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W Karzai

Publications and source records attributed to W Karzai.

At least 37 records · Page 2Linked to original sources
PubMed1999

G-CSF during Escherichia coli versus Staphylococcus aureus pneumonia in rats has fundamentally different and opposite effects.

We investigated if bacteria type alters outcome with prophylactic granulocyte colony stimulating factor (G-CSF) therapy during pneumonia. Rats received G-CSF or placebo daily for 6 d and after the third dose were intrabronchially inoculated with either Escherichia coli or Staphylococcus aureus. Without G-CSF, E. coli and S. aureus produced similar (p = NS) mortality rates (36 versus 38%) and serial changes in mean circulating neutrophil counts (CNC), but differing mean (+/- SE) tumor necrosis factor (TNF) levels (E. coli, 259 +/- 104 versus S. aureus, 51 +/- 17 pg/ml, p = 0.01). G-CSF prior to bacteria increased mean CNC more than six times compared with placebo (p = 0.001). However, with G-CSF in the first 6 h after E. coli, there was a greater than 20-fold decrease in mean (+/- SE) CNC (x 10(3)/ mm3) to below placebo (0.5 +/- 0.1 versus 0.8 +/- 0.1), whereas with G-CSF after S. aureus, there was only a fivefold decrease in mean CNC and CNC were greater than placebo (1.8 +/- 0.2 versus 0.8 +/- 0.1) (E. coli versus S. aureus decrease in CNC with G-CSF, p = 0.001). With E. coli, G-CSF worsened oxygenation and increased bacteremia and mortality, whereas with S. aureus, G-CSF improved oxygenation and decreased bacteremia and mortality (G-CSF therapy, E. coli versus S. aureus, p = 0.03, 0.05, and 0.001, respectively). Thus, during S. aureus pneumonia with low TNF levels, G-CSF increased CNC and bacterial clearance, resulting in less pulmonary injury and decreased death. During E. coli pneumonia with high TNF levels, G-CSF paradoxically decreased CNC, resulting in impaired bacterial clearance and worsened pulmonary injury and death. Bacterial species and the associated inflammatory mediator response can alter outcome with prophylactic G-CSF therapy during pneumonia.

Animals↗
PubMed1999

Editorial comment.

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Journal Article↗
PubMed1998

[Procalcitonin. A new diagnostic parameter for severe infections and sepsis].

Procalcitonin (PCT), a glycoprotein consisting of 116 amino acids, has been proposed as a new marker of severe infection. The site of production under this condition remains unknown. The serum PCT concentration is determined by an immunoluminometric assay of 40 microliters serum or plasma requiring approximately two hours. Elevations of PCT are for instance associated with levels of lipopolysaccharide and the cytokines TNF-alpha and IL-6. Bacterial, parasitic or fungal infections developing septic complications in contrast to local infections, often show values exceeding 2 ng/ml. The specificity of the parameter in this context increases with its concentrations. Therapeutic actions that confine the infection locally are reflected by a decrease of the PCT value. PCT may be elevated within the first days after extended surgery or polytrauma, in some malignancies, heat-stroke and during treatment of some hematologic diseases without an existing sepsis or severe infection. Previous studies indicate certain benefits of PCT compared to traditional markers of inflammation or sepsis, where the ability to indicate a generalized infection is the primary advantage.

Biomarkers↗
PubMed1998

Effect of plasma and LPS on respiratory burst of neutrophils in septic patients.

OBJECTIVE: To compare the respiratory burst of neutrophils in sepsis and control patients using lipopolysaccharide (LPS), autologous plasma, and a combination of the two. DESIGN: Prospective, consecutive case study. SETTING: A 16-bed intensive care unit (ICU) in a university teaching hospital. INTERVENTIONS: None. PATIENTS: Plasma was obtained from 23 healthy patients scheduled for minor surgery immediately prior to induction of anesthesia (controls) and from 23 ICU patients within 24 h of diagnosis of sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: Respiratory burst was determined by lucigenin chemiluminescence expressed as mean +/- SEM of peak values of relative light units per neutrophil. There were no significant differences between neutrophils of septic patients and controls for the stimuli saline, phorbol myristate acetate, formyl-methionyl-leucyl-phenylalanine, and LPS alone. Septic patients showed a lower respiratory burst than controls (p < 0.05) under the following stimuli: plasma alone (5911 +/- 803 vs 15,397 +/- 3038) and LPS and plasma combined (13,857 +/- 1537 vs 23,026 +/- 2640). However, when stimulated with plasma after priming with LPS, septic patients elicited a higher value than control subjects (11,373 +/- 1758 vs 5987 +/- 1234, p < 0.05). CONCLUSIONS: (1) Some components of the plasma of septic patients may have a profound effect on neutrophil response; (2) plasma as a respiratory burst stimulus differentiates between sepsis and non-sepsis samples better than other common stimuli; (3) precautions must be taken when using plasma together with LPS because of the different response depending on whether LPS-priming precedes the plasma stimulus or both are introduced simultaneously and whether septic or nonseptic plasma is used.

