Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Speech-controlled generation of radiology reports

Voice entry has been successfully employed to generate radiology reports with a word recognizer with a 1,000-word lexicon capacity. About 50% of reports were able to be dictated with a single 900-word lexicon. This was split into five sections by anatomic or subspecialty application. Each was augmented to 900 words. By switching from one lexicon to another, it was possible to dictate more than 70% of reports. With exclusive use of three lexicons in subspecialty areas (gastrointestinal radiology, neuroradiology, and mammography), and with further modification of the respective vocabulary, it has been possible to employ the system 88% of the time. Twelve percent of cases included wording that was beyond the scope of the lexicon. Computer subsets that allow different translations of some words when used in different contexts have been used. Some of these are used as triggers that will print whole lines, sentences, or even complete reports. Dictation times with voice entry take about 20% longer. Recognition reliability has been greater than 95%.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

Using the congestion quantifier seven-item test to assess change in patient symptoms and their impact.

Generally, nasal congestion is reported to be the most troublesome symptom of allergic rhinitis and has been shown to have negative effects on sleep, productivity, work, and school performance. A new patient-reported outcome (PRO) tool called the Congestion Quantifier Seven-Item Test (CQ7) was developed and shown to be a reliable and valid screening tool for nasal congestion. The purpose of this study was to assess the CQ7 as a tool for clinical use that can monitor changes in nasal congestion or determine if patients are showing meaningful improvement in symptoms. This study examined the responsiveness of the CQ7 to changes in nasal congestion and changes in relevant PRO to explore whether the CQ7 can serve as a monitoring tool and a valid screening tool for nasal congestion using latent growth curve models. Results showed that the CQ7 is sensitive to changes in patients' symptoms and their impact. Change in the CQ7 from baseline to day 15 was highly related to the change in symptom scores from baseline to day 15 (beta = -0.99); and regression coefficients for the relationships between the CQ7 and changes in the other PRO subscales also were very high (betas ranged from -0.79 to -0.95), lending evidence to support the use of the CQ7 as a monitoring tool. The large sizes of the coefficients suggest that the efficient, seven-item monitoring tool captures change in congestion very well. Analyses of responsiveness to change suggest that a three- to four-point improvement is meaningful to patients.     

Intracranial abnormalities in infants treated with extracorporeal membrane oxygenation: imaging with US and CT

Findings at neuroimaging in 100 consecutive infants treated with extracorporeal membrane oxygenation (ECMO) are presented. Imaging in these infants consisted of pretreatment cranial ultrasonography (US), daily US studies while on ECMO, and follow-up cranial computed tomography (CT) after treatment. There were findings of abnormalities in 43 patients. Thirty had intracranial bleeding, often of unusual extent and distribution. Thirteen additional infants had nonhemorrhagic abnormalities alone. Bleeding considered to be major was seen in 12% of infants. Large parenchymal hemorrhages and infarcts, cerebellar hemorrhages, and diffuse edema were the most significant abnormalities, with a 50% mortality (eight of 16 patients). No lateralization was noted with respect to distribution of bleeding sites or areas of nonhemorrhagic abnormalities. US was a sensitive but imperfect screening tool for intracranial abnormalities. Abnormalities missed with US included peripheral and small parenchymal lesions, subarachnoid hemorrhage, cerebral atrophy, and sagittal sinus thrombosis.     

Cardiorespiratory responses to aerobic training by patients with postpoliomyelitis sequelae

We examined the cardiorespiratory responses of 16 patients with postpoliomyelitis sequelae to a 16-week aerobic exercise program. The patients exercised at 70% of maximal heart rate. Dependent variables were resting and maximal heart rates, systolic and diastolic blood pressures, maximum oxygen consumption, maximum carbon dioxide consumption, respiratory quotient, and maximum expired volume per unit time. The exercise group was superior to the control group in watts, exercise time, maximum expired volume per unit time, and maximum oxygen consumption. No untoward events or loss of leg strength occurred as a result of the exercise regimen. We conclude that the aerobic training program employed in this study is a safe, short-term procedure and that patients with postpolio sequelae respond to training in a manner similar to healthy adults.