Self-reported Dysphagia and Pharyngeal Volume Following Whiplash Injury.

Difficulty swallowing has been reported following whiplash injury; however, the reasons remain poorly understood. A possible factor may be the observed changes in pharyngeal volume. The current exploratory study was designed to examine the prevalence of self-reported dysphagia after whiplash and the relationship with recovery status and change in pharyngeal volume. Data were available from a longitudinal study of adults with whiplash. Data included magnetic resonance imaging (MRI) of the cervical spine, the Dysphagia Handicap Index (DHI), and Neck Disability Index (NDI) collected over four timepoints (< 1 week, 2 weeks, 3 months, and 12 months post-injury). Initial cross-sectional analysis examined 60 patients with DHI data from at least one timepoint. A second, longitudinal analysis was conducted on 31 participants with MRI, NDI, and DHI data at both early (< 1-2 weeks) and late (3-12 months) timepoints. The pharynx was contoured on axial T2-weighted MRI slices using OsiriX image processing software and pharyngeal volume (mm3) was quantified. In the 60-patient cohort, prevalence of self-reported dysphagia (DHI ≥ 3) was observed in 50% of participants at least once in 12 months (M = 4.9, SD 8.16, range 0-40). In the longitudinal cohort (n = 31), mean total DHI significantly (p = 0.006) increased between early and late stages. There was no relationship (p = 1.0) between dysphagia and recovery status, per the NDI% score. Pharyngeal volume remained stable and there was no relationship between dysphagia and pharyngeal volume change (p = 1.0). This exploratory study supports the need for further work to understand the nature of dysphagia, extent of functional compromise, and the underlying pathophysiology post-whiplash.

In-situ SEM observation of grain growth in the austenitic region of carbon steel using thermal etching.

A novel heat stage, recently developed for use within the Scanning Electron Microscope, has facilitated Secondary Electron imaging at temperatures up to 850°C. This paper demonstrates one of the applications of in-situ elevated temperature Scanning Electron Microscope imaging: observation and quantification of grain growth within the austenitic region of carbon steels. The resulting Secondary Electron data have used the technique of thermal etching to capture possible 'abnormal grain growth' in the austenitic region. Previous ex-situ and post-heating results from carbon steels indicate normal, non-linear grain growth. Therefore, this new dataset provides greater insight into the heat treatment of steels. From comparison of the in-situ data with the overall grain growth, measured ex-situ, it is further concluded that abnormal grain growth is representative of the growth at temperature. Thus, the heating and cooling parts of the heat treatment are likely to account for the non-linearity previously documented in ex-situ results and, hence, the range of powers recorded when fitting power law models for steel grain growth. The ability of data derived from in-situ thermal etching to represent the microstructure of the entire surface and the bulk material is also considered. LAY DESCRIPTION: A novel heating stage has recently been developed for use within the Scanning Electron Microscope (SEM); an instrument that uses electrons to image specimen surfaces at very high magnifications. The development of the heating stage has facilitated imaging at temperatures up to 850°C of the structure and topographic features of metals using two different detectors. This study focusses on observation and quantification of grain growth in steels at temperatures of 800  C. In Materials Science, grains refer to crystals of varying, randomly distributed, small sizes that together make up a solid metal. The temperature of 800  C is used as it is the desired temperature to heat treat steels in order to produce more favourable physical properties. It is also the temperature above which the material undergoes a phase change; phase change is a transition where the atoms rearrange from one order within a grain to another. In the case of steel, at room temperature atoms will be in what is called a ferrite phase (one order) but at 800  C, they will be in a different order within the grains, known as the austenite phase. Hence, the uniqueness of this dataset as the grain growth captured is in the high temperature steel phase of austenite. The steel samples used are made up of 0.4% Carbon, 99% iron and some manganese and other trace elements. The resulting data have, for the first time, shown so called 'abnormal grain growth' which is represented by a linear relationship between grain size and time. Abnormal grain growth is also observed in the images where it can be seen how larger grains grow at a high rate at the expense of smaller ones. Previous data taken after cooling of steels indicate normal non-linear grain growth. Therefore, it is reasonable to suggest, this new dataset provides greater insight into the heat treatment processing of steels, demonstrating that they are potentially more complex than previously thought.

