Forensic biomarkers of elder abuse: what clinicians need to know.
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The Cardiac Troponin T and I are highly cardiac specific biochemical markers of myocardial injury. They are very sensitive markers to detect all kinds of myocardial injury, and are able to distinguish myocardial injury and skeletal injury. Furthermore, They are independent predictor of future cardiac events. Such markers are now widely used in the clinic practice. It is prospective to use them in Forensic Medical Science.
The diagnosis of the vital origin of wounds in many cases remains an unsolved problem for the forensic pathologist. Practical experience enables the expert to diagnose the vital or postmortem origin of wounds on the basis of macroscopic examination. In some cases, optic microscopy is used to confirm the diagnosis. In many other cases, additional more sensitive and specific markers of vitality are required. In the past 50 years, comprehensive research on this topic has resulted in a better understanding of the acute inflammatory reaction. The development and application of sensitive and specific markers through research in the areas of histochemistry, enzymology, and biochemistry has provided a partial solution to the problems involved in wound vitality diagnosis. A review of this challenging area of forensic pathology, including an explanation of these methods and markers, is presented in this paper.
The aim of the present study was to clarify the relationships between testosterone and alcohol abuse, alcohol dependence and specific personality characteristics and behaviors in a forensic psychiatric population. Serum levels of total testosterone (TT), free testosterone (FT-DPC) and sex hormone-binding globulin (SHBG) were determined in 61 male subjects undergoing forensic psychiatric examinations. All subjects had been detoxified from drugs and alcohol during previous incarceration in jail or hospital. TT and FT-DPC were found to be highly correlated (r=0.63, P < 0.0001). High concentrations of TT and SHBG were consistently related to type II alcoholism, but not pure alcohol dependence. TT and SHBG were also related to antisocial personality disorder. Furthermore, TT and SHBG were related to socially deviant behavior, reflected in factor 2 in the Psychopathy Checklist (PCL-R). In a multiple regression, FT-DPC was also clearly associated with the psychopathy-related scales of the Karolinska Scales of Personality (KSP) when age and signs of hepatic damage were kept under control.
We attempted to develop a method for the determination of liver injuries, using a liver-specific antigen as a marker. The liver-specific antigen (LSA) was purified from the human liver and the antibody to the human LSA only reacted with the liver extract using the immuno-dot-blotting technique. Depending on the immunohistochemical study, the LSA was found to be located within the cytoplasm of hepatocytes. A sensitive and specific sandwich enzyme immunoassay was then developed for the measurement of LSA. The detection limit of human LSA was 1 fmol/tube (52 pg/tube) and this assay was not affected by hemolysis. The LSA levels in serum and blood from healthy subjects were distributed within a range below the detection limit. The LSA levels in the blood from cadavers whose livers had been damaged, were markedly elevated in comparison with the normal levels found in other cadavers (10-140 fold). No cross-reaction was observed with the liver extracts from several species (mouse, rat, guinea pig and rabbit). These results suggest that the measurement of LSA levels in blood will become a useful marker for the detection of liver injury.
The measurement of the myeloperoxidase activity was used to quantify the acute granulocyte reaction. A 35% loss of blood resulted in a clear decrease of the myeloperoxidase activity at the edges of experimental incision wounds in rat skin in the first day after inflicting the wounds. After 12 h only about one-third and after 24 h about half of the activity observed in the wounds without the loss of blood remained. After 3 days however the activity had returned to the same level as in the wounds without any loss of blood. In very deep excoriations of the rat skin where only a narrow zone of the dermis was left about double the activity increase was observed after 12 and 24 h when compared to values observed in very superficial or moderate excoriations. When the same type of excoriations were made in both thin inguinal skin and thick dorsal skin then a much higher peroxidase activity increase was observed over 4, 12 and 24 h in the thin inguinal skin than in the excoriations made in the thick dorsal skin.
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We investigated the possibility of identification of human skin left under various conditions using our original enzyme immunoassay (EIA) for squamous cell carcinoma-related (SCC) antigen. The antigen could be detected in specimens under the following conditions : purified or dried at room temperature for at least 12 months, immersed in fresh water at room temperature for 3 weeks and heated at 100 degrees C for 72 h.
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The quantity of usual alcohol consumption is a fact that can be determined from the anamnesis of patients. In many cases patients do not inform their doctors in detail, in some cases they want to keep it a secret. The diagnosis of alcohol abuse based on objective data is a necessary requirement in clinical, insurance, as well as in forensic medicine. Among the different biomarkers of chronic alcohol abuse, carbohydrate-deficient transferrin is recognized world wide as the most reliable indicator. The authors review the pathomechanism of carbohydrate-deficient transferrin in the human organism, the methods for its measurement and its role in the diagnostic procedures of alcohol induced clinical diseases, as well as its decisive role for life insurance and in forensic medicine.
