive screening findings, 518 (65%) were confirmed by a second LC-MS-MS analysis including solid-phase extraction. Confirmed analytical findings included 22 cases positive for N-benzylpiperazine, 88 for 3,4-methylenedioxy-N-methylamphetamine and metabolites, 4 for 1-phenyl-2-butylamine, 24 for zolpidem and metabolites, 118 for zopiclone and metabolites, and 1 for zaleplon. In conclusion, LC-MS-MS was found to be a robust alternative for drugs of abuse screening, offering high sensitivity compared with immunochemical screening methodology.

Alcohol and drugs in drivers fatally injured in traffic accidents in Sweden during the years 2000-2002.

During the years 2000-2002, alcohol, pharmaceuticals and illicit drugs were analysed in blood samples from fatally injured drivers in Sweden. The total number of drivers was 920 and in 855 of these, corresponding to 93%, a toxicological investigation was performed. About 85% of the drivers were men and 15% were women. All but three women (96%) were car drivers while the corresponding figure for men was about 78% and about 13% were motorcyclists. The number of positive cases increased from 38.9% in year 2000 to 45.9% in year 2002 and alcohol was the most common drug with frequencies of 19.8%, 25.0% and 21.8% for the studied years 2000, 2001 and 2002, respectively. The median blood alcohol concentration ranged from 1.6 to 2.0mg/mL for men and from 1.2 to 1.8 mg/mL for women. There was a decrease in cases where alcohol was the only drug detected, from 52 out of 58 cases (90%) in year 2000 to 41 out of 61 cases (67%) in 2002. At the same time there was an increase, from 5.4% to 10.0% of illicit drugs, mainly amphetamine, and the cases with multiple drug intake increased from 10% to 26%. The prevalence of pharmaceuticals as the only drug or drugs detected decreased from 14.0% to 10.4% and in the majority of these cases the drug concentrations were within the therapeutic range.

Stability of drugs in stored postmortem femoral blood and vitreous humor.

The stability of 46 drugs in postmortem femoral blood stored for one year at -20 degrees C was investigated. The drugs included benzodiazepines, antidepressants, analgetics and hypnotics. For seven drugs we found a significant change in the concentration between the first and second analysis. Five substances; ethanol, desmethylmianserin, 7-amino-nitrazepam, THC and zopiclone showed a decrease in the concentration whereas the concentrations of two substances; ketobemidone and thioridazine increased. However, the changes observed were not of such an order that it would affect the interpretation in normal forensic casework. We also investigated the possible influence of potassium fluoride on the concentrations of the 46 drugs in vitreous humor after storage for one year. For two substances, ethanol and zopiclone, there were significantly lower concentrations in the samples without potassium fluoride. Furthermore, we also studied the correlation between the concentrations in femoral blood and vitreous humor. For 23 substances there was a significant difference between the concentrations in the vitreous humor and femoral blood. Significant correlations between the concentrations in these two specimens were found for 23 substances, indicating that vitreous humor can be an alternative specimen when blood samples are not available, provided that such correlation exists for the particular substance. Statistical analysis also revealed a correlation between the degree of protein binding of the different drugs and percentage of vitreous/femoral blood concentrations.

Proactive management promotes outcome in extremely preterm infants: a population-based comparison of two perinatal management strategies.

OBJECTIVE: There is a need for evidence-based knowledge regarding perinatal management in extreme prematurity. The benefit of a proactive attitude versus a more selective one is controversial. The objective of the present study was to analyze perinatal practices and infant outcome in extreme prematurity in relation to different management policies in the North (proactive) and South of Sweden. METHODS: A population-based, retrospective, cohort study design was used. Data in the Swedish Medical Birth Register (MBR) from 1985 to 1999 were analyzed according to region of birth and gestational age (22 weeks + 0 days to 27 weeks + 6 days). A total of 3 602 live-born infants were included (North = 1040, South = 2562). Survival was defined as being alive at 1 year. Morbidity in survivors, based on discharge diagnoses of major morbidity during the first year of life, was described by linking the MBR to the Hospital Discharge Register. RESULTS: In infants with a gestational age of 22 to 25 weeks, the proactive policy was significantly associated with 1) increased incidence of live births, 2) higher degree of centralized management, 3) higher frequency of caesarean section, 4) fewer infants with low Apgar score (<4) at 1 and 5 minutes, 5) fewer infants dead within 24 hours, and 6) increased number of infants alive at 1 year. There were no indications of increased morbidity in survivors of the proactive management during the first year of life, and the proportion of survivors without denoted morbidity was larger. CONCLUSION: In infants with a gestational age of 22 to 25 weeks, a proactive perinatal strategy increases the number of live births and improves the infant's postnatal condition and survival without evidence of increasing morbidity in survivors up to 1 year of age.

Fatal intoxications in a Swedish forensic autopsy material during 1992-2002.

