Biomedical subjects

P G Raijmakers

Publications and source records attributed to P G Raijmakers.

14 recordsLinked to original sources

PubMed1998

The 67gallium-transferrin pulmonary leak index in patients at risk for the acute respiratory distress syndrome.

OBJECTIVE: To determine the occurrence and clinical importance of increased pulmonary microvascular permeability in patients at risk for acute respiratory distress syndrome (ARDS). DESIGN: Prospective, cohort study. SETTING: Medical and surgical intensive care unit (ICU) and department of nuclear medicine of a university hospital. PATIENTS: Thirteen consecutive patients at risk for ARDS with sepsis (n = 4), multiple trauma (n = 3), hemorrhagic pancreatitis (n = 5), and near-drowning (n = 1), admitted into the ICU. All patients were intubated and mechanically ventilated in the course of the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 67gallium-transferrin pulmonary leak index (PLI) (upper limit of normal in patients scheduled for major surgery 14.7 x 10(-3)/min) was measured within 24 hrs of admission. In addition, radiographic, gas exchange, and ventilatory variables allowing calculation of the Lung Injury Score, were obtained on the day of the PLI (day 0) and from days 1 to 7. Patients were followed until discharge or death in the ICU. No patient developed ARDS (Lung Injury Score of >2.5 in the absence of congestive heart failure) and all but four patients survived. The PLI (median [range]) was 18.5 (7.0 to 81.9) x 10(-3)/min and was supranormal in 8 of 13 patients (p < .001 vs. normal). The PLI correlated with the Simplified Acute Physiology Score (SAPS) II (r[s] = .79, p < .01) and was higher in nonsurvivors than in survivors (p < .05), with a tendency for a higher SAPS II in the nonsurvivors. On day 0, the chest radiographic score of alveolar abnormalities was 0 (0 to 4), indicating absence of radiographic abnormalities in most patients. Also, on day 0, the median PaO2/FIO2 ratio was 257 (range 119 to 460). The Lung Injury Score on day 0 was 1.0 (0 to 2.0), which is consistent with mild acute lung injury in all but one patient. In the course of time, the oxygenation ratio was lower and the Lung Injury Score was higher in nonsurvivors than in survivors, particularly for the Lung Injury Score on days 1 and 2. The PLI correlated directly with the Lung Injury Score on days 0 and 1. On day 0, the PLI correlated inversely with the oxygenation ratio. On the last evaluable day of the first ICU week, the PLI correlated directly with the Lung Injury Score and the positive end-expiratory pressure level. The duration of mechanical ventilation tended to be longer in patients with a supranormal PLI. CONCLUSIONS: In this small population, 61% of patients at risk for ARDS and with only mild respiratory changes exhibited increased microvascular permeability in the lungs at ICU admission. Increased permeability may be an early marker of acute lung injury and its clinical features, and may be associated with a relatively complicated respiratory course during the first week after admission, even in the absence of progression to ARDS. Finally, increased pulmonary microvascular permeability may be associated with severe underlying disease and ultimate mortality in the ICU.

Adult↗

PubMed1997

The inflammatory response to vascular surgery-associated ischaemia and reperfusion in man: effect on postoperative pulmonary function.

OBJECTIVES: To characterise the inflammatory response to vascular surgery and ischaemia/reperfusion (I/R) in man, regarding release of inflammatory mediators, recruitment and activation of neutrophils, and their relation to postoperative pulmonary function. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Circulating neutrophil counts and plasma levels of elastase-alpha 1-antitrypsin (AT), a neutrophil degranulation product, were measured before and approx. 2.5 h (group 1, n = 19) after elective abdominal aortic surgery, and approx. 2.9 h after elective peripheral vascular surgery (group 2, n = 6), together with concentrations of neutrophil agonists, including activated complement (C3a), secretory phospholipase A2 (sPLA2), tumor necrosis factor (TNF-alpha), interleukin (IL)-6, IL-8 and granulocyte colony-stimulating factor (G-CSF). At the time of blood sampling, respiratory variables allowing computation of the lung injury score (LIS) were obtained in patients admitted after surgery in the intensive care unit (ICU), i.e. all group 1 patients and one group 2 patient. RESULTS: Median (range) neutrophil counts rose by 80% (-28-208) and 90% (10-147) in groups 1 and 2, respectively (n.s. between groups). The increase (p < 0.05) in elastase-alpha 1-AT level was 121% (-5-439) in group 1 and 82% (18-792) in group 2 (n.s. between groups). There was a rise (p < 0.05) in C3a level by 93% (-42-751) and of sPLA2 level by 68% (-40-1400) after surgery for the groups together (n.s. between groups), and the rise of the elastase-alpha 1-AT related to that of the C3a levels. IL-6 and G-CSF concentrations increased more in group 1 than 2. The IL-8 concentration increased in group 1 only, and TNF-alpha was unchanged in all groups. In ICU patients, the LIS related to the postoperative rise in IL-6 level only, even though the rise in plasma concentrations of cytokines interrelated. No patient developed ARDS and all survived. CONCLUSIONS: Vascular surgery and I/R in man activates complement, releases cytokines (except for TNF-alpha), and induces neutrophil recruitment and degranulation, which may primarily depend on complement activation. In contrast to the latter, the release of cytokines may depend on the extent of I/R and may contribute to transient pulmonary dysfunction after extensive I/R.