Impact of time of day on radiology image interpretations.

AIM: To examine the impact of the time of day on radiologists' mammography reading performance. MATERIALS AND METHODS: Retrospective mammographic reading assessment data were collected from the BreastScreen Reader Assessment Strategy database and included timestamps of the readings and reader-specific demographic data of 197 radiologists. The radiologists performed the readings in a workshop setting with test case sets enriched with malignancies (one-third of cases were malignant). The collected data were evaluated with an analysis of covariance to determine whether time of day influenced radiologists' specificity, lesion sensitivity or the jackknife alternative free-response receiver operating characteristic (JAFROC). RESULTS: After adjusting for radiologist experience and fellowship, specificity varied significantly by time of day (p=0.027), but there was no evidence of any significant impact on lesion sensitivity (p=0.441) or JAFROC (p=0.120). The collected data demonstrated that specificity during the late morning (10.00-12.00) was 71.7%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. Specificity during the late afternoon (16.00-18.00) was 73.95%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. CONCLUSION: The results indicated that the time of day may influence radiologists' performance, specifically their ability to identify normal images correctly.

In the digital era, architectural distortion remains a challenging radiological task.

AIM: To compare readers' performance in detecting architectural distortion (AD) compared with other breast cancer types using digital mammography. MATERIALS AND METHODS: Forty-one experienced breast screen readers (20 US and 21 Australian) were asked to read a single test set of 30 digitally acquired mammographic cases. Twenty cases had abnormal findings (10 with AD, 10 non-AD) and 10 cases were normal. Each reader was asked to locate and rate any abnormalities. Lesion and case-based performance was assessed. For each collection of readers (US; Australian; combined), jackknife free-response receiver operating characteristic (JAFROC), figure of merit (FOM), and inferred receiver operating characteristic (ROC), area under curve (Az) were calculated using JAFROC v.4.1 software. Readers' sensitivity, location sensitivity, JAFROC, FOM, ROC, Az scores were compared between cases groups using Wilcoxon's signed ranked test statistics. RESULTS: For lesion-based analysis, significantly lower location sensitivity (p=0.001) was shown on AD cases compared with non-AD cases for all reader collections. The case-based analysis demonstrated significantly lower ROC Az values (p=0.02) for the first collection of readers, and lower sensitivity for the second collection of readers (p=0.04) and all-readers collection (p=0.008), for AD compared with non-AD cases. CONCLUSIONS: The current work demonstrates that AD remains a challenging task for readers, even in the digital era.

Mammography test sets: reading location and prior images do not affect group performance.

AIM: To examine how the location where reading takes place and the availability of prior images can affect performance in breast test-set reading. MATERIALS AND METHODS: Under optimized viewing conditions, 10 expert screen readers each interpreted a reader-specific set of images containing 200 mammographic cases. Readers, randomly divided into two groups read images under one of two pairs of conditions: clinical read with prior images and laboratory read with prior images; laboratory read with prior images and laboratory read without prior images. Region-of-interest (ROI) figure-of-merit (FOM) was analysed using JAFROC software. Breast side-specific sensitivity and specificity were tested using Wilcoxon matched-pairs signed rank tests. Agreement between pairs of readings was measured using Kendall's coefficient of concordance. RESULTS: Group performances between test-set readings demonstrated similar ROI FOMs, sensitivity and specificity median values, and acceptable levels of agreement between pairs of readings were shown (W = 0.75-0.79, p < 0.001) for both pairs of reading conditions. On an individual reader level, two readers demonstrated significant decreases (p < 0.05) in ROI FOMs when prior images were unavailable. Reading location had an inconsistent impact on individual performance. CONCLUSION: Reading location and availability of prior images did not significantly alter group performance.

Wireless 'mini' multichannel intraluminal impedance-pH: what is the optimal design of a miniature wireless device?