Compilations of substances detected in fatal intoxications are important in order to observe changes in intoxication patterns, to monitor effects of preventive work and to discover new trends in drug usage. The aim of the present study was to describe the current pattern of substances detected in fatal intoxications in Sweden. Fatal intoxications investigated at the Department of Forensic Chemistry, Linköping, Sweden, during 1992-2002, were analysed. All suicides, uncertain cases and accidents where the cause of death were fatal intoxications (ICD-9: E950, E980 and E859) were included and substances detected in more than 50 fatal intoxications (in femoral blood) were listed. For each substance, a cut off value was set, above which concentrations were considered toxic. Fatal intoxications were detected by forensic-chemical analyses in 12% (6998/60,314) of the forensic autopsies during the study period. Among the suicides, an average of 3.8 substances were detected per case, the corresponding figure for uncertain cases and accidents were 3.5 and 4.1 substances, respectively. Ethanol was by far the most frequently detected substance, detected in 43% (3039) of the fatal intoxications, of which 32% (960) had toxic concentrations, followed by propoxyphene, detected in 27% (1863) of the fatal intoxications of which 74% (1370) had toxic concentrations. The number of cases where ethanol and propoxyphene were detected decreased during the study period. Moreover, other CNS-active drugs such as antidepressants, analgesics and anxiolytics were also frequently detected. The drugs with high proportions of cases with toxic concentrations detected were propoxyphene, amitriptyline, zolpidem, carisoprodol, alprazolam, thioridazine, methadone and ketobemidone. Selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressants (TCA) were detected in 12% (833) and 10% (665), respectively. A significantly (P <0.001) higher proportion of cases where TCA were detected had toxic concentrations when compared with cases where SSRI were detected (64% versus 31%).

Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19.

Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (+/- standard deviation) S/R ratio for citalopram was 0.67 +/- 0.25 and for desmethylcitalopram, 0.68 +/- 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.

A2 (N-benzylpiperazine) a new drug of abuse in Sweden.

N-Benzylpiperazine was tested in the beginning of the 1970s as a possible antidepressant drug. However, in both animal and human studies, it was shown to possess amphetamine-like properties, and any further studies were stopped. In a forensic autopsy case in 1999, we found a substance so far unknown to us in the chromatogram of our method used for amphetamines. We could swiftly identify this compound as N-benzylpiperazine because of information given to us by a newly formed network comprising, among others, customs and the police. Since then, we have found N-benzylpiperazine in several cases, among them 11 cases from a number of prisons.

Caffeine fatalities--four case reports.

Four cases of fatal intoxications with caffeine are described. Caffeine is widely available in beverages and in different OTC-products, in many of them in combinations with other drugs like ephedrine. Caffeine is not as harmless as one might believe. An overdose of caffeine alone, intentional or not, might be deadly. It seems to be warranted to include caffeine in the drug-screening of forensic autopsy cases. It is not motivated from a medical point of view to sell pure caffeine over the counter.

The role of benzodiazepines in elderly suicides.

AIMS: In Sweden, suicides by drug poisoning have decreased in the population at large during the past two decades. However, drug poisoning suicides increased among the elderly during this period. Suicides by benzodiazepine poisoning increased in this age group despite a reduction in prescription sales of these drugs. This study aims therefore to determine the role of benzodiazepines in suicide late in life. METHODS: Information concerning all definite suicides and deaths due to "undetermined" causes recorded among Swedish citizens aged 65 and above during 1992 - 96 was obtained from the Cause-of-Death Register. Death certificates were scrutinized to determine the type of drug employed in drug-related suicides. Results of the post mortem screening for drugs and alcohol were then examined. RESULTS: A benzodiazepine was implicated in 216/548 (39%) of the drug poisoning suicides recorded among the elderly. Death certificates revealed that a benzodiazepine was the sole agent in 72% of these cases. Flunitrazepam or nitrazepam were implicated in 90% of the single benzodiazepine suicides. In addition to the suicides classified as drug poisonings, 82 cases were found in which a drug may have contributed to the cause of death. Benzodiazepines predominated. The terminal cause of death was drowning, often in the victim's own bathtub, in three-quarters of these cases. The annual fatality ratios for the newer benzodiazepine-like hypnotics zopiclone and zolpidem appear to be on the rise. CONCLUSION: Benzodiazepines, especially the hypnotics flunitrazepam and nitrazepam, are common in drug poisoning suicides in the elderly and should be prescribed with caution for this age group.

Codeine and morphine blood concentrations increase during blood loss.

During extensive blood loss, a plasma volume refill will take place by transfer of extravascular fluid into the circulation. Drugs present in this fluid may follow and cause a rise or a drop in blood drug concentration, depending on their levels and accessibility in the restoration fluid. This study explored the possible changes of codeine, and its metabolite morphine, in whole blood during a standardized exsanguination in the rat. Three doses containing 5 mg codeine were given orally. In eight rats, blood loss was accomplished by slowly withdrawing 0.8 mL blood at 10 min intervals during 70 min. In control rats, blood was withdrawn only at 0 and 70 min. At 70 min, the final/initial codeine and morphine concentration ratios were 0.70 +/- 0.38 and 0.88 +/- 0.47, respectively, in controls, but increased to 1.28 +/- 0.44 (p = 0.014) and 1.41 +/- 0.34 (p = 0.021), respectively, in exsanguinated rats. It is concluded that blood loss can affect blood drug concentrations.