Non-Graft-versus-Host Disease Enterocolitis Following Cord Blood Transplantation is Real, with Poorly Understood Pathophysiology, and Requires Distinct Management, with Eventual Resolution without Immune Suppression.

Enterocolitis is common after cord blood transplantation (CBT) and a specific, non-graft-versus-host disease (GVHD) entity with specific histopathologic features ("cord colitis") has been described in some cases in selected series. Immune suppression is not without risk, and we have used it only when biopsy features are consistent with classical GVHD. In the absence of biopsy features of classical GVHD, our management of intestinal failure has been supportive, and we have withdrawn immune suppression to allow immune reconstitution and better prevent relapse of malignant disease and reduce infectious complications.

Correction: Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism.

[This corrects the article DOI: 10.1371/journal.pone.

Increased proliferation and altered cell cycle regulation in pancreatic stem cells derived from patients with congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is characterised by inappropriate insulin secretion causing profound hypoglycaemia and brain damage if inadequately controlled. Pancreatic tissue isolated from patients with diffuse CHI shows abnormal proliferation rates, the mechanisms of which are not fully resolved. Understanding cell proliferation in CHI may lead to new therapeutic options, alongside opportunities to manipulate β-cell mass in patients with diabetes.

Clinical Diversity in Focal Congenital Hyperinsulinism in Infancy Correlates With Histological Heterogeneity of Islet Cell Lesions.

Congenital Hyperinsulinism (CHI) is an important cause of severe and persistent hypoglycaemia in infancy and childhood. The focal form (CHI-F) of CHI can be potentially cured by pancreatic lesionectomy. While diagnostic characteristics of CHI-F pancreatic histopathology are well-recognized, correlation with clinical phenotype has not been established.

Atypical Forms of Congenital Hyperinsulinism in Infancy Are Associated With Mosaic Patterns of Immature Islet Cells.

Objectives: We aimed to characterize mosaic populations of pancreatic islet cells from patients with atypical congenital hyperinsulinism in infancy (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in β-cells but suppressed in δ-cells in the mature pancreas.

Patients/methods: Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy.

When Parents Choose Gender: Intersex, Children, and the Law.

In England and Wales, it is usually lawful for those with parental responsibility to consent to treatment on children who have not acquired legal capacity, providing that they are acting in the child's best interests. Whilst in most instances this process is unproblematic and the decisions made are non-controversial, there are troubling examples where this is more problematic. The difficulties for a family with a child who has an intersex condition will be considered to illustrate that there may be cases of medical and surgical treatment where even though both parents and doctors agree on a course of action in good faith, the treatment administered may not necessarily be in the best interests of the child.

Enhanced Islet Cell Nucleomegaly Defines Diffuse Congenital Hyperinsulinism in Infancy but Not Other Forms of the Disease.

Objectives: To quantify islet cell nucleomegaly in controls and tissues obtained from patients with congenital hyperinsulinism in infancy (CHI) and to examine the association of nucleomegaly with proliferation.

Methods: High-content analysis of histologic sections and serial block-face scanning electron microscopy were used to quantify nucleomegaly.

Results: Enlarged islet cell nuclear areas were 4.

Deficiency of the myogenic factor MyoD causes a perinatally lethal fetal akinesia.

Background: Lethal fetal akinesia deformation sequence (FADS) describes a clinically and genetically heterogeneous phenotype that includes fetal akinesia, intrauterine growth retardation, arthrogryposis and developmental anomalies. Affected babies die as a result of pulmonary hypoplasia. We aimed to identify the underlying genetic cause of this disorder in a family in which there were three affected individuals from two sibships.

What do we do about women athletes with testes?

Elite sport and the measures imposed to prevent 'men' from 'cheating' by posing as women in women's events cast interesting light on notions of sex and gender. Some women have testes, organs that produce testosterone, because they are trans women or they have an intersex state. Testosterone is recognised as a performance-enhancing substance in at least some circumstances, and therefore, women with testes may possess an advantage when competing in some sport against women without testes, though this has never been subjected to rigorous scientific testing.

Altered Phenotype of β-Cells and Other Pancreatic Cell Lineages in Patients With Diffuse Congenital Hyperinsulinism in Infancy Caused by Mutations in the ATP-Sensitive K-Channel.

Diffuse congenital hyperinsulinism in infancy (CHI-D) arises from mutations inactivating the KATP channel; however, the phenotype is difficult to explain from electrophysiology alone. Here we studied wider abnormalities in the β-cell and other pancreatic lineages. Islets were disorganized in CHI-D compared with controls.

Increased plasma incretin concentrations identifies a subset of patients with persistent congenital hyperinsulinism without KATP channel gene defects.

Congenital hyperinsulinism causes profound hypoglycemia, which may persist or resolve spontaneously. Among 13 children with congenital hyperinsulinism, elevated incretin hormone concentrations were detected in 2 with atypical, persistent disease. We suggest that incretin biomarkers may identify these patients, and that elevated hormone levels may contribute to their pathophysiology.

