Lymph-node and thymus pathology in fatal drug addiction

Lymph-node sections from the porta hepatis, the lung hilus, the para-aortic and axillary regions and from the neck from totally 50 drug addicts submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen were studied together with tissue sections from 23 normal persons. In addition thymus sections from 30 drug addicts and 20 normal persons were investigated. Enlargement of lymph-nodes was found significantly more often in active drug addicts compared to normals except for the nodes on the neck. Birefringent material was seen in portal lymph-nodes in 42% of addicts, in para-aortic and lung hilus nodes in 18% each and in the axillary nodes in 12%. Signs of antigenstimulation evaluated by the number of germinal centre and plasma cells were found in about 60% or more in active drug addicts compared to about 30-40% in normals. There was not significant relation between the size of the lymph-nodes and the immunoactivity nor to the duration of the abuse. Examination of the thymus showed that the average weight in active drug addicts was 34 g, in normals 25 g. Histologically the tissue was in 48% of the active addicts composed of more than 80% lymphatic tissue compared to 15% of the normals. The results indicate that the enlargement and histological signs of activation in all the lymph-nodes investigated are caused by continuous antigenstimulation due to repeated injections of various antigens. The same may in part be applied to the thymus changes demonstrated.     

The nature and the occurrence of birefringent material in different organs in fatal drug addiction

Insoluble birefringent tablet filler materials commonly found in tablets used in solution by drug addicts as intravenous injections were investigated microscopically. The following filler materials were investigated: talc, potato- and maize-starch, microcrystalline cellulose, magnesium stearate and siliciumoxid. The morphological characteristics of the different materials are described. Tissue sections (lung, liver, spleen, heart, bone-marrow, kidney, lymph-nodes and endocrine glands) from 33 consecutive fatality cases of intravenous drug addicts autopsied at the University Institute of Forensic Medicine in Copenhagen were studied with special reference to the occurrence and nature of birefringent material. Birefringent material was most often demonstrated in lung tissue (94%), followed by spleen (76%), liver (55%), lymph-nodes (portal: 39%) and bone-marrow (24%). The material was always localized intracellularly. Granulomatous reaction was only seen in the lungs. Except for one case, talc was the only foreign material seen in other organs than the lungs, undoubtedly due to its smaller size. The presence of insoluble foreign material in lung tissue of drug addicts indicates a habit of intravenous administration and the amount of the material indicates whether the addict usually injects tablets or only does so occasionally. The presence of birefringent material in the organs have only rarely any obvious clinical implications.     

Heroin associated nephropathy – a post-mortem study

Renal specimens were obtained from 179 autopsies of persons autopsied in the Institute of Forensic Medicine, University of Bonn, from 1987 to 1997. All persons were known as intravenous drug addicts. All renal specimens were examined with hematoxylin-eosin, PAS, Siriusred and Gomori (methenamine silver trichrome stain) and investigated with primary antibody against LCA (leucocyte common antigen), CD 68, IgG and IgM. 105 specimens (61.7%) showed a mono-lymphocytic membranoproliferative glomerulonephritis (MPGN), 48 specimens (45.7%) deposits of IgM. No case with focal segmental glomerulosclerosis (FSGS) as reported in male African–American intravenous drug addicts was found. In 37 out of 54 cases, hepatitis antibodies were detected in serum and three out of these 54 cases were HIV-positive. Chronic hepatitis B and C are known to be associated with glomerulonephritis. We found some cases without detection of hepatitis antibodies but with severe glomerulonephritis. In contrast to African–American drug addicts, European drug addicts do not develop a FSGS but a MPGN, partly due to heroin or other adulterants and apparently independent from hepatitis infection.     

Morphological findings in fatal drug addiction. An investigation of injection marks, endocrine organs and kidneys

Tissue sections from injection marks from 30 drug addicts and sections from endocrine organs and kidneys from an additional 33 addicts were studied together with endocrine organs and kidneys from 20 'normal' persons. All 83 persons were submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen. In fresh injection marks haemorrhage in dermis and subcutis was present histologically in all cases. Acute inflammation was present in 38% and acute inflammation together with chronic changes in 41%. Fibrotic thickening of vein wall was seen in 14% and thrombosis in 10%. Birefringent foreign material occurred in 35%. In old injection marks and scars chronic inflammatory changes were observed in 93%, fibrotic thickening of vein wall in 20% and thrombosis in 10% of the cases. Birefringent material occurred in 17%. By comparison of changes in injection marks with the size and histological changes in the corresponding axillary lymph nodes, there was a tendency to a relation between chronic inflammatory changes in old injection marks/scars and enlargement of the lymph nodes in question, but no correlation to the histological degree of immunoactivity. Regarding alterations in the endocrine organs and the kidneys no important differences were demonstrated between drug addicts and 'normal' persons.     

