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Biomedical subjects

D Scheidegger

Publications and source records attributed to D Scheidegger.

At least 19 recordsLinked to original sources

Migration and function of antigen-primed nonpolarized T lymphocytes in vivo.

Upon antigenic stimulation, naive T lymphocytes proliferate and a fraction of the activated cells acquire a T helper cell type 1 (Th1) or Th2 phenotype as well as the capacity to migrate to inflamed tissues. However, the antigen-primed T cells that receive a short T cell receptor (TCR) stimulation do not acquire effector function and remain in a nonpolarized state. Using TCR transgenic CD4(+) T cells in an adoptive transfer system, we compared the in vivo migratory capacities of naive, nonpolarized, Th1 or Th2 cells. Although all cell types migrated to the spleen, only naive and nonpolarized T cells efficiently migrated to lymph nodes. In addition Th1, but not Th2, migrated to inflamed tissues. In the lymph nodes, nonpolarized T cells proliferated and acquired effector function in response to antigenic stimulation, displaying lower activation threshold and faster kinetics compared with naive T cells. These results suggest that nonpolarized T cells are in an intermediate state of differentiation characterized by lymph node homing capacity and increased responsiveness that allows them to mount a prompt and effective secondary response.

Animals↗

Team performance in the emergency room: assessment of inter-disciplinary attitudes.

In-hospital emergency medicine in central Europe relies on inter-disciplinary co-operation. To improve team performance in the emergency room (ER), a questionnaire for assessment of attitudes and judgements in resuscitation procedures was developed. A total of 43 items were evaluated according to a five-point Likert scale. With a response rate of 81%, 143 questionnaires were evaluated. Assessment of data was performed with regard to professional speciality and level in the medical hierarchy. Factorial analysis identified four main factors: Assessment of 'quality of performance' (F1), 'importance of structure' (F2), 'quality of team culture' (F3), and 'importance of hierarchy' (F4). Influences from the categories 'speciality' and 'hierarchy' and from the covariate 'gender' on these main factors were evaluated by two-factorial analysis of variance. For all four factors, 'speciality' produced significant differences. Surgeons accorded high values to F1 and low values to F2, whereas anaesthesiologists accorded low values to F1 and high values to F2. F3 showed a low ranking from within the ER nursing staff and the residents in internal medicine, whereas F4 received high scores by medical residents and staff members. For F1 and F3, there was a tendency towards hierarchy dependency, whereas no factor was influenced by gender. In conclusion, team performance in the ER is mainly influenced by different perceptions and attitudes of the different disciplines involved in the resuscitation process.

Analysis of Variance↗

The visual analog scale allows effective measurement of preoperative anxiety and detection of patients' anesthetic concerns.

UNLABELLED: The advent of managed care, reduction of costs, and advances in medical technology place increasing demands on anesthesiologists. Preoperative anxiety may go unnoticed in an environment that stresses increased productivity. The present study compares different methods for measuring preoperative anxiety, identifies certain patient characteristics that predispose to high anxiety, and describes the quantity and quality of anxiety that patients experience preoperatively. Seven hundred thirty-four patients participated in the study. We assessed aspects of anxiety by means of visual analog scales (VAS) and the State Anxiety Score of the Spielberger State-Trait Anxiety Inventory (STAI). The mean STAI anxiety score was 39 +/- 1 (n = 486) and the mean VAS for fear of anesthesia was 29 +/- 1 (n = 539). Patients feared surgery significantly more than anesthesia (P < 0.001). The VAS measuring fear of anesthesia correlated well with the STAI score (r = 0.55; P < 0.01). Young patients, female patients, and patients with no previous anesthetic experience or a previous negative anesthetic experience had higher anxiety scores. Patients worried most about the waiting period preceding surgery and were least concerned about possible awareness intraoperatively. Factor analysis of various anxiety items showed three distinct dimensions of fear: 1) the fear of the unknown 2) the fear of feeling ill, and 3) the fear for one's life. Among these dimensions, fear of the unknown correlated highest with the anxiety measuring techniques STAI and VAS. The simple VAS proved to be a useful and valid measure of preoperative anxiety. IMPLICATIONS: The study of qualitative aspects of anxiety reveals three distinct dimensions of preoperative fear: fear of the unknown, fear of feeling ill, and fear for one's life. Groups of patients with a higher degree of preoperative anxiety and their specific anesthetic concerns can be identified using the visual analog scale.

