Fatal iatrogenic iodine toxicity in a nine-week old infant.

BACKGROUND: Povidone-iodine has been used since the 1950s for various labelled uses as a topical antiseptic. The toxicity of an excessive dose in internal use is described in this case report. CASE REPORT: A 9-week old infant was treated for colic by a pediatric gastroenterologist with loperamide and the elimination of nonhuman milk. Without improvement he was hospitalized and given an enema of 50 mL of povidone-iodine diluted in 250 mL of a bowel irrigant. The enema was promptly expelled and 50 mL of the described solution was given hourly for three doses by nasogastric tube. The infant was found lifeless three hours after the last dose and resuscitation was unsuccessful. Autopsy showed a corroded and necrotic intestinal tract, serous fluid in body cavities, a blood total iodine of 14,600 micrograms/dL, protein-bound iodine of 3,400 micrograms/dL and inorganic iodine of 11,700 micrograms/dL.

Interpretation of unusual wounds caused by firearms.

The interpretation of the range of fire of gunshot wounds requires coordination of information and observations from the autopsy surgeon, scene investigator, and laboratory analyst. Opinions based on incomplete information often lead to misinterpretation of the wound. The effects of interposed targets such as clothing, windows, and body parts are discussed. Case examples are given for interposed targets that cause confusing patterns and even lead to misidentification of the points of entrance and exit of the projectile in the body. The splitting of tissue in areas of bony prominence can be mistaken for evidence of discharge of a firearm at close range.

Leydig cell cytoplasmic content is related to daily sperm production in men.

The relationship between the abundance of specific Leydig cell organelles and daily sperm production (DSP) was determined. Testes from 10 men (26-53 years of age) were obtained at autopsy within 10 h of traumatic death or heart failure and fixed by vascular perfusion. Testicular tissue was processed for light and electron microscopy. DSP/testis and Leydig cell cytoplasmic volume/testis were determined by stereology of histologic sections. The Leydig cell organelle content was determined by point counting electron micrographs for smooth endoplasmic reticulum (SER), rough endoplasmic reticulum, mitochondria, lipofuscin pigment, lipid, Golgi bodies, and Reinke crystals. Men were divided equally into two groups based on DSP/testis. Men with low DSP/testis had less SER volume density (P less than 0.01) and lower SER volume per testis (P less than 0.05) than men with high DSP. Other organelles were unrelated to DSP. When all men were combined, the volume density of SER (r = 0.80; P less than 0.01), the volume SER per testis (r = 0.69; P less than 0.05), and the volume SER per Leydig cell (r = 0.84; P less than 0.01) were significantly related to DSP. Hence, there appears to be a significant relationship between Leydig cell SER and the level of spermatogenesis in men.

Increased germ cell degeneration during postprophase of meiosis is related to increased serum follicle-stimulating hormone concentrations and reduced daily sperm production in aged men.

Aged men, known to have high serum gonadotropin levels and reduced spermatogenic potential, were used to study the relationship between serum follicle-stimulating hormone (FSH) and germ cell degeneration. Serum hormones were measured from blood obtained at autopsy. Phase-contrast cytometry was used to enumerate germ cells in homogenates of fixed testes from 13 younger (24-51 yr) and 14 aged (69-90 yr) men. The developmental steps of spermatogenesis during which germ cells degenerate were determined by comparing potential daily sperm production based on primary spermatocytes with daily sperm production based on two different types of spermatids. During spermiogenesis, there was no significant degeneration in the younger or aged men. During postprophase of meiosis, aged men had more (p less than 0.01) germ cell degeneration, significantly lower (p less than 0.05) serum testosterone, and greater (p less than 0.01) serum FSH than did younger men. Germ cell degeneration during postprophase of meiosis was negatively correlated (p less than 0.01) to daily sperm production and significantly (p less than 0.01) related to serum concentrations of FSH. As revealed in these aged men, meiotic germ cell degeneration has a direct effect on daily sperm production and is significantly related to serum FSH concentrations.

