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Biomedical subjects

M Quintel

Publications and source records attributed to M Quintel.

At least 19 recordsLinked to original sources

[Cerebral effects of perfluorocarbons].

For the usage as blood substitutes perfluorocarbons (PFC) have been developed as artificial oxygen carriers. In addition they may have potency for protective use in ischemic tissue. Formulation improvement achieved higher oxygen carrying capacity and better compatibility than the first generation of PFC. Preclinical studies have been performed in animal heart and brain. Former and progressed emulsification for intravascular use have been investigated for infarction and reperfusion injury. This investigations are reviewed and the potencies for the use of PFC in neurology, neurosurgery, diagnostics today and in the future are emphasized.

Animals↗

[Horizontal deceleration trauma with diffuse decollement bleeding--a casuistry].

Treatment of severe haemorrhage caused by multiple trauma is a serious challenge to preclinical as well as clinical management. This is a case report of a motorcycle accident in which a patient sustained total amputation of both legs. Following adequate preclinical care, vital indication led to the patient's immediate surgical treatment. After initially successful haemodynamic stabilisation, the patient developed a horizontal deceleration trauma which resulted in an extended decollement of the muscles of the back and buttock. During the further clinical course, soft tissue bleeding occurred that affected the whole torso. Due to its extent, the bleeding could not be treated surgically, nor did it allow of haemodynamic stabilisation despite continuous massive transfusion. Retrospectively, the impressing amputation injury was treated successfully. In spite of all available surgical and intensive care efforts, however, the slowly demasking monstrous decollement with diffuse tissue bleeding proved to be an injury pattern leading to the patient's death.

Accidents, Traffic↗

Hypertonic saline solution for control of elevated intracranial pressure in patients with exhausted response to mannitol and barbiturates.

Critically elevated intracranial pressure (ICP) represents the most important cause of morbidity and mortality in patients suffering from severe traumatic brain injury (TBI) and is a serious complication after subarachnoid hemorrhage (SAH). Thus new strategies for the control of ICP are required. Based on the evidence available hypertonic saline solution (HSS) may be a promising approach. It was therefore the aim of the present study to evaluate in a prospective manner the effects of HSS on ICP and cerebral perfusion pressure (CPP) in patients with therapy-resistant elevation of ICP. A total of 48 bolus infusions of HSS (7.5%, 2 ml kg-1 b.w.; infusion rate 20 ml min-1) were given intravenously (range 1-15 per patient) to 10 patients (age 41 +/- 6 years) with TBI and SAH. Only patients with ICP > 25 mmHg not responding to standard ICP-management protocol and plasma sodium (Na+) concentration < 150 mmol l-1 were included in the study. Within the first hour after HSS application, ICP decreased from 33 +/- 9 mmHg to 19 +/- 6 mmHg (p < 0.05) and further to 18 +/- 5 mmHg at the time of maximum effect (98 +/- 11 min post bolus). Decrease of ICP was accompanied by a rise of CPP from 68 +/- 11 mmHg to 79 +/- 11 mmHg (p < 0.05) after 1 h and further to 81 +/- 11 mmHg at the time of maximum effect. Plasma Na+ concentration was 141 +/- 6 mmol l-1 before and 143 +/- 5 mmol l-1 1 h after HSS bolus. Corresponding values for plasma osmolality were 302 +/- 11 and 308 +/- 12 mOsm l-1. When the ICP lowering effect was transient, subsequent HSS bolus was necessary 163 +/- 54 min after previous dosing. The present results indicate that repeated bolus application of HSS (7.5% NaCl, 2 ml kg-1 b.w.) is an effective measure to decrease ICP which is otherwise refractory to standard therapeutic approaches. Whether or not the therapy scheme is also suited as primary measure for the control of ICP remains to be established.

Adult↗

HLA-DR expression in acute pancreatitis.

OBJECTIVE: To investigate the role of the monocyte/macrophage system in acute pancreatitis DESIGN: Prospective clinical study SETTING: University clinic, Germany SUBJECT: 37 consecutive patients who presented with acute pancreatitis. MAIN OUTCOME MEASURE: Correlation between function of monocytes measured by HLA-DR expression and outcome RESULTS: Patients were divided into three groups according to outcome: those with severe pancreatitis who died (n = 10), those with severe pancreatitis who survived (n = 15), and those with mild pancreatitis who survived (n = 12). There was a clear and significant difference between those with severe and those with mild disease. HLA-DR expression was initially depressed in both groups, but after the third day of treatment it started to recover significantly in those with mild disease (p < 0.05). The difference was also significant from day 7 onwards between those with severe disease who died and those with severe disease who survived (p < 0.05). CONCLUSION: Monocyte function as measured by HLA-DR expression (CD14+DR+) is reduced in patients with acute pancreatitis and does not recover in patients who are going to die (median < 20 relative antigen density units; RU).

