Are radiographers an influencing factor in the radiation protection practices of speech-language therapists performing videofluoroscopic swallowing studies?

INTRODUCTION: A videofluoroscopic swallowing study (VFSS) is a fluoroscopic examination conducted by radiographers and speech-language therapists (SLTs) to assess dysphagia. Given the potential of SLTs to feed patients during the procedure, they may be exposed to radiation. The research aimed to assess radiation protection practices utilised by SLTs to determine if radiographers have a role in providing ongoing practical education. METHODS: An online questionnaire was distributed to SLTs from six countries (Australia, Canada, Ireland, New Zealand, United Kingdom and United States of America). Responses were analysed quantitatively using frequencies and chi-square analysis (p = 0.05) and supported by written comments. RESULTS: A total of 224 responses were analysed. Thyroid shields (94%) were used more frequently than full aprons (72%). Differences (p < 0.0001) were seen between Australian and USA participants regarding the use and position of radiation monitors; 43% of Australian participants stating they always used a monitor, compared to 75% of USA participants. Nearly all Australian SLTs wore monitors under shielding (92%) and at waist level (69%), while USA participants reported wearing them outside shielding (97%) and at thyroid level (94%). Participants' radiation practice was influenced primarily by other SLTs (64%), followed by radiographers (57%). However, written comments revealed the significance of the radiographer in providing training as "radiographers are excellent at ensuring we [use] right equipment, stand in the right places and use exposure monitoring". CONCLUSION: SLTs did not always adopt the ICRP principle of shielding and there were inconsistencies with regards to the use and placement of radiation monitors. Radiographers are well positioned to provide advice with regards to safe practice. IMPLICATIONS FOR PRACTICE: Opportunities to enhance radiation protection practices are evident, as is the advising role of radiographers.

Semiautomatic brain region extraction: a method of parcellating brain regions from structural magnetic resonance images.

Structural MR imaging has become essential to the evaluation of regional brain changes in both healthy aging and disease-related processes. Several methods have been developed to measure structure size and regional brain volumes, but many of these methods involve substantial manual tracing and/or landmark identification. We present a new technique, semiautomatic brain region extraction (SABRE), for the rapid and reliable parcellation of cortical and subcortical brain regions. We combine the SABRE parcellation with tissue compartment segmentation [NeuroImage 17 (2002) 1087] to produce measures of gray matter (GM), white matter (WM), ventricular CSF, and sulcal CSF for 26 brain regions. Because SABRE restricts user input to a few easily identified landmarks, inter-rater reliability is high for all volumes, with all coefficients between 0.91 and 0.99. To assess construct validity, we contrasted SABRE-derived volumetric data from healthy young and older adults. Results from the SABRE parcellation and tissue segmentation showed significant differences in multiple brain regions in keeping with regional atrophy described in the literature by researchers using lengthy manual tracing methods. Our findings show that SABRE is a reliable semiautomatic method for assessing regional tissue volumes that provides significant timesavings over purely manual methods, yet maintains information about individual cortical landmarks.

Effect of direct injection of melanin-concentrating hormone into the paraventricular nucleus: further evidence for a stimulatory role in the adrenal axis via SLC-1.

Melanin-concentrating hormone (MCH) is implicated in the control of a number of hormonal axes including the hypothalamic-pituitary adrenal (HPA) axis. Previous studies have shown that there is evidence for both a stimulatory and an inhibitory action on the HPA axis; therefore, we attempted to further characterize the effects of MCH on this axis. Intracerebroventricular injection of MCH increased circulating adrenocorticotropic hormone (ACTH) at 10 min post injection. Injection of MCH directly into the paraventricular nucleus (PVN) was found to increase both circulating ACTH and corticosterone 10 min after injection. Additionally, MCH was found to increase corticotropin-releasing factor (CRF) release from hypothalamic explants, and this effect was abolished by the specific SLC-1 antagonist SB-568849. Neuropeptide EI, a peptide from the same precursor as MCH was also found to increase CRF release from explants. These results suggest that MCH has a stimulatory role in the HPA axis via SLC-1, and that MCH exerts its effects predominantly through the PVN CRF neuronal populations

Sub-lethal concentrations of activated complement increase rat lymphocyte glutamine utilization and oxidation while lethal concentrations cause death by a mechanism involving ATP depletion.

Nucleated cells are more resistant to complement-mediated cell death than anucleated cells such as erythrocytes. There are few reports concerning the metabolic response of nucleated cells subjected to sub-lethal complement attack. It is possible that the rate of utilization of specific metabolic fuels by the cell is increased to enhance cell defence. We have measured the maximum activity of hexokinase, citrate synthase, glucose 6-phosphate dehydrogenase and glutaminase in rat mesenteric lymphocytes exposed to sub-lethal concentrations of activated complement (present in zymosan-activated serum, ZAS). These enzymes were carefully selected as they indicate changes of flux in glycolysis, TCA cycle, pentose phosphate pathway and glutaminolysis, respectively. The only enzyme activity to change on exposure of lymphocytes to ZAS was glutaminase, which was enhanced approximately by two-fold. Although rates of both glutamine and glucose utilization were enhanced by exposure to ZAS, only the rate of oxidation of glutamine was increased. Complement kills anucleated cells by simple osmotic lysis. However, it is likely that some nucleated cells will display characteristics of an ordered death mechanism and we have demonstrated that the concentration of lymphocyte ATP is dramatically decreased by activated complement. Nevertheless, the extent of cell death could be significantly reduced by the addition of inhibitors of the nuclear enzyme poly (ADP-ribose) polymerase (PARP). We conclude that glutamine metabolism is not only important for lymphocyte proliferative responses but is also important for cell defence from sub-lethal concentrations of activated complement. The rapid rate of complement-induced lymphocyte death reported here is suggested to be a consequence of over-activation of the nuclear enzyme PARP and ATP depletion.

Enterotachogram analysis to distinguish irritable bowel syndrome from Crohn's disease.

Crohn's disease is often initially misdiagnosed as irritable bowel syndrome. The goal of this research was to determine if computerized auscultation (fasting enterotachogram analysis) could have a role in distinguishing between these diagnoses. Patients with irritable bowel syndrome, Crohn's disease, and a control group were enrolled in the study. The fasting sound-to-sound interval, standard deviation of the interval, sounds per minute, and percentage time involved with bowel sounds was determined by computerized enterotachogram analysis. The mean sound-to-sound interval for the Crohn's group (1232 msecs) and the controls (1706 msecs) was significantly higher than the irritable bowel group (511 msecs, P < 0.0001). We conclude that Crohn's is not characterized by a shortened interval. The high negative predictive value of the fasting enterotachogram for irritable bowel syndrome suggests that an interval greater than 740 msecs should trigger a search for an alternative diagnosis to irritable bowel. Crohn's disease should be included in that differential.

Ca(2+) entry through store-operated channels in mouse sperm is initiated by egg ZP3 and drives the acrosome reaction.

Fertilization occurs after the completion of the sperm acrosome reaction, a secretory event that is triggered during gamete adhesion. ZP3, an egg zona pellucida glycoprotein, produces a sustained increase of the internal Ca(2+) concentration in mouse sperm, leading to acrosome reactions. Here we show that the sustained Ca(2+) concentration increase is due to the persistent activation of a Ca(2+) influx mechanism during the late stages of ZP3 signal transduction. These cells also possess a Ca(2+) store depletion-activated Ca(2+) entry pathway that is open after treatment with thapsigargin. Thapsigargin and ZP3 activate the same Ca(2+) permeation mechanism, as demonstrated by fluorescence quenching experiments and by channel antagonists. These studies show that ZP3 generates a sustained Ca(2+) influx through a store depletion-operated pathway and that this drives the exocytotic acrosome reaction.

Nursing directors' perceptions of the dental components of the Minimum Data Set (MDS) in nursing homes.

The Directors of Nursing (DON's) of all 428 nursing homes in the state of Iowa were sent a pre-tested questionnaire. The aim of the study was to examine the perceptions by nursing directors on the utility of a dental component of the Minimum Data Set (MDS) in identifying residents with dental problems in their facility. The return rate was 55.1% from the DON's. It was reported that 66.4% of the homes had a training program for the MDS and that in 38.0% of the homes there was only one person doing the assessments. The majority (76.0%) of the DON's stated that the MDS was useful in tracking residents and that it did help them to identify dental problems. When asked how often it was useful in the identification of dental needs, only 9% stated that it was often useful. Also, regarding frequency of dental appointments for the residents, a mean of 51.0% of residents were estimated to have received some dental care during the previous year (means of 33.2% at the facility, 22.4% at a dental office, and 0.4% in a hospital). If change is to occur, the dental profession must try to get the nursing home assessors to convince the nursing homes to use the oral/nutritional/dental sections of the MDS as they were intended under the OBRA regulations.

