Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

[What motivates patients with atopic diseases to search the internet-a focus group study on expectations and demands]. / Was motiviert Patienten mit atopischen Erkrankungen zur Suche nach Informationen im Internet? Ergebnisse einer Fokusgruppenstudie zu Erwartungen und Anforderungen.

BACKGROUND: People affected by allergies with mild-to-moderate symptoms are often not treated adequately, despite the availability of prevention and self-therapy measures. Given their good and quick accessibility when seeking information, evidence- and web-based services that are user-friendly may strengthen a more independent way of handling an allergy and may also increase health literacy. In order for such services to be found and read, developers and providers need to know about information needs, demands and users' behavior. OBJECTIVES: On which occasions does the target group search for allergy-specific information? Which preferences and demands do affected persons have regarding a web-based service? MATERIALS AND METHODS: Three individual interviews and four focus groups with 37 participants (19-81 years; hay fever, n = 30; asthma, n = 17; eczema, n = 15) were conducted in four German cities. These were recorded and transcribed verbatim. A multiprofessional team developed a system for coding the texts (two independent encoders, MAXQDA analysis software). RESULTS: Those who are affected usually seek information only in case of a concrete need for action. Impulses are, among others, symptoms, suggestions from the social environment, the beginning of the allergy season or an allergy-related contact with the health system. A web-based service should primarily include information about treatment options, provide individualized support for everyday life action strategies, and promote adequate self-management skills. DISCUSSION: In order to promote self-management skills, a web-based service should focus on allergy symptoms, treatment options and day-to-day help.

Concomitant inhalation of cigarette smoke and aerosolized protein activates airway dendritic cells and induces allergic airway inflammation in a TLR-independent way.

Cigarette smoking is associated with the development of allergic asthma. In mice, exposure to cigarette smoke sensitizes the airways toward coinhaled OVA, leading to OVA-specific allergic inflammation. Pulmonary dendritic cells (DCs) are professional APCs involved in immunosurveillance and implicated in the induction of allergic responses in lung. We investigated the effects of smoking on some of the key features of pulmonary DC biology, including trafficking dynamics and cellular activation status in different lung compartments. We found that cigarette smoke inhalation greatly amplified DC-mediated transport of inhaled Ags to mediastinal lymph nodes, a finding supported by the up-regulation of CCR7 on airway DCs. Pulmonary plasmacytoid DCs, which have been involved in inhalational tolerance, were reduced in number after smoke exposure. In addition, combined exposure to cigarette smoke and OVA aerosol increased surface expression of MHC class II, CD86, and PDL2 on airway DCs, while ICOSL was strongly down-regulated. Although inhaled endotoxins, which are also present in cigarette smoke, have been shown to act as DC activators and Th2-skewing sensitizers, TLR4-deficient and MyD88 knockout mice did not show impaired eosinophilic airway inflammation after concomitant exposure to cigarette smoke and OVA. From these data, we conclude that cigarette smoke activates the pulmonary DC network in a pattern that favors allergic airway sensitization toward coinhaled inert protein. The TLR independency of this phenomenon suggests that alternative immunological adjuvants are present in cigarette smoke.

Navigating the health care system: perceptions of patients with chronic pain.

A new framework is needed for patients with chronic pain and their primary care physicians that acknowledges the individual's experiences and provides evidence-informed education and better linkages to community-based resources. This study describes the experience of 19 chronic-pain sufferers who seek relief via the health care system. Their experiences were recorded through in-depth semistructured interviews and analyzed through qualitative methods. The participants reported early optimism, then disillusionment, and finally acceptance of living with chronic pain. Both individuals with chronic pain and their health care professionals need evidence-informed resources and information on best practices to assist them to manage pain. Empathetic communication between health care professionals and individuals with chronic pain is crucial because insensitive communication negatively affects the individual, reduces treatment compliance and increases health care utilization.

Cigarette smoke exposure facilitates allergic sensitization in mice.