Adult↗

PubMed1997

The 67gallium-transferrin pulmonary leak index in pneumonia and associated adult respiratory distress syndrome.

1. The aim of the study was to determine the role of increased microvascular protein permeability, as measured by the 67gallium (Ga)-transferrin pulmonary leak index, in pneumonia and associated adult respiratory distress syndrome (ARDS). 2. Eighteen consecutive patients with microbiologically confirmed pneumonia (radiographic infiltrates, purulent sputum) and needing respiratory monitoring (n = 2) or mechanical ventilation (n = 16) in the intensive care unit were studied prospectively. The pulmonary leak index using 67Ga-transferrin and 99mTc red blood cells was measured with a mobile probe system over both lung apices (normal value below 14.1 x 10(-3) min-1) within 72 h of intensive care unit admission, and the lung injury score was calculated from radiographic, ventilatory and lung mechanical data. 3. Patients with pneumonia (lung injury score < 2.5, n = 10) had a lower (P < 0.01) pulmonary leak index, averaged for both lungs, with a median of 23.9 [range (7.0-47.0) x 10(-3) min-1] than patients with pneumonia-associated ARDS (lung injury score > or = 2.5, n = 8), and an average pulmonary leak index of 37.5 [(23.4-144.2) x 10(-3) min-1], so that, for all patients, the pulmonary leak index, averaged for both lungs, directly related to the lung injury score (r2 = 0.61, P < 0.01). A normal average pulmonary leak index excluded pneumonia-associated ARDS. Patients with unilateral pneumonia had a greater inter-lung difference (P < 0.01) in the pulmonary leak index between affected and unaffected lung than patients with bilateral pneumonia. The index did not have prognostic significance. 4. The 67Ga-transferrin pulmonary leak index parallels the degree of radiographic, ventilatory and lung mechanical abnormalities of pneumonia and evolving ARDS. The data support the idea that the clinical manifestations of pneumonia culminating in ARDS directly relate to the degree of microvascular injury. Conversely, the pulmonary leak index may be used to monitor the effect of anti-inflammatory drugs in the adjunctive treatment for severe pneumonia aimed at circumventing mechanical ventilation in future studies.

Adult↗

PubMed1997

Acute lung injury after aortic surgery: the relation between lung and leg microvascular permeability to 111indium-labelled transferrin and circulating mediators.

BACKGROUND: Aortic surgery is a risk factor for acute lung injury and this may relate to ischaemia/reperfusion (I/R) of the lower body and release of inflammatory mediators. The aim of this study was to define the changes in microvascular protein permeability and circulating inflammatory mediators after aortic surgery. METHODS: In 11 consecutive patients who underwent elective aortic surgery microvascular permeability in lung and leg was measured before and a median of 2.8 hours after completion of surgery using 111indium (In)-labelled transferrin and 99mtechnetium (Tc)-labelled red blood cells, yielding a protein leak index (PLI) that is specific for protein permeability. Circulating leucocyte counts and levels of inflammatory mediators were determined. RESULTS: In the lung the PLI rose from a median of 0.6 (range -0.5 to 2.2) x 10(-3)/min before surgery to 5.4 (-2.3 to 33.5) x 10(-3)/min after surgery, and in the leg from 0.3 (-1.6 to 1.7) x 10(-3)/min to 5.0 (1.0 to 27.8) x 10(-3)/min. The increase in PLI in the lung was related to that in the leg. Levels of activated complement C3a and tumour necrosis factor-alpha did not change, but levels of interleukin (IL)-6, IL-8 and elastase-alpha 1-antitrypsin increased. After surgery there was slight neutrophilia and the leucocyte counts were inversely related to the IL-8 level. The rise in lung but not in leg PLI was greatest in patients with the highest IL-8 levels and the lowest leucocyte counts. CONCLUSIONS: Early after aortic surgery microvascular protein permeability increases in the leg and lung. Leg I/R injury may result in neutrophil activation and release of IL-8, which may induce neutrophil sequestration and subsequently increased pulmonary microvascular permeability. These findings may help to explain the occurrence of acute lung injury after I/R in man.