Effect of age on the composition of seminiferous tubular boundary tissue and on the volume of each component in humans.

Seminiferous tubular boundary tissue thickens with age. The objective was to characterize the composition of boundary tissue in 16 young adult (20 to 29 years) and 18 older adult (51 to 84 years) men. Testes were perfused with glutaraldehyde, placed in osmium, and embedded in Epon 812 (Ladd Research Industries, Burlington, VT). Paired testicular weight, length of tubules, volume of seminiferous epithelium, and daily sperm production were significantly reduced in older men. Although the thickness of boundary tissue was greater (P less than 0.01) in older men, the volume of boundary tissue per man was similar between age groups. The percentages and volumes per man of boundary tissue myoid cells, collagen, microfibrils, and other components also were similar (P greater than 0.05) between age groups. This study confirms that age-related thickening of boundary tissue occurs without the new deposition (augmentation) of collagen or other extracellular components.

Quantification of human spermatogenesis: germ cell degeneration during spermatocytogenesis and meiosis in testes from younger and older adult men.

Germ cell degeneration during spermatocytogenesis and meiosis was investigated to explain the age-related decline in daily sperm production (DSP). Numbers of Types A-dark, A-pale, and B-spermatogonia, potential daily sperm production per g parenchyma (PDSP) based on type B-spermatogonia, early primary spermatocytes, and late primary spermatocytes, and DSP per g based on early spermatids were determined in 15 men aged 20 to 48 yr (mean +/- SEM, 33 +/- 2 yr) and 15 men aged 52 to 90 yr (65 +/- 3 yr). Testes obtained within 15 h of death (largely due to trauma or heart failure) were perfused vascularly with glutaraldehyde. The number of each cell type per g parenchyma was calculated as the product of the percentage of nuclei in the parenchyma times a correction factor for section thickness and nuclear diameter divided by the volume of a single nucleus of that cell type. Paired testicular weight was lower (p less than 0.01) in older men (33 +/- 3 g) than in the younger men (49 +/- 3 g). Younger and older men had similar numbers of A-dark, A-pale, and B-spermatogonia per g parenchyma. PDSP based on late primary spermatocytes and DSP based on early spermatids were lower (p less than 0.01) in older men than in younger men. In younger men, PDSP was similar (p greater than 0.05) between B-spermatogonia and late primary spermatocytes, whereas DSP measured at the spermatid level was abruptly lower than that estimated from younger cell types. Older men showed reduction in PDSP between early and late primary spermatocytes, with further reduction occurring in DSP at the spermatid level.(ABSTRACT TRUNCATED AT 250 WORDS)

Seminiferous tubules and daily sperm production in older adult men with varied numbers of Leydig cells.

Previous studies of adult men have failed to reveal a relationship between numbers of Leydig cells in the testes and rates of sperm production, perhaps because of a functional excess of these cells in younger men. Hence, a possible relationship between Leydig cell numbers and sperm production was sought in 50 older men, aged 50-90 years, in whom the Leydig cell population had been depleted by age-related attrition. When these men were sorted by increasing numbers of Leydig cells per man into two, three, or five groups, no difference could be found between or within these groups when daily sperm production per man (DSP); seminiferous tubular volume, diameter, or length; or seminiferous epithelial volume was examined. Furthermore, no significant correlation could be detected between Leydig cell numbers and DSP in these 50 men. The only relationship between numbers of Leydig cells and spermatogenesis appeared to be a threshold effect, in that men with fewer than 60 million Leydig cells (4 in this study) had drastically reduced DSP. Men with few Leydig cells tended to have larger Leydig cells, and the increased size was due to more cytoplasm instead of nucleoplasm. There were weak but significant positive correlations between total Leydig cell cytoplasm per man and DSP and between average size of a Leydig cell and DSP. These findings suggest that a relationship may exist between sperm production and the amount of cytoplasm containing testosterone-producing organelles in surviving Leydig cells of older men.