Liver pathology in fatal drug addiction

Liver sections from 273 drug addicts submitted to medicolegal autopsy at the Institute of Forensic Medicine in Copenhagen in the period 1975 – 1979 were studied. In 65% of the cases non-specific portal inflammation only was found. Birefringent foreign material — identified as the mineral talc (magnesium silicate) was observed in 38% of the cases; in these cases non-specific portal inflammation was always present. Changes compatible with acute or chronic persistent hepatitis or hepatitis sequelae were observed in 8% of the cases; cirrhosis in 3%. HBs-antigen was detected in 4%. In 22% fatty infiltration was present; in 4% as the only abnormal finding. Finally no pathological changes were found in 6%. The results were related to anamnestic information of kind and duration of drug abuse and to the cause of death. Furthermore a comparison was performed between the groups with and without birefringent material. The data suggest that the birefringent material may be of importance to the pathogenesis of the non-specific portal inflammation.     

Histopathological findings in 851 autopsies of drug addicts, with toxicologic and virologic correlations

This investigation was carried out on 851 consecutive judicial autopsies of drug addicts who died mostly of heroin overdose from 1977 to 1996. Research of anti-HIV/HBV/HCV antibodies was performed, and histologic sections were retrospectively reviewed. More than 65% were HBV/HCV-positive and about 17% HIV-positive; females were HIV-positive more often than males. Intracranial microhemorrhages were frequently found; cerebral infectious diseases were rare. Inflammatory heart lesions, myocardial fibrosis, and acute ischemia were common. Interstitial nephritis (found in about 8%) was more frequent in females, in older patients, and in those carrying HIV infection; glomerular sclerosis was detected in about 12%. Acute bronchitis and/or pneumonia was demonstrated in 12%, without significant association with HIV infection; pulmonary hemorrhages, foreign body granulomas, and food aspiration were also commonly seen; hyperplasia of pulmonary perivascular lymphatic tissue was rather characteristic. Liver was carrying steatosis in 66.3% and/or hepatitis in 64.5%; acute hepatitis was more frequent in females, chronic hepatitis in older subjects and in those proven positive for hepatotropic viruses; cirrhosis occurred more often in older patients, in those carrying virus infection, and in consumers of nonnarcotics drugs such as ethanol. No pathologic finding was clearly related to drug abuse; therefore, during autopsy, drug addiction can be suspected, but anamnestic and circumstantial data are needed to lead pathologists to request toxicologic analysis to ascertain the cause of death. The present investigation emphasizes that, in addition to the risk of death by overdose, the high incidence of acute and chronic diseases could seriously undermine the health status of heroin and/or other drug consumers.     

Forensic medical evaluation of the morphological alterations of the liver in drug abuse

Application of a morphometric method for investigation of chronic virus hepatitis in drug addicts and persons rejecting drug abuse is described. Chronic hepatitis in narcomania runs with frequent formation of lymphoid follicules in the portal tracts, relatively inactive portal hepatitis in marked lobular component of inflammation, pronounced fibrosis and early formation of micronodular hepatic cirrhosis, proliferation of biliary ducts, high neutrophil, eosinophil and macrophage content in the infiltrate, accumulation of macrophages in the portal tracts by granuloma type. These criteria are recommended for diagnosis of narcomania by morphological findings.     

NARCOTIC ADDICTS AND CRIME Analysis of Recent Trends

This study attempts to shed light on the types of crime committed by drug addicts and the possible changes in criminal behavior over time. The study revealed that arrests for crimes against the person are becoming more prominent among addicts although acquisition of property appeared to be the prime motive in these offenses Over the four-year period analyzed, arrests for crimes against property and drug offenses remained the more numerically important categories even though arrests for crimes against the person increased. It was also found that, for each type of offense, more persons were arrested after than before they initiated thew drug abuse patterns.     

