Incidence of moderate-to-severe traumatic brain injuries after reduction in alcohol prices.

OBJECTIVE: Alcohol may be involved in 40-50% of traumatic brain injuries (TBI). In Finland, the cutting of alcohol taxes by one third in 2004 resulted in a marked increase in per capita alcohol consumption. We investigated the consequences of increased alcohol consumption on the incidence of moderate-to-severe traumatic brain injury among a defined population. MATERIAL AND METHODS: We identified all residents of Northern Ostrobothia with acute moderate-to-severe TBI admitted to Oulu University Hospital in 1999 and in 2007 as well as those who died on the scene without being admitted to the hospital. Alcohol involvement was recorded by similar methods and equally often during both years. Incidence rates were calculated as number of subjects per 100,000 population. Logistic regression was performed to determine which factors predicted fatal TBI and associated with alcohol-related TBI. RESULTS: No significant increase from 1999 to 2007 occurred in the incidence of alcohol-related moderate-to-severe TBIs among the population of Northern Ostrobothnia. The total number of alcohol-related TBIs were 61/135 (45.2%) in 2007 and 52/126 (41.3%) 1999. Fall-related TBIs were more frequent in 2007 than in 1999. Alcohol and older age predicted fatal outcome. Alcohol was significantly (P < 0.001) more often present in fatal TBIs (83/156, 53.2%) than in non-fatal TBIs (30/105, 28.6%). Male sex, fall, suicide, and assault significantly associated with alcohol-related TBI. CONCLUSIONS: The reduction in alcohol prices and the concomitant increase in alcohol consumption did not increase the incidence of alcohol-related moderate-to-severe TBI.

Causes of death in pedigrees with the 3243A>G mutation in mitochondrial DNA.

BACKGROUND: Causes of death of patients with the 3243A>G mutation have been described in case reports or case series with a limited number of subjects. METHODS: Eighty-two maternally related sibships of 11 families with 3243A>G were included in this survey. The lifespan of each subject in these families was compared with the life expectancy of the general population, adjusted with respect to year of birth and gender. Causes of death were determined among 3243A>G carriers and their first-degree maternal relatives. RESULTS: We identified 123 deceased subjects in families with 3243A>G and found an excess mortality during the early years of life and young adulthood. The median age at death for 3243A>G carriers and their first-degree maternal relatives was significantly lower than that of the general population. Neurological and cardiovascular diseases made up one-third of the causes of death. Sudden and unexpected death was not uncommon in patients with cardiovascular diseases, diabetes and epilepsy. CONCLUSIONS: 3243A>G carriers and their first-degree maternal relatives died younger than was predicted by their life expectancy at birth. Neurological disease was the most common cause of death.

Immunohistochemical detection of human brown adipose tissue uncoupling protein in an autopsy series.

We used an immunohistochemical method for the inner mitochondrial membrane uncoupling protein (UCP) to examine whether human brown adipose tissue UCP could be detected by an anti-rat UCP antibody. Samples of human brown adipose tissue were obtained at medicolegal autopsies. Fat tissue was excised from around the common carotid arteries and in the subscapular region and from around the thoracic aorta. The subjects were either known alcohol consumers, in which thermogenically active brown adipose tissue (BAT) is often found, or victims of sudden infant death syndrome (SID). UCP was detected in all the cases examined, even when the post-mortem time from death to autopsy reached several days, but the intensity of the immunostaining was variable. Intense staining was observed in three cases with a post-mortem time under 24 hr, but in the SID cases a strong positive staining was seen even with a post-mortem delay of 4 days. These results show that an anti-rat UCP antibody can be used for immunohistochemical detection of UCP in human brown adipose tissue and that it provides a useful method for distinguishing between white and brown fat in paraffin-embedded samples. It can be used to detect UCP in the BAT of obese and diabetic individuals and probably also in the histopathological diagnosis of brown adipose tissue lipoma, known as hibernoma.

Influence of two beta-adrenoceptor antagonists, propranolol and pindolol, on cold adaptation in the rat.

