CMV Primary Infection Is Associated With Donor-Specific T Cell Hyporesponsiveness and Fewer Late Acute Rejections After Liver Transplantation.

Viral infections, including cytomegalovirus (CMV), abrogate transplantation tolerance in animal models. Whether this also occurs in humans remains elusive. We investigated how CMV affects T cells and rejection episodes after liver transplantation (LT). Phenotype and alloreactivity of peripheral and allograft-infiltrating T cells from LT patients with different CMV status were analyzed by flow cytometry. The association of CMV status with early and late acute rejection was retrospectively analyzed in a cohort of 639 LT patients. CMV-positivity was associated with expansion of peripheral effector memory T cell subsets after LT. Patients with CMV primary infection showed donor-specific CD8(+) T cell hyporesponsiveness. While terminally differentiated effector memory cells comprised the majority of peripheral donor-specific CD8(+) T cells in CMV primary infection patients, they were rarely present in liver allografts. Retrospective analysis showed that R(-) D(+) serostatus was an independent protective factor for late acute rejection by multivariate Cox regression analysis (hazard ratio [HR] = 0.18, 95% CI = 0.04-0.86, p = 0.015). Additionally, CMV primary infection patients showed the highest Vδ1/Vδ2 γδ T cell ratio, which has been shown to be associated with operational tolerance after LT. In conclusion, our data suggest that CMV primary infection may promote tolerance to liver allografts, and CMV status should be considered when tapering or withdrawing immunosuppression.

Patients treated with high-dose intravenous immunoglobulin show selective activation of regulatory T cells.

Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (Tregs ) in humans in vivo. Blood was collected from IVIg-treated patients with immunodeficiency or autoimmune disease who were treated with low-dose (n = 12) or high-dose (n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+)) Tregs and of conventional CD4(+) FoxP3(-) T-helper cells (Tconv) were measured. The suppressive capacity of Tregs purified from blood collected at the time-points indicated was determined in an ex-vivo assay. High-dose, but not low-dose, IVIg treatment enhanced the activation status of circulating Tregs , as shown by increased FoxP3 and human leucocyte antigen D-related (HLA-DR) expression, while numbers of circulating Tregs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified Tregs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of Tconv was not affected by IVIg. We conclude that high-dose IVIg treatment activates Tregs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders.

Refined characterization and reference values of the pediatric T- and B-cell compartments.

Work in the past years has led to a refined phenotypical description of functionally distinct T- and B-cell subsets. Since both lymphocyte compartments are established and undergo dramatic changes during childhood, redefined pediatric reference values of both compartments are needed. In a cohort of 145 healthy children, aged 0-18 years, the relative and absolute numbers of the various T- and B-cell subsets were determined. In addition, we found that besides thymic output, naive (CD27(+)CD45RO(-)) T-cell proliferation contributed significantly to the establishment of the naive T-cell compartment. At birth, regulatory (CD25(+)CD127(-)CD4(+)) T cells (Tregs) mainly had a naive (CD27(+)CD45RO(-)) phenotype whereas 'memory or effector-like' (CD45RO(+)) Tregs accumulated slowly during childhood. Besides the CD27(+)IgM(+)IgD(+) memory B-cell population, the recently identified CD27(-)IgG(+) and CD27(-)IgA(+) memory B-cell populations were already present at birth. These data provide reference values of the T- and B-cell compartments during childhood for studies of immunological disorders or immune reconstitution in children.

Participation in daily life of children with asthma.

Asthma can have a negative effect on psychological and social well-being in childhood. Sports participation, school attendance, and quality of life are important issues for children with asthma and their parents. However, a structural evaluation of these factors is not always incorporated in the routine medical approach of children with asthma. Moreover, goals in asthma treatment, such as minimal symptoms and normal activity levels, are achieved in a minority of children. This review describes determinants that are important for the well-being of children with asthma and their parents. Besides the control of symptoms, factors such as sports participation, socializing in peer groups, school attendance, and quality of life must be considered. These issues are relevant when evaluating the management of children and adolescents with asthma. A multidisciplinary evaluation by a pediatrician, school nurse, gym teacher, and psychologist might contribute to an important decrease in the impact of asthma on daily life.

Incidence and determinants of lower extremity running injuries in long distance runners: a systematic review.

