PubMed Health⌕ Search

Biomedical subjects

H Druid

Publications and source records attributed to H Druid.

At least 19 recordsLinked to original sources

Flunitrazepam: an evaluation of use, abuse and toxicity.

The benzodiazepine flunitrazepam is extensively prescribed to patients with insomnia in many countries, but has also become popular among alcohol- and drug abusers. Several reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. Furthermore, flunitrazepam is involved in many fatal intoxications in Sweden. This study was designed and conducted to explore the negative consequences of flunitrazepam abuse in Sweden, and to assess the trends in its use and abuse. The occurrence of flunitrazepam in cases referred to the Department of Forensic Chemistry in Linköping, Sweden 1992-1998, was investigated in detail. The detections were studied separately for different groups; medicolegal death investigations, drug abuse cases, driving under influence cases, and other medicolegal cases. These data were further compared with the sales, and seizures by the Swedish Customs and the Swedish Police. During 1992-1998, 641 fatalities occurred, where the cause of death was attributed to intoxication with flunitrazepam solely (130) or in combination with other drugs, or concomitant conditions (511). In 78% of all driving under influence cases, where flunitrazepam was detected, the analyses also disclosed the presence of illicit drugs. A similar association was seen in drug abuse cases. The seizures reported by the Swedish Customs revealed a substantial and increasing illegal trade. Cases, where flunitrazepam seemingly induced violent behavior were identified, and one of these is described in some detail. It is concluded that the abuse pattern and the toxicity of flunitrazepam should be kept in mind by forensic investigators and that this panorama also should be considered when decisions about the registration and classification of flunitrazepam are made in different countries.

Anti-Anxiety Agents↗

[GHB--dangerous, addictive and uncontrollable "party drug"].

This report reviews the pharmacology, toxicity and abuse pattern of gamma-hydroxybutyrate (GHB). The legislative changes pertaining to this substance are also addressed. Examples of abuse, driving under the influence and fatal intoxication are given. It is concluded that GHB is widely abused, particularly among the younger generation, and that further cases of severe intoxication are likely to occur as long as the substance is easily available from countless sources, including via the Internet. Despite the classification of GHB as a narcotic in Sweden and several other countries, continued problems are expected since the precursors gamma-butyrolactone (GBL) and 1,4-butanediol (BD) are widely--and legally--available.

4-Butyrolactone↗

Postmortem measurements of thyroid hormones in blood and vitreous humor combined with histology.

The aim of this study was to investigate whether clinical reference premortem values can be used to assess postmortem concentrations of thyroxine, triiodothyronine, and thyroid stimulating hormone (TSH), to compare the postmortem concentrations in blood and vitreous humor, and to study the possibility of diagnosing hyperthyroidism by comparing thyroid histologic appearance and postmortem hormone values. Biochemical analyses of free thyroxine (FT4), free triiodothyronine (FT3), and TSH in femoral blood and vitreous humor were made in 38 cases. In 40 cases, the hormones and thyroid histologic appearance were studied; 22 had no significant pathologic changes, and 18 showed focal hyperplasia of the follicular epithelium. A positive correlation was seen between the femoral blood and vitreous humor concentrations of FT4 (R = 0.66) but not between the corresponding concentrations of FT3 and TSH. A positive correlation was also seen between FT3 and FT4 in femoral blood (R = 0.74). In cases with normal thyroid histologic appearance, 58% were found to have FT4 values >24 pmol/L (clinical reference interval 9-24 pmol/L), mean value 27.5 +/- 9.4 pmol/L), which did not differ from the FT4 values in the cases with hyperplasia, 31.6 +/- 15 pmol/L. Only 5% of the T3 measurements in the group with normal histologic appearance were >9 pmol/L (clinical reference interval 3-9 pmol/L). The mean value of FT3 in cases with normal histologic appearance was 3.4 +/- 1.3 pmol/L, and in the group with hyperplasia 8.6 +/- 6.1 pmol/L. The difference was statistically significant P < .005). It is concluded that postmortem values of FT3 and FT4 in femoral blood are fairly comparable to premortem clinical reference values, but the upper normal limit, especially for T4, has to be adjusted upward. Analysis of vitreous humor cannot be used post mortem to assess thyroid function. Histologically, hyperplastic changes correlate well with elevated FT3 in femoral blood.

