Kaisa Lalu

Age-Dependent Association of Apolipoprotein E Genotype With Coronary and Aortic Atherosclerosis in Middle-Aged Men An Autopsy Study

BACKGROUND Apolipoprotein E (apoE) polymorphism is one of the genetic determinants of serum cholesterol values. The apoE epsilon4 allele has been associated with advanced coronary heart disease (CHD) diagnosed by angiography, but the role of the apoE genotype in atherosclerosis has not been confirmed at vessel-wall level, nor is any age-dependent effect of the apoE genotype on the development of CHD known. METHODS AND RESULTS The right and left anterior descending coronary arteries (RCA and LAD) and the aorta from 700 male autopsy cases (Helsinki Sudden Death Study) in 1981-1982 and 1991-1992 (average age 53 years, range 33 to 70 years) were stained for fat, and all areas covered with fatty streaks, fibrotic plaques, and complicated lesions were measured. In the RCA and LAD, the apoE genotype was significantly associated with the area of total atherosclerotic lesions in men <53 years old but not with that in older men (P=0.0085 and P=0.041, respectively, for age-by-genotype interaction). Men <53 years old with the epsilon4/3 genotype showed 61% larger total atherosclerotic lesion area in the RCA (P=0.0027) and 26% larger area in the LAD (P=0.12) than did men with the epsilon3/3. The apoE epsilon4/3 was also associated with atherosclerotic lesions in the abdominal (P=0.014) and thoracic (P=0.12) aorta, but this effect, unlike that of the coronary arteries, was not age-related. CONCLUSIONS In men, the apoE epsilon4 allele is a significant genetic risk factor for coronary atherosclerosis in early middle age. This suggests that at older age, other known risk factors of CHD play a more important role in the atherosclerotic process than apoE polymorphisms.

Glycoprotein IIIa Pl A Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly

Glycoprotein IIIa (GPIIIa) has a key role in the aggregation of thrombocytes, and it also mediates intimal hyperplasia after endothelial injuries; the possible association of the Pl(A1/A2) polymorphism of the gene for GPIIIa with coronary thrombosis and with the progression of coronary artery disease (CAD) is still to be confirmed. Therefore, the association of the Pl(A) polymorphism with the development of coronary atherosclerosis, coronary narrowing, and myocardial infarction (MI) was studied in a prospective, consecutive autopsy series of 300 middle-aged, white Finnish men (33 to 69 years) suffering sudden out-of-hospital or violent death. Coronary atherosclerosis was measured morphometrically and the coronary stenosis percentage determined from a cast rubber model of the coronary tree. We found a significant inverse relation (P=0.01) between the Pl(A2)-positive genotype and coronary artery stenosis. The frequency of possessing the Pl(A2) allele was significantly (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.22 to 0.98) lower among men with >50% coronary stenosis (18.3%) than among those with <25% stenosis (32.9%). Although the Pl(A) polymorphism was not directly associated with MI, the Pl(A2) allele was present in 11 of the 22 men (50%) with MI and coronary thrombosis (OR 6.6, 95% CI 2.1 to 22.8) but in only 6 of the 47 (12.8%) with MI associated with severe stenosis in the absence of thrombosis. In line with this result, men possessing the Pl(A2) allele also had a larger area of fissured and ulcerated complicated lesions in their coronary arteries (P<0.05). The present results suggest that the Pl(A) polymorphism is involved in the development of CAD and MI. Men with the Pl(A2) allele may harbor more thin-walled, vulnerable coronary plaques, plaques prone to rupture, leading to massive, fatal thrombosis. In contrast, men homozygous for the Pl(A1) allele may more often show stable plaques and present with infarction caused by progressive coronary stenosis.

Forensic osteological investigations in Kosovo

A team of Finnish forensic experts performed investigations of alleged mass graves in Kosovo under the mandate of the European Union (EU). Human skeletal remains from two locations were examined. The remains contained three almost complete skeletons, and individual bones and bone fragments, part of which were burned. Injuries, pathological changes, and findings for identification purposes were examined and documented using standard methods of forensic pathology and osteology. Gunshot injuries were found in some cases, but reliable determination of the cause and manner of death was not possible. A discrepancy arose between the number of victims reported in information received from the presiding district court, and results of the investigations. The estimation of the minimum number of victims was mostly acquired by DNA analysis.

