Protein tyrosine phosphatase PTPN22 in human autoimmunity

The discovery that a single-nucleotide polymorphism (SNP) in lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, is associated with type 1 diabetes (T1D) has now been verified by numerous studies and has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus, Graves' disease, generalized vitiligo and other human autoimmune diseases. In this paper, we discuss the association of PTPN22 with autoimmunity, the biochemistry of the PTPN22-encoded phosphatase, and the molecular mechanism(s) by which the disease-predisposing allele contributes to the development of human disease.     

Galectin-3 deficiency enhances type 2 immune cell-mediated myocarditis in mice

Experimental autoimmune myocarditis (EAM) is a mouse model of immune-mediated myocarditis and cardiomyopathy. The role of Galectin-3 (Gal-3), a β-galactoside-binding lectin, in autoimmune myocarditis has not been studied. Therefore, the aim of this study was to delineate the role of Gal-3 in myosin peptide-induced autoimmune myocarditis in mice. EAM was induced in relatively resistant C57BL/6J mice (wild type, WT) and in mice with a targeted deletion of Gal-3 gene (Gal-3KO) by immunization with myosin peptide MyHCα_334–352. Gal-3KO mice developed more severe myocarditis and more pronounced heart hypertrophy than WT mice. Increased infiltration of CD45⁺ leucocytes, CD3⁺ T cells, F4/80⁺ macrophages, and eosinophils was observed in hearts of Gal-3KO mice compared to WT mice on day 21 after EAM induction. Moreover, hearts of Gal-3KO mice had more T helper type 2 (Th2) cells, alternatively activated M2 macrophages, higher amounts of IgG deposits, and higher serum levels of IL-4 and IL-33 than WT mice. Ablation of Gal-3 in Th1-dominant C57BL/6J mice that are relatively resistant to EAM resulted in more severe disease characterized by type 2 cardiac inflammation. The complex effects of Gal-3 on EAM progression might be important in the consideration of therapeutic options for the treatment of EAM.     

Solitary fibrous tumour of the cheek: An unusual presentation of a rare soft tissue tumour

This case report discusses the unusual presentation and ultrasound features of a solitary fibrous tumour of the face. Solitary fibrous tumour is an uncommon form of soft tissue tumour which, although seen predominantly within the lung pleura, can occur throughout the body in sites such as the peritoneum, mediastinum and head and neck. Ultrasound is an excellent imaging modality in the assessment of soft tissue masses in the head and neck. The ultrasound features demonstrated by this example of solitary fibrous tumour are reviewed. This report also highlights that ultrasound alone is ultimately limited in reaching a definitive diagnosis. The roles of other investigations such as ultrasound-guided biopsy and cross-sectional imaging are discussed.     

Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C)

Data on the distribution of beta thalassemia among over 6,000 Melanesians reveals a major difference in the carrier rates between populations in the malarious coastal regions of New Guinea and those living in the historically malaria-free Highlands. The island of Maewo in Vanuatu has a particularly high incidence of beta + thalassemia associated with a single restriction enzyme haplotype. Direct cloning into a plasmid vector and sequence analysis demonstrate that the mutation is a G to C transversion at position 5 of intron 1 of the beta- globin gene. Oligonucleotide probe surveys indicate that this variant accounted for all cases of beta thalassemia studied from Maewo. It is also common in coastal Papua New Guinea where haplotype and oligonucleotide probe data suggest that the molecular basis of beta thalassmia is more heterogeneous.     

Delayed presentation of vernix caseosa peritonitis

INTRODUCTION

Vernix caseosa peritonitis (VCP) is a rare and poorly recognised condition resulting from a sustained foreign body reaction to the vernix caseosa of the baby. This case-based review aims to highlight its importance for any medical team managing patients with peritonitis who have undergone a recent Caesarean section.

CASE REPORT

A 31-year-old woman presented 5 weeks after a Caesarean section with symptoms and signs of peritonitis.

CONCLUSIONS

Laparotomy and peritoneal lavage is the mainstay of treatment for VCP. Knowledge of the condition may stop inadvertent resection of normal intra-abdominal organs. Greater awareness of VCP is required to ensure earlier recognition as patients can recover well following timely operative intervention.     

Effect of corticosteroids on arginine vasopressin after pediatric cardiac surgery

Introduction

Arginine vasopressin’s (AVP) efficacy in the treatment of refractory hypotension is, in part, dependent upon preinfusion endogenous AVP concentration. Corticosteroids, also commonly used to treat refractory hypotension, have been shown to suppress endogenous AVP release. We aimed to determine if corticosteroids affect endogenous AVP concentrations in children recovering from cardiac surgery.

Materials and methods

We reviewed the records of children who underwent cardiac surgery between January 2008 and January 2009 and had AVP concentrations available as part of a prior prospective study. Doses of hydrocortisone, methylprednisolone, and dexamethasone administered within the first 48 hours after cardiopulmonary bypass were quantitated. Multivariable linear regression was performed to determine if corticosteroids had a significant effect on 48-hour plasma AVP concentration.

Results

Sixty-nine children with plasma AVP concentrations available were reviewed, 34 (49%) of which received corticosteroids within 48 hours after cardiopulmonary bypass. On multivariable regression, greater number of corticosteroid doses but not cumulative corticosteroid dosage was significantly associated with low 48-hour AVP concentration (β = − 4.0; 95% confidence intervals, − 6.5 to − 1.4).

Conclusions

Children who receive multiple doses of corticosteroids after cardiac surgery, regardless of potency, are likely to have low endogenous AVP concentrations. Children who remain unstable despite corticosteroids may respond favorably to exogenous AVP therapy.