Limitations of the forensic external examination in determining the cause and manner of death.

The accuracy of the cause and manner of death based on a medical examiner external examination of the body and review of other evidence was investigated. The authors retrospectively identified 185 such forensic cases in which an autopsy was performed subsequently at a major teaching hospital. Autopsy disclosed a change in the manner of death in only one instance. Of the 89 natural deaths, the cause of death based on external examination was erroneous in 26 (29 per cent). The majority of the errors was the result of an overdiagnosis of arteriosclerotic cardiovascular disease, hypertensive cardiovascular disease, and cancer.

Disaster planning for air crashes. A retrospective analysis of Delta Airlines flight 191.

The effectiveness of previously untested disaster plans was demonstrated during the aftermath of the crash of Delta Airlines Flight 191 at D/FW International Airport on Friday, August 2, 1985. These plans, in effect for years and subjected to periodic review, were as yet untried before this first disaster at D/FW International since its opening. This paper outlines the disaster plans, the actual problems encountered, the logistics of a disaster of this kind, and insights gained from the experience.

Age-related variation in seminiferous tubules in men. A stereologic evaluation.

Tubular boundary tissue and seminiferous epithelia were evaluated stereologically in testes from 28 men aged 20 to 48 years and 28 men aged 50 to 90 years. Testes obtained at autopsy within 15 hours of death were perfused with glutaraldehyde, embedded in Epon (Ladd Research Industries, Inc., Burlington, VT), sectioned at 0.5 micron, and stained with toluidine blue. Volume densities (percentage of the testicular parenchyma) of various parameters determined by point counting and diameter measurements were used to calculate total volumes, length of tubules, and number of cells. Electron microscopy was used to determine the volume density of myoid cells in the boundary tissue. Significant (P less than 0.01) age-related reductions occurred in paired testicular weights, paired parenchymal weights, total volume of seminiferous tubules and of seminiferous epithelium, and length of tubules. The volume density and thickness of boundary tissue increased (P less than 0.01) with age. The volume of boundary tissue per man and the volume density of myoid cells in the boundary tissue did not vary with age. Although the number of myoid cells per man tended to be lower in the older group, the number of myoid cells per cross section of seminiferous tubule was increased (P less than 0.01) in older men. The age-related thickening of the boundary tissue was not due to an increase in boundary tissue but resulted from a reduction in the length of the seminiferous tubules.

Sudden death caused by embolization of trophoblast from hydatidiform mole.

A 16-year-old pregnant female presented to a hospital emergency room with vaginal bleeding and uterine cramping. She underwent a hysterotomy and curettage and, during the procedure, her pulse dropped from 130 to 30 beats/minute, her pO2 fell to 10 mm of mercury, and she could not be resuscitated. At autopsy, she was found to have massive pulmonary embolization of syncytiotrophoblast from a hydatidiform mole of the uterus. This is the sixth reported case of trophoblastic embolization from a hydatidiform mole ending in death. This fatal termination may occur after a period of respiratory symptoms and may occur regardless of the mode of treatment.

Age-related change in numbers of other interstitial cells in testes of adult men: evidence bearing on the fate of Leydig cells lost with increasing age.

The number of Leydig cells in the adult human testis declines as a function of increasing age, but whether these cells disappear by transforming into another cell type or by undergoing death and dissolution has not been resolved. This question was addressed in 30 men between 20 and 76 years of age who were known as a group to have experienced significant age-related loss of Leydig cells. If the loss of Leydig cells resulted from transformation into another cell type, other testicular interstitial cells in these men should have increased with age. Testes obtained at autopsy were perfused with glutaraldehyde less than 15 h after sudden death due to trauma or heart attack. Numbers of other interstitial cells were determined by quantitative histometric estimation of the proportion of testicular parenchyma occupied by other interstitial cell nuclei of measured average volume. Other interstitial cell nuclei declined significantly with advancing age (rho = -0.41, P less than 0.05). Mean number of other interstitial cell nuclei per individual was significantly reduced in the 15 men 50 yr old or older compared to the 15 younger men (460 +/- 34 million vs. 609 +/- 43 million; P less than 0.05). There was no tendency for individuals with reduced numbers of Leydig cells to have increased numbers of other interstitial cells. These findings argued against the persistence of Leydig cells in aged testes as dedifferentiated mesenchymal elements. Instead, light and electron microscopic observation of testes from these men revealed evidence of Leydig cell degeneration and dissolution.