Radiology in forensic expert team operations

Radiological methods are widely used in forensic pathology. Their most common applications are in complementing human identification, particularly in investigations of mass disasters and decomposed bodies, and in searching for foreign material inside corpses. A team of Finnish forensic experts investigated human skeletal remains in Bosnia and Herzegovina (1996) and in Kosovo, the Federal Republic of Yugoslavia (1998). It also investigated more recently deceased victims in Kosovo (1999). In these investigations, the benefit of X-ray was in the detection of foreign material inside victims and their remains. For identification purposes, X-rays were mainly used to provide the best evidence possible of any pathological changes, physical characteristics, and injuries present.

Independent forensic autopsies in an armed conflict: investigation of the victims from Racak, Kosovo

In January 1999, a team of Finnish forensic experts under the mandate of the European Union (EU forensic expert team, EU-FET) performed forensic investigations in a sovereign state, in Kosovo, the Federal Republic of Yugoslavia (FRY). The team served as a neutral participant in the forensic investigation of victims of an incident at Racak, which was receiving considerable international attention. The Finnish team performed forensic autopsies, monitored forensic autopsies performed by local experts and verified findings of earlier executed autopsies. The victims had sustained varying numbers of gunshot wounds, which were established to be the cause of death. The manner of death remained undetermined by the EU-FET, because the scene investigation and the chain of custody for the bodies from the site of the incident to the autopsy were impossible to verify by the team. The events at Racak were the first of those leading to charges by the International Criminal Tribunal for the former Yugoslavia (ICTY) against the highest authorities in power in the FRY for crimes against humanity and violations of the laws or customs of war.

Genotyping of five short tandem repeat loci via triplex and duplex PCR

We have developed a triplex PCR method for D3S1359, HumTH01 and HumTPO tetranucleotide loci and a duplex PCR method for HumFES/FPS and HumvWA31A tetranucleotide loci using high resolution polyacrylamide gel electrophoresis and silver staining. The methods were evaluated for paternity testing and individual identification and allele frequencies at these loci are reported for 189-3387 unrelated individuals in the Finnish population. The D3S1359 locus, especially, was found to be a highly informative locus. Seventeen alleles were found in the D3S1359 locus with a highest observed allele frequency of 0.199, a high exclusion power (PE) in paternity testing (0.78) and a high observed heterozygosity (0.89). The combined PE for these five loci was 0.99.

Autopsy rate in suicide is low among elderly in Denmark compared with Finland

National differences in the legislation on cause and manner of death investigation are reflected in a high autopsy rate in suicides in Finland and a low corresponding rate in Denmark. The consequences for mortality statistics of these different investigation practices on deaths classified as suicides in Denmark and Finland, respectively, are not known in detail. The aim of this article was to analyse autopsy rates in deaths classified as suicides, and to identify any differences in investigation practices in deaths with a comparable cause of death, but classified as unnatural deaths other than suicide. Data from the mortality registries were summarised for the years 2000, 2005 and 2010. Autopsy rates (total, forensic and medical) were analysed with regard to deaths classified as suicide, and they were compared for three age groups (1-50 years, 51-70 years and ≥71 years) and for causes of death. Deaths classified as suicide were compared with other unnatural classifications, and comparable causes of death were coded into six subgroups: poisonings, suffocations/strangulations, firearm discharges, drowning/submersions, explosions/flames and other/unspecified causes. The total autopsy rate for suicides was 99.8% in Finland and 13.2% in Denmark. Almost all of these autopsies were conducted as forensic autopsies. In the age group ≥71 years, Danish suicides outnumbered Finnish suicides (410 versus 283). The total autopsy rate was lower in the more senior age group in Denmark (19.5%, 9.9%, 5.6%), whereas it was consistently high in Finland (99.8%, 99.9%, 99.6%). Among Danish deaths due to poisonings, the autopsy rate was 89.5% when these were classified as accidents, but only 20.7% for cases classified as suicides. The number of deaths in the two Danish subgroups was comparable (550 versus 553). In Denmark, the decision regarding the need, if any, for a forensic autopsy is made during the external forensic examination of the body. Our study showed that the limited use of forensic autopsy to confirm the cause of death in deaths classified as suicides raises doubts about the accuracy of the Danish suicide mortality statistics. Our finding is emphasised by those cases in which the cause of death was registered as intentional self-poisoning. The high number of suicides among the elderly in Denmark is striking and begs further investigation and research. Overall, our data from Finland and Denmark reveal striking differences between the two countries and warrant further comparative studies on the subject in other countries.

