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Biomedical subjects

A Dawson

Publications and source records attributed to A Dawson.

At least 37 records · Page 2Linked to original sources

Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies.

Bone mineral density (BMD) measurements are widely used to estimate the risk of osteoporotic fractures. In addition, many other risk factors have been identified, some of which are known to add to the risk independently of BMD measurements. The combination of BMD with such risk factors increases the gradient of risk/standard deviation (SD) than that achieved by BMD alone. In this paper, we report the fracture probabilities according to age, gender, and relative risk, and have investigated the effects of changes in the gradient of risk for osteoporotic fractures on the sensitivity and specificity of assessments, modeled on the population of Sweden. Ten-year risks of hip, clinical vertebral, forearm, or proximal humeral fracture were computed with increments in gradient of risk that varied from 1.5 to 6.0 per SD change in skeletal risk. The identification of high-risk groups had little effect on the specificity of assessments, but increased the sensitivity over a wide range of assumptions. The inclusion of all four fracture types had little effect on sensitivity, but increased the positive predictive value of the test. Positive predictive value also increased with age, so that values greater than 50% were obtained testing women at the age of 65 years with modest gradient of risk of 2.0-2.5/SD when small segments of the population were targeted (0.5-5%). Screening of women to direct intervention at the age of 65 years and targeting 25% of the population could save up to 23% of all fractures in women over the next 10 years by the use of multiple tests with a moderate gradient of risk (RR = 2.0/SD). Such gradients might be achieved with the use of multiple risk factors to identify patients at risk.

Age Factors↗

Changes in basal hypothalamic chicken gonadotropin-releasing hormone-I and vasoactive intestinal polypeptide associated with a photo-induced cycle in gonadal maturation and prolactin secretion in intact and thyroidectomized starlings (Sturnus vulgaris).

Chicken gonadotropin-releasing hormone-I (GnRH-I) and the avian prolactin-releasing hormone, vasoactive intestinal polypeptide (VIP), were measured in the basal hypothalamus in male starlings during photo-induced gonadal growth and the subsequent development and maintenance of reproductive photorefractoriness. Comparisons were made with thyroidectomized birds, which maintain breeding condition irrespective of changes in photoperiod. In intact birds, basal hypothalamic GnRH-I increased four-fold after photostimulation and then decreased 115-fold over 12 weeks to values characteristic of long-term photorefractoriness. Pituitary and plasma prolactin increased after photostimulation, reaching peak values when the testes were regressing, and returned to low values in long-term photorefractory birds. Basal hypothalamic VIP did not change after photostimulation in intact birds. In photostimulated thyroidectomized birds, values for basal hypothalamic GnRH-I and VIP, and for pituitary and plasma prolactin, remained no different to those of nonphotostimulated intact birds. These observations confirm that reproductive photorefractoriness is related to a decrease in hypothalamic GnRH-I. However, photorefractoriness in terms of prolactin secretion is not similarly related to a decrease in basal hypothalamic VIP. The mechanisms responsible for the decrease in prolactin in long-term photorefractory birds and for the total lack of photoperiodic responses in thyroidectomized birds remain unresolved.

Animals↗

Salvage of major joint prostheses in aggressive non-specific panniculitis.

Panniculitis is a relatively rare condition, which is usually treated non-operatively. We present a case of panniculitis causing an acute septicaemic episode and threatening the integrity of underlying joint prostheses. The situation was salvaged by radical debridement of the affected areas, and reconstruction using split-skin grafts. Considerations in the management of patients with this condition are discussed.

Aged↗

DNA-binding activity and subunit interaction of the mariner transposase.

Mos1 is a member of the mariner/Tc1 family of transposable elements originally identified in Drosophila mauritiana. It has 28 bp terminal inverted repeats and like other elements of this type it transposes by a cut and paste mechanism, inserts at TA dinucleotides and codes for a transposase. This is the only protein required for transposition in vitro. We have investigated the DNA binding properties of Mos1 transposase and the role of transposase-transposase interactions in transposition. Purified transposase recognises the terminal inverted repeats of Mos1 due to a DNA-binding domain in the N-terminal 120 amino acids. This requires a putative helix-turn-helix motif between residues 88 and 108. Binding is preferentially to the right hand end, which differs at four positions from the repeat at the left end. Cleavage of Mos1 by transposase is also preferentially at the right hand end. Wild-type transposase monomers interact with each other in a yeast two-hybrid assay and we have used this to isolate mutations resulting in reduced interaction. These mutations lie along the length of the protein, indicating that transposase-transposase interactions are not due to a single interaction domain. One such mutation which retains both DNA-binding and catalytic activity has greatly reduced ability to excise Mos1 from plasmid DNA through coordinate cleavage of the two ends and transposition in vitro is lowered to a level 20-fold below that of the wild-type. This suggests that transposase-transposase interaction is required to form a synaptic complex necessary for coordinate cleavage at the ends of Mos1 during transposition. This mutant enzyme allows insertion at dinucleotides other than TA, including sequences with GC base pairs. This is the first example of a mariner/Tc1 transposase with altered target specificity.

Amino Acid Sequence↗

The effects of a single long photoperiod on induction and dissipation of reproductive photorefractoriness in European starlings.

In many birds, long photoperiods stimulate gonadal maturation but also cause photorefractoriness, leading to gonadal regression. While much is known about the neuroendocrinology of photostimulation, little is known about photorefractoriness, partly due to lack of an experimental model. This study aimed to develop a model to test whether a single long photoperiod (LP) initiates the mechanism leading to photorefractoriness. It made use of the fact that in castrated European starlings, luteinizing hormone (LH) is low in photorefractory birds and high in photosensitive birds. In the first experiment, groups of castrated photorefractory birds were transferred from a long to a short photoperiod and then exposed to one LP every 5, 10, 20, 30, 40, or 60 days. In birds exposed to one LP every 5 days, LH stayed low. In birds exposed to one LP every 10 days, each LP caused a pulse in LH, but mean LH remained low. One LP every 20 days increased LH 6 days later, followed by a decrease at 11 days and then a further increase, so that overall, LH increased slowly. In birds exposed to one LP every 30, 40, or 60 days, LH increased at the same rate as in short photoperiod controls. Each LP did not cause a significant increase in LH, but did cause a decrease. A second experiment examined the changes in LH following a LP in more detail. Castrated starlings had been exposed to one LP every 14 days for 16 weeks. On the day of the final LP, LH values were midway between photorefractory and photosensitive values. The LP caused an increase in LH from the second day to a peak after 7 days. Thereafter, LH declined to initial values after 14 days, followed, in the absence of further LP, by a second increase to photosensitive values. These results suggest that the mechanisms causing photostimulation and photorefractoriness are both initiated during the first long photoperiod. That gonadal maturation precedes regression must reflect the relative rates at which the two processes reach completion.

Animals↗

Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds.

The objectives of the present study were to estimate 10 year probabilities of osteoporotic fractures in men and women according to age and bone mineral density (BMD) at the femoral neck. Risks were computed from the incidence of a first hip, distal forearm, proximal humerus and symptomatic vertebral fracture from patient records in Malmö, Sweden and future mortality rates for each year of age from Poisson models using the Swedish patient register and statistical year book. Fracture probability was computed using the Swedish population and cut-off values for T-scores based on the NHANES III female population. We assumed that the risk of fracture increased with decreasing BMD as assessed by meta-analysis in independent studies. The 10-year probability of any fracture was determined from the proportion of individuals fracture-free from the age of 45 years. With the exception of forearm fractures in men, 10 year probabilities increased with age and T-score. In the case of hip and spine fractures, fracture probabilities for any age with low BMD were similar between men and women. The effect of age on risk independently of BMD suggests that intervention thresholds should not be at a fixed T-score but vary according to absolute probabilities. Intervention thresholds based on hip BMD T-scores are similar between sexes.

Age Factors↗

Cost-effectiveness of preventing hip fracture in the general female population.

The aims of this study were to determine whether treatments that reduce the incidence of hip fracture might be used in the general female population rather than screening or case-finding strategies. Cost-effectiveness, measured as cost per quality-adjusted life-year (QALY) gained using threshold values for cost-effectiveness of $20,000 or $30,000/QALY gained, was assessed during and after treatment using a computer simulation model applied to the female population of Sweden. The base case assumed a 5-year intervention that reduced the risk of hip fracture by 35% during the treatment period, and an effect that reversed to the pretreatment risk during the next 5 years. Sensitivity analyses included the effects of age, different treatment costs and effectiveness. Cost-effectiveness was critically dependent upon the age and costs of intervention. Reasonable cost-effectiveness was shown even with relatively high intervention costs for women at average risk at the age of 84 years or more. For the cheapest interventions ($63/year) cost-effectiveness could be found from the age of 53 years. Variations in effectiveness (15-50% risk reduction) had marked effects on the age that treatment was worthwhile. We conclude that segments of the apparently healthy population could be advantaged by treatment if efficacy were supported by randomized controlled studies.

Age Factors↗

The burden of osteoporotic fractures: a method for setting intervention thresholds.