Adult↗
PubMed1998

Changes in pulmonary mechanics after fiberoptic bronchoalveolar lavage in mechanically ventilated patients.

OBJECTIVE: We prospectively assessed the impact of bronchoalveolar lavage (BAL) on respiratory mechanics in critically ill, mechanically ventilated patients. STUDY DESIGN: Mechanically ventilated patients underwent BAL of one lung segment using 5 x 20 ml of sterile, physiologic saline with a temperature of 25-28 degrees C. The fractional inspired oxygen was increased to 1.0, but ventilator settings were otherwise left unchanged. Static pulmonary compliance, pulmonary resistance, alveolar ventilation, and serial dead space were measured 60 min and 2 min before and 8, 60, and 180 min after BAL to assess the consequences of the procedure. In addition, blood gases [partial pressure of carbon dioxide in arterial blood (PaCO2) and arterial oxygen tension (PaO2)], hemodynamic variables (heart rate, systolic and diastolic blood pressure), and body temperature were recorded at the same time points. SETTING: Intensive care unit of a university hospital. PATIENTS: 18 consecutive critically ill, mechanically ventilated patients. RESULTS: Pulmonary compliance decreased by 23% (p < 0.05) and pulmonary resistance increased by 22% (p < 0.05) shortly after BAL. The changes in pulmonary compliance and resistance were more than 30% in one third of the patient population. One hour after the procedure, PaO2 was significantly lower and PaCO2 significantly higher than before the procedure. Three hours after the procedure, pulmonary resistance returned to pre-BAL values but compliance remained 10% below baseline values (p < 0.05). CONCLUSION: BAL in mechanically ventilated patients is associated with deterioration of pulmonary mechanics and function.

Adult↗
PubMed1998

Oxygen consumption in hemodialysis patients undergoing cardiopulmonary bypass.

OBJECTIVES: Cardiopulmonary bypass (CPB) can be successfully performed in patients on hemodialysis. However, ischemic complications occur more often in these patients. This could partly be because of shunting through the arteriovenous (AV) fistula during CPB, resulting in reduced peripheral flow and oxygen (O2) delivery. Inadequate oxygen delivery during CPB should be reflected in a lower oxygen consumption (VO2) compared with patients without an AV fistula. DESIGN: To test the hypothesis, the authors analyzed VO2 in three groups of patients retrospectively. Group 1 included 14 patients with end-stage renal failure (creatinine level 9.1 +/- 0.3 mg/dL, urea level 126 +/- 8 mg/dL) requiring hemodialysis through an AV fistula. Group 2 included 13 patients with compensated renal insufficiency (creatinine level 3.1 +/- 0.4 mg/dL, urea level 106 +/- 10 mg/dL) without an AV fistula. Group 3 included 14 patients with normal renal function (creatinine level 1.0 +/- 0.1 mg/dL, urea level 44 +/- 4 mg/dL). SETTING: An operating room of a university hospital. PARTICIPANTS: Patients undergoing cardiac surgery requiring CPB. MEASUREMENTS AND MAIN RESULTS: VO2 was calculated from the recorded hemodynamic and blood gas data using standard formulae. Data were analyzed using a two-way analysis of variance with a repeated measurement on one factor. Before undergoing CPB, VO2 was similar in all three groups. VO2 decreased in all three groups during hypothermic CPB (standard flow rate 2.2 L/min/m2, standard temperature 29 degrees C) and returned to prebypass levels during rewarming. There was no difference in VO2 among the three groups during hypothermic CPB or during rewarming. Only base excess decreased more in group 1 patients compared with the other groups (p < 0.001). CONCLUSION: During hypothermic CPB at a flow rate of 2.2 L/min/m2, shunting through an AV fistula is unlikely to lead to decreased VO2 in dialysis patients.

