The importance of clearly communicating the essence of harm reduction.
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Biomedical subjects
Publications and source records attributed to N Hunt.
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The capacity of three novel iron chelators, namely 1-[N-ethoxycarbonylmethylpyridoxylidenium]-2-[2'-pyridyl]hydrazine bromide (EPH), 1-[5'-bromosalicylidene]-2-[2"-pyridyl]hydrazine (BsPH), and 1-pyridoxylidene-2-[1'-phthalazyl]hydrazine dihydrochloride (PPhH), to inhibit the proliferation of mitogen-stimulated murine lymph node cells was examined in vitro. All three are of the aryl hydrazone class, the prototype of which is pyridoxal isonicotinoyl hydrazone. The chelators inhibited lymphoproliferation at low micromolar concentrations. EPH and PPhH had an inhibitory capacity comparable to that of desferrioxamine (IC(50): 3 and 2 microM, respectively), whereas BsPH was more potent (IC(50) < 1 microM). The inhibitory effects of the chelator were not due to cell cytotoxicity and could be abrogated by pretreating the chelator with iron. Time-course studies established a site of action for the chelators at the G(1)/S phase transition. These agents warrant further investigation for their potential as immunosuppressants.
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Prior studies of oligonucleotide microarray-based mutational analysis have demonstrated excellent sensitivity and specificity except in circumstances where a frameshift mutation occurs in the context of a short repeated sequence. To further evaluate this circumstance, a series of nucleic acid samples having heterozygous mutations within repetitive BRCA1 sequence tracts was prepared and evaluated. These mutations included single nucleotide insertions and deletions in homopolymer runs, insertions and deletions of trinucleotide repeats, and duplications. Two-color comparative hybridization experiments were used wherein wild type reference and test targets are co-hybridized to microarrays designed to screen the entire BRCA1 coding sequence for all possible sequence changes. Mutations in simulated heterozygote samples were detected by observing relative losses of test target hybridization signal to select perfect match oligonucleotide probes. While heterozygous mutations could be readily distinguished above background noise in 9/19 cases, it was not possible to detect alterations in a poly dA/dT tract, small triplet repeat expansions, and a 10 bp direct repeat. Unexpectedly, samples containing (GAT)(3) triplet repeat expansions showed significantly higher affinity toward specific perfect match probes relative to their wild type counterparts. Therefore, markedly increased as well as decreased test sample hybridization to perfect match probes should be used to raise a suspicion of repetitive sequence changes.
An interactional model of stress that integrates current research on competitive affects and emphasizes the temporal dimensions of the stress process is forwarded. The literature reveals that the study of athletes' affective responses to competition has been narrowly focused on pre-competitive anxiety. Equivocal findings on temporal patterning of competitive anxiety suggest that a fundamental change in the empirical approach is needed because the current conceptualization of anxiety and other complex emotions is imprecise. The analysis of secondary emotions as patterns of discrete basic emotions, as suggested by differential emotions theorists, is proposed for consideration in future research. In this view, competitive anxiety is considered as a set of patterns of emotions rather than a unitary affect. The adoption of this approach could result in better operationalization of competitive anxiety as well as other secondary performance-related emotions. We propose that research on competitive affects should follow two parallel lines. The first should focus on the description of complex emotional states that reflect the idiosyncratic emotional experience and vocabulary of the athlete. The second should examine the sets of basic emotions experienced throughout competition, and focus on individual differences and factors determining those differences. The integration of the two approaches could lead to a better understanding of whether, how and why individuals differ in the interpretation of specific secondary emotions and their effect on performance. Moreover, it would permit the analysis of intra-individual variations in labelling secondary emotions with respect to different competitive contexts and temporal aspects.
The cAMP-responsive element modulator (CREM) gene encodes a transcription factor that is essential for spermatogenesis. In mouse testis, several CREM repressors and activators have been identified. In contrast to the situation for the mouse, however, little is known about CREM isoforms in the primate testis. We analyzed CREM isoforms and mRNA expression in a clinically relevant primate model, the cynomolgus monkey (Macaca fascicularis). A cDNA library was generated from monkey testis; and two activator isoforms (tau2 with and without exon gamma) were identified, which displayed high sequence identity to mouse and human isoforms. The insertion of exon gamma was observed for the first time in the primate testis. CREM activator expression was confined to the testis, where it was seen in late pachytene spermatocytes and round spermatids in specific spermatogenic stages, as revealed by in situ hybridization. Comparison of the mRNA and the recently described protein expression indicated a lack of translational delay of CREM expression. Comparative analysis of testicular CREM expression by reverse transcription-polymerase chain reaction yielded several transcripts in the rat, mouse, hamster, and marmoset; two transcripts in cynomolgus and rhesus monkeys; and one transcript in men. These findings suggest an evolutionary trend from multiple activator isoforms to a single activator transcript in men.