Adult↗

Incomplete shored exit wounds: a report of three cases.

Typical and atypical exit wounds are well described in the forensic literature. Included in the descriptions of atypical exit wounds are perforating, "shored" exit wounds, in which the perforation of the skin is associated with an abrasion, whether or not the bullet fully exits the body. The authors describe an atypical, incomplete, shored exit wound in which the skin was abraded by supporting material at the site the bullet was recovered, but there was no associated perforation of the skin. Recognition of this injury pattern can be important in reconstruction of the crime scene in relation to the victim at the time of the shooting.

Adult↗

Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results.

Debrisoquine hydroxylase (CYP2D6) is involved in the metabolism of many toxicologically important drugs. The gene encoding for this enzyme displays a polymorphic distribution in all populations examined. We report a study on 46 cases, where analyses of the CYP2D6 gene were conducted on postmortem femoral blood in order to investigate the occurrence of poor metabolizers (PM). A polymerase chain reaction (PCR) method, designed and routinely used for therapeutic drug monitoring, was employed, only slightly modified. Samples from 22 cases, where the parent drug to metabolite ratio was unexpectedly high were analyzed as well as samples from 24 control cases. Genotyping could be carried out in all but one case. Previous freezing or addition of potassium fluoride as preservative did not prevent analysis. Only one PM (from the control group) was discovered, implying an occurrence of only 2.2% as compared to the reported frequency of approx. 7% in Sweden. Among the extensive metabolizers (EM), however, a number of individuals with mutated genes were identified. Although it seems reasonable to suspect a PM genotype in cases with a high concentration of a drug metabolized by CYP2D6, but without suspicion of acute overdose, our study does not support the opinion that this interpretation pitfall is particularly common. This study rather indicates that drug interactions in EMs constitute a more frequent and important problem.

Adult↗

Psychotropics and suicide prevention. Implications from toxicological screening of 5281 suicides in Sweden 1992-1994.

BACKGROUND: Systematic clinical investigations of consecutive suicides have found psychiatric disorders in 90-95% of subjects (depressive disorder 30-87%). AIMS: To investigate use of psychotropics in men and women of different ages who commit suicide. METHOD: Results of toxicological screening in 5281 suicides in Sweden 1992-94 were studied. RESULTS: Psychotropics were detected in 45.3% of the suicides. Antidepressants were detected in 12.4% of the men and 26.2% of the women (7.2% and 14.2%, respectively, of those under 30 years of age). Neuroleptics or antiepileptics (in the absence of antidepressants) were detected in 8.3%, and anxiolytics/hypnotics alone in 20.5% of the subjects. Overdose by an antidepressant was the probable cause of death in 2.1% of the men and 7.9% of the women. CONCLUSIONS: The pattern of psychotropics detected in toxicology was incongruent with the pattern of diagnoses found in the clinical investigations of suicides mentioned above. Depression appears to be under treated in individuals committing suicide, especially in men and in subjects under 30 years of age.

Adolescent↗

Effect of anticoagulation on renal function and protein excretion in experimental acute ischemic renal failure.

