Teenage asthma after severe early childhood wheezing: an 11-year prospective follow-up

The role of factors related to early wheezing and their associations with subsequent development of asthma are controversial. We reevaluated 81 children who had been prospectively followed up since hospitalization for wheezing at less than 2 years of age. The baseline data on characteristics of the children, family-related factors, and viral causes of wheezing were collected on entry into the study. At the median age of 12.3 years, current symptoms suggestive of asthma and allergy were recorded. As part of the clinical examination, an outdoor exercise challenge test and skin prick tests to common inhalant allergens were performed. Asthma, as indicated by current inhaled anti-inflammatory medication or repeated wheezing and positive result in the challenge test, was present in 32 (40%) children, and 90% of them were sensitized to at least one allergen. Early asthma-predictive factors were atopic dermatitis (odds ratio (OR), 3.5; 95% confidence interval (CI), 1.2-10.1) and the presence of specific IgE to inhalant allergens (OR, 11.3; 95% CI, 1.9-67.6). Respiratory syncytial virus (RSV) identification during wheezing in infancy was relatively rare (20%) among later asthmatics compared with other or no viral identification (52%) or rhinovirus identification (58%). Since the prevalence of childhood asthma in our area is 4.0-5.0%, we conclude that the increased risk of asthma persists until the teenage years after hospitalization for wheezing in infancy. The risk was about 5-fold after respiratory syncytial virus-induced wheezing, and more than 10-fold after rhinovirus-induced wheezing in the present study.     

Nifedipine for Suspected Type II Sphincter of Oddi Dyskinesia

Endoscopic sphincterotomy may be the treatment of choice in type I sphincter of Oddi dyskinesia, but in type II dyskinesia the results are controversial, the complication rate may be high, and technically endoscopic sphincterotomy is not always possible. Nifedipine has been observed to relax the sphincter of Oddi and to enhance biliary drainage, especially in patients suffering from sphincter of Oddi dyskinesia. Therefore, nifedipine (10 mg, three times a day) was compared with placebo in treating suspected type II sphincter of Oddi dyskinesia in 13 cholecystectomized patients in a 16-wk study period in a double-blind "cross-over" manner. Daily, the patients completed a diary of the pains, need of pain medication, and headache. Clinical examinations and blood tests for liver chemistry were performed at 4-wk intervals. Nifedipine diminished the number of days on which the patients experienced biliary-type pains (10.5 ± 8.6 vs. 5.8 ± 4.1, p = 0.042), and the number of days when pain medication was needed was slightly reduced (5.2 ± 3.9 vs. 3.6 ± 3.2, p = 0.066). After the study, one patient preferred to undergo endoscopic sphincterotomy, eight patients preferred to continue with nifedipine, and four patients preferred analgesics only. Liver chemistry remained unchanged in this study. Also heart rate, blood pressure, and the number of days of headache were not different between the nifedipine and placebo periods. We conclude that nifedipine is well tolerated in patients with type II sphincter of Oddi dyskinesia, and nifedipine may be tried for reducing the number of painful days and need for analgesics in patients with this disorder.     

A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen

A unique characteristic of the hepatitis B virus is the production of a secreted form (precore or HBeAg) of the structural nucleocapsid (core or HBcAg). By using T cell receptor (TCR) transgenic (Tg) and TCR x HBc/HBeAg double- and triple-Tg pairs, we demonstrate that HBeAg elicits T cell tolerance, whereas HBcAg is nontolerogenic in this system. In fact, TCR x HBc double-Tg mice spontaneously seroconvert to IgG anti-HBc positivity at an early age. However, the presence of HBeAg in the serum of TCR x HBc x HBe triple-Tg mice prevents anti-HBc seroconversion. HBeAg mediates its immunoregulatory effect by eliciting tolerance in HBc/HBeAg-specific T cells. The results suggest that hepadnaviruses have retained a secretory form of the nucleoprotein because it functions as a T cell tolerogen and regulates the immune response to the intracellular nucleocapsid. This HBeAg-mediated immune regulation may predispose to chronicity during perinatal infections and prevent severe liver injury during adult infections.     

NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic Jews with Crohn's disease

OBJECTIVE: NOD2/CARD15 has been identified as a major susceptibility gene for Crohn's disease (CD). Three mutations, Arg702Trp, Gly908Arg, and Leu1007fsinsC, are associated with CD. The incidence and prevalence rate of inflammatory bowel diseases is two- to four-fold higher in Ashkenazi Jews as compared to non-Jewish Caucasians. The aim of this study was to determine the significance of the NOD2/CARD15 mutations in Jewish CD patients in Israel, and more specifically, to compare the significance of the mutations to the expression of CD in the Ashkenazi and Sephardic Jewish populations. METHODS: Allele frequencies of the mutations were determined in 180 Jewish CD patients, 73 ulcerative colitis patients, and 159 ethnically matched controls. Variants were detected using allele-specific PCR and restriction enzyme digestion assay. Demographic and phenotypic characterizations of the CD patients were determined. RESULTS: The carrier rate of the three mutations in the entire Jewish Israeli CD cohort is 41.1% versus 10.7% in controls (p < 0.0001). The Ashkenazi Jewish CD patients have an increased carrier rate compared to Sephardic Jews (47.4%vs 27.45%, p= 0.034). Association analyses in Ashkenazi Jews reveal odds ratios of 10.5, 9, and 4.8 for carriage of Gly908Arg, Arg702Trp, and Leu1007fsinsC mutations, respectively. Significantly higher rates of smoking, family history of inflammatory bowel diseases, and extraintestinal manifestations were found among the Sephardic CD patients. CONCLUSIONS: NOD2/CARD15 CD-associated mutations confer increased risk mainly to the Ashkenazi Jewish CD patients in Israel. This suggests that NOD2/CARD15 mutations could contribute to the higher incidence and prevalence rates of CD among Ashkenazi Jews.     

How do tutors intervene when conflicts on knowledge arise in tutorial groups?

Recent research on problem-based learning (PBL) has shown that students need support when dealing with conflicting ideas in PBL-tutorial discussions. In the present study, we examined tutor facilitation during tutorial discussions, and particularly how the facilitation helped students to collaboratively resolve conflicts on knowledge. The study involved four PBL-tutorial sessions that included altogether 33 first-year medical and dental students. The sessions were videotaped and analysed using qualitative interaction analysis. Our aim was to find out how the tutor interventions encouraged students to elaborate on conflicting ideas, and how the interventions differed between conflict and non-conflict situations. We also examined how the tutors intervened during conflicts about factual or conceptual knowledge. The tutorial discussions included 92 tutor intervention episodes and 43 conflict episodes. The tutors intervened during 24 of the conflict episodes and resolved 13 of these episodes. Generally, the tutors often intervened by confirming what the students had said or by giving explanations, but they rarely asked questions that would stimulate the elaboration of knowledge. During conflicts on knowledge the tutors gave more explanations, but did little to encourage the students to deal with conflicting ideas. The tutors more often resolved conflicts on factual knowledge than conceptual knowledge. The findings suggest that tutor training should focus on promoting tutors’ understanding on when to give direct explanations, and when and how to encourage students to collaboratively elaborate on conflicting ideas.     

Outcomes of transoral laser microsurgery and transoral robotic surgery in oropharyngeal squamous cell carcinoma

ObjectiveTransoral robotic surgery (TORS) has evolved to a standard therapy modality for oropharyngeal carcinoma, especially in T1/ T2 tumors involving the base of the tongue due to its advantages compared with open surgery. However, knowledge about its benefits compared with transoral laser microsurgery (TLM) are scarce. This study compares oncological and functional results of TLM or TORS in the treatment of oropharyngeal squamous cell carcinoma (OPSCC).MethodsThis retrospective analysis comprises all patients with OPSCC treated with TLM (n = 30) or TORS (n = 24) between April 2003 and May 2018 (follow-up 43 ± 38.3 months). Both treatment groups (TLM and TORS) were comparable in terms of the stage of the disease, prognosis-determining factors, and adjuvant therapy modalities.ResultsThere were no significant differences regarding to the resection status (p = 0.272), the rate of local- (p = 0.834) and distant- recurrence (p = 0.416), with a disease-free survival of 86.7 % and 87.5 %, respectively (p = 0.892). In addition, we could not confirm any differences regarding to operating time (p = 0.860), intraoperative blood loss (p = 0.660), inpatient stay (p = 0.585) and postoperative bleeding rate (p = 0.245). The frequency of tracheostomy and percutaneous endoscopic gastrostomy between both groups is comparable, with a longer duration of tube feeding in patients who have received TLM (p = 0.030).ConclusionIn conclusion, TORS allows for similar oncological outcomes compared with TLM at comparable perioperative risks. The postoperative swallowing function may benefit from TORS.     

