Sten W. Jakobsson

Causes of death in a cohort of 50 465 young men : validity of recorded suicide as underlying cause of death

We studied causes of death in a cohort of all young males (n = 50 465) conscripted for military service in 1969–70. Six hundred eighty three deaths occurred in the cohort during the follow-up through 1983. Injury-related deaths accounted for 75% of all deaths. Of these, 38% were definite suicides, 10% undetermined suicides and 30% motor vehicle accidents. The validity of officially recorded causes of death was studied by scrutinizing all death certificates (n = 683) and forensic reports, including police reports, toxicological and histological data, from a sample (n = 322) of deaths with unclear circumstances. Of 161 officially recorded suicides (E950–959), only one case was reevaluated into poisoning, “undetermined” (E980). Of 47 cases officially recorded “undetermined” (E980–989), 9 were reevaluated into definite suicide (E950–959) although we believe that this is still an underestimation of “true” suicide cases. An alcohol concentration of more than 0.1 g% was found in 45% of all violent deaths (E800–999), 34% of all suicides and 60% of all “undetermined” deaths. We conclude that the causes of death in most cases of injury related death in young age are recorded with high accuracy. Reevaluation of recorded deaths from “undetermined” causes revealed a number of definite suicides, although the “true” number of suicides is difficult to assess even after close scrutiny of the information available.

Fatty acid inducible cytochrome P-454 of rat kidney cortex microsomes

Abstract Cytochrome P-454 of rat kidney cortex microsomes and cytochrome P-454 of liver microsomes are involved in the ω-oxidation of fatty acids catalyzed at approximately equal rates by both tissues. In contrast to liver microsomes, kidney cortex microsomes catalyze the oxidative demethylation of aminopyrine at a very slow rate and reveal no measurable testosterone hydroxylation activity. Whereas laurate gives rise to a type I spectral change when added to either kidney cortex or liver microsomes, testosterone produces a type II spectral change with kidney cortex microsomes. When rats are fed a standard diet supplemented with approximately 10 % lauric acid the cytochrome P-454 level, as well as the binding capacity of the kidney cortex microsomes for laurate, increases markedly, whereas the ω-oxidation activity is moderately enhanced. Phenobarbital treatment, on the other hand, has no measureable effects on either the cytochrome P-454 level or the ω-oxidation activity of the kidney cortex microsomes. The results suggest that there exist differences in substrate specificity as well as in response to various inducing agents between the CO-binding hemoproteins of rat kidney cortex and liver microsomes.

Induction of microsomal aryl hydrocarbon (3,4-benzo(α)pyrene) hydroxylase and cytochrome P-450k in rat kidney cortex: I. Characteristics of the hydroxylase system☆

Abstract Both the rat kidney cortex aryl hydrocarbon hydroxylase activity and cytochrome P-450 K are induced by benzo(α)pyrene treatment. Following a single injection of benzo(α)pyrene, maximal hydroxylase activity and cytochrome P-450 K content occur at 24 hr, returning to control levels within 72–96 hr. Induction of both the enzyme activity and hemoprotein is inhibited by cycloheximide. The enzyme system is localized in the microsomal fraction, has an absolute requirement for NADPH and molecular oxygen, and a pH optimum at 7.4; the induced activity is linear with microsomal protein concentration up to 0.8 mg and with time up to 20 min. Both the hydroxylase activity and cytochrome P-450 K follow the same pattern of inactivation with increasing temperature. The apparent K m for the induced hydroxylase was 7.7 μ m and V was increased fourfold above control value. In the presence of laurate, a substrate for the kidney microsomal cytochrome P-450 K -dependent monooxygenase system, the amount of inhibition of hydroxylase activity corresponded to the level of activity present in untreated kidney cortex microsomes. α-Naphthoflavone (10 −5 m ), a type I inducer (36) produced a greater inhibitory effect on the induced hydroxylase activity than on the control (55% vs 20%). The presence of cytochrome c or carbon monoxide markedly decreased hydroxylase activity. This evidence in addition to aforementioned characteristics of the enzyme suggests a cytochrome P-450 K -dependent aryl hydroxylase activity which differs from that present in the control rat.

A rapid method for the isolation of viable cardiac myocytes from adult rat

Abstract A technique is described for the isolation of viable heart muscle cells from adult rat by perfusion with a Ca 2+ -free modified Hanks buffer containing crude collagenase. A yield of about 45 × 10 6 myocytes/heart is usually obtained, which approximately corresponds to 50% of the total cell mass of the heart. The viability tested by trypan blue exclusion was 40–50%. Approx. 60% of the viable cells were rod-shaped and contracted with various frequencies. Contractile myocytes survived at room temperature for 24 h, at +4 °C in Ficoll ® for 5 days. Cellular morphology examined by light, scanning and transmission electron microscopy corresponded in general to that of intact cells in situ. Contractility and trypan blue exclusion were correlated to plasma membrane integrity as evaluated by determining the oxygen consumption in the absence and presence of succinate and by recording the NADH penetration to the cells upon addition of NADH and pyruvate to the medium. Gasing with carbogen, temperature lowering and the use of Ficoll ® increased the yield and survival of the intact myocytes, while exposure to N 2 , large variations of perfusion pressure, variations in pH and presence of fatty acids or Ca 2+ in the perfusion medium resulted in cellular damage. The described isolation procedure is relatively simple, rapid and gives reproducible yields of viable cells.

