Medicine & Health

Publication Search Results

Now showing 1 - 10 of 19
  • (2008) Wakefield, Claire; Meiser, Bettina; Gaff, C; Barratt, Anthony; Patel, Minoo; Suthers, G; Lobb, Elizabeth; Ramsay, J; Mann, G
    Journal Article
    Purpose: Despite the established importance of the role of family history in prostate cancer, relatively little research encompasses the psychosocial issues relevant to unaffected men with a family history of prostate cancer. To determine the completeness and quality of available literature on the issues faced by men with a high risk of prostate cancer, we conducted a multidisciplinary review of the literature to provide some guidance on the information that clinicians might provide to men who are concerned about family history. Materials and Methods: A structured literature search was conducted by a multidisciplinary team of clinicians and researchers who reviewed the medical and psychosocial literature, and identified 21 relevant studies. Results: Research suggests that many high risk patients are concerned about the risk of prostate cancer, and some may significantly overestimate that risk. Several studies have shown high screening rates among high risk patients and high levels of interest in genetic testing for prostate cancer risk should it become available, yet many men also report a desire for more information about their personal risk and risk management options. Conclusions: Given the lack of clear data on the efficacy of prostate cancer screening among high risk patients, clinicians could consider providing men who are concerned about family history with information on their personal risk, help them to clarify the potential benefits, limitations and harms of prostate cancer screening in their situation, and then support their choice regarding the management of prostate cancer risk.

  • (2008) Wakefield, Claire; Meiser, Bettina; Homewood, J; Peate, Michelle; Taylor, Adrian; Lobb, Elizabeth; Kirk, J; Young, Mark; Williams, Robyn; Dudding, T; Tucker, Katherine
    Journal Article
    Purpose To measure the effectiveness of a tailored decision aid (DA) designed to help women make informed decisions about genetic testing for breast/ovarian cancer risk. Methods A total of 145 women were randomized to receive the DA or a control pamphlet at the end of their first genetic counseling consultation. Of these, 120 (82.8%) completed two questionnaires, 1 week and 6 months post-consultation. Results While the DA had no effect on informed choice, post-decisional regret or actual genetic testing decision, the trial showed that women who received the DA had higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet (chi(2)(2) = 6.82; P = 0.033; chi(2)(1) = 4.86; P = 0.028 respectively). The DA also helped women who did not have blood drawn at their first consultation to clarify their values with regards to genetic testing (chi(2)(1) = 5.27; P = 0.022). Women who received the DA were less likely to share the information with other family members than women in the control condition (chi(2)(1) = 8.78; P = 0.003). Conclusions Decision aids are an effective decision-support strategy for women considering genetic testing for breast/ovarian cancer risk, and are most effective before the patient has made a decision, which is generally at the point of having blood drawn.

  • (2008) Power, M; Marlon, J; Ortiz, N; Bartlein, P; Harrison, Simon; Mayle, F; Ballouche, A; Bradshaw, R; Carcaillet, C; Cordova, C; Mooney, Scott; Moreno, P; Prentice, I; Thonicke, K; Tinner, W; Whitlock, C; Zhang, Yanling; Zhao, Yong; Ali, Amna; Anderson, Richard; Beer, R; Behling, H; Briles, C; Brown, Katherine; Brunelle, A; Bush, M; Camill, P; Chu, G; Clark, J; Colombaroli, D; Connor, Stuart; Daniau, A; Daniels, M; Dodson, John; Doughty, E; Edwards, Meredith; Finsinger, W; Foster, Douglas; Frechette, J; Gaillard, M; Gavin, D; Gobet, E; Haberle, Simon; Hallett, D; Higuera, P; Hope, G; Horn, S; Inoue, J; Kaltenrieder, P; Kennedy, Liz; Kong, Z; Larsen, C; Long, C; Lynch, Jodi; Lynch, E; McGlone, M; Meeks, S; Mensing, S; Meyer, G; Minckley, T; Mohr, J; Nelson, D; New, J; Newnham, R; Noti, R; Oswald, W; Pierce, J; Richard, P; Rowe, C; Goni, M; Shuman, B; Takahara, H; Toney, J; Turney, C; Urrego-Sanchez, D; Umbanhowar, C; Vandergoes, M; Vanniere, B; Vescovi, E
    Journal Article
    Fire activity has varied globally and continuously since the last glacial maximum (LGM) in response to long-term changes in global climate and shorter-term regional changes in climate, vegetation, and human land use. We have synthesized sedimentary charcoal records of biomass burning since the LGM and present global maps showing changes in fire activity for time slices during the past 21,000 years (as differences in charcoal accumulation values compared to pre-industrial). There is strong broad-scale coherence in fire activity after the LGM, but spatial heterogeneity in the signals increases thereafter. In North America, Europe and southern South America, charcoal records indicate less-than-present fire activity during the deglacial period, from 21,000 to ∼11,000 cal yr BP. In contrast, the tropical latitudes of South America and Africa show greater-than-present fire activity from ∼19,000 to ∼17,000 cal yr BP and most sites from Indochina and Australia show greater-than-present fire activity from 16,000 to ∼13,000 cal yr BP. Many sites indicate greater-than-present or near-present activity during the Holocene with the exception of eastern North America and eastern Asia from 8,000 to ∼3,000 cal yr BP, Indonesia and Australia from 11,000 to 4,000 cal yr BP, and southern South America from 6,000 to 3,000 cal yr BP where fire activity was less than present. Regional coherence in the patterns of change in fire activity was evident throughout the post-glacial period. These complex patterns can largely be explained in terms of large-scale climate controls modulated by local changes in vegetation and fuel load.

  • (2008) Szczesniak, Michal Marcin
    The work presented in this thesis concerns neurophysiology and pharmacology of the oesophageal afferent pathways involved in oesophago-pharyngeal reflexes and oesophageal nociception. Disturbances of reflexes governing contractile and relaxation responses of the upper oesophageal sphincter (DOS) are likely to be implicated in the pathophysiology of conditions involving excessive oesophago-pharyngeal regurgitation, impaired oesophageal clearance, and an abnormal belch reflex. Visceral hypersensitivity, a heightened perception of gastrointestinal sensation is frequently observed in functional gastrointestinal disorders and provides compelling evidence that it plays an important role in the pathogenesis of functional heartburn and non-erosive reflux disease. The work in this thesis explores the neurophysiology, pharmacology and pathophysiology of oesophago-DOS reflexes in humans by experimentally inducing DOS relaxations in healthy controls and patients with reflux laryngitis, and by recording DOS motor responses during spontaneous oesophago-pharyngeal regurgitation. Nociception was assessed by measuring oesophageal sensitivity to electrical stimulation and oesophageal acid perfusion in healthy controls, which was then compared with several heartburn populations (functional heartburn, erosive and non-erosive reflux disease). Additional studies were performed to evaluate the potential role of intraluminal impedance in defining antegrade bolus flow through the pharyngo-oesophageal segment during swallowing as a prelude to the adaptation of the technique to find a more accurate method for the detection of oesophago-pharyngeal regurgitation. The main findings from this work are as follows. 1) Mucosal lignocaine-sensitive afferents mediate the distension-induced oesophago-DOS relaxation reflex and lignocaine insensitive, presumably muscular mechanoceptors, mediate the distension-induced oesophago-DOS contractile reflex. The latter reflex is also upregulated by oesophageal acidification indicative of a possible protective mechanism. 2) Prolonged studies in patients with proven oesophago-pharyngeal regurgitation demonstrated that the most common mechanism of oesophago-pharyngeal regurgitation is a transient, non-swallow related, relaxation of the DOS. 3) Experimental evaluation of the oesophago-DOS relaxation reflex revealed that it is upregulated in patients with reflux laryngitis, suggesting that the aberrant afferent signalling in the oesophagus may be a contributory factor mediating oesophago-pharyngeal regurgitation. 4) Measurement of oesophageal sensory thresholds in response to electrical stimulation and acid perfusion revealed that all patients, irrespective of the presence or absence of mucosal injury, exhibit acid-induced hypersensitisation. 5) The viscro-somatic referral pattern of acid- and electrically-induced chest pain is increased in patients with functional heartburn and non-erosive reflux disease. These findings support the hypothesis that central sensitisation of nociceptive pathways may contribute to symptom reporting in these heartburn populations.

