ABSTRACT
Subject(s)
Latent Tuberculosis/epidemiology , Schools , Adolescent , Age Distribution , Child , Cohort Studies , Female , Humans , Latent Tuberculosis/diagnosis , Latent Tuberculosis/transmission , Male , Prevalence , Socioeconomic Factors , South Africa/epidemiology , Young AdultABSTRACT
The carnitine ester spectrum was studied using ESI tandem mass spectrometry in a 2.5-year-old male Roma child with homozygous deletion of 844C of the SLC22A5 gene, presenting with hepatopathy and cardiomyopathy. Besides the dramatic decrease of plasma free carnitine (1.38 vs 32.7 mumol/L in controls) all plasma carnitine esters were severely decreased in the proband: the total esters were 31.4% of the controls. In three heterozygous siblings the free carnitine level was 62.3% of the normal controls, while the levels of the individual carnitine esters ranged between 15.5% and 163% (average 70.9%). The heterozygous parents exhibited the same pattern. The proband was supplemented with 50 mg/kg per day of L-carnitine oral solution. After 2 months of treatment, his hepatomegaly, elevated transaminases and the pathological cardiac ultrasound parameters normalized. The plasma free carnitine rose to 12.8 mumol/L (39% of the controls). All of the carnitine esters also increased; however, the individual esters were still 8.5-169.7% of the controls (average 55.5%). After 13 months of treatment there was a further increase in free carnitine (15.9 mumol/L) as well as in the level of the individual esters, ranging between 16.1% and 140.3% of the controls (average 66.9%). The data presented here show that, besides the dramatic decrease of free carnitine, the carnitine ester metabolism is also affected in OCTN2 deficiency; the replenishment of the pools under treatment is slow. Despite an impressive clinical improvement, the carnitine metabolism can be still seriously affected.
Subject(s)
Carnitine/blood , Metabolism, Inborn Errors/enzymology , Metabolism, Inborn Errors/genetics , Organic Cation Transport Proteins/deficiency , Organic Cation Transport Proteins/genetics , Adult , Carnitine/administration & dosage , Carnitine/deficiency , Case-Control Studies , Child, Preschool , Consanguinity , Frameshift Mutation , Genetic Carrier Screening , Homozygote , Humans , Male , Metabolism, Inborn Errors/blood , Metabolism, Inborn Errors/drug therapy , Solute Carrier Family 22 Member 5 , Spectrometry, Mass, Electrospray IonizationABSTRACT
BACKGROUND: The conventional coeliac disease antibody tests require patient's sera, and are laborious and time-consuming. AIM: To evaluate a newly developed rapid whole blood test in coeliac disease antibody detection, and its suitability for office use. METHODS: Endogenous tissue transglutaminase found in red blood cells in a whole blood fingertip or venous sample is liberated upon haemolysis and complexes with tissue transglutaminase antibodies, if present. The complexes, captured by a lateral flow system, are visualized within 5 min. Stored samples from 121 untreated, 106 treated coeliac disease patients and 107 controls were evaluated and compared with serum endomysium and tissue transglutaminase antibody tests and histology; 150 patients were prospectively tested on site in the doctor's office. RESULTS: The rapid test showed sensitivity (96.7%) comparable with the serum endomysium and tissue transglutaminase antibody tests from stored samples; specificity was slightly lower (93.5%). When tested on site the results were concordant in 96.7% of cases compared with endomysium and tissue transglutaminase antibody results. The test recognized the disappearance of tissue transglutaminase antibodies on a gluten-free diet. CONCLUSIONS: The self tissue transglutaminase-based rapid test can be easily carried out from a fingertip blood sample on site in the physician's office for both coeliac disease case finding and dietary monitoring purposes.
Subject(s)
Antibodies/blood , Celiac Disease/diagnosis , Point-of-Care Systems/standards , Transglutaminases/blood , Adolescent , Child , Female , Humans , Immunologic Tests/methods , Immunologic Tests/standards , Male , Self Care/standards , Transglutaminases/immunologyABSTRACT
OBJECTIVE: to investigate the early immunological effects of Pneumococcus vaccination in SLE patients and healthy controls. METHODS: First-four-week follow-up of 18 patients and 9 healthy controls by repeated measurements of anti-nuclear antibodies, anti-dsDNA, C-reactive protein, complement factor 3 (C3) and 4 (C4), total IgG, IgA and IgM. Specific antibody response, percentage of blood lymphocyte populations and whole blood chemiluminescence measurements were carried out in six patients and six controls. RESULTS: No disease flare was detected in the vaccinated patients. all side effects were mild. The concentrations of serum IgG, IgA, C3 and C4 decreased significantly, but still remained within the normal range. The other changes were statistically non-significant. The specific antibody responses to 6B and 23F Pneumococcus serotypes showed striking individual differences. CONCLUSION: There was no short-term immunological effect of Pneumococcus vaccination in the patients with SLE. The non-responders. without any sign of disease activation should possibly be given more immunogenic, new vaccines to avoid life-threatening Pneumococcus infections.