Adult↗

The interplay between the duration of TCR and cytokine signaling determines T cell polarization.

Development of Th1 and Th2 effector lymphocytes is driven primarily by IL-12 or IL-4, but is also influenced by the strength of antigenic stimulation. However, the mechanism by which TCR signaling contributes to T cell polarization remains elusive. We show that in the presence of IL-12 a short TCR stimulation can lead to efficient Th1 polarization and IL-12 exerts its effect when present during, as well as after, TCR signaling. In contrast, Th2 polarization requires a prolonged TCR stimulation and IL-4 is effective only when present during the period of TCR triggering. The simultaneous stimulation by TCR and IL-4 is required to induce demethylation of IL-4 and IL-13 genes that accompanies the stochastic generation of Th2 cells producing either or both cytokines. Thus, the duration of TCR stimulation represents a crucial parameter that influences the response to polarizing cytokines and the acquisition of T cell effector functions.

Animals↗

Gastric intramucosal pH-guided therapy in patients after elective repair of infrarenal abdominal aneurysms: is it beneficial?

OBJECTIVE: To determine if gastric intramucosal pH (pHi)-guided therapy reduces the number of complications and length of stay in the intensive care unit (ICU) or the hospital after elective repair of infrarenal abdominal aortic aneurysms. DESIGN: Prospective, randomized study. SETTING: Surgical intensive care unit (SICU) of a University Hospital. PATIENTS: Fifty-five consecutive patients randomized to group 1 (pHi-guided therapy) or to group 2 (control). INTERVENTIONS: Patients of group 1 with a pHi of lower than 7.32 were treated by means of a prospective protocol in order to increase their pHi to 7.32 or more. MEASUREMENTS AND RESULTS: pHi was determined in both groups on admission to the SICU and thereafter at 6-h intervals. In group 2, the treating physicians were blinded for the pHi values. Complications, APACHE II scores, duration of endotracheal intubation, fluid and vasoactive drug treatment, treatment with vasoactive drugs, length of stay in the SICU and in the hospital and hospital mortality were recorded. There were no differences between groups in terms of the incidence of complications. We found no differences in APACHE II scores on admission, the duration of intubation, SICU or hospital stay, or hospital mortality. In the two groups the incidence of pHi values lower than 7.32 on admission to the SICU was comparable (41% and 42% in groups 1 and 2, respectively). Patients with pHi lower than 7.32 had more major complications during SICU stay (p < 0.05), and periods more than 10 h of persistently low pHi values (< 7.32) were associated with a higher incidence of SICU complications (p < 0.01). CONCLUSIONS: Low pHi values (< 7.32) and their persistence are predictors of major complications. Treatment to elevate low pHi values does not improve postoperative outcome. Based on these data, we cannot recommend the routine use of gastric tonometers for pHi-guided therapy in these patients. Further studies are warranted to determine adequate treatment of low pHi values that results in beneficial effects on the patient's postoperative course and outcome.

APACHE↗

[Perioperative gastrointestinal ischemia in abdominal aortic aneurysm operations].

QUESTIONS UNDER STUDY: Surgery of abdominal aortic aneurysms involves a high risk of postoperative complications. It has been suggested that the incidence of postoperative complications is related to the development of gastrointestinal acidotic episodes of the mucosa. The goal of this study was, therefore, to determine the incidence of gastrointestinal acidotic episodes during repair of abdominal aortic aneurysms, and to test the hypothesis that these episodes predict an adverse postoperative course. METHODS: In 49 consecutive patients undergoing elective surgery for repair of an abdominal aneurysm, intramucosal gastric pH (pHi) was measured perioperatively. The length of the surgical procedure, perioperative intravenous fluid intake, use of vasoactive drugs, APACHE-II scores, days with an endotracheal tube in place, days of intensive care and major postoperative complications were prospectively assessed. The patients were assigned to either a group with a pHi > or = 7.35 or a group with pHi < 7.35 measured towards the end of the surgical procedure, and then compared. RESULTS: The pHi decreased from 7.42 +/- 0.09 after induction of anesthesia to 7.37 +/- 0.07 (p < 0.05) during clamping of the aorta, and continued to decrease to 7.34 +/- 0.08 (p < 0.001) towards the end of surgery and on admission to the surgical intensive care unit (mean +/- standard deviation). The percentage of patients with pHi < 7.35 increased from 10% at the beginning of the operation to 55% on admission to the intensive care unit (p < 0.0001). There was no difference in the postoperative course between patients with pHi > or = 7.35 and those with pHi < 7.35 measured after declamping of the aorta. Patients who had a major complication during their stay in the intensive care unit had lower perioperative pHi values than patients without complications (p < 0.001). CONCLUSIONS: Perioperative gastrointestinal acidotic episodes of the mucosa are common during repair of abdominal aortic aneurysms. The perioperative course, however, is not influenced by these acidotic episodes, despite the fact that patients with complications during their stay in the intensive care unit had lower perioperative pHi values. The routine use of pHi measurements during elective surgery of abdominal aortic aneurysms, therefore, is not justified.

Acid-Base Equilibrium↗

Mannose receptor-mediated uptake of antigens strongly enhances HLA class II-restricted antigen presentation by cultured dendritic cells.

Dendritic cells (DC) efficiently take up antigens by macropinocytosis and mannose receptor-mediated endocytosis. Here we show that endocytosis of mannose receptor-antigen complexes takes place via small coated vesicles, while non-mannosylated antigens were mainly present in larger vesicles. Shortly after internalization the mannose receptor and its ligand appeared in the larger vesicles. Within 10 min, the mannosylated and non-mannosylated antigens co-localized with typical markers for major histocompatibility complex class II-enriched compartments and lysosomes. In contrast, the mannose receptor appeared not to reach these compartments, suggesting that it releases its ligand in an earlier endosomal structure. Moreover, we demonstrate that mannosylation of protein antigen and peptides resulted in a 200-10,000-fold enhanced potency to stimulate HLA class II-restricted peptide-specific T cell clones compared to non-mannosylated peptides. Our results indicate that mannosylation of antigen leads to selective targeting and subsequent superior presentation by DC which may be applicable in vaccine design.

Amino Acid Sequence↗

Effect of different drugs on end-tidal carbon dioxide during rodent CPR.

The purpose of this study was to investigate the effect of non-adrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2 (ETCO2) during CPR in a rodent model. Our results suggested that: 1) coronary perfusion pressure (CPP) after drugs infusion was increased significantly by methoxamine, arginine vasopresin (AVP) and angiotension-II (ANG-II), but not by endothelin-1 (ET-1); 2) ETCO2 prior to defibrillation was decreased significantly by a pure alpha 1 adrenergic agents, methoxamine and were increased significantly by non-adrenergic agents, ANG-II and ET-1 during rodent CPR; 3) a significant positive correlation between ETCO2 and CPP was observed in AVP group, suggesting that AVP have little effect on pulmonary circulation; and 4) methoxamine, AVP and ANG-II have similar effect on resuscitability during rodent CPR.

Adrenergic alpha-Agonists↗

Occlusive mesenteric ischemia and its effects on jejunal intramucosal pH, mesenteric oxygen consumption and oxygen tensions from surfaces of the jejunum in anesthetized pigs.

OBJECTIVE: To investigate the effects of superior mesenteric artery (SMA) flow reduction on the jejunal intramucosal pH (pHi) and to compare these effects with corresponding changes of mesenteric oxygen transport variables and oxygen tensions on the surfaces of the jejunal serosa and mucosa. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 20 domestic pigs. INTERVENTIONS: Mechanical flow reduction in the SMA. The animals were randomized to have an SMA flow of 0%, 25%, 38%, 50% or 100% (control). MEASUREMENTS AND MAIN RESULTS: Measurements (baseline, ischemia, reperfusion) consisted of hemodynamic and oxygen transport variables, SMA blood flow, mesenteric oxygen transport variables, pHi and oxygen tensions of the jejunal serosa and mucosa. Flow reduction in the SMA resulted in a significant decrease of pHi indicating ischemia earlier than mesenteric oxygen transport variables. The relationship between mesenteric oxygen delivery (DO2ms) and pHi during acute ischemia is best described by a sigmoid curve. There was a linear correlation between the changes of the jejunal surface oxygen tensions and pHi due to SMA flow reduction. CONCLUSION: The sigmoid relationship between pHi and DO2ms indicated that pHi is a sensitive parameter for detecting ischemia at 50% of the baseline oxygen delivery and that below 25% there was no further decrease of pHi. In contrast, mesenteric and whole body oxygen transport parameters were not indicative of impaired mucosal oxygen supply.

