Increased incidence of CPR-related rib fractures in infants--is it related to changes in CPR technique?

OBJECTIVE: A recent increase in the number of infants presenting at autopsy with rib fractures associated with cardio-pulmonary resuscitation (CPR) precipitated a study to determine whether such a phenomenon was related to recent revision of paediatric resuscitation guidelines. METHODS: We conducted a review of autopsy reports from 1997 to 2008 on 571 infants who had CPR performed prior to death. RESULTS: Analysis of the study population revealed CPR-related rib fractures in 19 infants (3.3%), 14 of whom died in the 2006-2008 period. The difference in annual frequency of CPR-related fractures between the periods before and after revision of paediatric CPR guidelines was statistically highly significant. CONCLUSIONS: The findings indicate that CPR-associated rib fractures have become more frequent in infants since changes in CPR techniques were introduced in 2005. This has important implications for both clinicians and pathologists in their assessment of rib fractures in this patient population.

Expression of the human P2Y6 nucleotide receptor in normal placenta and gestational trophoblastic disease.

The P2Y family of purinergic receptors are members of the G-protein-coupled receptor superfamily. The P2Y6 subtype is expressed at particularly high levels in the placenta, suggesting that P2Y6 plays an important role in placental function. However, the cellular localization of P2Y6 within the placenta is unknown. This study examined the expression of P2Y6 in first-trimester and full-term placental tissues, as well as examples of gestational trophoblastic disease, by Northern blot analysis and in situ hybridization. P2Y6 message was present at similar levels in first-trimester and full-term placenta, and in situ hybridization revealed that message was most abundant in the cytotrophoblast of the villi and chorionic plate at both gestational stages. The syncytiotrophoblast harbored lower levels of P2Y6 in first-trimester placenta, and by full-term, the syncytiotrophoblast only focally expressed P2Y6 transcripts. Neither the intermediate trophoblast nor nontrophoblastic elements of the placenta expressed P2Y6. Molar disease expressed P2Y6 in the villous trophoblast but not in the proliferative intermediate trophoblast, recapitulating the pattern of first-trimester placenta. Neither choriocarcinoma nor the choriocarcinoma cell lines JEG-3 and JAr expressed P2Y6 transcript. These findings reveal that P2Y6 mRNA production is highly characteristic of the epithelial-like cytotrophoblast and syncytiotrophoblast, whereas expression is absent in the mesenchymal-like intermediate trophoblast. Thus, P2Y6 may play an important role in trophoblastic development, differentiation, and neoplasia.

Expression of the P2Y6 purinergic receptor in human T cells infiltrating inflammatory bowel disease.

The human P2Y6 receptor is a member of the G-protein-coupled P2Y purinergic receptor family that responds to extracellular uridine diphosphate (UDP). In previous work, we cloned the human P2Y6 receptor from an activated T-cell library, and others have shown that it is expressed as a 1.9-kb transcript in several lymphoid tissues. This suggests a role for P2Y6 in T-cell function. However, the precise cellular expression pattern and regulation of P2Y6 in immune cells have not yet been established. In this study, we have examined the expression of P2Y6 in a range of tissues containing leukocytes by a combination of in situ hybridization (ISH), Northern blot analysis, and RT-PCR. Northern hybridization revealed that activated peripheral T cells show increased levels of P2Y6 mRNA. Furthermore, RT-PCR analysis of CD4+ and CD8+ subsets illustrated strong expression in both activated CD4+ and CD8+ T cells. Stimulation of resting and activated T cells with the P2Y6 ligand UDP caused a rise in the intracellular free calcium concentration in only the activated subset, indicating the presence of functional receptor. By ISH, P2Y6 expression was detected in the T cells of the thymic medulla and spleen, whereas no signal was detected in the bone marrow, fetal liver, or lymph nodes. T cells are thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD), and because a recent finding has suggested a role for extracellular nucleotides in mediating colonic epithelial cell damage in IBD, we speculated that the P2Y6 nucleotide receptor may be expressed in the T cells infiltrating IBD. ISH results reveal that P2Y6 is highly expressed in the T cells infiltrating active IBD, whereas P2Y6 expression was absent from the T cells of unaffected bowel. These results demonstrate expression and regulation of P2Y6 expression in T cells, and suggest a role for P2Y6 in the pathogenesis of IBD-mediated intestinal damage.

Multiple leiomyosarcomas of both donor and recipient origin arising in a heart-lung transplant patient.

The occurrence of Epstein-Barr virus-associated smooth-muscle tumors in immunocompromised patients has been reported, particularly in the pediatric population. In posttransplantation tumors, the tissue of origin has been either donor or recipient. Mixed-genotype sarcomas within the same patient have not yet been reported. We describe the occurrence of multiple leiomyosarcomas of both donor (arising in the lung allograft) and recipient (arising in the host liver) origin in a 15-year-old boy 3 years after heart-lung transplantation. Analysis of premortem lung tumors demonstrated the presence of Epstein-Barr virus DNA. Despite decreasing immunosuppression and commencing acyclovir, the patient died of systemic Pseudomonas infection. Immunohistochemical analysis revealed that both lung and liver tumors were negative for the Epstein-Barr virus receptor (CD21), and suggests that Epstein-Barr virus entry into the cells was not via this receptor but via an alternate mechanism such as cell fusion.

Chromosomal localization of the human P2y6 purinoceptor gene and phylogenetic analysis of the P2y purinoceptor family.

The G-protein-coupled P2Y purinoceptors mediate a variety of physiological effects in response to extracellular nucleotides. With the recent discovery of several new members from a variety of species, the P2Y purinoceptor family now encompasses types P2Y1 to P2Y6. By fluorescence in situ hybridization and utilization of the National Center for Biotechnology Information (NCBI) database, the human P2Y6 gene was localized to chromosome 11q13.5, between polymorphic markers D11S1314 and D11S916. NCBI database analysis of the remaining human P2Y purinoceptor genes revealed that P2Y2 and P2Y6 mapped to within less than 4 cM, and thus constitute the first described chromosomal clustering of this gene family. Phylogenetic analysis of the P2Y purinoceptor family demonstrated the presence of five evolutionary branches and suggests the occurrence of an ancient gene duplication event.

Juvenile laryngeal papillomatosis in a pediatric population: a clinicopathologic study.

A series of 22 children with juvenile laryngeal papillomatosis treated over a 31-year period is presented. The majority of patients were diagnosed when less than 5 years of age. Two patients died from the disease and four patients still had active disease at the completion of the study period. The duration of disease and number of recurrences were extremely variable. The number of recurrences was inversely related to the age of onset. The histologic findings were very similar in all patients, and no particular histologic feature had prognostic significance. In 20 patients, laryngeal biopsies were positive for human papillomavirus (HPV) 6/11 by either in situ hybridization (17) or polymerase chain reaction (19) or both (16). The number of patients who were HPV negative was small (two); interestingly, neither case had aggressive disease. Our findings suggest that age of onset and HPV status may be of prognostic value in determining the clinical course of the disease.

Coexistent T-cell lymphoblastic lymphoma and an atypical myeloproliferative disorder associated with t(8;13)(p21;q14).

This report describes a neoplasm exhibiting both lymphoid and myeloid differentiation associated with an acquired balanced translocation between chromosomes 8 and 13 occurring in a 10-year-old boy. Serial lymph node biopsies revealed the presence of both lymphoblastic lymphoma and an atypical myeloproliferative disorder within the same node. Immunophenotyping was consistent with the presence of an immature T-cell population within the nodal biopsy specimens. Cytogenetic analysis of the bone marrow and lymph node biopsy specimens revealed a unique translocation, t(8;13) (p21;q14). Molecular analysis revealed rearrangement of the immunoglobulin heavy chain gene and germline configuration of the T-cell receptor gene. The patient had a poor response to classical T-cell acute lymphocytic leukemia/lymphoma therapy and was changed to a myeloid leukemia protocol with good response. He underwent bone marrow transplantation but died soon after of overwhelming graft-versus-host disease. We found five similar cases in the literature, suggesting the existence of a subset of mixed lymphoid/myeloid disorders with 8p;13q translocations, in which the clinical picture is dictated by the myeloid element.

Molecular cloning and sequencing of a novel human P2 nucleotide receptor.

A novel human P2 nucleotide receptor has been cloned from a T-cell cDNA library. The predicted amino acid sequence shows characteristics of a G-protein-coupled receptor, and shares 88% homology with a recently characterised rat P2 nucleotide receptor sequence. Distinctive features include an extremely short cytoplasmic tail with only one putative protein kinase C phosphorylation site. Northern blot analysis revealed a 1.9 kb transcript expressed in the placenta.

Familial adenomatous polyposis in a 5 year old child: a clinical, pathological, and molecular genetic study.

A girl aged 5 years 8 months presented with rectal bleeding; her father had had familial adenomatous polyposis (FAP) and a colectomy at the age of 23. Endoscopy showed extensive polyposis and she had a colectomy. The proband and her father had the common codon 1309 5 bp deletion APC mutation. This mutation predisposes to early onset of FAP, and consideration needs to be given to having molecular testing of at risk members of these families done in childhood.

Squamous cell carcinoma of the tongue in a child with Fanconi anemia: a case report and review of the literature.

This report documents a case of squamous cell carcinoma (SCC) of the tongue in a child with Fanconi anemia (FA). FA is an autosomal recessive syndrome defined by chromosomal breakage in response to diepoxybutane or mitomycin C in which many patients present with pancytopenia, hypoplastic bone marrow, hyperpigmentation of the skin, skeletal malformations, small stature, hypogonadism, and chromosomal aberrations. Such patients are prone to the development of hematological malignancies and squamous cell carcinoma, especially of the head and neck. Although FA appears to be genetically heterogeneous, all cases display abnormalities of DNA repair. A gene defective in one of the four subsets of FA patients has been defined. Defects in this gene are thought to play a role in the development of neoplasia in FA patients. However, many other factors may also contribute to the development of malignancies, including immune deficiencies, therapeutic strategies, and bone marrow transplantation. This report reviews the association of FA and SCC and highlights the many factors involved in the development of neoplasia within a single patient, including FA, cyclophosphamide, immunosuppression, X-irradiation, and chronic oral graft-versus-host disease. In addition, the human papillomavirus status, although negative, is documented for the first time in such a case.

Allocation of cells to the inner cell mass and trophectoderm of 3/4 mouse embryos.

The allocation of cells to the inner cell mass (ICM) and trophectoderm (TE) was investigated at 6-h intervals from 78 h to 102 h after hCG injection in 3/4 mouse embryos to determine the effect of removal of a single blastomere at the 4-cell stage on early differentiation. The procedures used to produce 3/4 embryos had little effect on embryo development. Embryos that had a single blastomere removed and then re-aggregated (RA embryos) had the same total number of cells as untreated (UT) embryos except at 78 h (P less than 0.05) and 102 h (P less than 0.01) post hCG where there were slightly less cells in RA embryos. Three-quarter embryos always had significantly fewer cells than RA embryos (P less than 0.001), with an average of 74% of the total cell number of RA embryos. As expected, 3/4 embryos always had significantly fewer cells in the ICM and TE compared with RA embryos (P less than 0.001). However, the ICM:TE ratio was also significantly lower in 3/4 embryos compared with RA embryos at 84, 96, and 102 h post hCG, indicating that the allocation of cells to the ICM and TE was disturbed. The ICM:TE ratio of 3/4 embryos could not be manipulated if either an early- or late-dividing blastomere was selectively biopsied at the 4-cell stage; this suggests that the known preferential contribution of an early-dividing blastomere to the ICM is not cell autonomous.