The purpose of this study was to present a systematic overview of published reports on the incidence and associated potential risk factors of lower extremity running injuries in long distance runners. An electronic database search was conducted using the PubMed-Medline database. Two observers independently assessed the quality of the studies and a best evidence synthesis was used to summarise the results. The incidence of lower extremity running injuries ranged from 19.4% to 79.3%. The predominant site of these injuries was the knee. There was strong evidence that a long training distance per week in male runners and a history of previous injuries were risk factors for injuries, and that an increase in training distance per week was a protective factor for knee injuries.

[Diagnostic image (321). A girl with 'bruises' on her abdomen]. / Diagnose in beeld (321). Een meisje met 'blauwe' plekken op de buik. Erythema ab igne.

A 12-year-old girl presented with a reticular skin abnormality on her abdomen, which was caused by the frequent use of hot water bottles to relieve her chronic stomachache. This skin condition is called erythema ab igne.

Lung function abnormalities in children with type I diabetes.

Recent developments in intrabronchial administration of insulin raise lung function in patients with type I diabetes as important issue. Several studies in adults report abnormalities of lung function of these patients. The aim of this study was to investigate lung function in children with type I diabetes. Twenty-seven children with type I diabetes performed measurement of airway obstruction (forced flow-volume curves), lung volumes and airway resistance (bodyplethysmography) and of pulmonary carbon monoxide diffusion capacity Mean age (+/- SD) of the children was 12.8 +/- 5 years. Mean time between the detection of type I diabetes and the lung function tests was 5.5 years with a variation from I to 17 years. The total airway resistance (Raw) was significantly higher compared to the reference values (P < 0.001). The other lung function parameters were not significantly different from reference values (P > 0.05). In this relatively small study no relationship between lung function abnormalities and age, the duration of disease or level of HbA1c was observed. Our data show that increase of airway resistance do occur in children withtype I diabetes. Progressive abnormalities in lung function might interfere with the promising results of treatment with intrabronchial administration of insulin.

[Pseudotuberculosis in goats also in the Netherlands. A literature review]. / Pseudotuberculose bij de geit, ook in Nederland. Een literatuuroverzicht.

Pseudotuberculosis or caseous lymphadenitis in goats is marked by superficial abscesses and was recently observed in the Netherlands. The literature on this disease is reviewed, concerning the incidence, aetiology, pathogenesis, symptoms, diagnosis, therapy and preventive measures. The damage which the disease could cause to goat husbandry in the Netherlands, is discussed. Although the losses from death and diminished production will probably be small, treatment is time-consuming and requires much labour. The greatest damage will possibly consist in the fact that breeders will not be able to sell their animals when caseous lymphadenitis occurs in their herd. Particularly, the export of breeding stock could be menaced by this disease.

Value of an automatic external defibrillator printout as a diagnostic tool after successful AED use on a child.

A 6-year-old girl without any medical history experienced a drowning incident for a duration of 2 min, according to witnesses. This was followed by cardiopulmonary resuscitation, during which the automatic external defibrillator (AED) detected a shockable rhythm and subsequently delivered a single electroshock. At the time of admission, her medical history was unclear, and as her chest had been wet, it was not clear if the AED had been capable of correctly analysing the rhythm. The AED printout, however, revealed ventricular fibrillation (VF), which proved to be a primary cardiac cause at the time of the incident. This case report confirms the assumption that the AED can adequately perform rhythm analysis on children and convert VF into sinus rhythm. Moreover, the AED printout can provide information about the rhythm that is necessary for the diagnosis of an underlying cardiac disease.

Adherence to follow-up recommendations in asthma.

A cross-sectional study showed that 130 out of 1758 (8%) primary school children without a previous asthma diagnosis had undiagnosed asthma. Thirty-eight per cent of their parents refused to visit a general practitioner for this disorder. Factors associated with the refusal were high maternal education, mild symptoms and absence of airway reversibility.

Poor perception of dyspnoea in children with undiagnosed asthma.