Female Sprague-Dawley rats underwent right nephrectomy and 40 min left renal artery occlusion (RAO). After 15 min of reflow, polyethylene glycol 1000 (PEG1000) was infused to induce osmotic diuresis and to enable glomerular filtration rate (GFR) measurements. Urine was collected during a 90 min period, and the concentrations of PEG1000, albumin, IgG, IgM and fibrin(ogen)/degradation products (FIB) were assessed both in plasma and urine by radial immuno diffusion technique Groups of rats were subjected to saline + RAO, warfarin + RAO or sham-operation. GFR as measured by PEG1000 clearance averaged 0.61, 0.036 and 0.094 mL/min/100g BW/kidney in sham-operated, saline + RAO and warfarin + RAO rats, respectively. Urinary excretion of albumin and IgG increased substantially in both ischemic groups. IgM was not detected in any of the urine samples. FIB excretion was lowest in the saline + RAO group, possibly due to retention of FIB-containing obstructions in the tubules. Rats subjected to warfarin + RAO had significantly higher excretion of FIB. This result suggests that warfarin does not prevent the glomerular sieving of macromolecules in the glomerular filter, but reduces tubular obstruction by preventing fibrin formation, which may explain its positive effect on GFR.

Acute Kidney Injury↗

Alzheimer changes are common in aged drivers killed in single car crashes and at intersections.

With increasing age, diseases affecting the cognitive functions are more frequent. These diseases may increase the risk for fatal car crashes. We analyzed the frequency of neuropathological alterations characteristic of Alzheimer's disease (i.e. neuritic and diffuse plaques, and neurofibrillary tangles) in two association areas of the brain, parietal and frontal cerebral cortex, from 98 fatally injured aged drivers. In the age groups of 65-75 and over 75 years of age, 50% and 72% of the drivers, respectively, had neuritic plaques in either parietal and/or frontal cortex. In 14% of all killed drivers the number of neuritic plaques reached the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) age-related histologic score C, which indicates the diagnosis of Alzheimer's disease (AD), and an additional 33% had score B, which suggests the diagnosis of AD. Neuropathological AD changes were most common in the brains of drivers killed in single vehicle crashes, followed by multivehicle crashes at intersections and least common in multivehicle crashes elsewhere, but the differences did not reach statistical significance. In a great majority (80-85%) of cases the killed aged driver was the guilty party of the crash. The results imply, that incipient AD may contribute to fatal crashes of aged drivers, and therefore the forensic autopsy of these victims should include neuropathological examination.

Accidents, Traffic↗

Fatal injections of heroin. Interpretation of toxicological findings in multiple specimens.

We report two fatalities due to injection of heroin. The first case was witnessed but during the early phase of the police investigation the question was raised whether the injection was self-administered. Multiple samples were collected from different sites and analysed in order to establish drug distribution and to determine the site of injection. Fresh injection marks were found in both antecubital fossae but histological examination failed to settle which one was the last. However, toxicological analysis of the tissues at the injection sites indicated that the injection in the right arm was the last one. This was consistent with the suspicion that the victim was given the injection by another person although probably in agreement with the deceased. In the second case, a similar toxicological procedure was used. This fatality was not witnessed, however ample evidence indicated that it was an isolated event in a former intravenous heroin addict and there was only one fresh injection mark. Even in this case, the concentration of morphine was much higher in the tissue sample from the injection mark than in any of the blood samples.

Adult↗

Effect of anticoagulation upon nephron obstruction in experimental acute ischaemic renal failure. A morphological study.

Ischaemic-reperfusion injury as a model of acute renal failure (ARF) results in increased macromolecular permeability, tubular obstruction, and renal oedema. To investigate the role for coagulation in this model, anticoagulated and saline-pretreated rats were subjected to 60 min unilateral renal artery occlusion (RAO). After 15 min of reflow, specimens were collected for electron and light microscopic examination. Morphometry was employed to study podocyte changes and Bowman's space dilatation as measures of increased permeability and tubular obstruction, respectively. After 15 min of reflow, Bowman's space increased significantly and the podocytes were markedly widened and flattened. Rats pretreated with heparin or warfarin showed less widening of Bowman's space than saline-treated rats, whereas no significant difference was seen regarding the podocyte changes. In saline-treated rats, fibrin-positive material was seen in the tubules but not in the urine sediments collected after 90 min of reflow, either due to fibrinolysis or poor urinary elimination. The results suggest that anticoagulation does not preclude the glomerular sieving of macromolecules, but seems to reduce tubular obstruction, probably by preventing conversion of filtered fibrinogen into fibrin.