Acid-Base Imbalance↗
PubMed1998

Role of fiberoptic bronchoscopy in conjunction with the use of double-lumen tubes for thoracic anesthesia: a prospective study.

BACKGROUND: Fiberoptic bronchoscopy has been recommended to verify the position of double-lumen tubes (DLT), but this remains controversial. The authors studied the role of bronchoscopy for placing and monitoring right- and left-sided DLTs after blind intubation and after positioning the patient. METHODS: Two hundred patients having thoracic surgery requiring DLT insertion were prospectively studied. "Blind" tracheal intubations were done with 163 left-sided and 37 right-sided disposable polyvinyl chloride Robertshaw tubes. Bronchoscopy was performed by a different anesthesiologist after intubation and conventional clinical verification of correct placement and after patient positioning for thoracotomy. A DLT was considered malpositioned when it had to be moved >0.5 cm to correct its position. Critical malpositions were those that might have affected patient safety or influenced the surgical procedure if left uncorrected. RESULTS: After "blind" DLT intubation, clinical evidence of malpositioning was found in 28 patients. This was confirmed by fiberoptic assessment. In 172 patients in whom placement was judged correct by clinical assessment, malpositioning was detected by bronchoscopy in 79 cases, 25 of which were critical. After patient positioning, DLTs were found to be displaced in 93 patients, 48 of which were critical. Right-sided DLTs were significantly more likely to be malpositioned than were left-sided DLTs. Two complications were related to unsatisfactory lung separation in the 200 patients studied. CONCLUSIONS: After blind intubation and patient positioning, more than one third of DLTs required repositioning. Routine bronchoscopy is therefore recommended after intubation and after patient positioning.

Adolescent↗
PubMed1998

Total plasma antioxidant capacity is not always decreased in sepsis.

OBJECTIVE: To compare total plasma antioxidant capacity and selected individual antioxidants in patients with varying degrees of severity of sepsis. DESIGN: A prospective, observational, consecutive case study. SETTING: A 16-bed intensive care unit (ICU) in a university teaching hospital. INTERVENTIONS: None. PATIENTS: Forty-six healthy controls, ten ICU patients, nine patients with systemic inflammatory response syndrome (SIRS), 11 septic patients, and 14 septic shock patients. Plasma was obtained in healthy patients scheduled for minor surgery immediately before anesthesia and in ICU patients within 24 hrs of admittance to the unit or diagnosis of SIRS, sepsis, or septic shock. MEASUREMENTS AND MAIN RESULTS: Using the total peroxyl radical trapping method, we found plasma antioxidant capacity to be lower in septic patients but higher in septic shock patients, as compared with controls. Bilirubin was the greatest contributor to the increase with shock, followed by uric acid. Neopterin also correlated with the peroxyl radical trapping antioxidant parameter values. CONCLUSION: Although total plasma antioxidant capacity is decreased from normal levels in septic patients, an increase in some oxidants contributes to an increased total antioxidant capacity in septic shock patients.

Adolescent↗
PubMed1998

Effects of desflurane and propofol on arterial oxygenation during one-lung ventilation in the pig.

BACKGROUND: Desflurane depresses hypoxic pulmonary vasoconstriction (HPV) in vitro. During one-lung ventilation (OLV), HPV may reduce venous admixture and ameliorate the decrease in arterial O2 tension by diverting blood from the non-ventilated to the ventilated lung. Accordingly, this study compares the effects of desflurane with those of propofol on oxygenation during two-lung (TLV) and OLV in vivo. METHODS: Ten pigs (25-30 kg) were premedicated (flunitrazepam 0.4 mg/kg i.m.), anaesthetized (induction: propofol 2 mg/kg i.v.; maintenance: N2O/O2 50%/50%, desflurane 3%, propofol 50 micrograms kg-1 min-1, and vecuronium 0.2 mg kg-1 h-1 i.v.), orally intubated and mechanically ventilated. Femoral arterial and thermodilution pulmonary artery catheters were placed, and the orotracheal tube was replaced by a left-sided 28-Ch double-lumen tube (DLT) via tracheotomy. After DLT placement, N2O and propofol were discontinued, FiO2 was increased to 0.85, and anaesthesia continued randomly with either desflurane (1 MAC) or propofol 200 micrograms kg-1 min-1. Using a cross-over design, in each animal the effects of a), changing from TLV to OLV (left lung) during both desflurane and propofol and b), the effects of changing between the two anaesthetics during OLV were studied. RESULTS: When changing from TLV to OLV, PaO2 decreased more (p < 0.05) during desflurane (mean 75%) than during propofol (mean 60%). Changing between desflurane and propofol during OLV resulted in small but consistent (P < 0.05) increases in PaO2 (mean 15%) during propofol. CONCLUSION: Consistent with in vitro results on HPV, 1 MAC desflurane impaired in vivo oxygenation during OLV more than did propofol.

Anesthesia↗
PubMed1998

Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis.

We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O2 concentrations (FIO2) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 x 10(10) colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing FIO2 (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial PO2 [-0.3 +/- 0.6, 3 +/- 1, 13 +/- 4, 10 +/- 9 (mean +/- SE) Torr, respectively] and decreased the mean arterial-alveolar O2 gradient (0.5 +/- 0.3, 4 +/- 2, -8 +/- 7, -10 +/- 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean PO2 with increasing FIO2 (2 +/- 1, -5 +/- 3, -2 +/- 3, and -12 +/- 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O2 gradient (0.3 +/- 0.04, 2 +/- 2, 1 +/- 3, 11 +/- 5 Torr; P < 0.05 compared with infected animals). In normal and infected animals alike, only at FIO2 < or = 0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonary artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high FIO2 and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects.

Administration, Inhalation↗
PubMed1998

Effects of L-NMMA and fluid loading on TNF-induced cardiovascular dysfunction in dogs.

We investigated the effects of N(omega)-monomethyl-L-arginine (L-NMMA) and fluid loading on tumor necrosis factor (TNF)-induced cardiovascular dysfunction in awake dogs. L-NMMA (40 mg x kg(-1) given intravenously over a period of 10 min, and followed by dosing at 40 mg x kg(-1) x h(-1) for 6 h) and TNF (20 or 45 microg x kg(-1) given intravenously for 20 min), given alone or in combination, significantly decreased stroke volume, cardiac index, oxygen delivery, and left-ventricular (LV) function plots over a period of 6 h. Of note was that the cardiac-depressant effects of TNF and L-NMMA given together were significantly less than additive. Thus, the combination was beneficial (or significantly less harmful to cardiac performance than expected), possibly because L-NMMA augmented cardiac preload as shown by significant increases in both pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP). Fluid challenges at 6 h (Ringer's solution at 80 ml x kg(-1) given over a period of 30 min) also significantly increased PCWP and CVP, and abolished the beneficial preload effect of L-NMMA on cardiac performance. Thus, after fluid loading, the cardiac-depressant effects of TNF and L-NMMA given together became equal to the sum of those produced by TNF and L-NMMA given separately. Although L-NMMA significantly decreased serum nitrite/nitrate levels, TNF did not increase these end products of nitric oxide (NO) production relative to controls. Therefore, after preload abnormalities were eliminated with fluid loading, L-NMMA had no beneficial effect on TNF-induced cardiac depression, and TNF did not increase end products of NO production. These findings are not consistent with NO being the mechanism of TNF-induced acute cardiac depression.

Animals↗
PubMed1998

Sepsis: definitions and diagnosis.

There have been many attempts to provide a uniform definition for the diagnosis of sepsis that can be used for research and clinical purposes. Several definitions are too broad and, as a result, clinicians are unable to direct appropriate therapies to patients. Disappointing immunomodulatory trials have led many researchers to the conclusion that the current diagnostic criteria of sepsis fails to identify patients who could benefit from immunomodulatory therapies. In order to restore clinical and experimental relevance, many researchers and clinicians believe that sepsis should be defined as an inflammatory response to infection with signs of remote organ dysfunction. However, because common clinical signs of systemic inflammation are neither specific nor sensitive for sepsis, other markers may be helpful. Markers of the systemic inflammatory response to infection could include cytokines such as tumour necrosis factor alpha, interleukin 1, 6 and 8 and the propeptide procalcitonin. As well as identifying patients who may benefit from pro- or anti-inflammatory therapies, these markers may gauge the extent of the inflammatory response and could be used for monitoring the immune status of the patient.