We report a detailed experimental study of the superlattice structures formed in dense binary mixtures of hard-sphere colloids. The phase diagrams observed depend sensitively on the ratio alpha=R(S)/R(L) of the radii of the small (S) and large (L) components. Mixtures of size ratio alpha=0.72, 0.52, 0.42, and 0.39 are studied. The structures of the colloidal phases formed were identified using a combination of light-scattering techniques and confocal fluorescent microscopy. At alpha=0.39, ordered binary crystals are formed in suspensions containing an equal number of large and small spheres which microscopy shows have a three-dimensional structure similar to either NaCl or NiAs. At the larger size ratio, alpha=0.52, we observe LS2 and LS13 superlattices, isostructural to the molecular compounds AlB2 and NaZn13, while at alpha=0.72 the two components are immiscible in the solid state and no superlattice structures are found. These experimental observations are compared with the predictions of Monte Carlo simulations and cell model theories.
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The aim of the present study was to identify patients who were at particular risk of violent behaviour, over a period of one month in a psychiatric high dependency unit, and to examine whether particular patients could be identified at admission who would subsequently be violent. Medical records, and other documents for 52 inpatients were included. Demographic, historical and clinical data available at admission were noted. All violent incidents were recorded and classified. Seventeen of 52 patients committed physical violence, usually to the staff. Most incidents were carried out by a small number of individuals. Identifying the violent, using variables available at admission, was not possible. The ward admitted a group with a subsequent high rate of violence. Prediction within this high-risk group was not possible. Measures aimed at preventing violence on a local secure ward should apply to all patients and should not be targeted just at those that would appear to be the most likely to be violent.
The use of a valgus brace can effectively relieve the symptoms of unicompartmental osteoarthritis of the knee. This study provides an objective measurement of function by analysis of gait symmetry. This was measured in 30 patients on four separate occasions: immediately before and after initial fitting and then again at three months with the brace on and off. All patients reported immediate symptomatic improvement with less pain on walking. After fitting the brace, symmetry indices of stance and the swing phase of gait showed a consistent and immediate improvement at 0 and 3 months, respectively, of 3.92% (p = 0.030) and 3.40% (p = 0.025) in the stance phase and 11.78% (p = 0.020) and 9.58% (p = 0.005) in the swing phase. This was confirmed by a significant improvement at three months in the mean Hospital for Special Surgery (HSS) knee score from 69.9 to 82.0 (p < 0.001). Thus, wearing a valgus brace gives a significant and immediate improvement in the function of patients with unicompartmental osteoarthritis of the knee, as measured by analysis of gait symmetry.
This study assessed the factor structure of the Impact of Event Scale (IES), a measure of intrusion and avoidance, using a sample of World War II and Korean War veterans who had experienced combat 40-50 years earlier. A series of 3 confirmatory factor analytic models were specified and estimated using LISREL 8.3. Model 1 specified a 1-factor model. Model 2 specified a correlated 2-factor model. Model 3 specified a 2-factor model with additional cross-factor loadings for Items 2 and 12. Model 3 was found to fit the data. In addition, this model was found to be a better explanation of the data than the other models. Also in addition, the correlations between the Intrusion and Avoidance factors and the 4 subscales of the 28-item General Health Questionnaire were examined to determine the distinctiveness of the two IES factors.
The Index of Orthodontic Treatment Need (IOTN) is a visual-based index and has been widely used. This paper describes the development and evaluation of tactile graphics representing the aesthetic component (AC) of IOTN for the use of visually impaired patients (VI). Four tactile graphics were produced corresponding to IOTN photographs 1 (graphic 1, no treatment - mild need), 5 (graphic 2, moderate need), 8 (graphic 3, severe need; increased overjet) and 10 (graphic 4, severe need). Nine (30-50 years) expert consumers from the Royal National Institute for the Blind (RNIB) and 13 VI schoolchildren (11-16 years) evaluated the graphics. The evaluation was in terms of design features, complexity of information and ease of use. Each individual was asked to arrange the graphics in order of severity of malocclusion. The procedure was repeated after 30 min to test individual reliability (www.clinorthodres.com/cor-c-084/). The consumer group was able to identify the main features in each graphic and found them easy to use. Six had arranged the graphics correctly at the first attempt and five on their second. The children were able to distinguish the different oral features, except the overjet presentation in graphic 2. Nine children arranged the graphics correctly at the first attempt, but only six at the second. The confusion centred for both groups on presenting an increased overjet with graphic 2. A modification was undertaken to enhance the anterior-posterior nature of the image. Fifteen VI schoolchildren reassessed the modified graphics, 14 arranged them correctly at the first attempt and 13 at the second. The study concluded that IOTN tactile graphics were well accepted and showed a good reliability.
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We reviewed histologically the incidence and pathogenesis of the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the pseudocapsule, femoral and acetabular membranes and periprosthetic tissue at revision of 789 cases of failed total hip replacement. In 13, periprosthetic tissues were found to have deposits of CPPD crystals in areas of cartilaginous metaplasia; four also showed evidence of localised deposition of amyloid. None of the patients had a history of chondrocalcinosis in the hip or other joints. Cartilaginous metaplasia and other changes in periprosthetic tissues may predispose to the deposition of CPPD and associated localised amyloid.
The market for medical devices is governed by the need to have validated products and processes, clean manufacturing environments and proven shelf-life. All this, often for products that are disposable, low-unit-cost items and, as such, highly price sensitive. This, in turn, has an impact on the businesses supplying the market. This article considers one such supply market, packaging, and the steps taken by packaging manufacturers to respond to these pressures while maintaining long-term, viable products.
Pairs of high density oligonucleotide arrays (DNA chips) consisting of >96 000 oligonucleotides were designed to screen the entire 5.53 kb coding region of the hereditary breast and ovarian cancer BRCA1 gene for all possible sequence changes in the homozygous and heterozygous states. Single-stranded RNA targets were generated by PCR amplification of individual BRCA1 exons using primers containing T3 and T7RNA polymerase promoter tails followed by in vitro transcription and partial fragmentation reactions. Fluorescent hybridization signals from targets containing the four natural bases to >5592 different fully complementary 25mer oligonucleotide probes on the chip varied over two orders of magnitude. To examine the thermodynamic contribution of rU.dA and rA.dT target.probe base pairs to this variability, modified uridine [5-methyluridine and 5-(1-propynyl)-uridine)] and modified adenosine (2,6-diaminopurine riboside) 5'-triphosphates were incorporated into BRCA1 targets. Hybridization specificity was assessed based upon hybridization signals from >33 200 probes containing centrally localized single base pair mismatches relative to target sequence. Targets containing 5-methyluridine displayed promising localized enhancements in hybridization signal, especially in pyrimidine-rich target tracts, while maintaining single nucleotide mismatch hybridization specificities comparable with those of unmodified targets.
The external nose is generally considered to have a relatively static shape. Movement of the nose and the potential for change of external shape and the internal airway have been assessed by (1) cadaver dissection and (2) dynamic studies during a standardized series of facial expressions in 13 subjects; video recording of the movement of skin markers, electromyography, and moving magnetic resonance images. A standard description of muscle anatomy is presented. The dynamic investigations indicated the following. Video analysis showed the components of muscle action: dilatation, constriction of the nostril, depression of the tip, vertical contraction in the bridge, and elevation of the alar, in different expressions. Electromyography confirmed muscle actions during expression and phonation. Magnetic resonance imaging demonstrated large changes in the external shape of the nose and nasal aperture due to muscle actions. Muscle function should be given greater consideration in aesthetic and cleft rhinoplasty.
Mutational analysis of large genes with complex genomic structures plays an important role in medical genetics. Technical limitations associated with current mutation screening protocols have placed increased emphasis on the development of new technologies to simplify these procedures. High-density arrays of >90,000-oligonucleotide probes, 25 nucleotides in length, were designed to screen for all possible heterozygous germ-line mutations in the 9.17-kb coding region of the ATM gene. A strategy for rapidly developing multiexon PCR amplification protocols in DNA chip-based hybridization analysis was devised and implemented in preparing target for the 62 ATM coding exons. Improved algorithms for interpreting data from two-color experiments, where reference and test samples are cohybridized to the arrays, were developed. In a blinded study, 17 of 18 distinct heterozygous and 8 of 8 distinct homozygous sequence variants in the assayed region were detected accurately along with five false-positive calls while scanning >200 kb in 22 genomic DNA samples. Of eight heterozygous sequence changes found in more than one sample, six were detected in all cases. Five previously unreported sequence changes, not found by other mutational scanning methodologies on these same samples, were detected that led to either amino acid changes or premature truncation of the ATM protein. DNA chip-based assays should play a valuable role in high throughput sequence analysis of complex genes.