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Biomedical subjects

H F Krous

Publications and source records attributed to H F Krous.

At least 19 recordsLinked to original sources

Research and sudden infant death syndrome: definitions, diagnostic difficulties and discrepancies.

The diagnosis of causes of sudden infant death is an often complex and difficult process. Variable standards of autopsy practice and the use of different definitions for entities such as sudden infant death syndrome (SIDS) have also contributed to confusion and discrepancies. For example, the term SIDS has been used when the requirements of standard definitions have not been fulfilled. In an attempt to correct this situation recent initiatives have been undertaken to stratify cases of unexpected infant death and to institute protocols that provide frameworks for investigations. However, if research is to be meaningful, researchers must be scrupulous in assessing how extensively cases have been investigated and how closely cases fit with internationally recognized definitions and standards. Unless this approach is adopted, evaluation of research findings in SIDS will be difficult and the literature will continue to be beset by contradictions and unsubstantiated conclusions.

Biomedical Research↗

Pathological findings in overlaying.

A 2-month-old girl is reported who was found in cardiorespiratory arrest beneath her unconscious mother. Full autopsy examination failed to reveal any features which would give an indication of the nature of the terminal event. This case confirms the non-specificity of autopsy findings in an infant who suffocated underneath an adult--a situation mimicking classical 'overlaying'. Given that there may be no specific histopathological findings when an infant suffocates underneath an adult, a diagnosis should not be formulated if a full death scene description is not available and no specific lesions or diseases are found. The manner of death should be designated as 'undetermined'.

Journal Article↗

Shared bathing and drowning in infants and young children.

OBJECTIVE: A study was undertaken to look at possible risks of shared bathing in early childhood. METHODS: Autopsy databases were searched at the Women's and Children's Hospital and State Coroner's Office, Adelaide, Australia, from January 1963 to December 1999, the Victorian Institute of Forensic Medicine, Melbourne, Australia, from January 1991 to December 1999, and the Children's Hospital-San Diego, San Diego, USA, from January 1990 to December 1999, for all cases registered as drowning in children aged 2 years and under who were in a bath with another child around the time of death. RESULTS: A total of 17 cases were found. The age range of the victims was 8-22 months (average=11.8 months), with a male to female ratio of 10:7. The surviving children (who were all siblings) were significantly older, with an age range of 19-48 months (average=30.4 months), and a male to female ratio of 12:5. (The survivors were on average 18.5 months older than the victims, range=11-32 months). In every case the children had been left unsupervised for variable periods of time. CONCLUSIONS: These cases represented a significant component -- between 22 and 58% -- of bath drownings in the 2 years and under age group. It would appear that shared bathing for young children and infants may only acceptable if adult supervision is constant, and that a young sibling is not an appropriate person to look after an infant or toddler in the bath. While the risk of leaving an infant in a filled bath may be exacerbated if an older child is also present, further population-based studies are required to examine this hypothesis.

Age Distribution↗

Specific dangers associated with infants sleeping on sofas.

AIM: A study was undertaken to examine specific circumstances that may lead to accidental asphyxial deaths in infants on sofas. METHODS: Coronial files in South Australia (Australia) from 1989 to 1998, and files at the Office of the Medical Examiner in San Diego County (USA) from 1991 to 1998 were searched for all cases of infant deaths occurring on sofas. RESULTS: A total of 10 cases with complete death scene descriptions were found. Four deaths were attributed to sudden infant death syndrome and six deaths to accidental asphyxia, of which four involved shared sleeping with an adult. Lethal circumstances involved infants being overlayed by an adult (n = 2), wedged between an adult and the back of a sofa (n = 1), sleeping with an intoxicated/sedated adult (n = 2), wedged between pillows and the back of a sofa (n = 1), and wedged into the back of a sofa (n = 1). CONCLUSIONS: Although shared sleeping of an adult with an infant on a sofa may result in accidental asphyxia, there is also the potential for wedging and accidental asphyxia of infants sleeping alone on a sofa. For this reason the use of sofas for both shared and solitary infant sleeping is discouraged.

