Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients’ fibroblast phenotypes are rescued with WT IFNAR1. Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.

Background Inborn errors of interferon-gamma (IFN-γ) –mediated immunity underlie disseminated disease caused by Mycobacterium bovis Bacillus Calmette-Guérin (BCG) live vaccines. We hypothesized that some patients with osteitis after BCG vaccination may have an impaired IFN-γ immunity. Our aim was to investigate IL-12 and IFN-γ ex-vivo production stimulated with BCG and BCG+IFN-γ or BCG+IL-12, respectively, in BCG osteitis survivors. Methods Fresh blood samples were collected from 132 former BCG osteitis Finnish patients now aged 21-49 years, and IL-12 and IFN-γ were measured in cell cultures with and without stimulation with BCG and with BCG+IFN-γ or BCG+IL-12, respectively. As a pilot study, known disease-causing genes controlling IFN-γ immunity (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, IRF8, NEMO and CYBB) were investigated in 20 selected patients by whole-exome -sequencing. Results By the limit of <5th percentile, ex-vivo IL-12 concentration and increase in concentration was low in five, and ex-vivo IFN-γ concentration and increase in concentration was low in six patients (including two samples with both IL-12 and IFN-γ findings). By the limit of <10th percentile, an additional six and four patients were respectively detected (including two samples with both findings). With two exceptions, low concentrations and low increases in concentrations picked-up the same cases. Mutations in known disease-causing IFN-γ-related genes were not found in any of these patients. Conclusion These findings call for searching of mutations in new genes governing IFN-γ-dependent immunity to live BCG vaccine.

Live-attenuated vaccines (LAVs) can protect humans against 12 viral and three bacterial diseases. By definition, any clinical infection caused by a LAV that is sufficiently severe to require medical intervention attests to an inherited or acquired immunodeficiency that must be diagnosed or identified. Self-healing infections can also result from milder forms of immunodeficiency. We review here the inherited forms of immunodeficiency underlying severe infections of LAVs. Inborn errors of immunity (IEIs) underlying bacille Calmette-Guérin (BCG), oral poliovirus (OPV), vaccine measles virus (vMeV), and oral rotavirus vaccine (ORV) disease have been described from 1951, 1963, 1966, and 2009 onward, respectively. For each of these four LAVs, the underlying IEIs show immunological homogeneity despite genetic heterogeneity. Specifically, BCG disease is due to inborn errors of IFN-γ immunity, OPV disease to inborn errors of B cell immunity, vMeV disease to inborn errors of IFN-α/β and IFN-λ immunity, and ORV disease to adaptive immunity. Severe reactions to the other 11 LAVs have been described yet remain Bidiopathic,^in the absence of known underlying inherited or acquired immunodeficiencies, and are warranted to be the focus of research efforts. The study of IEIs underlying life-threatening LAV infections is clinically important for the affected patients and their families, as well as immunologically, for the study of the molecular and cellular basis of host defense against both attenuated and parental pathogens.

SUMMARY Serum concentrations of C-reactive protein were studied in 23 patients with acute myocardial infarction. In 14 patients who did not receive thrombolytic treatment there was a linear relation between infarct size (determined by serial creatine kinase-MB determinations and thallium-201 isotope emission tomography) and the C-reactive protein response. The correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0-96. The correlation coefficient between the creatine kinase-MB concentration-time integral and the peak serum value of C-reactive protein was 0 93. In the nine patients who received intravenous streptokinase treatment there was also a positive correlation between the concentration-time integrals of creatine kinase-MB and C-reactive protein. The activity of serum creatine kinase-MB,7 but the correlation of C-reactive protein with infarct size has as yet been little studied. We found that serum Creactive protein may not rise in certain non-Q wave infarcts.8 Most non-Q wave infarcts result from an acute temporary imbalance between myocardial oxygen supply and demand with rapid restoration of adequate perfusion.9 Rapid perfusion of an infarcted myocardium could diminish the stimulus for Creactive protein synthesis in the liver by altering the development of the infarction. If this is the case, successful thrombolytic treatment of an acute myocardial infarct should have a similar effect.We studied serum concentrations of C-reactive protein in both streptokinase and non-streptokinase treated patients with acute myocardial infarction..25 on 12 May 2018 by guest. Protected by copyright.

Gene polymorphisms that regulate the function of the TLR2 subfamily play a role in the development of BCG osteitis in vaccinated infants.

1 The efficacy and safety of doxazosin and atenolol were compared following once-daily administration for up to 1 year, with a minimum of 20 weeks' active treatment. 2 According to response, patients received doxazosin 1-16 mg day-I or atenolol 50-100 mg day-1. Mean daily doses at the final efficacy assessment (between 20 weeks and 1 year) were doxazosin 11.8 mg and atenolol 94.2 mg. 3 Atenolol produced somewhat greater falls in blood pressure than doxazosin. The differences were statistically significant in the supine but not in the standing position. A small mean reduction in heart rate was produced by doxazosin whereas atenolol produced a marked bradycardia. Analysis of the same patient group at 20 weeks revealed similar overall profiles of activity except that atenolol produced greater falls in blood pressure than in the longer term analysis. 4 Serum concentrations of HDL/total cholesterol ratio were raised in the doxazosin treatment group and lowered in the atenolol group. Triglyceride concentrations fell in the doxazosin group and rose in the atenolol group. Significant differences (P < 0.001) were observed between treatment groups for these parameters, all differences being in favour of doxazosin. 5 Pharmacokinetics of doxazosin, measured at steady state in 36 patients, showed dose-related plasma concentrations, a mean half-life of about 12 h and relatively low intersubject variation. 6 The incidence of side-effects was slightly greater for patients in the doxazosin group. Drugrelated side-effects were mostly mild to moderate in severity with no serious drug-related occurrences in either treatment group. 7 No serious drug-related abnormalities in laboratory biochemistry and haematology tests were observed in either treatment group.

No abstract

In this study, tomographic 201Tl washout analysis and coronary angiography were compared in 100 subjects. Seventeen subjects with healthy coronary arteries were used as reference material, on the basis of which the reference ranges for both the total washout of the heart muscle and the regional washout were determined. With angiography as the standard, this material yielded the following sensitivity values for total myocardial washout: 80% for three vessel proximal disease (n = 30), 64% for peripheral three vessel disease (n = 14), 66% for two vessel disease (n = 29) and 71% for single vessel disease (n = 17). Specificity in the reference group was 94%. Sensitivity values for regional washout were 83%, 93%, 59% and 71%, respectively. Stress ECG gave about 10% lower sensitivities. As far as sensitivity is concerned, however, visual assessment of tomographic images proved to be the best single method. In three patients, washout analysis was necessary to reveal evenly distributed ischemia and in seven cases it was essential in order to confirm an uncertain diagnosis; in other words, washout analysis had diagnostic value in 10 of the 100 patients.