Cerebellar Inhibitory Output Shapes the Temporal Dynamics of Its Somatosensory Inferior Olivary Input

The cerebellum is necessary and sufficient for the acquisition and execution of adaptively timed conditioned motor responses following repeated paired presentations of a conditioned stimulus and an unconditioned stimulus. The underlying plasticity depends on the convergence of conditioned and unconditioned stimuli signals relayed to the cerebellum by the pontine nucleus and the inferior olive (IO), respectively. Adaptive timing of conditioned responses relies on the correctly predicted onset of the unconditioned stimulus, usually a noxious somatosensory stimulus. We addressed two questions: First, does the IO relay information regarding the duration of somatosensory stimuli to the cerebellum? Multiple-unit recordings from the IO of anesthetized rats that received periorbital airpuffs of various durations revealed that sustained somatosensory stimuli are invariably transformed into phasic IO outputs. The phasic response was followed by a post-peak depression in IO activity as compared to baseline, providing the cerebellum with a highly synchronous signal, time-locked to the stimulus’ onset. Second, we sought to examine the involvement of olivocerebellar interactions in this signal transformation. Cerebello-olivary inhibition was interrupted using temporary pharmacological inactivation of cerebellar output nuclei, resulting in more sustained (i.e., less synchronous) IO responses to sustained somatosensory stimuli, in which the post-peak depression was substituted with elevated activity as compared to baseline. We discuss the possible roles of olivocerebellar negative-feedback loops and baseline cerebello-olivary inhibition levels in shaping the temporal dynamics of the IO’s response to somatosensory stimuli and the consequences of this shaping for cerebellar plasticity and its ability to adapt to varying contexts.     

The Efficacy of Fludarabine,High Dose Cytosine Arabinoside with Granulocyte Colony Stimulating Factor (FLAG) Protocol as Salvage Therapy for Refractory/Relapsed Acute Leukemias in Adult Iraqi Patients

Refractory/relapsed acute leukemia has always been a challenging problem for hematologist. Over the past decade emphasis has been made in the development of regimens containing fludarabine, combined with cytosine arabinoside for the treatment of refractory/relapsed acute leukemias. The aim of this study is to evaluate the efficacy and toxicity of the combination of fludarabine, high dose cytarabine, and granulocyte colony stimulating factor in refractory relapsed cases of acute leukaemia, a prospective study is being conducted at the National Center of Hematology and hematology unit/Baghdad teaching hospital from July 2008 to July 2010. Twenty Patients with refractory/relapsed acute leukemia were treated with fludarabine 30 mg/m² and cytosine arabinoside (Ara-C) 2 g/m² for 5 days, and granulocyte colony stimulating factor G-CSF 300 µg/day from day 0 till neutrophil recovery (ANC > 1.0 × 10⁹/L). Response was evaluated by bone marrow examination on day 30 post chemotherapy. Patients included were refractory acute lymphoblastic leukemia (ALL) (five patients), relapsed ALL (four patients), refractory acute myeloid leukemia (AML) (eight patients), relapsed AML (three patients). Complete remission (CR) was achieved in nine (45 %) patients, while three (15 %) patients got partial remission. Three (15 %) patients died because of post chemotherapy complications and five (25 %) patient failed to achieve remission. Major complications encountered were: anemia, fever, bleeding, mucositis and bacterial infections. FLAG protocol is well tolerated and effective regimen in relapsed/refractory acute leukemias. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures.