A novel gene delivery method transduces porcine pancreatic duct epithelial cells.

Gene therapy offers the possibility to treat pancreatic disease in cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene; however, gene transfer to the pancreas is untested in humans. The pancreatic disease phenotype is very similar between humans and pigs with CF; thus, CF pigs create an excellent opportunity to study gene transfer to the pancreas. There are no studies showing efficient transduction of pig pancreas with gene-transfer vectors. Our objective is to develop a safe and efficient method to transduce wild-type (WT) porcine pancreatic ducts that express CFTR. We catheterized the umbilical artery of WT newborn pigs and delivered an adeno-associated virus serotype 9 vector expressing green-fluorescent protein (AAV9CMV.sceGFP) or vehicle to the celiac artery, the vessel that supplies major branches to the pancreas. This technique resulted in stable and dose-dependent transduction of pancreatic duct epithelial cells that expressed CFTR. Intravenous (IV) injection of AAV9CMV.sceGFP did not transduce the pancreas. Our technique offers an opportunity to deliver the CFTR gene to the pancreas of CF pigs. The celiac artery can be accessed via the umbilical artery in newborns and via the femoral artery at older ages--delivery approaches that can be translated to humans.

Prophylactic feeding tubes for patients with locally advanced head-and-neck cancer undergoing combined chemotherapy and radiotherapy-systematic review and recommendations for clinical practice.

GOALS: This work aimed to determine the benefits and risks of prophylactic feeding tubes for adult patients with squamous cell carcinoma of the head and neck who receive combined chemotherapy and radiotherapy with curative intent and to make recommendations on the use of prophylactic feeding tubes and the provision of adequate nutrition to this patient population. METHODS: A national multidisciplinary panel conducted a systematic review of the evidence and formulated recommendations to guide clinical decision-making. The draft evidence summary and recommendations were distributed to clinicians across Canada for their input. MAIN RESULTS: No randomized controlled trials have directly addressed this question. Evidence from studies in the target population was limited to seven descriptive studies: two with control groups (one prospective, one retrospective) and five without control groups. Results from ten controlled studies in patients treated with radiotherapy alone were also reviewed. CONCLUSIONS: The available evidence was insufficient to draw definitive conclusions about the effectiveness of prophylactic feeding tubes in the target patient population or to support an evidence-based practice guideline. After review of the evidence, of guidelines from other groups, and of current clinical practice in Canada, the multidisciplinary panel made consensus-based recommendations regarding comprehensive interdisciplinary clinical care before, during, and after cancer treatment. The recommendations are based on the expert opinion of the panel members and on their understanding of best clinical practice.

Randomized clinical trial of the effectiveness of emergency day surgery against standard inpatient treatment.

BACKGROUND: The aim of this study was to assess the feasibility of treating patients with minor and intermediate general surgical emergency conditions as day cases. METHODS: Emergency referrals for minor and intermediate general surgical conditions were assessed by a surgeon. Those fitting day-case criteria and requiring operation under general anaesthesia were randomized to receive standard inpatient care or day surgery. Patients in the latter group were booked on to day-case lists or gaps on inpatient elective lists for surgery within 48 h. The process was coordinated by an experienced theatre sister. RESULTS: One hundred patients were randomized. There was a reduction in the number of nights spent in hospital in the day-case group (median 0 versus 2 nights; P < 0.001). The median time from diagnosis to treatment was 1 day in both groups, although there was a small but significant delay in the day-case group (P = 0.018). There was no significant difference in postoperative outcome or patient and general practitioner satisfaction. The day-case option had no increased impact on primary care services but was associated with a significant saving of about pound sterlings 150 per patient (P < 0.001). CONCLUSION: Certain general surgical emergencies may be managed as day cases with cost saving but without detriment to patient care.

The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England and the national burden imposed.

