Sudden death due to isolated acute infarction of the His bundle.

A 29 year old black man considered to be in good health died suddenly and unexpectedly. At postmortem examination there were no significant gross abnormalities, all drug screens were normal and sicklemia was not present. Special studies of the cardiac conduction system demonstrated isolated acute infarction of the His bundle, with no similar evidence of myocardial infarction anywhere else in the heart. The atrioventricular (AV) node artery was moderately narrowed, but its branch supplying the His bundle was occluded greater than 95% by focal fibromuscular dysplasia. There were no other significant coronary lesions or other abnormalities in the heart.

3 alpha-androstanediol glucuronide in virilizing congenital adrenal hyperplasia: a useful serum metabolic marker of integrated adrenal androgen secretion.

To determine whether serum 3 alpha-androstanediol glucuronide (3AG) reflects the overall effect of integrated adrenal androgen secretion in the virilizing form of congenital adrenal hyperplasia (CVAH), circadian levels (0800, 1200, 1600, and 2000 h) of serum 3AG and 17-hydroxyprogesterone (17OHP) or 11-deoxycortisol (S), androstenedione (A), testosterone (T), and 24-h urinary 17-ketosteroids (17KS) were examined in seven patients (pts) with classical 21-hydroxylase deficiency (21OHD) and one pt with classical 11 beta-hydroxylase deficiency (11 beta OHD). Hormonal studies were conducted during the second day of dexamethasone (Dex) administration (2 mg/day). In five poorly controlled CVAH pts, including the 11 beta OHD pt, highly elevated baseline morning (AM) serum 17OHP or S as well as A levels, and elevated AM T levels in three pts decreased markedly in the evening (PM), while elevated serum 3AG showed no significant circadian changes; 17KS levels were markedly elevated for age. During Dex, moderately or slightly elevated AM 17OHP, A, or T in two to four pts with 21OHD decreased to the normal range in the PM. In the pt with 11 beta OHD, S, A, and T levels were suppressed. 3AG levels were modestly elevated or normal, without circadian changes, in these pts; 17KS levels were elevated or normal. In two other 21OHD pts, modestly elevated AM baseline 17OHP and A levels decreased in the PM; elevated AM T decreased in one pt in the PM; modestly elevated 3AG levels showed no circadian changes; 17KS levels were modestly elevated. During Dex, normal or slightly elevated serum steroids and 17KS levels were associated with normal or high normal 3AG levels without circadian changes. In one postpubertal female with 21OHD, modestly elevated AM baseline 17OHP levels decreased at 2000 h; normal A and T levels throughout the day and low normal 17KS were associated with slightly low 3AG levels, without circadian variation. During Dex treatment, normal 17OHP, A, T, and low 17KS levels were associated with low 3AG levels without circadian variation. In all pts as a group, an excellent correlation (r = 0.9) was found between either 0800 h or mean, or 2000 h serum 3AG levels and 17KS. In addition, AM and PM serum 3AG levels in five normal women were similar. We conclude that the high correlation between serum 3AG and urinary 17KS and the absence of a significant circadian variation in 3AG indicate that serum 3AG, regardless of sample time, is a useful metabolic index of integrated adrenal androgen secretion in CVAH.

Normal and elevated 3 alpha-androstanediol glucuronide concentrations in women with various causes of hirsutism and its correlation with degree of hirsutism and androgen levels.