Methanogenic flowthrough aquifer columns were used to investigate the potential of bioaugmentation to enhance anaerobic benzene-toluene-ethylbenzene-xylene (BTEX) degradation in groundwater contaminated with ethanol-blended gasoline. Two different methanogenic consortia (enriched with benzene or toluene and o-xylene) were used as inocula. Toluene was the only hydrocarbon degraded within 3 years in columns that were not bioaugmented, although anaerobic toluene degradation was observed after only 2 years of acclimation. Significant benzene biodegradation (up to 88%) was observed only in a column bioaugmented with the benzene-enriched methanogenic consortium, and this removal efficiency was sustained for 1 year with no significant decrease in permeability due to bioaugmentation. Benzene removal was hindered by the presence of toluene, which is a more labile substrate under anaerobic conditions. Real-time quantitative PCR analysis showed that the highest numbers of bssA gene copies (coding for benzylsuccinate synthase) occurred in aquifer samples exhibiting the highest rate of toluene degradation, which suggests that this gene could be a useful biomarker for environmental forensic analysis of anaerobic toluene bioremediation potential. bssA continued to be detected in the columns 1 year after column feeding ceased, indicating the robustness of the added catabolic potential. Overall, these results suggest that anaerobic bioaugmentation might enhance the natural attenuation of BTEX in groundwater contaminated with ethanol-blended gasoline, although field trials would be needed to demonstrate its feasibility. This approach may be especially attractive for removing benzene, which is the most toxic and commonly the most persistent BTEX compound under anaerobic conditions.
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A highly sensitive and specific sandwich enzyme immunoassay for human liver-specific antigen (LSA) was developed and its forensic application using LSA as a marker for the determination of liver injury were examined. The LSA was purified from human liver by immunoaffinity chromatography. Polystyrene ball coated with affinity-purified rabbit anti-human LSA IgG was incubated with the human LSA and then with affinity-purified anti-human LSA Fab'-horseradish peroxidase conjugate. Peroxidase activity bound to the polystyrene ball was assayed by fluorometry using 3-(4-hydroxyphenyl) propionic acid as a hydrogen donor. The detection limit for human LSA was 0.52 pg per assay. The serum LSA levels determined by this assay in healthy male and female adults were 1.5-1.6 ng/ml and 0.7-1.0 ng/ml, respectively. The recovery of LSA added to 5 microliters and 10 microliters serum samples was estimated to be 53.1-55.5% and 70.6-74.8%, respectively, and no difference in recovery between serum from males and females was observed. LSA antigenic activity in bloodstains containing LSA was detectable after storage for 30 days at room temperature. High levels of LSA were proved to exist in forensic samples taken from stabbed livers, and it was clearly possible to differentiate between samples from stabbed livers and those originating from other stabbed organs. These findings demonstrate that determination of LSA from forensic samples is useful for detecting liver injuries.
The time-dependent expression of ubiquitin (Ub) was examined in murine skin wounds and 55 human skin wounds with different wound ages (groups I: 0-12 h, II: 1-5 days, III: 7-14 days and IV: 17-21 days). In murine skin wound specimens, neutrophils, macrophages and fibroblasts showed intensive Ub-positive reactions in the nuclei. In the human wound specimens with wound ages between 4 h and 1 day, neutrophils with strong intranuclear positive reactions for Ub were observed. With increasing wound ages, the nuclei of macrophages and fibroblasts were more intensively stained with anti-Ub antibody. Morphometrically, the intranuclear Ub-positive ratios were very low in group I. The skin wound specimens in groups II and IV showed Ub-positive ratios of >10%, and all samples in group III had Ub-positive ratios of >20%. These results suggest that a ratio of >10% for Ub indicates a wound age of at least 1 day. In contrast, Ub-positive ratios of less than 10% indicate a wound age of <1 day. Moreover, there was a significant difference in the Ub-positive ratio between group III and the other three groups. Thus, Ub-positive ratios considerably exceeding 30%, possibly indicate a wound age of 7-14 days. From the viewpoint of a forensic pathology application, the present study showed that Ub is suitable as a marker of wound age determination.