HIV-related deaths outside medical institutions in Stockholm

During a 3-year period (August 1st, 1985 to July 31st, 1988) a systematic investigation of medico-legal autopsy cases with regard to the presence of antibodies for HIV-virus was carried out at the Department of Forensic Medicine in Stockholm, Sweden. Prior to autopsy, blood samples were taken from femoral or subclavian veins and were investigated by use of ELISA-screening and Western blotting test. During the first year of study, HIV infection was demonstrated in 11 out of 3464 deaths (0.32%), during the second year in 29 out of 3483 deaths (0.83%), and during the last year in 13 out of 3107 deaths (0.42%). It was shown that 48 out of the total of 53 HIV positive cases were previously registered, but information about the infection was available to the autopsist in only 27 cases. Drug addicts dominated 41 of 53 cases. There were only eight homo- and bisexual males, two non drug addict Central Africans and two persons who received blood transfusions. Eight of the 53 persons died of natural causes whereas 45 deaths were due to violence and drugs. The causes of death of the HIV positive drug addicts were compared to the causes of death of the HIV negative addicts. The HIV positive drug addicts tended to die suddenly in connection with the intravenous administration of heroin and at lower blood concentrations of morphine more often than the HIV-negative addicts. No increase in the suicide frequency was noted in drug addicts in Stockholm during the studied period.     

Morphometric assessment of testicular changes in drug-related fatalities

Testicular sections of 50 deceased drug addicts were examined by light microscopy using morphometric methods and determining the extent of spermatogenesis by application of the Johnsen score count. Twenty cases of violent death served as reference sample. The study was aimed at obtaining data about the degree of germinal gland damage following the duration of the individual drug career, which was correlated to the histologic findings. Progressively reduced maturation of germinal cells, decrease of tubular diameter and height of sperm-producing epithelium were found the longer the individual case history has been. The results clearly indicated a substantial impairment of male fertility in the course of a drug career, but etiology seems to be multifactorial, since most of the deceased were polytoxicomanic and more than 40% were under the influence of alcohol at the time of death. Testicular damage is obviously a sequel of long-lasting abuse and a very complex process, presumably progressing with the duration of the adverse habit.     

Thymus alterations related to intravenous drug abuse.

It has been noticed on forensic material that Hassall's corpuscles of the thymus are more often calcified in intravenous drug abusers than in healthy persons. Thymuses of 15 intravenous heroin addicts were histologically examined and compared with thymuses of 15 healthy persons. Acute bleeding and dystrophic calcification in the thymocyte's parenchyma were more common among intravenous drug abusers (p = .005 and p = .001, respectively). The degree of physiologic involution measured by fatty replacement and the clarity of border between cortex and medulla was equal. No significant diversity was found in the features of Hassall's bodies. Our study emphasizes the necessity for a defined criteria of morphologic changes in the thymus that could be expected in intravenous drug abusers. In that way it would be possible to complete the forensic findings as well as to examine immunologic system alterations of that risk population.     

Liver histopathology in autopsied drug-addicts

Liver specimens of 150 randomly selected autopsied drug addicts from the province of Milan (Italy) were studied using light microscopy, polarized light and immunohistochemical methods. Simple histological changes and the main diagnoses are described. The main histological diagnoses in order of frequency were: non-specific reactive hepatitis (NSRH) (52%), chronic aggressive hepatitis (CAH) (24%), acute hepatitis (AH) (12%), normal liver (6%), steatosis only (3.3%) and cirrhosis (2%). In 24 cases (16%) one or more viral antigens (HBsAg, HBcAg and Delta Ag) were detected in hepatocytes by immunohistochemical methods. Three liver specimens revealed epithelioid cell granulomas, but in no case was birefringent material identified in the liver. AH and CAH were more frequent in the group of livers with viral antigens. Our histological and immunohistochemical data confirm the current opinion that, in most cases, liver pathology in drug addicts has a viral aetiology, while no significant pathogenic role has been identified for drugs, alcohol or contaminants. Recurrent infections by one or several viruses possibly explain the relatively peculiar histological features of hepatitis in drug addicts.     

