The influence of cytokines on the central nervous system of transgenic mice.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
K Geiger
Publications and source records attributed to K Geiger.
Scoring system for nosocomial pneumonia in ICUs.
OBJECTIVE: To develop a scoring system for stratifying patients in intensive care units (ICUs) by risk of developing nosocomial pneumonia (NP), based on variables generally available in an ICU, and to determine the probability of a patient developing NO in the ICU. DESIGN AND SETTING: a 2-year prospective cohort study conducted in a medical and surgical ICU. PATIENTS: 756 patients admitted to the ICU for 48 h or more were followed up until the development of NP or death or discharge from the ICU. MEASUREMENTS AND RESULTS: 129 (17.1%) patients developed NP, 106 (14%) in the first 2 weeks. The following independent risk factors were identified by multivariate analysis: no infection on admission [relative risk (RR) = 3.1, 95% confidence intervals (CI) = 2.0 to 4.81; thorax drainage (RR = 2.1, 95% CI = 1.2 to 3.5); administration of antacids (RR = 2.1, 95% CI = 1.4 to 3.1); partial pressure of oxygen (PO2) > 110 mmHg (RR = 1.6, 95% CI = 1.0 to 2.6); administration of coagulation factors (RR = 1.8 95% CI = 1.0 to 3.2); male gender (RR = 2.7, 95% CI = 1.2 to 6.3); urgent surgery (RR = 2.4, 95% CI = 0.9 to 6.4); and neurological diseases (RR = 4.2, 95% CI = 1.9 to 9.4). To obtain a predictive risk index for NP, a scoring system was developed using a multivariate model. The probability of developing NP varied between 11.0% in the lowest risk group and 42.3% in the highest risk group. The patients' risk of acquiring NP was seven times higher in the highest score category (i.v.) than in the lowest one (I). CONCLUSIONS: ICU patients can be stratified into high- and low-risk groups for NP. No infection on admission, thorax drainage, administration of antacids, and PO2 > 110 mmHg were associated with a higher risk of NP during the entire 2-week period.
Adult↗
Different effects of early endotoxaemia on hepatic and small intestinal oxygenation in pigs.
OBJECTIVE: Study on simultaneous O2 supply/uptake relationships in liver and gut during endotoxaemia, to determine whether signs of dysoxia develop uniformly in the splanchnic region. DESIGN: Animal study to assess the early effects of endotoxaemia on oxygenation of both liver and small intestine. INTERVENTIONS: Eight anaesthetized pigs received a continuous portal venous infusion of lipopolysaccharide (0.5 microgram.kg-1.h-1) for 6 h. Systemic, pulmonary and splanchnic haemodynamics as well as systemic and splanchnic O2 supply/uptake relationships were determined. RESULTS: There was a multiphasic haemodynamic response pattern characterized by an early (within the 1st h) and a subsequent more prolonged phase (between the 2nd and 6th h) of decreases and recovery of hepatic arterial, portal venous and superior mesenteric arterial blood flows (electromagnetic flow probes) and splanchnic O2 deliveries. Unrelated to perfusion pressure and O2 delivery, there were early and sustained decreases in ileal mucosal surface partial pressure of oxygen (PO2) (multiwire PO2 electrode) and pH (tonometry). This was not reflected by ileal serosal surface PO2, O2 uptake and arteriomesenteric venous pH and partial pressure of carbon dioxide (PCO2) gradients. There was little evidence of concomitant hepatic dysoxia as evaluated by surface PO2. CONCLUSIONS: The study demonstrates early and sustained regional (mucosa) intestinal hypoxia with little evidence of simultaneous hepatic dysoxia during initial endotoxaemia.
Animals↗
Effect of inhaled nitric oxide on venous admixture depends on cardiac output in patients with acute lung injury and acute respiratory distress syndrome.
