Insulin murder and the case of Colin Norris

Although insulin is an essential medicine and a life-saving drug, it has also been incriminated in many poisoning deaths; accidental, suicidal and some with malicious intent. Overdosing with insulin precipitates a life-threatening state of hypoglycemia and if untreated leads to coma, irreversible brain damage and death. Normally, the pancreatic β-cells secrete equimolar amounts of insulin and C-peptide into the portal venous blood, although under physiological conditions the plasma concentration ratio (insulin/C-peptide) is less than unity, because insulin is more susceptible to hepatic first-pass metabolism. A high ratio of insulin/C-peptide in plasma from a poisoned patient is compelling evidence that pharmaceutical insulin was administered, which does not contain C-peptide. The analysis of insulin and C-peptide was traditionally done by immunoassay methods (RIA and/or ELISA), although high resolution LC-MS/MS is more suitable for forensic purposes and permits the identification of insulin analogues. Use of insulin as a murder weapon is exemplified by the case of Colin Norris, a male nurse found guilty of murdering four elderly patients and the attempted murder of a fifth by injecting them with insulin. However, the prosecution evidence against Norris was mainly circumstantial and hearsay. Toxicological evidence against Norris consisted of a high insulin/C-peptide concentration ratio in plasma from one of the victims. This analysis was done by an immunoassay method at a clinical laboratory and not a forensic laboratory. Analytical procedures, including chain-of-custody routines, are more stringent at forensic laboratories. Since his conviction, some of the medical evidence against Norris has been called into question, especially the prevalence of spontaneous attacks of hypoglycemia in elderly and frail patients with co-morbidities.     

Genetic analysis of sudden cardiac death victims: a survey of current forensic autopsy practices

Autopsy-negative sudden cardiac deaths (SCD) seen in forensic practice are most often thought to be the result of sudden arrhythmic death syndrome. Postmortem genetic analysis is recommended in such cases, but is currently performed in only a few academic centers. In order to determine actual current practice, an on-line questionnaire was sent by e-mail to members of various forensic medical associations. The questions addressed routine procedures employed in cases of sudden cardiac death (autopsy ordering, macroscopic and microscopic cardiac examination, conduction tissue examination, immunohistochemistry and electron microscopy, biochemical markers, sampling and storage of material for genetic analyses, toxicological analyses, and molecular autopsy). Some questions concerned the legal and ethical aspects of genetic analyses in postmortem examinations, as well as any existing multidisciplinary collaborations in SCD cases. There were 97 respondents, mostly from European countries. Genetic testing in cases of sudden cardiac death is rarely practiced in routine forensic investigation. Approximately 60% of respondents reported not having the means to perform genetic postmortem testing and 40% do not collect adequate material to perform these investigations at a later date, despite working at university hospitals. The survey demonstrated that many of the problems involved in the adequate investigation of SCD cases are often financial in origin, due to the fact that activities in forensic medicine are often paid by and dependent on the judicial authorities. Problems also exist concerning the contact with family members and/or the family doctor, as well as the often-nonexistent collaboration with others clinicians with special expertise beneficial in the investigation of SCD cases, such as cardiologists and geneticists. This study highlights the importance in establishing guidelines for molecular autopsies in forensic medicine.     

Sudden infant death due to Lactococcal infective endocarditis

Infective endocarditis (IE) of infants is rare, most of which occur associated with congenital heart disease or its cardiac surgery. We experienced a case of sudden death of a four-month-old male infant without congenital heart disease. It was elucidated by postmortem examination that the dead had suffered severe IE, which led him to death. In the microbiological genetic analysis using histological section, the pathogen causing inflammation in the present case was identified as Lactococcus lactis subspecies, although Staphylococci have been reported to be common and important one. Previously reported infectious diseases by Lactococcus lactis subspecies were all adult cases and this is the first report of an infantile death due to Lactococcal IE according to our knowledge. Any fatal disease may be included in sudden death cases targeted for forensic autopsy, even if it is rare. It is expected for forensic pathologists that they note such case and share each experience among themselves and other medical fields to develop a strategy for prevention.     

The role of histology in forensic autopsies: Is histological examination always necessary to determine a cause of death?

In England and Wales there is a conflict between the law and advice from regulatory bodies in relation to the sampling of human tissue for histological examination following medico-legal post-mortem examinations. Considering the results of previous publications, we performed a specific study to investigate the role of histology in determining the cause of death in cases at a forensic unit. A retrospective study of 500 adult forensic cases was performed. Cases were categorized by the role the histological examination played in determining a cause of death and its contributory factors. Furthermore, cause of death, manner of death, organ systems involved, and discrepancies were assessed. Of the 500 cases, histology was undertaken in 287 cases (58 %). Microscopic examination provided the cause of death in 2 % of cases where histology had been undertaken, and it added to the cause of death in 8 %. In 61 % of cases microscopy confirmed the macroscopic findings, and in 30 % it did not influence the medical cause of death. Histological examination of all organs in all forensic cases for the purpose of providing a medical cause of death is not supported. Practice guidance should be adjusted to reflect that, while histological examination is essential in certain circumstances, the decision to retain material for histology should be made on a case by case basis at the pathologist’s discretion.     

Re-establishment of rigor mortis: evidence for a considerably longer post-mortem time span

Re-establishment of rigor mortis following mechanical loosening is used as part of the complex method for the forensic estimation of the time since death in human bodies and has formerly been reported to occur up to 8–12 h post-mortem (hpm). We recently described our observation of the phenomenon in up to 19 hpm in cases with in-hospital death. Due to the case selection (preceding illness, immobilisation), transfer of these results to forensic cases might be limited. We therefore examined 67 out-of-hospital cases of sudden death with known time points of death. Re-establishment of rigor mortis was positive in 52.2% of cases and was observed up to 20 hpm. In contrast to the current doctrine that a recurrence of rigor mortis is always of a lesser degree than its first manifestation in a given patient, muscular rigidity at re-establishment equalled or even exceeded the degree observed before dissolving in 21 joints. Furthermore, this is the first study to describe that the phenomenon appears to be independent of body or ambient temperature.

     

Forensische Veterinärmedizin

Forensic veterinary medicine is covered by different disciplines because there is no independent discipline comparable to legal medicine. A major area of forensic veterinary medicine focuses on offences against animal protection legislation. Other fields of activities include examination of causes of death and identification of species involved in forensic cases. Interdisciplinary collaboration with legal medicine in criminal cases is a further important aspect of forensic veterinary medicine. Findings in cases of cruelty to animals reveal that expansion and intensification of the existing co-operation between forensic veterinarians and forensic pathologists is necessary. A systematic analysis of cases of cruelty to animals and a correlation with subsequent violence to humans is required. This area should be a task for future interdisciplinary research activities.     

Sudden death victims <45 years: Agreement between cause of death established by the forensic physician and autopsy results

PurposeThe goal of this study was to ascertain accordance between cause of death established by the forensic physician and autopsy results in young sudden death victims in the Netherlands.MethodsSudden death victims aged 1–45 years examined by forensic physicians operating in the participating regions which also underwent an autopsy between January 2006 and December 2011 were included (n = 70). Cause of death established by the forensic physician based on the external medicolegal examination was compared with autopsy findings using the ICD10-classification.ResultsAutopsy findings revealed that the majority of sudden death victims have died from a cardiac disease (n = 51, 73%). Most of the presumed heart disease related cases were confirmed by autopsy (n = 13, 87%). On the contrary, a large number of deaths caused by circulatory diseases were not recognised by the forensic physician (n = 38, 75%). In most of these cases, the forensic physician was forced to report an undetermined cause due to the lack of a solid explanation for death. Cause of death reported by the forensic physician appeared to be in agreement with the autopsy results in 12 cases (17%).ConclusionsCause of death determination in young sudden death victims is a difficult task for forensic physicians due to the limited tools available during the medicolegal examination. An effort should be made to standardize extensive post-mortem investigation after sudden death in the young. Autopsy can provide valuable information regarding the cause of death, which is of great importance in view of the identification of inheritable diseases among decedents and their families.     

