Neurokinin-1 receptor antagonism attenuates neuronal activity triggered by stress-induced reinstatement of alcohol seeking.

Substance P (SP) and its cognate neurokinin-1 receptor (NK1R) are involved in alcohol-related behaviors. We have previously reported that NK1R antagonism attenuates stress-induced reinstatement of alcohol seeking and suppresses escalated alcohol self-administration, but does not affect primary reinforcement or cue-induced reinstatement. Here, we administered an NK1R antagonist or vehicle prior to footshock-induced reinstatement of alcohol seeking, and mapped the resulting neuronal activation using Fos immunohistochemistry. As expected, vehicle treated animals exposed to footshock showed induction of Fos immunoreactivity in several regions of the brain stress circuitry, including the amygdala (AMG), nucleus accumbens (NAC), dorsal raphe nucleus (DR), prefrontal cortex (PFC), and bed nucleus of the stria terminalis (BNST). NK1R antagonism selectively suppressed the stress-induced increase in Fos in the DR and NAC shell. In the DR, Fos-induction by stress largely overlapped with tryptophan hydroxylase (TrpH), indicating activation of serotonergic neurons. Of NAC shell neurons activated during stress-induced reinstatement of alcohol seeking, about 30% co-expressed dynorphin (DYN), while 70% co-expressed enkephalin (ENK). Few (<1%) activated NAC shell neurons coexpressed choline acetyltransferase (ChAT), which labels the cholinergic interneurons of this region. Infusion of the NK1R antagonist L822429 into the NAC shell blocked stress-induced reinstatement of alcohol seeking. In contrast, L822429 infusion into the DR had no effect, suggesting that the influence of NK1R signaling on neuronal activity in the DR is indirect. Taken together, our results outline a potential pathway through which endogenous NK1R activation mediates stress-induced alcohol seeking.

White matter integrity, as measured by diffusion tensor imaging, distinguishes between impaired and unimpaired older adult decision-makers: A preliminary investigation.

In the context of normal ageing, some individuals experience cognitive changes that affect their decision-making abilities. We investigated whether such cognitive changes could be related to the integrity of cortical white matter, as measured by diffusion tensor imaging (DTI). Participants were administered a well-validated laboratory decision-making task, and were subsequently grouped as either poor decision-makers (older-impaired, n = 9) or strong decision-makers (older-unimpaired, n = 7). Participants also underwent magnetic resonance imaging (MRI) that collected high-resolution structural images, including DTI of the brain. The key variable of interest to be contrasted between the groups was fractional anisotropy (FA), as calculated from the tensor images. We hypothesised that FA values would be lower (indicating poorer integrity of tracts) in the older-impaired participants. The results supported our hypothesis, indicating significant differences in FA values between the participant groups for the entire brain as well as several subregions. The results suggest that poorer decision-making abilities are associated with the integrity of cortical white matter across multiple regions of the brain, and support the call for additional research in this area.

Adherence to TB preventive therapy for HIV-positive patients in rural South Africa: implications for antiretroviral delivery in resource-poor settings?

OBJECTIVES: To explore patient and health worker perspectives on adherence to tuberculosis preventive therapy (TBPT), and to derive lessons for improving access to care amongst human immunodeficiency virus (HIV) infected individuals in resource-poor settings. DESIGN: Both quantitative and qualitative methods were employed. Patient records were reviewed for HIV-positive individuals attending a hospital-based HIV clinic between January 2000 and March 2002. Eighteen patients and two health care workers underwent in-depth interviews exploring perspectives around adherence. RESULTS: Of 229 HIV-positive clinic attendees, 94 (41.0%) were eligible for TBPT. Of 87 patients initiating a 6-month TBPT course of isoniazid 300 mg daily, 41 (47.1%) completed TBPT. Of the 46 interrupters, 16 (34.7%) did not return to the clinic after receiving their first dose of TBPT. Barriers to adherence included fear of stigmatization, lack of money for food and transport, the belief that HIV is incurable, competition between Western and traditional medicine, and a reluctance to take medication in the absence of symptoms. Disclosure of HIV status, social and family support, and a supportive clinic environment positively influenced adherence. CONCLUSION: Interventions to improve the accessibility and quality of the care delivery system have the potential to support adherence to TBPT and other HIV care regimens, including antiretroviral therapy.

Cancer screening coverage of south Asian women in Wakefield.

OBJECTIVE: To measure the cervical and breast screening coverage of south Asian women in Wakefield, compared with other city residents. DESIGN: Pairwise measurement of screening histories of women whose names appeared to be south Asian, and of non-Asian women matched by date of birth and general practice. DATA SOURCE: Computerised records of screening histories held by West Yorkshire Central Services Agency, for the eight general practices in central Wakefield. RESULTS: 67% of south Asians and 75% of non-Asians had acceptable (not overdue) cervical screening histories (chi(2)=13.75, p<0.001). 53% of south Asians and 78% of non-Asians had acceptable breast screening histories (chi(2)=8.5, p<0.01) CONCLUSION: Interventions should be designed to improve coverage for breast screening among south Asian women. The need for such interventions for cervical screening is equivocal.