Adult↗

Oronasal blood in sudden infant death.

Oronasal secretions are observed frequently in sudden infant death syndrome (SIDS), but overt blood is uncommonly reported. The literature on oronasal blood in sudden infant death is limited. The goal of this study was to determine the frequency of oronasal blood in sudden infant deaths and to examine possible causative factors. Oronasal blood was described in 28 (7%) of 406 cases of sudden infant death. Oronasal blood could not be attributed to cardiopulmonary resuscitation in 14 cases, including 10 (3%) of 300 cases of SIDS, 2 (14%) of 14 accidental suffocation cases, and 2 (15%) of 13 undetermined cases. Eight of the 10 infants in cases of sudden infant death were bedsharing: 5 with both parents, 2 between both parents. The infant in 1 SIDS case was from a family that had had three referrals to Child Protective Services. Oronasal blood not attributable to cardiopulmonary resuscitation occurs rarely in SIDS when the infant is sleeping supine in a safe environment. Bedsharing may place infants at risk of suffocation from overlaying. Oronasal blood observed before cardiopulmonary resuscitation is given is probably of oronasal skin or mucous membrane origin and may be a sign of accidental or inflicted suffocation. Sanguineous secretions that are mucoid or frothy are likely of remote origin, such as lung alveoli. The use of an otoscope to establish the origin of oronasal blood in cases of sudden infant death is recommended.

California↗

Environmental hyperthermic infant and early childhood death: circumstances, pathologic changes, and manner of death.

Infant and early childhood death caused by environmental hyperthermia (fatal heat stroke) is a rare event, typically occurring in vehicles or beds. The aims of this study were to describe the demographics, circumstances, pathology, and manner of death in infants and young children who died of environmental hyperthermia and to compare these cases with those reported in the literature. Scene investigation, autopsy reports, and the microscopic slides of cases from three jurisdictions were reviewed. The subjects in 10 identified cases ranged in age from 53 days to 9 years. Eight were discovered in vehicles and 2 in beds. When the authors' cases were grouped with reported cases, the profile of those in vehicles differed from those in beds. The former were older, were exposed to rapidly reached higher temperatures, and often had more severe skin damage. The latter were mostly infants and were exposed to lower environmental temperatures. Hepatocellular necrosis and disseminated intravascular coagulation were reported in victims who survived at least 6 hours after the hyperthermic exposure. The consistent postmortem finding among nearly all victims was intrathoracic petechiae, suggesting terminal gasping in an attempt at autoresuscitation before death. The manner of death was either accident or homicide. Recommendations for the scene investigation are made.

Accidents↗

Early adolescent suicide: a comparative study.

A study was undertaken of suicides in children and adolescents aged 16 years and under in South Australia, (Australia), and in San Diego County (USA) from January 1985 to December 1997. In South Australia there were 48 cases of youth suicide, representing 2% of the total number of 2251 suicides over that time. There were 34 males and 14 females (age range 13 to 16 years; mean = 15.3 years), with 22 hangings (46%), six gunshot wounds (13%), five train deaths (10%), four drug overdoses (8%), four jumping deaths (8%), three self immolations (6%), three carbon-monoxide inhalations (6%) and one electrocution (2%). In San Diego County there were 70 cases, representing 1.6% of the total number of 4492 suicides. There were 48 males and 22 females (age range 11 to 16 years; mean = 14.7 years), with 41 gunshot wounds (59%), 21 hangings (30%), six drug overdoses (9%), and two jumping deaths (3%). Preferred methods of suicide differed between the two areas, with significantly more gunshot suicides in San Diego compared to South Australia. The methods of suicide also differed in South Australia from older age groups, with more hangings, jumping deaths and self immolations, and fewer firearm and carbon monoxide inhalation deaths. Suicides in adolescents under the age of 17 years in both populations were, however, rare, with no demonstrable increase in numbers over the time of the study.

