Biomedical subjects

S Schroeder

Publications and source records attributed to S Schroeder.

At least 19 recordsLinked to original sources

PubMed2003

cMap: the comparative genetic map viewer.

UNLABELLED: cMap, a www comparative genetic map graphical utility, has a search capability and provides comparison of two genetic maps within or between species with dynamic links to data resources and text lists of the shared loci, running in a relational database environment. Currently, maps from three species (maize 'Zea mays L.', rice 'Oryza sativa L.', and sorghum 'Sorghum bicolor L.'), representing over 13,800 distinct loci, are available for comparison at http://www.agron.missouri.edu/cMapDB/cMap.html. AVAILABILITY: cMap source code is available without cost on request for non-commercial use.

Database Management Systems↗

PubMed2002

Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury.

OBJECTIVE: To investigate the kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury (ALI). DESIGN: Prospective observational cross-over study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twelve mechanically ventilated patients with ALI. INTERVENTIONS: Mechanical ventilation was transiently changed from a lung protective setting with PEEP of 15 cmH(2)O and a V(T) of 5 ml/kg predicted body weight to a more conventional ventilatory setting with PEEP of 5 cmH(2)O and V(T) of 12 ml/kg predicted body weight for a period of 6 h. MEASUREMENTS AND RESULTS: We examined the profile of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor in the plasma of all patients, and in the bronchoalveolar lavage (mini-BAL) fluid of six of these patients. Measurements were performed at baseline, 1 h, and 6 h after each change of the ventilatory setting. Switching to conventional mechanical ventilation was associated with a higher PaO(2) ( P < 0.05) and a marked increase ( P < 0.05) of measured plasma cytokines in patients with and without mini-BAL with a maximum after 1 h. Similarly, intraalveolar cytokine concentrations increased with conventional mechanical ventilation. While plasma cytokine levels returned to baseline values, intraalveolar cytokine concentrations further increased when lung protective mechanical ventilation was reestablished. CONCLUSIONS: In patients with ALI, initiation of low PEEP and high V(T) mechanical ventilation is associated with cytokine release into circulation which occurred within 1 h. It is independent from BAL procedures and can be reversed by reinstitution of lung protective mechanical ventilation.

Bronchoalveolar Lavage Fluid↗

PubMed2002

Non-invasive coronary angiography with high resolution multidetector-row computed tomography. Results in 102 patients.

AIMS: A new generation of multidetector-row CT (MDCT) scanners allows complete coronary coverage using retrospective ECG gating and 1mm slices. The purpose of this study was to investigate the potential of high resolution MDCT angiography with retrospective gating for detection of coronary artery stenoses. METHODS AND RESULTS: A total of 102 patients underwent both conventional and MDCT coronary angiography. After intravenous injection of a non-ionic contrast medium the entire heart was scanned within a single breath hold using 1mm slices. All MDCT data sets were reconstructed with retrospective gating at 20% to 80% in increments of 10% relative to the cardiac cycle. Two blinded independent reviewers analysed image quality for segments 1-4 (right coronary artery), 5-8 (left main, left anterior descending), and 11, 12 (left circumflex). These segments were evaluated for the presence or absence of significant (>or=50%) stenoses. The results were compared with those of invasive coronary angiography in a blinded fashion. Overall sensitivity for the detection of significant stenoses (>or=50%) were 0.86 (reader 1) and 0.93 (reader 2), specificity 0.96 (reader 1) and 0.97 (reader 2), negative predictive value 0.98 (reader 1) and 0.99 (reader 2). CONCLUSIONS: High resolution MDCT angiography with retrospective gating permits the non-invasive detection of coronary artery stenoses with high accuracy if image quality is optimized for each of the three major coronary arteries.

Coronary Angiography↗

PubMed2002

Virtual coronary angioscopy using multislice computed tomography.