Insulinoma in childhood: clinical, radiological, molecular and histological aspects of nine patients.

Background: Insulinomas are a rare cause of hyperinsulinaemic hypoglycaemia (HH) in children. The clinical features, investigations, management and histology of these rare pancreatic tumours in children have not been described in a large cohort of patients.

Methods: We conducted a retrospective review of cases diagnosed between 2000 and 2012, presenting to two referral centres in the United Kingdom.

Childhood medulloblastoma in northwest England 1954 to 1997: incidence and survival.

The incidence, survival patterns, and presenting symptoms of children with medulloblastoma were studied. Data were ascertained from the Manchester Tumour Registry which is population-based and has collected data on all childhood malignancies in northwest England since 1954. Incidence rates standardized to the European standard population were calculated and Poisson regression models were used to examine temporal changes in the incidence rates during the period 1954 to 1997.

Fatal Pseudomonas septicemia and vasculitis in a premature infant.

A characteristic vasculitis is an uncommon but well-recognized complication of severe Pseudomonas aeruginosa infection in the neonate. Although it is one of the most common gram-negative organisms responsible for overall nosocomial infection, it is a rare cause of intrauterine or intrapartum infection of the newborn. We describe a fatal Pseudomonas aeruginosa infection occurring in a very premature infant with widespread skin necrosis.

Phenotypic diversity in the Smith-Lemli-Opitz syndrome.

The phenotype of four cases of Smith-Lemli-Opitz syndrome (SLO) with proven defects in cholesterol biosynthesis are compared, and shown to be markedly disparate even between sibs, and demonstrate the dilemma for the clinician. The advent of a biochemical test for SLO has been enormously valuable in determining which patients are truly affected by the condition, but because of the wide phenotypic variation, a diagnosis on clinical features alone remains problematic.

The choroid plexus carcinomas of childhood: histopathology, immunocytochemistry and clinicopathological correlations.

Anaplastic choroid plexus carcinoma is a tumour with a predilection for the posterior fossa of infants and can be difficult to distinguish histologically from medulloblastoma without the aid of immunocytochemistry using a panel of antibodies. Of a series of 17 choroid plexus carcinomas (five of which were classed as moderately differentiated and 12 as anaplastic) 17 expressed antigens to transthyretin, transferrin and cathepsin and 16 expressed carbonic anhydrase II. Eleven expressed at least one epithelial marker (cytokeratin or epithelial membrane antigen).

Oligohydramnios sequence: the spectrum of renal malformations.

Objective: To assess the value of the autopsy findings on a series of infants dying with features of the oligohydramnios sequence, with particular reference to anomalies of the renal tract.

Design: Retrospective review.

Setting: Pathology departments serving three maternity units in Manchester.

Fatal disseminated adenovirus type 2 infection following bone marrow transplantation for Hurler's syndrome: a primary infection.

A 5-month-old girl given an allogeneic bone marrow transplant for Hurler's syndrome succumbed to fatal pneumonia 5 weeks after the transplant. Adenovirus type 2 was isolated from her urine before she died. Immunoperoxidase and electron microscopical studies of liver and lungs post mortem confirmed a disseminated adenovirus infection.

Clear cell sarcoma of the kidney in a 4-month-old infant: a case report.

A case of clear cell sarcoma of the kidney is described in a 4-month-old male infant. The tumor had a typical histological pattern, consisting of sheets of tumor cells possessing "empty" nuclei set within a delicate capillary network. There was extensive necrosis and tumor cell cytoplasm contained vimentin.

Systemic amyloidosis of beta 2 microglobulin type.

A patient receiving haemodialysis for 15 years developed systemic amyloidosis of beta 2 microglobulin type. Noticeable deposits of amyloid were present in the myocardium, intervertebral discs, joint cartilages and tendons. Less conspicuous amounts were present in blood vessel walls in the lungs, liver, adrenal glands and brain, and within the stroma of the prostate, testis and kidney, often with foci of calcification.

[Beta 2-microglobulin amyloidosis].

A 35-year-old man who had been treated by hemodialysis for 15 years suffered from systemic amyloidosis. It was identified as a beta 2-microglobulin type according to immunohistochemistry. Extensive amyloid deposits were found in myocardium, cartilages of intervertebral discs and in carpal tunnel ligament.

Junctional epidermolysis bullosa: a mild variant in two Indian sisters.

Two sisters developed a bullous skin disease in early childhood. The disease had features of junctional epidermolysis bullosa but differed clinically from previously recorded variants.

Adenocarcinoma of the pancreas with osteoclast-like giant cells: a case report with immunocytochemistry.

Histological examination of a tumor centered in the body of the pancreas of a 65-year-old Iranian man revealed it to have a substantial component in which osteoclast-like giant cells were set within a stroma of pleomorphic mononuclear cells though other areas were composed of conventional adenocarcinoma. Immunocytochemistry was used to investigate the differentiation of the various component cells of the tumor. The carcinoma cells of the usual type expressed epithelial antigens (EMA and cytokeratin).