Adult↗

PubMed1997

Systemic coagulation and fibrinolysis in patients with or at risk for the adult respiratory distress syndrome.

The authors sought to evaluate the pathogenetic and prognostic role of a procoagulant and hypofibrinolytic state in the adult respiratory distress syndrome (ARDS). Twenty-two consecutive patients admitted to the intensive care unit (ICU) for respiratory monitoring (n = 2) or mechanical ventilation (n = 20) were studied, of whom 13 had ARDS and 9 were at risk for the syndrome. Plasma levels of thrombin-antithrombin III complexes (TAT), the plasmin-alpha2-antiplasmin complexes (PAP), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were measured within 48 h after admission, together with respiratory variables allowing computation of the lung injury score (LIS), and pulmonary microvascular permeability [67Gallium-transferrin pulmonary leak index (PLI)], as measures of pulmonary dysfunction. Blood was also sampled 6-hourly until 2 days after admission. The LIS and PLI were higher in ARDS than at risk patients, in the presence of similar systemic morbidity and mortality. TAT complexes were elevated in a minority of patients of both groups, whereas the PAP, tPA and PAI levels were elevated above normal in the majority of ARDS and at risk patients, but groups did not differ. Neither circulating coagulation nor fibrinolysis variables correlated to either LIS or PLI. Furthermore, the course of haemostatic variables did not relate to outcome. These data indicate that systemic activation of coagulation and impaired fibrinolysis do not play a major role in ARDS development and outcome in patients with acute lung injury.

Adult↗

PubMed1996

What is the cause of pulmonary oedema after acute myocardial infarction? A case study.

A patient is described with an acute myocardial infarction (AMI) and pulmonary oedema, necessitating mechanical ventilation, at a mean pulmonary capillary wedge pressure (PCWP) below 13 mmHg. The 67Ga-transferrin pulmonary leak index (PLI), a measure of microvascular permeability, was normal. A study of the course of the PCWP revealed intermittent elevations up to 22 mmHg, owing to intermittent mitral regurgitation. Pulmonary oedema after an AMI can thus be caused by pressure factors, even at sporadic elevations of PCWP, following intermittent, ischaemia-induced dysfunction of the posterior papillary muscle. Conversely, the measurement of a normal 67Ga-PLI may help to diagnose hydrostatic as opposed to permeability pulmonary oedema, if sporadic elevations of the PCWP are not recognised.

Humans↗

PubMed1996

The 67gallium pulmonary leak index in assessing the severity and course of the adult respiratory distress syndrome.

OBJECTIVE: To establish the value of the 67Gallium (Ga) pulmonary leak index, a marker of increased permeability edema of the lungs, in assessing the severity and course of the adult respiratory distress syndrome (ARDS). DESIGN: Prospective observational study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Seventeen consecutive, mechanically-ventilated ARDS patients. Eleven patients (recovering from ARDS) improved, as defined by the ability to taper the level of positive end-expiratory pressure (PEEP) to 0 cm H2O at a median of 7 days after admission. Ten patients survived. Six patients did not recover and died a median of 3.5 days after admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pulmonary leak index (i.e., upper limit of normal 14.1 x 10(-3)/min) was measured within 72 hrs after admission, and repeated within 48 hrs at the time of recovery in recovering patients. At admission and recovery, respiratory variables were recorded and a lung injury score was calculated. At admission, the pulmonary leak index was increased in each patient to 32.3 (range 15.6 to 52.4) and 28.7 (range 26.0 to 40.8) x 10(-3)/min in recovering and nonrecovering patients, respectively (NS). Groups did not differ with respect to the oxygenation ratio, the level of PEEP, radiographic abnormalities, and the lung injury score. At recovery, the pulmonary leak index in recovering patients had decreased in each patient and had normalized in four patients, averaging 15.2 (range 5.6 to 25.9) x 10(-3)/min, concomitantly with an increased oxygenation ratio, less radiographic abnormalities, and a decreased lung injury score (p < .01 vs. admission). For pooled recovering and nonrecovering patient data, the pulmonary leak index directly related to the lung injury score (p < .005). CONCLUSIONS: The 67Ga pulmonary leak index may be a clinically useful tool to quantify the severity and course of ARDS, since clinical recovery from the syndrome may be characterized by amelioration of increased microvascular permeability.

