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Effect of prenatal stress on opioid component of exploration in different experimental situations.

Prenatal stress interferes with the expression of opioid systems in rats. The present study determined the effect of prenatal stress on the opioid-influenced component of exploratory behavior, defined as the difference between the behavior of vehicle-treated and naloxone-treated rats, in three novel situations previously shown to cause different degrees of arousal. Pregnant rats were stressed three times weekly on a random basis by noise and flashing lights. Experiments were performed on 60-70-day-old offspring (male and female) of control and stressed dams. Fifteen minutes after injection of vehicle or naloxone (1 mg/kg), the proportion of time spent in eight different behavioral parameters, including locomotion, rearing, sniffing, hole poking, pivoting, and grooming, was assessed during 4 min of exposure to an open field, either with or without prior exposure to a hole box. The magnitude of the depressant effect of naloxone on exploration depended on the nature of the environment, previous experience of the animal in another situation, and the parameter of exploration assessed. The opioid-influenced component of locomotion and rearing was significantly reduced by prenatal stress, particularly in female rats. Further studies using a cross-fostering design are needed to assess the relative contributions of pre- and postnatal factors to the reduction of opioid activity in prenatally stressed rats. More specific opioid antagonists could be used to determine the nature of the opioid receptors involved.

Animals↗

Following the water, the new program for Mars exploration.

In the wake of the loss of Mars Climate Orbiter and Mars Polar Lander in late 1999, NASA embarked on a major review of the failures and subsequently restructured all aspects of what was then called the Mars Surveyor Program--now renamed the Mars Exploration Program. This paper presents the process and results of this reexamination and defines a new approach which we have called "Program System Engineering". Emphasis is given to the scientific, technological, and programmatic strategies that were used to shape the new Program. A scientific approach known as "follow the water" is described, as is an exploration strategy we have called "seek--in situ--sample". An overview of the mission queue from continuing Mars Global Surveyor through a possible Mars Sample Return Mission launch in 2011 is provided. In addition, key proposed international collaborations, especially those between NASA, CNES and ASI are outlined, as is an approach for a robust telecommunications infrastructure.

Equipment Design↗

Modeling international cooperation in human space exploration for the twenty-first century.

The policy process of international cooperation in space exploration. including optimistic and pessimistic scenarios for the twenty-first century, is modeled and examined in this study. In the optimistic scenario, international cooperation involves a balanced and interdependent distribution of capabilities between states, their respective national space agencies and communities of space scientists and space engineers. Cooperation is characterized by interstate participation in critical path components and joint research and development. In the pessimistic scenario, international cooperation is structured and dominated politically and economically by powerful states vis-a-vis weaker states. Cooperation is limited to coordination of separate nationally approved projects and augmentation of capabilities in noncritical path components. On the basis of these two scenarios, policy predictions and implications relevant to exploration missions in the twenty-first century, such as a human-tended lunar base and human missions to Mars, are presented and discussed.

Europe↗

Randomised trial of laparoscopic exploration of common bile duct versus postoperative endoscopic retrograde cholangiography for common bile duct stones.

BACKGROUND: The management of stones in the common bile duct in the laparoscopic era is controversial. The three major options are preoperative endoscopic retrograde cholangiography (ERCP), laparoscopic exploration of the common bile duct (LECBD), or postoperative ERCP. METHODS: Between August, 1995, and August, 1997, 471 laparoscopic cholecystectomies were done in our department. In 427 (91%), satisfactory peroperative cholangiography was obtained. In 80 (17%) of these cases there were stones in the common bile duct, 40 patients were randomised to LECBD and 40 to postoperative ERCP. If LECBD failed, patients had either open exploration of the common bile duct or postoperative ERCP. If one postoperative ERCP failed, the procedure was repeated until the common bile duct was cleared of stones or an endoprosthesis was placed to prevent stone impaction. The primary endpoints were duct-clearance rates, morbidity, operating time, and hospital stay. Analyses were by intention to treat. FINDINGS: Age and sex distribution of patients was similar in the randomised groups. Duct clearance after the first intervention was 75% in both groups. By the end of treatment, duct clearance was 100% in the laparoscopic group compared with 93% in the ERCP group. Duration of treatment was a median of 90 min (range 25-310) in the laparoscopic group (including ERCPs for failed LECBD) compared with 105 min (range 60-255) in the postoperative ERCP group (p = 0.1, 95% CI for difference -5 to 40). Hospital stay was a median of 1 day (range 1-26) in the laparoscopic group compared with 3.5 days (range 1-11) in the ERCP group (p = 0.0001, 95% CI 1-2). INTERPRETATION: LECBD is as effective as ERCP in clearing the common bile duct of stones. There is a non-significant trend to shorter time in the operating theatre and a significantly shorter hospital stay in patients treated by LECBD.

Cholangiopancreatography, Endoscopic Retrograde↗

Hepatic subcapsular biloma: a rare complication of laparoscopic cholecystectomy and common bile duct exploration.

PURPOSE: Description of an unusual complication of laparoscopic cholecystectomy and common bile duct exploration. METHODS: Case report from experience at an Air Force tertiary care hospital in a 70-year-old woman undergoing laparoscopic cholecystectomy. Literature search for journal articles reporting similar complications using Medline, PubMed, and Ovid Internet search systems. RESULTS: A hepatic subcapsular biloma was diagnosed on postoperative day 11 from an elective laparoscopic cholecystectomy and common bile duct exploration. Review of the literature found only 2 other reports of this complication. CONCLUSIONS: Hepatic subcapsular biloma is a rare complication of laparoscopic cholecystectomy. Computed tomography is highly sensitive for diagnosing bilomas, and percutaneous drainage procedures are appropriate treatment. Imaging of the biliary tree should be performed early to determine the location and extent of bile leaks.

Aged↗

Does directed exploration influence locomotor activity in a holeboard test?

The effects of three drugs, chosen for their differential effects on directed exploration and locomotion (ethanol, caffeine, and FG 7142), were examined on the locomotor activity of mice in a holeboard apparatus containing either a solid floor or one with four holes in it. The dose-related effect of all three drugs on locomotor activity was not changed by the presence of the holes, although activity was slightly higher when a solid floor was used. The results indicated that the two measures can vary independently and that the directed exploration component (head-dipping) of the holeboard test does not significantly influence the locomotor activity component.

Animals↗

Prior test experience compromises the anxiolytic efficacy of chlordiazepoxide in the mouse light/dark exploration test.

It is now well established that prior test experience can alter behavioural baselines and attenuate/abolish the anxiolytic efficacy of benzodiazepines in the elevated plus-maze paradigm. In view of evidence that different models of anxiety measure qualitatively distinct forms of anxiety-like behaviour, it is important to establish whether the effects of prior experience extend to other widely-used tests. The present study assessed the behavioural and pharmacological sequelae of a single undrugged prior exposure to the light/dark exploration (L/D) test in mice, using ethological scoring methods. One group of adult male Swiss-Webster mice was given a single undrugged exposure to the L/D test 24 h prior to drug testing, while another group was completely naïve to the apparatus. On test day, half the animals in each experiential condition were treated with saline and half with an anxiolytic dose (10 mg/kg) of chlordiazepoxide (CDP). When administered to test-naïve animals, CDP induced a clear reduction in anxiety-like behaviour as evidenced by significant increases in exploration of the light compartment (line crossings, % line crossings, and % time) as well as reductions in stretched attend postures (SAPs) and the proportion of SAPs displayed toward the light compartment. The behavioural specificity of these effects was confirmed by the absence of a drug effect on line crossings in the dark compartment, total rearing and grooming. In complete contrast, with the sole exception of a decrease in total SAPs, CDP was without significant behavioural effect in test-experienced mice. As prior test experience did not significantly alter behavioural baselines in the L/D test, a second experiment was designed to investigate the possibility that handling/intraperitoneal injection may have precluded detection of experientially-induced changes in baseline behaviour. Results showed that handling/injection had no effect upon L/D behavioural profiles in either test-naïve or test-experienced subjects, and confirmed that prior experience itself did not modify the primary indices of anxiety in this test. Present data indicate that prior test experience seriously compromises the anxiolytic efficacy of CDP (10 mg/kg) in the mouse L/D test and, together with recent findings in the four-plate test, appear to confirm that an experientially-induced reduction in sensitivity to the anxiolytic effects of benzodiazepines is by no means unique to the elevated plus-maze.

Animals↗

Regulatory behaviour, exploration and locomotion following NMDA or 6-OHDA lesions in the rat nucleus accumbens.

The effects of bilateral, N-methyl-D-aspartate (NMDA)-induced lesions of the nucleus accumbens (N.Acc.) on regulatory and behavioural responding were studied in rats and compared with the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions. After postoperative body weight, food and water intake had been monitored for a period of 4 weeks, rats were tested in an exploration-choice box. Spontaneous locomotion and the locomotor and stereotypy responses to different doses of dopaminergic agonists were measured subsequently. Detailed assessment of NMDA-induced lesion volumes showed that on average 81.53% of total N.Acc. area was damaged, depending on excitotoxin dose. Tyrosine hydroxylase immunohistochemistry was used to confirm loss of mesolimbic dopamine neurones following 6-OHDA. Analysis of the behavioural data showed that NMDA N.Acc. lesions significantly enhanced exploratory behaviour, spontaneous locomotor activity and the locomotor response to a low dose of D-amphetamine. By comparison, 6-OHDA lesions did not affect exploration and spontaneous locomotion but significantly attenuated the locomotor response to a low dose of D-amphetamine. Regulatory responses were unaffected 28 days after surgery, although NMDA-lesioned rats took longer to recover from postoperative hypodipsia. The results suggest that NMDA N.Acc. lesions induce a deficit in the control of general locomotor output and are consistent with the hypothesis that the N.Acc. functions as an interface between sensory input and locomotor output and that it is needed to channel activity levels appropriately.

Animals↗

Efficacy of ceruletide controlled saline infusion for retained ductal stones after cholecystectomy and exploration of the common bile duct.

The synthetic peptide ceruletide induces maximal relaxation of the sphincter of Oddi. In a preliminary communication, ceruletide controlled saline infusion of the common bile duct (CBD) was found to be effective in promoting the passage of retained ductal calculi after cholecystectomy and exploration of the common bile duct. This paper reports on the further experience with this simple treatment which was administered to 27 patients with retained ductal calculi in 16 different hospitals within the U.K. The success of the procedure was documented by repeat T-tube cholangiography. Passage of stones into the duodenum was documented in 13 patients (48%) with complete clearance in 9 (33%) following one saline infusion/ceruletide treatment. The radiological stone size ranged from 3 to 15 mm. Within this range, there was no correlation between a successful outcome and size of retained stones. The duration of the saline T-tube infusion during ceruletide treatment averaged 54.7/min (SD 14.3). There was no correlation between flow rate of saline through the T-tube and a successful outcome. A significant inverse correlation was observed between the CBD pressure during ceruletide controlled saline T-tube infusion and successful stone passage (chi 2 = 9.9, P less than 0.01). Ampullary impaction by a stone was encountered in one patient. These results are encouraging and indicate that pharmacological dilatation of the sphincter of Oddi together with saline infusion is effective in the management of retained stones after exploration of the common bile duct. This treatment, which does not require any special expertise, should be tried in the first instance before more invasive procedures are used.

Adult↗

Comparison of neurokinin SP with diazepam in effects on memory and fear parameters in the elevated T-maze free exploration paradigm.

The elevated T-maze was combined with a free exploration protocol, which, in contrast to the conventional procedure, dispenses with handling of the animals during the experimental sessions. This allows measurement of fear indexes derived from the elevated plus-maze as well as assessment of acquisition of open arm avoidance and open arm escape in one continuous session. Retention of the different fear-responses is measured 72 h later without drug treatment. In order to assess the effects of two known anxiolytics in this paradigm, rats received an IP injection of diazepam (1 to 4 mg/kg), substance P (5 to 500 microg/kg) or vehicle (1 ml/kg) and were tested on the T-maze for 5 min. Diazepam elevated open arm activity, indicative of an anxiolytic effect. The drug also increased the latency to escape from the open arms, but did not significantly affect acquisition of open arm avoidance. During the retention trial, diazepam in higher doses impaired the performance of both fear-responses, suggestive of an anterograde amnesic effect. Substance P did not influence acquisition and retention of open arm avoidance and escape. However, in high doses, the peptide increased the sojourn time in the central arena of the maze, indicating reduced fear and, hence, a dissociation between anxiolytic and amnesic effects. The present findings demonstrate that the elevated T-maze free exploration paradigm is sensitive to anxiolytic and memory-modulating effects of drugs.

Animals↗

A critical exploration of "Working Together, Learning Together"--does it meet the learning needs of nurses?

Recent government educational initiatives have emphasised the need for lifelong learning to facilitate and equip nurses with the appropriate knowledge and skills to operate in a dynamic healthcare delivery system. In this paper I will critically explore a recent educational framework from an educational ideology and curriculum design perspective. It is recognised that any educational program cannot be devised or constructed in a socio-political vacuum and any developments must acknowledge this influence on the context in which nurse education operates. The framework is debated from an ideological perspective and I surmise that an ideological change from Romanticism to Revisionism will facilitate change in curriculum design that is in keeping with the realties of healthcare needs. The educational initiative is explored from a curriculum design perspective utilising Beattie's Fourfold Model. I further surmise that the educational initiative fails to acknowledge the uniqueness of nursing knowledge and the integral learning processes such as reflection thus marginalising nursing as a profession. In this paper I suggest that any educational initiative must recognise the evolving role of nursing, the profession and the realties of healthcare systems to ensure the present and future workforce is skilled and empowered to aspire to these multifaceted demands.

Curriculum↗

An exploration of midwives' attitudes to research and perceived barriers to research utilisation.

OBJECTIVE: To explore midwives' views about research and their perceived barriers to research utilisation. SETTING: Thirty-two midwives from four midwifery units in the north west of England. The units ranged in size from a small district unit (52 midwives, and 1200 deliveries per annum), to a large regional centre (290 midwives, 6500 deliveries per annum). METHODS: Midwives' opinions concerning research were explored using focus group interviews; within the interviews midwives were asked to discuss how they viewed the relevance of research to midwifery care, the constraints which they felt prevented them from delivering research-based care and existing and potential methods of disseminating research. FINDINGS: There was a consensus among the midwives that they aspired to deliver research-based care. However, there are clearly a number of barriers preventing this. Research was poorly accessible to most midwives, both in terms of its physical location and complexity. Furthermore, midwives felt they lacked the knowledge and skills to appraise research, and lacked the confidence to judge when research should be implemented. CONCLUSIONS: The current trend to demedicalise childbirth demands that midwives become proficient users of research. However, the means of disseminating research findings to midwives in the north west of England does not meet their needs.

Attitude of Health Personnel↗

Issues of exploration: human health and wellbeing during a mission to Mars.

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart.

Adaptation, Physiological↗

Why do women use dietary supplements? The use of the theory of planned behaviour to explore beliefs about their use.

Dietary supplements use is increasing, despite the lack of evidence to suggest they are needed to meet dietary deficiency in the majority of people. Reasons for consuming dietary supplements are likely to be complex, combining social, psychological, knowledge and economic factors. The Theory of Planned Behaviour (TPB) is a widely used model of social cognition, which has recently been applied to the nutrition field. It was used in a questionnaire, along with a number of additional measures, to explore dietary supplement use in a cohort of women. Data from 303 questionnaires were included in the analysis. The results showed that intentions were the major predictor of dietary supplement use. Health value and susceptibility to illness were also significant predictors of dietary supplement use (total of 82.9% of respondents correctly classified as users or non-users). Intentions themselves were most strongly predicted by attitude, with 70% of variance explained by attitude, subjective norms and perceived behavioural control. Other significant predictors of intentions were control beliefs, normative beliefs and health value. Beliefs underlying dietary supplement use revealed differences between supplement users and non-users in relation to the notion that taking dietary supplements acts as an insurance against possible ill-health, with supplement users believing more strongly than non-users that taking dietary supplements would stop them getting ill and help them to be healthy. Both users and non-users of supplements also perceived the media, in the form of books and magazines, to be a powerful influence on a person's decision to use supplements. The findings of this study highlight the potential of the TPB in exploring supplement-taking behaviour, while throwing light on the factors influencing an individual's motivations to use dietary supplements.

Case-Control Studies↗

[Mediastinoscopy in the diagnosis of mediastinal disease. An analysis of 181 explorations].

To validate our experience with standard cervical mediastinoscopy (SCM) and extended cervical mediastinoscopy (ECM) to diagnose mediastinal nodes and masses, we studied 181 patients between January 1992 and February 2001. SCM and ECM were indicated for diagnostic staging of nodes related to bronchogenic carcinoma (Group I) or of mediastinal masses (Group II). An SCM was performed in all cases to explore the paratracheal region (2R, 2L, 4R, 4L, 7, 10R and 10L); in 21 additional cases, an ECM was performed to explore the aortopulmonary window or the subaortic region (area 5) and the para-aortic region (area 6). In Group I, the sensitivity of SCM was 93.6% and specificity was 100%; the positive predictive value (PPV) was 100%, the negative predictive value (NPV) was 82.8%, and the diagnostic yield was 95.1%. The sensitivity of ECM was 91% and specificity was 100%; PPV was 100%, NPV 93.3% and yield was 96%. In Group II, the sensitivity was 93.3%, specificity 100%, PPV 100%, NPV 81.2% and diagnostic yield 94.8%. The sensitivity of ECM in this group was 80%, specificity was 100%, PPV 100%, NPV 66.7% and yield 85.7%. A 2.7% complication rate was observed, with one case of bleeding after injury to the superior vena cava, one tracheal lesion, one recurring paralysis and two cases of surgical wound infection. The mean postoperative stay was 36 hours and mortality was zero. We conclude that SCM is highly specific for the evaluation of mediastinal node involvement in bronchogenic carcinoma and it is the approach of choice when a diagnosis of lesions located in the mid-mediastinal region has not been reached. ECM is a valid, safe alternative to anterior mediastinotomy for staging nodes and masses occupying para-aortic zones or the aortopulmonary window, with good diagnostic yield, low morbidity and absence of mortality.