Catheter-based methods for multichannel intraluminal impedance-pH monitoring are invasive and uncomfortable. The current alternative is a wireless system that clips to the esophageal mucosa, but which only measures pH. A shorter two-site wireless sensor that detects impedance and pH, and can be clipped to the esophagus, would be desirable. This study compares sensor positions and separations to determine the optimal configuration of a two-site wireless sensor. Records of 20 patients (10 on and 10 off proton pump inhibitor) who had ambulatory reflux testing with a multichannel intraluminal impedance-pH system (Sandhill Scientific Inc., Highlands Ranch, CO, USA) with six impedance and two pH sensors were reviewed. An investigator was blinded to four combinations of impedance channels plus pH. He read a 3-hour postprandial section from each of the combinations (total of 80 studies) and marked reflux episodes. Results were compared with his own interpretation of the full tracing. Two hundred and two total reflux episodes were analyzed, 113 acid (pH < 4) and 89 nonacid (pH > 4). Mean and median numbers of total reflux episodes were calculated. In the full study, the interpreter detected a mean of 10 reflux episodes per study. In the 5 cm and 7 cm, 3 cm and 7 cm, and 3 cm and 5 cm studies, the interpreter found a mean of 8.1, 11.1, and 9.8 reflux episodes per study, respectively. One-way analysis of variance yielded a P-value of 0.43. The trend of these preliminary findings suggests that the 3 cm and 5 cm site is the most sensitive and the 5 cm and 7 cm is the least, with the 3 cm and 7 cm site perhaps as the preferred location. The lack of a significant difference, at the very least, suggests that any of the 'mini' locations could be used. The small number of observations could have resulted in a Type II statistical error.

Cardiorespiratory responses during functional electrical stimulation cycling and electrical stimulation isometric exercise.

STUDY DESIGN: Prospective experimental. OBJECTIVES: To compare the cardiorespiratory responses with electrical stimulation (ES) producing either dynamic leg cycling or intermittent isometric leg contractions using the same ES protocol. SETTING: Sydney, Australia. METHODS: Eight paraplegics (T4-T11) performed ES exercise sessions on two separate days. On day 1, cardiorespiratory responses were measured during 5 min of rest followed by 35 min of cycling, and finally 15 min of intermittent isometric exercise using the same ES parameters. On the second day, after 5 min of rest, 35 min of isometric exercise was performed followed by 15 min of cycling. RESULTS: There were no significant differences during the first 35 min of exercise on each day comparing the two modes of exercise for average rate of oxygen consumption (cycling, 534±128 ml min(-1); isometric 558±146 ml min(-1); P=0.451), the average heart rate (cycling, 93±15 b.p.m.; isometric 95±17 b.p.m.; P=0.264) or minute ventilation (cycling, 23.0±6.5 l min(-1); isometric 23.8±6.7 l min(-1); P=0.655). In addition, there were no significant differences between exercise modes for any peak cardiorespiratory values recorded during the initial 35 min of exercise or the following 15 min crossover exercise phase. CONCLUSION: The current data found that intermittent ES leg isometric exercise elicited a similar cardiorespiratory response compared with functional ES leg cycling, suggesting it should be investigated as a viable alternative intervention for increasing whole body metabolic rate during sustained exercise training sessions for individuals with paralyzed muscles.

Risk factors associated with reduced work productivity among people with chronic knee pain.

OBJECTIVE: To determine the burden and risk factors associated with reduced work productivity among people with chronic knee pain. METHOD: A longitudinal study, nested within a randomised controlled trial (RCT) evaluating the long-term effects of dietary supplements, was conducted among people with chronic knee pain in paid employment (n = 360). Participants recorded days off work (absenteeism) and reduced productivity while at work (presenteeism) for seven days every two months over a 12-month period in a study specific diary. Examined risk factors included knee pain severity, occupational group, radiographic disease severity, physical activity, body mass index (BMI), health-related quality of life (SF-12) and co-morbidity. RESULTS: Over the 12-month follow up period, 50 (14%) participants reported one or more days off work due to knee problems, while 283 (79%) reported reduced productivity while at work (presenteeism <100%). In multivariate analysis, the only significant risk factor for absenteeism was having an SF-12 Mental Component Summary (MCS) score <40 (OR: 2.49 [95% CI: 1.03-5.98]). Significant risk factors for presenteeism included; reporting an; SF-12 Physical Component Summary (PCS) score <50 (OR: 1.99 [95% CI: 1.05-3.76]), semi-manual labour (OR: 2.23 [1.09-4.59]) or manual labour (OR: 6.40 [1.44-28.35]) or a high maximum knee pain (4-6 out of 10) (OR: 2.29 [1.17-4.46]). CONCLUSIONS: This longitudinal study found that among this cohort of people with chronic knee pain, the burden of reduced work productivity is mainly attributable to presenteeism rather absenteeism. This study demonstrated that effective strategies to increase work productivity should focus on reducing knee pain or physical disability especially among workers in manual or semi-manual labour.