We investigated peripheral androgen metabolic activity in 54 hirsute females (HF) by evaluating the serum 3 alpha-androstanediol glucuronide (3AG) concentration, hirsutism score (HS), and etiology of hirsutism. Based on basal and ACTH-stimulated steroid profiles (1 h post-Cortrosyn, 0.25 mg, i.v. bolus), the causes of hirsutism were determined to be increased adrenal androgen production (greater than 2 SD above normal mean), increased ovarian testosterone (T) production (greater than 2 SD above normal mean basal T of ovarian source only), or idiopathic cause (normal steroid profile). Serum 3AG levels in each group of HF were significantly higher (P less than 0.01-0.001) than those in normal females [normal: 2.9 +/- 0.94 nmol/L (n = 28); HF: increased adrenal androgen production of undefined cause, 7.7 +/- 7.5 nmol/L (n = 14); 21-hydroxylase deficiency, 7.6 +/- 7.4 nmol/L (n = 5); increased ovarian T production 5.5 +/- 3.5 nmol/L (n = 18); idiopathic cause, 5.8 +/- 4.8 nmol/L (n = 17)]. However, normal 3AG levels (less than 5.2 nmol/L) were present in 50-67% of HF in each group. Collectively, 3AG levels in HF correlated significantly (P less than 0.01) with dehydroepiandrosterone (DHEA; r = 0.41) and DHEA sulfate (DS; r = 0.44), while the correlation with androstenedione (r = 0.15) or T (r = 0.19) was not significant. Serum 3AG and adrenal androgen levels decreased in all subjects after dexamethasone treatment (0.5-1 mg at hour of sleep; 2 mg/day for 3-5 days). The correlation between 3AG and HS was significant (r = 0.6-0.74; P less than 0.01-0.001) only in HF with increased adrenal androgen secretion and idiopathic cause, and was not significant (r = 0.42) in HF with increased ovarian T secretion. There was no significant correlation between androgen levels and HS. We conclude that the serum 3AG level was not consistently elevated in HF and did not differ significantly between the various causes. Significant correlations between 3AG and DHEA/DS levels, and the simultaneous decrease in 3AG and adrenal androgens after dexamethasone administration in HF suggest that adrenal androgens contribute significantly to 3AG production. The significant correlation between 3AG and HS in HF with increased adrenal androgen secretion and idiopathic cause indirectly suggests an adrenal androgen contribution to both 3AG production and hirsutism in these HF. The insignificant correlation between 3AG and HS in HF with increased ovarian T secretion may result from a confounding effect of ovarian T on hirsutism.

Combined bromocriptine and growth hormone (GH) treatment in GH-deficient children with macroprolactinoma in situ.

Experience with PRL-secreting macroadenomas in the pediatric and adolescent population is limited. Although use of synthetic GH after treatment of central nervous system tumors in children without active disease is accepted practice, reports of GH use in patients with central nervous system tumors in situ are rare. Furthermore, the effect of GH on tumor growth is not known. We report GH treatment (10 and 11.5 months), concomitant with bromocriptine (BC; dopamine agonist) therapy in two children, a 15.5-yr-old male and a 15.5-yr-old female, with PRL-secreting macroadenomas in situ. Surgical resection was deemed undesirable because of the risk of major morbidity due to the large size of the tumors and the close proximity to major vessels. Both patients were GH deficient and had heights below the fifth percentile coupled with arrested pubertal progress. During BC therapy, a decrease in tumor size and a reduction in serum PRL levels occurred in both patients, which continued after the addition of GH treatment. Neither patient experienced changes in visual acuity during combined treatment, and both experienced marked improvement in growth velocity. We conclude that in children with PRL-secreting tumors and GH deficiency in whom surgery is not advised, combined treatment with BC and GH appears to be safe and efficacious. To our knowledge, these patients represent the first report of the combined therapeutic use of BC and GH as the primary mode of treatment in children with prolactinoma in situ with documented GH deficiency.

3 alpha-Androstanediol glucuronide in premature and normal pubarche.

