Jorma Hirvonen

The occurrence of brown adipose tissue in outdoor workers.

SummaryHistochemical reactions and activities of mitochondrial enzymes in adipose tissue around the neck arteries and in pericardium were studied in men who had been outdoor workers in northern Finland. The purpose was to study the occurrence of brown fat in workers having been exposed to cool or cold ambient temperature. Indoor workers of the same age were used as controls.Histochemically, no mitochondrial enzyme reactions were seen in the adipose tissues taken from the indoor workers, whereas some outdoor workers had some multilocular adipose tissue, mostly around the neck arteries. Biochemical parameters also showed increased enzyme activities of aerobic energy metabolism in the adipose tissue of these people.The present results suggest that working in the cold can retain brown adipose tissue in “strategic” places in human adults.

Necropsy findings in fatal hypothermia cases

A series of 22 cases of fatal accidental or suicidal hypothermia is presented. Necropsy findings on which the diagnosis can be based were analysed. Purple skin and swelling of face, hands and feet, as well as violet patches on elbows or knees were the most frequent external signs (Frequency 54--59%). The most conspicuous internal macroscopic signs were gastric erosions or haemorrhages, which were seen in half of the cases. Other less frequent signs were pulmonary oedema and acute renal and hepatic degeneration. Microscopically the myocardium showed small degenerative foci and/or fuchsinophilic fibres in two thirds of the cases. The myocardium was macroscopically normal. Histamine and serotonin assays from urine did not indicate increased excretion during exposure. Catecholamine concentrations in urine were high (greater than 0.1 mug/ml) in most hypothermia deaths indicating increased excretion due to cold. The best diagnostic signs seem to be purple skin and oedema in face and ears, stomach erosions, degenerative foci in myocardium and high concentration of catecholamines in the urine.

Paradoxical undressing in fatal hypothermia

The phenomenon called paradoxical undressing has been described from 33 cases of hypothermia collected from Swedish police reports. The cases were almost evenly distributed with regard to sex, age, and geographical distribution. The cases occurred more frequently in open land although cases from town areas were also found. Most incidents were recorded from November to February at low ambient temperatures, although cases were also reported at temperatures above 0 degree C. Arteriosclerosis and chronic alcoholism were important concomitant illnesses, the latter being frequent in middle-aged men. Epilepsy, diabetes, and pregnancy were present in single cases. Ethanol and other drugs were present in 67% of the males and in 78% of the females, ethanol predominating in men and various psychotropic agents in women. The mean blood ethanol concentration in males was 0.16% and in females, 0.18%. Most frequent findings at necropsy were purple spots or discoloration on the extremities, pulmonary edema, and gastric hemorrhages. It is concluded that paradoxical undressing might be explained by changes in peripheral vasoconstriction in the deeply hypothermic person. It represents the last effort of the victim and is followed almost immediately by unconsciousness and death.

Increased Urinary Concentration of Catecholamines in Hypothermia Deaths

Observations are presented on 24 hypothermia deaths, either accidental or suicidal. Most cases occurred in dry, cold circumstances, the air temperature being below 0 degree C. More cases were seen in early winter, suggesting a lack of acclimatization to the cold. Purple skin and swelling of the ears and nose (mild frostbite) were the most frequent external signs of exposure. Frequent internal signs were stomach ulcerations or hemorrhagic gastritis and small degenerative foci in the myocardium. High blood alcohol (about 200 mg/dL) was the most common contributory factor, but psychotropic drugs were detected in a few cases. The total urinary catecholamine content was increased in the hypothermia deaths, with levels of 0.20 +/- 0.16 microgram/mL (mean +/- standard deviation) versus 0.07 +/- 0.07 microgram/mL in sudden natural deaths and 0.02 +/- 0.02 microgram/mL in rapid violent deaths. Adrenaline was more abundant than noradrenaline. It is suggested that urine catecholamine measurements can give useful information for the diagnosis of acute hypothermia.