Establishing research priorities for Australian radiation therapists: what patient care priorities need to be addressed?

Much of the research conducted in radiotherapy focuses on technology advances; however, research may also be warranted in the area of patient care. The aims of this paper are to (1) identify patient care-related research priorities in radiation therapy and (2) describe similarities and differences in radiation therapists' responses to research priorities related to patient care by subgroups revealed through cluster analysis. A Delphi process was used, examining problems in research that radiation therapists face. Three hundred and seventy-four problems were identified. These were translated into 53 research areas which were then prioritised. Participant subgroups were identified using a hierarchical cluster procedure. Agreement and disagreement between subgroups for the subscale of 'Patient Care' were analysed with ANOVA and post hoc Scheffe multiple comparisons. The three subgroups had varying degrees of research interest in patient care. The groups agreed on the importance of research in relation to patient care in reducing and managing side effects, patient education and support, and treatment techniques. However, there was disagreement about the importance of conducting research into the role of radiation therapists, radiation therapists communicating and educating patients, and psychosocial support. Further research is warranted to determine radiotherapy patients' priorities and improve evidence-based practice.

Is fascia iliaca compartment block or intravenous opioid analgesia better when positioning patients with fractured neck of femur for spinal anaesthesia?

Patients with a fractured neck of femur require effective analgesia to improve positioning before the administration of spinal anaesthetic. This article discusses the evidence to show whether fascia iliaca compartment block or intravenous opioid analgesia is preferable in this situation.

Haplotypes of the interleukin 7 receptor alpha gene are correlated with altered expression in whole blood cells in multiple sclerosis.

IL7 regulates T cell survival, differentiation and proliferation. The alpha chain of its receptor, CD127, is polymorphic, and its haplotypes are associated with recovery from transplantation and with the autoimmune disease multiple sclerosis (MS), especially primary progressive MS (PPMS). We demonstrate that two CD127 haplotypes are highly associated with the proportion of the mRNA encoding the soluble isoform of CD127 (P

Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis.

Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in the set of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P < 10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P = 0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P = 0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.

Brainstem serotonergic neurons in chronic alcoholics with and without the memory impairment of Korsakoff's psychosis.

There are several lines of evidence to suggest that serotonergic neurons in the brain are detrimentally affected by chronic alcohol consumption. The present study aims to quantify pathological changes in brainstem regions containing serotonergic neurons in chronic alcoholics compared to age-matched non-alcoholic controls. An antibody specific for tryptophan hydroxylase was used to immunohistochemically demonstrate serotonergic neurons in serial sections of postmortem brainstem. The cases analyzed were divided into four groups on the basis of their clinical and pathological presentation; chronic alcoholics with Wernicke's encephalopathy, chronic alcoholics with additional Korsakoff's psychosis, non-alcoholic controls, and a single chronic alcoholic without neurological complications. There was an overall reduction in the number of serotonergic neurons in all alcoholic cases when compared with controls. All brainstem regions were affected, but the largest neuronal loss was found in areas of the medullary and caudal pontine reticular formation (reduced by 80-90%). Alcoholics with Korsakoff's psychosis did not differ in the amount or extent of pathology from the other alcoholic cases analyzed. The data indicate that significant numbers of serotonergic neurons degenerate in chronic alcoholics. Such a loss is likely to have significant clinical consequences.

TAP2 polymorphisms in Australian multiple sclerosis patients.