Causes of death in hospitalized intravenous drug abusers

The authors reviewed at autopsy the causes of death of 274 patients with evidence of intravenous drug abuse who had been admitted to a large public hospital. There were 127 who died from diseases unrelated to intravenous drug abuse, and in 41% of these, chronic alcoholism was implicated. Deaths from overdose syndromes and drug-related organ pathology comprised only 11% of all cases. The mean age at death was 39 years. There was a male/female ratio of 3.6:1. Half of all patients died from infection--72 from acquired immunodeficiency syndrome (AIDS) alone. These findings indicate that persons hospitalized with a history of intravenous drug abuse usually die from causes other than overdose and that AIDS and chronic alcoholism are significant problems. Emphasis should be placed upon detecting "hidden" intravenous drug deaths to provide more accurate statistical information.     

Histologic findings of the sinus node and the perinodal area in street heroin addicts, victims of sudden unexpected death

Sudden unexpected death is frequent in street heroin addicts. We conducted a histologic study of the sinus node (SN) to offer some evidence about the possible arrhythmogenic cause of death. Postmortem coronary angiography and microscopic examination of the SN and the perinodal area were performed in 50 heroin addicts (group 1) and in 50 nonaddicts (group 2), all men (16-40 years old). In heroin addicts, fatty and/or fibrous tissue replaced SN tissue in 21 cases (42%). Perinodal infiltration was found in 15 cases (30%). Fibromuscular dysplasia in branches of the sinus node artery (SNA) was found in eight cases (16%). Inflammation with focal and/or diffuse concentration of round cells was detected in the SN in 22 cases (44%). Old mural thrombi were also found in 13 cases (26%). The histologic changes in the SN and perinodal area offer an explanation about the possible mechanism of arrhythmia and sudden death in this population.     

The occurrence of HIV antibodies in drug addicts autopsied at the University Institute of Forensic Medicine in Copenhagen in 1987

In 1987 a total of 89 intravenous drug addicts were admitted to medico-legal autopsy at the University Institute of Forensic Medicine in Copenhagen. Totally 10 cases were reactive by the Elisa test and five of these, or 7% of the total material tested, could be confirmed by the immuno-blotting test. The other five cases must be considered as false positive, possibly due to antibodies against cellular antigens. Among the five real positive cases, four were known before-hand while in one case the HIV-positivity was not known. These findings - together with the possibility of false negative reactions - especially regarding persons with acute HIV-infection, requires special precautionary measures when autopsies of drug addicts are performed.     

Prevalence of HIV-1 antibodies in drug addicts autopsied at the University Institute of Forensic Pathology in Copenhagen 1988-1991.

In the period 1988-1991 the HIV-1 antibody test was performed in a total of 389 autopsied drug addicts. The HIV-1 incidence rose from 6% in 1988 to 14% in 1990 and 14% in 1991. There was no significant difference between the cumulated incidence in males and females. The HIV-1-positive addicts were compared to the HIV-1 negative addicts as regards mean age, duration of abuse, residence and cause and manner of death. Except for residence, where significantly more HIV-1-positive than negative addicts lived in Copenhagen, there were no significant differences between the two groups. In about one-third of the HIV-1-positive cases, equal both for males and females, the HIV-1-positivity was not known beforehand. The results are discussed in relation to the findings in other countries and to the findings in selected groups of living addicts in Copenhagen. It is concluded, that the diagnosis of HIV-1 infection in autopsied drug addicts is important from epidemiologic and hygienic points of view.     

Pathogenesis of heroin-associated glomerulonephritis. Correlation between the inflammatory activity and renal deposits of immunoglobulin and complement?

Renal specimens from 19 autopsies of persons known to be intravenous heroin-addicts and with severe lympho-monocytic glomerulonephritis were investigated to correlate the inflammatory activity and deposits of immunoglobulin and complement. In all sections, there were 10 or more LCA-positive cells/glomerulum, counted in 20 glomerula but only up to 3 LCA-positive cells in a control-group of 10 autopsied persons without drug addiction and any renal diseases. In some cases diffuse granular deposits of immunoglobulin were found together with deposits of Clq. Although these changes cannot be demonstrated in all cases, deposits of Clq point to an activation of the classical way of the complement binding system in heroin-associated glomerulonephritis. The underlying process, activation of the complement binding system by heroin/morphin itself and adulterants or by hepatitis B and C infection, which are frequent in heroin-addicts, is still unclear.     