Adult↗

PubMed1996

Diagnostic value of the gallium-67 pulmonary leak index in pulmonary edema.

UNLABELLED: We studied the value of a noninvasive, bedside, dual-radionuclide method (67Ga-circulating transferrin and 99mTc-red blood cells) to measure pulmonary microvascular permeability in efforts to discriminate between pulmonary edema due to adult respiratory distress syndrome (ARDS) and hydrostatic pulmonary edema (HPE). METHODS: Patients had respiratory insufficiency and bilateral alveolar pulmonary edema on chest radiographs. All patients, except one, were mechanically ventilated. Patients, were divided into groups according to various sets of etiologic, hemodynamic and ventilatory factors. Group 1 (n = 8) had risk factors for HPE only. Group 2 (n = 5) had risk factors for both ARDS and HPE, such as a pulmonary capillary wedge pressure (PCWP) above 18 torr. Group 3 (n = 13) had risk factors for ARDS only and a PCWP below 18 torr. Patients were also classified on the basis of a lung injury score, using radiographic and ventilatory variables. Group 4 (n = 12) had a score below 2.5 and Group 5 (n = 14) above 2.5, arbitrarily defined as ARDS. Any radioactivity measurements over the lungs and in blood within 72 hr after admission were used to calculate the 1 hr pulmonary leak index as a measure of microvascular permeability (upper limit of normal 14.1 x 10(-3).min-1). RESULTS: The PLI ( x 10(-3).min-1) was median 10.2 (range 4.4-16.2) in Group 1, 26.8 (14.2-31.9) in Group 2 and 32.3 (23.0-52.4) in Group 3 (p < 0.001). It was 13.3 (4.4-39.9) in Group 4 and 31.1 (14.2-52.4) in Group 5 (p < 0.01). Using the various definitions, the sensitivity of a supranormal pulmonary leak index for ARDS was 100% and the specificity varied between 46% and 75%. In receiver operating characteristic curves, the pulmonary leak index performed best when ARDS and HPE were defined on the basis of risk factors only, and performed better than hemodynamic and equally well as ventilatory variables in discriminating between edema types, if definitions of the latter were mainly based on hemodynamic and ventilatory variables, respectively. CONCLUSION: The 67Ga pulmonary leak index is a useful tool to differentiate ARDS from HPE.

Aged↗

PubMed1995

Interleukin 8-related neutrophil elastase and the severity of the adult respiratory distress syndrome.

The interaction between activated neutrophils and pulmonary endothelium is thought to contribute to the pathogenesis of the adult respiratory distress syndrome (ARDS), but its relation to ARDS severity, which may support a pathogenetic role, is unclear. Therefore, circulating inflammatory mediators, including the neutrophil chemoattractant and activator interleukin 8 (IL-8), the acute phase cytokine IL-6, and the neutrophil product elastase complexed to alpha 1-antitrypsin (alpha 1-AT), were measured prospectively, together with gas exchange, ventilatory and radiographic variables, in 13 mechanically ventilated patients with ARDS, mostly owing to sepsis, at admission into the intensive care unit. Measurements were repeated in the eight improving patients at the time that positive end-expiratory pressure could be reduced to 0 cm H2O. From the gas exchange, ventilatory and radiographic abnormalities, a lung injury score (LIS) was calculated. For pooled data, the LIS and the arterial PO2/inspiratory O2 fraction, the oxygenation ratio, correlated with plasma levels of IL-8 (rs = 0.60, P < 0.01 and rs = -0.65, P < 0.005, respectively), with levels of IL-6 (rs = 0.60, P < 0.01, and rs = -0.68, P < 0.005, respectively), and the oxygenation ratio related to elastase-alpha 1-AT (rs = -0.70, P < 0.005). Levels of IL-8 and IL-6 interrelated (rs = 0.61, P < 0.01) and related to the elastase complexes (rs = 0.45, P < 0.05). Hence, our data support a role of cytokine-induced activation of neutrophils in the clinical severity of ARDS.

Adult↗

PubMed1995

Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Delayed resolution of pulmonary oedema after cocaine/heroin abuse.

Pulmonary oedema lasting six days occurred in a 68 year old man after sniffing cocaine. He also had evidence of parenteral self-administration of heroin. Pulmonary microvascular filtration pressure and permeability were normal. Delayed resolution of the pulmonary oedema may have been caused by a cocaine-induced impairment of sodium and thus fluid transport across alveolar epithelium. Recognition may be important, since lowering filtration pressure with diuretics may not hasten resolution of oedema.