The aim of the present study was to establish the differences in dyspnoea perception between children with undiagnosed and diagnosed asthma. A cross-sectional community-based study was performed, which included a parental questionnaire on the child's respiratory health and testing of airway reversibility and bronchial hyperresponsiveness (BHR). "Diagnosed asthma" was defined by a physician's diagnosis of asthma. "Undiagnosed asthma" was defined by the presence of asthma symptoms combined with either airway reversibility or BHR without a physician's diagnosis of asthma. Only children with a positive BHR test were selected for further analysis. Perception of dyspnoea was assessed using the Borg scale and the visual analogue scale (VAS), plotted against the percentage fall in forced expiratory volume in one second and expressed as the slope of the regression line. Of the initial 1,758 participating children, 70 had undiagnosed asthma and 38 had diagnosed asthma. The Borg and VAS slopes in children with undiagnosed asthma were less steep than those of children with diagnosed asthma (Borg: 0.07 and 0.14, respectively; VAS: 0.06 and 0.11, respectively). Among children with bronchial hyperresponsiveness, those without a parent's report of physician's diagnosis of asthma had a worse perception of dyspnoea than children with diagnosed asthma.

Exhaled nitric oxide and biomarkers in exhaled breath condensate indicate the presence, severity and control of childhood asthma.

BACKGROUND: Exhaled nitric oxide and inflammatory biomarkers in exhaled breath condensate may be useful to diagnose and monitor childhood asthma. Their ability to indicate an asthma diagnosis, and to assess asthma severity and control, is largely unknown. OBJECTIVE: To study (1) the ability of exhaled nitric oxide and inflammatory markers in exhaled breath condensate (nitrite, nitrate, hydrogen peroxide, 8-isoprostane, IFN-gamma, TNF-alpha, IL-2, -4, -5, -10 and acidity) to discriminate between childhood asthma and controls. (2) The ability of these biomarkers to indicate asthma severity and control. METHODS: One-hundred and fourteen children were included: 64 asthmatics (10.7+/-3.0 years, 67.2% atopic) and 50 controls (10.0+/-0.4 years). Condensate was collected using a glass condenser. RESULTS: Exhaled nitric oxide, IFN-gamma and IL-4 in exhaled breath condensate differed significantly between asthma and controls. Multivariate backward logistic regression models demonstrated that IL-4 (odds ratio 7.9, 95% confidence interval 1.2-51.0) was the only significant indicator of an asthma diagnosis. Asthma control was best assessed by exhaled nitric oxide, 8-isoprostane, IFN-gamma and IL-4 (sensitivity 82%, specificity 80%, P<0.05), whereas exhaled nitric oxide, 8-isoprostane, nitrate and nitrite in condensate were the best indicators of asthma severity (sensitivity 89%, specificity 72%, P<0.05). CONCLUSION: Different markers in condensate are of an additional value to exhaled nitric oxide, and are needed in non-invasive inflammometry. They could be useful to diagnose asthma and to indicate asthma control and severity in childhood.

The lens production by Christiaan and Constantijn Huygens.

Ever since they began to take an interest in lens grinding, the brothers Christiaan and Constantijn Huygens searched for high-quality glass to turn in to lenses. Historical research in combination with optical measurements on preserved lenses has allowed the verification of the lenses ground by the brothers, and also provided information on who helped them with the necessary knowledge and material.

DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis.

Respiratory insufficiency due to respiratory syncytial virus (RSV) bronchiolitis is partly due to the abundance of thickened mucus and the inability to clear it from the airways. Mucus in RSV bronchiolitis contains necrotic inflammatory and epithelial cells. The viscoelastic properties of purulent airway secretions are largely due to the presence of highly polymerized deoxyribonucleic acid (DNA). Recombinant human deoxyribonuclease (rhDNase) is known to liquefy such mucus in patients with cystic fibrosis, whereas case reports described a beneficial effect in other respiratory disorders. The authors hypothesized that rhDNase would diminish atelectasis and mucus plugging in infants with severe RSV bronchiolitis. Two infants with RSV bronchiolitis with massive unilateral atelectasis in whom mechanical ventilation was imminent due to exhaustion, and three mechanically ventilated infants (two neonates, one with bronchopulmonary dysplasia) with RSV bronchiolitis with pneumonia received treatment with 2.5 mg nebulized rhDNase twice daily. Following administration of nebulized recombinant human deoxyribonuclease, clinical and radiological parameters improved quickly. Mechanical ventilation could be avoided in two infants while in three infants on artificial ventilation, clinical recovery started following the first dose of the drug. A therapeutic trial of recombinant human deoxyribonuclease may be an option in the treatment for atelectasis in severe or complicated respiratory syncytial virus bronchiolitis in infancy.