Unusual methods of suicide: complexities in investigation

Differentiation between suicide and homicide often becomes difficult owing to the unusual methods of suicide used by the victim and the complexities thus posed. Investigating the cases of unusual suicides provides a considerable challenge to the authorities concerned. The issue of homicide should often be ruled out in such cases, which require careful evaluation. This is best done by correlating the morbid anatomical findings at autopsy with the death scene analysis coupled with psychological autopsy. Many forensic practitioners have reported unusual methods of suicide at their respective workplaces. Various types of unusual methods of suicide and the complexities involved in their investigation are presented and discussed.     

Sudden death from ruptured intracranial vascular malformation

Central nervous system (CNS) vascular malformations are well-known entities that may cause sudden death from rupture and intracranial hemorrhage. Despite this, relatively few papers deal with these lesions in the forensic literature. Here, we present four cases of sudden, non-traumatic death caused by ruptured CNS vascular malformations. In all four cases, the definitive source of bleeding was not identified grossly, being diagnosed only after relatively extensive histologic examination. When a source of intracranial hemorrhage is not readily identified at autopsy, it is common for forensic pathologists to rule the cause of death in such cases as “spontaneous intracerebral hemorrhage” or “spontaneous subarachnoid hemorrhage,” depending on the location of the hemorrhage. Whether or not histologic evaluation is performed in such cases depends on pathologist preference or office policy, and may be influenced by limited available funding for such studies. Because vascular malformations are not always grossly visible at autopsy when accompanied by intracranial hemorrhage, we contend that it is important to thoroughly investigate the underlying cause of such hemorrhage through a meticulous gross examination as well as histologic examination. Such examination will lead to a more accurate assignment of the cause of death, which may have important implications for surviving family members, and will lead to a better understanding of the natural history of these intracranial lesions. A brief discussion of the histologic classification of CNS vascular malformations is provided.     

Suicide by combined insulin and glipizide overdose in a non-insulin dependent diabetes mellitus physician: a case report

A case of self-injected insulin intoxication with an oral hypoglycaemic agent glipizide overdose in a type-II/non-insulin dependent diabetes mellitus (NIDDM) individual, a physician by profession, is presented with a review of the literature. The case demonstrates the need for thorough scene investigation, perusal of clinical details and complete autopsy to certify the death caused by combined insulin and glipizide overdose, and the manner of death. A meticulous search in the English literature reveals that hardly any fatal cases of combined insulin and glipizide overdose have been reported, with almost no cases from India, thus making this case report relevant and unique.     

Medical death certification by forensic physicians in the Netherlands: Validity and interdoctorvariation

The aim of the study was to assess interdoctorvariation and validity in death certification by forensic physicians using 19 written scenarios. The scenarios described typical cases from forensic-medical practice. Physicians were asked to determine the manner of death (natural/unnatural) and to provide an ICD-10 code for the cause of death. In contrast to most studies on this topic, the measure of agreement among physicians was chance-corrected and a standard was used to assess the correctness of the assigned cause and manner of death. Forty-seven physicians participated in the survey. The study demonstrated that forensic physicians varied widely in their conclusions. With respect to manner of death, adequate agreement (defined as kappa>0.70) was achieved in six scenarios (32% of all scenarios). Concerning the underlying cause of death, adequate agreement was reached in three cases (16% of all scenarios). Furthermore, predictors for the correctness of manner and cause of death were studied using logistic regression. Years of experience as a forensic physician significantly predicted the correctness of cause of death (p < 0.05). Other predictors remained insignificant. With regard to manner of death, none of the studied predictors proved to be significant. To conclude, there appears to be a lack of consistency among forensic physicians regarding death certification. The ICD-10 coding of causes of death applied by forensic physicians is questionable. Less experienced physicians need supervision by more experienced colleagues when making judgments concerning the cause of death. Altogether, there is an urgent need to work out consensus-based guidelines for forensic physicians on how to certify deaths.     

