Cynthia Trevenen

Congenital heart defect case ascertainment by the Alberta Congenital Anomalies Surveillance System

BACKGROUNDnCongenital heart defects (CHDs) are the most common type of congenital anomaly, with a wide range of reported birth prevalence estimates. This quality assurance study describes CHD case ascertainment by the Alberta Congenital Anomalies Surveillance System (ACASS).nnnMETHODSnACASS data for CHD cases were compared with additional sources including the two Pediatric Cardiology clinics in Alberta, the Alberta Childrens Hospital Department of Pathology, and hospital records. Cases included live births, stillbirths, and fetal deaths at less than 20 weeks gestation born in Alberta, Canada, between 1995 and 2002. The birth prevalence of cases and chi-square linear trend analyses were calculated for specific types of heart defects for the total study period.nnnRESULTSnThe ascertainment of CHD cases by ACASS was 45%. The total prevalence of CHD cases was 5.59 per 1000 total births (TBs; 95% confidence interval [CI], 5.32-5.86) when ACASS was the only data source and increased to 12.42 per 1000 TBs (95% CI, 12.03-12.83) when all data sources were used. Although the total prevalence of CHD cases remained stable during 1995 to 2002, the prevalence of atrial septal defect (ASD) and cases with an ASD and ventricular septal defect (VSD) significantly increased. The prevalence of left ventricular outflow tract obstruction cases significantly decreased during the study period.nnnCONCLUSIONSnPediatric cardiology clinics are worth including as additional ascertainment sources to contribute to more accurate prevalence estimates. The significant increases of ASD and cases with both an ASD and VSD may reflect differences in diagnostic and ascertainment practices.

Expression of markers shared between human natural killer cells and neuroblastoma lines

SummaryNeuroblastoma is a tumor of neuroectodermal origin arising most commonly from the adrenal medulla. We have examined the ability of several monoclonal antibodies which recognize markers predominantly expressed on human natural killer (NK) cells to react with neuroblastoma cell lines in vivo derived sections of tumor. HNK-1 (Leu 7) is a monoclonal IgM antibody which recognizes a carbohydrate epitope on NK cells and a wide range of tumor cell types. We have shown that HNK-1 recognizes the human neuroblastoma lines SMS-KCNR, SMS-KAN, NMB/N7, and IMR/5. Expression of this antigen on cell lines can be slightly increased by retinoic acid-induced differentiation of the cells. N901 (NKH1), a monoclonal antibody raised against interleukin 2-dependent human NK cell lines also recognizes all human neuroblastoma cell lines examined. This expression is independent of differentiation induction and levels remain unaltered following retinoic acid treatment of the cell lines. Lastly, with monoclonal antibody 49H.8, it has been found that reactivity of the lines is weak until induction of differentiation, after which highly significant increases of reactivity are seen. 49H.8 recognizes several cryptic carbohydrate antigens with varying affinities, shown to identify mouse and rat NK cells. In contrast to other NK markers, human neuroblastoma cell lines did not express significant reactivity with B73.1, Leu 11b, or Leu 18. Immunohistochemical staining of sections of human neuroblastoma tumors correlated with the in vitro findings; however, staining with N901 and 49H.8 was only seen on frozen sections, not paraffin-embedded. The significance of shared NK cell-neuroblastoma/neuron antigens is currently under investigation.

Metastatic renal cell carcinoma in a child: 11‐Year disease‐Free survival following surgery

A child with metastatic renal cell carcinoma (RCC) is presented. This case is unusual in that the patient has remained disease free for 11 years following surgery and only one course of chemotherapy prior to thoracotomy. The management of metastatic RCC is reviewed and the genetic mechanisms leading to its development briefly discussed.

