Achlorhydria and stomach carcinoma

Patients with achlorhydria are suspected to have an increased risk of developing gastric adenocarcinoma. However, in the literature the reported risk varies considerably. In The Netherlands no such data are available. The risk of developing gastric adenocarcinoma was investigated in 129 achlorhydric patients. During a mean observation period of 12.3 yrs gastric adenocarcinoma was diagnosed in six patients. The expected incidence was 1,275, calculated by making use of age, sex and calendar specific incidence and mortality rates of gastric cancer in the Dutch population. The relative risk to develop gastric cancer was 4.7 (95% confidence limits: 1.7-10.2; p less than 0.05). Despite a significantly increased risk, screening of achlorhydric patients for gastric cancer is not advised.     

Cicatricial pemphigoid in the upper aerodigestive tract: diagnosis and management in severe laryngeal stenosis

Pemphigoid is a group of rare, acquired, autoimmune subepithelial blistering diseases. The condition has been subclassified into bullous pemphigoid and cicatricial pemphigoid (CP). Diagnosis is based on clinical presentation, evidence of subepithelialvesicles or bullae on routine histologic analysis, and direct and indirect immunofluorescence studies. Cicatricial pemphigoid is characterized by linear deposition of immunoreactants, principally IgG and complement factor 3, along epithelial basement membranes. Cicatricial pemphigoid usually leads to mucosal scarring. We present a case of severe CP that led to laryngeal and subglottic stenosis and involvement of both eyes and the oral, nasal, and nasopharyngeal mucosae. Treatment with dapsone, corticosteroids, azathioprine sodium, cyclosporine A, cyclophosphamide, methotrexate sodium, and mycophenolate mofetil between 1997 and 2001 only resulted in temporary disease control. The patient has been treated with leflunomide for the past 8 months, and there have been no relapses. Treatment of CP with leflunomide has not been described in the literature until now.     

User tests with the multi-mode compression architecture

The Multi-Mode Compression (MMC) architecture is a new system for better speech understanding, listening comfort and user acceptance. This study reports on the user tests that have been performed to verify the benefits of the concept and the quality of the fitting process for the individual hearing impaired. The study concentrates on the 4-channel version of a new series of digital instruments with this MMC architecture.     

Distinct effects of sphingosine-1-phosphate, lysophosphatidic acid and histamine in human and mouse dendritic cells

Dendritic cells (DC) are specialized antigen presenting cells characterized by their ability to migrate into target sites and secondary lymphoid organs in order to process antigens and activate naive T cells. Previously, we have shown that several secretion products from platelets and mast cells such as histamine, sphingosine-1-phosphate (S1P), and lysophosphatidic acid (LPA) have chemotactic activity towards immature human DC. Furthermore, they limit the capacity of mature human DC to initiate and amplify T helper cell type 1 (Th1) immune responses by inhibition of interleukin (IL)-12 and upregulation of IL-10 secretion. In this study we focused on the effect of these agents on murine DC. In murine DC no influence on IL-10 and IL-12 release by these agents was observed. Moreover, histamine and LPA failed to stimulate chemotaxis and actin reorganization in mouse DC. Instead, S1P had chemotactic activity and induced actin polymerization in immature as well as mature mouse DC. Therefore, our in vitro data implicate that in contrast to humans the function and immunological capacity of murine DC are not so tightly controlled by mast cell and platelet-derived secretion products such as histamine, S1P and LPA. These findings suggest that mouse models might underestimate the complex regulative network between mast cells, platelets and DC.     

The low molecular weight Dextran 40 inhibits the adhesion of T lymphocytes to endothelial cells

Dextrans are complex colloidal macromolecules widely used as haemorrheologic substances and anti-thrombotic agents. Here we describe a novel function of Dextran 40 by demonstrating an inhibition of T lymphocyte adhesion to endothelial cells (EC). We applied an established microassay in which constitutive and tumour necrosis factor-alpha (TNF-α)-induced binding of mouse T lymphoma cells (TK-1) to mouse endothelioma (eEND.2) cells is mediated by the interaction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on EC with their counter-receptors the LFA-1 heterodimer (CD11a/CD18) and VLA-4 on T cells. Dextran 40 in therapeutically achievable levels (2–32 mg/ml) reduced both constitutive and TNF-α-stimulated TK-1 adhesion to eEND.2. Selective preincubation of eEND.2 or TK-1 revealed that Dextran 40 acted exclusively on the T cells. To explore further the mechanisms by which Dextran 40 interfered with TK-1 adhesion, their LFA-1 and VLA-4 expression was analysed by FACS. The surface expression levels of neither receptor were affected by Dextran 40. However, confocal microscopy revealed that Dextran 40 interfered with the activation-dependent capping and clustering of LFA-1 and VLA-4 on the surface of TK-1. We conclude that Dextran 40 inhibits the capacity of TK-1 T cells to adhere to eEND.2 endothelial cells and thus may be useful for therapeutic intervention in diseases associated with enhanced T lymphocyte binding to microvascular endothelium.     

Are asthma patients at increased risk of clinical depression? A longitudinal cohort study

Objective: In this study, we assessed whether adult patients with asthma are more likely to be diagnosed with depression than diabetes patients or “healthy” controls during follow-up in primary care. Methods: Data from the Nijmegen Continuous Morbidity Registration were used to assess the risk for a first depression. Patients with asthma were compared with patients with diabetes and with two healthy controls matched on age, gender, socioeconomic status and attending general practice. With Cox proportional hazard analysis, we compared the risk of depression between these groups. These analyses were corrected for relevant covariates including a time-depending variable for multimorbidity. Explorative subgroup analyses were done for age, gender, socioeconomic status and multimorbidity. Results: Cumulative incidence of depression in asthma patients was 5.2%, in DM patients 4.1% and in control subjects 3.3%. The hazard ratios for a first episode of depression in the asthma patients (n?=?795) compared to DM patients (n?=?1033) and control subjects after correction for covariates were 1.11 (95% CI 0.60–2.04) and 1.18 (95% CI 0.78–1.79), respectively. Exploratory analyses showed that asthma patients without multimorbidity were at higher risk for a depression compared to reference groups, while asthma patients with multimorbidity were at lower risk for depression. Conclusion: Asthma patients were not more likely to be diagnosed with a first depression compared to “healthy” control subjects or diabetes patients. The influence of multimorbidity on depression risk in asthma patients warrants further study.     

Switch in syndecan-1 and syndecan-4 expression controls maturation associated dendritic cell motility

Dendritic cells (DCs) need to mobilize within the extracellular matrix (ECM) during their maturation and concomitant migration from peripheral sites to lymphoid organs. Syndecans are cell surface proteoglycans that mediate the interaction of DCs with the ECM. Here we investigated the influence of syndecans on dendritic cell motility and morphology. Langerhans cells of the epidermis and monocyte-derived DCs were found to undergo a switch in syndecan expression during maturation. Syndecan-1 was downregulated and syndecan-4 was strongly upregulated within the first hours of lipopolysaccharide-induced dendritic cell maturation and during Langerhans cell emigration from human skin, as shown by flow cytometry and qRT-PCR. Syndecan-1 downregulation was inhibited by syndecan-4 siRNA knock-down, indicating a functional interconnection between enhanced syndecan-4 expression and syndecan-1 downregulation. Syndecan-4 upregulation is functionally involved in dendritic cell motility, as inhibition of syndecan-4 function by means of blocking antibodies or through siRNA knock-down decreased dendritic cell motility. In other experiments, the cytoskeletal component a-actinin was observed to be upregulated in DCs as a consequence of the induction of maturation, and was found to colocalize with syndecan-4. Furthermore, lammellopodial spreading by DCs on fibronectin (FN)-coated surfaces was dependent on syndecan-4. This binding of syndecan-4 to FN and its association with the cytoskeleton may be relevant for syndecan-4-dependent dendritic cell motility. We conclude that the switch in syndecan expression during dendritic cell maturation controls the motility of DCs in a way that appears to be crucial for their mobilization from peripheral sites and subsequent migration to lymphoid tissues.