Accuracy of non-contrast PMCT for determining cause of death

The aim of this study was (1) to compare levels of accuracy regarding the categorization of causes of death between non-contrast post-mortem computed tomography (PMCT) and the final forensic report as well as between autopsy and the final forensic report, and (2) to assess levels of confidence regarding the categorization of causes of death after non-contrast PMCT and after autopsy. This prospective study was conducted over a 5 month period during which 221 cases were admitted to our institute for forensic investigations. Whole-body PMCT and forensic autopsy were performed in every case. Of these, 101 cases were included in the final study population. Inclusion criteria were: (1) age > 18 years, (2) presence of at least one of the two principal investigators at the time of admission. One radiologist and one forensic pathologist independently read all PMCT datasets using a report template. Cause of death category and confidence levels were determined by consensus. Forensic autopsy was performed by two forensic pathologists; both unblinded to imaging results. Both post-imaging and post-autopsy cause of death categorization were compared against the final cause of death, as stated in the forensic expert report, which included findings from histology and/or toxicology. Accuracy of post-imaging cause of death categorization in reference to the final cause of death category was substantial (82%, 83/101 cases, Kappa 0.752). Accuracy of post-autopsy cause of death categorization in reference to the final cause of death category was near perfect (89%, 90/101 cases, Kappa 0.852). Post-imaging sensitivity and specificity regarding the categorization of causes of death were 82% and 97%, respectively. Post-autopsy sensitivity and specificity regarding the categorization of causes of death were 89% and 98%, respectively. There was a high consistency between the accuracy of post-imaging cause of death categorization and post-imaging levels of confidence. There was less consistency between accuracy of post-autopsy cause of death categorization and post-autopsy levels of confidence. In this study categorization of causes of death based on non-contrast enhanced PMCT alone, and on PMCT and macroscopic autopsy together, proved to be consistent with the final cause of death-category as determined based on all available information including PMCT, autopsy, and (if available) histology and/or toxicology in more than 82% and 89% of all cases, respectively. There was higher consistency between levels of confidence and accuracy of causes of death categorization was higher post-imaging than post-autopsy. These results underline the fact that the diagnostic potential of PMCT goes beyond the assessment of trauma cases.     

Maternal and pregnancy-related death: causes and frequencies in an autopsy study population

Background

Maternal deaths during pregnancy, both from pregnancy-related or other causes, are rare in Western industrialized countries. In this study we report maternal and pregnancy-related deaths in a large autopsy population focusing on medical history, autopsy findings and histological examinations.

Materials and methods

Medico-legal autopsy files (n = 11,270) from the Institute of Legal Medicine and Forensic Sciences, University Medical Centre Charité, University of Berlin, and the State Institute of Legal and Social Medicine, Berlin, from 2005 to 2010 were reviewed. All female cases between 15 and 49 years were checked for maternal and pregnancy-related death, and deaths of pregnant women from non-natural causes were also included. Fatalities that met the chosen criteria were classified as “direct gestational death,” “indirect gestational death” or “non-gestational death.”

Results

13 female fatalities (0.12 %) met the chosen criteria (median age 28 years ± 6.87 SD). Eight (61.5 %) women died in-hospital, four (30.8 %) at home, and one woman died in public. Three cases (23.1 %) were “non-gestational deaths,” and one case (7.7 %) remained unclear after autopsy and additional examinations. Of the remaining nine cases, six cases (46.5 %) were “direct gestational deaths,” and two cases (15.4 %) were “indirect gestational deaths.” One case (7.7 %) was not to be defined as “late maternal death,” but the cause of death seemed to be directly related to previous gestation [“(very) late maternal death”].

Conclusion

Maternal deaths during pregnancy, both from pregnancy-related or other causes, remain an uncommon event in routine forensic autopsy practice. We report on the collection and analysis of maternal and pregnancy-related deaths in a large autopsy population, with particular attention to the phenomenology of pregnancy, pathophysiological changes in different organ systems and their detection, and the forensic autopsy assessment.     

Trends in forensic autopsy in Chiba prefecture over the past decade

The death investigation system in Japan is in the midst of a great transformation. As part of efforts to revise this system, in this study we analyzed the reasons the police refer unnatural death cases for forensic autopsy and, from an understanding of the trends of such referrals, we discuss the future direction of handling unnatural deaths in our country. For 1618 forensic autopsy cases handled by the First Investigation Division of Chiba Prefectural Police that were referred to our institution for forensic autopsy between 2003 and 2012, we tallied the number of autopsies by sex, age group, and reason for forensic autopsy for each year and investigated trends in the referrals over time. The results revealed that the number of autopsies increased annually from 2003 to 2012, with a marked increase from 2010. The number of autopsies increased particularly for cases of suspected criminal deaths, where it was unclear to the police before the forensic autopsy whether or not the death resulted from a criminal act. Our findings suggest that the number of forensic autopsies will continue to increase into the future in Chiba prefecture, and is a trend that is inevitable if we are to prevent criminal death cases from being overlooked. Although referrals for forensic autopsy in Japan are made only when criminal activity is suspected, the original purpose of death investigations is not only to avoid overlooking crimes, but also to flag public health issues. Therefore, together with the police, we need to review the original purpose and conduct more in-depth discussions about when referrals are necessary.     

One small scan for radiology, one giant leap for forensic medicine - Post-mortem imaging replaces forensic autopsy in a case of traumatic aortic laceration

The questions of cause and manner of death are the most pressing ones in any forensic investigation. Traditionally, autopsy is the means to provide answers to these questions and despite the increasing use of CT and MR in the post-mortem setting, imaging has usually been an adjunct to forensic autopsy. Here we describe a case where post-mortem CT and MR were performed instead of autopsy, at the request of the responsible public prosecutor. The forensic conclusions derived from imaging, including cause and manner of death were accepted by the legal authorities, thereby setting precedence for future cases. This case represents a landmark in forensic medicine and is another step toward the full realization of minimally invasive forensic autopsy.     

Accidental mechanical asphyxia of children in Germany between 2000 and 2008

Accidents constitute one of the greatest risks to children, yet there are few medical reports that discuss the subject of accidental asphyxia. However, a systematic analysis of all documented cases in Germany over the years 2000-2008 has now been conducted, aiming at identifying patterns of accidental asphyxia, deducing findings, defining avoidance measures and recommending ways of increasing product safety and taking possible precautions. The analysis is based on a detailed retrospective analysis of all 91 relevant autopsy reports from 24 different German forensic institutes. A variety of demographic and morphological data was systematically collected and analysed. In 84 of the 91 cases, the sex of the victim was reported, resulting in a total of 57 boys (68 %) and 27 girls (32 %). The age spread ranged between 1 day and 14 years, with an average of 5.9 years. Most accidents occurred in the first year of life (20 %) or between the ages of 1 and 2 years (13 %). In 46 % of cases, the cause of death was strangulation, with the majority occurring in the home environment. In 31 % of all cases, the cause of death was positional asphyxia, the majority resulting from chest compression. In 23 % of cases, the cause of death was aspiration, mainly of foreign bodies. Today, accidental asphyxiation is a rare cause of death in children in Germany. Nevertheless, the majority of cases could have been avoided. Future incidence can be reduced by implementing two major precautions: increasing product safety and educating parents of potentially fatal risks. Specific recommendations relate to children's beds, toys and food.     

