Evaluation of the effect of azapropazone on neutrophil migration in regional myocardial ischaemia/reperfusion injury in rabbits.

1. The purpose of the present study was to determine the myocardial cytoprotective efficacy of azapropazone (AZA) and its potential site of action on neutrophil infiltration into reperfused/ischaemic myocardium with or without in vivo activation of neutrophils in rabbits. 2. AZA, 100 mg kg-1, was administered i.v. 10 min after occlusion of the left circumflex (LCX) artery in rabbits with and without pretreatment with phorbol myristate acetate ester (PMA). The LCX occlusion was then released at 10 min after AZA administration. Haemodynamic parameters (heart rate, LV pressure, mean arterial blood pressure and dp/dt) were monitored throughout the experiment. After 60 min reperfusion, the area at risk was delineated and the heart was then excised and divided into epi- and endocardial pieces for analysis of myeloperoxidase activity. 3. AZA inhibited neutrophil infiltration into the reperfused/ischaemic rabbit myocardium with and without PMA treatment. The inhibition of neutrophil infiltration was more apparent in the epicardium than in the endocardium. Additionally, AZA inhibited to a similar extent the in vivo PMA-stimulated neutrophil migration into the epicardium and endocardium area at risk. AZA had no significant effect on the haemodynamic parameters as compared to control. 4. AZA administered in an anaesthetized rabbit model of LCX occlusion/reperfusion resulted in the reduction of infarct size. 5. It is concluded that AZA has significant inhibitory effects on neutrophil migration which might contribute to its myocardial cytoprotective effect.     

Effects of group socialization procedures on the social interactions of preschool children

We investigated the effects of group socialization procedures on the social behavior of preschool children in two studies. Group socialization procedures consisted of teachers using antecedent and consequent events to promote social interaction during children's games. During intervention, teachers discussed friendship with the children and then prompted and praised child-child social responding within the context of games. Children's social behavior was assessed during two sessions, group game periods (i.e., intervention sessions) and nonintervention play periods (i.e., generalization sessions). In both studies, a multiple baseline design across two target children and peers in their respective group was used to evaluate the effects of group socialization procedures. During group game periods, after intervention, target children increased their rates of both prompted and unprompted social interactions with peers. Also, in nonintervention play periods, target children improved both the rate and the duration of their social responding with peers. Results indicated that group socialization procedures were a practical and effective method for improving young children's social interaction during both structured games and unstructured play activities.     

To stay or not to stay: are fears about shorter postnatal hospital stays justified?

Common concerns raised during a Ministerial Review of Birthing Services in Victoria, Australia about the potential detrimental effects of shorter hospital stays after birth were examined in a study of women's actual experiences of and opinions about their hospital stays. Just under one in four women left hospital within five days of the birth, with the greater majority staying five days or more. Satisfaction with length of stay was high in the sample, with 82% of women feeling their stay had been about right, 11% feeling it had been too long and only 7% of women feeling their stay had been too short. A number of the concerns about the consequences of shorter lengths of stay were not borne out. Women who left hospital earlier than the traditional 5-7 day stay were not less likely to breast feed, nor were they more likely to be depressed 8-9 months after the birth. They were also much more likely to feel confident about looking after their baby when they went home than women who stayed five days or more. Implications for further research and for policy development concerning length of stay are considered.     

The kidney in hypertensive pregnancies--victim and villain.

Many changes in renal function occur in normal pregnancy. Without a proper understanding of these changes, routine clinical investigations may easily be misinterpreted. Women with preeclampsia have further alterations in renal function and, in occasional cases, develop acute renal failure. Understanding of abnormal renal physiology and hormonal changes in these women allows the clinician to interpret biochemical tests appropriately and make proper use of vasodilator therapy with careful attention to volume homeostasis. Women who undertake pregnancy with a primary renal disease, most commonly glomerulonephritis or reflux nephropathy, have a higher risk of adverse fetal and maternal outcomes. Awareness of these risks provides a basis for proper preconceptual counseling, as well as careful monitoring of maternal blood pressure and renal function and fetal growth during such pregnancies. These strategies will optimize the chances of a successful pregnancy outcome for both mother and baby.     

Solitary pulmonary nodule: CT evaluation of enhancement with iodinated contrast material--a preliminary report.

The authors hypothesized that the degree of contrast material enhancement of a pulmonary nodule, measured with computed tomography (CT), may indicate the likelihood of malignancy. Fifty-two patients with uncalcified solitary pulmonary nodules (diameter, 6-30 mm) were studied. Five single serial thin-section CT scans were obtained at 1-minute intervals after injection of 100 mL of nonionic contrast material. Twenty-two patients were excluded because the diagnosis was not clearly established: The observation period was less than 2 years, or the examination was technically inadequate. Malignant nodules were identified in 23 of the 30 remaining patients, and benign nodules were identified in seven. Within the first 2 minutes after the injection, all the malignant nodules had enhanced by 20 HU or greater (only one benign nodule had that degree of enhancement). The authors conclude that the degree of contrast material enhancement of pulmonary nodules as measured with CT may indicate the likelihood of malignancy.     

The cigarette controversy.

This study examines the history of the cigarette controversy using the tobacco documents as a roadmap to explore the following four questions: (a) What did tobacco companies know about the health risks of smoking and when did they know it? (b) What evidence is there that tobacco companies conspired to deliberately mislead the public about the health risks of smoking? (c) How were scientists involved in the cigarette controversy? (d) Have tobacco companies changed the way they do business since signing the 1998 Master Settlement Agreement? The tobacco companies knew and for most part accepted the evidence that cigarette smoking was a cause of cancer by the late 1950s. The documents also reveal that the tobacco companies helped manufacture the smoking controversy by funding scientific research that was intended to obfuscate and prolong the debate about smoking and health. Today, the tobacco companies acknowledge that smoking is a cause of disease, but they have not materially altered the way they do business. In our opinion, it is not sufficient for the tobacco industry to merely concede the obvious point that smoking is a cause of disease when it is evident that decades of misinformation has resulted in a public that is massively ignorant about the risks of smoking low-tar cigarettes, nicotine addiction, and secondhand smoke exposure. Public education efforts are still needed to correct these misperceptions along with government oversight to ensure that the industry is not permitted to mislead the public further. If the past 50 years have taught us anything, it is that the tobacco industry cannot be trusted to put the public's interest above their profits no matter what they say.     

Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-substituted-4-(phenylamino)quinolines.

Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show that, for compounds bearing such a substituent, only a particular combination of properties provides high activity, both in vitro and as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the Cquin-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion after oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.