Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type-1 Long-QT Syndrome

Background: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac events.
Methods and Results: The study population involved 492 LQT1 patients with 54 missense mutations in the transmembrane region of the KCNQ1 channel. The amino acid sequences of the transmembrane region of 38 human voltage-gated potassium channels were aligned. An adjusted Shannon entropy score for each amino acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon entropy scores. The lowest tertile (score 0–0.469; n = 146) was used as a reference group; patients with intermediate tertile scores (0.470–0.665; n = 150) had no increased risk of cardiac events (HR = 1.19, P = 0.42) or aborted cardiac arrest/sudden cardiac death (HR = 1.58, P = 0.26), and those with the highest tertile scores (>0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P <0.001) and aborted cardiac arrest/sudden cardiac death (HR = 2.62, P = 0.04). The increased risk in patients with the highest conservation scores was independent of QTc, gender, age, and beta-blocker therapy.
Conclusions: Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta-blocker therapy.     

The Influence of Race and Phenotype on the Erythrocyte D Antigen Studied by I131--labeled Anti--D

A method for the preparation of I¹³¹-labeled anti-D eluates (I^[unknown] anti-D)specific for the D antigen by adsorption and elution from intact D positivered cells is presented. A standard D antigen reference system for the quantitative comparison of the red cell D antigen from various donors was developedon the basis of kinetic studies of the effect of pH, temperature and antigenconcentration on the I^[unknown] anti-D reaction with the D antigen. The red cell Dantigen determinations of the blood from 33 Negro and 102 Caucasiandonors showed wide monomodal frequency distributions which indicate aheterogeneity of quantitative D antigen reactivity consistent with previousserologic and I¹³¹-labeled anti-D studies. The average red cell D antigenreactivity of the 20 probable D homozygote and 14 established D hemizygoteCaucasian donors was similar to the D antigen reactivity of the 102 randomCaucasian donors. The red cell D antigen reactivity was strongly depressedby the C antigen (or C gene) in Caucasian bloods and enhanced by the Eantigen (or E gene) in Negro bloods. The E antigen (or E gene) may alsohave enhanced the D antigen reactivity in red cells from Caucasian donors,but the difference in D zygosity provides an alternative explanation for theresults. The marked influence on red cell D antigen reactivity in the presenceof the C and E antigen may well have obscured any lesser influence of Dzygosity.

Accepted on December 6, 1962     

Health claims for food made in Australian magazine advertisements

Aim: The aim was to describe the level of health claims being used in magazine advertisements, the categories of foods carrying health claims, and the types of benefits being claimed for particular foods or food ingredients. Data were compared with similar studies of food labels and Internet sites to reflect the impact of rule governance of the different media and highlight implications for the current proposed changes in food standards legislation. Methods: From January to June 2005, a survey of all print advertisements for food in Australia's 30 top‐selling magazines was undertaken. The results were compared with those from a 1996 survey of health claims in Australian magazines and more recent surveys of claims for food on product labels and on Internet sites. Results: The survey found that 29.5% of 390 advertisements for food carried a health claim. Many of the claims were high‐level claims (29%) or therapeutic claims (8%), which are not permitted by current food standards. The most common benefits being promoted related to cardiovascular disease, energy, cancer and weight control, and most claims referred to the effect of the whole food, rather than specific ingredients. Results were similar to previous studies of food labels and Internet sites. Conclusion: Health claims are being used widely in the print advertising of food products in Australia. Moreover, the presence of high‐level and therapeutic claims in this media bears significant implications for the implementation of rules governing health claims on foods across the different media.     

A comparison of prostaglandin E2 pessaries and laminaria tents for ripening the cervix before termination of pregnancy

Summary. Forty primigravid womcn aged 15–45 years were randomly allocated to receive either an intravaginal pessary of 3 mg prostaglandin E, (PGE₂) or an intracervical 5-mm laminaria tent (LT) 12–16 h before termination of pregnancy at 6–14 weeks gestation. The degree of dilatation of the cervix a t operation and its resistance t o further dilatation during the procedure were assessed by a 'blind' operator. Laminaria tents were more effective in achieving dilatation and softening of the cervix than were PGE₂ pessaries and in 40% of women no further dilatation was necessary. There were no associated side-effects or complications. A cervical tear occurred in two of 20 patients treated with PGE₂ pessaries and all 20 required further dilatation of the cervix. Laminaria tents provide a simple. safe, acceptable and effective means of 'ripening' the cervix prior to termination of early pregnancy.     

Evidence for a role of cow's milk consumption in chronic functional constipation in children: Systematic review of the literature from 1980 to 2006

Aim:  This article examines the evidence for a role of cow's milk protein in chronic functional constipation in children.
Methods:  A literature search was conducted using Ovid and Pubmed, the Cochrane data bases, CINHAHL and EBSCO. Keywords searched included: constipation, cow's milk, intolerance, allergy, children and intestinal motility. This systematic review focused on dietary intervention studies in children (aged from 7 days to 15 years) with chronic functional constipation. All articles were required to include measures of cow's milk protein allergy or intolerance and include resolution of constipation as an outcome measure.
Results:  The keyword search identified 125 articles. Seven of these articles met the criteria for inclusion, including one double-blind, randomised controlled trial. The results of this review provide support for the hypothesis that a proportion of children with chronic functional constipation respond well to the removal of cow's milk protein from the diet, particularly if serum analysis shows abnormalities of immune mechanisms.
Conclusion:  The evidence surrounding cow's milk constipation was limited with only one of the assessed studies being at level II of evidence according to the NHMRC. In order to develop evidence-based guidelines, further high-level evidence is required to clarify the physiological, immunological and biochemical changes that occur in some constipated children who respond to the removal of cow's milk protein from the diet.     

Prediction of outcome of preterm infants with severe bronchopulmonary dysplasia

Abstract Forty-four preterm infants of less than 30 weeks gestation and birthweight £ 1250 g, with severe bronchopulmonary dysplasia requiring mechanical ventilation for at least 28 days, were reviewed. Twenty-seven infants (61%) survived; 17 died. There were no significant differences between survivors and non-survivors with respect to birthweight, gestational age, sex, Apgar score at 5 min or pulmonary diagnosis. Non-survivors displayed more severe changes on chest X-ray than the survivors. Peak inspiratory pressure (PIP), ventilator rate (VR), ventilator index and mean airways pressure were significantly higher in the non-surviving infants on days 2, 3, 4, 7, 14, 21 and 28, with non-survivors also having significantly higher alveolar-arterial oxygen gradients and lower arterial-alveolar oxygen ratios than the survivors. Discriminant analysis with cross-validation by pairing PIP and VR on day 28 produced a positive predictive value for non-survival of 88% and a negative predictive value of 89%. This result was better than was obtained for any other pair of ventilator parameter or oxygenation index. Discriminant analysis by combining X-ray appearances with ventilator settings did not improve the prediction. Having established a statistical model based on the PIP and VR of ventilator-dependent preterm infants on day 28, the outcome can be predicted with a high degree of confidence. This has the immediate potential application of indicating to staff in the neonatal unit a realistic approach to take when counselling parents of these infants.     

METHYLCELLULOSE FOR ENDOTHELIAL CELL PROTECTION

A randomised trial of three types of endothelial cell protection for patients undergoing posterior chamber intraocular lens implant is described. The results confirm the superiority of a viscoelastic fluid over air as a form of endothelial cell protection. No statistically significant difference was found between sodium hyaluronate and hydroxypropylmethykellulose (HPMC). As the cost of sodium haluronate is prohibitive, a manufacturing technique for HPMC is given.     

Factor structure of the Motivation Assessment Scale

The Motivation Assessment Scale (MAS) was developed to provide clinical information on four hypothesized functions that may control problem behaviour in persons with developmental disabilities. The original four-factor structure of the MAS was based on face validity, with the items being grouped in terms of each of the hypothesized functions. Validation of the scale was provided in terms of correlations between teacher ratings of eight children on the MAS and ranking of the controlling variables from functional analogue tests. In this study, staff in residential facilities rated 60 residents and teachers in schools rated 96 students on the MAS. The target behaviour rated for both samples was self-injury, with the institutional sample engaging in the behaviour more than 15 times an hour and the school sample, less than 15 times an hour. The results of factor analyses, with varimax rotation, provided a conceptually meaningful factor structure with the institutional sample, but not with the school sample. The 16 MAS items resolved into four factors that were conceptually related to four conditions that may maintain problem behaviour (i.e. sensory, escape, attention and tangible). The results suggested that the original MAS has a robust factor structure and may be clinically useful in predicting the controlling functions of problem behaviours, if the target behaviours occur at a rate no less than 15 responses per hour.     

Cannabis use correlates with schizotypy in healthy people

Cannabis use or high scores on self-report schizotypy questionnaires predict an increased risk of developing clinical psychosis. We tested whether cannabis use correlated with schizotypal and other personality traits in 211 healthy adults. Subjects who had used cannabis showed higher scores on schizotypy, borderline and psychoticism scales than never-users. Multivariate analysis, covarying lie scale scores, age and educational level indicated that high schizotypal traits best discriminated subjects who had used cannabis from never-users, whether or not they reported having used other recreational drugs. These results indicate that cannabis use is related to a personality dimension of psychosis-proneness in healthy people.