Physical activity and health-related quality of life in chronic non-bacterial osteomyelitis.

Background: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of the skeletal system of yet unknown etiology. Patients present with local bone pain and inflammation and - to our experience - often suffer from functional impairment with significant disabilities of daily life. The objective of this study was to assess physical activity, fitness and health-related quality of life (HRQOL) in adolescents with established diagnosis of CNO versus healthy controls (HC).

Prenatal and family risks of children born to mothers with epilepsy: effects on cognitive development.

The offspring of mothers with epilepsy are considered to be at developmental risk during pregnancy from: (1) generalized maternal seizures (hypoxia); (2) teratogenicity of antiepileptic drugs (AEDs); and (3) adverse socio-familial conditions associated with having a chronically sick mother. Sixty-seven children of mothers with epilepsy and 49 children from non-affected mothers, matched for control variables, were followed from birth to adolescence (53 males, 63 females; mean age 14y 2mo, range 10-20y). Prediction of intellectual performance of these children during adolescence was calculated from the following variables: maternal generalized seizures, prenatal exposure to AEDs, and quality of family stimulation (HOME Inventory) assessed in children at 2 years of age.

Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: insights into the measurement of hepatic cytochrome P450 1A2 induction.

Objective: The correct in vivo quantification of aryl hydrocarbon receptor-mediated induction of cytochrome P450 1A2 (CYP1A2) in humans is a long-standing question. We compared the performance of several modifications of the caffeine test for measurement of CYP1A2 activity in subjects with exceptionally high, low, or absent enzyme induction.

Methods: CYP1A2 activity was measured in 2 women highly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in 1 man moderately exposed, and in 50 control subjects (30 nonsmokers and 20 heavy smokers).

Assessing lymphocyte functions in neonates for revealing abnormal prenatal development of the immune system.

Because it is difficult to assess prenatally induced functional deficits of the human immune system, we developed an ex vivo method for differentiation and maturation of peripheral lymphocytes of newborn, preferentially using umbilical cord blood. Many lymphocyte subsets of newborn infants are "immature" with respect to defined surface receptors. An example of such an immaturity is the almost complete lack of "memory"-type helper T cells (also designated as helper-inducer cells), characterized by expressing the surface receptors: CD4(+)CD45R0(+)CD45RA(-)CD29(high).

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system: 3. Plasma immunoglobulins and cytokines of workers with quantified moderately-increased body burdens.

The concentrations of immunoglobulins (IgA, IgD, IgG, IgM) and of several cytokines were measured in the plasma of volunteers with clearly, but moderately, increased body burdens of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), using monoclonal antibodies and an enzyme-linked immuno-sorbant assay. Two groups of workers with different body burdens of PCDD/PCDF were studied: (trial I) persons with mainly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and (trial II) persons with mainly penta- and hexachlorinated dibenzofurans (P5CDF/H6CDF) in their blood fat. Including the reference group, 158 volunteers were investigated.

Time course of PCDD/PCDF/PCB concentrations in breast-feeding mothers and their infants.

PCDD/PCDF/PCB concentrations were measured in samples from four mothers (at delivery and during lactation) and their infants (at birth and the end of first year of life). For two of these mothers it was the second delivery and breast-feeding period, and additional data were available from first lactation period and the first-born infant at the age of 11 to 12 months. Five of the six infants were fully breast-fed for at least 17 weeks.

Evaluation of the age-dependent development of lymphocyte surface receptors in children.

Components and functions of the immune system change during postnatal development, not only in the first years of life, but well through adolescence and even into adult life. These age-dependent changes within the immune system greatly complicate any attempt to assess pathological alterations of immunologic variables in children. The need for studies on possible substance-induced changes, including risk assessment of environmental chemicals, has increased the necessity to establish reference ranges for certain immunologic variables against which an abnormal developmental status can be evaluated.

Prevalence of Helicobacter pylori infection in Nicaraguan children with persistent diarrhea, diagnosed by the 13C-urea breath test.

Background: The impairment of gastric acid barrier caused by Helicobacter pylori (H. pylori) at the onset of infection may predispose to small bowel bacterial overgrowth, which could contribute to persistent diarrhea.

