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Konrad Reinhart

Publications and source records attributed to Konrad Reinhart.

At least 19 recordsLinked to original sources
PubMed2006

"Euthanasia": A confusing term, abused under the Nazi regime and misused in present end-of-life debate.

BACKGROUND: Legal provisions in The Netherlands and Belgium currently allow physicians to actively end a patient's life at his or her request under certain conditions. The term that is used for this is "euthanasia." DISCUSSION: The same term, "euthanasia," was used in Germany during the Nazi regime for a program of cleansing the "German nation" in which untold thousands of persons were denied human empathy or medical care and were thereby condemned to death. The medical profession played a leading role in the planning, administration, and supervision of this "euthanasia" program, with a large proportion of German physicians proactively shirking all moral responsibility and ultimately paving the way for the Holocaust. CONCLUSION: The term "euthanasia" was so abused during the Nazi regime as a camouflage word for murder of selected subpopulations with the willing participation of physicians, we believe that, regardless of the benevolent goals of current euthanasia practices, for historical reasons the term "euthanasia" must not be used with regards to current end-of-life care.

Attitude of Health Personnel↗
PubMed2006

An evaluation of systemic inflammatory response syndrome signs in the Sepsis Occurrence In Acutely Ill Patients (SOAP) study.

OBJECTIVE: To define the frequency and prognostic implications of SIRS criteria in critically ill patients hospitalized in European ICUs. DESIGN AND SETTING: Cohort, multicentre, observational study of 198 ICUs in 24 European countries. PATIENTS AND INTERVENTIONS: All 3,147 new adult admissions to participating ICUs between 1 and 15 May 2002 were included. Data were collected prospectively, with common SIRS criteria. RESULTS: During the ICU stay 93% of patients had at least two SIRS criteria [respiratory rate (82%), heart rate (80%)]. The frequency of having three or four SIRS criteria vs. two was higher in infected than non-infected patients (p < 0.01). In non-infected patients having more than two SIRS criteria was associated with a higher risk of subsequent development of severe sepsis (odds ratio 2.6, p < 0.01) and septic shock (odds ratio 3.7, p < 0.01). Organ system failure and mortality increased as the number of SIRS criteria increased. CONCLUSIONS: Although common in the ICU, SIRS has prognostic importance in predicting infections, severity of disease, organ failure and outcome.

Aged↗
PubMed2006

Markers for sepsis diagnosis: what is useful?

Timely diagnosis of the different severities of septic inflammation is potentially lifesaving because therapies that have been shown to lower mortality should be initiated early. Sepsis and severe sepsis are accompanied by clinical and laboratory signs of systemic inflammation but patients with inflammation caused by noninfectious causes may present with similar signs and symptoms. It is important to identify markers for an early diagnosis of sepsis and organ dysfunction. This article presents currently interesting sepsis biomarkers. Other novel markers and their potential role are discussed.

Acute-Phase Proteins↗
PubMed2006

Platelet-derived microvesicles induce differential gene expression in monocytic cells: a DNA microarray study.

Platelet-derived microvesicles (PMV) that are shed from the plasma membrane of activated platelets, expose various platelet-type antigens on their surface and are able to adhere to other blood cells and endothelial cells. There are several clinical conditions with markedly increased numbers of PMV, e.g. acute coronary syndrome, thrombotic microangiopathy and sepsis. To prove whether PMV may contribute to an inflammatory response we used DNA microarray technology to study the effect of PMV on gene expression in the prototypic monocytic cell line MonoMac 6 (MM6). PMV were generated by activating human platelets in plasma with collagen and subsequent removal of platelets and plasma by repeated centrifugation. MM6 were incubated for 2 h with PMV in a ratio corresponding to 75 platelets/cell, or saline as control. After RNA isolation, reverse transcription and fluorescence labelling, cDNA was hybridized on a medium density microarray comprising 5308 probes addressing 4868 transcripts of 4730 human genes relevant to inflammation, immune response and related processes. The formation of PMV-MM6 conjugates was associated with significant variations in gene expression, i.e. 93 genes were found to be differentially expressed (P < 0.001; q < 0.087). Among them, 47 genes with annotated transcripts and proteins were identified. Using Ingenuity Pathway Analysis, 37 of the differentially expressed genes were identified as parts of networks associated with functional pathways including cell-to-cell signalling, cellular growth and proliferation, regulation of gene expression and lipid metabolism. For sphingosine kinase-1 the increased expression could be confirmed exemplarily not only by RT-PCR but also on the enzyme activity level. The data indicate that PMV signal differential expression of inflammation-relevant genes in monocytic cells and may represent a novel link between hemostasis and inflammation.

Blood Platelets↗
PubMed2006

Sepsis in European intensive care units: results of the SOAP study.

OBJECTIVE: To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight intensive care units in 24 European countries. PATIENTS: All new adult admissions to a participating intensive care unit between May 1 and 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data, comorbid diseases, and clinical and laboratory data were collected prospectively. Patients were followed up until death, until hospital discharge, or for 60 days. Of 3,147 adult patients, with a median age of 64 yrs, 1,177 (37.4%) had sepsis; 777 (24.7%) of these patients had sepsis on admission. In patients with sepsis, the lung was the most common site of infection (68%), followed by the abdomen (22%). Cultures were positive in 60% of the patients with sepsis. The most common organisms were Staphylococcus aureus (30%, including 14% methicillin-resistant), Pseudomonas species (14%), and Escherichia coli (13%). Pseudomonas species was the only microorganism independently associated with increased mortality rates. Patients with sepsis had more severe organ dysfunction, longer intensive care unit and hospital lengths of stay, and higher mortality rate than patients without sepsis. In patients with sepsis, age, positive fluid balance, septic shock, cancer, and medical admission were the important prognostic variables for intensive care unit mortality. There was considerable variation between countries, with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries. CONCLUSIONS: This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries. In addition to age, a positive fluid balance was among the strongest prognostic factors for death. Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission.

APACHE↗
PubMed2006

Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study.

OBJECTIVE: The optimal adrenergic support in shock is controversial. We investigated whether dopamine administration influences the outcome from shock. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight European intensive care units. PATIENTS: All adult patients admitted to a participating intensive care unit between May 1 and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed up until death, until hospital discharge, or for 60 days. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor catecholamines. Of 3,147 patients, 1,058 (33.6%) had shock at any time; 462 (14.7%) had septic shock. The intensive care unit mortality rate for shock was 38.3% and 47.4% for septic shock. Of patients in shock, 375 (35.4%) received dopamine (dopamine group) and 683 (64.6%) never received dopamine. Age, gender, Simplified Acute Physiology Score II, and Sequential Organ Failure Assessment score were comparable between the two groups. The dopamine group had higher intensive care unit (42.9% vs. 35.7%, p=.02) and hospital (49.9% vs. 41.7%, p=.01) mortality rates. A Kaplan-Meier survival curve showed diminished 30 day-survival in the dopamine group (log rank=4.6, p=.032). In a multivariate analysis with intensive care unit outcome as the dependent factor, age, cancer, medical admissions, higher mean Sequential Organ Failure Assessment score, higher mean fluid balance, and dopamine administration were independent risk factors for intensive care unit mortality in patients with shock. CONCLUSIONS: This observational study suggests that dopamine administration may be associated with increased mortality rates in shock. There is a need for a prospective study comparing dopamine with other catecholamines in the management of circulatory shock.

Aged↗
PubMed2006

Venous oximetry.

PURPOSE OF REVIEW: Mixed venous and central venous oxygen saturations reflect the balance between oxygen requirement and oxygen delivery, and thus may be used to assess the adequacy of tissue oxygenation. This review discusses recent data on the impact of using venous oximetry by obtaining mixed venous oxygen saturation or central venous oxygen saturation as useful monitoring parameters in critically ill patients. RECENT FINDINGS: Monitoring of changes in the central venous oxygen saturation after major surgery has been shown to be associated with outcome. Furthermore, early goal-directed therapy for patients with severe sepsis or septic shock, which includes treatment goals for mean arterial pressure, central venous pressure, and central venous oxygen saturation, was able to increase survival in these patients. In contrast, pulmonary artery catheter usage does not affect outcome in critically ill patients. SUMMARY: Early goal-directed therapy should be implemented in the initial resuscitation of septic patients. Central venous saturation may have prognostic significance following major surgery. Further evaluation of peri-operative trends in central venous saturation is required. Measurement of central venous oxygen saturation can easily be applied in intensive care unit patients and offers a useful, indirect indicator for the adequacy of tissue oxygenation.

Blood Gas Analysis↗
PubMed2006

Both gram-negative and gram-positive experimental pneumonia induce profound lymphocyte but not respiratory epithelial cell apoptosis.

To determine whether and by which pathway (via the death receptor or mitochondrial mediated pathway) lymphocyte apoptosis occurs in pneumonia and to determine if increased bronchial epithelial cell apoptosis occurs in pneumonia. Prospective randomized study in a university research laboratory. Male C57BL/6 mice (n = 30). Animals received an intratracheal injection of Streptococcus pneumoniae or Pseudomonas aeruginosa to induce gram-positive or gram-negative pneumonia, respectively and were killed 24, 30, or 48 h later. Presence of pneumonia was confirmed via gross visual examination of lungs and by histology. Lymphocyte apoptosis in spleen and thymus was analyzed by flow cytometry for active caspases 3, 8, and 9 and by immunohistochemical (IHC) staining for active caspase 3 and DNA strand breaks. Respiratory epithelial cell apoptosis was assessed by IHC. Histologically, pneumonia was present in all bacteria-treated animals but none in sham-treated mice. Extensive lymphocyte apoptosis in spleen and thymus was documented by characteristic morphological changes on hematoxylin and eosin staining and by IHC staining in both S. pneumonia and P. aeruginosa infection. Flow cytometry confirmed IHC and showed apoptotic lymphocytes positive for active caspases 3, 8, and 9 in both thymi and spleens in both infections. In contrast to the extensive lymphocyte apoptosis, only rare scattered apoptotic changes were seen in respiratory epithelial or endothelial cells in pneumonia due to either organism. Increased lymphocyte but not bronchial cell apoptosis occurs in both gram-positive and gram-negative pneumonia and probably involves both the extrinsic and intrinsic pathway.

Animals↗
PubMed2006

Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature.

INTRODUCTION: Systemic inflammatory response syndrome is common after surgery, and it can be difficult to discriminate between infection and inflammation. We performed a review of the literature with the aims of describing the evolution of serum procalcitonin (PCT) levels after uncomplicated cardiac surgery, characterising the role of PCT as a tool in discriminating infection, identifying the relation between PCT, organ failure, and severity of sepsis syndromes, and assessing the possible role of PCT in detection of postoperative complications and mortality. METHODS: We performed a search on MEDLINE using the keyword 'procalcitonin' crossed with 'cardiac surgery,' 'heart,' 'postoperative,' and 'transplantation.' Our search was limited to human studies published between January 1990 and June 2006. RESULTS: Uncomplicated cardiac surgery induces a postoperative increase in serum PCT levels. Peak PCT levels are reached within 24 hours postoperatively and return to normal levels within the first week. This increase seems to be dependent on the surgical procedure and on intraoperative events. Although PCT values reported in infected patients are generally higher than in non-infected patients after cardiac surgery, the cutoff point for discriminating infection ranges from 1 to 5 ng/ml, and the dynamics of PCT levels over time may be more important than absolute values. PCT is superior to C-reactive protein in discriminating infections in this setting. PCT levels are higher with increased severity of sepsis and the presence of organ dysfunction/failure and in patients with a poor outcome or in those who develop postoperative complications. PCT levels typically remain unchanged after acute rejection but increase markedly after bacterial and fungal infections. Systemic infections are associated with greater PCT elevation than is local infection. Viral infections are difficult to identify based on PCT measurements. CONCLUSION: The dynamics of PCT levels, rather than absolute values, could be important in identifying patients with infectious complications after cardiac surgery. PCT is useful in differentiating acute graft rejection after heart and/or lung transplantation from bacterial and fungal infections. Further studies are needed to define cutoff points and to incorporate PCT levels in useful prediction models.

Biomarkers↗
PubMed2005

Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study.

INTRODUCTION: Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. METHODS: In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. RESULTS: Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). CONCLUSION: Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients.

Age Distribution↗
PubMed2005

Communication of end-of-life decisions in European intensive care units.

OBJECTIVE: To examine end-of-life (EOL) practices in European ICUs: who makes these decisions, how they are made, communication of these decisions and questions on communication between the physicians, nurses, patients and families. DESIGN: Data collected prospectively on EOL decisions facilitated by a questionnaire including EOL decision categories, geographical regions, mental competency, information about patient wishes, and discussions with patients, families and health care professionals. SETTING: 37 European ICUs in 17 countries. PATIENTS: ICU physicians collected data on 4,248 patients. RESULTS: 95% of patients lacked decision making capacity at the time of EOL decision and patient's wishes were known in only 20% of cases. EOL decisions were discussed with the family in 68% of cases. Physicians reported having more information about patients' wishes and discussions in the northern countries (31%, 88%) than central (16%, 70%) or southern (13%, 48%) countries. The family was more often told (88%) than asked (38%) about EOL decisions. Physicians' reasons for not discussing EOL care with the family included the fact that the patient was unresponsive to therapy (39%), the family was unavailable (28%), and the family was thought not to understand (25%). CONCLUSIONS: ICU patients typically lack decision-making capacity, and physicians know patients' wishes in only 20% of EOL decisions. There were regional differences in discussions of EOL decisions with families and other physicians. In European ICUs there seems to be a need to improve communication.

Communication↗
PubMed2005

Transcription in response to physical stress--clues to the molecular mechanisms of exercise-induced asthma.

To clarify stress-induced immunological reactions and molecular events during exercise and the potential relevance to exercise-induced bronchoconstriction, transcriptional responses to standardized physical stress were determined. Six healthy, young volunteers underwent an endurance exercise of 90% of their individual anaerobic threshold for 90 min. Time-dependent alterations in the expression pattern of leukocytes from healthy, trained subjects were analyzed by DNA microarrays before and 2 h and 6 h after exercise. Starting out from a large collection of cDNA library clones comprising more than 70,000 human expressed sequence tags, we selected, designed, and immobilized oligonucleotide probes (60-70mers) for transcripts of 5000 stress- and inflammation-relevant genes. Exercise-induced stress provoked changes in the expression of 433 gene activities 2 h and/or 6 h after exercise, which could be grouped into six clusters. The most prominent feature was an enhanced transcription of two genes, coding for 5-lipoxygenase (ALOX5) and ALOX5-activating protein. Moreover, enhanced levels of leukotriene B4 (LTB4) and LTC4 (P<0.05) were detected in plasma after exercise. Our data demonstrate that exercise alters the activities of a distinct number of genes. In particular, they possibly provide novel insights into the molecular mechanisms of exercise-induced bronchoconstriction and suggest that enhanced transcription of ALOX5 and its activating protein together with a present predisposition of the subject critically contribute to exercise-induced asthma.

5-Lipoxygenase-Activating Proteins↗
PubMed2005

Venous oximetry.

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Cardiac Output↗
PubMed2005

Has mortality from acute renal failure decreased? A systematic review of the literature.

PURPOSE: To determine mortality rates in patients with acute renal failure during the past decades. METHODS: We performed a MEDLINE search using the keywords "acute renal failure" crossed with "outcome," "mortality," "ICU," "critically ill" or "prognosis" in the period from January 1970 to December 2004. Abstracts and full articles were eligible if mortality rates were reported. We also reviewed the bibliographies of available studies for further potentially eligible studies. The dates of the observation period for each study and not the publication dates were considered for the analysis, so the earliest data were from 1956. RESULTS: Of 85 articles fulfilling the criteria, 5 were excluded because of duplicate publications using the same database, so that 80 were included in our review with a total of 15897 patients. Mortality rates in most studies exceeded 30%, and there was no consistent change over time. CONCLUSION: Despite technical progress in the management of acute renal failure over the last 50 years, mortality rates seem to have remained unchanged at around 50%.

Acidosis↗
PubMed2005

Neutrophil stimulation with granulocyte colony-stimulating factor worsens ventilator-induced lung injury and mortality in rats.

BACKGROUND: Based on the association between the neutrophil and ventilator-induced lung injury, the authors hypothesized that neutrophil inhibition with fucoidin would be beneficial and stimulation with granulocyte colony-stimulating factor (G-CSF) would be harmful in a rat model of lethal ventilator-induced lung injury. METHODS: Animals (n = 111) were randomly assigned to be pretreated with fucoidin, G-CSF, or placebo (control) before 4 h of low-tidal-volume (10 ml/kg) or high-tidal-volume (40 ml/kg) mechanical ventilation. RESULTS: All low-volume animals survived. With high volumes, compared with controls, fucoidin did not improve survival (3 of 20 control animals and 5 of 20 fucoidin animals died; P = 0.51) but G-CSF significantly worsened it (18 of 22 animals died; P < 0.001). Circulating neutrophils were increased early with G-CSF and late with fucoidin with low and high tidal volumes (P < 0.05 for each treatment and tidal volume). Fucoidin decreased lung neutrophils, but these were only significant with high tidal volumes, whereas G-CSF increased lung neutrophils but only significantly with low tidal volumes (P < or = 0.01 for each). Fucoidin did not alter any cardiopulmonary measure significantly. Compared with control, G-CSF increased airway pressures with high tidal volumes and worsened lung edema and arterial oxygen with both tidal volumes (P < 0.05 for each). CONCLUSIONS: In this model, neutrophil stimulation by G-CSF increased lung dysfunction and with high tidal volumes worsened survival rates. Extrapolated clinically, neutrophil stimulation either by agents such as G-CSF or conditions such as sepsis may aggravate ventilator-induced lung injury.

Animals↗
PubMed2005

Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure.

OBJECTIVE: To determine whether changes in coagulation biomarkers during the first day of severe sepsis correlate with progression from single to multiple organ failure and subsequent death. DESIGN: Analysis of secondary endpoints in a prospective, randomized, placebo-controlled, multinational clinical trial (PROWESS). SETTING: The study involved 164 medical centers. PATIENTS: A total of 840 patients who met criteria for severe sepsis and were randomized to receive placebo plus supportive care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Coagulation biomarkers, prothrombin time, antithrombin activity, and D-dimer and protein C levels were measured, and Sequential Organ Failure Assessment was performed daily. Multiple logistic regression analysis identified baseline antithrombin activity <54% and changes in prothrombin time, D-dimer, and antithrombin activity during the first calendar day after the onset of the first sepsis-induced organ dysfunction (i.e., the first day of severe sepsis, day 1) as predictive of 28-day mortality (p < or = .01). A composite coagulopathy score was determined using points for predetermined levels of change from baseline to day 1. The composite coagulopathy score correlated with progression from single to multiple organ failure (p = .0007), time to resolution of organ failure (p = .0004), and 28-day mortality (p < .0001). Combining the composite coagulopathy score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score improved ability to identify patients who would progress to multiple organ failure (area under receiver operating characteristic curve 0.61 APACHE II vs. 0.65 APACHE II + composite coagulopathy score) and who would die (area under receiver operating characteristic curve 0.69 APACHE II vs. 0.74 APACHE II + composite coagulopathy score). CONCLUSIONS: Continuation or worsening of coagulopathy during the first day of severe sepsis was associated with increased development of new organ failure and 28-day mortality. These results further suggest that coagulation abnormalities contribute to organ failure and death.

APACHE↗
PubMed2005

The value of venous oximetry.

PURPOSE OF REVIEW: Maintenance of adequate tissue oxygenation is an important task in intensive care units. In this context, venous oximetry by obtaining mixed venous oxygen saturation or central venous oxygen saturation has been discussed as useful monitoring parameters. This review discusses the physiology and clinical application of these parameters. RECENT FINDINGS: No study has so far demonstrated that venous oxygen saturation monitoring can reduce mortality in critically ill patients although length of stay has been decreased in cardiac surgery patients. Furthermore, pulmonary artery catheter usage does not affect outcome in critically ill patients. In contrast, early goal directed therapy for patients with severe sepsis or septic shock, which includes treatment goals for mean arterial pressure, central venous pressure, and central venous oxygen saturation, was able to increase survival in these patients. There is also evidence that central venous oxygen saturation measurement is beneficial in other types of shock. SUMMARY: Early goal directed therapy should be implemented in the initial resuscitation of septic patients. Measurement of central venous oxygen saturation can easily be applied in intensive care unit patients and offers a useful indirect indicator for the adequacy of tissue oxygenation.

Blood Gas Analysis↗