Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles.

Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed monoclonal antibodies, to which streptavidin and subsequently biotinylated dextran-magnetite particles were coupled. This labeling resulted in a strong and selective negative contrast enhancement of lymphocyte suspensions at 2.0 T, caused predominantly by the specific increase of R2 with a small but significant specific increase of R1. The R1 was found to decrease with increasing field strength. The immunolabeling procedure described here may be used for the selective signal depletion of target cells in MR imaging.     

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children

BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. OBJECTIVE: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. RESULTS: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.     

Nocturnal hypoglycaemia in Type 1 diabetic patients,assessed with continuous glucose monitoring: frequency,duration and associations

Aims We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple‐injection therapy (MIT) using a continuous subcutaneous glucose sensor. Methods A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA_1c 7.8 ± 0.9%) and 33 patients on MIT (HbA_1c 8.7 ± 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA_1c, diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated. Results Nocturnal hypoglycaemia ≤ 3.9 mmol/l occurred in 33.3% of both the CSII‐ (8/24) and MIT‐treated patients (11/33). Mean (± sd ; median, interquartile range) duration of hypoglycaemia ≤ 3.9 mmol/l was 78 (± 76; 57, 23–120) min per night for the CSII‐ and 98 (± 80; 81, 32–158) min per night for the MIT‐treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia. Conclusions Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.     

Effect of ambient oxygen concentration upon the acute toxicity of chlorophenols and heavy metals to the groundwater copepod Parastenocaris germanica (Crustacea).

Acute static toxicity experiments have been performed under normoxic and hypoxic conditions. The test animals used were adults of the groundwater-adapted copepod Parastenocaris germanica. The animals originated from a sandy, gravelly phreatic aquifer of the Meuse valley in The Netherlands. Toxicants applied were pentachlorophenol, 3,4-dichlorophenol, zinc, and cadmium. The results were statistically evaluated by a log-logistic model. LC50 and LC5 values with 95% confidence limits were calculated. Response models of application under both oxygen conditions were compared. The influence of ambient oxygen concentration on sensitivity appeared to be very small; only in the case of pentachlorophenol were hypoxic and normoxic models slightly but significantly different. Comparisons with the sensitivity of other organisms are made and the results are discussed against the specific physiological adaptations of the organisms to groundwater conditions.     

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.     

Large animal models of fulminant hepatic failure in artificial and bioartificial liver support research

Among the large range of organs involved in the field of tissue engineering (skin, blood vessels, cartilage, etc.) the liver has been given broad attention in the last decade. Liver support systems encompassing artificial and bioartificial systems are applied to treat patients with fulminant hepatic failure (FHF) as a bridge to orthotopic liver transplantation or to liver regeneration. To test safety, technical applicability and therapeutic effect of liver support systems, reliable animal models are needed. Due to the complexity of FHF many diverse attempts have been made to develop an adequate animal model to study liver failure, liver regeneration and liver support systems. In this paper an overview is given of the different models and their advantages and disadvantages are discussed. Suggestions are made for the most suitable large animal model to test liver support systems.     

Sperm quality in Hodgkin's disease versus non-Hodgkin's lymphoma

The study was conducted to determine the deleterious effect of lymphoma disease on spermatogenesis and to evaluate the possibility that the disease is mediated primarily by inherent mechanisms in Hodgkin's disease and non-Hodgkin's lymphoma patients. A total of 89 patients with lymphoma disease (Hodgkin's and non-Hodgkin's) were referred for sperm preservation prior to adjuvant treatments. A comparison was made of pre- and post-thaw sperm quality between lymphoma patients and healthy volunteers who applied for sperm donation. This was followed by further assessment of the differences between patients with Hodgkin's disease and non-Hodgkin's lymphoma in terms of sperm variables, clinical parameters and blood hormone concentrations. It was found that patients with lymphoma disease had significantly impaired pre-freeze and post-thaw sperm quality compared with that of healthy volunteers. Patients with non-Hodgkin's lymphoma had spermatozoa of higher quality than patients with Hodgkin's disease. No differences were found in the clinical or hormonal parameters between these two groups. As expected, reduced testicular size and abnormal testicular consistency were correlated with decreased sperm quality. The mere presence of cancer disease has a direct negative effect on spermatogenesis, which is probably not related to incidental side-effects. A variable degree of impairment should be expected with different categories of cancer.      

The effect of bacillus Calmette-Guérin immunization depends on the genetic predisposition to Th2-type responsiveness

The aim of this study was to investigate whether the effect of bacillus Calmette-Guérin (BCG) immunization on ovalbumin-induced allergic inflammation in a rat model depends on the genetic predisposition to react with a T helper cell (Th) 2-type cytokine response. This study was performed in an inbred Th2-predisposed "asthma prone" rat strain (brown Norway [BN]) and in an outbred nonpredisposed strain (Sprague Dawley [SD]), to differentiate between genetic and environmental factors. BCG decreased numbers of lung eosinophils and macrophages in the SD rat. This effect was not seen in the BN rat. In the BN rat, but not in the SD rat, BCG downregulated levels of total serum IgE. No significant differences were found with respect to frequencies of IFNgamma- or interleukin-4-producing cells in the lung in both rat strains. These results indicate that the degree and pathway of immunomodulatory effect of BCG in two genetically different rat strains is dependent on the genetic predisposition to develop a Th2-type response. Therefore, differences in genotype in relation to environment may result in difference in involvement of contributing pathogenic factors and thus different responsiveness to therapeutic strategies.