Analysis of Variance↗

Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.

We investigated the possibility that T helper cells might enhance the stimulatory function of dendritic cells (DCs). We found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12. Other stimuli such as microbial agents, TNF-alpha or LPS are much less effective or not at all. In addition, CD40L is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs. These effects of CD40 ligation result in an increased capacity of DCs to trigger proliferative responses and IFN-gamma production by T cells. These findings reveal a new role for CD40-CD40L interaction in regulating DC function and are relevant to design therapeutic strategies using cultured DCs.

Antigen-Presenting Cells↗

A human killer inhibitory receptor specific for HLA-A1,2.

Killer inhibitory receptors (KIRs) are transmembrane glycoproteins, expressed on NK cells and a small subset of T cells, that inhibit cell-mediated cytotoxicity upon binding to polymorphic MHC class I determinants on target cells. Although human KIRs specific for HLA-C and HLA-B molecules have been characterized, none have been shown to interact with HLA-A. Here we demonstrate that a member of the KIR cDNA family, designated NKAT4, encodes a 70-kDa receptor specific for HLA-A3.

Antibodies, Monoclonal↗

Repeated dural punctures increase the incidence of postdural puncture headache.

Previous studies have failed to find a significant correlation between the number of dural punctures and the incidence of postdural puncture headache (PDPH), questioning the hypothesis that leakage of cerebrospinal fluid (CSF) through the dural tear is the cause of PDPH. We hypothesized that insufficient statistical power of these studies was the cause for this unexpected finding, and re-examined whether repeated dural punctures increase the incidence of PDPH by analyzing prospectively collected data on 8034 spinal anesthetics. Uneventful spinal anesthetics, including a single subarachnoid injection of local anesthetics, occurred in 7865 (97.9%) cases, whereas failed spinal anesthetics requiring repeated dural puncture for a second subarachnoid injection of local anesthetics occurred in 165 (2.1%) cases. The two groups were similar with regard to age, sex, and ASA physical status. We found that repeated dural punctures significantly increased the incidence of PDPH. We conclude that increased risk of PDPH is a disadvantage of performing a second subarachnoid injection of local anesthetics after a failed spinal anesthetic. Moreover, this result suggests that leakage of CSF through the dural tear is the most plausible cause of PDPH.

Adolescent↗

Three cases of blunt chest trauma caused by constant compression mechanisms.

Three patients (survivors) with isolated blunt chest traumas caused by constant compression mechanisms with known forces are reported on. The low velocity but high compression forces of the accidents, the effect on ventilation and oxygenation, specific early management and follow-up, clinical signs, and underlying complications of these patients are described and discussed.

Accidents↗

[Emergency therapy of burns].

Burns are among the most common accidental injuries, occurring in almost any environment to victims of all ages. Most of them are minor injuries and may be treated on an out-patient basis. Superficial (first-degree and superficial second-degree) burns will heal uneventfully in about two weeks without scarring, as long as no infection complicates the healing process. Major burns, however, are life-threatening, and professional treatment is crucial for survival. The intensive care and the surgical treatment in these patients demand a major commitment in terms of personnel and material resources; in addition, emotional reactions by any person involved in the case are not uncommon. A skilled and knowledgeable on-scene emergency treatment may diminish the depth of the burn wound and will furthermore reduce the number of complications like hypovolemic shock and infection. A complete clinical assessment including the patient history gives the rationale for any therapy and will help determine the appropriate referral center. The emergency treatment primarily includes the cooling of the burn wound to stop the burning process and to reduce pain, the insertion of an intravenous line, including the infusion of 1 to 2l of an isotonic electrolyte solution per hour, and the management of pain with intravenous boluses of morphine. The patient should also receive supplemental oxygen, and the burn wound should be covered by sterile drapes. Finally, every burn victim requires tetanus prophylaxis. Major burns and burn wounds at sensitive locations such as head and hands should be treated in specialized burn centers. This provides best chances for survival and increases the probability for a good cosmetic result.

Adult↗