A Preliminary Study of Clinical Practice and Prenatal Nutrition in Rural Kansas.

Introduction: The primary purpose of this study was to determine if new recommendations for prenatal supplements of docosahexaenoic acid (DHA) and choline have been implemented into care by physicians who care for pregnant women in rural Kansas communities. Both nutrients are inadequate in the diet of most pregnant women in the U.S., and not all prenatal supplements provide DHA and choline. Methods: A cross sectional web-based survey was developed and provided by the University of Kansas Medical Center (KUMC) students to 44 rural Kansas clinics believed to have physicians who provide obstetrical care. Questions about DHA and choline were embedded in a larger survey focused on prenatal care. A total of 29 surveys were returned, however, only 21 were completed by physicians who provided obstetrical care. Results: DHA (3/21) and choline (0/21) rarely were singled out for recommendation in contrast to folic acid (16/21) and iron (14/21). Participants stated that most women sought prenatal care during the first trimester of their pregnancy and indicated that they recommended prenatal vitamins at the first visit. Eleven gave patients a prescription for prenatal vitamins. The remaining patients either chose traditional over the counter prenatal vitamin capsules or less traditional chewable (gummy) vitamins, which provided lower concentrations of nutrients. Common barriers to nutritional counseling were limited resources and time constraints. Clinicians assessed their confidence and ability to provide nutritional counseling as moderate and competent, respectively. Conclusions: New nutritional recommendations for DHA and choline have not been implemented into standard of care in rural Kansas.

Learning person-centredness interprofessionally: an uneasy student journey.

Patient- or person-centered care is a discourse embraced by most clinicians involved in interprofessional care but generally overlooks thepersons of the practitioners and students involved. This paper explores students' developing perceptions of person-centered care during participation in an interprofessional education program where interprofessional pairs of students partner with patients living with a long-term condition or life-changing event. Weekly focus groups with students and educators over the 7 weeks of the program revealed a rich evolving understanding of person-centredness amongst participant students as they built relationships with both their patient and student partner. Students and educators identified shifts in students' interprofessional person-centered perspectives and practices, growing awareness of patient personhood and of stories as key to creating and maintaining space for listening and dialogue, and conscious attention to thoughtful, non-judgmental listening and responses. Although initially uncomfortable, uncertain and "stuck" students came to value working in a holistic relational partnership to explore what mattered to the patient, looking beyond the diagnosis to the multi-faceted nature of living with a life-changing condition or event. Importantly, students' growing self-awareness and participation as persons enhanced person-centredness, leading to questioning of previous healthcare practice experiences where mutual person-centredness was overlooked. Uncertainty about student capability led some educators to reassert control of the process, which students perceived as counterproductive usurping of their personhood and professional autonomy. The research findings suggest that an interprofessional program focused on person-centered relationship building develops student awareness and understanding of mutual personhood but requires high levels of reciprocal trust.

Long Sun-Exposures Influencing High Sub-Cutaneous Synthesis of Vitamin-D3 may be Associated with Exacerbation of Symptoms in Allergic-Asthma.

OBJECTIVES: Does excessive sun-exposure, non-use of sunscreen and/or high doses of vitamin-D3 supplements provoke exacerbation of asthma? DESIGN: Clinical examinations, retrospective records-access and questionnaire surveys were distributed to a convenience sample of allergic-asthma patient (n=183). SETTING: Patients (19-89 years) attending the outpatient respiratory clinics at Maidstone Hospital were enrolled. RESULTS: 90.3% of patients (total IgE levels ≥75 kU/L ; n=103) exposed to direct sunlight of ≥ 15 minutes per day continuously for 6-7 days presented with wheeze (χ2(1) = 7.46; p< 0.05) compared to only 9.7% patients of similar atopy-status, presenting with wheeze if exposed to sunlight of < 15 minutes per day for 6-7 days. 68.9% patients (with IgE levels ≥ 75 kU/L ; n=103), non-users of sunscreen (SPF 30 and above), exposed to direct sunlight of ≥ 15 minutes per day continuously for 6-7 days developed a wheeze, compared to fewer users of sunscreen (9.7%, n=103), exposed to the same duration of sunlight who developed asthma symptoms (p< 0.05). Vitamin-D3 supplementation in asthma-patients with clinical signs of hypovitaminosis-D (n=21), produced symptoms of morning chest-tightness (76.2%), allergic rhinitis (61.9%) and wheeze (100%), 2 weeks after initiation of treatment. CONCLUSIONS: Our results advocate direct sunlight exposure < 15 minutes per day and use of sunscreen as a novel approach to preventing atopic-asthma symptoms in allergic-asthma patients.. Activated vitamin-D3 is well-recognised to shift the immune-balance towards Th2 predominance, favouring allergic asthma. These results suggest that limiting subcutaneous synthesis of vitamin-D3 in asthma patients and re-addressing dosage of vitamin-D3 supplementation is necessary may contribute to prevent exacerbation of symptoms.

Individuals living with lupus: findings from the LUPUS UK Members Survey 2014.

Systemic lupus erythematosus (SLE) is a complex and unpredictable disease which varies greatly among patients and has a significant impact on an individual's daily living and quality of life. A better understanding of the patients' experiences with the disease is vital to the effective management of the disease. LUPUS UK, a national UK-registered charity supporting people with systemic and discoid lupus, conducted a UK-wide survey of individuals living with lupus in order to provide foundation information to support and identify gaps needing further research. An anonymous survey was sent to 5660 LUPUS UK members in order to obtain demographic, diagnosis, symptom and treatment information. A total of 2527 surveys were returned by 2371 females (mean age 56.9 years, SD 13.6) and 156 males, (mean age 60.9 years, SD 15.7). Individuals reported a mean (SD) time to diagnosis from the first symptom of 6.4 (9.5) years, with 47% ( n = 1186) initially being given a different diagnosis prior to lupus. Fatigue/weakness (91%, n = 2299) and joint pain/swelling (77.4%, n = 1957) were the most common symptoms that interfere with daily activities, while 73% ( n = 1836) noted having some problems that make them unable to carry out their usual daily activities. Thirty-two per cent ( n = 806) were also seeking support beyond traditional pharmacological treatments, such as acupuncture and massage. This study highlights the range and frequency of symptoms difficult to live with on a daily basis and support areas needing further research to improve patients' well-being.

Reducing health inequalities in people with learning disabilities: a multi-disciplinary team approach to care under general anaesthesia.

Background There remains significant inequality in health and healthcare in people with learning disabilities (LD). A lack of coordination and the episodic nature of care provision are contributory factors. Recognising the need to improve outcomes for this group, we evaluate a multi-disciplinary team (MDT) approach to care whereby additional medical procedures are carried out under the same episode of general anaesthesia (GA) as dental treatment for people with severe LD. This is the first published evaluation of its kind in the UK.Aim To evaluate the need and outcomes of an MDT approach to care among people with severe LD receiving dental treatment under GA.Method One hundred patients with severe LD and behaviour that challenges attended Barts Health Dental Hospital for dental assessment and subsequent treatment under GA. Details of failed or forthcoming medical interventions were determined. Where appropriate, care was coordinated with the relevant medical team.Findings Twenty-one percent (n = 21/100) had recent medical interventions attempted that had been abandoned, and 7.0% (n = 7/100) had future investigations or treatment planned under GA with medical specialties. An MDT approach was indicated in 28.0% (n = 28/100). For such complex cases, a successful MDT outcome was achieved in 89.3% (n = 25/28). This included ophthalmological/orthoptic, ENT and gastroenterological interventions in addition to medical imaging.Conclusion An MDT approach to care for people with LD offers improved patient-centred outcomes in addition to financial and resource efficiency. It requires a high level of cooperation between specialties, with consideration of the practicalities of a shared surgical space and equipment needs. Re-shaping of services and contractual flexibility are essential to support the future implementation of MDTs and to ensure long-term sustainability. Adoption of a holistic culture in the care of this vulnerable patient group is encouraged.