The aim of this study was to assess the relationship between morbidity from hip fracture and that from other osteoporotic fractures by age and sex based on the population of Sweden. Osteoporotic fractures were designated as those associated with low bone mineral density (BMD) and those that increased in incidence with age after the age of 50 years. Severity of fractures was weighted according to their morbidity using utility values based on those derived by the National Osteoporosis Foundation. Morbidity from fractures other than hip fracture was converted to hip fracture equivalents according to their disutility weights. Excess morbidity was 3.34 and 4.75 in men and women at the age of 50 years, i.e. the morbidity associated with osteoporotic fractures was 3-5 times that accounted for by hip fracture. Excess morbidity decreased with age to approximately 1.25 between the ages of 85 and 89 years. On the assumption that the age- and sex-specific pattern of fractures due to osteoporosis is similar in different communities, the computation of excess morbidity can be utilized to determine the total morbidity from osteoporotic fractures from knowledge of hip fracture rates alone. Such data can be used to weight probabilities of hip fracture in different countries in order to take into account the morbidity from fractures other than hip fracture, and to modify intervention thresholds based on hip fracture risk alone. If, for example, a 10-year probability of hip fracture of 10% was considered an intervention threshold, this would be exceeded in women with osteoporosis aged 65 years and more, but when weighted for other osteoporotic fractures would be exceeded in all women (and men) with osteoporosis.

Age Distribution↗

Use of ethylene vinyl alcohol copolymer for tubal sterilization by selective catheterization in rabbits.

PURPOSE: To assess the efficacy of ethylene vinyl alcohol copolymer (Uryx) in nonsurgically occluding the fallopian tube and achieving tubal sterilization in the rabbit model. MATERIALS AND METHODS: Ten mature virgin female New England rabbits underwent transvaginal selective bilateral fallopian tube cannulation with use of a coaxial catheter system under general anesthesia. Selective salpingography was performed bilaterally to assess patency of the fallopian tubes. Ethylene vinyl alcohol copolymer was injected unilaterally through a microcatheter to completely fill the middle portion of the tube. Three to seven days after injection, each animal was bred. Conception was determined by ultrasonography (US) 7-19 days after effective breeding. If pregnant, the rabbit was killed. Otherwise, it was permitted to rebreed until pregnancy was achieved. Histologic specimens of the fallopian tubes were prepared and analyzed. RESULTS: Patency of the fallopian tubes was demonstrated bilaterally in all animals by the free spillage of contrast material into the peritoneum. The delivery of ethylene vinyl alcohol copolymer into the fallopian tubes was successful in all animals but one, in which most of the plug almost immediately extruded into the uterus. Pregnancy was detected by US in the untreated fallopian tube in the nine rabbits that were receptive to breeding. No pregnancies were detected in the injected side. Histologic analysis demonstrated variable degrees of occlusion, fibrosis, and inflammation, with the majority of specimens demonstrating mild to moderate inflammation and moderate to marked fibrosis. CONCLUSION: Ethylene vinyl alcohol copolymer can reliably be placed nonsurgically via the transvaginal approach into the fallopian tubes with use of a coaxial catheter system. Ethylene vinyl alcohol copolymer appears to result in less fibrosis than previously investigated agents and demonstrates a 100% early sterilization rate in the rabbit model.

Animals↗

The ethical beliefs and behaviours of Victorian fitness professionals.

A survey based on those employed by Petitpas, Brewer, Rivera, and Van Raalte (1994), Pope, Tabachnick, and Keith-Spiegel (1987), Pope and Vetter (1992), and Tabachnick, Keith-Spiegel, and Pope (1991) was used to investigate the ethical beliefs and behaviours of Victorian fitness professionals. Although there is evidence that Victorian fitness professionals are knowledgeable about some general ethical principles, the results of this study suggest that there is some lack of consensus among Victorian fitness professionals about the ethical appropriateness of a number of complex issues relating to business practices, confidentiality, dual relationships, and personal and professional boundaries. The findings suggest there is a need to improve the professional and ethical education of fitness professionals and to develop comprehensive ethical principles and a code of conduct that is relevant to the individuals working in the Australian fitness profession.

Adult↗

Treatment of anticholinergic-induced ileus with neostigmine.