Mitochondrial DNA deletions in dilated cardiomyopathy: A clinical study employing endomyocardial sampling☆

OBJECTIVES The aim of this study was to assess the occurrence of the two most commonly encountered mitochondrial DNA (mtDNA) deletions in the hearts of patients with idiopathic dilated cardiomyopathy. BACKGROUND The mutation frequency of mtDNA is high, and sporadic cases of cardiomyopathies associated with mtDNA deletions have been described. Reports of increases in mtDNA deletions with advancing age also exist. METHODS We studied 15 consecutive patients with typical signs of idiopathic dilated cardiomyopathy, without a family history, together with 16 control hearts obtained at autopsy from patients who died of noncardiac causes. The patients underwent both right and left heart catheterization, during which endomyocardial biopsy samples were taken. The mtDNA in these samples and in the control hearts was analyzed by the polymerase chain reaction technique for the occurrence and proportion of 5- and 7.4-kilobase (kb) deletions (Cambridge sequence map positions from nucleotides 8469 to 13447 and 8637 to 16084, respectively). RESULTS The 5-kb mtDNA deletion was observed in the hearts of all of the patients with idiopathic dilated cardiomyopathy, accounting for 0.32 +/- 0.05% (mean +/- SEM) of the total mtDNA. The 7.4-kb deletion was found in 7 of the 15 patients with idiopathic dilated cardiomyopathy and comprised 0.28 +/- 0.08% of the total. The 5- and 7.4-kb deletions were detected in 12 and 9 control hearts, respectively, quantitatively similar to the patients with idiopathic dilated cardiomyopathy. A sigmoidal age dependency of the mtDNA deletions was found both in the patients with cardiomyopathy and in the control hearts, but after elimination of the confounding age variable, there was no difference between these groups. CONCLUSIONS Because of the similarity of the age-dependent increase in the frequency of mtDNA deletions in cardiomyopathic and control hearts, the deletions have no causal relation with idiopathic dilated cardiomyopathy. The present results confirm the notion of an increase in mtDNA deletions with advancing age and show that endomyocardial tissue sampling is a feasible method for detecting mtDNA defects in affected hearts.

IS MAINTAINED CRANIAL HYPOTHERMIA THE ONLY FACTOR LEADING TO IMPROVED OUTCOME AFTER RETROGRADE CEREBRAL PERFUSION? AN EXPERIMENTAL STUDY WITH A CHRONIC PORCINE MODEL

BACKGROUND Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcome after prolonged hypothermic circulatory arrest. Here we have compared two temperatures of retrograde cerebral perfusion (15 degrees C and 25 degrees C) with hypothermic circulatory arrest at systemic hypothermia of 25 degrees C to clarify whether the possible benefit of retrograde cerebral perfusion may only be due to improved cooling effect. METHODS Eighteen pigs (23-27 kg) were randomly assigned to undergo 15 degrees C retrograde cerebral perfusion at systemic hypothermia of 25 degrees C, 25 degrees C retrograde cerebral perfusion at 25 degrees C systemic hypothermia, or hypothermic circulatory arrest at 25 degrees C for 40 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg during retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were performed until 4 hours after the start of rewarming. Daily behavioral assessment was done until death or until the animals were killed on day 7. Histopathologic analysis of the brain was carried out on all animals. RESULTS Epidural temperatures were lower in the 15 degrees C retrograde cerebral perfusion group during the intervention (P <.05). In the 15 degrees C retrograde cerebral perfusion group, 4 (67%) of 6 animals survived for 7 days compared with 3 (50%) of 6 in both the 25 degrees C retrograde cerebral perfusion and hypothermic circulatory arrest groups. The median total histopathologic score was 5 in the 15 degrees C retrograde cerebral perfusion group and 7 in the 25 degrees C retrograde cerebral perfusion group (P =.04). CONCLUSIONS These findings suggest that enhanced cranial hypothermia is the major beneficial factor of retrograde cerebral perfusion when careful attention is paid to its implementation.

