Reproducibility of proton MR spectroscopic imaging (PEPSI): comparison of dyslexic and normal-reading children and effects of treatment on brain lactate levels during language tasks

BACKGROUND AND PURPOSE: We repeated a proton echo-planar spectroscopic imaging (PEPSI) study to test the hypothesis that children with dyslexia and good readers differ in brain lactate activation during a phonologic judgment task before but not after instructional treatment. METHODS: We measured PEPSI brain lactate activation (TR/TE, 4000/144; 1.5 T) at two points 1-2 months apart during two language tasks (phonologic and lexical) and a control task (passive listening). Dyslexic participants (n = 10) and control participants (n = 8) (boys and girls aged 9-12 years) were matched in age, verbal intelligence quotients, and valid PEPSI voxels. In contrast to patients in past studies who received combined treatment, our patients were randomly assigned to either phonologic or morphologic (meaning-based) intervention between the scanning sessions. RESULTS: Before treatment, the patients showed significantly greater lactate elevation in the left frontal regions (including the inferior frontal gyrus) during the phonologic task. Both patients and control subjects differed significantly in the right parietal and occipital regions during both tasks. After treatment, the two groups did not significantly differ in any brain region during either task, but individuals given morphologic treatment were significantly more likely to have reduced left frontal lactate activation during the phonologic task. CONCLUSION: The previous finding of greater left frontal lactate elevation in children with dyslexia during a phonologic judgment task was replicated, and brain activation changed as a result of treatment. However, the treatment effect was due to the morphologic component rather than the phonologic component.     

Executive Dysfunction in Female <Emphasis Type="Italic">FMR1</Emphasis> Premutation Carriers

There is now growing evidence of cognitive weakness in female premutation carriers (between 55 and 199 CGG repeats) of the fragile X mental retardation gene, including impairments associated with executive function. While an age-related decline in assessments of executive function has been found for male premutation carriers, few studies have explored whether female carriers show a similar trajectory with age. A total of 20 female premutation carriers and 21 age- and IQ-matched healthy controls completed a battery of tasks assessing executive function tasks, including the behavioural dyscontrol scale (BDS), symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), Haylings sentence completion test and the digit span task (forward and backward). Performance was compared between premutation carriers and healthy controls, and the association between task performance and age was also ascertained. Compared to controls, female premutation carriers had significant impairment on the BDS, SDMT, PASAT, and Haylings sentence completion task, all of which rely on quick, or timed, responses. Further analyses revealed no significant association between age and task performance for either premutation carriers or controls. This study demonstrates that a cohort of female premutation carriers have deficits on a range of tasks of executive function that require the rapid temporal resolution of responses. We propose that the understanding of the phenotype of premutation carriers will be advanced through use of such measures.     

Preservation of porcine non-heart-beating donor livers by sequential cold storage and warm perfusion

BACKGROUND: Normothermic perfusion has been shown to resuscitate and maintain viability of non-heart-beating donor (NHBD) livers that have undergone significant warm ischemic injury. However, the logistics of clinical organ retrieval are complex, and a period of cold storage before warm preservation would simplify the process. We have investigated the effects of short duration of cold preservation before normothermic preservation on the function of porcine NHBD livers. METHODS: Porcine livers were subjected to 60 minutes of warm ischemia and then assigned to the following groups: group W (n=5), normothermic preservation for 24 hours; and group C (n=4), cold preservation in University of Wisconsin solution for 4 hours followed by normothermic preservation for 20 hours (total preservation time 24 hours). Outcome parameters that were measured included bile production, serum transaminases and hyaluronic acid levels (cellular damage), and base deficit and glucose use (metabolic function). RESULTS: Group W livers had superior bile production, metabolic activity (base deficit and greater glucose use), and less evidence of hepatocellular damage (alanine aminotransferase, aspartate aminotransferase), and sinusoidal endothelial cell dysfunction (hyaluronic acid). Group C livers showed greater necrosis and destruction of architecture on histology. CONCLUSION: Normothermic perfusion failed to resuscitate porcine livers after 60 minutes of warm ischemia and 4 hours of cold preservation. Even a short period of cold ischemia is significantly deleterious to the function of ischemically damaged (NHBD) livers.     

Biliary atresia--a fifteen-year review of clinical and pathologic factors associated with liver transplantation

Purpose

The aim of this study was to identify clinical and pathologic factors associated with liver transplantation in infants with biliary atresia initially treated with Kasai hepatic portoenterostomy (KHPE).

Methods

Institutional Review Board approval was obtained. Records of patients with biliary atresia diagnosed between January 1986 and December 2000 were reviewed. Patients were divided into those who never required transplantation, those who underwent transplant in the first year after KHPE, and those who required transplantation later in childhood. Analysis of variance (ANOVA) compared multiple factors among the 3 groups. Proportional analysis compared those who required transplantation against those who did not. Statistical significance was considered achieved if P was less than .05.