Journal Article↗

Decreased serotonergic receptor binding in rhombic lip-derived regions of the medulla oblongata in the sudden infant death syndrome.

The sudden infant death syndrome (SIDS) is postulated to result from a failure of homeostatic responses to life-threatening challenges (e.g. asphyxia, hypercapnia) during sleep. The ventral medulla participates in sleep-related homeostatic responses, including chemoreception, arousal, airway reflex control, thermoregulation, respiratory drive, and blood pressure regulation, in part via serotonin and its receptors. The ventral medulla in humans contains the arcuate nucleus, in which we have shown isolated defects in muscarinic and kainate receptor binding in SIDS victims. We also have demonstrated that the arcuate nucleus is anatomically linked to the nucleus raphé obscurus, a medullary region with serotonergic neurons. We tested the hypothesis that serotonergic receptor binding is decreased in both the arcuate nucleus and nucleus raphé obscurus in SIDS victims. Using quantitative autoradiography, 3H-lysergic acid diethylamide (3H-LSD binding) to serotonergic receptors (5-HT1A-D and 5-HT2 subtypes) was measured blinded in 19 brainstem nuclei. Cases were classified as SIDS (n = 52), acute controls (infants who died suddenly and in whom a complete autopsy established a cause of death) (n = 15), or chronic cases with oxygenation disorders (n = 17). Serotonergic binding was significantly lowered in the SIDS victims compared with controls in the arcuate nucleus (SIDS, 6 +/- 1 fmol/mg tissue; acutes, 19 +/- 1; and chronics, 16 +/- 1; p = 0.0001) and n. raphé obscurus (SIDS, 28 +/- 3 fmol/mg tissue; acutes, 66 +/- 6; and chronics, 59 +/- 1; p = 0.0001). Binding, however, was also significantly lower (p < 0.05) in 4 other regions that are integral parts of the medullary raphé/serotonergic system, and/or are derived, like the arcuate nucleus and nucleus raphé obscurus, from the same embryonic anlage (rhombic lip). These data suggest that a larger neuronal network than the arcuate nucleus alone is involved in the pathogenesis of SIDS, that is, a network composed of inter-related serotonergic nuclei of the ventral medulla that are involved in homeostatic mechanisms, and/or are derived from a common embryonic anlage.

Arcuate Nucleus of Hypothalamus↗

Changing trends in the diagnosis of sudden infant death.

A study of 114 consecutive cases of unexpected infant death that occurred in South Australia over a 5-year period from January 1994 to December 1998 was undertaken. There were 45 deaths attributed to sudden infant death syndrome (SIDS), 19 to natural causes, 21 to accidents. and 5 to homicides; 24 cases were listed as "undetermined." Although there has been a genuine and continued decline in SIDS numbers in this population, there has also been an increase in the diagnosis of cases of accidental asphyxia due to unsafe sleeping environments and of cases in which the family background and autopsy findings suggested more complex mechanisms. The change in diagnostic profile has followed the introduction of more rigorous clinical history review, death scene examination, and autopsy testing. Thus, although diagnostic outcomes have altered in this population, it is more likely the result of more careful interpretation of the extensive investigations that are now undertaken rather than arbitrary reclassification.

Accidents↗

An analysis of the usefulness of specific stages in the pathologic investigation of sudden infant death.

Retrospective analysis of autopsy findings in 60 infants who had been found unexpectedly dead in their cribs or beds in South Australia from 1994 to 1998 was undertaken to determine the diagnostic usefulness of individual stages in the postmortem investigation. Positive findings occurred in 2 of 43 scene examinations (3%), 2 of 60 external examinations (3%), 2 of 11 radiologic examinations (18%), 8 of 60 internal examinations (13%), 7 of 60 histologic examinations (12%), and 3 of 58 microbiologic examinations (5%). No positive findings were detected on toxicologic screening. Not every case underwent each diagnostic step. This gave alternative diagnoses to sudden infant death syndrome (SIDS) in 15 cases (25%). This study demonstrates an increase in the percentage of cases of unexpected infant death due to causes other than SIDS; it also shows the diagnostic yield of individual stages in the postmortem evaluation of such cases. Negative findings were important in giving validity to the diagnosis in the 45 cases that were ultimately designated as SIDS.