BACKGROUND: Active and passive smoking are considered as risk factors for asthma development. The mechanisms involved are currently unexplained. OBJECTIVE: The aim of this study was to determine if cigarette smoke exposure could facilitate primary allergic sensitization. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) combined with air or tobacco smoke (4 exposures/day) daily for three weeks. Serology, lung cytopathology, cytokine profiles in bronchoalveolar lavage fluid (BALF) and on mediastinal lymph node cultures as well as lung function tests were performed after the last exposure. The natural history and the immune memory of allergic sensitization were studied with in vivo recall experiments. RESULTS: Exposure to OVA induced a small increase in OVA-specific serum IgE as compared with exposure to PBS (P < 0.05), while no inflammatory reaction was observed in the airways. Exposure to cigarette smoke did not induce IgE, but was characterized by a small but significant neutrophilic inflammatory reaction. Combining OVA with cigarette smoke not only induced a significant increase in OVA-specific IgE but also a distinct eosinophil and goblet cell enriched airway inflammation albeit that airway hyperresponsiveness was not evidenced. FACS analysis showed in these mice increases in dendritic cells (DC) and CD4+ T-lymphocytes along with a marked increase in IL-5 measured in the supernatant of lymph node cell cultures. Immune memory experiments evidenced the transient nature of these phenomena. CONCLUSION: In this study we show that mainstream cigarette smoke temporary disrupts the normal lung homeostatic tolerance to innocuous inhaled allergens, thereby inducing primary allergic sensitization. This is characterized not only by the development of persistent IgE, but also by the emergence of an eosinophil rich pulmonary inflammatory reaction.

EMLA and amethocaine for reduction of children's pain associated with needle insertion.

BACKGROUND: Children often experience pain from needle insertion procedures; therefore, several topical anaesthetics have been developed. OBJECTIVES: To compare the topical anaesthetics amethocaine and an eutectic mixture of local anaesthetics (EMLA) in terms of anaesthetic efficacy, ease of needle insertion and adverse events when used for intravenous cannulation and venipuncture in children. SEARCH STRATEGY: An exhaustive search that included over 30 databases and handsearching reference lists and journals. Language restrictions were not imposed. SELECTION CRITERIA: Randomized controlled trials were selected that compared EMLA and amethocaine for relieving children's pain from intravenous cannulation or venipuncture. DATA COLLECTION AND ANALYSIS: Two review authors independently determined eligibility for inclusion by assessing trial quality. Details of eligible studies were summarized. One author was contacted for additional information. Information about adverse events was obtained from the text of the trial reports. Review Manager 4.2 was used to perform a meta-analysis and compute relative risks (RR) with 95% confidence intervals. MAIN RESULTS: Six trials consisting of 534 children, three months to 15 years of age, were included in this review. A meta-analysis was done comparing amethocaine with EMLA on anaesthetic efficacy, ease of needle procedure and resultant skin changes. For anaesthetic efficacy, amethocaine significantly reduced the risk of pain compared to EMLA when all pain data were combined into a common pain metric (RR 0.78, 95% CI 0.62 to 0.98); when pain was self-reported by children (RR 0.63, 95% CI 0.45 to 0.87); or when pain was observed by researchers (sensitivity analysis: RR 0.71, 95% CI 0.52 to 0.96). Compared to EMLA, amethocaine significantly reduced the risk of pain when drugs were applied for the following durations: for 30 to 60 minutes (RR 0.61, 95% CI 0.41 to 0.91); when applied according to manufacturer's instructions (sensitivity analysis: RR 0.64, 95% CI 0.46 to 0.89); and when applied for over 60 minutes (RR 0.70, 95% CI 0.51 to 0.96). Amethocaine was also significantly more efficacious than EMLA when used specifically for intravenous cannulation (RR 0.70, 95% CI 0.55 to 0.88). Insufficient data were available to compare anaesthetic efficacy for venipuncture.A comparison of amethocaine and EMLA for ease of a needle procedure was not significant; only one trial reported data that could be included. For skin changes, EMLA was favoured in the analysis of erythema (RR 14.83, 95% CI 2.28 to 96.36). Erythema was observed after use of amethocaine whereas blanching was observed after using EMLA. Adverse effects included itching and one case of conjunctival irritation. AUTHORS' CONCLUSIONS: Although EMLA is an effective topical anaesthetic for children, amethocaine is superior in preventing pain associated with needle procedures.

Determinants of success and failure of EMLA.