A sudden death with lung embolism after inadvertent infusion of zinc oxide shake lotion

A 74-year old woman in postoperative treatment after a colonic surgery died immediately after perfusion of about 1.5 mL of a white emulsion which was believed to contain 1% propofol via cardiac catheter into the right atrium. It was strongly suspected that a syringe with a zinc oxide shake lotion (consisting of 20% ZnO, 20% talc, 25% glycerol and 35% water) which was intended for external treatment had been mistaken for the propofol syringe. During autopsy, an anatomic cause of death could not be found. In order to exclude an intoxication and to determine the significance of the perfusion fluid in this context, toxicological and histological investigations were performed. Propofol and other drugs applied to the patient were found in therapeutic or sub-therapeutic range. However, in comparison to a control case, the zinc concentrations determined by AAS were about 200 times higher in lung tissue, 10 times higher in heart blood and 3–4 times higher in kidney and liver tissue. No increase was seen in venous blood. Histology showed a strong embolism of the lung tissue with birefingent sharp-edged crystals, which were identified as the talcum, and an amorphous component (ZnO). The same embolism was seen to a medium extent also in the brain sections and to a low extent in heart, liver, pancreas and kidney. Pulmonary embolism by talcum and zinc oxide was established as the cause of death which occurred by syringe swap due to insufficient security precautions in the drug administration. The results are discussed in context of pulmonary microembolism cases frequently described for drug addicts after injection of crashed talcum containing tablets.     

Fatal intoxications in the Nordic countries. A forensic toxicological study with special reference to young drug addicts

Fatal intoxications in the 15-34 age group in the five Nordic countries during the years 1984 and 1985 (Sweden only in 1984) were investigated. The known drug addicts were studied separately. The highest incidence of intoxications, calculated per 10(5) population, was found in Finland (11.3), followed by Denmark (10.3), Sweden (8.5), Iceland (7.2) and Norway (6.6). The percentage of intoxications caused by drugs was 92 in Denmark, 71 in Norway, 66 in Sweden, 50 in Finland and 17 in Iceland. Ethanol intoxications were seen 5-7 and 2-3 times as frequently in Finland and in Iceland, respectively, than in the other three countries. Carbon monoxide intoxications accounted for two-thirds of all fatal intoxications in Iceland. Drug addicts accounted for 62% of all fatal intoxications in the Danish material. The corresponding figures were 33% in the Norwegian, 16% in the Swedish and 5% in the Finnish material. No deaths in drug addicts were found in Iceland. Most drug addicts in Denmark, Norway and Sweden died of hard drugs and most in Norway and Sweden, from heroin or morphine, whereas in Denmark other strong analgesics, such as methadone, dextropropoxyphene and ketobemidone, accounted for 40% of all hard-drug-related fatal intoxications. To a certain extent the results reflect differences in the legal autopsy routines in the various Nordic countries. However, the ascertainment of drug addicts is assumed to be near-complete in each country.     

Iliac cancellous bone in drug addicts: a histomorphometric study

Histomorphometry was used to determine structural bone changes in drug addicts. Iliac crest bone biopsies were obtained at autopsy from 28 subjects (21 male, 7 female, aged 18 to 45 years) who had a history of drug abuse and had died due to overdose of illicit drugs. For histomorphometry, undecalcified sections were investigated using the Merz grid. The following histomorphometric indices were measured and calculated: BV/TV, BS/BV, Tb.Th, Tb.N, Tb.Sp, OV/TV, OS/BS, Ob.S/BS, O.Th, ES/BS, Oc.S/BS, and N.Oc/T.A. In 28 controls (24 male, 4 female, aged 17 to 47 years) trabecular bone specimens were investigated in the same way. The parameters in drug addicts did not show any correlation to age, body weight, height or sex differences. Trabecular bone volume and trabecular thickness were slightly but not significantly increased (BV/TV: 23.37 +/- 5.77% (mean, SD), controls 22.23 +/- 5.08%, p = 0.434; Tb.Th: 172.67 +/- 36.83 mcm, controls 169.73 +/- 36.13 mcm, p = 0.764). Only the eroded surface was significantly different to the controls (ES/BS: 8.16 +/- 2.04%, controls 6.96 +/- 2.17%, p = 0.038). We conclude that the incidence of metabolic bone disease in drug addicts is low.