Comparison of IgE and IgG antibody-dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma.

Allergic reactions are mediated by IgE antibodies bound to high-affinity receptors on mast cells in peripheral tissues and are characterized by their immediacy and hypersensitivity. These properties could also be advantageous in immunotherapy against cancer growth in peripheral tissues. We have constructed chimeric IgE and IgG1 antibodies with murine V regions and human C regions corresponding to the MOv18 monoclonal antibody against the human ovarian tumor-associated antigen, folate binding protein. The antibodies exhibited the expected binding affinities for antigen and Fc receptors, and effector activities with human basophils and platelets in vitro. The protective activities of MOv18-IgE and MOv18-IgG1 were compared in a SCID mouse xenograft model of ovarian carcinoma. The beneficial effects of MOv18-IgE were greater and of longer duration than those of MOv18-IgG1. Our results suggest that the allergic reaction could be harnessed for the suppression of ovarian tumors.

Computerized auscultation applied to irritable bowel syndrome.

The purpose of this study was to investigate the potential of a computerized auscultation method for providing an objective, quantitative measure characteristic of irritable bowel syndrome. Bowel sounds from irritable bowel patients and normal controls were digitized using an electronic stethoscope. Computerized analysis indicated that the character of the bowel sounds did not differ significantly between groups. However, the fasting sound-to-sound interval was significantly different between groups (1931 +/- 365 msec for normals and 452 +/- 35 msec for the irritable bowel group; P = 0.0001). Using the sound-to-sound interval as a test for irritable bowel syndrome, the cutoff value of 640 msec resulted in a sensitivity of 89%, and a specificity of 100%. We conclude that computerized analysis of bowel sounds has the potential to be a noninvasive, quantitative, and objective test providing positive criteria in the diagnosis of irritable bowel syndrome.

Absence of association between Alzheimer disease and the -491 regulatory region polymorphism of APOE.

A novel polymorphism (-491 A/T) within the regulatory region on the apolipoprotein E gene has recently been reported to be associated with risk for Alzheimer disease (AD). To test this association in an independent data set, we have examined this polymorphism in a sample of 88 well-characterized AD cases and compared the allele frequency and genotype frequencies for this polymorphism with those observed in 112 cognitively normal subjects drawn from the same ethnic group. These results suggest that in the current data set at least, the -491 A/T polymorphism is not associated with risk for AD, but may be in partial linkage disequilibrium with the APOE epsilon2/epsilon3/epsilon4 polymorphism.

Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity.

CONTEXT: Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, and a recent study has suggested a locus on chromosome 12. OBJECTIVE: To confirm or refute the existence of a familial AD susceptibility locus on chromosome 12 in an independent sample of familial AD cases. DESIGN: Retrospective cohort study. DNA data for 6 chromosome 12 genetic markers were evaluated using parametric lod score and nonparametric linkage methods and linkage heterogeneity tests. The latter include the admixture test of homogeneity in the total group of families and the predivided sample test in families stratified by the presence or absence of an apolipoprotein E (APOE) epsilon4 allele among affected members. Parametric analyses were repeated assuming autosomal dominant inheritance of AD and either age- and sex-dependent penetrance or zero penetrance for the analysis of unaffected relatives. SETTING: Clinical populations in the continental United States, Canada, Argentina, and Italy. PATIENTS: Fifty-three white families composed of multiple members affected with AD, from whom DNA samples were obtained from 173 patients with AD whose conditions were diagnosed using established criteria and from 146 nondemented relatives. MAIN OUTCOME MEASURE: Presence of an APOE epsilon4 allele among affected family members. RESULTS: Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families. However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1). The estimated proportion of linked families within the 53 families examined varied between 0.40 and 0.65, depending on the genetic model assumed and APOE status. The precise location of the AD gene could not be determined, but includes the entire region suggested previously. Nonparametric linkage analysis confirmed linkage to chromosome 12 with the strongest evidence at D12S96 (P<.001). CONCLUSIONS: Our data provide independent confirmation of the existence of an AD susceptibility locus on chromosome 12 and suggest the existence of AD susceptibility genes on other chromosomes. Screening a larger set of families with additional chromosome markers will be necessary for identifying the chromosome 12 AD gene.

