Little is known about airway responsiveness in infancy. The bronchial response to incremental doses of nebulised histamine (to a maximum dose of 8 g/l) was measured in 11 wheezy infants with a mean age of 8.7 months. The study was repeated after a 30-40 minute recovery period in seven infants and again on a separate day in 10. The index of response was the provoking concentration of histamine that produced a 30% fall in the maximum expiratory flow at functional residual capacity (PC30), taken from partial forced expiratory flow-volume curves produced in a pressure jacket. Nine of 11 infants had a PC30 of less than 8 g/l. The response was consistent between tests in both the nine responders and the two who failed to respond at 8 g/l. The PC30 was lower in infants with more severe baseline airway obstruction. Spontaneous recovery after challenge was complete in 30 minutes in seven of eight infants studied. The highest doses of histamine caused changes in the configuration of the flow-volume curves and symptomatic cough and wheeze in addition to a change in forced flow rates. This study provides clear evidence of intrathoracic airway responsiveness to histamine in infancy.,Unwieldy by nature, unsolicited diaries and their study, this article contends, have the potential to offer deeper insights into the experience of illness but only if they receive due consideration from scholars. This article uses a series of historic diaries to examine the concept of ‘professional patienthood’ or being a full-time patient, and, while it found the narrative medicine approach to be very useful, it also found it limiting. The recent methodological trends in biomedicine and social sciences towards structured mechanisms like questionnaires—surveying and evaluating performance, satisfaction and experience—can only go so far. This article makes a case for the unsolicited, the unorthodox and the unstructured.
In 1989, Susan Wolf convincingly warned of a troublesome consequence that should discourage any movement in American society towards physician-assisted death—a legal backlash against the gains made for limiting life-sustaining treatment. The authors demonstrate that this dire consequence did not come to pass. As physician-assisted suicide gains a foothold in USA and elsewhere, many other slippery slope arguments are being put forward. Although many of these speculations should be taken seriously, they do not justify halting the new practice. Instead, our courts, regulatory agencies, journalists, professional organisations and researchers should carefully monitor and study it as it unfolds, allowing continuous improvement just as our society has done in implementing the practice of limiting life-sustaining treatment.,Data from the analysis of lung dust in 16 metal grinders who had been exposed to hard metals between five and 44 years is reported. The mean latent time between the first exposure and analysis in biopsy or necropsy specimens was 33.6 years. Mineralogical and elementary analysis by a variety of techniques showed small or trace amounts of hard metal in all lungs. Many specimens, however, did not contain all hard metal components, cobalt, for example, being detected in four cases only. All the lungs contained quartz and silicates and in most of the necropsy cases carborundum and corundum could also be shown. Histologically no specific pattern was found. The appearances included mixed dust nodular pneumoconiosis, diffuse interstitial lung fibrosis, and foreign body and sarcoid like granulomatous changes. In view of the mixed dust exposure of the hard metal grinders and the variable histological appearance we think that the term "mixed dust pneumoconiosis in hard metal grinders" is more appropriate than "hard metal lung" to describe this condition.,Background: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that constitutes the most common genetic cause of renal failure in the first three decades of life. Using positional cloning, six genes (NPHP1-6) have been identified as mutated in NPHP. In Joubert syndrome (JBTS), NPHP may be associated with cerebellar vermis aplasia/hypoplasia, retinal degeneration and mental retardation. In Senior–Løken syndrome (SLSN), NPHP is associated with retinal degeneration. Recently, mutations in NPHP6/CEP290 were identified as a new cause of JBTS. Methods: Mutational analysis was performed on a worldwide cohort of 75 families with SLSN, 99 families with JBTS and 21 families with isolated nephronophthisis. Results: Six novel and six known truncating mutations, one known missense mutation and one novel 3 bp pair in-frame deletion were identified in a total of seven families with JBTS, two families with SLSN and one family with isolated NPHP.
BackgroundSleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking.ObjectiveWe conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD.MethodsWe searched the following electronic databases with no language, date or type of document restriction up to 23 May 2018: PubMed, PsycInfo, Embase+Embase Classic, Ovid Medline and Web of Knowledge. Random-effects models were used. Heterogeneity was assessed with Cochran’s Q and I2 statistics. Publication (small studies) bias was assessed with final plots and the Egger’s test. Study quality was evaluated with the Newcastle Ottawa Scale. Analyses were conducted using Review Manager and Comprehensive Meta-Analysis. FindingsFrom a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9.Discussion and clinical implicationsA number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.