1. Adult male rats were treated with propranolol (2.0 mg kg-1 day-1 i.p.), pindolol (0.2 mg kg-1 day-1 i.p.) or 0.9% NaCl day-1 i.p. and exposed to +4 degrees C for 42 days, or treated with 0.9% NaCl day-1 i.p. and kept at +23 degrees C for 42 days. They were weighed once a week, when a 24 h urine sample was also collected and colon temperature measured. 2. Urinary noradrenaline (NA), adrenaline (Ad) and dopamine were analysed by high-performance liquid chromatography with an electrochemical detector. After the acclimatization period the interscapular brown adipose tissue was excised and weighed and the activity of the oxidative enzymes succinate dehydrogenase and cytochrome oxidase measured. 3. The pindolol-treated and propranolol-treated rats gained weight during the cold-acclimatization period. The amount of interscapular brown adipose tissue increased in the cold, but the increase was lowest in the pindolol-treated group. No changes were seen in the other brown adipose tissue parameters in cold-exposed animals. The excretion of catecholamines followed the same pattern in all three cold-exposed groups, with an initial rise in noradrenaline and adrenaline excretion and a slight rise in dopamine excretion. 4. The results suggest possible connections between beta-adrenoceptor antagonists, weight gain and cold acclimatization. Pindolol had a slight inhibitory effect on cold-induced brown adipose tissue hypertrophy in rats.

Chronic alcohol intake induces the oxidative capacity of brown adipose tissue in the rat.

The present study was carried out to elucidate the effect of long-term alcohol intake on the oxidative capacity of brown adipose tissue in the rat. Rats housed at room temperature were given water containing 10% ethanol for six months, while controls received water alone. Fully cold-acclimated rats (exposed to +4 degrees C for 6 weeks) served as the second control group. Alcohol did not alter the food intake of the rats compared with the controls kept at room temperature, but it did cause a mean decrease of 8 ml in fluid consumption. There was no difference in the increase in body weight between the groups housed at room temperature. Body weight of the rats exposed to cold did not change during cold acclimation. No morphological liver changes were observed in alcohol-fed rats, but some changes related to long-term alcohol consumption were found in the myocardium. Chronic alcohol intake increased the quantity of brown adipose tissue and its protein content but changes were not as great as in the cold-acclimated rats nor did alcohol increase protein content per unit of the adipose tissue as did cold. On the other hand, the specific activity of mitochondrial cytochrome oxidase increased by 90% and that of succinate dehydrogenase by 130% in alcohol-fed rats, whereas specific activities of these enzymes displayed little or no change in the cold-acclimated rats. Results suggest that chronic alcohol ingestion induces the oxidative capacity of the interscapular brown adipose tissue in the rat, increasing the mass of BAT and specific activities of mitochondrial enzymes.

Histochemical and biochemical detection of alcohol dehydrogenase in rat brown adipose tissue.

Alcohol dehydrogenase (ADH) was studied histochemically in rat brown adipose tissue (BAT), white adipose tissue (WAT) and liver, and its activity was also measured in these tissues. A positive ADH reaction was seen histochemically in the liver and BAT, but not in the WAT, and similarly ADH activity was detected biochemically in the liver and BAT, but there was no measurable activity in the WAT. ADH activity was 80% higher in the liver than in the BAT. It is suggested that the occurrence of an ethanol metabolizing enzyme in brown adipose tissue may be connected with the previously reported ethanol-induced increase in the oxidative capacity of BAT, or, at least, that BAT is able to use ethanol as a substrate for thermogenesis.

Hypothalamic and serum catecholamines in ethanol and acetaldehyde treated guinea-pigs. Relation to moderate short-term cold exposure.