Adenocarcinoma↗

Exploring the opioid system by gene knockout.

The endogenous opioid system consists of three opioid peptide precursor genes encoding enkephalins (preproenkephalin, Penk), dynorphins (preprodynorphin, Pdyn) and beta-endorphin (betaend), proopiomelanocortin (POMC) and three receptor genes encoding mu-opiod receptor (MOR), delta-opiod receptor (DOR) and kappa-opiod receptor (KOR). In the past years, all six genes have been inactivated in mice by homologous recombination. The analysis of spontaneous behavior in mutant mice has demonstrated significant and distinct roles of each gene in modulating locomotion, pain perception and emotional behaviors. The observation of opposing phenotypes of MOR- and DOR-deficient mice in several behaviors highlights unexpected roles for DOR to be further explored genetically and using more specific delta compounds. The analysis of responses of mutant mice to exogenous opiates has definitely clarified the essential role of MOR in both morphine analgesia and addiction, and demonstrated that DOR and KOR remain promising targets for pain treatment. These studies also show that prototypic DOR agonists partially require MOR for their biological activity and provide some support for the postulated mu-delta interactions in vivo. Finally, data confirm and define a role for several genes of the opioid system in responses to other drugs of abuse, and the triple opioid receptor knockout mutant allows exploring non-classical opioid pharmacology. In summary, the study of null mutant mice has extended our previous knowledge of the opioid system by identifying the molecular players in opioid pharmacology and physiology. Future studies should involve parallel behavioral analysis of mice lacking receptors and peptides and will benefit from more sophisticated gene targeting approaches, including site-directed and anatomically-restricted mutations.

Animals↗

Results of treatment of midfacial fractures. Indications for exploration and drainage of the maxillary sinuses.

The results of late follow-up of 45 patients with midfacial fractures are reported. The intervals between accident and follow-up ranged from 6 months to 6 years. Methods of treatment are discussed, with emphasis on frontomaxillary or zygomaticomaxillary wire suspension and external fixation. The late results and complications in this series are compared with those previously described in the literature. Since opinions differ as to the basic necessity for surgical exploration and drainage of the sinuses following midfacial fracture, the influence of the latter procedure was investigated statistically. In the group of Le Fort II and III fractures the results following revision were compared with those in sinuses which were not revised: the radiographs (chi2 0.415) and sensory testing (chi2 1.668) showed no significant differences. This supports our opinion that surgical exploration and drainage of the sinuses should continue to be limited to cases which fulfill the strict criteria described in this paper.

Adolescent↗

Crime scene investigations using portable, non-destructive space exploration technology.

The National Institute of Justice (NIJ) and the National Aeronautics and Space Administration's (NASAs) Goddard Space Flight Center (GSFC) have teamed up to explore the use of NASA developed technologies to help criminal justice agencies and professionals solve crimes. The objective of the program is to produce instruments and communication networks that have application within both NASA's space program and NIJ programs with state and local forensic laboratories. A working group of NASA scientists and law enforcement professionals has been established to develop and implement a feasibility demonstration program. Specifically, the group has focused its efforts on identifying gunpowder and primer residue, blood, and semen at crime scenes. Non-destructive elemental composition identification methods are carried out using portable X-ray fluorescence (XRF) systems. These systems are similar to those being developed for planetary exploration programs. A breadboard model of a portable XRF system has been constructed for these tests using room temperature silicon and cadmium-zinc telluride (CZT) detectors. Preliminary tests have been completed with gunshot residue (GSR), blood-spatter and semen samples. Many of the element composition lines have been identified. Studies to determine the minimum detectable limits needed for the analyses of GSR, blood and semen in the crime scene environment have been initiated and preliminary results obtained. Furthermore, a database made up of the inorganic composition of GSR is being developed. Using data obtained from the open literature of the elemental composition of barium (Ba) and antimony (Sb) in handswipes of GSR, we believe that there may be a unique GSR signature based on the Sb to Ba ratio.

Antimony↗