Increased height in diabetes mellitus corresponds to the predicted and the adult height

This study was conducted to analyse the effect of childhood-onset diabetes mellitus on adult height. The height at time of diagnosis of 35 children with insulin-dependent diabetes mellitus (IDDM) was compared with growth reference data. Predictions of the adult height were made at the time of diagnosis using the target height and the Tanner-Whitehouse II method. The adult height was compared with both the predicted values and the height of healthy adults. The height at time of diagnosis of the prepubertal children was increased compared with growth reference data, in contrast to pubertal children who had normal heights. Only the prepubertal boys were taller at time of diagnosis. The adult height of the prepubertal patients was taller than growth reference data. The mean adult height in all patients did not differ significantly from the predicted heights. In conclusion, the increased height at the start of IDDM in prepubertal children persists until adulthood.     

Transplant associated infections—The role of the gastrointestinal microbiota and potential therapeutic options

Infectious complications are common following kidney transplantation and rank in the top five causes of death in patients with allograft function. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant‐associated infections. Different factors have emerged which may disrupt the interaction between the gastrointestinal microbiota and the immune system, which may lead to infective complications in kidney transplant recipients. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant‐associated infections. This review will discuss the structure and function of the gastrointestinal microbiota, the changes that occur in the gastrointestinal microbiota following kidney transplantation and the factors underpinning these changes, how these changes may lead to transplant‐associated infectious complications and potential treatments which may be instituted to mitigate this risk.     

Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease

Elevated homocysteine (Hcy) levels are observed in two apparently unrelated diseases: neural-tube defects (NTD) and premature vascular disease. Defective human methionine synthase (MS) could result in elevated Hcy levels. We sequenced the coding region of MS in 8 hyperhomocysteinaemic patients (4 NTD patients and 4 patients with pregnancies complicated by spiral arterial disease, SAD). We identified only one mutation resulting in an amino acid substitution: an A-->G transition at bp 2756, converting an aspartic acid (D919) into a glycine (G). We screened genomic DNA for the presence of this mutation in 56 NTD patients, 69 mothers of children with NTD, 108 SAD patients and 364 controls. There was no increased prevalence of the GG and AG genotypes in NTD patients, their mothers or SAD patients. The D919G mutation does not seem to be a risk factor for NTD or vascular disease. We then examined the mean Hcy levels for each MS genotype. There was no correlation between GG- or AG-genotype and Hcy levels. The D919G mutation is thus a fairly prevalent, and probably benign polymorphism. This study, though limited, provides no evidence for a major involvement of MS in the aetiology of homocysteine-related diseases such as NTD or vascular disease.      

Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells

The mouse Pim-1 gene encodes two cytoplasmic serine-threonine-specific protein kinases. The gene has been found to be activated (overexpressed) by retroviral insertion in hematopoietic tumors in mice. Transgenic mice that overexpress Pim-1 (E mu-Pim-1) have a low incidence of spontaneous T-cell lymphomas and an increased susceptibility to Moloney murine leukemia virus and N-ethyl-N- nitrosourea-induced lymphomas. Apart from a slight enlargement of the spleen, no abnormalities were found in prelymphomatous transgenic mice. Inactivation of the Pim-1 gene in the germline of mice resulted in mice with a surprisingly subtle phenotype. Therefore, we investigated whether subtle effects of the absence of Pim-1 could be made visible during in vitro culturing of hematopoietic cells. We found that bone marrow-derived mast cells (BMMC) lacking Pim-1 had a distinct growth disadvantage when grown on interleukin (IL)-3, but not when stimulated by the factors IL-4, IL-9, or Steel factor (SF). This indicates a role for Pim-1 as a modulator of the IL-3 signal transduction pathway.     

Post‐Transplantation Immunoadsorption Can Be Withheld in ABO‐Incompatible Kidney Transplant Recipients

After ABO‐incompatible kidney transplantation, postoperative plasma exchange (PE) or immunoadsorption (IA) is performed per protocol or depending on postoperative A/B‐titers to prevent acute rejection. However, the need for postoperative PE or IA is not known. Since 2006, 30 consecutive patients received three standard postoperative IAs. Starting from 2009, the last 46 patients received only preoperative IA. Preoperative desensitization consisted of rituximab, tacrolimus, mycophenolate mofetil, prednisone and intravenous immunoglobulins. Antigen‐specific IA was performed pre‐operatively with the Glycosorb device. Biopsy‐proven acute rejections either antibody‐mediated (AMR) or mixed cellular and antibody‐mediated (MAR) within 3 months were recorded. The postoperative titer in patients with postoperative IA did not exceed 1:16 (IgG 1:4 [<2–16] median and range). The postoperative IgG titer was not significantly different after abandoning postoperative IA, although three patients had titers of 1:32 and one patient even 1:128. Rejections tended to be more frequent in the group with postoperative IA: 6 AMR and 3 MAR were recorded in 30 patients, vs. 4 AMR and 1 MAR in the 46 patients without postoperative IA (30 vs. 11%, P = 0.067). Baseline characteristics differed however: in the group with postoperative IA the vast majority had blood group O (87 vs. 52%, P = 0.003). Also, the IgG titer on the day of transplantation was higher (1:4 [<2–16] vs. 1:2 [<2–32], P = 0.007). All 14 patients with AMR and MAR rejections had postoperative IgG titers ≤1:16. Postoperative removal of A/B‐antibodies can be safely removed from the ABOi transplantation protocol using strict preoperative criteria for antibody lowering.     

The oral mucosa: A barrier site participating in tissue‐specific and systemic immunity

In the oral cavity, the immune system is constantly exposed to unique tissue‐specific signals, including a rich community of commensal microbes and their metabolites, continuous tissue damage from mastication, and antigens from food and airborne particles. How this unique combination of signals participates in the training of specialized immunity at this site is not well understood, yet imbalance of local responses is linked to tissue‐specific disease susceptibilities with the prototypic disease being periodontitis. However, the oral mucosa is also well recognized as a site where systemic inflammatory and autoimmune diseases often manifest, indicating that systemic immune deregulation is reflected in the function of the oral immune system. This commentary will discuss both aspects of compartmentalized and systemic immunity at the oral mucosa.