Free radical production from controlled low-energy fires: toxicity considerations.

Most fire departments respond within the first 5 min of notification of a fire. If fire victims are found at that stage by the firefighters, then incapacitation or death has occurred during the initial low-energy phase where smoke is being produced. Studies have shown that during this initial low-energy phase of the fire, gases commonly thought responsible for incapacitation or death are frequently not present in concentrations adequate to cause this result. In the current study free radicals, measured by electron spin resonance spectroscopy, were trapped in concentrations that we consider incapacitating, thus providing an explanation for "incapacitation without cause." This finding points the way to the design of more efficient temporary protective equipment for those who are in a high fire hazard environment, such as airline passengers, and suggests the idea of establishing a thermodynamic marker for the relative toxicity of building materials.

Studies of toxic gas production during actual structural fires in the Dallas area.

Gases produced during structural fires were studied as to their potential toxicities. Carbon monoxide was the only gas measured in concentrations considered to be lethal within a short period of time. No correlations were found between gases produced and materials burning. However, significant correlations were discovered between gases produced and the physical aspects of the fire (intensity, burning rate, and the like). The organic compounds identified within the gases gave insight as to another potential health hazard not yet considered. These organic compounds are the products of free radical reactions and as free radicals their potential as toxics is enormous.

Germ cell degeneration during postprophase of meiosis and serum concentrations of gonadotropins in young adult and older adult men.

Loss of potential sperm production during postprophase of meiosis was evaluated to determine if reduced daily sperm production in older men could be explained by an enhanced percentage of germ cell degeneration during this period of spermatogenesis. Evaluations were based on enumerating germ cells in homogenates of fixed testes using phase-contrast cytometry from 37 young adult (20-48 yr) and 34 older adult (50-85 yr) men. The time period in which germ cells degenerate was assessed in 10 men by comparing potential daily sperm production based on secondary spermatocytes with that based on primary spermatocytes or with daily sperm production based on spermatids. There was a significant (P less than 0.01) decline in sperm production potential based on primary spermatocytes and on spermatids in the older adult men such that the percentage of loss of potential production during postprophase was similar between the two age groups. Sperm production estimates based on primary spermatocytes and secondary spermatocytes were similar (P greater than 0.05); however, estimates based on secondary spermatocytes were significantly higher than those based on spermatids. Degeneration during postprophase of meiosis in humans appears to occur during or near the second meiotic division. Age-related reduced sperm production was significantly correlated with elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Age-related decline in sperm production could not be explained by enhanced germ cell degeneration during postprophase but may result from reduced germ cell numbers prior to pachytene primary spermatocytes.

Quantification of the human Sertoli cell population: its distribution, relation to germ cell numbers, and age-related decline.

The human Sertoli cell population was characterized in 14 men by histometric analysis and by direct counts of nuclei in testicular homogenates. Testes obtained at autopsy were perfused with glutaraldehyde and embedded in Epon. Nucleolar and nuclear volumes were determined by the formula of a sphere given the diameter of the nucleoli or average diameter of nuclei measured at the height and width. Nuclear volume was also estimated by adding volumes of nuclear profiles in 0.5-micron serial sections. Sertoli cell number/g was calculated by the product of the percentage nucleoli or nuclei in the parenchyma, parenchymal volume, and histologic correction factor divided by the volume of a single nucleolus or nucleus. Also, Sertoli cell nuclei were counted directly in homogenates of fixed parenchyma. Number of Sertoli cells/g was similar (P greater than 0.05) whether determined by serial sections or in homogenates, but the estimate based on the nucleolar method was higher (P less than 0.01) and the nuclear measurement method was lower (P less than 0.01) than that for serial sections. A group of 37 men aged 20 to 48 yr had significantly (P less than 0.01) more Sertoli cells than did 34 men aged 50 to 85 yr. It is concluded that: 1) the homogenate method is valid for quantification of the Sertoli cell population, 2) Sertoli cells are evenly distributed in different regions of the testis, 3) the average human Sertoli cell supports relatively few germ cells, 4) the human Sertoli cell population declines with age, and 5) there is a significant relationship between sperm production rates and number of Sertoli cells.

Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men.

Age-related changes in Leydig cell number, daily sperm production, and circulating hormone levels were studied in 15 men between 20 and 48 yr of age and 15 men between 50 and 76 yr of age. Testes and blood samples were obtained at autopsy less than 15 h after death due to trauma or heart attack. Leydig cell number was determined by quantitative histometric estimation of the proportion of glutaraldehyde-perfused, decapsulated testicular parenchyma occupied by Leydig cell nuclei of measured average volume in both testes of each subject. Daily sperm production was determined by phase contrast cytometry of round spermatid nuclei in homogenates of both fixed testes from each individual. LH, FSH, PRL, and testosterone in serum from the heart or large veins were quantified by RIA. No relationship was detected between any of the testicular or hormonal values and postmortem time. The average total number of Leydig cells was reduced by 44% in the older men and was negatively correlated with age (p = -0.62) in all men. Mean serum LH was elevated more than 2-fold in the older men and was positively correlated with age (p = +0.53) in all men. Neither serum testosterone nor serum PRL changed significantly with age. Daily sperm production was more than 50% lower in older men and was negatively correlated with age (p = -0.76) in all men. Serum FSH was more than 3-fold higher in the older men and was positively correlated with age (p = +0.72) in all men. The highest FSH levels were found in men with the lowest rates of sperm production, and FSH and daily sperm production were inversely correlated even after the effects of age were removed. These findings show that the response of the human testis to aging is variable and that the predictive value of age for most testicular characteristics is weak at the level of individual men. Nevertheless, age accounts for more than a third of the variation in Leydig cell number, and it explains more than half the variation in daily sperm production. Hence, age is the largest single contributing factor yet identified in the search for explanations underlying the variation in testicular structure and function found in groups of normal men.

Influence of age on sperm production and testicular weights in men.

Age-related changes in daily sperm production (DSP) and testicular weights were investigated in paired testes from 89 men aged 21-50 years and 43 men aged 51-80 years. For both DSP/testis and DSP/g parenchyma, remarkably large standard deviations exceeded 50% of mean values. However, DSP/g and DSP/testis for both right and left testes were approximately 30% higher in the younger than in the older group (P less than 0.01) and were negatively correlated with age (P less than 0.01) when data from both groups were pooled. Weights of whole testes and of testicular parenchyma were similar in both age groups and were not significantly correlated with age. However, testicular tunic weights were 29% higher in the older group (P less than 0.001) and were positively correlated with age (P less than 0.001). Both testicular tunic weight and the % of total testis occupied by tunic were negatively correlated with DSP/g (P less than 0.01); these correlations were weakened by removing the effect of age. Although total testicular weight and testicular parenchymal weight did not change with age, these values were about 10% lower on the left than on the right (P less than 0.001). In addition to its increase with age, testicular tunic weight was about 8% greater for right than for left testes in all men (P less than 0.001). Although the average size of the testis varied from right to left, DSP/g was similar in paired testes (P = 0.15), and the correlation between right and left DSP/g was high (rho = +0.89, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)