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Biomedical subjects

Marcus J Schultz

Publications and source records attributed to Marcus J Schultz.

68 records · Page 4Linked to original sources
PubMed2004

Acute pancreatitis in mice impairs bacterial clearance from the lungs, whereas concurrent pneumonia prolongs the course of pancreatitis.

OBJECTIVE: Nosocomial pneumonia is a feared complication in the critically ill patient. Serious acute pancreatitis is frequently complicated by infections. The objectives of this study were to determine the influence of acute pancreatitis on host defense against Pseudomonas pneumonia and to determine the influence of Pseudomonas pneumonia on the severity of concurrent pancreatitis. DESIGN: A controlled, in vivo laboratory study. SETTING: Research laboratory of a health sciences university. SUBJECTS: Female C57Bl/6 mice. INTERVENTIONS: Pancreatitis was induced by 12 hourly intraperitoneal injections of cerulein (pancreatitis) or saline (sham) immediately followed by intranasal administration of Pseudomonas aeruginosa (to induce pneumonia) or saline (controls). Mice were killed 24 hrs later. Hence, four groups were studied: sham/control, pancreatitis/control, sham/pneumonia, and pancreatitis/pneumonia mice. MEASUREMENTS AND MAIN RESULTS: When compared with sham/pneumonia mice, pancreatitis/pneumonia mice demonstrated exaggerated lung inflammation, higher bacterial counts in lungs and pancreas, and enhanced dissemination of the infection. Concurrently, pneumonia prolonged the course of pancreatitis, as reflected by histopathology and higher plasma amylase and relative pancreas weights (all p < .05 for the difference between pancreatitis/pneumonia and pancreatitis/control mice), which was associated with the localization of Pseudomonas in the pancreas. CONCLUSIONS: Acute pancreatitis impairs host defense against Pseudomonas pneumonia, whereas pneumonia prolongs the course of pancreatitis.

Acute Disease↗
PubMed2004

Is surfactant a promising additive drug in ALI/ARDS-patients?

The rationale for surfactant replacement therapy in patients with acute respiratory distress syndrome (ARDS) is to restore the normal composition of the surfactant system, as well as to overcome ongoing inactivation of present surfactant. Indeed, surfactant replacement therapy can normalize the composition of the surfactant system and restore its surface activity, which results in restoration of the gas exchange. Several phase II- and phase III-studies have been performed to investigate safety and efficacy of surfactant replacement therapy in patients with ARDS. In this manuscript we will discuss the differences in the composition of exogenous surfactant, the diverse modes of delivery of surfactant, and timing of therapy, in relation to the efficacy of surfactant instillation in several published and yet unpublished studies.

Clinical Trials as Topic↗
PubMed2004

Modulation of innate immune responses in the treatment of sepsis and pneumonia.

In the last decades several preclinical models for sepsis have been used to study the pathophysiologic processes during sepsis. Although these studies revealed promising immunomodulating agents for the treatment of sepsis, clinical trials evaluating the efficacy of these new agents in septic patients were disappointing. It should be realized that most of the preclinical models for sepsis lack a localized infectious source from which the infection disseminates. Studies on the effects of several immunomodulating strategies have demonstrated strikingly opposite results when using models for sepsis with a more natural route of infection, such as pneumonia, and when using models for sepsis lacking an infectious focus. In this review we will compare models for sepsis and models for pneumonia. We advise to use a combination of models, including models for sepsis and models for localized infections, to test new immunomodulating strategies before starting any clinical trial evaluating a new immunomodulating therapy.

Adjuvants, Immunologic↗
PubMed2003

Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia.

OBJECTIVE: To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP). DESIGN: Non-directed bronchial lavage (NBL) was performed every 48 h in critically ill mechanically ventilated patients. Serial measurements of the cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-10 and the cytokine inhibitors soluble TNFalpha receptor type I (sTNFalphaRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA. SETTING: An adult medical and surgical university hospital intensive care unit. PATIENTS: Nine patients who developed VAP and nineteen patients who did not develop VAP served as controls. INTERVENTIONS: None. RESULTS: Plasma concentrations of the measured cytokines and cytokine inhibitors did not change significantly in any patients. In control patients, NBL fluid concentrations of sIL-1RII decreased significantly over time (P=0.01). In patients who developed VAP, NBL fluid concentrations of TNFalpha, sTNFalphaRI, IL-1alpha, and IL-1beta increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively). Furthermore, NBL fluid/plasma concentration ratios for TNFalpha, sTNFalphaRI, IL-1alpha, IL-1Ra and IL-6 increased significantly as VAP developed (P=0.001, P=0.001, P=0.04, P=0.03, and P=0.04, respectively). CONCLUSION: Our results suggest that the production of important cytokines and cytokine inhibitors is compartmentalised within the lung in critically ill mechanically ventilated patients who develop VAP.

Adult↗
PubMed2003

Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.

BACKGROUND: Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care. METHODS: We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria. FINDINGS: In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0.02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus. INTERPRETATION: In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria.

Adolescent↗
PubMed2003

Bronchoalveolar coagulation and fibrinolysis in endotoxemia and pneumonia.

OBJECTIVES: To review the involvement of coagulation and fibrinolysis in the pathogenesis of acute lung injury during severe infection. To review the cross-talk between coagulation and inflammation that may affect this response. DATA SOURCES: Published articles on experimental and clinical studies of coagulation and fibrinolysis during infection, inflammation, acute lung injury, and evolving acute respiratory distress syndrome. CONCLUSIONS: Fibrin deposition is an important feature of pulmonary infection or severe inflammation. The mechanisms that contribute to this fibrin deposition are bronchoalveolar tissue factor-mediated thrombin generation and localized depression of urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. These effects on pulmonary coagulation and fibrinolysis are regulated by various proinflammatory cytokines. Rather than being a unidirectional relationship, the interaction between inflammation and coagulation involves significant cross-talk. Coagulation and fibrinolytic proteins may have an additional role beyond fibrin turnover and inflammation, e.g., in mechanisms mediating cell recruitment and migration.

Bronchoalveolar Lavage Fluid↗
PubMed2003

Anticoagulant therapy for acute lung injury or pneumonia.

Pulmonary changes in thrombin formation in patients with acute lung injury or pneumonia are remarkably similar to systemic changes in coagulation observed in septic patients. Since anticoagulant therapy has proven to be successful in the treatment of patients with sepsis, the same therapeutic strategy may benefit patients with acute lung injury or pneumonia. Based on the fact that inflammation not only leads to dysregulation of the coagulation system, but vice versa, activation of coagulation amplifies inflammatory processes as well, it can be questioned whether the advantage of anticoagulant therapy is solely related to its influence on disturbed thrombin formation. In this paper we will discuss local changes in the haemostatic balance during acute lung injury, both in pre-clinical and clinical studies. Until now, pre-clinical studies have demonstrated that interventions aimed at correction of coagulation abnormalities may form an important strategy in patients with acute lung injury in the future. Pre-clinical studies on use of anticoagulants during pneumonia are presently performed and data are underway.

Animals↗
PubMed2002

Modulation of pulmonary innate immunity during bacterial infection: animal studies.

Both the increasing number of immunocompromised patients susceptible to pneumonia and the development of bacterial resistance are significant problems related to the treatment of pneumonia. The primary outcome of treatment for pneumonia is to tip the balance towards a successful host response. An ideal approach would be a combination of immunomodulation and conventional antimicrobial therapy. It is of increasing importance to understand the components of innate immunity, before immunomodulatory therapy can be applied to patients. Much of our knowledge of the role of alveolar macrophages, cytokines and chemokines in the pathogenesis of pneumonia is derived from animal studies on experimental pneumonia. This article summarizes current information on the role of an alveolar macrophage (AM) and AM-derived mediators in host defense against pneumonia.

Animals↗
PubMedDate not supplied

Clinically relevant differences in accuracy of enteral nutrition feeding pump systems.

BACKGROUND: There are clinically relevant discrepancies between prescribed volumes and delivered volumes of enteral nutrition (EN) in intensive care unit (ICU) patients. Next to EN-protocol violations due to insufficient care, we hypothesized technical factors to be responsible for this deficit. The aim of this study was to determine the accuracy of EN feeding pump systems frequently used in the ICU. METHODS: Thirteen commercially available EN feeding pumps with their own delivery systems were tested in 12 sessions with different EN feeding tubes and EN formulas in a laboratory setting. The reproducibility of the measurements was determined for the 8 best performing EN feeding pump systems. RESULTS: There were clinically important differences between prescribed volumes and delivered volumes of EN in the tested EN feeding pump systems. The deficit in volume ranged from +66 mL (surplus of 66 mL) to -271 mL (deficit of 271 mL) per 24 hours (14% of prescribed volume). Viscosity of test fluids (water/EN feeding formulas) and resistance of test tubes had no influence on the delivered volume by the tested EN feeding pump systems, because differences between prescribed volumes and delivered volumes were consistently found for each system while varying these test settings. CONCLUSIONS: Differences between prescribed and delivered EN volumes are caused by the function and construction of EN feeding pump systems. To improve nutrition therapy, the flow rate has to be adjusted or the best-performing EN feeding pump has to be purchased.

Energy Intake↗
PubMedDate not supplied

Can we abandon daily routine chest radiography in intensive care patients?

Two different schools of thought exist on the utility of daily routine chest radiographs in intensive care unit (ICU) patients: some ICU physicians argue that daily routine chest radiographs are indicated in all patients who have cardiopulmonary problems or are receiving artificial ventilation. Others state that chest radiographs should be made on indication only, for example, following a change in clinical status or change of supportive devices. Most studies on this topic have simply reported the existence of several findings on chest radiographs; some investigators tried to determine whether such findings were new and/or unexpected and whether they caused a therapy change. A restrictive strategy has been compared with a daily routine strategy in only 2 clinical trials: 1 study conducted in a pediatric ICU (pediatric ICUs usually have low mortality rates), and the other a rather small (and probably underpowered) study. The debate about discontinuing daily routine chest radiographs in the ICU is still not settled.

Adult↗
PubMedDate not supplied

Two cases of tetanus?

Tetanus is a rare infectious disease in Western countries that leads to diagnostic difficulties. Several diseases may mimic tetanus, and diagnostic considerations can at times be difficult, especially in critically ill patients, who need prompt treatment. Two patients are presented who were diagnosed with and treated for tetanus. However, the course of these patients' diseases strongly suggested that the diagnoses were incorrect. The article includes reflections on these 2 difficult diagnostic cases. These 2 cases illustrate the importance of proposing alternative diagnoses in suspected tetanus in Western countries. This may prevent loss of valuable time and prevent a delay of possibly effective therapy.

Adult↗