Does maggot therapy promote wound healing? The clinical and cellular evidence.

The larvae of Lucillia sericata, or maggots of the green-bottle fly, are used worldwide to help debride chronic, necrotic and infected wounds. Whilst there is abundant clinical and scientific evidence to support the role of maggots for debriding and disinfecting wounds, not so much emphasis has been placed on their role in stimulating wound healing. However, there is accumulating evidence to suggest that maggots and their externalized secretions may also promote wound healing in stubborn, recalcitrant chronic ulcers. There are a growing number of clinical reports which support the observation that wounds which have been exposed to a course of maggot debridement therapy also show earlier healing and closure end-points. In addition, recent pre-clinical laboratory studies also indicate that maggot secretions can promote important cellular processes which explain this increased healing activity. Such processes include activation of fibroblast migration, angiogenesis (the formation of new blood vessels from pre-existing vessels) within the wound bed, and an enhanced production of growth factors within the wound environment. Thus, in this review, we summarize the clinical evidence which links maggots and improved wound healing, and we précis recent scientific studies which examine and identify the role of maggots, particularly individual components of maggot secretions, on specific cellular aspects of wound healing.

A preclinical evaluation of the PI3K alpha/delta dominant inhibitor BAY 80-6946 in HER2-positive breast cancer models with acquired resistance to the HER2-targeted therapies trastuzumab and lapatinib.

The PI3K pathway is a key mechanism of trastuzumab resistance, but early attempts to indirectly target this pathway with mTOR inhibitors have had limited success. We present the results of a preclinical study of the selective alpha/delta isoform dominant PI3K inhibitor BAY 80-6946 tested alone and in combination with HER2-targeted therapies in HER2-positive cell lines, including models with acquired resistance to trastuzumab and/or lapatinib. A panel of HER2-positive breast cancer cells were profiled for their mutational status using Sequenom MassARRAY, PTEN status by Western blot, and anti-proliferative response to BAY 80-6946 alone and in combination with the HER2-targeted therapies trastuzumab, lapatinib and afatinib. Reverse phase protein array was used to determine the effect of BAY 80-6946 on expression and phosphorylation of 68 proteins including members of the PI3K and MAPK pathways. The Boyden chamber method was used to determine if BAY 80-6946 affected cellular invasion and migration. BAY 80-6946 has anti-proliferative and anti-invasive effects when used alone in our panel of cell lines (IC50s 3.9-29.4 nM). BAY 80-6946 inhibited PI3K signalling and was effective in cells regardless of their PI3K, P53 or PTEN status. The combination of HER2-targeted therapies and BAY 80-6946 inhibited growth more effectively than either therapy used alone (with clear synergism in many cases), and can restore sensitivity to trastuzumab and lapatinib in cells with acquired resistance to either trastuzumab and/or lapatinib. The addition of BAY 80-6946 to HER2-targeted therapy could represent an improved treatment strategy for patients with refractory metastatic HER2-positive breast cancer, and should be considered for clinical trial evaluation.

Calcium phosphate particulates increase friction in the rat knee joint.

OBJECTIVE: Basic calcium phosphate (BCP) particulates are commonly found in cartilage and synovial fluid of osteoarthritis (OA) joints with the amount of BCP correlating with knee OA severity. How cartilage mineralization affects joint degeneration has yet to be determined. The objective of this study was to determine whether BCP in the synovial fluid affects the rat knee joint coefficient of friction (COF). METHODS: The COFs of knees from both hind limbs of four mature male rats were measured post mortem using a pendulum apparatus with an infrared tracking system. The three conditions evaluated were (1) the naïve state, (2) after the injection of 100 µL of phosphate buffered saline (PBS) (sham) and (3) after the injection of 100 µL of a 1 mg/mL BCP suspension. The decrease in the pendulum amplitude (decay) was fit using two friction models: (1) a one parameter Stanton linear decay model and (2) a two parameters combination Stanton linear decay and viscous damping exponential decay model. RESULTS: The COF increased 17.6% after injection of BCP compared to the naïve (P = 0.0012) and 16.0% compared to the saline injected (P = 0.0018) joints as derived from the one parameter model. The COF did not differ between naïve and saline injected joints. Results from the two parameters model showed a similar increase in COF after injection of BCP while the viscous damping was not significantly different between conditions. CONCLUSIONS: The increased joint friction with BCP particulates suggests BCPs may play a role in articular surface degradation and OA development.

Effects of dietary combination of n-3 and n-9 fatty acids on the deposition of linoleic and arachidonic acid in broiler chicken meats.

To minimize the amount of n-6 fatty acids in broiler chicken meat, 120 Cobb × Ross male broilers were divided into 6 different groups and fed a basal corn-soybean meal diet containing 5% fat from 5 different lipid sources: 1) a commercial mix of animal and vegetable oil, 2) soybean oil and olive oil (2.5% each), 3) flaxseed oil and olive oil (2.5% each), 4) flaxseed oil, eicosapentaenoic acid (C20:5; EPA; n-3), and olive oil (2.45, 0.05, and 2.5% respectively; FEO), 5) flaxseed oil, docosahexaenoic acid (C22:6; DHA; n-3), and olive oil (2.45, 0.05, and 2.5% respectively; FDO), and 6) fish oil and olive oil (2.5% each; FHO). At 6 and 9 wk, one bird per pen (4 pens per treatment) was processed, and liver, breast, and thigh samples were collected and used for fatty acid profiles or Δ6- and Δ9-desaturase mRNA gene expression levels. The deposition of linoleic acid (C18:2; n-6) or arachidonic acid (C20:4; n-6) was decreased in breast and thigh muscles of chickens fed n-3 fatty acids for 9 wk compared with chickens fed animal and vegetable oil and soybean oil and olive oil diets (P < 0.05). The addition of EPA to the diet (FEO; P > 0.05) did not reduce the deposition of linoleic acid and arachidonic acid as much as DHA (FDO; P < 0.05), and it suppressed the expression of Δ6- and Δ9-desaturase. When EPA and DHA were blended (FHO) and supplied to broiler chickens for 9 wk, EPA and DHA combination effects were observed on the deposition of LA and arachidonic acid in breast and thigh muscles. Thereby, the addition of a mixed EPA and DHA to a broiler chicken diet may be recommendable to reduce arachidonic acid accumulation in both broiler chicken breast and thigh meats, providing a functional broiler chicken meat to consumers.

The identification and mapping of candidate genes and QTL involved in the fatty acid desaturation pathway in Brassica napus.

We constructed a linkage map for the population QDH, which was derived from a cross between an oilseed rape cultivar and a resynthesised Brassica napus. The linkage map included ten markers linked to loci orthologous to those encoding fatty acid biosynthesis genes in Arabidopsis thaliana. The QDH population contains a high level of allelic variation, particularly in the C genome. We conducted quantitative trait locus (QTL) analyses, using field data obtained over 3 years, for the fatty acid composition of seed oil. The population segregates for the two major loci controlling erucic acid content, on linkage groups A8 and C3, which quantitatively affect the content of other fatty acids and is a problem generally encountered when crossing "wild" germplasm with cultivated "double low" oilseed rape cultivars. We assessed three methods for QTL analysis, interval mapping, multiple QTL mapping and single marker regression analysis of the subset of lines with low erucic acid. We found the third of these methods to be most appropriate for our main purpose, which was the study of the genetic control of the desaturation of 18-carbon fatty acids. This method enabled us to decouple the effect of the segregation of the erucic acid-controlling loci and identify 34 QTL for fatty acid content of seed oil, 14 in the A genome and 20 in the C genome. The QTL indicate the presence of 13 loci with novel alleles inherited from the progenitors of the resynthesised B. napus that might be useful for modulating the content or extent of desaturation of polyunsaturated fatty acids, only one of which coincides with the anticipated position of a candidate gene, an orthologue of FAD2.

Amino acid derivatives from Lucilia sericata excretions/secretions may contribute to the beneficial effects of maggot therapy via increased angiogenesis.

BACKGROUND: Maggot therapy, utilizing the larvae of Lucilia sericata, has been reported to reduce the bacterial load within wounds and also to enhance wound healing. Maggot excretions/secretions (ES) have been shown to have a role in the success of maggot therapy. While the protein content of ES has been investigated, to date little research has focused on the small metabolites present in ES and their potential contribution to the therapy. Study of the molecular composition of the secretions and the potential bioactivities present will allow for a more detailed evaluation of the efficacy of maggot therapy. OBJECTIVES: We studied the amino acid-like compounds present in ES of L. sericata larvae in order to determine the compounds present and their potential role in the wound healing process. METHODS: These included thin-layer chromatography/mass spectrometric analysis of ES to identify amino acid-like components, a turbidometric assay to investigate their potential antibacterial activity and cell proliferation studies to investigate their potential mitogenic ability. RESULTS: Three prominent compounds were detected and identified as histidine, valinol and 3-guanidinopropionic acid. While these amino acids were not shown to exhibit antibacterial activity, a proliferative effect on the growth of human endothelial cells, but not fibroblasts, was noted. CONCLUSIONS: The demonstrated proliferative effect, selectively on endothelial cells, suggests that the amino acid-like compounds present in maggot ES may have a role in wound healing, by stimulating angiogenesis.

A comparative linkage map of oilseed rape and its use for QTL analysis of seed oil and erucic acid content.

We have developed a new DH mapping population for oilseed rape, named TNDH, using genetically and phenotypically diverse parental lines. We used the population in the construction of a high stringency genetic linkage map, consisting of 277 loci, for use in quantitative genetic analysis. A proportion of the markers had been used previously in the construction of linkage maps for Brassica species, thus permitting the alignment of maps. The map includes 68 newly developed Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of A. thaliana. The use of these markers permits the alignment of our linkage map with the A. thaliana genome sequence. An additional 74 loci (31 newly developed STS markers and 43 loci defined by SSR and RFLP markers that had previously been used in published linkage maps) were added to the map. These markers increased the resolution of alignment of the newly constructed linkage map with existing Brassica linkage maps and the A. thaliana genome sequence. We conducted field trials with the TNDH population at two sites, and over 2 years, and identified reproducible QTL for seed oil content and erucic acid content. The results provide new insights into the genetic control of seed oil and erucic acid content in oilseed rape, and demonstrate the utility of the linkage map and population.

Maintenance of body temperature in the neonatal lamb: effects of breed, birth weight, and litter size.

To survive, the newborn lamb must be able to maintain body temperature and to stand and move to the udder to suck colostrum to fuel heat production. The objective of this study was to investigate whether neonatal lambs showing slow behavioral progress to standing and sucking also have an impaired ability to maintain body temperature. The time taken to stand and suck after birth, rectal temperatures, and blood samples were collected from 115 newborn single, twin, and triplet lambs of 2 breeds, Scottish Blackface and Suffolk, which are known to show variations in their neonatal behavioral progress. Blood samples were assayed for thyroid hormones, known to be involved in heat production, and cortisol, which plays a role in tissue maturation before birth. In addition, colostrum samples were collected from the 56 ewes that gave birth to the lambs, and assayed for protein, fat, and vitamin contents. Heavy lambs (more than 1 SD above the breed mean), Blackface lambs, and singleton or twin lambs were quicker to stand and suck from their mothers than lightweight (more than 1 SD below the breed mean), Suffolk, or triplet lambs. Low birth weight lambs also had lower rectal temperatures than heavier lambs (P < 0.01), as did Suffolk compared with Blackface lambs (P < 0.001). Lambs that were slow to suck after birth had lower rectal temperatures than quick lambs, and this difference persisted for at least 3 d after birth. Within breed, heavy lambs had greater plasma triiodothyronine and thyroxine immediately after birth than light lambs. Blackface lambs had greater plasma triiodothyronine and thyroxine than Suffolk lambs but tended to have less cortisol. Colostrum produced by Blackface ewes had a greater fat content than that of Suffolk ewes (P < 0.001). Thus, lambs that are behaviorally slow at birth are also less able to maintain their body temperature after birth. Although part of their lower body temperature might be attributable to behavioral influences on thermoregulation, the data also suggest that physiological differences exist between these animals. These differences may be related to different degrees of maturity at birth.

Study of five cell salvage machines in coronary artery surgery.

We evaluated the effectiveness, ease of use and safety of five machines for blood salvage during coronary artery surgery. All were equally effective in concentrating red cells. We measured haemoglobin, packed cell volume, free haemoglobin, white cells, neutrophil elastase, platelets, thrombin-antithrombin complex (TAT), prothrombin activation peptide F1.2, fibrin degradation product (d-dimers), tissue plasminogen activator (tPA) and heparin in wound blood, in washed cell suspensions and in a unit of bank blood prepared for each patient. All machines were equally safe and easy to use and were equally effective in removing heparin and the physiological components measured. There were no adverse effects on patients. Clotting factors are severely depleted both in salvaged blood, even before washing, and in bank blood. Cell savers are a valuable adjunct to coronary artery surgery, but careful monitoring of coagulation is required when the volumes of either bank blood or salvaged blood are large.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Evaluation of a novel vitamin E coated cellulosic membrane hollow fiber dialyzer.

Adverse physiologic effects accompany hemodialysis. Biocompatible dialyzer membranes may both limit oxidative stress and decrease beta2-microglobulin production, thereby reducing patient morbidity. We compared standard solute clearance, lipid, and antioxidant effects of a novel cellulosic membrane dialyzer modified with covalently bonded vitamin E (Excebrane Clirans E15, Terumo Australia) with standard cellulosic and polysulphone membrane dialyzers. Stable adult hemodialysis patients taking no lipid lowering or antioxidant therapy (n = 17; 9 male, 8 female) were recruited into a 10 week, prospective, unblinded study. Measurements were made at baseline on their usual dialyzer and after 2, 4, and 10 weeks of Excebrane use. Excebrane demonstrated good in vivo clearance of standard solutes relative to surface area. Predialysis beta2-microglobulin levels were unchanged with time and were significantly lower postdialysis than with cellulose acetate (p < 0.05). Oxidized low density lipoprotein levels as measured by nitrotyrosine residues were high predialysis, but tended to decrease with both membranes (p > 0.05). Total antioxidant status fell during dialysis (p < 0.0005), but plasma vitamin A and E concentrations increased (p = 0.007 and p = 0.02, respectively). Baseline vitamin A levels were high in all patients and, along with vitamin E, total antioxidant status and lipid profiles did not change over time with Excebrane use. Excebrane is an efficient, biocompatible membrane with no deleterious effects on beta2-microglobulin or lipids. More long-term study is merited.

L-arginine and substance P reverse the pulmonary endothelial dysfunction caused by congenital heart surgery.

