Spatial Orientation Adjustments in Children with Autism in Hong Kong

Abnormal spatial orientation and body postures in children with autism often interfere with visual abilities to attend tasks and social interactions. Twenty-four children diagnosed with autism from Kowloon, Hong Kong were assessed for spatial orientation and spatial management abilities. Positive changes in spatial orientation were evident when the children wore ambient prism lenses and included changes in posture from slanted to erect. Adjustments in spatial management were evident in improved ball catching ability, a task requiring visual tracking and eye-hand coordination. The findings suggest that alterations to the sensory systems may lead to behavioral change in some children.     

Digital subtraction angiography of the arteries of the head and neck

The advantages and disadvantages of intravenous and intra-arterial digital subtraction angiography of the arteries of the head and neck are discussed. The clinical applications of the two techniques are compared.     

CpG island promoter hypermethylation of a novel Ras-effector gene RASSF2A is an early event in colon carcinogenesis and correlates inversely with K-ras mutations

We report in silico identification and characterisation of a novel member of the ras association domain family 1 (RASSF1)/NORE1 family, namely, RASSF2, located at chromosomal region 20p13. It has three isoforms, all contain a ras association domain in the C-terminus. The longest isoform RASSF2A contains a 5' CpG island. RASSF2A was cloned from a brain cDNA library and directly sequenced, confirming the genomic gene structure. In previous reports, we and others have demonstrated that RASSF1A is epigenetically inactivated in a variety of cancers, including sporadic colorectal cancer (CRC). In the present report, we analysed the methylation status of RASSF2A promoter region CpG island in sporadic CRC and compared it to K-ras mutation status. RASSF2A promoter region CpG island was hypermethylated in a majority of colorectal tumour cell lines (89%) and in primary colorectal tumours (70%), while DNA from matched normal mucosa was found to be unmethylated (tumour-specific methylation). RASSF2A expression was reactivated in methylated tumour cell lines after treatment with 5-aza 2-deoxycytidine. RASSF2A methylation is an early event, detectable in 7/8 colon adenomas. Furthermore, 75% of colorectal tumours with RASSF2A methylation had no K-ras mutations (codons, 12 and 13) (P=0.048), Fisher's exact test). Our data demonstrate that RASSF2A is frequently inactivated in CRCs by CpG island promoter hypermethylation, and that epigenetic (RASSF2A) and genetic (K-ras) changes are mutually exclusive and provide alternative pathways for affecting Ras signalling.     

Identification of novel VHL target genes and relationship to hypoxic response pathways

Upregulation of hypoxia-inducible factors HIF-1 and HIF-2 is frequent in human cancers and may result from tissue hypoxia or genetic mechanisms, in particular the inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene (TSG). Tumours with VHL inactivation are highly vascular, but it is unclear to what extent HIF-dependent and HIF-independent mechanisms account for pVHL tumour suppressor activity. As the identification of novel pVHL targets might provide insights into pVHL tumour suppressor activity, we performed gene expression microarray analysis in VHL-wild-type and VHL-null renal cell carcinoma (RCC) cell lines. We identified 30 differentially regulated pVHL targets (26 of which were 'novel') and the results of microarray analysis were confirmed in all 11 novel targets further analysed by real-time RT-PCR or Western blotting. Furthermore, nine of 11 targets were dysregulated in the majority of a series of primary clear cell RCC with VHL inactivation. Three of the nine targets had been identified previously as candidate TSGs (DOC-2/DAB2, CDKN1C and SPARC) and all were upregulated by wild-type pVHL. The significance for pVHL function of two further genes upregulated by wild-type pVHL was initially unclear, but re-expression of GNG4 (G protein gamma-4 subunit/guanine nucleotide-binding protein-4) and MLC2 (myosin light chain) in a RCC cell line suppressed tumour cell growth. pVHL regulation of CDKN1C, SPARC and GNG4 was not mimicked by hypoxia, whereas for six of 11 novel targets analysed (including DOC-2/DAB2 and MLC2) the effects of pVHL inactivation and hypoxia were similar. For GPR56 there was evidence of a tissue-specific hypoxia response. Such a phenomenon might, in part, explain organ-specific tumorigenesis in VHL disease. These provide insights into mechanisms of pVHL tumour suppressor function and identify novel hypoxia-responsive targets that might be implicated in tumorigenesis in both VHL disease and in other cancers with HIF upregulation.     

Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury

BACKGROUND: This study analyzes the role of T lymphocytes and neutrophils (PMN) in intestinal ischemia and reperfusion injury (IRI) using either P-selectin blockade or elimination. METHODS: Using a model of severe mouse warm intestinal IRI, the following groups were performed: group 1: wild type C57BL6 no treatment; group 2: wild type treated with r-PSGL1-Ig; group 3: C57BL6 genetically deficient in P-selectin. Survival was assessed at day 7; intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), inflammatory cytokines, hemoxygenase-1 (HO-1), and CD3 lymphocytes. Standard statistical comparison was undertaken. RESULTS: The survival was significantly (P < 0.01) improved in the treatment groups: group 1, 50%; group 2, 90%; group 3, 100%. Graded histopathology and crypt apoptosis were improved in groups 2 and 3. MPO and CD3 positive cells were significantly reduced in groups 2 and 3. A significant reduction in inflammatory/Th1-type cytokines was seen in groups 2 and 3 as compared to group 1. Conversely, a significant increase in Th2-type cytokines and HO-1 production was seen selectively in groups 2 and 3. CONCLUSIONS: This study demonstrates the importance of P-selectin signaling in warm, murine intestinal IRI in that either the blockade of or the genetic deficiency in P-selectin confers a survival advantage and reduction in tissue injury/inflammation. The mechanism involves a reduction of PMN and CD3 T cell infiltration and an alteration in the cytokine microenvironment in favor of a Th2 profile. These data implicate T lymphocyte as an important regulatory cell in this inflammatory process.     

Medical students' retention of knowledge of physics and chemistry on entry to a course in physiology.

In this paper we have assessed the extent to which two cohorts of medical students retained skills acquired in two of their basic science courses, i.e. physics and chemistry. It has been shown that a great deal of attrition takes place with respect to factual information and also, therefore, the capacity to apply this information in a relevant manner. It has been argued that this occurs, in part, because students do not appear to regard chemistry and physics as a useful part of their preparation as doctors and, in part, because of the methods used to teach these basic science subjects. Finally, some implications of this preliminary study have been discussed.     

Does provider adherence to a treatment guideline change clinical outcomes for patients with bipolar disorder? Results from the Texas Medication Algorithm Project

BACKGROUND: Despite increasing adoption of clinical practice guidelines in psychiatry, there is little measurement of provider implementation of these recommendations, and the resulting impact on clinical outcomes. The current study describes one effort to measure these relationships in a cohort of public sector out-patients with bipolar disorder.METHOD:Participants were enrolled in the algorithm intervention of the Texas Medication Algorithm Project (TMAP). Study methods and the adherence scoring algorithm have been described elsewhere. The current paper addresses the relationships between patient characteristics, provider experience with the algorithm, provider adherence, and clinical outcomes. Measurement of provider adherence includes evaluation of visit frequency, medication choice and dosing, and response to patient symptoms. An exploratory composite 'adherence by visit' score was developed for these analyses.RESULTS: A total of 1948 visits from 141 subjects were evaluated, and utilized a two-stage declining effects model. Providers with more experience using the algorithm tended to adhere less to treatment recommendations. Few patient factors significantly impacted provider adherence. Increased adherence to algorithm recommendations was associated with larger decreases in overall psychiatric symptoms and depressive symptoms over time, but did not impact either immediate or long-term reductions in manic symptoms.CONCLUSIONS: Greater provider adherence to treatment guideline recommendations was associated with greater reductions in depressive symptoms and overall psychiatric symptoms over time. Additional research is needed to refine measurement and to further clarify these relationships.     

Electroencephalogram biofeedback for reading disability and traumatic brain injury

The application of electroencephalogram (EEG) biofeedback with reading disability and traumatic brain injury (TBI) is relatively recent. There are many studies regarding the effectiveness (improving attention and IQ scores) of EEG biofeedback in patients with attention deficit hyperactivity disorder, who are known to have a high rate of comorbidity for learning disabilities. This suggests the possibility that EEG biofeedback specifically aimed at remediating reading disability and TBI would be effective. This article provides strong initial support for this idea and provides reason to believe that assessment and training under task conditions are likely to be fruitful. Given the significance of these problems and the absence of very effective alternatives for remediation of these conditions, efforts to complete the needed research seem warranted. Clinical use of this intervention seems to be warranted with informed consent.     

Outcomes of teaching medical students core skills for women's health: the pelvic examination educational program

OBJECTIVE: The purpose of this study was to evaluate the outcomes of introducing an educational program that teaches medical students how to approach taking relevant and sensitive gynecologic histories and to perform pelvic examinations with the use of role-play with well women from the general community. STUDY DESIGN: Medical students and the women recorded their perceptions of the program over a 2-year period. The outcomes of the program were evaluated by a comparison of medical student perceptions of confidence, competence, and anxiety; the mean number of pelvic examinations that were performed during their course both before and after the introduction of the program and results of students' continuous and summative assessment are given. RESULTS: In the year before the introduction of the program, students performed a mean of 2.6 pelvic examinations (95% CI, 2.1, 3.0) compared with 4.1 pelvic examination (95% CI, 3.8, 4.4) in the first year of implementation and 4.0 (95% CI, 3.7, 4.3) in the second year of implementation (P <.05). Students reported improved competence and reduced anxiety to perform a pelvic examination without supervision (P <.05). All students passed their continuous assessment. Between 92% and 100% of students and women agreed that the program had clear learning objectives, was well organized, and was a useful and appropriate method of teaching that helped prepare them for the clinical setting. CONCLUSION: This pelvic examination educational program has been evaluated positively by students and participant women and has resulted in a significant improvement in the amount of pelvic examination experience that medical undergraduates obtain.