Methods: Using the 13C-urea breath test, we determined the prevalence of H.

Intake, fecal excretion, and body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans in breast-fed and formula-fed infants.

To assess toxicokinetics of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), oral intake and fecal excretion were measured in two breast-fed infants and one formula-fed infant during the 1st y of life. The intake of these compounds was up to 50 times higher in the breast-fed infants. In these children, fecal excretion of the main tetra- to hexachlorinated congeners was less than 9% of the intake at age of 1 and 5 mo, indicating almost complete intestinal absorption during breast-feeding.

Antiepileptic drug treatment in pregnancy: drug side effects in the neonate and neurological outcome.

Antiepileptic drugs taken by pregnant epileptic women are known human teratogens. They may also cause pharmacological side effects in the newborn, i.e.

Cross-reactivity of antihuman monoclonal antibodies with cell surface receptors in the common marmoset.

In this report we demonstrate that a large number of monoclonal antibodies (mAbs) against human epitopes cross-react with surface receptors on white blood cells of Callithrix jacchus, indicating species similarities. However, a variety of other mAbs do not exhibit any cross-reactivity, thus also providing evidence for distinct differences in the structure of these receptors among nonhuman primates. Such differences have to be known and taken into consideration when attempting extrapolations between species.

Proliferative capacity of marmoset lymphocytes after tetanus vaccination and lack of 2,3,7,8-tetrachlorodibenzo-p-dioxin to reduce a booster effect.

Marmosets (Callithrix jacchus) were vaccinated with tetanus toxoid and boostered 3 months and 1 year following the initial immunization. During this period, the proliferative response of lymphocytes (3H-thymidine incorporation) to the recall antigen was measured in vitro in blood samples 7 times. The experimental procedure proved to be suitable to monitor a defined but complex function of the immune system, and to assess possible substance-induced alterations with minimal stress or discomfort for the non-human primates.

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system. 2. In vitro proliferation of lymphocytes from workers with quantified moderately-increased body burdens.

Lymphocyte proliferation responses were studied in workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin and other polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/PCDFs, calculated as International Toxicity Equivalencies [I-TE]). Mitogens (pokeweed mitogen [PWM], phytohemagglutinine [PHA], concanavalin A [Con A]), as well as an anti-human monoclonal antibody against CD3 were used as proliferation stimulators in vitro. Additionally, the feasibility of using the lymphocyte response to tetanus toxoid was assessed, and the response to this recall-antigen was included in this trial.

Thalidomide and the immune system. 4. Down-regulation of the CD26 receptor, probably involved in the binding of HIV components to T cells in primates.

Thalidomide (Thd) is capable of down-regulating the CD26 receptor on CD4+ lymphocytes after treatment of healthy volunteers. Similar effects are observed when marmosets (Callithrix jacchus) are treated with Thd. The Ta1 epitope of the CD26 receptor has recently been shown to bind the HIV-1 Tat trans-activating protein, and CD26 has also been suggested to be a coreceptor for the binding of the V3 loop of the gp120 HIV envelope protein.

Intake and fecal excretion of PCDDs, PCDFs, HCB and PCBs (138, 153, 180) in a breast-fed and a formula-fed infant.

Intake and fecal excretion of PCDDs, PCDFs, HCB and PCBs (IUPAC Nos. 138, 153, 180) were measured in a breast-fed and a formula-fed infant at the age of 1 and 5 months. As expected, the intake of these compounds was clearly higher in the breast-fed infant.

The psychological development of children of epileptic parents. II. The differential impact of intrauterine exposure to anticonvulsant drugs and further influential factors.

After obtaining evidence that tetratogenic effects were operant in a sample of children born to epileptic mothers, we analyzed the effects of type of medication and further influential factors. Children with prenatal exposure to polytherapy had significantly lower scores than controls for a large number of psychological tests. In addition to polytherapy, there were even stronger effects of socioeconomic status and sex was found to be less influential than polytherapy.

The psychological development of children of epileptic parents. I. Study design and comparative findings.