Adult guinea-pigs were treated with ethanol (2.5 g/kg, IP) or acetaldehyde (100 mg/kg, IP) and exposed to moderate cold (+4 degrees C) for 50 minutes. Controls were given 0.9% NaCl solution. The hypothalamic catecholamines norepinephrine (NE) and dopamine (DA) and also norepinephrine and epinephrine (E) in the serum were analyzed by high-performance liquid chromatography with an electrochemical detector. Blood glucose, free fatty acids and glycogen in the liver and skeletal muscle were also measured. Acetaldehyde caused a similar drop in colon temperature as did ethanol, but neither could prevent cold-induced vasoconstriction in the ear lobe. Ethanol significantly reduced the concentration of NE in the hypothalamus compared to the controls. Acetaldehyde had a tendency to lower hypothalamic NE. There was no significant difference between drug-treated groups in NE concentration. Neither ethanol nor acetaldehyde had any effect on hypothalamic DA. In the ethanol group serum E and glucose were significantly elevated compared to the acetaldehyde group. Serum glucose was also higher compared to the controls, and the difference in serum E concentration near the level of significance. No significant differences were found between the groups in serum NE, FFA or skeletal muscle and liver glycogen concentration. The results point to a possible central effect of ethanol during a short-term moderate cold exposure. The effects of acetaldehyde on neuronal tissue remain speculative, but a possible effect on noradrenergic neurons cannot be ruled out. Although the hypothermic effect of acetaldehyde corresponded that of ethanol, further experiments are required to elucidate the role of acetaldehyde in ethanol-induced hypothermia.

Pulmonary and serum surfactant phospholipids and serum catecholamines in strangulation. An experimental study on rats.

Elevations of phospholipid and catecholamine concentrations in the blood are regarded as the vital reactions in asphyxial deaths, which leave few or no morphological signs in the body. These vital reactions were tested here, under strict experimental conditions, employing rapid asphyxia. Rats anaesthetized with barbiturate were strangled with a rope 2 mm thick tightened with a force of 29.4 N (3 kp). The main surfactant components, phosphatidyl choline and phosphatidyl ethanol amine, were measured in serum and lung samples, and catecholamines in the serum. The lungs were also investigated histologically. The serum phospholipid concentration in the strangulated rats was 1.36 +/- 0.32 g/l, versus 1.04 +/- 0.17 g/l in the controls (barbiturate intoxication), P < 0.001, but no change in their content was observed in the lungs (26.21 +/- 4.04 mg/g vs. 25.15 +/- 3.64 mg/g dry weight). Histologically, focal emphysema and tiny haemorrhages were seen in the lungs of both groups with similar frequency. Mean serum noradrenaline (NA) and adrenaline (A) concentrations were significantly higher in the strangulation group (NA = 5.4 +/- 2.6 ng/ml vs. 2.8 +/- 0.1 ng/ml, P < 0.001 and A = 6.0 +/- 3.4 ng/ml vs. 3.8 +/- 3.0 ng/ml, P < 0.05). The results support the notion that phospholipid and catecholamine concentrations are increased in the blood upon suffocation and could thus be taken as indicators of hypoxia. Further investigations into postmortem phospholipid change or stability are needed. There are reports that phospholipid concentration remain quite stable for two days post mortem, whereas catecholamine concentrations tend to rise quite soon after death.

Urinary catecholamines in hyperthermia-related deaths.

A group of five hyperthermia-related deaths is presented in which urinary noradrenaline (NA) concentrations were elevated (172.1 +/- 119.4 ng/ml) compared with a control group of rapid violent deaths (43.7 +/- 26.1 ng/ml). Urinary adrenaline (A) concentrations were not elevated in the hyperthermia cases, nor were there any significant differences in urinary dopamine (DA) concentrations between the two groups. All except one of the hyperthermia victims were under the influence of ethanol. It is suggested that a combination of heat stress and ethanol consumption was responsible for the elevated urinary NA in the hyperthermia cases, reflecting increased sympathetic nervous system activity. A combination of high urinary NA with low A seems to be characteristic of hyperthermia fatalities, in contrast to hypothermia deaths, where both NA and A are usually elevated.

Thrombosis in a mechanical aortic valve prosthesis during subcutaneous heparin therapy in pregnancy; a case report.