Transatrial access to the normal pericardial space for local cardiac therapy: preclinical safety testing with aspirin and pulmonary artery hypertension.

The reliability, rapidity, and safety of nonsurgical, transatrial pericardial access for local cardiac therapy have been demonstrated in healthy animals. Since many patients take aspirin or have increased right-sided pressures, we evaluated the procedure's safety under these conditions. Transatrial pericardial access was performed in anesthetized pigs following aspirin administration (162 mg p.o., n = 6) or during experimental pulmonary artery hypertension (n = 4 different animals) and required only 3 minutes following guide catheter positioning. Platelet aggregability testing with arachidonic acid confirmed aspirin effectiveness. Mean pericardial fluid hematocrit was 0.1 +/- 0.1% after 2 days of aspirin therapy and 1.9 +/- 1.1% at sacrifice 24 hours later (NS). Mean pericardial fluid hematocrit was 1.0 +/- 0.5% after 45 minutes of pulmonary artery hypertension and 4.3 +/- 0.8% at sacrifice 30 minutes later (NS). Histologic analysis in both groups revealed a small thrombus and localized inflammation at the site of puncture. Neither aspirin use nor pulmonary artery hypertension causes significant bleeding into the pericardial space following transatrial access and thus does not preclude this route for local cardiac drug delivery.

Perceptions and experiences of primary nursing in an ICU: a combined methods approach.

With the introduction of the Patient's Charter, greater emphasis has been placed on 'named nursing' (Department of Health 1991). While there is much literature extolling the benefits of this method of delivering care to patients (Reed 1988; Manley 1989; Macguire 1991); there is a dearth of empirical studies exploring primary nursing in an adult intensive care unit (ICU). In addition, little is known about how nurses feel about being a 'primary nurse'. The aim of this study was to determine qualified nurses' perceptions and experiences of the effect of primary nursing on patient care in an intensive care environment (ICU) and to explore nurses' experiences of being a primary nurse. This study was carried out in an ICU in Northern Ireland. Primary team nursing was the system of organizing care within this unit. This system consisted of teams of 'primary' and 'associate' nurses. A total of 65 qualified nurses were surveyed. Sixteen nurses took part in focus group interviews. A combined methods approach comprising a questionnaire and focus group interviews was employed for the study. Part one of the questionnaire provided data on professional and demographic details. Part two facilitated nurses to elaborate on their feelings and perceptions of the concept of primary nursing. The focus groups facilitated in-depth exploration of the respondents' personal feelings and experiences about their role as a primary nurse. The data obtained from the two-part questionnaire were analysed using descriptive statistic and content analysis. The data obtained from the focus groups were analysed using content analysis and the development of emerging themes. Analysis of the data revealed that the nurses' views were similar to those highlighted in the existing literature. Nurses perceived primary nursing to relate to the responsibility for the care of one patient, from admission to discharge with the primary nurse assessing, planning, implementing and evaluating care and the associate nurse assisting in the delivery of this care. Thus, continuity of care was seen as the major advantage of primary nursing. The findings, however, suggested that further teaching on the concept of primary nursing was required. In addition, many of the nurses admitted they experienced considerable stress, particularly in relation to their close proximity over a long period of time, with patients and their relatives. This is an important finding and highlights the need for primary nurses in ICU to have the opportunity (in some instances), to be relieved of their responsibility for a named patient, thereby reducing some of the potential for stress. It is acknowledged that the findings of this study may not be generalized beyond the identified sample. Further empirical studies exploring nurses' perceptions and experiences of primary nursing in an ICU are therefore needed.

Intrapericardial beta-adrenergic blockade with esmolol exerts a potent antitachycardic effect without depressing contractility.