Australia↗

Petechial hemorrhages and unexpected infant death.

The significance of petechial hemorrhages in cases of unexpected infant death remains uncertain. While intrathoracic petechiae occur in the majority of cases of sudden infant death syndrome (SIDS), their relationship to terminal mechanisms has been debated. Facial, conjunctival and external upper chest petechiae are not a feature of SIDS and raise the possibility of underlying illness such as sepsis, or of forceful coughing or vomiting. Alternatively the presence of cutaneous or conjunctival petchiae may suggest trauma or asphyxia due to chest or neck compression. Given the possibility of alternative mechanisms of death it is preferable to designate the cause and manner of death as 'undetermined', rather than 'SIDS', when petechiae are found in unusual locations.

Journal Article↗

Laryngeal basement membrane thickening is not a reliable postmortem marker for SIDS: results from the Chicago Infant Mortality Study.

It has been suggested that laryngeal basement membrane (LBM) thickening is a pathognomonic postmortem marker for sudden infant death syndrome (SIDS) and is not seen in other causes of explained sudden infant death. To test this hypothesis, we evaluated longitudinal sections of the right hemilarynx taken through the midpoint of the true vocal cord from 129 SIDS cases and 77 postneonatal sudden infant death controls. Using a five-point semi-quantitative scale, maximum LBM thickness (LBMT) for SIDS cases and controls was not statistically different (mean, 2.39 + 0.69 and 2.40 + 0.77, respectively). Likewise, scores based on the average thickness along the entire basement membrane (i.e., "average" score), were not found to be different between SIDS cases and controls. Average and maximum LBMT increased with age in both SIDS cases and controls and were not different between SIDS cases and controls within each age interval. Similar trends in the distribution of maximum and average LBMTs were found between black and Hispanic SIDS and controls; the number of white/non-Hispanic infants was too low for meaningful comparisons. Maximum and average LBMTs were not different in SIDS cases and controls exposed to environmental tobacco compared with unexposed infants. The LBMTs also increased significantly with body weight and length in both SIDS cases and controls. Finally, there were no differences in LBMT in infants intubated prior to death compared with those who were not intubated. From these data, we conclude that LBMT is not pathognomonic of SIDS, is present or absent with equal frequency in SIDS and controls, increases with postnatal age, and does not correlate with passive smoke exposure. Therefore, LBMT should not be used to diagnose SIDS.

Basement Membrane↗

Tritiated-naloxone binding to brainstem opioid receptors in the sudden infant death syndrome.

The sudden infant death syndrome (SIDS) is defined as the sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation, including a complete autopsy. We hypothesized that SIDS is associated with altered 3H - naloxone binding to opioid receptors in brainstem nuclei related to respiratory and autonomic control. We analyzed 3H - naloxone binding in 21 regions in SIDS and control brainstems using quantitative tissue receptor autoradiography. Three groups were analyzed: SIDS (n = 45); acute controls (n = 14); and a chronic group with oxygenation disorders (n = 15). Opioid binding was heavily concentrated in the caudal nucleus of the solitary tract, nucleus parabrachialis medialis, spinal trigeminal nucleus, inferior olive, and interpeduncular nucleus in all cases analyzed (n = 74). The arcuate nucleus on the ventral medullary surface contained negligible binding in all cases (n = 74), and therefore binding was not measurable at this site. We found no significant differences among the three groups in the age-adjusted mean 3H - naloxone binding in 21 brainstem sites analyzed. The only differences we have found to date between SIDS and acute controls are decreases in 3H - quinuclidinyl benzilate binding to muscarinic cholinergic receptors and in 3H - kainate binding to kainate receptors in the arcuate nucleus in alternate sections of this same data set. The present study suggests that there is not a defect in opioid receptor binding in cardiorespiratory nuclei in SIDS brainstems.

Autoradiography↗

Brainstem 3H-nicotine receptor binding in the sudden infant death syndrome.

Maternal cigarette smoking during pregnancy has been shown to be a major risk factor for the sudden infant death syndrome (SIDS). We hypothesized that SIDS is associated with altered 3H-nicotine binding to nicotinic receptors in brainstem nuclei related to cardiorespiratory control and/or arousal. We analyzed 3H-nicotine binding in 14 regions in SIDS and control brainstems using quantitative tissue receptor autoradiography. Three groups were analyzed: SIDS (n = 42), acute controls (n = 15), and a chronic group with oxygenation disorders (n = 18). The arcuate nucleus, postulated to be important in cardiorespiratory control and abnormal in at least some SIDS victims, contained binding below the assay detection limits in all (SIDS and control) cases. We found no significant differences among the 3 groups in mean 3H-nicotine binding in the 14 brainstem sites analyzed. When a subset of the cases were stratified by the history of the presence or absence of maternal cigarette smoking during pregnancy, however, we found that there was no expected increase (upregulation) of nicotinic receptor binding in SIDS cases exposed to cigarette smoke in utero in 3 nuclei related to arousal or cardiorespiratory control. This finding raises the possibility that altered development of nicotinic receptors in brainstem cardiorespiratory and/or arousal circuits put at least some infants, i.e. those exposed to cigarette smoke in utero, at risk for SIDS, and underscores the need for further research into brainstem nicotinic receptors in SIDS in which detailed correlations with smoking history can be made.

Arcuate Nucleus of Hypothalamus↗

Changes in the epidemiologic profile of sudden infant death syndrome as rates decline among California infants: 1990-1995.

OBJECTIVES: To evaluate changes in the rates and epidemiologic patterns of sudden infant death syndrome (SIDS) after implementation of public health campaigns to promote back sleeping and reduce exposure to cigarette smoke and environmental risk factors for SIDS. METHODS: California vital statistics data were used to evaluate changes in SIDS rates (deaths/1000 live births) and in the proportions of SIDS deaths by age and season of occurrence for California infants of black or other races from 1990 through 1995. RESULTS: From 1990 through 1995, 3508 SIDS deaths occurred. SIDS rates declined from 2.69 to 2.15 for black infants and from 1.04 to 0.61 for others between 1990 and 1995. Most SIDS deaths occurred during the 2nd to 4th months of life; the proportion of SIDS deaths during this period was unchanged for blacks but decreased for others from 70% to 65%. Of all SIDS deaths, 62% occurred during the colder season (October through March); the proportion of deaths in each season did not change for either race. CONCLUSION: California SIDS rates declined 20% for blacks and 41% for others between 1990 and 1995. Declines coincided with campaigns to reduce environmental risk factors for SIDS. Blacks continue to be at increased risk for SIDS compared with others, and the SIDS rate for blacks relative to others has increased. Reductions in SIDS mortality coinciding with interventions were smaller for blacks than for others. New strategies are needed to reduce further SIDS rates and narrow the gap between blacks and others.

Black or African American↗

The syndrome of autoimmune interstitial nephritis and membranous nephropathy.

A 2-year-old male patient was evaluated for Fanconi syndrome with hypertension and failure to thrive. Renal biopsy revealed autoimmune interstitial nephritis with membranous nephropathy. The patient developed autoimmune hemolytic anemia and intractable diarrhea with villous atrophy of the jejunum. He progressed to end-stage renal disease and was transplanted without recurrent disease. Immune work-up done prior to immunosuppressive therapy showed marked elevation of IgE. Studies of T lymphocyte cytokine production showed normal production of interleukin-4 but depressed levels of interferon-gamma. The simultaneous occurrence of autoimmune interstitial nephritis and membranous nephropathy in a young male represents a unique syndrome. Abnormalities of T lymphocyte subpopulations and their cytokines may be involved in the pathogenesis of this disorder.

Autoimmune Diseases↗