Between April 1994 and May 1995 4000 adult patients admitted to selected specialties of a district general hospital were recruited to this study. Hospital-acquired infections presenting during the in-patient stay were identified using previously validated methods of surveillance, and information on daily resource use by both infected and uninfected patients was recorded and estimates of their cost derived. Linear regression modelling techniques were used to estimate how much of the observed variation in resource use and costs could be explained by the presence of an infection. Complete in-patient data sets were obtained for 3980 patients. Of these, 309 patients (7.8%; 95% CI; 7.0, 8.6) presented with one or more hospital-acquired infections during the in-patient period. Infected patients, on average, incurred hospital costs 2.9 (regression model estimate: 2.8; 95% CI; 2.6, 3.0) times higher than uninfected patients, equivalent to an additional pound3154 (regression model estimate pound2917). Both the incidence and the economic impact varied with site of infection and with admission specialty. Estimates of the burden of hospital-acquired infections occurring in adult patients admitted to similar specialties at NHS hospitals in England were derived from the results of this study. An estimated 320 994 (95% CI; 288 071, 353 916) patients per annum acquire one or more infections which present during the in-patient period, and these infections cost the hospital sector an estimated 930.62 million pounds (95% CI; 780.26 pounds; 1080.97 million pounds) per annum. The results presented represent the gross economic benefits that might accrue if these infections are prevented. Further research is required to establish the net benefits of prevention.

Dispositions and work reactions: a multilevel approach.

Multiple levels of analysis were used to examine the link between stable dispositions and more state-oriented work reactions such as job satisfaction. Participants in the study were employees from a large state education system and an urban hospital. The proportion of between-group variance in positive work affect, negative work affect, and job satisfaction increased after dispositional measures of neuroticism and extraversion were included, although the confidence intervals overlapped. Aggregate perceptions of excessive job demands explained more between-group variance in work reactions after dispositions were included. Previous research conducted at a single level of analysis suggests that the inclusion of stable dispositions can attenuate the link between work characteristics and work reactions. The present study suggests the opposite pattern when group-level variance is considered.

Linking manager values and behavior with employee values and behavior: a study of values and safety in the hairdressing industry.

Five theoretical processes that link values and behavior were identified: value congruence, value-behavior consistency, behavioral modeling, value internalization, and descriptive norms. A values questionnaire was administered to 219 employees and their managers. Values for preventive safety procedures and time urgency were linked to safety behavior of employees in the hairdressing industry. Hairdressers are frequently exposed to hazardous chemicals, and the safety behavior measured was wearing protective gloves. Results support value internalization (linking manager's and employee's values) and behavioral modeling (linking manager's and employee's behavior). Employee time urgency values were also negatively related to safety behavior (value-behavior consistency). Descriptive norms and value congruence were not supported. Strategies to align values within organizations and the management of safety at work are considered.

Perceptions of safety at work: a framework for linking safety climate to safety performance, knowledge, and motivation.

Research in the areas of organizational climate and work performance was used to develop a framework for measuring perceptions of safety at work. The framework distinguished perceptions of the work environment from perceptions of performance related to safety. Two studies supported application of the framework to employee perceptions of safety in the workplace. Safety compliance and safety participation were distinguished as separate components of safety-related performance. Perceptions of knowledge about safety and motivation to perform safely influenced individual reports of safety performance and also mediated the link between safety climate and safety performance. Specific dimensions of safety climate were identified and constituted a higher order safety climate factor. The results support conceptualizing safety climate as an antecedent to safety performance in organizations.

PHLS begins a national case control study of Escherichia coli O157 infection in England.

Infection with Vero cytotoxin producing Escherichia coli O157 (VTEC O157) is a growing public health problem and the commonest cause of acute renal failure in children in the United Kingdom. Foodborne outbreaks of VTEC O157 infection have been reported in the United Kingdom, other European countries, and North America. Most cases of infection are sporadic, however, and the contribution of food vehicles, animal contact, and person to person spread in the acquisition of infection needs to be clarified. The PHLS is starting a case control study in England to identify and estimate the relative importance of risk factors for the acquisition of VTEC O157 infection. The study will run for 12 months. This article describes its objectives and asks microbiologists, public health physicians, clinicians, and others who may be asked for details about cases or to find suitable controls for their help in achieving a successful outcome.