Maternal death due to thrombosis in a mechanical aortic valve prosthesis during heparin therapy is described. The patient had a normal pregnancy during warfarin therapy. In this pregnancy, warfarin therapy was replaced by subcutaneous heparin injections, and the patient died of massive thrombosis in the valvuloprosthesis at 20 weeks of pregnancy. The effectiveness of heparin therapy and difficulties in the follow-up of heparin treatment during pregnancy are discussed.

Drugs and alcohol in hypothermia and hyperthermia related deaths: a retrospective study.

Hypothermia and hyperthermia related cases recorded for the period 1973 to 1984 were collected from the files of the Department of Forensic Medicine, University of Oulu, and the necropsy protocols including toxicological results were analyzed. The fact that similar alcohol concentrations were found in both types of fatalities points to the poikilothermic effect of alcohol in humans, as found in animal studies. Both types of deaths seem to be associated with the alcohol elimination phase. Antidepressants and neuroleptics were most often found in the hypothermia cases, but benzodiazepines were also quite frequently present. In spite of the diminished use of barbiturates, these still appear in hypothermia fatalities. Certain other drugs that affect thermoregulation were also noted in solitary cases. Extended toxicological analysis was seldom made in the cases of hyperthermia deaths, and no firm conclusions on the poikilothermic effect of psychotropic drugs could be reached, for example. Therapeutic drug concentrations did not alone predispose the subjects to hypothermia, but appeared in connection with alcohol consumption or chronic diseases.

Estrogen receptor-1 genotype is related to coronary intima thickness in young to middle-aged women.

OBJECTIVE: The incidence of coronary disease in premenopausal women is about one-half that in men of similar age. The estrogen receptor-1 (ESR1, c.454-397T>C) CC variant genotype is associated with the severity of coronary artery disease (CAD) and an increased risk of myocardial infarction in men. The purpose of the present study was to investigate whether this ESR1 CC variant also disposes to atherosclerosis in women in terms of increased total coronary artery intima thickness. MATERIAL AND METHODS: A total of 125 forensic autopsy cases of women aged 15 to 49 years were investigated. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The ESR1 c.454-397T>C genotype was determined by polymerase chain reaction (PCR). RESULTS: The mean intima thicknesses in the three genotype groups were 428+/-298 microm (TT), 494+/-371 microm (CT) and 636+/-436 microm (CC). We found that, on average, women with the CC genotype had a thicker coronary intima compared with that of women with the TT genotype, even after adjusting for age and body mass index (BMI) (p = 0.030). The intermediate group (TC) did not significantly differ from either the CC or the TT genotype group in this respect. CONCLUSION: Our results point to the importance of ESR1 genotype in relation to cardiovascular disease susceptibility.

The -1C to T polymorphism in the annexin A5 gene is not associated with the risk of acute myocardial infarction or sudden cardiac death in middle-aged Finnish males.

OBJECTIVE: A common polymorphism (-1C to T) in the translation initiation sequence of annexin A5 (ANV) gene has recently been associated with a decreased risk of acute myocardial infarction (AMI). The aim of the present study was to analyze the association between the ANV genepolymorphism and the risk of AMI and ischemic sudden cardiac death (SCD) in middle-aged Finnish males. MATERIAL AND METHODS: A case-control study involving three distinct groups of subjects was carried out: (1) victims of SCD (n=98), (2) survivors of AMI (n=212), and (3) randomly selected control subjects without any history of coronary heart disease (n=243). The ANV polymorphism was genotyped in each study group. RESULTS: Among the control group of healthy Finnish males the prevalence rates of the CC, CT, and TT genotypes were 83.1%, 15.2%, and 1.6%, respectively. Among the survivors of AMI, the prevalence rates of CC, CT, and TT were 79.7%, 20.3%, and 0%, respectively, and among the victims of SCD 83.7%, 16.3%, and 0%, respectively. No significant differences in the genotype or allele distributions were observed between the study groups. CONCLUSION: The -1C to T polymorphism in the ANV gene is not associated with the risk of AMI or SCD in middle-aged Finnish males.