Acute Kidney Injury↗

A cluster of fentanyl-related deaths among drug addicts in Sweden.

During a 16-month period, nine fatalities occurred among white male drug-addicts, where fentanyl was detected at postmortem toxicological analysis. The street samples associated with these cases confirmed the presence of fentanyl as an additive in low-concentration amphetamine powders with caffeine, phenazone and sugar as cutting agents. In seven of the cases, an acute intoxication by fentanyl was considered to be the immediate cause of death, and in one case, it was likely, but no analysis of fentanyl was performed in blood, and in another case the death was suicide by hanging. This appears to be the first report of a cluster of fentanyl-related deaths outside the United States, and the occurrence of fentanyl in combination with amphetamine has not previously been reported. In addition, in all cases, femoral blood was collected, and samples were handled and analysed according to standardized, quality-controlled procedures. The previous history, circumstances surrounding the death, autopsy findings, histology and toxicology examination of each case are presented. The gas chromatographic-mass spectrometric method for fentanyl is also described. Fentanyl concentrations ranged from 0.5 to 17 ng g-1 blood, and from 5 to 160 ng ml-1 urine. Other drugs found were amphetamine (8 cases), ethanol (5 cases) and benzodiazepines (5 cases). Morphine was found in only one case. The average age of men was 33.9 years (range 22-44); six were found in their own of friend's apartment, two inside buildings (stairways) and one was found outdoors. We conclude that fentanyl is a dangerous substance that should be considered in drug-addict deaths even outside the United States, particularly when the remaining toxicology is unremarkable, and the cause of death cannot be ascertained

Adult↗

Site of entrance wound and direction of bullet path in firearm fatalities as indicators of homicide versus suicide.

In a retrospective study, 288 firearm deaths were analysed to identify factors indicating homicide. The cases were classified as suicides (213), homicides (54), accidents (14) and undetermined cases (7). A number of factors, related to the circumstances and the autopsy findings, were studied. Whereas 41% of the homicide victims were females, women only constituted 1.4% of the suicide victims. The mean age was 37 and 50 years among homicide and suicide victims, respectively. Most suicides were committed at or in the vicinity of the residence, whereas a majority of the homicides occurred elsewhere. The majority of the suicide victims had either left a suicide note or had medical records of previous psychiatric illness. In all groups, shotguns were the most frequent weapon used. Fifty-seven percent of the homicide victims, but only three percent of the suicide victims had sustained more than one gunshot wound. One-third of the homicide victims were shot at close range. Alcohol was present in one-third of both homicide and suicide victims. Whereas 38% of the homicidal gunshot wounds had their entrances at anatomical regions typical of suicide, the direction of the bullet path often differed from the directions recorded in suicides. Hence, in this material, an entrance wound in the right temple indicated suicide, but in combination with a direction back-to-front, the wound was more likely to be homicidal. This study suggests that an estimation of the direction of the internal bullet path should be conducted in firearm fatalities, and that this factor may assist in the determination of the manner of death.

Accidents↗

The utilization of antidepressants--a key issue in the prevention of suicide: an analysis of 5281 suicides in Sweden during the period 1992-1994.

