Mast cell activation syndrome

In 1984, interstitial cystitis (IC) was considered a rare psychosomatic disorder in post-menopausal women. In 2014, the Interstitial Cystitis Association of America (ICA) celebrated its 30^th anniversary. We’ve come a long way since 1984 and great progress has been made. IC is now recognized as a condition that afflicts both men and women of all ages, including children and teenagers. It is not a psychiatric disorder. Though it was once thought to be an orphan disease (defined as affecting less than 200,000 people), we now know that there are millions of women and men who suffer from IC/BPS (bladder pain syndrome). In looking back over this period, there were seven key reasons why the ICA became so successful: an extremely dedicated ICA staff, Board of Directors and volunteers; a very strong Medical Advisory Board and participation of many other urologists from across the country and around the world; cooperation of the media; epidemiological studies; the ICA’s Pilot Research Program; our representation in Congress; and a strong working partnership with the National Institutes of Health (NIH). Our history may prove useful to other advocacy groups.     

Is atrial fibrillation associated with pulmonary embolism?

Summary. Background: A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data. Objectives: To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF. Patients/methods: We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model. Results: The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42–1.11). However, when PE suspicion was based on new‐onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26–0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97–6.07). Conclusions: Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new‐onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.     

Child and parent speech and language following the Lidcombe Programme of early stuttering intervention

The Lidcombe Programme of early stuttering intervention incorporates operant methods, and outcome data indicate that the procedure is an effective treatment. However, the mechanism or mechanisms responsible for the effects of this treatment remain unknown. One possible mechanism could involve untargeted change to parameters of parent and child speech during the intervention. In this preliminary report, speech samples from nine children were studied before and after treatment. The purpose was to target independent variables for future research. In spite of clear reductions in disfluency and stuttering in the children, there were no corresponding changes in child or parent speech rate, interspeaker turn latencies, or pragmatic functioning, that might account for such treatment effects. In fact, data suggested changes that would not be theoretically predicted to be associated with reductions in disfluent and stuttered speech: Maternal speech rate increased in post-treatment speech samples and the mothers decreased the proportion of their utterances that contained a request for information. However, some children's language measures did not meet developmental expectations during the period of study. Nonetheless, all children's language measures were within or above developmental expectancies during the period of study, which ruled out the possibility that this treatment induces extensive curtailment of language functioning.     

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition including fat-emulsion sources: a clinicopathologic study of seven cases

Bone marrow examination revealed a lipid-laden histiocytosis in seven patients undergoing long-term total parenteral nutrition necessitated by extensive short-bowel surgical resection. Clinical abnormalities occurred during this treatment which required bone marrow examination. These included hepatosplenomegaly and peripheral blood cytopenia; the median time to the detection of these abnormalities was 64 months.   The most striking change within the bone marrow was the presence of many pigment-laden histiocytes which had the typical morphology of sea-blue histiocytes seen in the so-called idiopathic sea-blue histiocyte syndrome. The occurrence of sea-blue histiocytosis in the bone marrow in association with long-term parenteral nutrition for short-bowel syndrome has not, to our knowledge, been reported previously and should now be considered in the differential diagnosis of bone marrow sea-blue histiocytosis.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.