Results

Forty-five patients were identified. Survival after KHPE was 96% (43 of 45). Sixteen (37%) never required transplantation, 13 (30%) underwent transplant within 1 year after KHPE, and 14 (33%) underwent transplant more than 1 year after KHPE. ANOVA comparison showed that the duration of jaundice before KHPE as a predictor for liver transplantation approached significance (P = .082). Proportional analysis found that a longer initial duration of jaundice before KHPE (P = .016) and failure to establish biliary flow (P = .033) were also significant predictive factors. An initial requirement for phototherapy (P = .057) and ductules less than 200 μm in diameter (P = .060) showed a trend toward predictor of liver transplantation.

Conclusions

A longer duration of jaundice before KHPE, failure to establish bile flow, requirement for phototherapy in the neonatal period, and ductules smaller than 200 μm are associated with liver transplant after KHPE.     

Exome Sequence Data From Multigenerational Families Implicate AMPA Receptor Trafficking in Neurocognitive Impairment and Schizophrenia Risk

Schizophrenia is a mental disorder characterized by impairments in behavior, thought, and neurocognitive performance. We searched for susceptibility loci at a quantitative trait locus (QTL) previously reported for abstraction and mental flexibility (ABF), a cognitive function often compromised in schizophrenia patients and their unaffected relatives. Exome sequences were determined for 134 samples in 8 European American families from the original linkage study, including 25 individuals with schizophrenia or schizoaffective disorder. At chromosome 5q32–35.3, we analyzed 407 protein-altering variants for association with ABF and schizophrenia status. For replication, significant, Bonferroni-corrected findings were tested against cognitive traits in Mexican American families (n = 959), as well as interrogated for schizophrenia risk using GWAS results from the Psychiatric Genomics Consortium (PGC). From the gene SYNPO, rs6579797 (MAF = 0.032) shows significant associations with ABF (P = .015) and schizophrenia (P = .040), as well as jointly (P = .0027). In the Mexican American pedigrees, rs6579797 exhibits significant associations with IQ (P = .011), indicating more global effects on neurocognition. From the PGC results, other SYNPO variants were identified with near significant effects on schizophrenia risk, with a local linkage disequilibrium block displaying signatures of positive selection. A second missense variant within the QTL, rs17551608 (MAF = 0.19) in the gene WWC1, also displays a significant effect on schizophrenia in our exome sequences (P = .038). Remarkably, the protein products of SYNPO and WWC1 are interaction partners involved in AMPA receptor trafficking, a brain process implicated in synaptic plasticity. Our study reveals variants in these genes with significant effects on neurocognition and schizophrenia risk, identifying a potential pathogenic mechanism for schizophrenia spectrum disorders.Key words: schizophrenia, cognition, SYNPO, WWC1, synaptic plasticity     

The utilisation and diagnostic yield of radiological imaging in a specialist functional GI disorder clinic: an 11-year retrospective study

Objectives

The term functional gastrointestinal disorders (FGID) describes various aggregations of chronic gastrointestinal (GI) symptoms not explained by identifiable organic pathology; accordingly, their diagnosis rests on symptom-based criteria and a process of exclusion. Evidence is lacking on the appropriate use of abdominal imaging studies (AIS) in FGIDs.

Methods

We investigated the utilisation of AIS (site, modality, diagnostic yield/significance) at a tertiary FGID clinic over an 11-year period.

Results

Of 1,621 patients, 507 (31 %; 67.5 % women, mean age 43.9?±?17.37 years) referred from primary care had 997 AIS (1.7 per patient): ultrasonography (US) 36.1 %, fluoroscopy (FLS) 28.8 %, computed tomography (CT) 19.6 %, plain radiography (PR) 13.5 %, nuclear medicine (NM) 1 %). Of the 997 AIS, 55.6 % (554/997) were normal. Of the AIS with positive findings, 9.9 % (62/625) were deemed ‘probably significant’ and 14.7 % (92/625) ‘significant’. Of the CT and FLS studies, 12.3 % and 13.6 %, respectively, yielded ‘significant’ abnormalities compared to 2.2 % of the US studies and 2.1 % of the PR studies. CT identified five of seven neoplasms, associated with male sex, increasing age and symptom onset after age 50 years.

Conclusions

This study confirmed low use of AIS in tertiary FGID clinics and a high proportion of normal studies. Barium swallow/meal and CT were more likely to identify ‘probably significant’ or ‘significant’ findings, including neoplasms.

Key Points

? Imaging referral rates from a specialist functional gastrointestinal disorder clinic are low ? Despite this, normal studies are still frequent in those who are imaged ? Ultrasonography was the most frequent investigation, yet yielded significant findings infrequently ? Abdominal radiographs accounted for 13.5 % of investigations yet were normal in 71.8 % ? CT and fluoroscopy were more likely to yield positive findings     

Implementing nursing practice guidelines: a complex undertaking.

Clinical practice guidelines have been proposed to significantly reduce the gap between available scientific evidence and clinical practice. Evidence-based guidelines are also being produced at an ever-increasing pace. However, guidelines do not implement themselves, and the research to support implementation does not provide straightforward answers. What works in one setting does not necessarily work in another. In short, guideline implementation and change of practice is complex and messy. The purpose of this article is to discuss the implementation of clinical practice guidelines using the Promoting Action on Research Implementation in Health Services framework. More specifically, 3 key components are highlighted: (1) the evidence base for guideline recommendations, (2) the clinical context where guidelines are to be implemented, and (3) the nature of facilitation needed to ensure a successful change process. An overview of the literature in the field is provided, and the authors' experiences are shared, and a few recommendations are tentatively provided.     

Gait analysis of walking before and after medial opening wedge high tibial osteotomy

Introduction

Medial opening wedge high tibial osteotomy (HTO) is used to treat medial compartment osteoarthritis (OA) of the knee. HTO shifts the weight-bearing line from the medial compartment into the lateral compartment. The aim of this study was to investigate the functional biomechanical consequences of this alteration in alignment.

Methods

Eleven male patients with medial compartment osteoarthritis underwent three-dimensional gait analysis during level walking before 12 months and after medial opening wedge HTO. Nine male control subjects of a similar age were also tested using the same protocol. Sagittal and coronal angles and moments in both operated and non-operated knees were compared. Pre and postoperative radiographic coronal plane alignment was also measured.

Results

Walking speed increased significantly postoperatively (P = 0.0001) and was not different from controls. Preoperatively, maximum knee flexion in stance was reduced compared to control (P = 0.02). Postoperatively, maximum knee flexion increased significantly (P = 0.005) and was the same as the controls. Similar changes were observed for the maximum knee flexion moment. The mean maximum varus angle during stance was reduced from 13.5° preoperatively to 5.4° postoperatively (P = 0.0001) compared to (6.8°) in controls. The mean maximum adduction moment also reduced from 3.9 to 2.7 (% Bw/ht, P = 0.02), compared to 3.6 in control subjects. Interestingly, the adduction moments in the non-operated knee increased postoperatively from 3.3 to 4.1 (% Bw/ht, P = 0.02). The mean radiological mechanical alignment was changed from 172 degrees preoperatively to 180 degrees postoperatively (P < 0.001).

Conclusion

HTO resulted in normalisation of several dynamic knee function parameters such as walking speed, knee flexion and external knee flexion moment. As anticipated, HTO reduced the varus angle and adduction moments of the operated knee. An increased adduction moment in the non-operated knee over the first postoperative year was found.

Level of evidence

Prospective case–control clinical laboratory study, Level III.     

Changes in temporal gait characteristics and pressure distribution for bare feet versus various heel heights

The purpose of this study was to identify changes in temporal gait characteristics and pressure generation across the sole of the foot due to various heel heights in women's dress pumps. Thirty female subjects, aged 18-30 years, volunteered to participate. Subjects were required to have normal gait and to wear comfortably either size 7 or size 9 shoes. Subjects were tested initially in bare feet using electrodynography (Langer Biomechanics Group, 21 East Industry Court, Deer Park, NY 11729-9986) (EDG) at a cadence of ~100 steps/min set by metronome. EDG trials with 4 pairs of shoes were then performed in random order. Shoes were women's dress pumps identical except for heel height. Heel heights were 1.75, 3.12, 5.72 and 8.74 cm. Data were collected over ~ 30 steps and averaged over this period. Data were analyzed using a one-way ANOVA, and changes were only considered significant if the ANOVA identified significant variations bilaterally. Considering temporal gait variables, we concluded that: (1) stance phase was shortened in shoes vs. bare feet but was unaffected by heel height, (2) the percentage of stance spent in weight bearing on the lateral and medial calcaneus decreased above a 3.12 cm heel height, (3) the percentage of stance spent in weight bearing on the first and second metatarsal heads increased in shoes vs. bare feet but was unaffected by heel height, (4) the percentage of stance spent in weight bearing on the fifth metatarsal was less in the 8.74 cm heel than in any other shoe or in bare feet. With regard to pressure variables, we found that: (1) peak pressure under the fifth metatarsal head was inversely related to heel height, (2) pressure under the third metatarsal head peaked earliest in heels greater than 5.72 cm high, and (3) pressure under the medial calcaneus peaked latest in heels greater than 5.72 cm high.