Maple syrup urine disease: tailoring a plan for pregnancy

Maple syrup urine disease (MSUD) is an autosomal metabolic condition that can cause significant morbidity in pregnant women and their infants. Advances in nutritional management mean more mothers with congenital metabolic disorders are becoming pregnant, and presenting challenges in obstetric care. In particular, the increase in protein requirements during pregnancy and metabolic stress of childbirth require careful planning and caloric titration. We report a case of a second time mother with MSUD and demonstrate a treatment scaffold to help achieve successful pregnancies for women with this and similar conditions.     

Cannabis use and knowledge among medical students at the University of the Free State,Bloemfontein, South Africa

Objective: The study aimed to investigate the prevalence of cannabis use among undergraduate medical students of the University of the Free State (UFS), and the extent of their knowledge about the substance.

Method: This cross-sectional study included five year groups of undergraduate medical students. A self-administered, anonymous questionnaire was used.

Results: Of the 643 medical students, 541 (84.1%) completed the questionnaire. In total, 161 (30.9%) students reported that they had ever used cannabis. The percentage of males who had ever used cannabis was twice that of females (relative risk 2.04; 95% CI 1.56; 2.67). Of the cannabis users, less than 12% used it monthly or more often. A fifth (19.5%) of all students stated that they did not know the side effects of cannabis use. Nearly half (45.4%) indicated that they could not name any medicinal (medical) uses. The median knowledge score of students who used cannabis tended to be higher than that of students who did not use cannabis; this was statistically significant only in the third-year group.

Conclusions: Medical students generally have a low level of knowledge about cannabis. The reported lifetime prevalence and pattern of cannabis use are similar to those reported in other South African studies published over the past 35 years.     

Could ochratoxin A in food commodities be the cause of chronic kidney disease in Sri Lanka?

Ochratoxin A (OA) is a naturally occurring mycotoxin with nephrotoxic properties that can contaminate plant food products. OA concentrations were assessed in commonly consumed food items in the North Central Province of Sri Lanka, where chronic kidney disease is diagnosed at epidemic proportions. Ninety-eight randomly selected food samples were analysed. Mycotoxin was detected in the extract by using a MycoMonitor Ochratoxin A ELISA assay kit (Helica Biosystems Inc., USA). The levels of OA found in these food commodities were below the recommended statutory maximum limit and are unlikely to be a potential risk factor for nephropathy in the North Central Province of Sri Lanka.     

A pilot study of dose-dense adjuvant paclitaxel without growth factor support for women with early breast carcinoma

A female patient with HER2 positive, metastatic breast cancer presented with pulmonary infiltrates, and a plural effusion dyspnoea after several months of trastuzumab treatment. She had been treated without complications with six courses of docetaxel and trastuzumab in combination with dexamethasone with partial remission of disease. Malignancy, infection and cardiomyopathy were excluded as causes of dyspnoea. Pleural and broncheoalveolar fluid analyses (BAL) showed eosinophils. A diagnosis of trastuzumab-induced pneumonitis was made. After treatment with steroids there was gradual clinical improvement and disappearance of infiltrates. Although a causative association between trastuzumab and this patient’s pulmonary syndrome was not proven, the potential for this toxicity should be considered.     

Unrelated Hematopoietic Cell Transplantation in a Patient with Combined Immunodeficiency with Granulomatous Disease and Autoimmunity Secondary to RAG Deficiency

The use of HLA-identical hematopoietic stem cell transplantation (HSCT) demonstrates overall survival rates greater than 75 % for T-B-NK+ severe combined immunodeficiency secondary to pathogenic mutation of recombinase activating genes 1 and 2 (RAG1/2). Limited data exist regarding the use of HSCT in patients with hypomorphic RAG variants marked by greater preservation of RAG activity and associated phenotypes such as granulomatous disease in combination with autoimmunity. We describe a 17-year-old with combined immunodeficiency and immune dysregulation characterized by granulomatous lung disease and autoimmunity secondary to compound heterozygous RAG mutations. A myeloablative reduced toxicity HSCT was completed using an unrelated bone marrow donor. With the increasing cases of immune dysregulation being discovered with hypomorphic RAG variants, the use of HSCT may advance to the forefront of treatment. This case serves to discuss indications of HSCT, approaches to preparative therapy, and the potential complications in this growing cohort of patients with immune dysregulation and RAG deficiency.     

Anterior abdominal wall reconstruction

Reconstruction of the anterior abdominal wall is based on six basic principles. First, the anatomy of the abdominal wall and adjacent donor sites must be understood clearly. This includes a complete knowledge of the neurovascular anatomy and the arc of rotation of each subunit. The defect then has to be exposed completely before the definitive closure is attempted. Once the defect is established, abdominal domain is restored with some sort of support. The next phase of the repair involves reassigning local tissue to close the defect. Distant tissue then is imported from donor sites such as the thigh, if needed. Finally, the skin envelope is readjusted and closed. These principles help optimize function and restore form, hence achieving the best possible result.     

Diagnostic Tools for Inborn Errors of Human Immunity (Primary Immunodeficiencies and Immune Dysregulatory Diseases)

Purpose of Review

The purpose of this review is to provide an overview of diagnostic testing in primary immunodeficiency and immune dysregulatory disorders (PIDDs), particularly focusing on flow cytometry and genetic techniques, utilizing specific examples of PIDDs.

Recent Findings

Flow cytometry remains a vital tool in the diagnosis and monitoring of immunological diseases. Its utility ranges from cellular analysis and specific protein quantitation to functional assays and signaling pathway analysis. Mass cytometry combines flow cytometry and mass spectrometry to dramatically increase the throughput of multivariate single-cell analysis. Next-generation sequencing in combination with other molecular techniques and processing algorithms has become more widely available and identified the diverse and heterogeneous genetic underpinnings of these disorders.

Summary

As the spectrum of disease is further clarified by increasing immunological, genetic, and epigenetic knowledge, the careful application of these diagnostic tools and bioinformatics will assist not only in our understanding of these complex disorders, but also enable the implementation of personalized therapeutic approaches for disease management.

     

Modulation of insulitis and type 1 diabetes by transgenic HLA-DR3 and DQ8 in NOD mice lacking endogenous MHC class II

To evaluate the contributions of DR3 and DQ8 to the etiopathogenesis of type 1 diabetes in a diabetes-predisposing milieu, we developed human leukocyte antigen (HLA) transgenic mice on the nonobese diabetic (NOD) background in the absence of the endogenous class II molecule, I-A(g7) and studied the incidence of both spontaneous and experimental (induced) autoimmune diabetes. Transgenic expression of HLA-DR3 and -DQ8 (either alone or in combination) did not confer susceptibility to spontaneous or cyclophosphamide-induced type 1 diabetes. Expression of I-A(g7) was mandatory for development of spontaneous or cyclophosphamide-induced diabetes. However, multiple low doses of streptozotocin could induce diabetes in all groups of mice independent of the class II molecules expressed. In unmanipulated mice, only islets from I-A(g7+/+) mice revealed significant intra-islet infiltration. Although a characteristic peri-insulitis/peri-ductulitis was present in Abeta(0)/NOD mice, islets from DR3, DQ8 and DR3 x DQ8 double transgenic mice demonstrated significantly less infiltration. In conclusion, transgenic expression of HLA-DR3 and -DQ8 associated with predisposition to type 1 diabetes alone is not sufficient to induce spontaneous diabetes in NOD mice lacking endogenous class II molecules.