Congenital heart defects and major structural noncardiac anomalies in Alberta, Canada, 1995–2002

BACKGROUNDnAlthough the majority of congenital heart defects (CHDs) occur in isolation, a significant number occur with noncardiac anomalies. This study determined the proportion of noncardiac anomalies among CHD cases in Alberta.nnnMETHODSnRecords of infants and children born in Alberta between January 1, 1995, to December 31, 2002, were searched using multiple sources of ascertainment in addition to the Alberta Congenital Anomalies Surveillance System (ACASS) (Alberta Health and Wellness, 2012). Each case was assigned to one CHD category and was further categorized into one of the following groups: isolated CHD, syndromes, chromosomal, associations and sequences, teratogens, Mendelian, neoplasia, heterotaxy, multiple minor anomalies, and multiple major anomalies.nnnRESULTSnOf all 3751 CHD cases (prevalence 12.42/1000 total births: confidence interval, 12.03-12.83), 75% were isolated, 10% had a chromosomal etiology, and 9% had multiple major anomalies. All other categories accounted for <2% each. The most commonly associated major noncardiac anomalies were musculoskeletal (MSK) (24%) followed by anomalies of the urinary tract (14%), gastrointestinal system (GI) (11%), and central nervous system (CNS) (11%).nnnCONCLUSIONSnThis is both a population-based and clinical study using a classification scheme that could help to determine possible etiologic factors contributing to CHD. By eliminating known etiologies such as chromosomal and single gene, future studies can focus on the remainder to evaluate possible preventive measures. The most commonly associated major noncardiac anomalies involve the MSK system, followed by the urinary, GI, and CNS systems.

Cytoplasmic RNA in nervous system tumours in children: a fluorochromic histochemical study using acridine orange.

Acridine orange was used as a fluorochromic histochemical stain of nucleic acids, applied to 78 neoplasms of the central and peripheral nervous systems of 60 children. Some cases were compared with 5 adults and 4 other cases of chronic reactive gemistocytic gliosis. Opposite concentration gradients of cytoplasmic ribonucleic acid (RNA) was demonstrated in tumours of the neuronal/neuroectodermal series, and those of the glial/neuroepithelial series. Minimal AO-RNA fluorescence was seen in 8 cerebellar medulloblastomas and in a retinoblastoma; strong AO-RNA fluorescence occurred in one cerebellar medulloblastoma and in 3 primitive neuroectodemal tumours of the cerebral cortex. Intermediate intensity of fluorescence was found in neuroblastomas, and strong fluorescence was shown in well differentiated ganglioneuroma cells and in cells of chromaffin tumours. Among glial tumours, by contrast, the most anaplastic cells displayed the most RNA fluorescence, while better differentiated astrocytoma cells showed much less. Gradients also were found within some astrocytomas, corresponding to zones of relative anaplasia. Minimal or no fluorescence was detected in reactive gemistocytes or in oligodendroglioma cells. Ependymomas were weakly fluorescent and choroid plexus papillomas showed more fluorescence, similar to the findings in normal ependyma and choroid plexus. Several non-neuroepithelial tumours of the nervous system and Schwannomas also were studied. The acridine orange technique applied to either frozen or paraffin sections of nervous system tumours, has value as an adjunct in the diagnosis and grading of these neoplasms and perhaps in distinguishing reactive gliosis from benign astrocytoma.

Folic acid fortification and the birth prevalence of congenital heart defect cases in Alberta, Canada.

