Adenosine bronchial provocation with computerized wheeze detection in young infants with prolonged cough: correlation with long-term follow-up

BACKGROUND: Chronic cough in babies is often associated with bronchial hyperreactivity (BHR). The objective documentation of BHR in babies is difficult, and acoustic methods have been described (provocative concentration of a substance causing wheeze) for conducting bronchial provocation tests (BPTs). We conducted a study to evaluate automatic computerized wheeze detection (CWD) in determining BHR in young infants with prolonged cough, and its correlation with the subsequent development of wheezing. METHODS: Infants aged < 24 months with prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response determined by CWD and auscultation by a physician. Telephone interviews with parents were conducted after 1 month and yearly for the next 3 years. RESULTS: A total of 28 infants who were 4 to 24 months old with prolonged cough were included in the study. Twenty of these infants (71.4%) had BHR as determined by a positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier, and in 9 tests it occurred at the same step as auscultation by a physician. Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing and shortness of breath, and 3 were well. Six of the eight adenosine-negative patients completed 3 years of follow-up and had no symptoms of BHR. CONCLUSIONS: Acoustic BPT is a technically feasible test for the detection of BHR in young infants. CWD provides an earlier detection of wheeze than stethoscope auscultation. In our group of infants, a positive acoustic BPT result had high correlation with symptoms compatible with BHR over the next 3 years.     

Thrombophilic polymorphisms in Israel

Three thrombophilic polymorphisms, FV G1691A, FII G20210A and MTHFR C677T were investigated in Israeli populations by FRET, (fluorescence resonance energy transfer) real-time PCR. We observe extensive variability in the frequencies of each of the polymorphisms, as has been observed in the study of other polymorphisms in these populations. Very high allele frequencies for FV G1691A (the highest 0.087 in Turkish and Greek Jews) and FII G20210A (the highest 0.061 in Georgian Jews) in some of the Israeli populations justify a clinical investigation to assess their risk for venous thrombosis. Principal Coordinates Analysis demonstrates that the Jewish populations are interspersed among the non-Jewish populations. The resemblance of some Jewish populations to certain non-Jewish populations coincides with findings based on classical markers.     

Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia

We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo‐optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β‐catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development.     

Plasma homocysteine, methylenetetrahydrofolate reductase genotypes, and age at onset of symptoms of myocardial ischemia

Elevated fasting plasma homocysteine is a graded risk factor of coronary artery disease (CAD) and may accelerate onset of CAD. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is commonly but inconsistently associated with hyperhomocysteinemia. In the present study we examined the possible relation between levels of fasting plasma homocysteine and age at CAD onset in different MTHFR genotypes. We studied 182 patients with CAD, 74 patients with early onset CAD (aged < or = 45 years), and 108 patients with later onset CAD (aged 46 to 65 years). Plasma homocysteine levels in 90 subjects without CAD were used for control. Fasting plasma homocysteine levels in T/T homozygotes with early onset CAD (20.2 +/-12.5 micromol/L) was markedly higher than in T/T homozygotes with later onset CAD (13.4 +/- 6.8 micromol/L) and in patients with early onset CAD who were not T/T homozygotes (11.9 +/- 3.7 micromol/L; p = 0.034 and p = 0.0001, respectively). CAD developed earlier in T/T homozygotes who were hyperhomocysteinemic (>15 micromol/L) than in the T/T homozygotes who were not (p = 0.036). Plasma homocysteine levels had no effect on age at onset of CAD in patients who were non-T/T genotypes. Homocysteine levels in control subjects and in patients who were non-T/T genotypes were comparable and were not influenced by age. The results reveal an inverse relation between the level of fasting plasma homocysteine and age at onset of CAD in T/T homozygotes as opposed to no association in patients who were non-T/T genotypes. Additionally, these results show that hyperhomocysteinemia and the T/T genotype have a stronger effect on the pathogenesis of CAD when they are combined, and that a marked increase (>15 micromol/L) in fasting plasma homocysteine in T/T homozygotes is a risk factor for early onset of CAD.     

