Glenn P. Taylor

Rhabdomyosarcoma arising within congenital pulmonary cysts : report of three cases

Over the past 9 months, three cases of primary pulmonary rhabdomyosarcoma have been treated at British Columbia Childrens Hospital. Two patients (aged 24 and 37 months) presented with spontaneous pneumothoraces and had cystic changes in the affected lung on chest radiograph. The third patient (aged 42 months) was evaluated for chronic cough, fever, and failure to thrive. Chest x-ray showed a large mass in the left lower lobe as well as mediastinal adenopathy. All three of these lesions originated within congenital lung cysts, one a peripheral bronchogenic cyst and the others cystic adenomatoid malformations. This report suggests that there is a significant risk for the development of rhabdomyosarcoma within malformed pulmonary tissue.

Definition and Application of a Histopathological Scoring Scheme for an Animal Model of Acute Mycoplasma pneumoniae Pulmonary Infection

A histopathological scoring system was developed to assess the pathology of acute Mycoplasma pneumoniae pulmonary infection in a hamster model. A final score per animal (ranging 0–26) is obtained by averaging scores from each lung which have been accumulated by the addition of subscores from the assessments of quantity and quality of peribronchiolar and peribronchial infiltrates, luminal exudates, perivascular infiltrates, and parenchymal pneumonia. The scoring scheme was then applied to test the ability of a heat‐killed inoculum to induce pulmonary pathology and to the trial of a 43 kDa protein‐associated antigen as a vaccine immunogen. A heat‐killed inoculum delivered by both intratracheal and intranasal routes did not induce pulmonary pathology compared to a live inoculum (respective mean scores 0.1, 6.7; P<0.01). Animals prevaccinated with the 43 kDa antigen developed an accentuated pathological response after live challenge compared to those unvaccinated (respective mean scores 16.8, 5.8; P=0.00007). Hypersensitization to growth medium components may, however, have contributed to the accentuated disease since the lungs of vaccinated animals challenged with culture‐negative media also were affected (mean score 5.4). Reproducibility of the scoring system was measured by duplicate reading of histology slides which were randomized to the observer upon the second reading (r=0.93; P=0.000009). The scoring system has the ability to differentiate disease severity in small groups of animals.

Pulmonary vascular disease in neonates with transposition of the great arteries and intact ventricular septum.

BACKGROUND--Progressive pulmonary vascular disease in surgically unrepaired transposition of the great arteries with or without ventricular septal defect had been frequently described in the past. Occurrence of progressive pulmonary vascular disease has been reported even after atrial switch procedure done at three months of age. With the advent of neonatal surgical repair, this problem is virtually non-existent. There is a small subgroup of infants with transposition of the great arteries who show pulmonary vascular disease in the neonatal period that can adversely affect the surgical outcome. The clinico-pathological correlation in this group of patients was studied. OBSERVATIONS--Three patients, with transposition of the great arteries and intact ventricular septum, who showed histological evidence of pulmonary vascular disease in the neonatal period or early infancy are described. Two of these patients, continued to have poor systemic oxygenation despite adequate atrial communication. One patient had a close ductus arteriosus within the first two hours of birth while on prostaglandin E1 infusion. CONCLUSIONS--In the absence of left ventricular outflow tract obstruction, a poor response to atrial septostomy suggests pulmonary hypertension and pulmonary vascular disease. Antenatal constriction of the ductus arteriosus may contribute to such changes in pulmonary vasculature.

Abnormal pericyte recruitment as a cause for pulmonary hypertension in Adams-Oliver syndrome.

Adams–Oliver syndrome (AOS) consists of congenital scalp defects with variable limb defects of unknown pathogenesis. We report on two children with AOS plus additional features including intrauterine growth retardation (IUGR), cutis marmorata telangiectatica congenita (CMTC), pulmonary hypertension (PH), intracranial densities shown in one case to be sites of active bleeding and osteopenia. Autopsy in one case revealed defective vascular smooth muscle cell/pericyte coverage of the vasculature associated with two blood vessel abnormalities. Pericyte absence correlated with vessel dilatation while hyperproliferation of pericytes correlated with vessel stenosis. These findings suggest a unifying pathogenic mechanism for the abnormalities seen in AOS. These and previously reported cases establish that a subset of AOS patients is at high risk for PH.

Giant hydatid lung cysts in the Canadian northwest: Outcome of conservative treatment in three children☆

Hydatid lung disease due to Echinococcus granulosus in the Canadian northwest and Alaska is often asymptomatic and usually benign. We reviewed the course and outcome of three children with giant hydatid lung cyst seen over a 2-year period. All were North American Indian children aged 9 to 12 years who presented with cough, fever, and chest pain. One had a rash. There was a history of exposure to domestic dogs who had been fed moose entrails in each case. Chest x-rays showed solitary lung cysts with air-fluid levels, from 6 cm to 12 cm in diameter. Aspiration of each cyst demonstrated Echinococcus hooklets and protoscolices. Serology was unhelpful, being negative in two cases. Transient pneumonitis and pneumothorax were seen as complications of needle aspiration. Two cysts gradually resolved over the following 6 months. One child returned after 9 months with a lung abscess due to superimposed infection of the cyst remnant with Haemophilus influenzae, and eventually required lobectomy. The existence of an endemic benign variant of E granulosus in Canada is not widely known, and it is important to distinguish it from the more aggressive pastoral form of the disease seen in immigrants from sheep-rearing countries. The native Canadian disease usually resolves spontaneously, does not cause anaphylaxis, and does not implant daughter cysts if spilled. Surgical treatment should be avoided except for complications such as secondary bacterial infection.

