Gut protection by palifermin during autologous haematopoietic SCT.

Conditioning therapy in connection with haematopoietic SCT (HSCT) induces a disruption of the intestinal barrier function facilitating the permeation of bacteria and endotoxin through the bowel wall with subsequent increased risk of septicaemia and a worsening of GVHD in the allogeneic setting. Palifermin (recombinant human keratinocyte growth factor) reduces the severity of oral mucositis with HSCT. The present trial investigates its effect on intestinal barrier function. Seventeen lymphoma patients undergoing autologous HSCT received palifermin. Intestinal permeability was assessed before the conditioning therapy and on days +4 and +14. Clinical oral and gastrointestinal toxicity was prospectively assessed in parallel. A comparison was made with matched historical study patients (n=21). Patients treated with palifermin had a significantly better preserved intestinal barrier function (P=0.01 on day +4) and were in less need of total parenteral nutrition (P=0.005) as compared with controls. No significant reduction of clinical gastrointestinal or oral toxicity was observed. The intestinal barrier function, normally disrupted by the conditioning therapy, is preserved by palifermin. Whether intestinal barrier preservation protects from invasive infections, and in the allogeneic setting diminishes GVHD severity, remains to be investigated in randomized controlled trials.

The significance of oral health and dental treatment for the postoperative outcome of heart valve surgery.

The objective of this study was to evaluate the significance of preoperative dental treatment for the development of complications in the form of infections during the first postoperative weeks after heart valve surgery. In one group of patients (n = 149), oral health was examined and dental treatment performed 3-6 months prior to heart valve surgery. In a second group (n = 104), oral health was examined postoperatively and these patients did not receive any dental treatment before surgery. Infections were recorded for all patients during the first three weeks after surgery and correlated to the dental status at the time of surgery. Sepsis or endocarditis occurred in 5.4% of the first group and in 1.9% of the second group. Freedom from all infections for the two groups was 55% and 56%, respectively. The results did not reveal any significant differences between the groups regarding patients' oral health at the primary oral examination. The frequencies of postoperative complications such as focal infections, fever and increased CRP were also found to be similar for both groups. The combined scores of complications were 2.1% and 1.8%, respectively. Data from the present study do not support the suggestion that dental intervention will decrease the rate of early complications following heart valve surgery.

Functional analysis of a variant of the thyrotropin receptor gene in a family with Graves' disease.

Nucleotide sequence analysis of PCR fragments corresponding to the TSH-receptor (TSHR) amplified from genomic DNA collected from the four members of a family, two of which had Graves' thyrotoxicosis, revealed a nucleotide substitution in the first position of codon 36 of the TSH-receptor gene in the two patients. The nucleotide substitution was from G to C, leading to a 36D-->36H change (D36H) in the predicted amino acid sequence of the receptor. The altered sequence was also found in DNA obtained from their mother, but not in DNA from their father. We stably expressed the two receptor variants in NIH 3T3 cells, by transfection of cDNA encoding the wildtype (WT) and D36H variants of the TSHR. Neither the binding of 125I-TSH nor the responsiveness to TSH measured as cAMP formation, appeared to be different in the TSHR-D36H compared to the TSHR-WT. Furthermore, the D36H-receptor also became desensitized when exposed to TSH as did the WT-receptor.

Difference in capacity between macrophages and dendritic cells from rat incisor pulp to provide accessory signals to concanavalin-A-stimulated T-lymphocytes.

The present study compared the ability of dendritic cells and macrophages derived from the dental pulp to provide accessory signals to Concanavalin A (Con A)-stimulated T-lymphocytes. Pulpal cells from maxillary and mandibular rat incisors were enzymatically released with collagenase. T-lymphocytes were isolated from rat cervical lymph nodes. In initial experiments, suspensions of unseparated pulpal cells were found to provide co-stimulatory help to Con-A-treated T-lymphocytes. The proliferation rate correlated well with the number of cells in the pulp suspension and followed a time course characteristic of a Con-A-driven proliferation of T-lymphocytes. Depletion of class II molecule-expressing cells from the unpurified suspension of pulpal cells resulted in lost ability to provide accessory signals to Con-A-stimulated T-lymphocytes. In contrast, removal of ED2-positive cells, i.e., macrophages, did not affect the ability of the suspension to give this assistance. Partially purified class II molecule-expressing cells enhanced the proliferative response, while addition of enriched macrophages did not. It was concluded that cells in the normal dental pulp with the characteristics of dendritic cells have the capacity to provide help to Con-A-stimulated T-lymphocytes, while cells with the macrophage phenotype lack this ability.