Hyperadrenergic states of various etiologies can contribute to tachycardias. Systemic beta-adrenergic blockade suppresses sinus tachycardia but may adversely affect arterial blood pressure and contractility, because the drug gains access to myocardial cells as well as to the sinoatrial node. We examined whether intrapericardial beta-adrenergic blockade with esmolol could suppress tachycardia without reducing contractility as a result of limited drug diffusion, which would be sufficient to penetrate the superficial sinoatrial node but not the deeper myocardial layers. In five anesthetized pigs, we provoked a reflex heart rate increase of 50 beats/min with hemorrhage. The rapidly acting beta-adrenergic blocking agent esmolol (1 mg/kg) was administered intrapericardially using a new percutaneous transatrial access method and a catheter system that can be rapidly and safely introduced. Esmolol equivalently suppressed hemorrhage-induced sinus tachycardia when administered intrapericardially (from 192 to 158 beats/min at 5 min, p < 0.05) or intravenously (from 177 to 151 beats/min at 1 min, p < 0.05). The antitachycardic effect of intrapericardial esmolol was prolonged compared with intravenous esmolol (10 min vs. 3 min, p < 0.05). Intrapericardial esmolol did not affect blood pressure or left ventricular dP/dt max, an index of contractility, whereas intravenous esmolol decreased blood pressure at 1 min for 2 min (p < 0.05) and simultaneously decreased left ventricular dP/dt max at 1 min for < 2 min (p < 0.05). Intrapericardial esmolol suppresses adrenergically induced sinus tachycardia without decreasing contractility or blood pressure. The transatrial approach for intrapericardial delivery of certain 1-adrenergic blocking agents could be employed to control tachycardias in emergency care and surgical settings in patients with impaired cardiac contractility and propensity to hypotension.

The incidence of smoking amongst nurses: a review of the literature.

Over the years there has been an ongoing debate about the implications of the smoking behaviour of nurses in relation to their own health and in the context of their professional role and responsibilities. However it is difficult to determine with any degree of accuracy the current incidence of smoking amongst nurses and most of the available research is based on small samples which embrace nurses of different levels and status. Very few recent studies in the United Kingdom or elsewhere have focused on this issue. A confused picture therefore emerges. This paper presents a critical overview of the literature and where appropriate provides data about the incidence of smoking in comparable groups of the general population.

Why nurses smoke: a review of the literature.

The smoking behaviour of nurses has been widely debated in the context of their professional role and responsibilities. There has been much speculation about why nurses smoke and possible explanations include a stressful nursing environment, peer pressure and socio economic status and education. This paper provides an overview of the literature which offers insights into the reasons why nurses smoke and compares the findings from this literature with those studies examining the smoking behaviour of women in general and young women in particular. This review reveals that many students take up smoking before commencing their training and the factors which influence nurses smoking are similar to those that influence similar groups of females in the general population.

Impact of correlated factors on bone density in individuals with a family history of osteoporosis.

Previous studies have suggested that 14-47% of the variation in bone mineral density (BMD) can be predicted using clinical risk factors. The aim of our study was to determine, for the first time, the importance of these factors in individuals with evidence of a genetic predisposition to the disease. The subjects studied were 147 female and 86 male Caucasians, all with a family history of osteoporosis. Linear regression was used to determine whether age, height, weight, and years of reduced estrogen exposure were significant predictors of BMD. Males and females were examined separately, and BMD was measured at the hip and spine. The results show that these risk factors, known to be at work in the general population, are equally important in those with a family history of osteoporosis. It is clear, therefore, that they must be taken into account, and corrected for in genetic studies of the disease.

Preclinical safety testing of percutaneous transatrial access to the normal pericardial space for local cardiac drug delivery and diagnostic sampling.

The safety of a percutaneous method and streamlined catheter system to access the normal pericardial space via the right atrial appendage for drug delivery and diagnostic sampling was demonstrated in 20 anesthetized pigs. Access was successfully accomplished in all animals within 3 min of guide catheter positioning and was documented by fluoroscopic imaging and pericardial fluid sampling. The animals were sacrificed at 24 hr (n = 10) and 2 weeks (n = 10) for histopathologic analysis. Mean pericardial hematocrit was 1.1% +/- 0.3% at initial sampling, 4.3% +/- 1.4% at 24 hr (P = 0.005 vs. baseline), and 0.4% +/- 0.2% at 2 weeks (P = 0.13 vs. baseline). At 24 hr, there was local inflammatory reaction in the atrial wall and a small thrombus at the site of puncture. At 2 weeks, no significant inflammatory changes or pericarditis were evident. The technique is well tolerated with no apparent adverse complications. Advances in intrapericardial therapeutics and diagnostics will direct the clinical application of this novel approach in human subjects.

Heart rate surges during REM sleep are associated with theta rhythm and PGO activity in cats.

Rapid eye movement (REM) sleep is characterized by periods of profound cardiac autonomic activation evident in heart rate surges in humans and canines. Our goals were to determine whether or not the heart rate surge phenomenon occurs in cats and to characterize concurrent central nervous system activity. Cortical and hippocampal electroencephalogram, electromyogram, electrooculogram, pontogeniculooccipital (PGO) waves, subcutaneous electrocardiogram, and respiration were recorded. Bouts of sinus tachycardia lasting >/=3.5 s achieved a rate of 210 beats/min and were present predominantly during REM sleep. Heart rate during the surges rose an average of 26.4% from 132.5 +/- 2.0 beats/min before the surge to 167.5 +/- 2.6 beats/min (P < 0.001) and returned to 130.7 +/- 2.6 beats/min (P < 0.001). The heart rate surges were invariably accompanied by increased incidence and frequency of hippocampal theta waves and increased PGO wave frequency and incidence of PGO wave clusters and eye movement clusters. The occurrence of surges was dramatically reduced from 0.11 +/- 0.03 to 0.01 +/- 0.01/15 s of REM sleep (P = 0.02) by atenolol (0.6 mg/kg iv), indicating that the phenomenon is beta(1)-adrenergically mediated. These findings suggest a coupling between central activation of cardiac sympathetic nerves and the generation of hippocampal theta waves and PGO activity.

Evaluating the effectiveness of a smoking cessation intervention designed for nurses.

The purpose of this study was to evaluate the effectiveness of offering an individualised approach to smoking cessation to qualified nurses and student nurses in Northern Ireland. Twenty-two qualified nurses and 32 student nurses enrolled in the intervention. A further 23 qualified nurses and 33 student nurses expressed interest in giving up smoking, but did not wish to be included in the intervention. They were assigned to the comparison group. Objective verification utilising salivary cotinine measurements of continuous abstinence at 6 months and 1 year demonstrated that 24% of student and qualified nurses in the intervention groups stopped smoking compared with 7% of those in the comparison groups. Both of these differences are statistically significant (Fisher's Exact Probability Test p = < 0.05). This suggests that the individualised approach as used in this study is an appropriate method of helping motivated nurses to quit.

Persistent primary coronary dilation induced by transatrial delivery of nitroglycerin into the pericardial space: a novel approach for local cardiac drug delivery.

OBJECTIVES: We compared the effects of intrapericardial and intracoronary nitroglycerin on coronary cross-sectional area as assessed by intravascular ultrasound and demonstrated the feasibility of local cardiac drug delivery by a newly developed method to access the normal pericardial space through the right atrial appendage. BACKGROUND: Studies of nitric oxide (NO) donors have suggested that their antiarrhythmic and antiproliferative properties are more effective when administered by the intrapericardial rather than intravascular route. We postulated that NO donors delivered intrapericardially would also cause sustained coronary vasodilation without significant systemic hypotension. METHODS: Intrapericardial nitroglycerin (200 microg) was administered in five Yorkshire pigs. Coronary cross-sectional luminal area was measured with intravascular ultrasound at various time intervals. The effects of intracoronary nitroglycerin on coronary luminal area were used for comparison. RESULTS: Transatrial pericardial access required 1 to 3 min in all animals. Intrapericardial nitroglycerin was associated with a mean 31.7% increase in luminal area at 5 min (p < 0.001). Vasodilation peaked between 5 and 10 min and persisted for 15 min. In contrast, intracoronary nitroglycerin was associated with a smaller mean increase in luminal area (20.3% at 5 min, p < 0.01) that disappeared by 10 min. Significant systemic hypotension was observed at 3 min with intracoronary but not with intrapericardial nitroglycerin. CONCLUSIONS: Sustained coronary vasodilation can be achieved with intrapericardial delivery of nitroglycerin without systemic hypotension. Nitric oxide donors with longer half-lives could prove beneficial in the treatment of myocardial ischemic syndromes when administered through this route. Transatrial pericardial access offers a novel route for local cardiac drug delivery.

Deaf children's understanding of beliefs and desires.

Twenty-two children (5-12 year old) who were profoundly, prelingually deaf were given two tests designed to tap their 'theory of mind', that is, their ability to attribute independent mental states to other people. The tests were versions of Baron-Cohen, Leslie, and Frith's Sally-Anne task and of Baron-Cohen's breakfast task. Seventy percent of the children were successful on all questions requiring belief attribution, a considerably and significantly larger percentage than the 29% obtained by Peterson and Siegal for a similar sample, though it is still lower than would be expected on the basis on chronological age. Children were universally successful on questions requiring the attribution of desire. We discuss implications of the findings.

Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents.

A double blind randomized controlled trial was conducted in 71 adolescents aged 11-18 years. Inclusion in the trial required fulfilment of the diagnostic criteria, (Fukuda et al., 1994). Three infusions of 1 gm/kg (max 1 litre of 6 gm/100 ml in 10% w/v maltose solution) were given one month apart. The dummy solution was a 10% w/v maltose solution with 1% albumin of equivalent volume for weight. Efficacy was assessed by difference in a mean functional score including school attendance, school work, social activity and physical activity, between baseline, three months and six months after the final infusion. There was a significant mean functional improvement at the six month follow-up of 70 adolescents with Chronic Fatigue Syndrome of average duration 18 months. There was also a significant improvement for both groups from the beginning of the trial to the six month post infusion follow-up. Adverse effects were common with both solutions but not predictive of response. Neither solution could be identified by recipients.