  • (2008) Tao, Helen; Shen, Bojiang; Wei, Ai-Qun; Kishen, Thomas; Diwan, Ashish; Ma, David
    Journal Article

  • (2008) Lu, Jike; Bhargav, Divya; Wei, Ai-Qun; Diwan, Ashish
    Journal Article
    STUDY DESIGN: Posterolateral intertransverse process spinal fusion (PLF) was performed in ovariectomized female rats using recombinant human BMP-7 (OP-1) delivered on a composite carrier. OBJECTIVE: To investigate whether BMP-7 collagen on a composite carrier in a higher dose will enhance posterolateral spinal fusion in an estrogen deficiency rat model. SUMMARY OF BACKGROUND DATA: Osteoporosis is a systemic disease characterized by bone remodeling skewed in favor of excess bone resorption. This makes new bone formation and fixation of metallic implants difficult. Thus, treating osteoporotic patients who require posterior spinal fusion is challenging. Ovariectomized rats have been used as an osteoporotic model for posterolateral intertransverse process fusion. We have demonstrated in the past that endochondral bone formation in osteoporotic rats is delayed when compared with rats without osteoporosis. We have also shown that OP-1 Putty (BMP-7, collagen, and carboxy-methyl-cellulose) can overcome the effects of osteoporosis in a rat fracture model. However, it has not yet been demonstrated whether BMP-7 collagen composite carrier (Calstrux) can achieve a fusion in a process spinal fusion model in osteoporotic bone. METHODS: A total of 42 ovariectomized Sprague-Dawley female rats were randomly assigned to 4 control and 2 experimental groups: (1) no Calstrux, no BMP; (2) 400 mg Calstrux alone; (3) 30 microg lactose + 400 mg Calstrux; (4) 90 microg lactose + 400 mg Calstrux; (5) 30 microg rhBMP-7 + 400 mg Calstrux; and (6) 90 microg rhBMP-7 + 400 mg Calstrux. Spinal fusion was evaluated by manual motion testing, microradiographs, computed tomographic scans, DEXA scans, and histology. RESULTS: Ovariectomized rats receiving Calstrux alone or either dose of lactose and Calstrux did not show spinal fusion. Ovariectomized rats receiving 90 microg BMP-7 + 400 mg Calstrux showed significantly higher fusion rates than these control animals. (P < 0.0001). The rats receiving 30 microg BMP-7 + 400 mg Calstrux exhibited only partial fusion. CONCLUSION: BMP-7, delivered on a composite carrier, is able to overcome the detrimental effects of estrogen deficiency on posterolateral spinal fusion and generate a relatively robust fusion. The effect seems to be dose dependent.

  • (2008) Tassabehji, May; Fang, Z; McGaughran, J; Zhao, Zhongming; De Bock, Charles; Howard, Emma; Malass, Michael; Donnai, Dian; Diwan, Ashish; Manson, Forbes; Murrell, Deirdre; Clarke, Raymond
    Journal Article
    Klippel-Feil syndrome (KFS) is a congenital disorder of spinal segmentation distinguished by the bony fusion of anterior/cervical vertebrae. Scoliosis, mirror movements, otolaryngological, kidney, ocular, cranial, limb, and/or digit anomalies are often associated. Here we report mutations at the GDF6 gene locus in familial and sporadic cases of KFS including the recurrent missense mutation of an extremely conserved residue c.866T>C (p.Leu289Pro) in association with mirror movements and an inversion breakpoint downstream of the gene in association with carpal, tarsal, and vertebral fusions. GDF6 is expressed at the boundaries of the developing carpals, tarsals, and vertebrae and within the adult vertebral disc. GDF6 knockout mice are best distinguished by fusion of carpals and tarsals and GDF6 knockdown in Xenopus results in a high incidence of anterior axial defects consistent with a role for GDF6 in the etiology, diversity, and variability of KFS.

  • (2008) Wei, Ai-Qun; Brisby, Helena; Chung, Sylvia; Diwan, Ashish
    Journal Article
    Background context: Disc degeneration includes dysfunction and loss of disc cells leading to a decrease in extracellular matrix (ECM) components. Apoptosis has been identified in degenerated discs. Bone morphogenetic protein-7 (BMP-7) has been reported to stimulate ECM synthesis in the intervertebral disc (IVD), but its effect on disc cell viability is unknown. Purpose: To investigate whether BMP-7 can protect disc cells from programmed cell death while enhancing ECM production. Study design: An in vitro study to examine the effect of BMP-7 on apoptosis of IVD cells. Methods: Human nucleus pulposus (NP) cells were cultured in monolayer, and human recombinant pure BMP-7 (rhBMP-7) was added to the medium when the cells were in the second passage. Thereafter, apoptosis was induced by either tumor necrosis factor-alpha (TNF-α) or hydrogen peroxide (H2O2). Cellular apoptosis was evaluated by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay and caspase-3 activity. ECM synthesis was assessed by immunofluorescence for collagen-2 and aggrecan. To study the possibility of bone induction by rhBMP-7 in disc cells, alkaline phosphatase activity and Alizarin red-S staining were evaluated. Results: Apoptosis was induced by both TNF-α and H2O2. Addition of rhBMP-7 resulted in inhibition of the apoptotic effects caused by both inducers. Further, BMP-7 decreased caspase-3 activity. In the presence of BMP-7, ECM production was maintained by the cells despite being in an apoptotic environment. No osteoblastic induction of the disc cells was seen. Conclusions: BMP-7 was demonstrated to prevent apoptosis of human disc cells in vitro. One of the antiapoptotic effects of BMP-7 on NP cells might be a result of its inactivation of caspase-3. Collagen production was maintained by addition of rhBMP-7 in an apoptotic environment.

  • (2008) Williams, Lisa; Bhargav, Divya; Diwan, Ashish
    Journal Article
    Bone morphogenetic proteins are a diverse group of morphogens with influences not only on bone tissue, as the nomenclature suggests, but on multiple tissues in the body and often at crucial and influential periods in development. The purpose of this review is to identify and discuss current knowledge of one vertebrate BMP, Bone Morphogenetic Protein 13 (BMP13), from a variety of research fields, in order to clarify BMP13's functional contribution to developing and maintaining healthy tissues, and to identify potential future research directions for this intriguing morphogen. BMP13 is highly evolutionarily conserved (active domain >95%) across diverse species from Zebrafish to humans, suggesting a crucial function. In addition, mutations in BMP13 have recently been associated with Klippel-Feil Syndrome, causative of numerous skeletal and developmental defects including spinal disc fusion. The specific nature of BMP13's crucial function is, however, not yet known. The literature for BMP13 is focused largely on its activity in the healing of tendon-like tissues, or in comparisons with other BMP family molecules for whom a clear function in embryo development or osteogenic differentiation has been identified. There is a paucity of detailed information regarding BMP13 protein activity, structure or protein processing. Whilst some activity in the stimulation of osteogenic or cartilaginous gene expression has been reported, and BMP13 expression is found in post natal cartilage and tendon tissues, there appears to be a redundancy of function in the BMP family, with several members capable of stimulating similar tissue responses. This review aims to summarise the known or potential role(s) for BMP13 in a variety of biological systems.

  • (2008) Brillante, Divina; Johnstone, M; Howes, Laurence; O'Sullivan, Anthony
    Journal Article
    Aim: Angiotensin II type 2 (AT2) receptors are believed to become over-expressed in response to cardiovascular damage and to mediate beneficial effects (e.g. vasodilation). It is unknown whether AT2 receptors are functionally expressed in patients with insulin resistance (INSR). In this study, we investigated the role of the highly selective AT2 receptor antagonist, PD123319, on arterial stiffness and haemodynamic parameters in patients with INSR, compared with an age- and gender-matched control (N) group to determine whether there is functional expression of vascular AT2 receptors in patients with INSR. Methods: We studied 10 subjects with INSR [mean age 28 +/- 5 years, body mass index (BMI) 30.4 +/- 5.4 kg/m(2), mean cholesterol level 4.7 +/- 0.7 mmol/l, mean homeostasis model assessment 2.78 +/- 0.84] and 10 age- and gender-matched normal subjects (mean age 27 +/- 7 years, BMI 23.6 +/- 2.5 kg/m(2), mean cholesterol level 3.9 +/- 0.6 mmol/l). All were normotensive, non-smokers and on no medications. Subjects received a 3-min infusion of PD123319 (10 mu g/min). At the end of the infusion, arterial stiffness indices [stiffness index (SI) and reflective index (RI)] and haemodynamic parameters [cardiac index, systemic vascular resistance index (SVRI) and stroke index (ZI)] were measured. Results: RI (mean % change: INSR 13.8 +/- 15.5%, N -0.2 +/- 4.6, p = 0.04) and SVRI (mean % change: INSR 13.5 +/- 9.7%, N -1.5 +/- 5.7, p = 0.005) increased significantly in response to PD123319 infusion in patients with INSR compared with controls. There were no significant changes in SI, systolic blood pressure, diastolic blood pressure and ZI. Conclusion: The results suggest the functional expression of AT2 receptors in small vessels that determine the inflection of the digital volume pulse wave in patients with INSR, possibly as an indicator of early vascular damage.