Findings for current marks: Histopathological examination and energy-dispersive X-ray spectroscopy of three cases

We describe herein three cases of electrocution. As most deaths caused by electricity are due to cardiac arrhythmia or paralysis of the respiratory muscles, autopsy findings in electrocution cases are generally non-specific, with the exception of the presence of current marks. We detected metallization by histological examination and energy-dispersive X-ray spectroscopy (EDX) analysis in tissues of typical or atypical current marks. In addition, myofiber break-up was observed in one case. One patient was hospitalized before death and revealed patchy contraction band necrosis, along with infiltration of leucocytes and vacuolation in the diaphragm. The presence of current marks is the hallmark for forensic diagnosis of electrocution. Although specific findings are lacking at autopsy in cases of electrocution, detailed histological examination and EDX analysis provide useful information for forensic diagnosis.     

Another case of diethyl ether intoxication?: a case report focusing on toxicological analysis

Diethyl ether was widely used as an anesthetic agent in many countries in the second half of the 19th century and the first half of the 20th century. For this reason the majority of lethal cases involving diethyl ether reported during this period were associated with anesthesia. We present a case of asphyxial death by plastic-bag suffocation with additional detection of diethyl ether in autopsy specimens. Autopsy initially failed to reveal the cause of death. Macroscopic and microscopic findings as well as subsequent toxicological examination procedures and results are pointed out in the present case report. Headspace gas chromatography with flame ionization detection (HS-GC–FID) coupled with gas chromatography/mass spectrometry (GC–MS) proved to be the method of choice for fast and reliable analysis of unknown highly volatile substances (other than blood alcohol). In this case the detection of diethyl ether in autopsy specimens led to further investigations by the police at the death scene. During these investigations a bottle bearing a diethyl ether label was found and confiscated, which proved the insufficiency of prior death scene investigation.In order to evaluate the case from every possible angle, in such cases, especially when plastic-bag suffocation is suspected, we strongly recommend the collection of postmortem specimens in gas-tight vessels as well as the presence of a forensic expert at the death scene.     

Postmortem Multislice Computed Tomography and Magnetic Resonance Imaging of odontoid fractures,atlantoaxial distractions and ascending medullary edema

Non-invasive imaging methods are increasingly entering the field of forensic medicine. Facing the intricacies of classical neck dissection techniques, postmortem imaging might provide new diagnostic possibilities which could also improve forensic reconstruction. The aim of this study was to determine the value of postmortem neck imaging in comparison to forensic autopsy regarding the evaluation of the cause of death and the analysis of biomechanical aspects of neck trauma. For this purpose, 5 deceased persons (1 female and 4 male, mean age 49.8 years, range 20–80 years) who had suffered odontoid fractures or atlantoaxial distractions with or without medullary injuries, were studied using multislice computed tomography (MSCT), magnetic resonance imaging (MRI) and subsequent forensic autopsy. Evaluation of the findings was performed by radiologists, forensic pathologists and neuropathologists. The cause of death could be established radiologically in three of the five cases. MRI data were insufficient due to metal artefacts in one case, and in another, ascending medullary edema as the cause of delayed death was only detected by histological analysis. Regarding forensic reconstruction, the imaging methods were superior to autopsy neck exploration in all cases due to the post-processing possibilities of viewing the imaging data. In living patients who suffer medullary injury, follow-up MRI should be considered to exclude ascending medullary edema.     

RNA in forensic science

RNA analysis offers insight into diseases and mechanisms leading to death and could develop into a valuable tool for diagnosis of the cause of death in forensic pathology. Other possible applications include the determination of the age of wounds and injuries and of the post-mortem interval. The molecular identification of body fluids by analysis of cell-specific mRNA expression already represents a new technique supplementing DNA analysis in forensic cases. This review explains and discusses principles, techniques and applications by offering a complete and comprehensive overview of research results in forensic RNA work.