Subject(s)
Lupus Erythematosus, Systemic/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/adverse effects , Adult , Aged , Autoimmunity/immunology , Cohort Studies , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Luminescent Measurements , Lymphocyte Subsets , Male , Middle Aged , Phagocytosis/immunologyABSTRACT
Previous studies from our laboratory have shown that i.v. Ig (IVIG) exposure triggers superoxide anion (O2) generation by and increases bactericidal capacity of human blood granulocytes. However, the molecular interactions between IVIG and granulocytes have not been evaluated before. The objective of this study was to investigate the role of FcgammaRII and FcgammaRIII receptors in the immunomodulatory effects of IVIG concentrates on granulocytes. We found that four different IVIG preparations (concentration range, 1-10 mg/mL) shared the ability to stimulate O2- release in vitro by granulocytes in a dose-dependent manner. Dimers fractionated from IVIG were significantly more potent in inducing activity of the respiratory burst than were monomers. MAb (concentration range, 0.1-10 microg/mL) specific for FcgammaRII and FcgammaRIII receptors inhibited the IVIG-induced O2- release, with a more profound inhibitory effect observed with anti-FcgammaRIII. These findings suggest the involvement of Fcgamma receptors in triggering O2- release by granulocytes exposed to IVIG. We also report that IVIG added to granulocyte suspensions elicited a rapid and vigorous increase in the concentration of cytosolic free calcium, a finding suggesting direct activation and not priming of granulocytes by IVIG through FcgammaRII and FcgammaRIII receptors. The in vitro effects described here might occur in patients treated with IVIG and may, in part, be responsible for inflammatory reactions evoked by infused Ig concentrates as well as the immunomodulatory effect of Ig in patients with autoimmune and inflammatory diseases.
Subject(s)
Granulocytes/immunology , Receptors, IgG/immunology , Antibodies, Monoclonal/immunology , Calcium/metabolism , Granulocytes/metabolism , Humans , Immunoglobulins, Intravenous/administration & dosage , Lymphocyte Activation , Signal TransductionABSTRACT
Phagocytic and killing capacities of resident and cytokine-activated human macrophages against group B Streptococcus (GBS) type III were studied. Evidence is presented that monocyte-derived macrophages from cord and adults ingest serum-opsonized GBS but that killing of bacteria was negligible in resident cells. Treatment of adult macrophages with recombinant human gamma interferon (rhIFN-gamma; 100 U/ml) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 200 U/ml) resulted in significant increases of killing of GBS (P < 0.01 for each). The killing capacity of cord macrophages treated with rhGM-CSF was also enhanced compared to that of untreated cells (P < 0.01). However, treatment with rhIFN-gamma resulted in only a moderate increase in the capacity of cord macrophages to kill GBS (P > 0.1). These results mirrored the effect of rhIFN-gamma on candidacidal capacities of cord and adult macrophages, reported earlier from our laboratory. These data indicate differential modulation of neonatal macrophages by rhGM-CSF and rhIFN-gamma. We suggest that administration of rhGM-CSF to neonates with invasive GBS disease may enhance host resistance to these bacteria.
Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Interferon-gamma/pharmacology , Macrophages/microbiology , Phagocytes/microbiology , Recombinant Proteins/pharmacology , Streptococcus agalactiae/physiology , Umbilical Cord/microbiology , Adult , Granulocytes/microbiology , Humans , Infant, Newborn , Leukocytes, Mononuclear/microbiology , Opsonin Proteins/metabolism , Phagocytosis/drug effects , Streptococcus agalactiae/drug effects , Time FactorsABSTRACT
The role of salivary immunoglobulins (IgA, IgM, IgG) in caries etiology is not yet clearly known. Our aim was to study whether there might be a connection between the amount of immunoglobulins in the saliva and caries prevalence. It was found that there was a significant difference (p < 0.05 or less) in secretory IgA, IgM, IgG levels, as well as DMF-T, DMF-S (approx) indices between selective IgA deficient, hypogammaglobulinemic, and healthy children, who had primary teeth.
Subject(s)
Dental Caries/immunology , Saliva/immunology , Adolescent , B-Lymphocytes/immunology , Child , Child, Preschool , DMF Index , Dental Caries/epidemiology , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Immunologic Deficiency Syndromes , Male , PrevalenceABSTRACT
An ABO-incompatible term infant girl born to parents who are Jehovah's Witnesses was admitted to our neonatal unit with a high serum bilirubin level necessitating exchange transfusion. The parents signed a request that blood should not be administered under any circumstances. However, they authorized us to apply the possible alternative treatments of orally administered D-penicillamine (300 mg/kg per day divided in three doses for 3 days), phototherapy, intravenous fluids, and recombinant human erythropoietin (200 U/kg subcutaneously on every second day for 2 weeks). Herein, we report the outcome of this baby, who was discharged from the our unit in good condition after treatment. Her physical growth and motor milestones at 14 months of age revealed no red flags for neurodevelopmental maturation. To our knowledge, this is the first case of an infant who received such a combined alternative (and "bloodless") treatment of serious ABO hemolytic disease of the newborn.
Subject(s)
ABO Blood-Group System , Christianity , Erythroblastosis, Fetal/blood , Erythroblastosis, Fetal/therapy , Erythropoietin/therapeutic use , Female , Fluid Therapy , Humans , Infant, Newborn , Penicillamine/therapeutic use , Phototherapy , Recombinant Proteins/therapeutic use , Treatment OutcomeABSTRACT
Of 15 live births in one Hungarian village in 1989-90, 11 (73%) were affected by congenital abnormalities and 6 were twins. Of the 11, 4 had Down syndrome. Likely causes of such clusters (known teratogenic factors, familial inheritance, consanguinity) were excluded. A case-control study and environmental investigations pointed the finger of suspicion at the excessive use of trichlorfon at local fish farms. The content of this chemical was very high in fish (100 mg/kg) and several pregnant women, including all mothers of babies with Down syndrome, had consumed contaminated fish in the critical period for the congenital abnormalities observed.