To investigate the role of adrenal androgens in 3 alpha-androstanediol glucuronide (3AG) production in childhood, we compared serum 3AG and androgen levels [dehydroepiandrosterone (DHEA), DHEA sulfate (DS), androstenedione (delta 4-A), and testosterone (T)] in 32 children with premature pubarche due to idiopathic premature adrenarche (IPA; n = 26), partial 21-hydroxylase deficiency (n = 2), or 3 beta-hydroxysteroid dehydrogenase deficiency (n = 4) with those in 36 normal prepubertal (18 males and 18 females) and 22 normal pubertal Tanner II-III subjects (10 males and 12 females). Serum 3AG (2.7 +/- 2.0 nmol/L) and all androgen concentrations in children with IPA were significantly higher (P less than 0.05-0.001) than those in normal prepubertal children (3AG, 0.8 +/- 0.5 nmol/L). Serum 3AG and androgen levels, except T, in all children with premature pubarche due to 21-hydroxylase deficiency or 3 beta-hydroxysteroid dehydrogenase deficiency were higher than those in the normal prepubertal children. Serum 3AG and all androgen levels in normal Tanner II-III male (3AG, 3.8 +/- 1.7 nmol/L) or female (3AG, 1.74 +/- 0.52 nmol/L) subjects were also significantly higher (P less than 0.05-0.001) than those in prepubertal children. Serum 3AG, DHEA, DS, and delta 4-A levels in children with IPA were similar to those in normal Tanner II-III females or males, but serum T in children with IPA (0.37 +/- 0.2 nmol/L) was significantly lower (P less than 0.05-0.001) than that in normal pubertal females (0.71 +/- 0.37 nmol/L) or males (4.5 +/- 2.6 nmol/L). In the combined group (n = 88), 3AG levels correlated better with serum DS (r = 0.7), DHEA (r = 0.6), and delta 4-A (r = 0.52), than with T (r = 0.31) levels. These data suggest that the weak adrenal androgens DS, DHEA, and delta 4-A contribute substantially to 3AG production in premature and normal pubarche.

Subaortic stenosis and sudden death.

An obese white boy, 16 years old, collapsed and suddenly died while walking with friends. Since early childhood he had been known to have mild subaortic stenosis. At age 6 he exhibited first-degree heart block during an electrocardiographic exercise test. Neither then nor thereafter was he known to have any unusual symptoms until his death. Postmortem examination revealed marked cardiac enlargement without asymmetry or much dilatation. There was mild subaortic stenosis, but the heart was otherwise grossly normal. Special studies of his cardiac conduction system demonstrated fibrotic obliteration of the His bundle and proximal portions of both bundle branches. The same region had a much thickened central fibrous body from which the subaortic stenosis ridge protruded. Small arteries in the vicinity of the atrioventricular node were markedly narrowed. Because those vessels provide some of the blood supply to the His bundle region, their narrowing may have contributed to the fibrotic abnormalities observed. The extent of destruction of the His bundle makes a lethal failure of atrioventricular conduction the most likely terminal event.

Physical and chemical injury as causes of sudden cardiac death: the forensic forum.

Physical and chemical injuries account for the largest number of sudden, unexpected cardiac deaths in persons between the ages of 1 and 44 years. Blunt-force injuries, lacerations, avulsions, and contusions of the heart and great vessels sustained during motor vehicle crashes constitute the most prevalent type of lethal physical trauma to the cardiovascular system. The second most prevalent type of trauma is from penetrating and perforating wounds inflicted by firearms. The mechanisms of these injuries are discussed, with emphasis placed on those factors contributing to lethality. The three most prevalent chemicals associated with sudden cardiac death-ethyl alcohol, cocaine, and tricylic antidepressants-are briefly mentioned.

Investigation of the mechanism of hypertension in apparent mineralocorticoid excess.