Although EMLA is known to be an effective topical anesthetic, its rate of success is unknown. Indeed, researchers have suggested that EMLA may fail with young and apprehensive children. Therefore, the objectives of this study were to assess EMLA's rate of success as well as factors which predict success. A double-blind, placebo-controlled design was utilized. The sample included 258 children and adolescents aged 5-18 years who were having venipuncture or intravenous (i.v.) cannulation. After having their anxiety assessed, subjects were randomly assigned to have EMLA or placebo applied over the procedure site for 90 min. The visual analogue scale was used to assess pain caused by removal of the semi-permeable dressing and by the procedure. Other information that was collected included: duration of drug application, interval between drug removal and procedure, skin changes at bandage and drug sites and rated difficulty of the procedure. EMLA was successful 84% of the time for venipuncture and 51% of the time for i.v. cannulation. Factors which predicted success of EMLA included type of procedure, duration of drug application and anxiety. EMLA was less successful for i.v. cannulation compared to venipuncture even with duration of drug application controlled. Those who had a poor outcome were more anxious than those with a good outcome. Age of child was not a factor. Strategies for improving efficient use of EMLA were recommended.

Cognitive status and postoperative pain: older adults.

The purpose of this study was to assess older adults to determine (a) the course of postoperative pain, (b) influences of pain and analgesics on mental status, and (c) relationships among age, mental status and pain. Sixty adults, aged 50-80 yr, who had total hip replacement surgery were included in this study. All subjects had met a preoperative criterion for mental status. Data collection took place over 5 days following surgery. Pain intensity and distress were assessed three times a day for 5 days. Recalled night pain intensity, pain distress, and sleep disturbance from pain were assessed daily in the early morning prior to assessment of mental status. Although no within day or day-to-day pain patterns were observed, the greatest decreases in pain occurred during the first 2 days. Night pain also improved after the third day. One-third of subjects recorded one or more episodes where mental status declined below criterion after surgery. Multivariate analysis indicated that pain, not analgesic intake, predicted mental status decline. Age was not related to pain or mental status. In general, pain was poorly managed in this group of subjects. The results suggest an explanation for acute confusion in older patients after surgery and recommend improved pain management.

Children's coping with venipuncture.

Children's strategies for coping with the pain and distress of venipuncture were examined in this descriptive study. Eighty-five children (aged 5-13 years) were interviewed prior to and following blood collection. Prior to the procedure, children reported pain expectations and coping strategies that might be used. Self-reports of the pain experienced and coping strategies used were obtained immediately after the procedure. Twenty-seven different strategies were identified from the children's responses. These strategies were subsequently grouped into 11 coping categories: Active Involvement in Procedure, Behavior-Regulating Cognitions, Cognitive Reappraisal, Direct Efforts to Maintain Control, Diversionary Thinking, Emotion-Regulating Cognitions, Information Seeking, Reality-Oriented Working Through, Reliance on Health-Care Interventions, Support Seeking, and Avoidance and Catastrophizing. Direct Efforts to Maintain Control was the most frequently used category. Age and gender differences were observed in both number and type of strategies reported by the children. Further research is needed to examine the observed relationship between the type of coping strategies generated and the children's pain experience.

Assessing children's state anxiety.

Anxiety is an important component of children's pain and is routinely assessed in pain research. Two forms of the State-Trait Anxiety Inventory have been used frequently by researchers investigating children's pain and state anxiety (form C-1 and Y-1). We were unable to find psychometric information about this tool when used with a population of hospitalized children. Therefore, we undertook to assess reliability and validity, and identify problem items using data from 881 hospitalized children (aged 5-18 years) whom we had tested. Considering results of all analyses together, we concluded that the tools lack validity and reliability, and contain many problem items that are in need of revision.

Children's venipuncture pain: influence of technical factors.

Several aspects of venipuncture technique were evaluated to assess their relationship to reported pain. Subjects were 514 children aged 5-17 who had venipuncture performed by a technician in a hospital outpatient laboratory. A research assistant timed the duration of venipuncture and then obtained visual analogue pain scores from the children following venipuncture. Blood volume obtained from venipuncture was also measured. The technician who performed the procedure, amount of blood drawn, and time required to complete the venipuncture did not contribute to the prediction of children's pain. Age and anxiety, which were treated as covariates, were significant predictors of pain. The distribution of pain experienced by children was positively skewed and about one-third of children were above the mean pain score. From the results of this study, venipuncture pain can be recommended for the study of issues in children's pain. Further, the findings recommend the development and utilization of interventions to reduce children's venipuncture pain.

Biomechanics of the squat exercise using a modified center of mass bar.