Digital imaging colposcopy: corrected area measurements using shape-from-shading.

The quantitative measurement of areas on the cervix is of interest to researchers studying the natural history of human papilloma viral lesions. Measurement of areas from images obtained through a colposcope are, however, inherently in error due to the image being a two-dimensional projection of a three-dimensional object. The ability to correct for these errors through use of digital imaging colposcopy and a practical application of a shape from shading algorithm was developed in this study. The shape from shading technique requires empirical measurement of the relationship between observed light intensity and the viewing angle (referred to as a reflection map). It was found that a population mean reflection map provided a correction that was about as accurate as using an individual's own reflection map (making it unnecessary to measure a map for each exam). Digital red filtering of the images increased accuracy and precision of measurement.

Site-specific photobiotinylation of immunoglobulins, fragments and light chain dimers.

Herein we report a new method to rapidly photoinsert biotin into a specific and highly conserved site on the Ig structure using a mild photochemical activation step. This site resides in the Fv fragment and involves invariant residues which provide base stacking interactions to the purine ring of ATP (Rajagopalan et al. (1996) Proc. Natl. Acad. Sci. USA 93, 6019-6024). Biotin was coupled to either the phosphate or the ribose of the 8-azidopurine nucleotide or nucleoside photoaffinity probe and shown to insert into the affinity site efficiently. Several monoclonal and polyclonal antibodies, as well as enzymatic and recombinant antibody fragments and light chain dimers were photoaffinity biotinylated and used in ELISA, FACS and Western blots. The selectivity of this site-specific biotinylation method also allows for biotinylation of antibodies in culture supernatants and immune sera without prior purification. Because the biotinylation takes place under physiological conditions and within a short time period, photobiotinylation would be the preferred method for antibodies which are easily damaged by classical non-site specific random biotinylation chemistry.

Protein kinase C activation during progesterone-stimulated acrosomal exocytosis in human spermatozoa.

The involvement of protein kinase C (PKC) in exocytosis of the mammalian sperm acrosome is still a controversial issue. Work carried out thus far has failed to provide direct evidence for the activation of this enzyme upon stimulation with natural agonists of acrosomal exocytosis. We have therefore used progesterone stimulation of the acrosome reaction in human spermatozoa to clarify this issue. In spermatozoa preincubated under conditions known to support capacitation and fertilization in vitro, treatment with progesterone caused a time-dependent stimulation of phosphorylation of at least eight proteins ranging in size from approximately 20-220 kDa. The inclusion of the PKC inhibitors chelerythrine chloride or calphostin C reduced the observed phosphorylation in a concentration-dependent manner. Exogenously supplied phorbol 12-myristate-13-acetate (PMA) or the permeant diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol (OAG), synthetic activators of PKC, also stimulated phosphorylation in preincubated spermatozoa, but inclusion of calphostin C diminished the response. Furthermore, the prior inclusion of the 1,4-dihydropyridine Ca2+ channel antagonist nifedipine also inhibited phosphorylation, suggesting that PKC is activated downstream of Ca2+ channel opening. Exocytosis triggered by progesterone was significantly inhibited by chelerythrine chloride or calphostin C. Both PMA and OAG triggered exocytosis, but the inclusion of chelerythrine chloride significantly inhibited the response; exocytotic responses were seen only in capacitated cells. These results provide the first direct evidence that PKC activation plays a role in the signal transduction pathway underlying acrosomal exocytosis in progesterone-stimulated capacitated spermatozoa.

Role for Ca2+ channels in the signal transduction pathway leading to acrosomal exocytosis in human spermatozoa.

