The effects of competition and motor reprogramming on visuomotor selection in unilateral neglect

Patients with unilateral neglect following right hemisphere damage may have difficulty in moving towards contralesional targets. To test the hypothesis that this impairment arises from competing motor programs triggered by irrelevant ipsilesional stimuli, we examined 16 right hemisphere patients, eight with left visual neglect and eight without, in addition to eight healthy control subjects. In experiment 1 subjects performed sequences of movements using their right hand to targets on the contralesional or ipsilesional side of the responding limb. The locations of successive targets in each sequence were either predictable or unpredictable. In separate blocks of trials, targets appeared either alone or with a simultaneous distractor located at the immediately preceding target location. Neglect patients were significantly slower to execute movements to contralesional targets, but only for unpredictable movements and in the presence of a concurrent ipsilesional distractor. In contrast, healthy controls and right hemisphere patients without neglect showed no directional asymmetries of movement execution. In experiment 2 subjects were required to interrupt a predictable, reciprocating sequence of leftward and rightward movements in order to move to an occasional, unpredictable target that occurred either in the direction opposite to that expected, or in the same direction but twice the extent. Neglect patients were significantly slower in reprogramming the direction and extent of movements towards contralesional versus ipsilesional targets, and they also made significantly more errors when executing such movements. Right hemisphere patients without neglect showed a similar bias in reprogramming direction (but not extent) for contralesional targets, whereas healthy controls showed no directional asymmetry in either condition. On the basis of these findings we propose that neglect involves a competitive bias in favour of motor programs for actions directed towards ipsilesional versus contralesional events. We suggest that programming errors and increased latencies for contralesional movements arise because the damaged right hemisphere can no longer effectively inhibit the release of inappropriate motor programs towards ipsilesional events. Received: 1 October 1996 / Accepted: 21 October 1997     

Breast Carcinoma in Young Women: No Evidence of Increasing Rates of Metastatic Breast Carcinoma in a Single Tertiary Center Review

Breast carcinoma in young women aged less than 40 years attracts a high level of mainstream media coverage, and there is a gap between societal perceptions of the disease as a growing problem and epidemiological trends. Several population studies have reported that the overall incidence of breast carcinoma in young women is stable, while one recent article suggested that the relative proportion of breast carcinoma in young women that is metastatic at diagnosis is growing. We sought to establish whether these trends were apparent at our institution. In this study, the clinical database at a breast carcinoma tertiary center was reviewed in terms of clinicopathologic data on patient age, diagnosis, clinical and pathologic stage, hormone receptor status, and HER‐2 overexpression status for the period 2000–2011. Over the study period, young patients represented a decreasing proportion of all breast carcinoma cases (10.8% [2000–2003] to 8.7% [2008–2011]; p < 0.0001) treated at our institution. Young patients were more likely than patients aged 40 years or older to present with metastatic (M1) disease (5.4% versus 4.4%; p = 0.009), to be triple negative (21.6% versus 13%; p < 0.001), or to be HER‐2 positive (24.3% versus 14.8%; p < 0.01). Young patients with HER‐2‐positive cancers were significantly more likely to present with metastatic disease (8.3% versus 4.8%; p = 0.004). This study showed no demonstrable increase in the relative proportion of breast cancer occurring in patients aged <40 years over the 12‐year period 2000–2011 and no increase in the proportion of young patients presenting with metastatic disease.     

Dysphagia and swallowing-related quality of life in Friedreich ataxia

Dysphagia in Friedreich ataxia (FRDA) and its impact on quality of life is not adequately understood. The objective of this study was to characterise dysphagia in FRDA and to determine the impact of swallowing dysfunction on activities, participation, and sense of well-being. Thirty-six individuals with a confirmed diagnosis of FRDA were assessed via a clinical bedside examination (CBE), the Royal Brisbane Hospital outcome measure for swallowing, an oral-motor examination and the Australian therapy outcome measures for speech and swallowing (AusTOMS). Data on swallowing function, diet modification and swallowing strategies were collated. Thirty-three (91.67 %) participants exhibited clinical signs of dysphagia according to the CBE, and all participants received ratings indicating swallowing difficulties on at least one other measure. Dysphagia in FRDA is characterised by oral and pharyngeal stage impairment relating to incoordination, weakness and spasticity. A significant positive correlation was found between the severity of impairment, activity, participation and distress/well-being on the AusTOMS, suggesting that swallowing function decreases with overall reductions in quality of life. A significant correlation was found between activity on the AusTOMS and disease duration (r = ?0.283, p = 0.012). No significant correlations were found between dysphagia severity and GAA repeat length, age of onset or disease severity. Participants employing diet modification and swallowing strategies demonstrated higher dysphagia severity, activity limitations and participation restrictions. These data advocate a holistic approach to dysphagia management in FRDA. Early detection of swallowing impairment and consideration of the potential impact dysphagia has on quality of life should be key aspects in disease management.     

Researching sexual and reproductive behaviour: a peer ethnographic approach

In recent years, ethnographic research has challenged the notion within demography that fertility-related behaviour is the outcome of individualistic calculations of the costs and benefits of having children. Anthropology has further criticised the abstraction in demographic analysis of sexual behaviour and fertility decision-making from the socio-cultural and political context in which the individual or couple is located. Within demography itself, institutional and political-economic analyses have argued strongly that sexual and reproductive behaviour must be understood within locally specific social, cultural, economic and political contexts. Positivist and empiricist research methods, such as the sample survey and focus groups, which continue to dominate demographic inquiry and applied research into sexual and reproductive behaviour, have been shown to be limited in their ability to inform about the process of behaviour change and contexts within which different behaviours occur. The article introduces a new methodology for researching sexual and reproductive behaviour, called the peer ethnographic approach, which the authors have developed in an attempt to address some of the limitations of the methods which currently dominate research into sexual and reproductive behaviour. The peer ethnographic methodology is discussed in detail and the results of recent field-testing are reported, which show that, although the approach has limitations, it also has the potential to make a significant contribution to our understanding of sexual and reproductive behaviour.     

Muscarinic receptor protein expression in the ocular tissues of the chick during normal and myopic eye development

Muscarinic receptor signalling has been implicated in both the embryonic and postnatal development of ocular structures as well as in myopic eye growth. A radioligand binding assay was used to determine whether changes in muscarinic receptor density and/or affinity occurred in the chick retina, choroid and sclera during early post-hatching development or with the induction of myopia. Specific receptor binding sites were saturable with increasing concentrations of the muscarinic receptor ligand [3H]N-methyl-scopolamine in the retina and choroid but not in the sclera. In normal eyes, binding density in the retina was not altered from age P5 to P10 (447+/-14 vs. 411+/-13 fmol/mg of protein, P=0.07). However, in the choroid, the number of receptor binding sites significantly increased between P5 and P10 (637+/-39 vs. 1125+/-121 fmol/mg of protein, P<0.01). Binding affinity (K(D)) was not altered with age in either the retina or choroid. Myopia was induced in chicks by deprivation of form vision, using translucent diffusers, from age P3. Despite the induction of significant degrees of ocular elongation and myopia at P5 (-8.7+/-0.3 D, P<0.01) and P10 (-22.5+/-1.3 D, P<0.01), neither muscarinic receptor density nor affinity were altered in the retina or choroid of myopic eyes. These findings indicate that regulation of muscarinic receptor numbers in the chick choroid is occurring in normal post-hatching development of this tissue. However, myopic eye enlargement was not associated with changes in muscarinic receptor protein expression in the chick retina and choroid.     

Inflammatory mediators and growth factors in obstructive renal injury

Obstruction of the upper urinary tract poses a significant clinical challenge to the urologist, and the cascade of renal cellular and molecular events triggered by upper urinary tract obstruction result in a progressive, and eventually permanent, loss in renal function. These pathological changes include the development of renal fibrosis, tubular atrophy, interstitial inflammation, and apoptotic renal cell death. A myriad of cytokines and growth factors have been identified as major contributors to obstruction-induced renal fibrosis and apoptotic cell death, including transforming growth factor-beta1, angiotensin II, nuclear factor-kappaB, and tumor necrosis factor-alpha. This review examines the role of these mediators in obstruction-induced renal injury.     

The role of estrogen in cardiovascular disease

Cardiovascular disease is the number one cause of death among women, accounting for nearly 50% of female deaths. Statistics show that women on average develop cardiovascular disease 10 to 15 years later in life than men, and that the risk may increase after menopause. This observation has led to much speculation as to what physiological change(s) associated with menopause is responsible for the higher risk of atherosclerosis. Estrogen, with its potential as a cardioprotective agent and as an immunomodulator of the inflammatory response in atherosclerosis, has received the most attention. Understanding the mechanisms that lead to these differences may allow beneficial therapeutic intervention to enhance this effect in females and evoke this protection in males. This review will do the following: (1) characterize mechanisms of atherosclerosis, (2) explore the role of estrogen-replacement therapy, (3) define the effect of gender on inflammation, (4) compare and contrast the effects of estrogen and testosterone on endothelial functional, and (5) suggest mechanistic based therapeutic opportunities.