Validation of diogonses on death certificates for male alcoholics in Stockholm

The mortality and the causes of death have been studied in a cohort consisting of 1548 male alcoholics in Stockholm. During the period 1969-1981 there were 542 cases of death in this population. The mortality rates were triple those for males in Stockholm generally. Using the official causes of death there was a highly significant excess mortality in the following diagnostic groups: Cancer in the upper digestive region, primary hepatic cancer, cirrhosis in the liver, pancreatitis, pneumonia, alcoholism and alcoholic poisoning, suicides and other causes of violent death as well as ischemic heart disease. The underlying and contributing causes of death on the death certificates were reclassified according to ICD-rules using clinical records and autopsy protocols. It was found that the underlying cause of death was incorrect in 21.8% of the cases. Important information was withheld in further 19.8%. After validation there was no longer any excess mortality in ischemic heart disease. The number of alcohol-related diagnoses, i.e. alcoholic cardiomyopathy, cirrhosis and fatty liver with alcoholism and alcoholic intoxication, was much greater. It is concluded that there is a underreporting of alcohol-related diseases and injuries which has a great influence on the reliability of death statistics.

Lauric acid hydroxylation in human liver and kidney cortex microsomes

Abstract The ω- and (ω- 1 )-hydroxylation of the medium-chain fatty acid, dodecanoic or lauric acid, was studied in liver and kidney cortex microsomes from seven human cadavers. The rates of laurate hydroxylation in human liver microsomes were found to exceed the rates recorded in human kidney cortex microsomes by 4-to 30-fold. The mean specific activity of laurate hydroxylation from the seven human kidneys was six to fourteen times lower than the specific activities found in pig, rat or hamster kidney microsomes. The effects of several known inhibitors of the liver microsomal cytochrome P-450-dependent mono-oxygenase system were also studied. Metyrapone preferentially inhibited the (ω- 1)-hydroxylase activity of human liver microsomes, but did not affect the ω-hydroxylation reaction. In the presence of 7,8-benzoflavone, the human liver microsomal (ω- 1 )-hydroxylase activity was stimulated, but an inhibitory effect was observed on the ω-hydroxylation reaction. 2-Diethylaminoethyl-2,2-diphenylvaIerate (SKF 525A) inhibited both hydroxylase activities in human liver microsomes. Neither metyrapone nor SKF 525A inhibited the laurate hydroxylation reactions catalyzed by human kidney microsomes. These studies indicate that the cytochrome P-450-mediated hydroxylations of medium chain fatty acids in human kidney cortex microsomes are much less active than in kidneys of other species investigated. The effects of the inhibitors, metyrapone and SKF 525A, on ω- and (ω- 1)-hydroxylation of laurate in human liver and kidney microsomes were similar to the effects reported in other mammalian species.

Mortality among criminals with suspected mental disturbance

Mortality rates and cause of death are reported from a long-term follow-up study of 620 Swedish criminals who were subjects of a forensic psychiatric examination in 1965-1968. The results show that there is an increased mortality rate in criminals mainly due to violent deaths (suicides, accidents) and diseases related to alcohol abuse. The increased mortality was found in all age groups throughout the follow-up period of 13-16 years. The total mortality was 17%. An analysis of different mortality risk factors showed that drug abuse, type of crime (violent crimes or property crimes) and criminal recidivism did not further increase the mortality risk. There were relatively few deaths due to overdose of drugs. Alcohol abuse increased the mortality rate significantly.

Experiences with the hematoxylin basic fuchsin picric acid staining method for morphologic diagnosis of myocardial ischemia — An experimental study in forensic pathology☆

An investigation was performed on 148 medicolegal autopsy cases with the purpose of obtaining experience with the hematoxylin basic fuchsin acid staining method for morphologic diagnosis of early myocardial ischemia. A comparative study was performed on rats with induced myocardial infarcts. The uptake of the basic fuchsin stain in myocardial sections agreed well with eosinophilia, often occurred when myocardial infarction was suspected, but very often yielded false positive and negative results. This lack of reliability probably depended on the high sensitivity of the staining procedure, degree of autolysis, fixation time, thickness of the sections and mainpulative lesions. Although the HBFP-technique does not seem sufficiently reliable in medicolegal autopsy cases it probably produces accurate results under controlled experimental conditions.

Poisoning with sodium hypochlorite solution. Report of a fatal case, supplemented with an experimental and clinico-epidemiological study

A case of fatal poisoning in a 1-year-old girl after ingestion of a household cleanser containing 4.5% sodium hypochlorite (Klorin) in an alkaline solution (pH 12.0) is reported. The forensic medical and toxicological investigations were supplemented by animal studies. These studies indicate that 5, 10, and 15 ml of Klorin/kg body wt given to rats is highly toxic, and that local tissue damage and secondary systemic involvement develops with a severity corresponding to the amount administered. The rats, all of which died, showed various degrees of degeneration and necrosis of the esophagoventricular mucosus membranes, changes analogous to those found at the autopsy of the child. A follow-up investigation of similar cases reported to the Swedish Poison Information Centre, during a limited time, was made to complete the picture.

Solubilization and partial purification of cytochrome P-450 from rat lung microsomes

Abstract Cytochrome P-450 from rat lung microsomes has been solubilized and purified 8-fold by using affinity chromatography on an ω-amino- n -octyl derivative of Sepharose 4B. The purified fraction was free of cytochrome b 5 and NADPH-cytochrome c reductase and showed spectral characteristics similar to those of lung microsomal cytochrome P-450. When combined with NADPH-cytochrome c reductase partially purified from liver microsomes, the cytochrome P-450 fraction supported the hydroxylation of benzo (α)pyrene and the activity was proportional to the content of the hemoprotein. No absolute requirement for phosphatidylcholine was found.