Progesterone interaction with human spermatozoa promotes a rise in intracellular Ca2+ and can trigger acrosomal exocytosis in capacitated cells. We have used nifedipine, a 1,4-dihydropyridine Ca2+ channel antagonist, to investigate the possibility that Ca2+ channels play a role in the progesterone-stimulated exocytotic response. Cells were assessed biochemically for the generation of diacylglycerol (DAG) and microscopically for acrosome loss using chlortetracycline fluorescence. When motile cells were preincubated for 5 hr using culture conditions similar to those used for successful human in vitro fertilization, a short exposure to progesterone significantly stimulated DAG formation and acrosomal exocytosis. The addition of nifedipine (10 and 100 nM), either at time 0 or just prior to progesterone introduction, significantly inhibited both DAG formation and exocytosis, suggesting that Ca2+ channels are involved in the responses observed. Treatment of capacitated cells with a synthetic permeant DAG stimulated exocytosis irrespective of whether nifedipine was present, indicating that Ca2+ channels function prior to DAG generation. The possibility that an influx of Na+, as well as Ca2+, might be involved in the exocytotic pathway was investigated using the monovalent cation ionophores monensin and nigericin. Both significantly stimulated DAG generation and acrosome loss, but the prior inclusion of nifedipine significantly inhibited all responses. These results strongly suggest that the entry of Ca2+ through Ca2+ channels, with characteristics similar to those of L-type, voltage-sensitive Ca2+ channels found in cardiac and skeletal muscle, is a crucial step in the sequence of events leading to exocytosis in progesterone-stimulated human spermatozoa. An influx of Na+ also may play a role, but at a point prior to the opening of Ca2+ channels.

The cognitive assessment screening test (CAST) for dementia.

The purpose of this study was to assess the usefulness, the sensitivity, and the specificity of the Cognitive Assessment. Screening Test (CAST), a paper-and-pencil self-administered cognitive test designed to screen elderly people for possible dementia, for use in general physicians' offices, requiring little expertise or staff time. CAST consists of three parts: part A (relatively easy), part B (more demanding), and part C (self-report of concerns). CAST was administered in two studies to: (1) 19 patients known to be mildly to moderately demented versus 24 age-matched normal controls (to establish cutoff standards); and (2) a "real world" sample of 26 elderly patients not known to be demented, attending a general medicine clinic. The sensitivity and specificity of CAST were compared with the Mini-Mental State Examination (MMSE) and the Blessed Dementia Scale cognitive portion (BDS-cog). In study 1, controls were given a detailed neuropsychological battery; in study 2, all patients were given the neuropsychological battery, which served as the "gold standard" to identify individuals with cognitive impairment. In study 1, the cutoff scores for dementia using CAST (Parts A and B) were established. CAST discriminated demented patients from controls with a sensitivity of 95% and a specificity of 88%; the MMSE had a sensitivity of 74% and a specificity of 100%; and the BDS-cog had a sensitivity of 100% and a specificity of 96%. In study 2, CAST discriminated cognitive impairment with a sensitivity of 88% and a specificity of 100%, the MMSE had a sensitivity of 38% and a specificity of 100%; and the BDS-cog had a sensitivity of 50% and a specificity of 94%. Part C was not used to discriminate demented from normal elderly individuals, but to screen for those concerned about their cognitive functioning. CAST is highly useful as a dementia screening test, with sensitivity and specificity equal to or better than the MMSE and BDS-cog, yet requiring minimal examiner time and little training or experience to administer.

A role for diacylglycerol in human sperm acrosomal exocytosis.

Using human spermatozoa stimulated with either progesterone or the Ca2+ ionophore A23187 to undergo acrosomal exocytosis, we have investigated potential pathways for generation of diacylglycerol (DAG) and have examined the possibility that DAG plays an important role in the exocytotic response. Both treatments resulted in rapid and considerable generation of DAG, followed by a limited rise in phosphatidic acid (PA). Further experiments indicated that phospholipase C (PLC) activity is important in this generation of DAG, but phospholipase D activity probably is not. In addition, polyphosphoinositide-specific phosphoinositidase C activation and hydrolysis, of phosphatidylinositol 4,5-bisphosphate appears to be a necessary prerequisite for activation of the PLC pathway. Finally the DAG formed appears to be important in acrosomal exocytosis: (i) blocking DAG metabolism with a DAG kinase inhibitor resulted in both increased endogenous levels of DAG and a significantly increased exocytotic response in stimulated cells and (ii) exogenous DAG induced exocytosis in capacitated spermatozoa whereas PA did not. Taken together, these results suggest that DAG plays a key role in events leading to membrane fusion during human sperm acrosomal exocytosis stimulated by natural agonists.