Apparent mineralocorticoid excess (AME) is a rare form of low renin hypertension caused by deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), the enzyme responsible for conversion of cortisol to the bio-inactive metabolite, cortisone. This results in prolonged cortisol half-life, activation of type I (mineralocorticoid) receptors by cortisol, sodium and fluid retention, and consequent childhood-onset hypertension. The cortisol secretion rate is low, perhaps due to cortisol's binding to type II (glucocorticoid) receptors and suppressing corticotropin secretion. Patients with AME thus lack stigmata of Cushing's syndrome. To evaluate any potential contribution of the type II (glucocorticoid) receptor to the development of hypertension in AME patients, we administered RU486, a steroid analogue that acts as a pure type II receptor blocker. Selective glucocorticoid receptor blockade did not decrease blood pressure in our patient; instead, a significant increase in average blood pressure was observed (125.1 +/- 1.7 pre-RU486 v 144.7 +/- 1.2 during RU486 treatment, P = .0001). We conclude that the type II receptor does not contribute to the development of hypertension in patients with AME.

Atlanto-occipital subluxation/dislocation: a "survivable" injury in children.

Atlanto-occipital dislocation occurs more often in children due to the laxity of the ligamentous structures anchoring the occiput to the axial skeleton. The mechanism of action usually involves a sudden acceleration-deceleration force on the head of the child. The dislocation usually severs the spinal cord at the foramen magnum, resulting in acute respiratory arrest. We have managed four patients who sustained this injury and arrived at our trauma center with signs of life. Two patients were hemodynamically unstable, had positive diagnostic peritoneal lavage, and underwent splenectomy. Both patients had obvious separation of the occiput and C1 on lateral cervical spine films. Both remained very unstable and died soon after celiotomy. The other two patients were stabilized, and both met criteria for brain death; one family agreed to organ donation. A 5-year analysis revealed 57 pediatric deaths, with 10 patients sustaining atlanto-occipital dislocations (17.5%). Nine of 10 patients sustained other injuries, but in only 2 patients were the injuries immediately life-threatening. With continued improvement in emergency medical systems and pediatric trauma care, we can expect to see more pediatric patients with this injury arriving in trauma centers with signs of life. In our experience, 50 per cent of patients may meet organ donor criteria, and our incidence of this injury (17.5%) reveals atlanto-occipital dislocation as a major contributor to pediatric trauma mortality.

Cytoskeleton immunohistochemical study of early ischemic myocardium.

Previous studies on cytoskeletal changes of in vitro and in vivo animal models of ischemic myocardium have suggested the possibility of using alterations in cytoskeleton proteins as an early marker for the post-mortem diagnosis of myocardial ischemia in cases of sudden death due to coronary artery disease (CAD). In the present study, using the technique of ABC-immunohistochemistry, we examine the changes of three cytoskeletal proteins: vinculin, desmin and alpha-actinin in human myocardial samples taken from 14 cases of CAD sudden death and 13 cases of non-CAD death. Results of these examinations are compared with immunohistochemical changes of myoglobin and histochemical staining of hematoxylin and eosin and phosphotungstic acid, and Masson trichrome. Patchy and extensive loss of the three cytoskeletal proteins was demonstrated in the myocardium of victims who died 1 h or later following the onset of symptoms of ischemic myocardium. The pattern of cytoskeleton change is equivocal in the cases of CAD who died less than 1 h after the onset of symptoms and of the cases of non-CAD. In these cases, no significant histological change was observed. With less non-specific background changes and stronger positive staining, immunohistochemical staining of the three cytoskeletal proteins is more reliable than myoglobin, which has attracted the attention of many pathologists searching for anatomic evidence of ischemic myocardium in coronary artery disease.

Homicide in Alabama: an analysis of urban, suburban and rural murders in the Deep South.

Eleven hundred forty-four (1144) homicides occurring in Alabama, U.S.A. during a 2-year period are presented and analyzed according to the demographic parameters of the victims, location in urban, suburban, or rural community, type of homicide based on a medical examiner's classification, presence of drugs, weapon employed and other factors. Urban dwellers, Blacks and males are found to be at high risk. Alcohol is much more prevalent than other drugs in homicide victims. Although the handgun is the weapon most commonly used throughout the state, in the rural regions the longgun is used almost as often. The difficulty of making valid comparisons with other homicide studies is discussed and the establishment of a uniform classification of homicides urged.