The purpose of the study was to investigate the effects of load height on selected performance characteristics of a squat exercise. A lower center of mass bar was designed that allowed the integrity of the squat exercise to be maintained while possibly reducing the chances of injury. Five trials were performed with the center of mass of the bar was set at shoulder height (C1) and lowered 18% (C2) and 36% (C3) of the subject's height below the normal bar position using the inverted "U" bar. All trials were filmed as the subjects lifted on a force platform. A balloon catheter was inserted into the subject's recta to monitor intra-abdominal pressure (IAP). High correlations were found between IAP, joint moment, and force data. Many of the critical parameters occurred just after the lowest squat position. Significant differences (P less than 0.05) in trunk angle excursion and trunk angular velocity indicated a greater ease of hip extension for the center of mass bar conditions. No differences were observed between conditions for thigh and knee angles and joint moments indicating kinematic similarity for the lower extremity. IAP was always least for C2 and C3, while compression, shear, and back muscle forces did not differ. It was estimated that the greater IAP was responsible for relieving back muscle forces and compression by up to 15 and 21%, respectively, and increased stress with the weight at shoulder height stimulated a response for greater IAP to help alleviate the stresses on the spine.

Co-activation of sprinter and distance runner muscles in isokinetic exercise.

The purpose of this study was to investigate the extent of co-activation of quadriceps and hamstring musculature in sprinters and distance runners. Nine female intercollegiate track athletes performed maximal knee extensions and flexions on a modified orthotron isokinetic dynamometer at two speeds (100 degrees and 400 degrees X s-1). Simultaneous recordings of torque, joint position, and agonist/antagonist electromyographic activity from the quadriceps and hamstrings were computer-processed. The results revealed the hamstrings to be considerably more active during knee extension than the quadriceps during flexion. The integrated electromyographic activity of co-contracting hamstrings and quadriceps, throughout the joint range, averaged 33 and 6%, respectively, of the same muscle group during its agonist phase. Hamstring co-activation increased sharply during the last 25% of knee extension, generating 58% of the integrated electromyographic agonist activity. Co-activation of the sprinters' hamstrings was four times that of distance runners (57/14%), however, the faster speed of movement (400 degrees X s-1) increased hamstring coactivation of distance runners more acutely than sprinters in the final phase of extension. The data suggest that the hamstrings are used to a much greater extent than quadriceps for limb deceleration and that the distraction of antagonist muscle tension should be considered when analyzing agonist isokinetic torques. Furthermore, the relatively high co-activation of the hamstrings, particularly during the last 25% of extension, may induce hamstring soreness or strain in vulnerable subjects.

A comparison between free-weight and isokinetic bench pressing.

The purpose of the study was to evaluate selected parameters describing performance characteristics of a free-weight and isokinetic bench press. A secondary purpose was an attempt to clarify the technique requirements essential for a successful lift. Parameters describing the free-weight condition were generated from cinematographic data (150 fps) for five trials each at 90 and 75% of the subject's maximal performance (1RM). Isokinetic data were obtained from an instrumented Cybex Power Bench Press at two speeds corresponding to the average speeds for the free-weight conditions. Despite differences, accommodation appeared to occur for both methods when the lifts were performed maximally. A "sticking region" was defined as the portion of the free-weight activity when the subjects' force application was less than the weight of the bar. No significant difference (P less than 0.05) was observed between the 90% 1RM (26.02%) and 75% 1RM (26.94%) mean relative time values for these regions. For the Cybex device, the percentage of the activity which was isokinetic was longer for the slower speeds of rotation (0.47 rad X s-1 = 70%) and steadily decreased until the movement was only 50% isokinetic at 1.74 rad X s-1. The observed relationships between applied force-time data along with anatomical considerations suggest an ideal technique for the lift.

The effectiveness of weight-belts during the squat exercise.

The purpose of this study was to examine the effectiveness of weight-belts during the performance of the parallel squat exercise. Six subjects were filmed (40 fps) as they performed three trials at each of three belt conditions (NB, none; LB, light; HB, heavy) in random order and three load conditions (70, 80, 90% 1RM (one repetition maximum] in increasing order. The parameters examined were collected and interfaced to a computer via an analog-to-digital (A/D) converter: ground reaction forces, intra-abdominal pressure (IAP), and EMG for the rectus abdominus (RA), external oblique (EO), and erector spinae (ES) muscles. Most differences were observed during the 90% 1RM condition, and only they are presented in this paper. Maximum IAP values were always greater (P less than 0.05) for the weight-belt conditions (LB, 29.2; HB, 29.1 greater th an NB, 26,8 kPa). Similar results were observed for the mean IAP. The integrated EMG (iEMG) activity of the muscles and adjusted mean values for back compressive force and back muscle force followed a similar but opposite pattern, with NB being the greatest. ES mEMG/(L5/S1) values for HB (18.1%) were the least, followed by LB (20.01%) and NB (22.3%). Few differences were observed between belt types. These data suggest that a weight-belt can aid in supporting the trunk by increasing IAP.