Antidepressants detected by the National Department of Forensic Chemistry in 5281 suicides in Sweden during the period 1992-1994 were related to data on usage expressed in person-years of exposure. Antidepressants were detected in 874 subjects (16.5%). In relation to their use, fluvoxamine, citalopram, moclobemide, mianserin and trimipramine were found more often than the reference drug, amitriptyline (i.e. over-risks). Toxic concentrations of antidepressants were detected in 232 subjects (4.4%). Most people committing suicide were not taking antidepressants immediately before their death, even though 40-85% may have been depressed. Undertreatment and therapeutic failure are the main problems with antidepressants, not the risk of using antidepressants in overdose. Comparisons of new antidepressants should focus on efficacy in relation to reference tricyclics. The huge increase in the use of antidepressants in Sweden since 1990-1991 has been paralleled by a significant decrease in suicide rates.

Amitriptyline↗

A compilation of fatal and control concentrations of drugs in postmortem femoral blood.

A compilation of postmortem femoral blood concentrations of drugs is presented. The samples are collected from cases in which the cause of death was: A) certified intoxication by one substance alone, B) certified intoxication by more than one substance and/or alcohol, and C) certified other cause of death without incapacitation due to drugs. The concentrations were compared with blood concentrations detected in suspected drugged drivers (D), and with previously published fatal and therapeutic concentrations. The special features of this compilation are: 1) exclusively femoral blood concentrations are quoted, 2) all analyses are based on samples handled according to a standardized, quality-controlled procedure, 3) two control groups are included, and 4) one-substance-only intoxications are separated from other intoxications. The material is based on a selection of 15,800 samples sent to the Department of Forensic Chemistry in Linköping, Sweden, during 1992 to 1995 from the six forensic pathology units in Sweden, and the list includes 83 drugs. The compilation includes drugs, where previously published data are scarce. Furthermore, the data gathered from cases with other cause of death than intoxication (group C) constitute a new kind of reference information, which probably offers a better estimate of obviously non fatal levels in postmortem blood than any compilation of therapeutic concentrations in living subjects. The possible factors influencing postmortem drug concentrations are discussed.

Blood Chemical Analysis↗

Computer-assisted systems for forensic pathology and forensic toxicology.

A computer software, RättsBASE (RB), was developed for all forensic pathology units in Sweden and introduced in 1992. Simultaneously, a corresponding software, ToxBASE (TB), was developed for the Department of Forensic Toxicology, where all forensic toxicology in Sweden is managed. Both of the databases were created using dBASE IV, and the programming was carried out according to specifications from the staff at the forensic toxicology and forensic pathology units. since the development or RB and TB was coordinated, the systems can run together smoothly. The purpose of both systems was to automate the offices and to enable compilation of detailed statistics. Installation of Novell Netware and ISDN-connections (Integrated Service Digital Network) has enabled rapid communication between the units and easy compilation of nationwide statistics of forensic pathology and forensic toxicology. the systems offer a wide spectrum of reports and include a simple module for evaluation of the importance of the forensic efforts for th whole death investigation. The configuration of the softwares has also enabled processing of a large amount of related toxicological and autopsy data that in turn has yielded a base for compilation of toxicology interpretation lists. This article includes a summary of the features of the software and a discussion of its benefits and limitations.

Autopsy↗

Protective effect on postischemic renal edema by anticoagulation.

The effect of anticoagulation upon renal edema and plasma protein accumulation in acute ischemic renal damage was studied. Rats were subjected to unilateral renal artery occlusion for 60 min and 15 min of reflow. The kidney weight and the content of 125-I-fibrinogen and 131-I-albumin, injected 24 h priorly, were measured and the renal morphology studied. Groups of rats were pretreated with a heparin analogue with low anticoagulant effect, standard heparin, warfarin or saline. A marked increase in fibrinogen and albumin content and of the weight of the damaged kidney was noted. Heparin and warfarin both significantly attenuated these changes, whereas the heparin analogue did not. Microscopically, fibrin-positive material was seen in the peritubular capillaries, vasa recta and in the tubules of rats pretreated with saline or the heparin analogue, but not in rats pretreated with heparin or warfarin. The results support the hypothesis that fibrin deposition in the kidney is of importance for the development of renal edema in this model of ischemic renal damage.

Animals↗