Retroperitoneal chondrosarcoma presenting with pleural effusion: a case report.

An adolescent male patient presented with pleural effusion of undetermined etiology which was unresponsive to antituberculous therapy. He died suddenly a few months later and was found at autopsy to have suffered from acute catastrophic pulmonary occlusion, secondary to embolization from retroperitoneal chondrosarcoma which had invaded and occluded the pulmonary arteries via the inferior vena cava. The rarity of this phenomenon in children prompted this report.

Alcohol-associated deaths in the District of Columbia--a postmortem study.

Ethyl alcohol and its lethal effects were present either in the victim or in the environment, including persons responsible for a given death, in 53% of the cases autopsied during a six-month period at the Office of the Chief Medical Examiner in the District of Columbia. The results of this small, admittedly biased, sample indicate that the acute and chronic effects of alcohol are a major public health problem in this jurisdiction. Comparative figures from other medical examiner's systems suggest the national prevalence of the problem and confirm the gross inadequacy of data from death certificates for such research. Only when the combination of accurate pathological, toxicological, and historical information concerning all types of deaths is available can reliable statistics regarding the numbers and types of deaths related to alcohol be obtained.

Separation and detection of three aryltins by capillary electrophoresis-UV/VIS diode array.

The trialkyltins and triphenyltins have widespread application as fungicides, antifouling coatings for porous surfaces, herbicides, insecticides, and generic biocides. Due to the varied toxicity of each species of organotins, it is important that methods address the speciation of the organotins. Traditional methods call for the hydrolysis and subsequent derivatization of the organotins before analysis. These methods can be time consuming, derivatization can be incomplete, and high levels of background interference produce difficulties in identification and quantitation. The U.S. Environmental Protection Agency's (U.S. EPA) current methods do not address the speciation of organotins; instead they only analyze for total tin. It is important, because of the differing levels of toxicity of the various congeners of organotins, to speciate them from each other and inorganic tin. The research reported in this paper addresses the use of CE with UV/VIS diode-array detection to separate and detect three phenyltins (i.e., tri-, di-, and mono-), without the need to either derivatize or complex them.

Killing the canary: the international epidemiology of the homicide of media workers.

OBJECTIVES: To describe the international epidemiology of the homicide of media workers, and investigate country-level risk factors. METHODS: Data on the homicides occurring from 2002 to 2006 were collected and collated from five international databases. Analyses included consideration of seven existing international indices relating to human development, and to the social and political functioning of states. RESULTS: During the 5-year period, 370 deaths in 54 countries met our definitions of homicides and media workers. Almost all (89%) were nationals of the country in which they died. The annual number of such homicides globally has more than doubled, from 41 in 2002 to 104 in 2006 (including 49 in Iraq in 2006). Less than 25% of the homicides of media workers over the last 5 years have resulted in an arrest or prosecution. Statistically significant associations (p<0.001; Political Terror Scores, OR 1.15; Corruption Perceptions Index, OR 0.53; Overall Failed State Index, OR 1.05; Failed State Index 7, OR 1.52; Failed State Index 9, OR 1.55; Failed State Index 10, OR 1.61) were found on logistic regression between the occurrence of the homicide of media workers in countries and scoring on six of the seven indices associated with country-level sociopolitical development. These indices reflected high levels of political terror and corruption, low government legitimisation, poor human rights, and uncontrolled armed groups. However, in terms of the homicide rate for countries, these associations were significant for only four of the seven indices (the general functionality of government, ability of governments to control armed groups, the level of political terror, and the level of violation of rights). CONCLUSIONS: The homicide of media workers increased substantially in this 5-year period and was found to be particularly concentrated in selected countries such as Iraq. The authors were able to identify specific sociopolitical risk factors for homicide occurrence, and for homicide rates at the country level.