Practical and legal aspects of forensic autopsy expert team operations

Finnish forensic experts have investigated remains of the victims of alleged mass violence in the former Yugoslavia in 1996 under the mandate of the United Nations, and in 1998 and 1999 under the mandate of the European Union. The investigative documents later were surrendered to the International Criminal Tribunal for the former Yugoslavia (ICTY). The indictments issued by the ICTY include charges even against the highest authorities of the Federal Republic of Yugoslavia. This study describes the experience gained in organising forensic expert team operations in a foreign state by the Finnish team. The establishment and operation of a forensic expert team in a foreign state involve, among other things, legal issues, often related to differing legal systems. From an independent forensic expert team, great objectivity and self-constraint are expected. Moreover, a clear and sufficiently detailed agreement on the mandate of the team and on the possibility for unhindered and safe access of the experts to the alleged mass graves, as well as the assembling and briefing of the team members and provision of the necessary equipment should be completed before the beginning of the mission. Furthermore, the application of adequate and internationally recognised methods for processing and documenting the examination is essential for teams credibility.

Cost–consequence analysis of cause of death investigation in Finland and in Denmark

The 1990s 12-16% total autopsy rate in Denmark has until now declined to 4%, while in Finland, it has remained between 25 and 30%. The decision to proceed with a forensic autopsy is based on national legislation, but it can be assumed that the financing of autopsies influences the decision process. Only little is known about the possible differences between health economics of Finnish and Danish cause of death investigation systems. The aims of this article were to analyse costs and consequences of Finnish and Danish cause of death investigations, and to develop an alternative autopsy practice in Denmark with another cost profile. Data on cause of death investigation systems and costs were derived from Departments of Forensic Medicine, Departments of Pathology, and the National Police. Finnish and Danish autopsy rates were calculated in unnatural (accident, suicide, homicide and undetermined intent) and natural (disease) deaths, and used to develop an alternative autopsy practice in Denmark. Consequences for society were analysed. The estimated unit cost (€) for one forensic autopsy is 3.2 times lower in Finland than in Denmark (€1400 versus €4420), but in Finland the salaries for forensic pathologists working at the National Institute for Health and Welfare are not included in the unit cost. The unit cost for one medical autopsy is also lower in Finland than in Denmark; €700 versus €1070. In our alternative practice in Denmark, the forensic autopsy rate was increased from 2.2% to 8.5%, and the medical autopsy rate from 2.4% to 5.8%. Costs per 10,000 deaths were estimated to be 50% (±25%) higher than now; i.e. €3,678,724 (2,759,112-4,598,336), but would result in a lower unit cost for forensic autopsies €3,094 (2,320-3,868) and for medical autopsies €749 (562-936). This practice would produce a higher accuracy of national mortality statistics, which, consequently, would entail higher quality in public health, an accurate basis for decision-making in health politics, and better legislative safety in society. The implementation of this alternative practice in Denmark requires that legislation demands that forensic autopsy be performed if causality between unnatural death and cause of death cannot be clarified or if cause of death remains unknown. The Danish Health and Medicines Authority should provide guidelines that request a medical autopsy in natural deaths where more information about disease as a cause of death is needed. Our study results warrant similar health economic analyses of different cause of death investigations in other countries.

Radiographic Demonstration of Esophageal and Tracheal Fistulas at Autopsy Using a Contrasting Medium That Vulcanizes at Room Temperature

Esophageal and tracheal fistulas, which occur in 0.05% of medicolegal autopsies, were demonstrated in three cases by a postmortem radiographic technique using silicone rubber/lead oxide as a contrasting medium that vulcanizes at room temperature. In one 83-year-old male, a tracheoesophageal fistula was detected, which had developed after surgical repair of an esophageal rupture caused by a flexible fiberoptic endoscope. In a second case, carcinoma of the esophagus in a 78-year-old male had eroded the trachea and arcus of the aorta creating a fatal tracheoesophagoaortic fistula. In a third case, 55-year-old female developed a tracheobrachicephalic artery fistula as a result of an infiltrating cystic adenocarcinoma of the trachea, resulting in a fatal hemorrhage into the trachea. The results of this study indicate that diagnostic radiologic methods using a vulcanized contrasting medium are useful in supplementing normal dissection in autopsy cases with suspected fistulas of the esophagus or trachea.