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.

One fish, two fish, we QC fish: controlling data quality among more than 50 organizations over a four-year period.

EPA is conducting a National Study of Chemical Residues in Lake Fish Tissue. The study involves five analytical laboratories, multiple sampling teams from each of the 47 participating states, several tribes, all 10 EPA Regions and several EPA program offices, with input from other federal agencies. To fulfill study objectives, state and tribal sampling teams are voluntarily collecting predator and bottom-dwelling fish from approximately 500 randomly selected lakes over a 4-year period. The fish will be analyzed for more than 300 pollutants. The long-term nature of the study, combined with the large number of participants, created several QA challenges: (1) controlling variability among sampling activities performed by different sampling teams from more than 50 organizations over a 4-year period; (2) controlling variability in lab processes over a 4-year period; (3) generating results that will meet the primary study objectives for use by OW statisticians; (4) generating results that will meet the undefined needs of more than 50 participating organizations; and (5) devising a system for evaluating and defining data quality and for reporting data quality assessments concurrently with the data to ensure that assessment efforts are streamlined and that assessments are consistent among organizations. This paper describes the QA program employed for the study and presents an interim assessment of the program's effectiveness.

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.

Automated coding of injuries from autopsy reports.

Medical examiners have a unique database about trauma victims, many, if not most, of whom died at the scene or in transit to a hospital and who, thus, never had their injuries documented by trauma surgeons and so never entered into a local or regional trauma registry. These trauma registries have assisted in assessing the magnitude of traumatic injuries in the community and in evaluating the community's emergency medical systems. Without information about those who are dead at the scene or who die in transit, these trauma registries are incomplete and the evaluations based on them inaccurate. The data about the 50% of trauma victims who never enter the medical system are lacking in these registries. Such information is present in the death investigation and autopsy reports in the various medical examiner/coroner offices in the country. To access this important information more easily in trauma registries, an expert computer system was developed. This pilot study presents the results of using that system to gather medical examiner data. Injury descriptions were abstracted from autopsy reports of 50 consecutive nonhospitalized persons fatally injured in Mobile County, Alabama and its environs. Injury descriptions for all cases were successfully coded in International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) and the Abbreviated Injury Scale (AIS-90) by an expert system. For some cases the expert system "requested" and received clarifying information, all of which was present in the medical records. This research demonstrates the feasibility of gathering accurate and consistent information on the estimated 50% of trauma deaths who do not reach a hospital and who are not included in acute care registries. Without data on such patients, our evaluation of trauma systems is incomplete and resources directed at prevention and treatment may be misapplied.

XX sex reversal: molecular analysis of the SRY/ZFY regions.

PURPOSE: The mammalian sex determining gene, sex region Y chromosome (SRY), is now firmly established as the testis determining locus. The SRY locus is close to the short arm Y terminus and just distal to zinc finger Y region (ZFY), a locus previously thought to be involved in testicular differentiation and the male phenotype. We report on XX sex reversal, a rare sex chromosomal disorder in humans. MATERIALS AND METHODS: Routine amniocentesis revealed an XX fetal karyotype, although at birth the neonate was phenotypically male. Radiographic evaluation showed a normal male urethra and the absence of any female internal genitalia. Subsequent molecular analysis with polymerase chain reaction amplified sequences of the SRY and ZFY loci were positive. RESULTS: This case is the fourth in our series of XX sex reversed male individuals and to our knowledge the first to be diagnosed perinatally. In all cases the SRY and ZFY loci are present, presumably on the paternal X chromosome, as well as a Klinefelter phenotype. These sex reversing translocations are thought to be due to an unequal meiotic recombination of the distal X and Y short arms during male gametogenesis. The tendency for XY translocations to break between the SRY and ZFY loci was not seen in these apparent microtranslocation cases. CONCLUSIONS: These 4 cases demonstrate the usefulness of molecular followup of clinically perplexing sexual discordance. We conclude that SRY and ZFY polymerase chain reaction amplification studies should be performed when sexual discrepancies are noted on prenatal ultrasound and karyotype analysis.

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.

Detection of 2,4-dichlorophenoxyacetic acid using a fluorescence immunoanalyzer.

A flow immunoassay method for the measurement of 2,4-dichlorophenoxyacetic acid (2,4-D) was developed. The competitive fluorescence immunoassay relies on the use of antibody- or antigen-coated poly(methyl methacrylate) particles (98 microns diameter) as a renewable solid phase. The assay exhibits a dynamic range of 0.1-100 micrograms l-1 using a monoclonal antibody or alternatively 10 micrograms l-1 to 10 mg l-1 using commercially available antiserum. The assay is demonstrated in buffered saline solution as well as in aquatic environmental media. The relative errors for the environmental matrices were similar to those for the buffer control. The precision of concentration values calculated at 1 mg l-1 (for the assay using antiserum) were +/- 0.28, +/- 0.27 and +/- 0.43 mg l-1 for the buffer, well water and river water matrices, respectively. The method shows cross-reactivity with compounds of closely related structure but little cross-reactivity with compounds dissimilar in structure to 2,4-D. The proposed automated competitive immunoassay method is rapid (between 7 and 15 min per assay), simple and potentially portable.

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.

Portal vein embolization following shotgun-pellet injuries to the abdomen.

Multiple missile emboli are rare. The most likely setting for their occurrence is multiple penetrating injuries from birdshot. Such is this case of this 26-year-old man with birdshot injuries to the torso penetrating the portal vein and embolizing to the liver, producing infarcts and death.

Sickle cells and sudden death: morphologic abnormalities of the cardiac conduction system.

Sudden unexpected death has become increasingly recognized as an important clinical feature of both homozygous and heterozygous sickling syndromes, but the exact nature of its cause has remained unexplained. We have conducted special postmortem examinations of the cardiac conduction system and a coronary chemoreceptor from the hearts of two black males who had sickled erythrocytes. There were abundant foci of old and recent degeneration in the sinus node, atrioventricular node, and His bundle, as well as the coronary chemoreceptor. Many capillaries and small arteries were packed with sickled erythrocytes, among which small groups of aggregated platelets were also present. Focal fibromuscular dysplasia caused moderate to severe narrowing of many small coronary arteries, including those supplying the conduction system and chemoreceptor. These abnormalities are suggestive of electrical instability of the heart as at least one component of the lethal terminal events in some individuals with sickled erythrocytes. Both the foci of fibrosis and the focal fibromuscular dysplasia of small coronary arteries cannot be simply terminal or recent events but more likely take months or years in developing. For individuals with sickled erythrocytes, as in other examples of sudden death, there is a major element of chance concurrence of numerous otherwise independently less significant factors, but lethal cardiac electrical instability may be the final common pathway.

Comparison of adrenocorticotropin and adrenal steroid responses to corticotropin-releasing hormone versus metyrapone testing in patients with hypopituitarism.

We compared the responses of ACTH and cortisol (F) to corticotropin-releasing hormone (CRH) administration (ovine 1 microgram/kg i.v. bolus) with the responses of urinary 17-OH corticosteroids (17-OHCS) and serum deoxycorticosterone (DOC) to metyrapone administration (450 mg/m2/dose every 4 h x seven doses) in 16 hypopituitary patients. Glucocorticoid therapy for these patients was withheld for a minimum of 3 wk before testing. The CRH test was performed 3 d before or 3 wk after the metyrapone test was used to diagnose the ACTH reserve status. In nine ACTH-intact hypopituitary patients (post-metyrapone 17-OHCS > 12.2 mumol/m2/d; DOC > or = 11.5 nmol/L), the peak F (497-773 nmol/L) and ACTH (5.2-22 pmol/L) responses to CRH stimulation were similar to those of normal subjects (F peak = 554-993 nmol/L and ACTH peak = 6-25 pmol/L at 15-60 min). In one patient with partial ACTH deficiency (postmetyrapone 17-OHCS = 10.5 mumol/m2/d; DOC = 6 nmol/L), the peak F response was low and delayed (246 nmol/L at 180 min) and the peak ACTH response was normal (7 pmol/L). Six severely ACTH-deficient patients (postmetyrapone 17-OHCS < 5.4 mumol/m2/d; DOC < or = 3.4 nmol/L) had a low F response at 15-90 min in all, with a delayed rise in three at 120-180 min in response to CRH administration, whereas ACTH responses were variable: absent or low, normal, delayed, or persistently exaggerated. In conclusion, the CRH-stimulated F response pattern in hypopituitary patients was comparable to the urinary 17-OHCS and serum DOC response to metyrapone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Gunshot injuries in Mobile County, Alabama: 1985-1987.

Although much information about firearm fatalities has been published, few articles have characterized all types of gunshot victims, the weapons used, and the injuries sustained in a well-defined geopolitical unit. This study of 597 persons sustaining gunshot injuries serious enough to cause death or hospitalization in Mobile County Alabama during 1985-1987, addresses that deficit. The overall rate of these 597 seriously gunshot-injured victims was 53/100,000 population per annum. Of the 597 victims, 215 died, resulting in a rate of 18.9 per 100,000 population per annum. Demographic characteristics of the homicide victims, predominantly young black men, and the suicide victims, predominantly middle-aged and elderly white men, are similar to those reported from other parts of the country. Assault victims accounted for the largest (316) number of victims: again, young black men also constituted the largest demographic group among assault victims. Handguns accounted for 71% of the weapons used. No assault type weapons were employed. Head, neck, and chest wounds led with the greatest fatality rates. Information about nonfatally wounded victims, particularly data about the weapons, proved difficult to obtain. This was one of the many problems encountered in this type of project and, consequently, is discussed at some length. Additional population-based studies using prospective methods and a variety of investigators, including persons knowledgeable of firearms, are needed.

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.

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.

Demonstration of a fatal hemolytic transfusion reaction using immunoperoxidase techniques.

An immunoperoxidase technique coupled with monoclonal antibodies to the ABO blood group antigens was used to document a fatal ABO hemolytic transfusion reaction in a medical examiner's case. A case report with explanation of the technique is presented.

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.

Intimal tears of the right atrium of the heart due to blunt force injuries to the abdomen. Its mechanism and implications.

We present six cases involving intimal tears of the right atrium of the heart. A proposed mechanism for this injury is discussed, along with implications of the lesion in fatally abused children and traumatized older patients who survive until hospitalization.

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.