BACKGROUND: Considerable lives and money could be saved if one could detect early stages of lapsing/relapsing behavior in addicted persons (e.g., in safety-sensitive workplaces) and could disclose harmful drinking in social drinkers. Due to the serious public health problem of alcohol use and abuse worldwide, markers of alcohol use have been sought. Both ethyl glucuronide (EtG) and phosphatidyl ethanol (PEth) appear to have high sensitivity and specificity and a time frame of detection that may elucidate alcohol use not detected by standard testing. Our aim was to assess their potential for detecting recent covert alcohol use under controlled conditions. METHODS: Thirty-five forensic psychiatric inpatients in a closed ward who had committed a substance-related offense ( section sign 64 StGB), were followed for 12 months. The complete time spectrum of possible alcohol consumption was covered by the complementary use of breath and urinary ethanol (hours), urinary EtG (days), %carbohydrate-deficient transferrin (CDT)/PEth (weeks), and gamma-glutamyltranspeptidase (GGT)/mean corpuscular volume (MCV) (weeks-months). RESULTS: Fourteen of the 146 urine samples examined were positive for EtG. In all EtG-positive cases, patients reported alcohol consumption of between 40 and 200 g of ethanol 12-60 hr prior to testing. Urinary and breath ethanol were positive in only one case. In the blood samples, PEth was not positive in any case and %CDT did not exceed the reference value. Isoelectric focusing showed no abnormal Tf subtypes. CONCLUSIONS: The findings emphasize the diagnostic and therapeutic usefulness, specificity, and sensitivity of EtG as a marker of recent alcohol use. Such a test is needed in numerous settings, including alcohol and drug treatment (to detect lapse/relapse), in safety-sensitive work settings where use is dangerous or in other settings where use may be inappropriate (e.g., such as driving, workplace, pregnancy, or monitoring physicians or other professionals who are in recovery and working), or for testing other groups (such as children or those with medical problems) where alcohol use would be unhealthy or unsafe. The health, social and socioeconomic benefits arising from the future use of these markers is hard to overestimate.
Recent natural catastrophes with large-scale loss of life have demonstrated the need for a new technique to provide information for disaster victim identification when DNA methods fail to yield the identification of an individual, or in other situations where authorities need to determine the recent geographical life history of people. The latter may be in relation to the identification of individuals detained on suspicion of terrorism or in relation to people-trafficking or smuggling. One proposed solution is the use of stable isotope profiling (SIP) using isotope ratio mass spectrometry (IRMS). Exploiting the link between the isotopic signal of dietary components and the isotopic composition of body tissue, the aim of this study was to refine a non-invasive method of analysing human material such as scalp hair and fingernails using SIP and to assess the degree of natural variability in these profiles. Scalp hair and fingernail samples were collected from British and non-British volunteers at Queen's University Belfast every 2 weeks for a minimum of 8 months. Samples were analysed using IRMS to determine their isotopic composition for 13C, 15N, 2H and 18O. The results of this longitudinal study yielded information on the natural variability of the isotopic composition of these tissues. The data demonstrate the relatively low degree of natural variation in the 13C/15N isotopic abundance of scalp hair and fingernails whilst greater variations were recorded in the hydrogen and oxygen values of the same samples. The 15N and 18O values of nail are noticeably more variable than that of scalp hair from the same subject. A hypothesis explaining this trend is put forward based on the faster rate of formation of hair than of nails. This means that there is less time for the compounds forming hair to be affected by biochemical processes that could alter their isotopic signature.
Fibronectin has been proposed as the reliable marker of wound vitality and potent tool for age estimation in cases where survival time is at least few minutes. Cases of suicidal gunshot wounds were divided into two groups according to projectile energy and damage of the vital structures. Immunohistochemical reaction on fibronectin was evaluated with semiquantitative scale, which included sum of intensity and widespread of the reaction. Mann-Whitney test has shown statistical significant difference between groups (P< or =0.001).
UNLABELLED: The significance of haemolytic staining of the aorta is unclear. While it has been associated with freshwater drowning, data are lacking. To study this phenomenon further a prospective study looking at the colour of the intima of the pulmonary trunk and aortic root was undertaken in 47 randomly selected coronial control cases and in 13 consecutive fresh drowning deaths. There were 16 putrefied control cases each of which showed haemolytic staining of both great vessels. Of the other 44 non-putrefied cases (31 controls, 9 saltwater drownings, and 4 freshwater drownings), only one (a freshwater drowning) showed marked staining of the aortic root with no staining of the intima of the pulmonary trunk. CONCLUSION: This study has demonstrated that haemolytic staining of the aorta at autopsy, in the absence of significant staining of the pulmonary trunk and putrefaction, may be a pathological feature that is supportive of freshwater drowning. It is not, however, present in all cases. Given the relatively small numbers in this study further work is required to clarify this issue.