Aged↗

PubMed1993

Transvascular transport of 67Ga in the lungs after cardiopulmonary bypass surgery.

STUDY OBJECTIVE: To examine the effect of cardiac surgery with cardiopulmonary bypass (CPB) on pulmonary vascular permeability. DESIGN: A prospective, serial study. SETTING: Department of nuclear medicine and intensive care units of a university hospital. PATIENTS: Twelve consecutive patients were studied, before and immediately after elective cardiac surgery using CPB (group 1), and 4 consecutive, artificially ventilated patients with acute cardiogenic pulmonary edema (group 2). MEASUREMENTS AND RESULTS: The kinetics in blood and over both lungs were measured, using two mobile probes at the bedside, of intravenously injected 67Ga, assumed to bind to circulating transferrin, and in vitro 99mTc-labeled red blood cells to account for pulmonary blood volume. From data recorded in time (1 h), a pulmonary leak index (PLI), the time constant of transport of 67Ga from the intravascular to the extravascular space of the lung, was calculated and values for both lungs were averaged. In group 1, the PLI (.10(-3).min-1, mean +/- SD) was 8.2 +/- 3.7 before and 17.0 +/- 13.5 after CPB surgery (p < 0.01) and changes directly related to the duration of CPB. In four patients with a CPB duration > or = 120 min, the PLI, 31.1 +/- 16.3.10(-3).min-1, exceeded 2 SD plus mean preoperative PLI. Changes in PLI tended to relate inversely to changes in arterial WBC, which, in turn, inversely related to CPB duration. The PaO2/FIO2 ratio decreased and tended to relate inversely to PLI after surgery. No patient developed alveolar pulmonary edema on chest radiograph. In group 2, the PLI was 11.1 +/- 3.1.10(-3).min-1 (NS from group 1 preoperative PLI). CONCLUSIONS: Cardiopulmonary bypass induces a pulmonary vascular leak, as assessed by 67Ga kinetics using a bedside detection technique, in some cardiac surgery patients with prolonged CPB. This leak may reflect pulmonary vascular injury and increased permeability, following activation of leukocytes by CPB and subsequent pulmonary sequestration, rather than increased filtration through pressure factors. It may contribute to impaired gas exchange, even in the absence of manifest alveolar edema of the lungs, after surgery.

Acute Disease↗

PubMed1992

Transport of 67Ga and 111In across a membrane. Role of plasma binding and concentration gradients.

If i.v. injected radiogallium does not firmly bind to circulating transferrin in plasma, the transvascular transport of the radionuclide may be affected by diffusion of unbound radionuclide and interstitial transferrin, and may therefore not be specific for transferrin transport. Using equilibrium dialysis, the avidity of 67Ga and 111In to bind to plasma transferrin was compared by evaluating transport of unbound radionuclide across a semipermeable membrane, as a function of the plasma (transferrin) concentration gradient. One chamber of a dialysis cell was filled with human plasma and 67Ga or 111In, and the other, separated by the membrane, with increasing concentrations of plasma in normal saline. The half-time (mean +/- S.D.) for reaching equilibrium between the chambers decreased (P less than 0.05) for 67Ga from 13.1 +/- 3.3 to 4.9 +/- 1.6, 3.7 +/- 1.2 and 3.0 +/- 0.5 h, at plasma concentrations of 0, 25, 50 and 100%, respectively. The equilibrium half-time for 111In did not fall at increasing plasma concentrations and was higher (P less than 0.005) than for 67Ga at 25 to 100% plasma. Hence, 67Ga is not as avidly bound to plasma transferrin as 111In, since, in contrast to 111In, dissociation of the 67Ga-transferrin complex and transmembrane diffusion of unbound 67Ga increases when the plasma transferrin concentration gradient decreases. In vivo, the transvascular transport of 67Ga may be influenced by diffusion of unbound radionuclide, depending on the interstitial transferrin concentration, and may not be a specific indicator of transvascular protein transport.

Biological Transport↗

PubMed1991

Teaching the plantar reflex.

The efficacy of an instructional videotape about the interpretation of the plantar response was evaluated during a two week neurological clerkship. Experimental groups saw the videotape, control groups did not. All students (n = 65) assessed plantar responses of two to four different patients. Their judgment was compared with that of one senior neurologist. Only the students who had seen the videotape showed a significant improvement in performance on a second test (t-test, t = -2.26, p = 0.031). In addition, these students more frequently took account of the flexion synergy (Fisher exact test, p less than 0.001). Video can be an efficient tool in medical education.

Adult↗