We studied the genetic, neurobiological, teratogenic and psychosocial risks for the development of children born to epileptic parents in (a) children of epileptic mothers with intrauterine exposure to anticonvulsants, (b) children of epileptic mothers without intrauterine exposure to anticonvulsants and (c) children of epileptic fathers. In addition, three matched control groups were also considered. The longitudinal design of the study covered newborns to children of six years of age.

Dependence of the utilization of a phenylalanine-free amino acid mixture on different amounts of single dose ingested. A case report.

For patients with phenylketonuria the daily ingested phenylalanine-free amino acid mixture is the most important source of nitrogen. It is recommended to ingest one third of the total amount combined with main meals. Some patients, especially the older ones, do not follow this recommendation; they ingest the entire daily amount of amino acid mixture in one portion.

Risk assessment for possible effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related substances on components and functions of the immune system.

Numerous reports have been published on the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on components and functions of the immune system of animal species, almost exclusively of rodents. Many of the data, obtained with very different dosing schedules, are conflicting or have not been confirmed. Since the overwhelming majority of evaluations were performed with rodents, it is not possible to perform a reliable quantitative or even qualitative risk assessment for TCDD in man based on immunological data obtained from these experiments and to extrapolate them to the situation in humans.

Evaluation of possible effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and other congeners on lymphocyte receptors in Callithrix jacchus and man.

Using fluorescence-labeled monoclonal antibodies and flow cytometry (FACScan analysis) we measured surface receptors on peripheral lymphocytes in marmosets (Callithrix jacchus) treated with TCDD in the lower nanogram per kilogram range. Additionally, some polybrominated congeners were studied as well as a 2,3,7,8-substituted dioxin containing chlorine and bromine in the same molecule. Callithrix was found to be very sensitive to the action of TCDD and the other tetrahalogenated congeners; single doses of 10-30 ng/kg body weight reproducibly induced a decrease in the percentage and absolute number of 'memory' helper T cells [CD4+CD29(bright)] and of B cells (CD20+).

Thalidomide and the immune system. 3. Simultaneous up- and down-regulation of different integrin receptors on human white blood cells.

Time-dependent changes in the surface receptor expression of various maturational and integrin receptors on peripheral blood cells were studied in two healthy human volunteers following oral applications of thalidomide (Thd). In each measurement the receptor density was quantified by prior calibration of the flow cytometer with latex beads bearing a determined number of fluorescence molecules. The effects observed in the course of the Thd-treatment were practically identical or at least very similar in both the volunteers during four different trials, and were in accord with previous results obtained in large-scale studies (68 treated animals) with non-human primates.

Effects of small doses of dioxins on the immune system of marmosets and rats.

There is no doubt that TCDD is capable of inducing effects on a variety of components and functions of the immune system in a variety of species. In fact, such changes seem to belong to the most sensitive variables affected by TCDD. Some of the biological effects, induced at rather high doses of TCDD exhibiting general toxicity (> 3 micrograms TCDD/kg body wt), may be considered unspecific or the result of the pronounced thymus involution.

Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system. 1. Blood cell receptors in volunteers with moderately increased body burdens.

Using monoclonal antibodies (mAbs) and flow cytometry, we studied a variety of surface receptors on lymphocyte subpopulations of workers with moderately increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of other polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), expressed here as International-Toxicity Equivalencies (I-TE). The hypothesis to be tested was whether or not humans exhibit a similar susceptibility to PCDDs/PCDFs with respect to the surface receptors found previously to respond to small doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Callithrix jacchus. These are: helper-inducer (memory) T cells (CD4+CD45R0+CD45RA-CD29highCD11a+), CD20+ B cells, and cytotoxic T cells (CD8+CD56+/CD57+).

Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin.

Omeprazole has been shown to induce cytochrome P450IA1 and P450IA2 activity in vitro. To reflect cytochrome P450IA2 (CYP1A2) activity in vivo, the 13C-[N-3-methyl]-caffeine breath test was conducted in 18 volunteers: 12 extensive metabolizers, one intermediate metabolizer, and five poor metabolizers of S-mephenytoin. Breath tests were performed before treatment with an oral dose of 40 mg omeprazole, on the seventh day of treatment, and after a 7-day washout period.