The role of ADAM33 in the pathogenesis of asthma

While asthma is a disorder of the conducting airways characterised by Th2-directed inflammation, a second set of mechanisms is being increasingly recognised as fundamental to disease chronicity and severity, for which the term remodelling has been used. The cellular and mediator responses underpinning airway remodelling involve aberrant communication between the airway epithelium and underlying mesenchyme, involving the generation of growth factors that lead to proliferation of fibroblasts and smooth muscle and the deposition of matrix proteins to cause airway wall thickening linked to bronchial hyperresponsiveness and fixed airflow obstruction. The identification of ADAM33 on chromosome 20p13 from positional cloning as a novel candidate gene involved in the pathogenesis of these structural and functional changes has opened the way to further insight into these processes that contribute to corticosteroid refractoriness. The preferential expression of ADAM33 in mesenchymal cells and its multiple molecular actions provide ample opportunity for incriminating this molecule in chronic asthma. Its association with progressive asthma and in predicting reduced lung function in young children suggest that ADAM33 has an important role in the natural history and possibly the origins of asthma, a disease unique to humans.     

Effects of medial septal lesions on action-outcome associations in rats under conditions of delayed reinforcement

In operant tasks, control rats maintain high response rates under positive contingencies, when the probability of reinforcement is greater following a response (contingent reinforcement) than during the absence of that response. However, as contingencies approach zero, response rates decrease. In this experiment, under immediate contingent reinforcement, rats with medial septal lesions reduced their response rates, just like controls, when contingencies were shifted from positive toward zero. However, the septal rats were less sensitive to this contingency shift, compared with controls, when there was a 5-s delay between lever presses and contingent reinforcements. This lesion effect appeared to be due to a failure of voluntary response memory, which impaired sensitivity to operant contingencies when there was a delay between action and outcome.     

Recognising and treating the causes of chronic malodorous wounds

Malodorous wounds are not only debilitating to patients physically, they can also cause them major social problems. It is therefore crucial for practitioners to recognise problem wounds at the earliest opportunity and to undertake a holistic assessment of the patient and the wound, with a view to initiating an appropriate management plan to resolve the underlying causes.     

Effects of central administration of naloxone during the extinction of appetitive sexual responses

Several studies indicate that opioids are involved in the control of consummatory sexual behavior in male Japanese quail. Naloxone has been reported to increase copulatory responses. In the current study, the effect of naloxone on appetitive sexual behaviors was assessed during extinction test trials. Naloxone was found to substantially reduce appetitive responding, suggesting that opioids differentially affect anticipatory and contact components of sexual behavior.     

Manual removal of the placenta and postcesarean endometritis

OBJECTIVE: To determine if manual vs. spontaneous delivery of the placenta at cesarean section affects the rate of postoperative endometritis and amount of blood loss. STUDY DESIGN: A prospective, randomized study was carried out on patients who had cesarean delivery assigned either to spontaneous delivery of the placenta (group 1) or manual removal (group 2). We excluded patients undergoing emergency cesareans and those with possible placenta accreta or evidence of preexisting infection. Outcome measures (frequency of endometritis and quantitative decrease in hemoglobin) were compared for the two groups. RESULTS: Study criteria were met for 375 subjects: 177 in group 1 and 198 in group 2. Endometritis was diagnosed in 1.7% of the former and 2.5% of the latter. The change in hemoglobin, reflecting operative blood loss, was similar in both groups (-1.81 and -1.72 g/dL, respectively). CONCLUSION: We found no significant difference in either postoperative endometritis or blood loss regardless of the means used to effect delivery of the placenta. The frequency of febrile morbidity in our study cases was considerably lower than heretofore reported.     

Variability of Broca's area homologue in African great apes: implications for language evolution