BACKGROUND: The increase in pulmonary vascular resistance (PVR) seen in children after cardiopulmonary bypass has been attributed to transient pulmonary endothelial dysfunction (PED). We therefore examined PED in children with congenital heart disease by assessing the L-arginine-nitric oxide (NO) pathway in terms of substrate supplementation (L-arginine [L-Arg]), stimulation of endogenous NO release (substance P [Sub-P]), and end-product provision (inhaled NO) before and after open heart surgery. METHODS AND RESULTS: Ten patients (aged 0.62+/-0.27 years) with pulmonary hypertension undergoing cardiac catheterization who had not had surgery and 10 patients (aged 0.65+/-0.73 years) who had recently undergone cardiopulmonary bypass were examined. All were sedated and paralyzed and received positive-pressure ventilation. Blood samples and pressure measurements were taken from catheters in the pulmonary artery and the pulmonary vein or left atrium. Respiratory mass spectrometry was used to measure oxygen uptake, and cardiac output was determined by the direct Fick method. PVR was calculated during steady state at ventilation with room air, during FIO(2) of 0.65, then during additional intravenous infusion of L-Arg (15 mg. kg(-1). min(-1)) and Sub-P (1 pmol. kg(-1). min(-1)), and finally during inhalation of NO (20 ppm). In preoperative patients, the lack of an additional significant change of PVR with L-Arg, Sub-P, and inhaled NO suggests little preexisting PED. Postoperative PVR was higher, with an additional pulmonary endothelial contribution that was restorable with L-Arg and Sub-P. CONCLUSIONS: Postoperatively, the rise in PVR suggested PED, which was restorable by L-Arg and Sub-P, with no additional effect of inhaled NO. These results may indicate important new treatment strategies for these patients.

Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder.

BACKGROUND: The hypothesis that exaggerated startle in Vietnam veterans with posttraumatic stress disorder (PTSD) reflects an anxiogenic response to stressful contexts was tested. METHODS: Thirty-four nonmedicated Vietnam veterans with PTSD, and 17 combat and 14 civilian non-PTSD controls participated in two testing sessions over separate days. Acoustic startle stimuli were delivered alone or in a test of prepulse inhibition. In the first session, startle was assessed without experimental stress. In the second session, startle was investigated during a stressful "threat of shock" experiment, when subjects anticipated the administration of shocks during threat periods and during safe periods when no shocks were anticipated. RESULTS: The magnitude of startle did not differ significantly among the three groups in the first session, but was increased throughout the threat of shock experiment in the PTSD veterans in the second session. The actual increase in startle in the threat compared to the safe condition did not significantly differ among the three groups. Prepulse inhibition was reduced in the PTSD veterans, compared to the non-PTSD civilians, but not compared to the non-PTSD veterans. CONCLUSION: Exaggerated startle in Vietnam veterans with PTSD reflects an anxiogenic response to an environment that is experienced as stressful.

Effect of darkness on acoustic startle in Vietnam veterans with PTSD.

OBJECTIVE: Exaggerated startle is a symptom of posttraumatic stress disorder (PTSD), but empirical studies have not consistently documented elevated baseline startle in PTSD. The authors proposed in a previous study that Vietnam veterans with PTSD exhibit exaggerated startle only under stressful conditions. They reported that darkness facilitated startle in humans, suggesting that the startle reflex is sensitive to the aversive nature of darkness. In the present study they tested the hypothesis that the magnitude of facilitation of startle by darkness would be greater in Vietnam veterans with PTSD than in comparison groups of subjects without PTSD. Prepulse inhibition was also investigated. METHOD: The magnitude of startle and prepulse inhibition were assessed in alternating periods of darkness and light in 19 nonmedicated Vietnam veterans with PTSD, 13 Vietnam veterans without PTSD, and 20 civilians without PTSD. RESULTS: The overall startle level was higher in the veterans with PTSD than in either of the two groups of subjects without PTSD. Startle was facilitated by darkness, and the magnitude of this facilitation was greater in the veterans with PTSD than in the civilians without PTSD, but it was not greater in the veterans without PTSD. Prepulse inhibition was not affected by darkness and did not significantly differ among groups. CONCLUSIONS: Contrary to the hypothesis, elevated sensitivity to darkness was specific to individuals with combat experience, not to individuals with PTSD, perhaps because veterans had become aversively conditioned to darkness during their combat experiences. The more general increase in startle reactivity in the veterans with PTSD is consistent with clinical observations and descriptions of symptoms in DSM-IV.