BACKGROUND: With faster image acquisition times and thinner slice widths, multislice detector computed tomography (MSCT) allows visualisation of human coronary arteries with diagnostic image quality. In addition to conventional axial slices, virtual coronary angioscopies (VCA) can be reconstructed using MSCT datasets. OBJECTIVE: To evaluate the feasibility of reconstructing VCA and to determine the clinical value of this new application in detecting atherosclerotic coronary artery lesions. METHODS: Datasets obtained by contrast enhanced non-invasive coronary angiography using MSCT (Somatom VZ) were analysed from 14 consecutive patients. VCA were simulated in 14 coronary arteries (left anterior descending, n = 7; right coronary, n = 7). Lesion detection was undertaken on conventional contrast enhanced axial slices, as well as by VCA. Intracoronary ultrasound (ICUS) was used as the gold standard for in vivo plaque detection. RESULTS: 38 lesions were detected both on ICUS and on axial slices: 14 severe target lesions of > 75% area stenosis (11 calcified, three non-calcified), and 24 intermediate lesions of < or = 75% area stenosis (seven calcified, 17 non-calcified). Using VCA, all severe lesions (n = 14) and all calcified intermediate plaques (n = 7) could clearly be identified. However, non-calcified intermediate lesions (n = 17) could not be accurately distinguished from the vessel wall; they were recognised as vessel wall alterations without significant luminal narrowing. CONCLUSIONS: Current MSCT technology allows reconstruction of VCA with good image quality. Despite a more anatomical view of heart and coronary vessels on three dimensional reconstruction, conventional axial slices were found to be superior for detecting coronary lesions. Thus further technical innovations are required before VCA can become a useful technique in clinical cardiology.

Adult↗

PubMed2002

Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes.

We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 healthy control subjects were examined for expression of the chemokine receptors CXCR4 (naive T-cells), CCR5 and CXCR3 (Th1 associated), and CCR3 and CCR4 (Th2 associated) on CD3+ lymphocytes. Furthermore, we analyzed chemokine serum levels (monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (gamma-interferon [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]) and Th2 (interleukin [IL]-4 and -10)-associated cytokines by PBMC. The patients with newly diagnosed type 1 diabetes were followed for these parameters at 6-12 months after diagnosis. The PBMCs of patients with newly diagnosed but not with longstanding type 1 diabetes showed reduced expression of the Th1-associated chemokine receptors CCR5 (P < 0.001 vs. control subjects) and CXCR3 (P < 0.002 vs. control subjects). This reduction correlated with reduced IFN-gamma and TNF-alpha production of PBMCs after PHA stimulation and reversed 6-12 months after diagnosis to normal levels. CCR4 cells were reduced in both newly diagnosed and longstanding type 1 diabetic patients, which correlated to reduced PHA-stimulated IL-4 production. MIP-1alpha and MIP-1beta levels were considerably elevated in a subgroup of patients with newly diagnosed diabetes. We assume that Th1-associated peripheral T-cells are reduced in a narrow time window at the time of diagnosis of diabetes, possibly due to extravasation in the inflamed pancreas. Thus, chemokine receptor expression of peripheral blood lymphocytes may be a useful surrogate marker for the immune activity of type 1 diabetes (e.g., in intervention trials).

Adolescent↗

PubMed2001

Protective functions of intracellular heat-shock protein (HSP) 70-expression in patients with severe sepsis.

Intracellular expression of heat-shock-protein 70 (HSP70) arose early in evolutionary development as a tool to protect cellular homeostasis. HSP70 detects proteins that are incorrectly folded or denatured. They form a complex with such proteins which can lead to correct folding, compartmentalization in organelles, or to proteolytic degradation. HSP70 also appears to protect proteins from degeneration. Intracellular HSP70-expression is induced by a wide variety of stimuli including heat, fever, hypoxia, oxygen radicals, endotoxins, cytokines, and heavy metal ions. Pre-emptive induction of HSP70-expression reduces organ dysfunction and mortality in animal models of sepsis.

Animals↗

PubMed2001

Fluorescence-based analyses of the effects of full-length recombinant TAF130p on the interaction of TATA box-binding protein with TATA box DNA.

We have used a combination of fluorescence anisotropy spectroscopy and fluorescence-based native gel electrophoresis methods to examine the effects of the transcription factor IID-specific subunit TAF130p (TAF145p) upon the TATA box DNA binding properties of TATA box-binding protein (TBP). Purified full-length recombinant TAF130p decreases TBP-TATA DNA complex formation at equilibrium by competing directly with DNA for binding to TBP. Interestingly, we have found that full-length TAF130p is capable of binding multiple molecules of TBP with nanomolar binding affinity. The biological implications of these findings are discussed.

DNA↗

PubMed2001

Molecular regulation of CC-chemokine receptor 3 expression in human T helper 2 cells.

In developing T helper 1 (Th1) and Th2 cells the acquisition of effector function is intimately connected with the acquisition of new migratory capacities, as exemplified by differential expression of chemokine receptors. This study investigates the molecular mechanisms responsible for Th2-restricted expression of the CC-chemokine receptor 3 (CCR3). The minimal promoter in T cells was identified in the -149 base pair (bp) upstream sequence that contains a positive regulatory element. A strong negative element was also localized in the flanking intronic sequence. The study further investigates the role of chromatin remodeling in the regulation of this Th2-specific gene. Drugs that affect the chromatin structure facilitate CCR3 expression in T cells. Furthermore, in differentiating Th2 cells, selected regions are associated with acetylated-H3 histones and become more accessible to DNase I. These results suggest that in Th2 cells both cytokine production and migratory capacity are regulated through a similar mechanism involving chromatin remodeling.

CD4-Positive T-Lymphocytes↗

PubMed2001

Phylogenetic relationship of Ophiostoma piliferum to other sapstain fungi based on the nuclear rRNA gene.

The nuclear rRNA gene of Ophiostoma piliferum was analyzed to understand its phylogenetic relationships to other sapstain fungi. Phylograms based on nucleotide sequences of the rRNA gene showed that the relationships between O. piliferum and other Ophiostoma species varied depending on the regions of the rRNA gene analyzed. Intraspecies variation in O. piliferum was found in the internal transcribed spacer regions, and the variation was related to the geographic origin of O. piliferum strains. A useful molecular marker for differentiating O. piliferum from other sapstain Ophiostoma species was generated by the HaeIII restriction fragment length polymorphism of the 26S rRNA gene.

Ascomycota↗

PubMed2001

Noninvasive detection of coronary lesions by multislice computed tomography: results of the New Age pilot trial.

The reliable noninvasive assessment of coronary artery disease would constitute an important step forward in clinical cardiology. The aim of the New Age pilot trial was to evaluate the diagnostic accuracy of multislice computed tomography (MSCT) in determining coronary lesions. As a gold standard for in vivo plaque detection, intracoronary ultrasound (ICUS) was used. Forty plaques were detected by ICUS in 15 target vessels (LAD, n = 8; RCA, n = 7) in patients assigned for ICUS-guided PTCA. Preinterventional MSCT was performed in all patients and the results were compared to ICUS with regard to lesion detection and quantification. According to ICUS results, the 40 plaques were divided into three groups: group I, mild lesions < 50% (n = 14; 44.36% +/- 5.77%); group II, intermediate lesions 50%-75% (n = 12; 59.18% +/- 9.39%); and group III, severe lesions > 75% (n = 14; 91.47% +/- 3.68%). All MSCT scans showed sufficient image quality for analysis. Thirty of 40 (75%) plaques were detected by MSCT in a first blinded session. After unblinding the ICUS results, the remaining 10 (25%) plaques could be identified. Lesion severity was classified correctly in 34 of 40 (85%) plaques. Plaque calcifications were diagnosed correctly in 16 of 19 (84.2%) plaques. Quantification of vessel size revealed a good correlation to the ICUS results (r(2) 0.68; P = 0.004). Noninvasive MSCT angiography showed good diagnostic accuracy with regard to lesion detection and quantification of vessel size. The overall good image quality, makes this new technology a promising modality, which might become an alternative diagnostic approach in patients with known or suspected coronary artery disease. Cathet Cardiovasc Intervent 2001;53:352-358.

Adult↗

PubMed2001

Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis.

OBJECTIVE: To investigate the role of macrophage migration inhibitory factor (MIF) as a marker of severity of systemic inflammation in patients with severe sepsis and critically ill postsurgical patients. DESIGN: Prospective observational study in consecutive patients with severe sepsis, critically ill nonseptic postsurgical patients, and healthy blood donors. SETTING: A surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 19 patients with severe sepsis, 18 critically ill nonseptic postsurgical patients, and 10 healthy blood donors. MEASUREMENTS AND RESULTS: MIF plasma levels of patients and participants were measured. Interleukin 6 plasma levels were monitored as a control marker of inflammation. The median MIF plasma level was four to five times higher in patients with severe sepsis (2.70 ng/ml, range 0.31-19.59) and in critically ill nonseptic postsurgical patients (2.43 ng/ml, range 0.49-4.31) than in healthy blood donors (0.56 ng/ml, range 0.16-1.68). MIF plasma levels did not differ between the patient groups. CONCLUSIONS: MIF serves as a general marker for systemic inflammation in septic and nonseptic acute critical illness, but MIF does not discriminate for severity or differentiate between infectious and noninfectious origins of an acute critical illness.

Adolescent↗

PubMed2001

Non-invasive characterisation of coronary lesion morphology and composition by multislice CT: first results in comparison with intracoronary ultrasound.

The reliable non-invasive detection of coronary artery disease (CAD) is a prime goal for future developments in clinical cardiology. In addition to the documentation of high-grade stenoses, the detection of vulnerable plaques is of major importance for risk stratification and early treatment to prevent plaque rupture. Recently, a new generation of fast spiral CT has been introduced using a multi-slice technique (MSCT), which is the first real quantum leap in CT since the introduction of spiral CT in the early 1990s. We report on non-invasive differentiation of coronary plaque morphology by MSCT in patients with lesions in the proximal left anterior descending artery (LAD). The results were compared with the findings of intracoronary ultrasound (ICUS). The ICUS and MSCT scans were analysed in 6 patients scheduled for ICUS-guided PTCA. One target lesion was selected in each patient. On ICUS, two lesions were classified as soft, two as intermediate and two as calcified according to established criteria based on echogenicity. By multislice CT, density measurements (expressed in Hounsfield Units, HU) were performed at 16 randomly selected areas within the plaques. The two soft plaques showed a mean density of 6+/-28 and -5+/-25 HU, the two intermediate plaques of 83+/-17 and 51+/-19 HU, and the two calcified plaques of 489+/-372 and 423+/-111 HU. To our knowledge, this is the first report on non-invasive characterisation of coronary lesions by MSCT. Plaque composition could be clearly differentiated and classified according to the ICUS results by determining tissue density within the lesions. Thus, this new technology holds promise for non-invasive risk assessment in patients with known or suspected CAD since also rupture-prone soft coronary lesions can be detected by use of this new technique.

Aged↗

PubMed2001

Increased susceptibility to apoptosis in circulating lymphocytes of critically ill patients.

BACKGROUND AND AIMS: Lymphocyte apoptosis may influence immune responsiveness in systemic inflammation. Therefore, we investigated whether early signs of apoptosis (i.e., annexin-V binding and cell shrinkage) in peripheral lymphocytes were different among patients with severe sepsis, critically ill, nonseptic patients after major surgery, and healthy individuals. PATIENTS/METHODS: Ten patients with severe sepsis and ten critically ill, nonseptic patients after major surgery admitted to a surgical intensive care unit in a university hospital were included in the study. In addition, ten healthy blood donors were included for comparison. We investigated early signs of apoptosis using flow cytometric measurement of annexin-V binding to the cell surface and cell shrinkage of peripheral lymphocytes. RESULTS: The percentage of apoptotic lymphocytes determined as annexin-V positive and propidium iodide negative cells was increased in freshly prepared cells of patients with severe sepsis (11.4 +/- 0.5%) and critically ill, nonseptic patients after major surgery (18.5 +/- 2.0%) relative to healthy blood donors (4.4 +/- 0.5%) (P < 0.05). No significant difference between patients with severe sepsis and patients after major surgery were found. Annexin-V binding increased significantly after OKT-3 stimulation of lymphocytes in patients with severe sepsis (34.4 +/- 1.6%), patients after major surgery (33.8 +/- 3.4%), and healthy blood donors (21.1 +/- 2.8%). No significant difference among groups was detected following OKT-3 stimulation. Furthermore, freshly isolated peripheral lymphocytes of patients with severe sepsis and critically ill, nonseptic patients after major surgery revealed a significantly higher proportion of cell shrinkage than in healthy blood donors (55.0 +/- 2.2%, 21.5 +/- 2.4% vs 3.6 +/- 0.7%; P < 0.05). CONCLUSION: Circulating lymphocytes of critically ill patients show a high degree of early signs of cellular apoptosis. This may contribute to hyporesponsiveness of immune cells in systemic inflammation.

Adult↗

PubMed2001

Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography.

OBJECTIVES: The aim of the present study was to evaluate the accuracy in determining coronary lesion configuration by multislice computed tomography (MSCT). The results were compared with the findings of intracoronary ultrasound (ICUS). BACKGROUND: The risk of acute coronary syndromes caused by plaque disruption and thrombosis depends on plaque composition rather than stenosis severity. Thus, the reliable noninvasive assessment of plaque configuration would constitute an important step forward for risk stratification in patients with known or suspected coronary artery disease. Just recently, MSCT scanners became available for general purpose scanning. Due to improved spatial and temporal resolution, this new technology holds promise to allow for differentiation of coronary lesion configuration. METHODS: The ICUS and MSCT scans (Somatom Volume Zoom, Siemens, Forchheim, Germany) were performed in 15 patients. Plaque composition was analyzed according to ICUS (plaque echogenity: soft, intermediate, calcified) and MSCT criteria (plaque density expressed by Hounsfield units [HU]). RESULTS: Thirty-four plaques were analyzed. With ICUS, the plaques were classified as soft (n = 12), intermediate (n = 5) and calcified (n = 17). Using MSCT, soft plaques had a density of 14 +/- 26 HU (range -42 to +47 HU), intermediate plaques of 91 +/- 21 HU (61 to 112 HU) and calcified plaques of 419 +/- 194 HU (126 to 736 HU). Nonparametric Kruskal-Wallis test revealed a significant difference of plaque density among the three groups (p < 0.0001). CONCLUSIONS: Our results indicate that coronary lesion configuration might be correctly differentiated by MSCT. Since also rupture-prone soft plaques can be detected by MSCT, this noninvasive method might become an important diagnostic tool for risk stratification in the near future.

Adult↗

PubMed2001

Self-rated health and clinical status after PTCA: results of a 4-year follow-up in 500 patients.

Background: Data on the clinical long-term outcome of patients with coronary artery disease in the years following percutaneous interventions are rare. We therefore decided to conduct a study to: (1) analyze the efficiency of a retrospective inquiry using a questionnaire and (2) perform a clinical long-term follow-up of our patients. Methods and results: Some 45+/-7 months after PTCA, a questionnaire was sent to 549 patients who had been treated at our institution from July 1, 1989, to June 30, 1991. The response rate was 91.1%, with 49 patients (8.9%) lost to follow-up. A total of 115/500 patients (23%) had reinterventions due to severe angina (69 patients (13.8%) undergoing re-PTCA and 46 (9.2%) CABG). Sixteen patients (3.2%) had a myocardial infarction and 35 patients (7.0%) died. Multivariate analysis revealed that patients who were asymptomatic 3 months after PTCA were likely to have a good long-term outcome. This was not found when comparing the clinical status immediately after PTCA to follow-up. Medical therapy with beta-blockers/aspirin/lipid-lowering drugs decreased from 75.2/82.2/35.4% at hospital discharge to 54.6/76.7/25.2% at follow-up. Conclusions: The present study provided important quality data for our institution. The response rate to the questionnaire was surprisingly high (91.1%), indicating that retrospective inquiries may also be efficient. The rate of reinterventions during long-term follow-up (23%) was acceptably low. Good self-rated health 3 months after the intervention turned out to be a strong predictor for a good clinical long-term outcome. Furthermore, we observed an underuse of cardiac medication, something that will be the subject of further quality improvement measures.

Journal Article↗

PubMed2001

Accuracy and reliability of quantitative measurements in coronary arteries by multi-slice computed tomography: experimental and initial clinical results.

AIM: To evaluate the accuracy of non-invasive measurements within coronary arteries by multi-slice computed tomography (MSCT). We present experimental as well as clinical data. MATERIALS AND METHODS: Silicon tubes simulating coronary arteries (outer diameter 6 mm, lumen diameter within stenotic area 2 mm) were used for experimental studies. Clinical data were derived from 15 patients in whom vessel diameters were assessed by MSCT, intracoronary ultrasound (ICUS) and quantitative coronary angiography (QCA). MSCT were performed in a Somatom Volume Zoom(trade mark)CT system (Siemens, Forchheim, Germany) at 2 collimated slice widths (2.5 mm, 1.0 mm). RESULTS: Outer silicon tube diameters were overestimated by MSCT (6.56 mm +/- 0.32 mm). All measurements revealed significantly better results on 1.0 collimation compared to 2.5 mm collimation (outer diameter: 6.36 mm +/- 0.22 mm vs 6.76 mm +/- 0.27 mm, P < 0.0001; lumen diameters: 1.83 mm +/- 0.14 mm vs 1.51 mm +/- 0.19 mm, P < 0.0001). The comparison of vessel diameters within human coronary arteries revealed comparable results between ICUS and MSCT (4.89 mm +/- 0.67 mm vs 4.91 mm +/- 0.71 mm, P = 0.79, r = 0.79, P < 0.0001). QCA-measurements showed significantly lower results (3.67 +/- 0.71, P < 0.0001, r = 0.62, P < 0.001). CONCLUSIONS: Experimental as well as initial clinical results indicate acceptable reliability and accuracy of quantitative measurements by MSCT, when using thin collimated slice widths. Partial volume effects lead to a systematic overestimation of vessel size. MSCT has the potential to become an important non-invasive diagnostic tool in patients with coronary artery disease.

Coronary Angiography↗

PubMed2001

Cardiorespiratory effects of automatic tube compensation during airway pressure release ventilation in patients with acute lung injury.

BACKGROUND: Spontaneous breaths during airway pressure release ventilation (APRV) have to overcome the resistance of the artificial airway. Automatic tube compensation provides ventilatory assistance by increasing airway pressure during inspiration and lowering airway pressure during expiration, thereby compensating for resistance of the artificial airway. The authors studied if APRV with automatic tube compensation reduces the inspiratory effort without compromising cardiovascular function, end-expiratory lung volume, and gas exchange in patients with acute lung injury. METHODS: Fourteen patients with acute lung injury were breathing spontaneously during APRV with or without automatic tube compensation in random order. Airway pressure, esophageal and abdominal pressure, and gas flow were continuously measured, and tracheal pressure was estimated. Transdiaphragmatic pressure time product was calculated. End-expiratory lung volume was determined by nitrogen washout. The validity of the tracheal pressure calculation was investigated in seven healthy ventilated pigs. RESULTS: Automatic tube compensation during APRV increased airway pressure amplitude from 7.7+/-1.9 to 11.3+/-3.1 cm H2O (mean +/- SD; P < 0.05) while decreasing trans-diaphragmatic pressure time product from 45+/-27 to 27+/-15 cm H2O x s(-1) x min(-1) (P < 0.05), whereas tracheal pressure amplitude remained essentially unchanged (10.3+/-3.5 vs. 10.1+/-3.5 cm H2O). Minute ventilation increased from 10.4+/-1.6 to 11.4+/-1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from 52+/-9 to 47+/-6 mmHg (P < 0.05) without affecting arterial blood oxygenation or cardiovascular function. End-expiratory lung volume increased from 2,806+/-991 to 3,009+/-994 ml (P < 0.05). Analysis of tracheal pressure-time curves indicated nonideal regulation of the dynamic pressure support during automatic tube compensation as provided by a standard ventilator. CONCLUSION: In the studied patients with acute lung injury, automatic tube compensation markedly unloaded the inspiratory muscles and increased alveolar ventilation without compromising cardiorespiratory function and end-expiratory lung volume.

Adult↗

PubMed2001

The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered response to corticotropin-releasing hormone.

OBJECTIVE: To investigate the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with severe sepsis by stimulating with corticotropin-releasing hormone (CRH). DESIGN: Prospective observational study in consecutive intensive care unit patients with severe sepsis. SETTING: Surgical intensive care unit and outpatient department of endocrinology in a university hospital. PATIENTS: The study included 20 patients with the diagnosis of severe sepsis; six critically ill, nonseptic patients after major surgery; ten patients with primary adrenal insufficiency; ten patients with anterior pituitary insufficiency; and ten individuals without clinical signs of HPA axis disturbance. INTERVENTIONS: CRH tests were performed with an intravenous bolus injection of 100 microg of human CRH. MEASUREMENTS AND MAIN RESULTS: We studied the functional integrity of the HPA axis in patients with severe sepsis by performing the CRH test. In addition, during the period of severe sepsis, we repeatedly measured basal plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol. The mean basal plasma cortisol concentration was decreased significantly in nonsurvivors with severe sepsis (288.8 +/- 29.1 [sem] nmol/L) compared with survivors (468.1+/- 18.6 nmol/L; p <.01). By calculating the ACTH/cortisol indices, we found no evidence for adrenal insufficiency in patients with severe sepsis. The mean ACTH/cortisol indices of nonsurvivors with severe sepsis (0.02 +/- 0.008) and survivors (0.01 +/- 0.002) were significantly lower compared with the index of patients with primary adrenal insufficiency (6.8 +/- 1.0; p <.001). In contrast, in nonsurvivors with severe sepsis, the plasma cortisol response to CRH stimulation was impaired compared with survivors: The mean basal cortisol concentration within the CRH test was 269.4 +/- 39.8 nmol/L in nonsurvivors compared with 470.8 +/- 48.4 nmol/L in survivors and increased to a peak value of 421.6 +/- 72.6 nmol/L in nonsurvivors and 680.7 +/- 43.8 nmol/L in survivors (p <.02). However, the change in plasma cortisol, expressed as mean +/- sem and calculated by subtracting the basal cortisol from the peak cortisol after CRH stimulation, was not significantly different in survivors with severe sepsis (243.5 +/- 36.1, range 111.0-524.0 nmol/L, n = 15) compared with nonsurvivors (161.0 +/- 38.9, range 42.0-245.0 nmol/L, n = 5; p >.05). CONCLUSIONS: We found lower basal plasma cortisol concentrations in nonsurvivors compared with survivors of severe sepsis. In addition, the plasma cortisol response to a single CRH stimulation was impaired in nonsurvivors compared with survivors. Reduced responses to CRH stimulation may reflect a state of endocrinologic organ dysfunction in severe sepsis.

Adolescent↗