Polymorphism of the TAP2 gene locus, situated approximately 150 kb centromeric to the MHC class II loci HLA-DR, DQ was examined in 100 Australian patients with relapsing/remitting multiple sclerosis (MS), in 100 random controls and in 37 selected HLA-DRB1*1501-positive controls. The results were correlated with HLA class I and class II phenotypes. TAP2 encodes a protein involved in the transport and presentation of antigenic peptides by MHC class I molecules and hence is a candidate locus for a putative MS susceptibility gene either through functional interactions with class I alleles or as an explanation, via linkage disequilibrium (LD), for the known association between MS and the alleles DRB1*1501, DQA1*0102, DQB1*0602. Strong LD was found between the allele TAP2*01 and DRB1*1501 in both the MS and control populations. The MS-associated haplotype can therefore be extended to DRB1*1501, DQA1*0102, DQB1*0602, TAP2*01, and the putative gene locus could reside on the centromeric side of DQ. TAP2 typing, however, could not explain the DRB1*1501, DQA1*0102, DQB1*0602-negative patients in whom, interestingly, the frequency of TAP2*01 was decreased compared to controls. The results of this study exclude TAP2 as a locus for a necessary MS/MHC gene but indicate that an MS gene carried by the DRB1*1501, DQA1*0102, DQB1*0602 haplotype could reside centromeric of DQ.

A genome-wide screen for linkage disequilibrium in Australian HLA-DRB1*1501 positive multiple sclerosis patients.

The association of multiple sclerosis with alleles/haplotypes from the HLA region on chromosome 6p21 is well established although the remainder of the genome remains relatively unexplored. We have completed a genome-wide screen for linkage disequilibrium in a cohort of Australian multiple sclerosis patients positive for HLA-DRB1*1501. A total of 4346 microsatellite markers provided through the "Genetic Analysis of Multiple sclerosis in EuropeanS" (GAMES) collaborative were analysed in DNA separately pooled from cases (n=217) and controls (n=187). Associations were found in four genomic regions (12q15, 16p13, 18p11 and 19q13) previously identified in linkage genome screens. Three additional regions of novel association were also identified (11q12, 11q23 and 14q21). Further analysis of these regions is required to establish whether the associations observed are due to epistatic interaction with the HLA locus.

HLA-DMB gene and HLA-DRA promoter region polymorphisms in Australian multiple sclerosis patients.

The MHC region has been shown to contain a susceptibility locus for multiple sclerosis (MS). While the strongest association to date has been between HLA-DRB1*1501 and MS, the exact nature of the MHC association in MS remains unclear. Two candidate polymorphic loci within the MHC class II region, the HLA-DMB gene and the HLA-DRA promoter, which lie close to HLA-DRB1, were therefore examined in an Australian MS population. The HLA-DMB*0103 phenotype was increased in the MS patients (46% vs. 30%) and the frequency of the HLA-DRA promoter A allele was also increased (81% vs. 68%). When the subjects were stratified into HLA-DRB*1501 positive and negative individuals these associations were not significantly different. This is a result of the strong linkage disequilibrium between HLA-DRB*1501 and both HLA-DMB*0103 and the HLA-DRA promoter A allele. The complete linkage between DRB1*1501 and the HLA-DRA promoter A allele indicates that the MS susceptibility haplotype (DRB1*1501-HLA-DQB1*0602-HLA-DQA1* 0102) can be extended out to promoter of the HLA-DRA locus. Interactions between both HLA-DMB and the HLA-DRA promoter and other reported MS susceptibility loci were examined (TCRBV polymorphisms, HLA-DQA1 and HLA-DQB1). Some interactions between specific TCRBV polymorphisms and the HLA-DRA promoter were observed, which is consistent with other published reports suggesting an epistatic interaction between TCRBV and HLA-DRB1.

The DRB1 Val86/Val86 genotype associates with multiple sclerosis in Australian patients.

