Anthony J. Bourne

Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses

BackgroundInfluenza virus binds to cell receptors via sialic acid (SA) linked glycoproteins. They recognize SA on host cells through their haemagglutinins (H). The distribution of SA on cell surfaces is one determinant of host tropism and understanding its expression on human cells and tissues is important for understanding influenza pathogenesis. The objective of this study therefore was to optimize the detection of α2,3-linked and α2,6-linked SA by lectin histochemistry by investigating the binding of Sambucus nigra agglutinin (SNA) for SAα2,6Gal and Maackia amurensis agglutinin (MAA) for SAα2,3Gal in the respiratory tract of normal adults and children.MethodsWe used fluorescent and biotinylated SNA and MAA from different suppliers on archived and prospectively collected biopsy and autopsy specimens from the nasopharynx, trachea, bronchus and lungs of fetuses, infants and adults. We compared different methods of unmasking for tissue sections to determine if these would affect lectin binding. Using serial sections we then compared the lectin binding of MAA from different suppliers.ResultsWe found that unmasking using microwave treatment in citrate buffer produced increased lectin binding to the ciliated and glandular epithelium of the respiratory tract. In addition we found that there were differences in tissue distribution of the α2,3 linked SA when 2 different isoforms of MAA (MAA1 and MAA2) lectin were used. MAA1 had widespread binding throughout the upper and lower respiratory tract and showed more binding to the respiratory epithelium of children than in adults. By comparison, MAA2 binding was mainly restricted to the alveolar epithelial cells of the lung with weak binding to goblet cells. SNA binding was detected in bronchial and alveolar epithelial cells and binding of this lectin was stronger to the paediatric epithelium compared to adult epithelium. Furthermore, the MAA lectins from 2 suppliers (Roche and EY Labs) tended to only bind in a pattern similar to MAA1 (Vector Labs) and produced a different binding pattern to MAA2 from Vector Labs.ConclusionThe lectin binding pattern of MAA may vary depending on the supplier and the different isoforms of MAA show a different tissue distribution in the respiratory tract. This finding is important if conclusions about the potential binding sites of SAα2,3 binding viruses, such as influenza or human parainfluenza are to be made.

Potentially dangerous sleeping environments and accidental asphyxia in infancy and early childhood.

Infants and young children may be exposed to a variety of dangerous situations when left sleeping in cots, chairs, or beds. A review of 30 cases of accidental asphyxia occurring in infants and young children who had been left to sleep unattended was undertaken from the necropsy and consultation files of the Adelaide Childrens Hospital. Causes of death included hanging from loose restrainers, clothing, or a curtain cord (12 cases), positional asphyxia/wedging from slipping between a mattress and bed/cot sides or wall, or from moving into a position where the face was covered and the upper airway occluded (16 cases), and suffocation from plastic bed covers (two cases). Cases of co-sleeping in bed with an adult and of non-accidental asphyxia were not included in this review. As the pathological findings were on occasion identical to those that are typically found in sudden infant death syndrome, adequate death scene examination was vital in several cases to allow identification of lethal sleeping environments and to enable steps to be taken to minimise the risk of future deaths due to similar situations. For example, two cases in which infants asphyxiated in rocking cradles led to the investigation of the cradles and to formulation of specific safety recommendations regarding the angle of tilt. Two infants who died after becoming wedged between the back of a couch and a co-sleeping parent in one case and cushions in the other, would indicate that this also represents a potentially lethal sleeping position. Other dangerous situations involved infant car seat restraints, seats with loose harnesses, cots with movable sides or projecting pieces, thin plastic mattress/pillow coverings, and beds with spaces between the mattress and cot side or wall. Lack of supervision at the time of death was a feature of each case.

Toxigenic Escherichia coli Associated with Sudden Infant Death Syndrome

The role of Escherichia coli as a cause of sudden infant death syndrome was investigated prospectively. Strains of E. coli producing the heat labile enterotoxin (LT) or the Vero-cell cytotoxin (VT) were isolated from the intestinal contents of 21/46 infants who died from sudden infant death syndrome (SIDS). None were found in the contemporaneously sampled faeces of 24 normal live infants in the same area. Live infants were used as controls in the absence of dead infants who had not died of SIDS. This high incidence of toxigenic E. coli among the SIDS infants versus the low incidence in controls, together with the general rarity of finding such toxigenic E. coli in the community of a temperate developed country, made us conclude that there may be a causal relationship between toxigenic E. coli and SIDS. The O and H serotypes of the toxigenic E. coli associated with SIDS infants tended not to be those normally considered to be toxigenic. The toxigenicity appeared to be relatively labile. It is suggested that SIDS may be associated with the infant either acquiring these unusual types of E. coli or more likely that its normal resident E. coli acquire the plasmids to produce these toxins.

Sudden and Unexpected Death due to Hemorrhage from Occult Central Nervous System Lesions

A retrospective review of the Department of Histopathology files at the Adelaide Children’s Hospital was conducted to examine all cases where sudden death (defined as death occurring within 24 h of su

The association of lingual thyroglossal duct remnants with sudden death in infancy

Two cases of sudden infant death are described in which relatively large posterior lingual midline cysts were demonstrated at autopsy. Death in both patients was attributed to upper airway obstruction due to the cysts, both of which represented thyroglossal duct remnants.

Sudden and Unexpected Death-A Late Effect of Occult Intraesophageal Foreign Body

Acute upper airway obstruction in a 4-month-old male infant who presented as sudden infant death syndrome is described. At autopsy external tracheal compression and tracheobronchitis with plugging of the trachea and bronchi by an abundant mucopurulent exudate were found. The source of the inflammation was the adjacent esophagus where previous impaction of a coin had caused pressure necrosis with mucosal erosion and transmural granulation tissue formation. This case is reported to demonstrate that foreign bodies that remain in the esophagus, having by-passed the larynx, may still result in upper airway obstruction and death in early infancy by this unusual mechanism.

Testicular regression syndrome : a pathological study of 77 cases

Testicular regression syndrome is characterized by a rudimentary epididymis and spermatic cord with absence of testicular tissue. Although it has been well‐described in the surgical literature, few pathological studies have been performed. We report 77 cases of the syndrome, deriving from a 26‐year retrospective review. Typical gross descriptions described several cm of spermatic cord with a small mass of firm, fibrotic tissue at one end; elements of the vas deferens, spermatic artery and venous plexuses were usually present. Histologically, the distal expansion of most of the specimens was composed of dense fibrovascular tissue with no evidence of seminiferous tubules or normal testicular elements. Instead, scattered foci of calcification and brown pigment were present. The finding of dystrophic calcification and haemosiderin deposition, with no evidence of viable testicular tissue, in the presence of relatively normal spermatic cord elements, supports the concept of generally unilateral and occasionally bilateral anorchia secondary to remote infarction. The young age of the patients, coupled with the history of an absent testis from birth, is supportive of in utero damage. These histopathological findings provide support for the concept of in utero torsion of the testis as the basis for the testicular regression syndrome.

DEHYDRATION DEATHS IN INFANTS AND YOUNG CHILDREN

Dehydration in developed countries is an uncommon but important mechanism resulting in the death of infants and children. The clinicopathological features of a series of 37 fatal dehydration cases autopsied at the Adelaide Childrens Hospital over a 33-year period (1961-1993) are presented. Causative factors for dehydration included gastroenteritis (21 cases), gastroenteritis with high environmental temperature (one case), high environmental temperatures (six cases), neglect/failure to thrive (four cases), mental retardation/chromosomal abnormality (three cases), congenital adrenal hyperplasia (one case), and unsuspected cystic fibrosis (one case). The mean age at death was 11.4 months (range 2 weeks to 6.25 years; median 6 months; 95% confidence interval 6 months to 1 year and 4 months; male-to-female ratio, 19:18). Sixteen of the 22 cases of fatal gastroenteritis (73%) occurred during the fall/winter months (March to August). There were a total of seven aboriginal or part aboriginal children in the group (19%). Children with mental retardation were at higher risk of dehydration, and previously unsuspected cases of child abuse/neglect also presented with lethal dehydration. Vitreous humor electrolyte levels and immunoassay for rotavirus were useful diagnostic adjuncts.

Clostridium botulinum and sudden infant death syndrome: A 10 year prospective study

ABSTRACT It has been proposed that sudden and unexpected death in infants due to intestinal infection with Clostridium botulinum may mimic the clinicopathological features of sudden infant deathsyndrome. Between 3.3 and 3.8% of infants in some series have had this neurotoxin‐producing bacterium isolated on faecal culture. Prospective screening of 248 infants presenting with the sudden infant death syndrome to the Adelaide Childrens Hospital over a 10 year period from 1981to 1990 was conducted. Faecal samples were obtained from both small and large intestines and cultured specifically for C. botulinum. No samples were positive. The results of this study suggest that routine post‐mortem culture of faeces for C. botulinum has been of limited use within the South Australian infant population over the last decade, and that occult botulism has not been a significant factor in the causation of sudden death.

Trabecular and solid-cribriform types of basal cell adenoma: A morphologic study of two cases of an unusual variant of monomorphic adenoma☆

Monomorphic adenomas are a morphologically complex group of salivary gland tumors. Two unusual examples, one a trabecular and the other a solid form of basal cell adenoma, reveal the development of a cribriform growth pattern focally in the former example and diffusely in the latter. They illustrate the potential for cellular differentiation within this subgroup, organization of synthetic products by the tumor cells, and the histologic criteria useful for the distinction of basal cell adenoma from adenoid cystic carcinoma.