ET nurses: on the front line of health care reform.

The most important challenge at the forefront of the national agenda is the need for health care reform. Major concerns of the current system are cost and access to care. This article discusses numerous congressional proposals and strategies for addressing these concerns. ET nurses are in a unique position to influence health care delivery. The Wound Ostomy and Continence Nurses Society has implemented strategies that position ET nurses as part of the solution to the health care crisis. ET nurses must also market themselves in their individual settings as key players in health care reform.

Hyperthyroidism in the elderly.

It is not uncommon for thyrotoxicosis to appear in an atypical manner in older patients. The classical symptoms are often absent. The disease is frequently characterized by cardiac, gastrointestinal, neuromuscular, and neuropsychiatric symptoms. As hyperthyroidism is readily amenable to effective treatment that can improve the quality of life, the clinical suspicion of this disease is always indicated and exclusion of this diagnosis should always be pursued. Recognizing the admittedly great difficulty in making, or even suspecting, the diagnosis of hyperthyroidism in the elderly, our rule is to test for hyperthyroidism in essentially all geriatric patients presenting chronic systemic symptoms or signs. On the other hand, we do not recommend community-wide screening of persons over 60 for hyperthyroidism. Community-wide screening falls far below the break-even point in cost-benefit analysis. The most sensible detector of hyperthyroidism now widely available is the serum free T3 index (FT3I), but it may be falsely normal because of the effect of systemic illness on extrathyroidal T4-to-T3 conversion. The advent of ultrasensitive methods for TSH may change these statements considerably. It may become the single screening procedure for both hyper- and hypothyroidism.

Mode of action of ergonovine on isolated porcine coronary artery: the role of Ca2+.

Coronary vasoconstrictor responses to ergonovine were examined in helical coronary arterial strips of young swine. Both ergonovine and serotonin (5-hydroxytryptamine) produced dose-dependent contractions of the strips. The distal region (less than 1.00 mm outer diameter) of the circumflex coronary artery was most sensitive to the responses of serotonin and ergonovine. Methysergide and nifedipine significantly depressed the contractions induced by ergonovine and serotonin. Atropine, propranolol, and the alpha 1 blocker, prazosin, did not antagonize ergonovine-induced contractions. The ergonovine response may depend entirely upon extracellular Ca2+ while the effect of serotonin may be mediated in part through the mobilization of intracellular Ca2+ stores. Increases in 45Ca2+ cellular contents occurred after ergonovine or serotonin and these increases were blocked by methysergide or nifedipine at concentrations which blocked mechanical responses to the agonist. It is concluded that the contractions of the porcine coronary artery produced by ergonovine and serotonin are as follows: (i) regionally sensitive; (ii) blocked by Ca2+ antagonists and therefore may utilize Ca2+ channels similar to those described in other excitable tissues; (iii) blocked by methysergide. These studies indicate that the major mechanism of ergonovine's action in the porcine coronary artery is through the activation of serotonin receptors on coronary arteries which are, in turn, linked to Ca2+ channels. However, this mechanism of action may be different in an intact animal.

Punishment contras during free-operant avoidance.

Punishment of bar-pressing responses of rhesus monkeys with electric shock in one component of a multiple free-operant avoidance schedule suppressed responding in that component. These decreases were concomitant with response rate increases in the unpunished component (punishment contrast). Response rates in both components increased when punishment was removed and decreased in successive sessions. These effects of punishment on unpunished responding were similar to those obtained during single and multiple schedules of positive reinforcement and they suggest a further similarity in the development of discriminations during positive and negative reinforcement schedules.