Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmune disease. Both for food and clinical applications of lactobacilli, proper selection of wild type strains is crucial.For that purpose, eight different common Lactobacillus strains were analysed with respect to mucosal induction of pro- and anti-inflammatory cytokines, IgA-producing plasma cells in the gut, as well as systemic antibody responses against a parenterally administered antigen. Immunohistochemical analysis of cytokine-producing cells in the gut villi showed no significant induction of the cytokines IL-1alpha, IFN-gamma, IL-4 or IL-10 after oral administration of wild type Lactobacillus strains. In contrast, oral administration of L. reuteri and L. brevis induced expression of the proinflammatory/Th1 cytokines TNF-alpha, IL-2 and/or IL-1beta. Oral administration of these two strains and L. fermentum also significantly enhanced the IgG response against parenterally administered haptenated chicken gamma globulin (TNP-CGG). The five other strains did not show this adjuvanticity. L. reuteri induced relatively high levels of IgG2a compared to L. murines, a nonadjuving Lactobacillus strain.These findings imply that different Lactobacillus strains induce distinct mucosal cytokine profiles and possess differential intrinsic adjuvanticity. This suggests that rational Lactobacillus strain selection provides a strategy to influence cytokine expression and thereby influence immune responses.     

The application of electric heart assist devices in 3 patients with end-stage heart failure as a bridge to transplantation

Left-ventricular assist devices have already gained an international place in the treatment of end-stage heart failure. It is expected that in future they will be increasingly used as a temporary bridging following the recovery from heart failure and to a lesser extent as a bridge to heart transplantation. Three patients with end-stage heart failure, men aged 68, 57 and 49 years, received a left-ventricular assist device (LVAD) as a bridge to transplantation. The device chosen was a Heartmate Vented Electric System (ThermoCardiosystems; Woburn, Massachusetts, US). In this system a pump is implanted under the diaphragm and connected to the apex of the left ventricle and the pars ascendens aortae. The first two patients reached the time of transplantation and used the LVAD for 367 and 416 days respectively. The third patient died after the pump had been implanted, due to progressive right-ventricle failure. The first patient died shortly after the heart transplantation.     

Development of a Bioassay to Test the Possible Role of Thiamine Disturbance as a Mechanism Behind Pollution-Induced Reproductive Failures in Birds

A test system was developed to examine the effects of environmental contaminants on thiamine homeostasis in bird embryos. This system employs fresh chicken egg yolk lipids as a vehicle for use in egg injection studies. Furazolidone, an antibiotic suspected to interfere with thiamine metabolism, was used as a positive control to evaluate the utility of the test system. It was determined that fresh chicken egg yolk lipids were preferable over chemical vehicles as it resulted in lower mortality rates (16% versus 23–62%) and did not induce any observable effects in the embryo. Injection of 1 mg/egg of furazolidone at day 0 of development resulted in decreased respiration followed by death, with mortality rates being twice as high as in carrier controls. In addition, transketolase activity, which was measured as an indicator of thiamine availability in the body, was decreased 25% in brains of 19-day-old embryos. This mechanism may be of importance for effects of environmental contaminants in wild bird populations. Received: 3 November 1999/Accepted: 29 March 2000     

Physiological anticoagulants and activated protein C resistance in childhood stroke

Immunological and functional protein S, protein C and antithrombin III levels and anticoagulant responses to activated protein C were measured in 24 patients with stroke in childhood. No hereditary deficiencies were found. The protein S levels in healthy controls of younger age did not differ from the adult levels. For optimal screening of protein S deficiency, measurements using functional as well as immunological assays are recommended. Appropriate criteria for the diagnosis of the deficiencies must be carefully applied if unnecessary anxiety and inappropriate treatment of children are to be avoided.     

Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care

Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants.     

The influence of HLA-mismatches on phenotypic and functional characteristics of graft infiltrating lymphocytes after heart transplantation

We studied the influence of HLA mismatches on T lymphocyte cultures that were derived from endomyocardial biopsies (EMB) from 118 heart transplant recipients. From patients with DR mismatches, the majority of the EMB-derived cultures were dominated by CD4, while in patients without DR mismatches, CD8 was the predominant T cell subset. The majority (75) of the cultures were cytotoxic against donor antigens. A significantly (P < 0.005) lower proportion of the cultures showed cytotoxicity (36 %) against HLA-A antigens when compared to HLA-B (53 %) or HLA-DR (49 %). A dose effect phenomenon was detected for all HLA antigens, including HLA-A: a higher number of A, B or DR mismatches resulted in a higher number of cytotoxic cultures directed against these antigens. B and DR matching had the greatest influence on 6 month freedom from rejection. Both our experimental and clinical data indicated that HLA matching played a role in the immune response against a transplanted heart.     

Fibromatosis of bone in children

Radiographs, computed tomograms, and radionuclide bone scans were obtained preoperatively in three children with fibromatosis involving the bones and soft tissues of the extremities. Two of the children had identical scar-like bone lesions of the proximal tibia, which, to the authors' knowledge, have not been reported before in this disease. The lesions recurred in two children.     

Donor-specific CTL frequencies in peripheral blood in relation to graft vascular disease after clinical heart transplantation

Abstract Cellular mechanisms may play a role in the development of graft vascular disease (GVD). We previously demonstrated that GVD correlated with an increase of donor-specific T-helper 1 cytokine production by graft-infiltrating lymphocytes but not by peripheral blood mononuclear cells (PBMC). These T-helper 1 cytokines aid the generation of cytotoxic T-lymphocytes (CTL). In the present report, we investigated whether there is a relationship between the frequency of donor-specific CTL precursors (pCTL) in PBMC and the development of GVD. We tested PBMC samples of five patients with GVD and five patients without GVD in the periods 3–6 months, 1 year, and 3 years after heart transplantation. At all time points, GVD was not related to the number of pCTL. In conclusion, donor-specific cellular tests in peripheral blood could not be related to GVD. Apparently, donor-specific reactions associated with the induction of GVD can only be monitored in the graft.