Genetic susceptibility to multiple sclerosis (MS) has so far been strongly localized to the MHC class II region encoding the alleles of the haplotype HLA-DRB1*1501, -DQA1*0102, -DQB1*0602. However, this haplotype is not carried by approximately 40% of MS patients; a potential explanation could be that they carry other MHC class II alleles with similar function due to the sharing of nucleotide sequences encoding critical amino acid residues. The DRB1 gene is polymorphic at residue 86, encoding valine or glycine. In view of the increasing evidence for a functional role for DRB1 aa86 in the binding and presentation of autoantigenic peptides such as myelin basic protein, this study investigated associations with the residue 86 polymorphism in an Australian MS population. A significant increase in the Val86/Val86 genotype was observed in the MS patients, which was still present in the absence of the DRB1*1501 allele (p = 0.032). This suggest that DRB1 aa86 may have an independent role in contributing to MS susceptibility. The Val86/Val86 genotype was correlated with genotyping for other putative MS susceptibility genes, including T cell receptor beta chain germline polymorphisms, HLA-DMB alleles, and -DQA1 and -DQB1 alleles encoding critical amino acid residues, with a significant interaction only observed with DQB1 Leu26 (p = 0.014). Additional studies of the HLA-DRB1 aa86 polymorphism in MS, and its function, are needed to more fully understand this association.

The CCR5 deletion mutation fails to protect against multiple sclerosis.

Recent advances in the understanding and identification of chemokines and their receptors have provided evidence for their consideration as candidate loci with respect to genetic susceptibility/resistance to MS. Increased levels of the chemokine, macrophage inflammatory protein (MIP)-1 alpha, have been demonstrated in the cerebrospinal fluid of both patients with MS and mice with EAE, and anti-MIP-1 alpha antibodies have been shown to prevent EAE. Recently, a common deletion mutation in the gene for the major receptor for MIP-1 alpha, chemokine receptor 5 (CCR5) has been described. Homozygotes for the mutation fail to express this receptor. Moreover, homozygotes are highly protected against HIV infection this has potential implications for the cell entry of infectious agents in other multifactorial disease where a viral component may be involved. In view of these aspects, a group of 120 unrelated Australian relapsing remitting MS and 168 unrelated control subjects were screened for the CCR5 delta 32 mutation. There was no significant difference in the allele frequency of CCR5 delta 32 gene between the MS patients (0.1125) and the control population (0.0921). The presence of two CCR5 delta 32 homozygotes in the MS patients indicates that the absence of CCR5 is not protective against MS. These data suggest that CCR5 is not an essential component in MS expression, though this may be due to redundancy in the chemokine system where different chemokine receptors may substitute for CCR5 when it is absent.

An allelic cluster of DQ alpha restriction fragments is associated with multiple sclerosis: evidence that a second haplotype may influence disease susceptibility.

Extensive analysis of restriction fragment length polymorphism using HLA class II and T-cell receptor gene probes has been carried out in an attempt to identify genetic markers more strongly associated with multiple sclerosis than the classically defined antigens DR2, Dw2, and DQw1. The use of DNA pooled from groups of patients and controls from northeast Scotland enabled the screening of 14 restriction endonucleases with five HLA-D region probes (DP alpha, DP beta, DQ alpha, DQ beta, DR beta) and two T-cell antigen receptor probes. Restriction fragment length polymorphisms which discriminated between multiple sclerosis and control pools were identified with four restriction enzymes: Msp1 (DQ alpha), BamH1, Bgl11, and Taq1 (DQ beta). No discriminatory polymorphism was seen with any of the other enzyme/probe combinations. Subsequent Southern blot analysis of individual DNA samples was carried out using these enzymes and probes in two independently conducted studies, in Northern Ireland and northeast Scotland. Following Msp1-digestion and hybridization to DQ alpha, a 3.25-kb fragment was observed in 31% of Scottish patients but in only 4% of controls from the same population. Furthermore, when only DR2-positive individuals were analyzed, there was a significant excess of this fragment in patients from both Scotland (28, or 2.9%) and Northern Ireland (20, or 3.4%). Although the DQ alpha gene characterized by this fragment remains to be determined, this fragment exhibits apparent allelism to DQw1. Therefore, these data raise the possibility that two different DQ alleles, one on each haplotype, may jointly contribute to disease susceptibility.

Visual hallucinations due to indomethacin: a case report.

Visual hallucinations may be caused by organic cerebral lesions and by drugs including indomethacin. We report here a case of indomethacin-induced visual hallucinations in which a clear description of the phenomenology shows how a complex hallucinatory experience may arise from the relatively non-specific effects of cerebral irritation.