Adiposity, cardiac size and precursors of coronary atherosclerosis in 5 to 15-year-old children: a retrospective study of 210 violent deaths.

OBJECTIVE: To determine the relationship between cardiac size and various measures of adiposity in children and the occurrence of coronary fatty streaks in relation to childhood obesity. DESIGN: A retrospective study based on 210 medico-legal autopsies of 5-15 y old children who had suffered violent death in the Province of Oulu, Finland, in 1970-1995. METHODS: Autopsy reports with attached clinical data and police records were recovered from the archives of the Department of Forensic Medicine, University of Oulu, Finland. All 5-15 y old individuals who had died of external trauma and were not documented as having had any chronic illnesses were chosen for investigation. The following data were extracted from the papers: age, sex, height, body weight, heart weight, liver weight, total weight of the kidneys, thickness of the abdominal subcutaneous fat and description of the coronary arteries. Heart weight was indexed to height2.7, and liver weight and kidney weight were indexed to body weight, body surface area and height. The ponderal index (body weight/height3) was calculated, and relative body weight was determined as the percentage deviation of the weight from the mean weight for height according to a growth chart developed for Finnish children. RESULTS: The average absolute heart weight and heart weight/height2.7 were significantly higher in the boys than in the girls over 12 y of age. Abdominal subcutaneous fat was thicker in the girls, but there were no significant differences in the other indicators of obesity. After adjusting for age, there were significant positive correlations between the ponderal index and heart weight/height2.7 in both the boys (P = 0.000) and the girls (P = 0.038), between relative body weight and heart weight/height2.7 in the boys (P = 0.000) and the girls (P = 0.027), and between abdominal subcutaneous fat thickness and heart weight/height2.7 in the boys (P = 0.045) but not in the girls (P = 0.234). Multiple linear regression analysis showed the ponderal index to be a significant predictor of heart weight/height2.7. Coronary intimal fatty streaks were documented in six individuals (2.9%), five of them having a ponderal index above the average and all of them having a relative weight above the average. Kidney weights were higher in the boys and were positively correlated with the measures of obesity and with heart weight/height2.7. CONCLUSIONS: The results point to an important role of excess body weight and adiposity in the development of early myocardial and coronary changes in childhood: coronary fatty streaks were not found at all in the leanest individuals in this relatively large group and the cardiac size adjusted for body size indicated hypertrophy with increasing adiposity. Prospective autopsy studies are needed in order to determine whether adiposity and the regional distribution of fat, especially intra-abdominal fat accumulation, are associated with the earliest signs of myocardial hypertrophy and the initial phase of lesion development in the arterial intima of children.

Association between cardiac pathology and fat tissue distribution in an autopsy series of men without premortem evidence of cardiovascular disease.

OBJECTIVE: To determine the relationship between cardiovascular status and body fat tissue distribution in men without any premortem clinical evidence of cardiovascular disease. SUBJECTS: 30 forensic autopsy cases which consisted of sudden deaths resulting from accidental causes, suicides or homicides or from unexpected natural causes. METHODS: Body height and weight, the circumferences of the waist and hip and the thicknesses of the subscapular and abdominal subcutaneous fat were measured, and Body Mass Index (BMI) and Waist-to-Hip ratio (WHR) were calculated. Perirenal, omental and mesenterial fat deposits were weighed and supraclavicular-pericarotid and perirenal-periadrenal fat was excised and serial samples analyzed for brown adipose tissue (BAT) by computerized image analysis. The heart weight was indexed for height. The degree of coronary narrowing was determined in each artery, and myocardial collagen volume fraction and myocyte cross-sectional area were measured. RESULTS: There were significantly positive correlations between age and the degree of coronary arteriosclerosis and heart weight/height. After adjusting for age, BMI and waist circumference had a significant positive correlation with all the cardiac parameters. The degree of coronary narrowing and heart weight/height were related to tertiles of BMI and waist circumstance. The age-adjusted correlations between the subscapular fat thickness and cardiac parameters were significant and positive, and perirenal fat weight also had a significantly positive association with all the cardiac parameters. BAT decreased with age and when adjusted for age, the cervical BAT percentage had a significant negative correlation with waist circumference and WHR, and a significant negative correlation was also found between cervical BAT and the degree of coronary arteriosclerosis and between perirenal BAT and heart weight/height. CONCLUSIONS: The results suggest that body fatness is associated with coronary and myocardial pathology in men without any clinical evidence of cardiovascular disease. An abdominal accumulation of fat seems to be connected with both the severity of coronary lesions and myocardial hypertrophy in men, in whom there is also a connection between abdominal obesity and a relative scarcity of BAT. Future investigations will require more detailed analyses of the extent and ultrastructural of coronary artery lesions in order to obtain more specific information on the relationship of body fat distribution to the early asymptomatic phase of coronary disease in younger individuals.

Hyperthermia deaths in Finland in 1970-86.

All cases in which hyperthermia had been determined as the basic cause of death during the period 1970-86 were collected from the records of the Central Statistical Office of Finland. Of the total of 230 cases, 228 were included in the present study; the two remaining victims died abroad, and no autopsy was performed in Finland. Most of the hyperthermia deaths occurred while the decedent was taking a sauna bath; most decedents were men aged 42-62 years. An increase in the total number of hyperthermia deaths, and of male victims, was noted from the beginning of the 1970s onward; the number of female victims remained at a relatively steady level throughout, with the exception of a slight rise in 1986. Acute alcohol consumption was detected in most of the victims; in some cases there was also a reference to chronic alcoholism or recent long-term heavy drinking. The findings suggest that in addition to the acute hazardous effect of ethanol on thermoregulatory mechanisms, the long-term consumption of alcohol may have promoted fatal hyperthermia in these subjects.

Myocardial infarction and coronary pathology in severely obese people examined at autopsy.

OBJECTIVE: To find out the severity of coronary atherosclerosis and its relationship to body structure and adiposity in severely obese people with body mass index (BMI) > or = 35.0 kg/m(2) and to examine the incidence and characteristic features of myocardial infarction and other fatal coronary events in this population. DESIGN: Autopsy reports were analyzed, including data on age, height, weight, abdominal subcutaneous fat thickness, heart weight, coronary atherosclerosis, histopathology and toxicology. Myocardial collagen and arteriolar structure were examined by computerized image analysis. SUBJECTS: Forensic autopsy cases (n=166) with a BMI > or = 35.0 kg/m(2) examined in 1992-1998 were collected from the files of the Department of Forensic Medicine, University of Oulu, Finland. RESULTS: In a large number of the severely obese individuals, the coronary arteries were either lesion-free or only fatty streaks were observed (38% of men, 44% of women) and coronary thrombosis was rare (3.8% of men and 1.6% of women). Cardiac causes of death predominated, cardiomyopathy being the commonest. Myocardial infarction was the immediate cause of death in 14.4% of men and 12.9% of the women, and it was associated with increased heart size in men. Coronary atherosclerosis without any infarction had been determined as the cause of death in 8.6% of the men and 8.1% of the women. Abdominal subcutaneous fat thickness had a significant negative association with the severity of coronary atherosclerosis in the women, and a decrease in the arteriolar media/lumen ratio with increasing BMI was observed in the men. CONCLUSIONS: A considerable number of severely obese people have only fatty streaks and no marked stenosis in their coronary arteries, even at an advanced age. The large amounts of subcutaneous adipose tissue in obese women may provide some protection against coronary lesion development, which could be an estrogen effect. Myocardial infarction in severely obese men is associated with cardiac hypertrophy. The significance of the BMI-related dilatation of the myocardial arterioles in men and its relationship to a remodelling of the epicardial arteries will require future investigations.

Expression of estrogen receptors in the coronary arteries of young and premenopausal women in relation to central obesity.

OBJECTIVE: To examine the relationship of coronary estrogen receptor (ER) expression with atherosclerotic lesions and central fat accumulation in premenopausal women. SUBJECTS: A total of 52 female forensic autopsy cases aged between 18 and 49 y. METHODS: Height, body weight and waist and hip circumferences were measured and body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Intima thickness or maximal thickness of the plaque were measured from samples taken from the left anterior descending artery (LAD). Macrophage infiltration and smooth muscle cells were localized by immunostaining. ER was detected immunohistochemically and by Western blot analysis, and the ER immunopositive area in the intima was measured. RESULTS: ER immunoreactivity was observed in the intima in 60% of the samples, and it was most intense in the advanced plaques near the lipid core next to the maximal intensity of macrophage staining. The ER immunopositive area had a significant positive correlation with LAD intima thickness, which in turn was significantly correlated with waist circumference and WHR when adjusted for age and BMI. CONCLUSIONS: Premenopausal women with the central type of fat accumulation have advanced coronary plaques in which ER expression is localized near the lipid-rich and macrophage-rich zone. The higher expression of ER in the arterial plaques may represent a compensatory mechanism against atherosclerosis.

Extent and composition of coronary lesions and degree of cardiac hypertrophy in relation to abdominal fatness in men under 40 years of age.

The relationship of the extent and composition of coronary lesions and the degree of cardiac hypertrophy to anthropometric indicators of abdominal fatness and the amount of intra-abdominal fat was investigated in a group of 32 forensic autopsy cases that consisted of sudden deaths from violent causes of previously healthy men under 40 years of age. Body height and weight, waist and hip circumferences, and the thickness of the subscapular and abdominal subcutaneous fat were measured; the body mass index (BMI) and waist-to-hip ratio (WHR) were calculated; and omental, mesenteric, and perirenal fat deposits and the heart were weighed. The degree of coronary narrowing was determined visually, and the extent of coronary lesions was measured by planimetry. The thickness of the intima and intima-media was measured by computerized image analysis. Intimal macrophage foam cells and smooth muscle cells were detected by immunohistochemistry. Significant positive correlations were found between WHR and the overall degree of coronary narrowing and the intima-media thicknesses of the left anterior descending artery and right coronary artery when adjusted for age. Intima-media thickness was also related to tertiles of WHR. Heart weight indexed to height showed a significant positive correlation with BMI, waist circumference, WHR, and the size of intra-abdominal fat deposits, of which WHR was the best predictor of mild cardiac hypertrophy. The results indicate that the severity of clinically silent lesions in the atherosclerosis-prone regions of the coronary arteries is associated with WHR in young male individuals who also have mild myocardial hypertrophy associated with abdominal fatness and an accumulation of intra-abdominal fat. These associations between fat distribution and early cardiovascular changes point to a powerful need for preventive action with respect to weight gain in young men to alleviate progression of the lesions.

Fatal complications of intramuscular and intra-articular injections.

Four fatalities related to intramuscular and intra-articular injections are reported. In two of these cases a Staphylococcus aureus sepsis developed, as a consequence of injections into the left hip joint in one and in the lateral upper quadrant of the gluteal region in the other. The intra-articular injection of triamcinolone produced severe pain, but no marked signs of purulent arthritis were seen at autopsy, probably because of the anti-inflammatory effect of the corticosteroid. A cutaneous infection was seen in the gluteal region of the other patient, but no apparent abscess formation. In another case of intra-articular injection, purulent knee joint arthritis developed after an injection of glucosaminoglycan. The patient died of renal insufficiency, which was probably connected with the treatment of the arthritis with tobramycin and cefuroxim. The fourth case was that of a mentally ill patient who suffered sudden cardiac arrest after an intramuscular injection of chlorpromazine, but with no apparent signs of an anaphylactic reaction. It is suggested that vasodilatation and drop in blood pressure caused by the chlorpromazine could have had some effect, while cardiotoxicity of other psychotropic drugs with which he had been treated cannot be ruled out.