Suicide mortality among medical doctors in Finland: are females more prone to suicide than their male colleagues?

BACKGROUND Suicide mortality among medical practitioners is in many countries significantly higher compared with other professionals and the general population. Differences between male and female physicians are difficult to estimate reliably because previous comparisons are mainly based on crude mortality rates. METHODS Age-specific mortality rates were calculated for physicians, other professionals and the general population, males and females separately, as well as standardized mortality ratios (SMR) comparing physicians with the other groups. Crude mortality rates were calculated for the specialist groups. RESULTS The SMR for male (female) physicians was 0.9 (2.4) compared with the general male (female) population and 2.4 (3.7) compared with other male (female) professionals. The SMR between male and female physicians was 1.2 (95% CI 0.9-1.7). CONCLUSIONS Our results do not support the claim that female physicians have a greater risk of suicide than their male colleagues, but are concordant with previous observations of a higher suicide rate in female physicians compared with the general population and other female professionals.

Causes of sudden unexpected deaths in young and middle-aged persons

The incidence and causes of sudden and/or unexpected deaths in the 15-49-year old population were investigated. The material was collected from 1492 cases in which either a medico-legal or a medical autopsy had been carried out. The necropsy rate was 42% of all deaths. There were 77 sudden deaths in this age-group, involving 64 males (82%) and 13 females (18%). This is 2% of all deaths and 5% of autopsied cases. The incidence per 100,000 persons in 1 year was 19.3 for males and 3.1 for females. Cardiovascular illnesses were the cause of death in 83% of cases. Coronary artery disease was the most common cause, accounting for almost half of these (49.3%). The next most common vascular cause was subarachnoidal haemorrhage (10.4%). The incidence of coronary deaths per 100,000 inhabitants in 1 year was 8.7 for males and 0.7 for females. In all cases the coronary stenosis was due to atheromatosis or more advanced atherosclerosis. Severe stenosis was located in the left descending artery in 58%, and in 52% the disease was only in one vessel. Thrombosis was found in 52%. Alcoholism (5.2%) was the next most common cause after the cardiovascular diseases. Coronary disease was very rare in age-matched victims of violent death. Deaths due to infections were rare, only 3.9%. Other solitary causes of sudden death were carcinomas, epilepsy, diabetes mellitus, intestinal occlusion and atopic dermatitis via sepsis.

Hypothermia markers: serum, urine and adrenal gland catecholamines in hypothermic rats given ethanol

The effect of ethanol (2 g/kg) on body temperature and catecholamine (CA) secretion in the cold (-20 degrees C) was investigated in adult male and female rats. The temperature dropped more rapidly in the females, being approximately 10 degrees C after 3 h as compared with 18 degrees C in the males. Controls received the same dose of ethanol but were kept at +20 degrees C. Increased concentrations of adrenaline (A) and noradrenaline (NA) were already observed in the serum and urine of the females after 0.5 h of exposure, but at 1 h in the males. Serum values were low in the females after 2 and 3 h and urine values high in connection with the deep hypothermic state. The urine values of the males were also high at the end of exposure, when they, too, were hypothermic. Depletion of amines was observed in the adrenals during the hypothermia phase, while CA concentrations tended to rise in the serum of the rats kept in the warm. The CA index (A:NA) was generally > 1 in both the serum and urine of the cold-exposed rats. The results show that female rats are less resistant to hypothermia than males, as indicated by their more rapid drop in body temperature and exhaustion of CA secretion. It is also apparent that urine CAs are worth measuring in cases of accidental hypothermia and possibly also other types of stress. An elevated CA index (> 1) seems to be an additional marker of hypothermia, showing a proportionally greater increase in the secretion of A than NA during cold stress.

The Role of Cerebral Microdialysis in Predicting the Outcome after Experimental Hypothermic Circulatory Arrest

Objective –To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model. Design –Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20°C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed. Results –Brain glucose concentrations were higher in animals that survived ( p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period ( p = 0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance. Conclusion –Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations.