Underestimated risks of recurrent long-range ash dispersal from northern Pacific Arc volcanoes.

Widespread ash dispersal poses a significant natural hazard to society, particularly in relation to disruption to aviation. Assessing the extent of the threat of far-travelled ash clouds on flight paths is substantially hindered by an incomplete volcanic history and an underestimation of the potential reach of distant eruptive centres. The risk of extensive ash clouds to aviation is thus poorly quantified. New evidence is presented of explosive Late Pleistocene eruptions in the Pacific Arc, currently undocumented in the proximal geological record, which dispersed ash up to 8000 km from source. Twelve microscopic ash deposits or cryptotephra, invisible to the naked eye, discovered within Greenland ice-cores, and ranging in age between 11.1 and 83.7 ka b2k, are compositionally matched to northern Pacific Arc sources including Japan, Kamchatka, Cascades and Alaska. Only two cryptotephra deposits are correlated to known high-magnitude eruptions (Towada-H, Japan, ca 15 ka BP and Mount St Helens Set M, ca 28 ka BP). For the remaining 10 deposits, there is no evidence of age- and compositionally-equivalent eruptive events in regional volcanic stratigraphies. This highlights the inherent problem of under-reporting eruptions and the dangers of underestimating the long-term risk of widespread ash dispersal for trans-Pacific and trans-Atlantic flight routes.

Congenital cystic dysplasia of the rete testis.

Cystic dysplasia of the rete testis (the network of straight seminiferous tubules within the mediastinum testis leading to the efferent ductules) is a rare congenital anomaly. There are only 15 cases reported in the literature to date and only one report of the US findings [1-5]. This report highlights the characteristic appearance of the lesion on ultrasound examination and its association with renal abnormalities in two patients.

Airway gene transfer in mouse nasal-airways: importance of identification of epithelial type for assessment of gene transfer.

Mouse nasal airways are often used for the assessment of both reporter and cystic fibrosis transmembrane conductance regulator (CFTR) gene transfer to respiratory epithelia. However, the mouse nasal cavity is lined by both olfactory (OE) and respiratory epithelium (RE). Previous gene transfer studies have suggested that OE may be more efficiently transduced by adenoviral vectors than RE. However, to provide data pertinent to CFTR gene transfer in humans, measurements of CFTR function in mice by transepithelial potential difference (TPD) should be directed towards respiratory rather than olfactory epithelium. We report a new technique to mark the position of the TPD sensing cannula tip in the mouse nasal cavity that permitted us to correlate TPD measurements with epithelial cell type. Using this technique, we found TPD values did not discriminate between respiratory and olfactory epithelia. We next assessed relationships between anatomic regions accessed by the TPD cannula and epithelial type. The frequently used insertion depth of approximately 5 mm from the nose tip predominantly recorded the TPD from anterior dorsal olfactory epithelium. Measurement of the TPD of respiratory epithelium in our study was maximized by insertion of the TPD cannula probe to 2.5 mm depth. Because TPD measurements are not sensitive to epithelial type, adequate control of position and TPD catheter insertion depth are required to ensure accurate estimation of CFTR gene transfer into the target RE in the mouse nasal cavity.

Inflammatory pseudotumour of the pancreas in a child.

We describe a 4-year-old girl with an inflammatory pseudotumour of the pancreas, which was preceded by varicella-zoster infection. Inflammatory pseudotumour may involve a variety of tissues, the lungs and liver being typical sites of predilection. Imaging and laboratory tests are nonspecific, and for this reason the diagnosis of inflammatory pseudotumour is rarely made prior to surgery. These benign but locally aggressive masses simulate malignancy in the majority of cases. Inflammatory pseudotumour should, therefore, be considered when a mass arises in an unusual location in the paediatric age group.

Non-alcoholic steatohepatitis in children and adolescents.

We describe 17 children with non-alcoholic steatohepatitis. All had elevated levels of serum liver enzymes and 16 were morbidly obese. Liver biopsy showed variable steatosis and fibrosis in nine patients. At follow-up, 12 of 14 patients had persistent morbid obesity and 11 had elevated liver enzyme levels.

Childhood deaths and cargo barriers in cars.

To analyse features of childhood deaths associated with the absence or presence of car cargo barriers, three cases were taken from the files of the Department of Histopathology at the Women's and Children's Hospital and State Forensic Science Centre, Adelaide, Australia, over a 5-year period from January 1993 to December 1997. Case 1: A 6-year-old boy who was a rear passenger sustained fatal crush injuries from unrestrained luggage moving forward after an accident. No cargo barrier was in place. Cases 2 and 3: Two children aged 3 and 9 years, respectively, died from acute hyperthermia after they became trapped in the back of a station wagon with a fixed cargo barrier in place. Although car cargo barriers are excellent devices for preventing injury from unrestrained objects striking or crushing passengers, designing barriers that can be opened easily from the rear of the cabin would prevent children being trapped in potentially dangerous circumstances.

Sudden death due to intravenous infusion of hair conditioner.

A case of sudden death in a 14-year-old girl due to self administration of hair conditioner through an intravenous infusion pump is described. This report demonstrates difficulties that may occur in determining the manner of death in such cases and outlines a specific danger that may occur when adolescents have unsupervised access to intravenous infusion equipment.

Insulin-like growth factor-I (IGF-I) stimulates regrowth of the damaged intestine in rats, when administered following, but not concurrent with, methotrexate.

BACKGROUND: We tested the ability of insulin-like growth factor-I (IGF-I) to reduce damage to the intestinal mucosa (mucositis) in rats injected with methotrexate. IGF-I was infused concurrent with methotrexate administration and compared to IGF-I administered following the withdrawal of methotrexate. METHODS: Rats were injected with methotrexate at the start of days 1, 2 and 3. IGF-I was infused for 5 days, commencing at the start of day 1 [concurrent administration] or at the start of day 4 [post-methotrexate administration]. RESULTS: IGF-I administered coincident with methotrexate failed to restore mucosal integrity to the damaged small intestine. IGF-I administered post methotrexate stimulated regrowth of the damaged intestine, particularly the ileum, with 22%, 32% and 29% increases in small intestinal weight, ileal villus height and ileal crypt depth respectively. CONCLUSIONS: Following intestinal damage of methotrexate, IGF-I primarily induced growth of the distal small intestine. The ineffectiveness of concurrently administered IGF-I may have represented an IGF-I induced recruitment of proliferating epithelial cells to the anti-proliferative effects of methotrexate.

Hepatocellular carcinoma following neonatal hepatitis.

Hepatocellular carcinoma is an uncommon malignancy in young children associated with a variety of congenital and acquired conditions. It has been generally held that idiopathic neonatal hepatitis is not an antecedent of hepatocellular neoplasia in childhood. We report a 28-month-old girl in whom a diagnosis of neonatal giant cell hepatitis was confirmed by liver biopsy at 4 months of age who was followed up with serial liver biopsies. Hepatitis B and C virus infection and metabolic abnormalities had been excluded by appropriate testing. There was no history of parenteral nutrition. The morphologic criteria for a diagnosis of cirrhosis were satisfied in a liver biopsy undertaken at 23 months of age. At 28 months a laparotomy was performed because of continuing jaundice and the development of an abdominal mass. Biopsy of the mass revealed a hepatocellular carcinoma. Ploidy studies showed an aneuploid tumor and a hyperdiploid karyotype was confirmed by chromosomal analysis. This case demonstrates by sequential biopsy the progression from neonatal hepatitis to cirrhosis and hepatocellular carcinoma in a young child.

Conservative surgery for benign non-parasitic splenic cysts.

Benign, non-parasitic splenic cysts are an uncommon cause of splenomegaly in children. Potentially they may enlarge, causing pain, rupture, or haemorrhage, or become infected. Traditional management has been total splenectomy. We report two cases of true epithelial-lined splenic cysts successfully treated by partial splenectomy using an oxidised cellulose gauze 'sandwich' technique.

The Apert syndrome hand: pathologic anatomy and clinical manifestations.

The Apert syndrome hand demonstrates many typical clinical features including syndactyly, symbrachyphalangism, and growth disturbances. This is due to the grossly abnormal anatomy of both the skeletal and soft-tissue structures associated with a progressive disease process. This paper presents a clinical, radiologic, and histologic analysis of the Apert syndrome hand anatomy and correlates it with the clinical manifestations. It also links hand and craniofacial dysplasia to other regions of the skeleton as well as the overall disease process. From our analysis, we conclude that there is a genetic anomaly causing variable and uncoordinated differentiation of the mesenchyme at the time of embryologic separation into its various skeletal components, particularly in the distal limb bud and craniofacial skeleton. This disease process continues postnatally in endochondral bone growth center malformation and malfunction as well as ectopic cartilage ossification in soft tissues. We discuss the role of abnormal musculotendinous anatomy and altered biomechanical forces in relation to these processes.

High-resolution ultrasonography in the differential diagnosis of cystic diseases of the kidney in infancy and childhood: preliminary experience.

Autosomal recessive polycystic kidney disease, autosomal dominant polycystic disease, and glomerulocystic disease may all appear in the perinatal period as bilaterally enlarged echogenic kidneys. Current ultrasonographic equipment can better demonstrate the underlying pathologic state and assist in the differentiation of these conditions. The primary abnormality in autosomal recessive polycystic kidney disease is at the level of the collecting ducts, which are dilated and saccular. The nephrons remain normal. These dilated ectatic tubules are seen in their usual distribution as a radial array, with major ducts being perpendicular to the renal capsule, in both the renal cortex and the medulla. The peripheral renal cortex does not normally contain collecting ducts and remains unaffected in patients with mild disease. Autosomal dominant polycystic disease is characterized by cystic changes involving both the nephron and the collecting ducts. The nephron may become cystic at any point. Multiple discrete cysts of varying sizes are seen in both the renal cortex and the medulla in the severely affected infant. Subcapsular cysts are seen regularly. Glomerulocystic disease is an unusual sporadic condition characterized by the cystic dilation of the space of Bowman and the proximal convoluted tubule. On ultrasonographic examination tiny, isolated cysts, usually smaller than those occurring in autosomal dominant polycystic kidney disease, are seen in the echogenic renal cortex and may extend to the periphery of the kidney. No cysts are seen in the renal medulla. Correlation between pathologic findings and sonographic images is of value in correctly diagnosing these conditions.

Brain tumours in infancy: a clinicopathological study.

To investigate the clinicopathological features of brain tumours occurring in the first year of life, the records of the Department of Histopathology at the Adelaide Children's Hospital were examined for cases where the initial diagnosis of intracranial neoplasm had been made in infancy. Surgical material was available for review from 1972 to 1993 and autopsy cases were reviewed for an additional 12 years from 1962 to 1993. Twenty-four infants with intracranial neoplasms were diagnosed ranging in age from 5 days to 1 year (average = 7 months). There were 23 surgical cases and 1 autopsy case. The male to female ratio was 17:7. Fifty-eight percent of the tumours were located in the supratentorial region. Although the incidence is relatively low, this study demonstrates that a wide range of brain tumours, which differ significantly in both clinical presentation and location from those found in the older child, do occur during the first year of life. The location of the primary tumour may be affected by associated congenital malformations, and metastatic malignancy, although rare, may occur. Antenatal ultrasound examination may be useful in identifying congenital intracranial tumours.

Effects of epidermal growth factor administration on repair of acetic acid-induced colonic ulcerations in rats.

The effect of subcutaneous and luminal epidermal growth factor (EGF) administration on acetic acid-induced colonic ulceration was determined in adult rats. Application of acetic acid to the distal colonic lumen caused epithelial denudation, mucosal ulceration and inflammation in the exposed segment. Re-epithelialization was detectable 5 to 7 days later, with near-complete resolution of the lesion by 14 days post-injury. Luminal EGF (1.6 mg/kg bw/day) or subcutaneous EGF (200 micromilligrams/kg bw/day), administered for 4 or 6 days from the time of ulceration failed to enhance re-epithelialization of the acid-exposed segment. However, mucosal and submucosal thickening was attenuated 20-40% by subcutaneous EGF, reflecting a reduction in edema. Luminal EGF had a similar but less substantial effect in the submucosa, but was more effective at attenuating muscularis thickening adjacent to the lesion. In conclusion, administration of exogenous EGF for up to 6 days failed to enhance re-epithelialization of acetic acid-induced colonic ulcerations but did attenuate the associated edematous response.

Mesh-sided cots--yet another potentially dangerous infant sleeping environment.

Two cases of accidental asphyxia involving an 11.5 month old boy and a 3.5 month old boy who each died after being trapped between the elastic mesh side of their cots and the cot mattress are reported. In both cases the original cot mattress has either been replaced or augmented by a less well fitting, thicker mattress. Particular problems that exist with these type of mesh sided cots are the potential for considerable stretching of the side of the cot admitting the relatively larger, poorly supported infant head, with elastic recoil of the mesh holding the head in potentially dangerous positions. To help determine whether accidental asphyxia has occurred, death scene examination in cases of sudden infant death during sleep should include reconstruction of the position of the body in the cot or bed, with careful examination of the structure of the cot/bed.

Cranial suture disease in the Apert's syndrome infant.

The histologic findings from sutural specimens remove during early cranial surgery in Apert's syndrome infants have been reviewed. Coronal sutures are uniformly fused histologically in their inferolateral extent, showing a progression to lesser changes at the superior margin. These findings correspond with radiographic changes. The lambdoid sutures occasionally show histologic evidence of fusion, with the same pattern of inferior to superior progression, but a lack of objective radiographic changes.

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 Children's 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.

Comparative toxicity and virulence of Escherichia coli clones expressing variant and chimeric Shiga-like toxin type II operons.

Shiga-like toxin (SLT)-producing strains of Escherichia coli are known to cause diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome in humans. The SLTs, particularly those related to type II (SLT-II), are a diverse family of toxins which may have differing in vitro or in vivo properties. To examine the impact of naturally occurring SLT-II sequence variation on the capacity of a given E. coli strain to cause disease, operons encoding four different SLT-II-related toxins, designated SLT-II/O111, SLT-II/OX3a, SLT-II/OX3b, and SLT-II/O48, were cloned in the same orientation in pBluescript. French pressure cell lysates of E. coli DH5 alpha derivatives carrying these plasmids differed markedly in cytotoxicity for Vero cells, with 50% cytotoxic doses ranging from 20 to 328,000/ml. The strains also differed in oral virulence for streptomycin-treated mice, as judged by survival rate and/or median survival time, but virulence did not necessarily correlate with in vitro cytotoxicity. The SLT-II type associated with the lowest oral virulence was SLT-II/O111. Both the overall survival rate and the median survival time of mice challenged with clones producing this toxin were significantly greater than that for mice challenged with a clone producing the closely related SLT-II/OX3a. Experiments with clones carrying chimeric O111/OX3a SLT-II operons indicated that the reduced virulence was associated with an Arg-176-->Gly substitution in the mature A subunit. Clones producing SLT-II/O48 and SLT-II/OX3b had similarly high cytotoxicities for Vero cells, but the latter was more virulent when fed to streptomycin-treated mice, as judged by median survival time. Experiments with clones carrying chimeric O48/OX3b SLT-II operons indicated that the increased virulence was a function of the A subunit of SLT-II/OX3b, which differs from the A subunit of SLT-II/O48 by only two amino acids (Met-4-->Thr and Gly-102-->Asp, respectively). These findings raise the possibility that naturally occurring SLT-II sequence variations may impact directly on the capacity of a given SLT-producing E. coli strain to cause disease.

Unexpected infant death in association with suspended rocking cradles.

We report on the deaths of two infants aged 10 1/2 and 11 weeks who were found face down in the angle between the base and side of their frame-suspended rocking cradles. Locking pins designed to prevent tilting of the cradles were not in place in either case. Investigation of the two cradles associated with the infant deaths and six other similar rocking cradles available for purchase in South Australia revealed either marked angles of tilt or inadequate or nonchildproof locking devices in all cases. A study of live control infants placed in similar situations demonstrated support for the possibility of positional asphyxia. We consider that these cases represent another potentially lethal sleeping environment for infants and emphasize the importance of death scene examination in all cases of unexpected infant death.

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 Children's 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.