The cortical circuits subserving neural processing of human language are localized to the inferior frontal operculum and the posterior perisylvian region. Functional language dominance has been related to anatomical asymmetry of Broca's area and the planum temporale. The evolutionary history of these asymmetric patterns, however, remains obscure. Although testing of hypotheses about the evolution of language areas requires comparison to homologous regions in the brains of our closest living relatives, the great apes, to date little is known about normal interindividual variation of these regions in this group. Here we focus on Brodmann's area 44 in African great apes (Pan troglodytes and Gorilla gorilla). This area corresponds to the pars opercularis of the inferior frontal gyrus (IFG), and has been shown to exhibit both gross and cytoarchitectural asymmetries in humans. We calculated frequencies of sulcal variations and mapped the distribution of cytoarchitectural area 44 to determine whether its boundaries occurred at consistent macrostructural landmarks. A considerable amount of variation was found in the distribution of the inferior frontal sulci among great ape brains. The inferior precentral sulcus in particular was often bifurcated, which made it impossible to determine the posterior boundary of the pars opercularis. In addition, the distribution of Brodmann's area 44 showed very little correspondence to surface anatomy. We conclude that gross morphologic patterns do not offer substantive landmarks for the measurement of Brodmann's area 44 in great apes. Whether or not Broca's area homologue of great apes exhibits humanlike asymmetry can only be resolved through further analyses of microstructural components.     

Role of self-efficacy and behaviour change

Behaviour change is an important concept in relation to health promotion and disease prevention. Self-efficacy has been identified as an important determinant of health behaviour, future health behaviour and health behaviour change. In order to effectively facilitate behaviour change, it is essential that interventions are research based, and emphasize the utility of theory in practice. The effective practice of health promotion and disease prevention requires a full understanding of the processes of patient behaviour. This article presents the role of the nurse in influencing health-related behaviour change. Self-efficacy and related but distinct theories that underpin behaviour change are discussed. The empirical evidence that supports the link between self-efficacy and predictions of health behaviours is also examined.     

Missing Omo L338y-6 occipital-marginal sinus drainage pattern: ground sectioning, computer tomography scanning, and the original fossil fail to show it

The Omo L338y-6 occipital region has been recently studied by White and Falk (1999), who claim that it shows a readily identifiable enlarged left occipital-marginal sinus (O/M). These observations are contrary to the direct observations of previous investigators (Rak and Howell, 1978; Kimbel, 1984; Holloway, 1981; Holloway, 1988). White and Falk (1999) further argue that the presence of this enlarged O/M strongly suggests that the Omo L338y-6 hominid was indeed a "robust" Australopithecus. We used direct sectioning and CT scanning to analyze magnified sections of a high-quality first-generation cast of the newly cleaned original fossil. These methods fail to show any evidence of a morphological landmark that can be interpreted as an enlarged O/M, either as an eminence or a sulcus. In contrast, the same techniques used with both SK 1585 and OH5 ("robust" Australopithecus with an enlarged O/M) show extremely visible and palpable enlarged O/M's. Examination of the original Omo fossil confirms that it lacks an O/M. This evidence clearly shows that an enlarged O/M cannot be identified on either the original fossil or a first-generation cast, although this does not rule out the possibility that the Omo L338y-6 hominid was a "robust" Australopithecus. We believe that the differences between observers regarding this feature are most probably due to displacement caused by a crack and the different source materials employed, i.e., the difference between a first-generation cast of the original fossil and a third- or fourth-generation cast of the endocast made two decades ago.     

Distinctive patterns of gene expression in premalignant gastric mucosa and gastric cancer

Current epidemiological evidence supports a pathogenetic model of gastric cancer involving intermediate stages that include chronic gastritis and intestinal metaplasia. This study explores the molecular features of gastric cancer and premalignant stages using DNA microarray-based gene expression profiling and relates these findings to clinical, pathological, and ethnic parameters. A total of 124 tumor and adjacent mucosa samples were analyzed using spotted cDNA microarrays containing 9381 nonredundant gene elements. Tumor specimens were diffuse, intestinal, or mixed gastric cancer and adjacent mucosa, which generally displayed signs of chronic gastritis or intestinal metaplasia. Expression patterns could be discerned that readily defined premalignant and tumor subtypes. Chronic gastritis exhibits a pronounced mitochondrial gene expression signature, which may be linked to Helicobacter pylori pathogenesis. Intestinal metaplasia was associated with increased expression of many intestinal differentiation genes, many of which were not overexpressed in tumors. Samples were obtained from 91 Australian and 33 Chinese patients to explore potential variation in gene expression between these populations. Despite differences in the incidence, and potentially the etiology, of gastric cancer between these ethnic groups, we found the tumors to be molecularly similar. The identification of molecular signatures that are characteristic of subtypes of gastric cancer and associated premalignant changes should enable further analysis of the steps involved in the initiation and progression of this disease.