BACKGROUNDnCongenital heart defects (CHDs) are the most common type of congenital anomaly. The precise etiology is unknown and the development of successful primary prevention strategies is challenging. Folic acid may have a protective role; however published results have been inconsistent. This study examines the impact of mandatory folic acid fortification (FAF) on the prevalence of CHDs.nnnMETHODSnCHD cases were ascertained using the Alberta Congenital Anomalies Surveillance System, Pediatric Cardiology Clinics, Pathology, and hospital records. The birth prevalence and odds ratios (OR) of isolated CHD cases (i.e., without noncardiac anomalies) were calculated comparing pre-FAF (1995-1997) with post-FAF (1999-2002).nnnRESULTSnThe prevalence of isolated CHD cases remained relatively unchanged when pre-FAF (9.34, 95% confidence interval [CI] 8.79-9.92) was compared with post-FAF (9.41, 95% CI, 8.93-9.91). Left ventricular outflow tract obstruction (LVOTO) decreased post-FAF (OR, 0.76; 95% CI, 0.61-0.94). Coarctation of the aorta contributed to this decline (OR, 0.55; 95% CI, 0.32-0.92). Atrial septal defect (ASD) (OR, 1.42; 95% CI, 1.13-1.80) and ASD with ventricular septal defect (OR, 1.52; 95% CI, 1.10-2.10) increased post-FAF. The remaining types of CHDs were unchanged.nnnCONCLUSIONnFAF alone does not have an impact on the prevalence of CHDs as a group and the majority of selected types of CHDs in Alberta. The decrease in LVOTO, particularly coarctation of the aorta, may be due to FAF or other environmental factors. The increase in ASD and ASD with ventricular septal defect may reflect an increase in diagnosis and ascertainment.

Detection of HPV DNA in genital condylomata acuminata in female prepubertal children

Abstract In situ DNA hybridization using biotin-labeled probes for HPV types 6, 11, 16, and 18 was performed on paraffin-embedded anogenital condylomata acuminata from four children. Three, age 9 years, 22 months, and 10 months, were positive for human papillomavirus (HPV) 6. The first two were also positive for HPV 11. A fourth child, age 6 years, was negative for all four HPV types. The mother of the 10-month-old infant had a condylomatous infection of the cervix as detected by cytology, histology, and colposcopy but dot blot hybridization of cervical tissue was negative for the four HPV types. These cases form the nucleus of a long-term prospective study of anogenital HPV infection in children, as the significance of various HPV types of infection in differing anogenital locations is poorly understood.

Comparison of Presentation, Course, and Outcome of Congenital and Acquired Cytomegalovirus Infection in Twins

Backgroundu2003Cytomegalovirus (CMV) is one of the most common causes of serious viral intrauterine infections. It is universally distributed among the human population with an average incidence of 0.15 to 2%. Indeed, at least half of the women in the reproductive age have evidence of prior CMV infection. Epidemiology and Pathogenicityu2003However, it is not a usual practice to screen asymptomatic pregnant woman or neonates for CMV. Even if a mother developed a primary CMV infection during pregnancy, up to 90% of the newborns with congenital CMV will be asymptomatic at the time of birth. Only 5 to 7% of the infected babies will be acutely symptomatic, and the typical clinical presentation includes intrauterine growth restriction, microcephaly, various cutaneous manifestations (including petechiae and purpura), hematological abnormalities (particularly resistant thrombocytopenia), hepatosplenomegaly, chorioretinitis, hepatitis, etc. In contrast, acquired CMV infection is extremely unlikely to cause any serious sequelae for the infant. Casesu2003 We present a case of congenital and acquired CMV infection in twins with a focus of dissimilarity in presentation, clinical course, and outcome.

Infant Heart Dissection in a Forensic Context: Babies are Not Just Small Adults

Medical examiners who investigate infant deaths are required to consider a large number of natural and non-natural causes due to the broad differential diagnosis of unexpected infant death. Among the myriad of causes are those related to disorders in structure and function of the cardiovascular system. Adult hearts are routinely and efficiently evaluated by medical examiners because of the large anatomic structures and limited spectrum of commonly encountered diseases. Infant deaths are comparatively rare. Although infant hearts may be evaluated with similar efficiency, the pathologist must first have a detailed knowledge of developmental cardiovascular anatomy and of the subtleties of a broad spectrum of infantile cardiovascular pathology. Furthermore, the pathologist must be aware of additional details to be observed and documented in infant cardiac studies, and of the dissection techniques that facilitate acquisition of that data. Rote dissection of an infant heart as if it were an adult heart may lead to overlooked malformations and diseases that may have been the underlying cause of death. This brief review paper covers the fundamentals of pediatric cardiovascular anatomy and dissection techniques as they apply to the practice of pediatric forensic pathology.