The effectiveness of weight-belts during multiple repetitions of the squat exercise.

The purpose of this study was to examine the effectiveness of weight-belts during multiple repetitions of the parallel back squat exercise. Five subjects were filmed (50 fps) as they performed eight consecutive trials at each of two weight-belt conditions [with belt = WB, without belt = WOB] in random order at their eight-repetition maximum effort. Other parameters examined were ground reaction forces, intra-abdominal pressure (IAP), and mean electromyography (mEMG) for the external oblique (EO), erector spinae (ES), vastus lateralis (VL), and bicep femoris (BF) muscles. All parameters were collected and interfaced to a computer via an A/D converter. WB repetitions were generally performed faster than WOB repetitions, especially by the later repetitions (3.34 vs 3.56 s). WB IAP values were consistently greater (P less than 0.05) than WOB values by 25-40%. IAP increased by approximately 11.5% from the first to the last repetitions. No differences were observed for ES and EO mEMG for belt usage, but values increased by up to 20% across repetitions. Several differences were observed between WB and WOB for the VL and BF mEMG, with WB values being significantly greater. These data suggest that a weight-belt aids in supporting the trunk by increasing IAP, and that any differential effect due to wearing a weight-belt did not occur over eight repetitions.

Effects of technique variations on knee biomechanics during the squat and leg press.

PURPOSE: The specific aim of this project was to quantify knee forces and muscle activity while performing squat and leg press exercises with technique variations. METHODS: Ten experienced male lifters performed the squat, a high foot placement leg press (LPH), and a low foot placement leg press (LPL) employing a wide stance (WS), narrow stance (NS), and two foot angle positions (feet straight and feet turned out 30 degrees ). RESULTS: No differences were found in muscle activity or knee forces between foot angle variations. The squat generated greater quadriceps and hamstrings activity than the LPH and LPL, the WS-LPH generated greater hamstrings activity than the NS-LPH, whereas the NS squat produced greater gastrocnemius activity than the WS squat. No ACL forces were produced for any exercise variation. Tibiofemoral (TF) compressive forces, PCL tensile forces, and patellofemoral (PF) compressive forces were generally greater in the squat than the LPH and LPL, and there were no differences in knee forces between the LPH and LPL. For all exercises, the WS generated greater PCL tensile forces than the NS, the NS produced greater TF and PF compressive forces than the WS during the LPH and LPL, whereas the WS generated greater TF and PF compressive forces than the NS during the squat. For all exercises, muscle activity and knee forces were generally greater in the knee extending phase than the knee flexing phase. CONCLUSIONS: The greater muscle activity and knee forces in the squat compared with the LPL and LPH implies the squat may be more effective in muscle development but should be used cautiously in those with PCL and PF disorders, especially at greater knee flexion angles. Because all forces increased with knee flexion, training within the functional 0-50 degrees range may be efficacious for those whose goal is to minimize knee forces. The lack of ACL forces implies that all exercises may be effective during ACL rehabilitation.

Children's pain predictions and memories.

A cross-sectional descriptive design was utilized to explore expected, experienced and recalled pain, and anxiety. Subjects were 138 children (5-17 yr) who were attending an outpatient laboratory for venipuncture. They reported state anxiety and expected visual analogue scale pain prior to having venipuncture. Following venipuncture, they reported sensory and affective pain. Two months afterward, subjects were contacted and asked to recall sensory and affective pain from the venipuncture. Analysis of data determined that children's recall of pain was quite good although better for affective pain than sensory pain. Prediction accuracy for pain was not good. From analysis it was determined that overestimation of pain was related to anxiety but not to greater experienced pain. Four patterns of responses were identified when prediction and recall accuracy were further examined. These patterns were designated as realism, irrelevance, over-reaction and denial. It was suggested that these patterns of response may provide clues about avoidance and coping behavior for children's pain. In general, the results of this study did not support previous research. It was demonstrated that various statistical techniques which have been employed in research on this topic have influenced the interpretation of pain prediction and recall data.