Impaired T-lymphocyte function in B-chronic lymphocytic leukaemia as measured by the local xenogeneic graft-versus-host reaction

The immunological dysfunction observed in B-chronic lymphocytic leukaemia (B-CLL) is often related to T-lymphocyte incompetence. The local xenogeneic graft-vs.-host reaction (XGVHR), an assay to evaluate T-lymphocyte function, was performed in 112 untreated B-CLL patients. The XGVHR results significantly correlated with clinical parameters: 37.1% of the patients in the stable phase (Rai stage 0–1–2) and only 13.3% of the patients in the progressive phase (Rai stage 3–4) had positive XGVHR results. Patients with negative results had a higher number and percentage of lymphocytes (25 247 vs. 17 071/μl and 75.9% vs. 65.6%, respectively), much lower T/B lymphocyte ratio (0.37 vs. 0.93), higher WBC count (30 977 vs. 23 458/μl), lower platelet count (158 068 vs. 181 684/μl) and lower levels of IgA and IgM (115.6 vs. 200.5 mg/dl and 80.4 vs. 124.3 mg/dl, respectively) compared to those with positive results. Among those with negative XGVHR results, a higher mortality rate was found in those who had infections compared with those who did not (73.7% vs. 9.1%). In conclusion, the XGVHR assay significantly correlates with important characteristics of B-CLL and may be useful in the clinical evaluation of B-CLL patients.     

Self-reported symptoms in healthy young adults to predict potential coronavirus disease 2019

ObjectiveTo assess the utility of self-reported symptoms in identifying positive coronavirus disease 2019 (COVID-19) cases among predominantly healthy young adults in a military setting.MethodsA questionnaire regarding COVID-19 symptoms and exposure history was administered to all individuals contacting the Israeli Defence Forces Corona call-centre, before PCR testing. Surveyed symptoms included cough, fever, sore throat, rhinorrhoea, loss of taste or smell, chest pain and gastrointestinal symptoms. Factors were compared between positive and negative cases based on confirmatory test results, and positive likelihood ratios (LR) were calculated. Results were stratified by sex, body mass index, previous medical history and dates of questioning, and a multivariable analysis for association with positive test was conducted.ResultsOf 24 362 respondents, 59.1% were men with a median age of 20.5 years (interquartile range 19.6–22.4 years). Significant positive LRs were associated with loss of taste or smell (LR 3.38, 95% CI 3.01–3.79), suspected exposure (LR 1.33, 95% CI 1.28–1.39) and fever (LR 1.26, 95% CI 1.17–1.36). Those factors were also associated with positive PCR result in a multivariable analysis (OR 3.51, 95% CI 3.04–4.06; OR 1.86, 95% CI 1.65–2.09; and OR 1.34, 95% CI 1.19–1.51, respectively). Reports of loss of taste or smell increased gradually over time and were significantly more frequent during the late period of the study (63/5231, 1.21%; 156/7941, 1.96%; and 1505/11 190, 13.45%: p < 0.001).ConclusionLoss of taste or smell, report of a suspicious exposure and fever (>37.5°C) were consistently associated with positive LRs for a positive SARS-CoV-2 PCR test result, in a population of predominantly young and healthy adults.     

Use of Cone-beam Computed Tomography as a Critical Component in the Diagnosis of an Infected Nasopalatine Duct Cyst Mimicking Chronic Apical Abscess: A Case Report

Nasopalatine duct cysts (NPDCs) and other nonodontogenic lesions of the oral cavity may mimic odontogenic pathoses. We present a case of a 22-year-old man with a history of dental trauma and a lesion displaying the typical clinical and radiographic signs of a chronic apical abscess— a buccal sinus tract that was traced to a radiolucent area in the periapex of a maxillary central incisor. A comprehensive diagnostic process that included a cone-beam computed tomographic scan and a histopathologic examination of the lesion after complete enucleation led to the final diagnosis of an infected NPDC. The adjacent tooth was vital at the 1-year posttreatment follow-up, and a radiograph demonstrated complete healing of the periradicular structures. This case demonstrates the ability of NPDCs to present clinical and radiographic signs similar to apical inflammatory lesions and the need for a meticulous diagnostic process in order to avoid unnecessary endodontic intervention. The article also discusses the differential diagnoses of nonodontogenic lesions in the premaxillary area.