A 33-year-old man with a history of recreational benztropine abuse presented to the emergency department with confusion, abdominal pain, and distention. An abdominal radiograph revealed gross fecal loading. He was initially treated with intravenous fluids and opiate analgesia. Subsequently, a diagnosis of anticholinergic poisoning was made, based on tachycardia, delirium, dry mucosa, and reduced bowel sounds. Treatment with tacrine reversed the delirium, and a history of repeated benztropine use was obtained. Persistent ileus was treated with repeated doses of neostigmine, and gastrointestinal motility returned with prompt defecation. Neostigmine appears to be useful in reversing ileus caused by anticholinergic drug overdose. Theoretically, it may be useful in reversing anticholinergic ileus resulting from acute drug overdose, allowing or enhancing decontamination, but the safety and potential efficacy of neostigmine in this scenario have not been established.

Adult↗

Epithelial-myoepithelial carcinomas of the bronchus.

Epithelial-myoepithelial carcinomas are very rare in the lung, and little is known about the relationship of their histologic features to prognosis. We describe five primary pulmonary epithelial-myoepithelial carcinomas with details on clinical presentation, histology, and immunohistochemical profiles. We also reviewed the literature to detail further their prognosis. The patients' ages ranged from 33 to 57 years (average 51 years). The tumors were all endobronchial and the patients presented with symptoms or imaging features of airway obstruction. The tumors were completely resected; none showed nodal involvement. All five patients are alive and free of disease 4 months to 8 years (average 4.2 years) after surgery. Four tumors showed a mixed pattern of glands lined by a dual layer of cells and solid sheets of either spindle cells or clear cells, the glandular and solid components being present in variable proportions. The fifth tumor comprised purely spindle cells. The mitotic rate was <1/20 high power fields in both the glandular and spindle/clear cell components. In one case there was focal nuclear pleomorphism. The inner layer of the glands stained for cytokeratins and epithelial membrane antigen, and the outer layer for S-100 and smooth muscle actin. In one case the spindle cells stained for CD34. A review of published cases shows the majority of tumors behave in an indolent fashion, the rare aggressive tumors being predominantly myoepitheliomatous. Nevertheless, the term epithelial-myoepithelial carcinoma is preferred because of their malignant potential. A high mitotic rate, tumoral necrosis, and nuclear pleomorphism appear to be adverse prognostic factors.

Actins↗

Photoperiodic control of seasonality in birds.

This review examines how birds use the annual cycle in photoperiod to ensure that seasonal events--breeding, molt, and song production--happen at the appropriate time of year. Differences in breeding strategies between birds and mammals reflect basic differences in biology. Avian breeding seasons tend to be of shorter duration and more asymmetric with respect to changes in photoperiod. Breeding seasons can occur at the same time each year (predictable) or at different times (opportunistic), depending on the food resource. In all cases, there is evidence for involvement of photoperiodic control, nonphotoperiodic control, and endogenous circannual rhythmicity. In predictable breeders (most nontropical species), photoperiod is the predominant proximate factor. Increasing photoperiods of spring stimulate secretion of gonadotropin-releasing hormone (GnRH) and consequent gonadal maturation. However, breeding ends before the return of short photoperiods. This is the consequence of a second effect of long photoperiods--the induction of photorefractoriness. This dual role of long photoperiods is required to impart the asymmetry in breeding seasons. Typically, gonadal regression through photorefractoriness is associated with a massive decrease in hypothalamic GnRH, essentially a reversal to a pre-pubertal condition. Although breeding seasons are primarily determined by photoperiodic control of GnRH neurons, prolactin may be important in determining the exact timing of gonadal regression. In tropical and opportunistic breeders, endogenous circannual rhythmicity may be more important. In such species, the reproductive system remains in a state of "readiness to breed" for a large part of the year, with nonphotic cues acting as proximate cues to time breeding. Circannual rhythmicity may result from a temporal sequence of different physiological states rather than a molecular or cellular mechanism as in circadian rhythmicity. Avian homologues of mammalian clock genes Per2, Per3, Clock, bmal1, and MOP4 have been cloned. At the molecular level, avian circadian clocks appear to function in a similar manner to those of mammals. Photoperiodic time measurement involves interaction between a circadian rhythm of photoinducibility and, unlike mammals, deep brain photoreceptors. The exact location of these remains unclear. Although the eyes and pineal generate a daily cycle in melatonin, this photoperiodic signal is not used to time seasonal breeding. Instead, photoperiodic responses appear to involve direct interaction between photoreceptors and GnRH neurons. Thyroid hormones are required in some way for this system to function. In addition to gonadal function, song production is also affected by photoperiod. Several of the nuclei involved in the song system show seasonal changes in volume, greater in spring than in the fall. The increase in volume is, in part, due to an increase in cell number as a result of neurogenesis. There is no seasonal change in the birth of neurons but rather in their survival. Testosterone and melatonin appear to work antagonistically in regulating volume.

Animals↗