Biomarkers↗
PubMed1997

A controlled study of leukocyte activation in septic patients.

OBJECTIVE: Qualitative and quantitative evaluation of leukocyte activation in septic patients in comparison to two control groups. DESIGN: A prospective clinical study in which the leukocyte oxidative output of whole blood was measured in three groups of patients. Two chemiluminescence markers (luminol or lucigenin), indicative of either total oxidant output or superoxide production, and three stimuli (opsonized zymosan, formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate) (PMA), representing different pathways of leukocyte activation, were used. Tumor necrosis factor, interleukin-6 and C-reactive protein (TNF, IL-6, and CRP) were determined to evaluate the severity of the inflammatory process. SETTING: Intensive care and surgical units of a university hospital. PATIENTS: Seventy-four healthy patients, ten ICU patients without signs of sepsis or systemic inflammatory response syndrome and 19 septic patients were studied. MEASUREMENT AND MAIN RESULTS: With all three stimuli, whole blood total oxidative output and superoxide production were generally increased in septic patients. This was most likely due to the increased leukocyte numbers in these patients. When the chemiluminescence values were normalized per phagocyte (granulocytes and monocytes), the total oxidative output of septic phagocytes decreased with opsonin and fMLP but increased with PMA, while superoxide output decreased regardless of the stimuli used. TNF, IL-6 and CRP, although increased in septic patients as compared to ICU controls, correlated weakly with oxidant output. CONCLUSIONS: The oxidative output of whole blood was increased in septic patients compared to controls because of elevated leukocyte numbers. However, oxidant output normalized for phagocyte numbers generally decreases during sepsis for most stimuli. Cytokines and CRP do not appear to be associated with the extent of oxidant output during sepsis.

Adult↗
PubMed1997

Rapid increase in inspired desflurane concentration does not elicit a hyperdynamic circulatory response in the pig.

The effects of a rapid increase in inspired desflurane concentration on systemic haemodynamics and plasma catecholamines were studied in seven pigs (22-30 kg). Following premedication (flunitrazepam 0.4 mg/kg i.m.), anaesthesia was induced (propofol 2.5 mg/kg i.v., vecuronium 0.2 mg/kg i.v.), the trachea orally intubated, and ventilation controlled. Anaesthesia was maintained with N2O/O2 (70%/30%), propofol (50 micrograms/kg/min), desflurane (2% end-tidal concentration), and vecuronium (0.3 mg/kg/h). After cannulation of both femoral arteries for subsequent simultaneous systemic pressure measurements and blood sampling for determination of epinephrine (E) and norepinephrine (NE) plasma levels, N2O and propofol were discontinued, and FiO2 and end-tidal concentration of desflurane increased to > 0.9 and 3%, respectively. Forty minutes later, the inspired concentration of desflurane was abruptly increased to 15%. Mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of E and NE were determined before and 1, 2, 4, 8, 16, and 32 min after increasing the desflurane concentration. Plasma concentrations of E and NE were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Data were analysed by repeated measures ANOVA (significance level P < 0.05). The abrupt increase in inspired desflurane concentration caused an insignificant increase (11%) in HR at 1, 2 and 4 min. There was an immediate decrease in MAP. Plasma levels of E and NE remained unchanged throughout. In conclusion, in contrast to findings in humans, a rapid increase in inspired desflurane concentration does not cause a hyperdynamic circulatory response in the pig.

Anesthesia↗
PubMed1997

Immune modulation and sepsis.

The pathogenesis of sepsis involves not only microbial toxins but also activated host inflammatory mediators. Therefore, besides conventional antibiotic or surgical treatment of infection and supportive intensive therapy, modulating host inflammatory mediators as a conjunctive therapeutic option has been explored in the past decade. Although successful in animal models of sepsis, inhibiting host inflammatory response in human sepsis has failed to improve survival or otherwise show efficacy. Studies are needed which better describe the circumstances under which these therapies may ultimately prove successful.

Adjuvants, Immunologic↗