BACKGROUND: It has been shown that inhaled nitric oxide (NO) reduces intrapulmonary venous admixture (QVA/QT) and improves oxygenation in patients suffering from acute respiratory distress syndrome (ARDS). The change in QVA/QT during NO inhalation varies individually. Factors known to influence the respiratory response to NO are the NO concentration and the level of shunt before NO administration. Other factors that may modify the effect on gas-exchange during NO breathing are unknown. METHODS: We studied the effect of 40 ppm inhaled NO on pulmonary gas-exchange and haemodynamics in 37 patients with acute lung injury (ALI) and ARDS, respectively, and factors that may influence the respiratory response to NO. RESULTS: Inhalation of 40 ppm NO produced a decrease in mean pulmonary artery pressure (MPAP) from 33.1 +/- 7.2 to 30.2 +/- 6.8 (mean +/- SD) mmHg (P < 0.0001) while pulmonary artery wedge pressure (PAWP), cardiac output and mean arterial pressure remained constant. Change in QVA/QT during NO inhalation depended on the preinhalation cardiac output and had no association with mixed venous oxygen tension, MPAP-PAWP, and QVA/QT before NO delivery. QVA/QT decreased in 26 patients (group 1) and increased in 11 patients (group 2) during NO inhalation. In group 1, cardiac output was lower than in group 2 (8.6 vs 12.2 l.min-1; P < 0.0005). CONCLUSION: We conclude that the change in venous admixture during inhalation of 40 ppm NO depends on cardiac output. If preinhalation cardiac output is high, 40 ppm NO can adversely affect gas exchange in patients with ALI and ARDS.
Acute Disease↗
The knowledge base of bee navigation
Navigation in honeybees is discussed against the background of the types of memories employed in the navigational task. Two questions are addressed. Do bees have goal-specific expectations, and when are novel routes travelled? Expectations are deduced from (1) context stimuli as determinants for local cue memories, (2) landmark-dependent path integration, (3) sequential learning of landmarks, and (4) motivation- and context-dependent memory retrieval. Novel routes are travelled under two conditions: (1) goal-cue-based piloting and (2) integration of simultaneously activated vector memories. Our data do not support the conclusion that memory integration in bees is organised by a cognitive map. The assumption of purely separate memories that are only retrieved according to the chain of events during navigational performance also appears to be inadequate. We favour the view that multiple memories are integrated using external and internal sources of information. Such configural memories lead to both specific expectations and novel routes.
Journal Article↗
[Anesthesia and the liver].
Explore the source record for details and available documents.
Anesthesia↗
[The normal value of intramucosal CO2 partial pressure (piCO2)].
Explore the source record for details and available documents.
Acid-Base Equilibrium↗
[Experimental studies of acid-base balance and lactate metabolism by the liver].
Explore the source record for details and available documents.
Acid-Base Equilibrium↗
Inhaled nitric oxide reduces pulmonary transvascular albumin flux in patients with acute lung injury.
BACKGROUND: In acute lung injury, when pulmonary microvascular permeability is enhanced, transvascular fluid filtration mainly depends on pulmonary capillary pressure. Inhaled nitric oxide has been shown to decrease pulmonary capillary pressure. Therefore, the effect of inhaled nitric oxide at a concentration of 40 ppm on pulmonary transvascular albumin flux was studied in nine patients with acute lung injury. METHODS: Transvascular albumin flux was measured by a double radioisotope method using 99mTc-labeled albumin and 51Cr-labeled autologous red blood cells. Radioactivity of both isotopes was externally measured over the right lung by a gamma scanner and simultaneously in arterial blood. The normalized ratio of 99mTc/51Cr lung to 99mTc/51Cr blood (normalized index) was calculated. The normalized slope index which is the slope of the regression line of the normalized index versus time represents the accumulation rate of albumin in the interstitial space of the lungs. Normalized slope index and pulmonary capillary pressure were determined before, during, and after inhalation of 40 ppm nitric oxide. Pulmonary capillary pressure was estimated using the visual analysis of the pressure decay curve after pulmonary artery occlusion. RESULTS: Normalized slope index decreased from 0.0077 +/- 0.0054 min-1 (SD) off nitric oxide to -0.0055 +/- 0.0049 min-1 (P < 0.01) during nitric oxide and increased to 0.0041 +/- 0.0135 min-1 after nitric oxide. Pulmonary capillary pressure declined from 24 +/- 4 mmHg off nitric oxide to 21 +/- 4 mmHg during nitric oxide (P < 0.01), whereas pulmonary artery wedge pressure and cardiac output did not change. CONCLUSIONS: It is concluded that 40 ppm inhaled nitric oxide decreases pulmonary transvascular albumin flux in patients with acute lung injury. This effect may be the result of the decrease in pulmonary capillary pressure.
Acute Disease↗
Differential effects of dobutamine, dopamine, and noradrenaline on splanchnic haemodynamics and oxygenation in the pig.
Supranormal oxygen (O2) transport may benefit critically ill patients. Catecholamines are clinically employed for this purpose. However, their effects on splanchnic haemodynamics and oxygenation are now well defined. The effects of dobutamine (DOBU), dopamine (DOPA), and noradrenaline (NA) on splanchnic blood flows electromagnetic flow probes), O2 deliveries and uptakes (catheterisation of portal and hepatic veins) were studied in nine anaesthetised (ketamine/flunitrazepam), ventilated, paralysed, and laparotomised pigs. All three catecholamines (DOPA at 15 micrograms.kg-1.min-1, DOBU at 13 micrograms.kg-1.min-1, NA at 0.4 micrograms.kg-1.min-1) significantly (P < 0.05) increased cardiac output and systemic O2 delivery. Only DOPA increased small intestinal and total hepatic blood flows, and O2 deliveries, and decreased O2 extractions. The same parameters did not change during DOBU. During NA, total hepatic blood flow and O2 delivery decreased, and hepatic O2 extraction increased. During all three catecholamines, small intestinal and total hepatic O2 uptakes did not change significantly. Whereas hepatic arterial blood flow decreased during both DOPA and NE, portal venous flow increased during DOPA. These data suggest that in the experimental model used splanchnic O2 supply and O2 reserve capacity appear improved by DOPA, unaffected by DOBU, and impaired by NA.
Adrenergic beta-Agonists↗
Local production of IFN-gamma abrogates the intraocular immune privilege in transgenic mice and prevents the induction of ACAID.
The eye represents an immunologically privileged site with specific properties mediated by immunosuppressive constituents of the intraocular fluids. This system, termed ACAID (anterior chamber-associated immune deviation), was originally attributed to the anterior chamber of the eye, and is characterized by impairment of the cellular immune response, including a lack of delayed type hypersensitivity (DTH) reaction in response to intraocularly presented Ag and decreased cytotoxicity of T cells. We created a transgenic mouse with ectopic expression of IFN-gamma in the photoreceptors of the retina to study the effects of this cytokine on the immunosuppressive properties of the eye with special regard to the posterior chamber. BALB/c-derived transgenic and nontransgenic mice were challenged intravitreally either with allogeneic splenocytes from C57Bl/6 mice or with BSA, in IFA, and tested for the delayed type hypersensitivity reaction to BSA by intrapinnal injection of the same Ag in the ear 7 days later. Pathologic changes of the eyes were evaluated by histology and immunohistochemistry. We found that transgenic mice developed an increased amount of ocular inflammation in response to both Ags compared with the nontransgenic controls. Furthermore, transgenic mice showed a marked DTH reaction to BSA, whereas nontransgenic mice did not. Our results indicate that local IFN-gamma production disturbs the immunosuppressive properties of the eye and prevents the induction of ACAID in response to intraocularly presented Ag. The data confirm the extension of the intraocular immune privilege to the posterior chamber of the eye.
Animals↗
Inhaled nitric oxide lowers pulmonary capillary pressure and changes longitudinal distribution of pulmonary vascular resistance in patients with acute lung injury.
In acute lung injury (ALI), where pulmonary microvascular permeability is increased, transvascular fluid filtration depends mainly on the hydrostatic capillary pressure. In the presence of intrapulmonary vasoconstriction pulmonary capillary pressure (PCP) may increase thereby promoting transvascular fluid filtration and lung oedema formation. We studied the effect of 40 ppm inhaled nitric oxide (NO) on PCP and longitudinal distribution of pulmonary vascular resistance (PVR) in 18 patients with ALI. PCP was estimated by visual analysis of the pressure decay profile following pulmonary artery balloon inflation. Contribution of venous pulmonary resistance to total PVR was calculated as the percentage of the pressure gradient in the pulmonary venous system to the total pressure gradient across the lung. Inhalation of 40 ppm NO produced a prompt decrease in mean pulmonary artery pressure (PAP) from 34.1 +/- 6.8 to 29.6 +/- 5.7 (s.d.) mmHg; (P < 0.0001). PCP declined from 24.8 +/- 6.2 to 21.6 +/- 5.2 mmHg; (P < 0.0001) while pulmonary artery wedge pressure (PAWP) did not change. PVR decreased from 166 +/- 73 to 128 +/- 50 dyn.sec.cm-5; (P < 0.0001). Pulmonary venous resistance (PVRven) decreased to a greater extent (from 76 +/- 41 to 50 +/- 28 dyn.sec.cm-5; (P < 0.001) than pulmonary arterial resistance (PVRart) (from 90 +/- 36 to 79 +/- 29 dyn.sec.cm-5; (P < 0.01). The contribution of PVRven to PVR fell from 44.3 +/- 10.8 to 37.8 +/- 11.9%; (P < 0.01). Cardiac output (CO) remained constant. The findings demonstrate that NO has a predominant vasodilating effect on pulmonary venous vasculature thereby lowering PCP in patients with ALI.
Administration, Inhalation↗
Ectopic expression of gamma interferon in the eye protects transgenic mice from intraocular herpes simplex virus type 1 infections.
Transgenic (rho gamma) mice provide a model for studying the influence of gamma interferon (IFN-gamma) produced in the eye on ocular and cerebral viral infection. To establish this model, we injected BALB/c- and C57BL/6-derived transgenic and nontransgenic mice of different ages intravitreally with herpes simplex virus type 1 (HSV-1) strain F. Eye and brain tissues of these mice were assessed for pathological and immunocytochemical changes. HSV-1 infection induced severe retinitis of the injected eyes and infection of the brain in all mice. In transgenic mice inoculated with HSV-1, the left, nontreated eyes were protected from retinitis, whereas nontransgenic mice developed bilateral retinitis. Additional intravitreal injection of IFN-gamma with the virus protected the noninoculated eyes of nontransgenic mice. Three-week-old nontransgenic mice died from HSV-1 infection, whereas transgenic mice of the same age and nontransgenic mice intravitreally treated with IFN-gamma survived. Ocular IFN-gamma production increased the extent of inflammation in transgenic mice but did not have a significant influence on the growth of HSV-1 until day 3 after inoculation and did not influence the neuroinvasion of this virus. Thus, the effects of IFN-gamma were not caused by an early block of viral replication. Possible mechanisms of IFN-gamma action include activation of the immune response, alteration of the properties of the virus, and direct protection of neurons.
Animals↗
Paraffin induced sclerosing lipogranuloma of eyelids and anterior orbit following endonasal sinus surgery.
During the past 5 years we have seen 10 patients who had developed sclerosing lipogranuloma of the lid and orbit after endonasal sinus surgery with subsequent ipsilateral monocular haematoma. The histopathological examination of all and the additional nuclear magnetic resonance spectroscopic examination of four surgical specimens in combination with the typical clinical course led to the conclusion that the granulomas were caused by small paraffin droplets. These in turn stemmed from the ointment plugs applied to the sinuses at the end of the operation, and were washed out into the surrounding tissues by the postoperative haemorrhage. As the chronic and recurring granulomas can lead to considerable cosmetic and functional impairment, the application of ointment plugs at the end of sinus surgery should be abandoned, especially when peri- or postoperative bleeding occurs.
Adult↗
Relationship of plasma epinephrine and circulating eosinophils to nocturnal asthma.
The mechanisms of nighttime airway obstruction are not fully established, but include circadian fluctuations in epinephrine and cortisol. To evaluate the relationship of circadian patterns in epinephrine and cortisol to nighttime airflow obstruction, 10 young adult asthma patients (ages 19 to 25 yr) were admitted to a hospital clinical research unit for a 3-day study during which plasma concentrations of epinephrine, cortisol, and histamine were determined along with white blood cell and eosinophil counts every 6 h (1600, 2200, 0400, and 1000 h). Six of the 10 patients experienced at least one episode of nocturnal asthma (defined by more than a 15% decrease in antemeridian (A.M.) to postmeridian (P.M.) FEV1 values). Plasma epinephrine levels (pg/ml) showed a circadian pattern, and the concentration at 2200 h was significantly (p = 0.039) different for the nocturnal and non-nocturnal asthma groups. Circulating eosinophil numbers were greater in subjects who had more frequent episodes of nocturnal asthma, and correlated with the frequency of nocturnal asthma (r = 0.732, p = 0.02, Spearman rank correlation) and average percent decrease in FEV1 (r = 0.667, p = 0.035). Plasma cortisol concentrations also showed circadian patterns, but no direct association with nocturnal asthma; plasma histamine concentrations showed no circadian patterns and no association with nocturnal asthma. Our findings indicate that changes in plasma epinephrine precede the development of nocturnal airway obstruction and contribute to the likelihood of nighttime airflow obstruction.
Adult↗
[Long term course of catecholaminergic polymorphic ventricular tachycardia in children. Apropos of 20 cases with an 8 year-follow-up].
BACKGROUND: Primary ventricular arrhythmias are rarely seen in children. Some of them have a poor prognosis; they should be diagnosed because adequate treatment can prevent sudden death. POPULATION AND METHODS: Twenty children (11 male, nine female), aged 3 to 16 years (mean: 7.7 +/- 4), with apparently normal hearts and normal QTc intervals were referred for stress or emotion-induced syncope. Primary ventricular arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvos eventually degenerating into ventricular fibrillation, was reproducibly induced by physical exertion. The syncopal events and "torsades de pointe" disappeared with beta-blocking therapy. A total of four syncopal events and two sudden deaths occurred during a mean follow-up of 8 years, probably due to discontinuation of treatment. DISCUSSION: Fifty-four-cases of stress-induced severe polymorphous ventricular arrhythmia have been reported in the literature. There were four sudden deaths in 37 patients on beta-blocking therapy, and ten sudden deaths in 21 untreated patients. CONCLUSION: Clinically close to the congenital long QT syndrome, this primary ventricular arrhythmia must be looked for in cases of stress or emotion-induced syncope. The diagnosis relies on Holter monitoring and a stress test. Life-long beta blocker therapy is required.
Adolescent↗
Transgenic mice expressing IFN-gamma in the retina develop inflammation of the eye and photoreceptor loss.
PURPOSE: Inflammatory mediators such as interferon-gamma (IFN-gamma) are thought to play a role in ocular disease. Although IFN-gamma was found in the vitreous of mice with experimentally induced autoimmune uveitis, intracameral injection of this cytokine did not induce intraocular inflammation in mice. Therefore, the authors created a transgenic mouse line using the rhodopsin promoter to direct the expression of IFN-gamma in the photoreceptor cells of the retina. These mice, designated rho gamma, enabled them to model intraocular inflammatory disease. METHODS: The authors fused a 2.1 kb 5' Hind III fragment from the murine rhodopsin gene to the IFN-gamma gene and introduced the DNA construct into fertilized zygotes. These were implanted into pseudopregnant C57BL/6 mice, and the resulting progeny were crossed back to balb/c mice. The transgene was identified by Southern blot hybridization. Eyes from the rho gamma mice were either fixed in zinc formalin and stained with hematoxylin and eosin or were frozen in OCT compound and processed for immunostaining using the indirect immunoperoxidase method with DAB as a chromogen. RESULTS: The rho gamma transgenic mice developed intraocular disease, manifested as intraocular cellular infiltration, loss of photoreceptors, corneal clouding, cataract formation, and epithelial and microglial proliferation. Additionally, rho gamma mice exhibited antigenic changes, comprising GFAP expression on Müller cells, accumulation of neurofilament on photoreceptors, and expression of MHC class I and class II molecules on retinal cells. CONCLUSIONS: IFN-gamma alters the antigenic properties of intraocular tissue and induces intraocular inflammation in mice. The results suggest a key position of IFN-gamma in the development of pathologic conditions related to intraocular inflammation and provide a useful animal model for the further study of inflammatory disorders, including autoimmune diseases.
Animals↗
Exogenous or endogenous reservoirs of nosocomial Pseudomonas aeruginosa and Staphylococcus aureus infections in a surgical intensive care unit.
OBJECTIVE: A 4 month prospective study was performed to assess the incidence and routes of endogenous or exogenous colonization and nosocomial infection caused by Staphylococcus aureus and Pseudomonas aeruginosa in surgical critically ill patients. DESIGN: A total of 4634 specimens were obtained. Patient's nasal, scalp, and rectal swabs as well as tracheal secretion (TS) were cultured every second day beginning on the day of admission. Nasal swabs and hand cultures of the personnel as well as cultures from gowns were also taken. All isolates of S. aureus were phage typed and 116 of these isolates were also plasmid typed. P. aeruginosa isolates were sero- and pyocin typed. Resistance patterns were determined in all isolates. SETTING: The study was carried out in the surgical intensive care unit (SICU) of an teaching hospital. PATIENTS: During the study period each patient (a total of 153 patients) admitted to the SICU entered the study. RESULTS: P. aeruginosa and S. aureus colonisation rate on admission were 5% and 36.5% respectively. Only 10 patients (6.5%) were colonized with P. aeruginosa during hospitalization, and only 7 patients (4.5%) acquired S. aureus in the surgical intensive care unit (SICU). The most common primary colonisation site of P. aeruginosa was the rectum, whereas S. aureus was predominantly found in nasal cultures. Horizontal transmission of S. aureus occurred in only 2 patients. CONCLUSION: The study suggests that colonisation with P. aeruginosa and S. aureus occurs from endogenous rather than from exogenous sources and that the endogenous acquisition of both bacteria play a more important role in development of nosocomial infections than the exogenous route of transmission.
Cross Infection↗