Sudden, Unexpected, Natural Death in Childhood

One thousand nine hundred and fifty four autopsies performed at British Columbias Childrens Hospital during a 7-year period were reviewed to determine the causes of sudden unexpected natural death in the age group from birth to 17 years. Of the 126 cases found, the largest group, 86 cases, was sudden infant death syndrome (SIDS). Nine deaths were the result of infection: 4 cases of H. influenza meningitis, 2 cases of meningococcemia, 2 cases of acute epiglottitis, and 1 case of necrotizing tracheobronchitis. Epilepsy, ruptured AV malformations, and brain tumors combined to make up an equally large group of 9 cases. Cardiac lesions were the third largest group, 6 cases. The three groups that posed the most difficulty in assigning a cause of death were (a) the group that were like SIDS yet had other confounding features, (b) the group in which metabolic death was suspected but not proven, and (c) death in epilepsy.

A Study into the Nature and Organ Source of Digoxin-Like Immunoreactive Substance(s) in the Perinatal Period

Digoxin-like immunoreactive substance(s) (DLIS) was isolated from sera and autopsy-derived tissue obtained from premature and full-term neonates. The highest tissue level of DLIS was in the small bowel followed by the adrenal, gallbladder and liver. Of the fluids examined, meconium had the highest level of DLIS. Preparative high performance liquid chromatography fractionation of cord blood generated at least six different fractions which not only contained DLIS material but also inhibited canine kidney Na+/K+-ATPase activity. Recovery/inhibition studies indicated that 72% of the canine kidney Na+/K+-ATPase inhibition within one fraction could be accounted for on the basis of progesterone content of the fraction.

Cardiac abnormalities and nonimmune hydrops fetalis: a coincidental, not causal, relationship.

Few conditions associated with nonimmune hydrops fetalis have had a demonstrable causal relationship. Congenital heart disease is often said to be a cause of nonimmune hydrops fetalis and antenatal closure of the foramen ovale is the cardiac abnormality most frequently reported in association with hydrops. In order to examine the role of congenital heart disease in hydrops, and, in particular, that of antenatal closure of the foramen ovale, we reviewed all autopsy cases with hydrops fetalis over an 11 year period and compared cardiac anomalies with those of nonhydropic controls. The incidence of various congenital heart malformations was not significantly different among these groups, suggesting that factors in addition to cardiac anomalies must be considered in the pathogenesis of nonimmune hydrops fetalis.

Mycoplasma pneumoniae reinfection and vaccination: protective oral vaccination and harmful immunoreactivity after re-infection and parenteral immunization

Animal model studies of Mycoplasma pneumoniae infection after live respiratory challenge were conducted to investigate the issues of challenge-rechallenge associated accentuated pathology, postparenteral vaccination associated accentuated pathology, and oral vaccination. Live M. pneumoniae inocula were grown in hamster serum-based medium in order to reduce the potential for the serum growth component to participate in the hyperaccentuated histopathological response as seen with challenge-rechallenge experiments which have used horse serum-based growth media. Despite the use of homologous animal serum, an early hyperaccentuated response occurred (day 3 score 13.3 vs day 10 score 7.7; P = 0.02) which included perivascular infiltrates, and histopathological scores for early (day 3) and late (day 10) disease were similar (P > 0.10) between experiments of challenge-rechallenge when either homologous or heterologous sera were used in inoculum growth media. Parenteral vaccination with heat-killed bacteria also led to an early hyperaccentuated histopathological response after live respiratory challenge (scores on day 3: vaccinated 18.3, unvaccinated 6.2; P < 0.01) and this response was not significantly diminished when inocula were cleaned of growth medium components. An early accentuated response did not follow oral vaccination with heat-killed bacteria (score on day 3: vaccinated 5.7) and the late reaction was significantly less after challenge (scores on day 10: vaccinated 10.3, unvaccinated 14.6; P = 0.011). Studies of parenteral vaccination should include analyses for early disease after live challenge. Oral vaccination offers a promising route for stimulating protective immunity while minimizing undesirable recall immune events.

Bases for the early immune response after rechallenge or component vaccination in an animal model of acute Mycoplasma pneumoniae pneumonitis

The pathology of Mycoplasma pneumoniae pulmonary infection for a hamster model was examined after whole bacterium rechallenge or component vaccination. Animals which, after an initial infection, were rechallenged with either live or heat-killed M. pneumoniae inocula developed severe early recall lesions in the first 3 days. In contrast, animals infected once develop maximum histopathology at approximately 10-14 days. A severe perivascular inflammatory cellular infiltrate developed in the rechallenged groups, and pulmonary pathology could also be elicited by rechallenge with bacterial growth medium components. Component vaccination with protein P1 did not reduce disease in comparison to once-infected controls, and vaccination promoted an early immune recall response as well. We conclude that an early immune response needs to be sought in all future experiments of challenge/rechallenge or vaccination. Vaccine studies will require an understanding of both protective and harmful immunogens.