Adult↗

[Partial liquid ventilation].

Partial liquid ventilation (PLV) is a relatively new therapeutic approach to acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). The idea of combining the intrapulmonary application of an oxygen-carrying substance and positive pressure ventilation was introduced by Fuhrman in 1991 and originally called perfluorocarbon-associated gas exchange (PAGE). Nowadays, the technique is mostly known as partial liquid ventilation (PLV). The efficacy of PVL treatment has been demonstrated in numerous animal studies in different models of lung injury. The results of those studies led to multicenter phase I-II studies in patients of all age groups in the United States and Canada. Recently, the first randomized, controlled study in 90 adult patients suffering from ALI and ARDS was completed and first results have been published. Comparison of overall mortality and number of ventilator-free days (VFD's) in a 28-day period showed no differences between PLV and conventionally treated patients. A post-hoc stratification by age (< 55 years) demonstrated a tendency to lower mortality (PLV 25.6%; CMV 36.8%) and a significant increase of VFD (PLV 8.95 days; CMV 4.11 days; p = 0.03) in PLV when compared to conventionally treated patients. Perfluorocarbons (PFCs) are chemically stable and inert. They are mostly eliminated via exhalation (> 99%). The unique physicochemical properties of PFCs permit access to atelectatic, non-ventilated lung areas, enhance gas exchange and decrease inflammation. The dense PFCs prevent the endexpiratory collapse of alveoli and reestablish functional residual capacity (FRC). Comparable to positive endexpiratory pressure (PEEP), these effects have been described as "liquid or fluid PEEP". These properties offer a new approach to the underlying pathophysiology of ALI and ARDS. In addition, the combination with other therapeutic approaches to ALI and ARDS like high-frequency oscillations (HFO), inhaled nitric oxide (NO) therapy, and surfactant replacement can be considered and is already the subject of recent publications. However, combination therapy is still experimental and further investigation is necessary to evaluate efficacy and potential risks. Many questions still exist which need to be answered by experimental as well as human pilot studies. Based on these studies, the results of ongoing human trials can be assessed properly and new multicenter trials can be planned effectively.

Blood Gas Analysis↗

Effects of partial liquid ventilation on lung injury in a model of acute respiratory failure: a histologic and morphometric analysis.

OBJECTIVE: To compare the histopathologic changes observed in a sheep model of oleic acid-induced acute respiratory failure during partial liquid ventilation with perflubron with gas ventilation. DESIGN: Randomized, controlled study. SETTING: Animal laboratory and pathology laboratories of a university hospital. SUBJECTS: Fourteen healthy adult sheep, weighing 64.9 +/- 6.4 kg. INTERVENTIONS: Lung injury was induced with oleic acid (0.15 mL/kg). A tracheostomy tube was inserted, along with systemic and pulmonary artery monitoring catheters. Animals were randomized to undergo either partial liquid ventilation (n = 7) or gas ventilation (n = 7). Animals underwent euthanasia at the end of the 90-min study period, after which the endotracheal tube was clamped with the lungs in expiratory hold at a positive end-expiratory pressure of 5 cm H2O. En bloc excision of the heart and lungs was performed by thoracotomy. Perfusion of the isolated lung vasculature with 2.5% paraformaldehyde and 0.25% glutaraldehyde in a 0.1-M phosphate buffer was performed. Histologic analysis followed. MEASUREMENTS AND MAIN RESULTS: Gas exchange increased markedly in the animals that underwent partial liquid ventilation compared with the gas-ventilated animals (PaO2 at 90 mins: gas ventilation-treatment group, 40 +/- 8 torr [5.3 +/- 1.1 kPa]; partial liquid ventilation-treatment group, 108 +/- 60 torr [14.4 +/- 8.0 kPa]; p = .004). Lung histologic analysis demonstrated a better overall diffuse alveolar damage score (partial liquid ventilation-treatment group, 12.4 +/- 1.4; gas ventilation-treatment group, 15.0 +/- 1.7; p = .01). In the partial liquid ventilation-treatment group, we observed an increase in mean alveolar diameter (partial liquid ventilation-treatment group, 82.4 +/- 2.9 microm; gas ventilation-treatment group, 67.7 x 3.9 microm; p = .0022) and a decrease in the number of alveoli per high-power field (partial liquid ventilation-treatment group, 25.7 +/- 0.9, gas ventilation-treatment group, 31.4 +/- 2.5; p = .0022), in septal wall thickness (partial liquid ventilation-treatment group, 6.0 +/- 0.6 microm; gas ventilation-treatment group, 8.3 +/- 1.0 microm; p = .0033), and in mean capillary diameter (partial liquid ventilation-treatment group, 13.0 +/- 0.8 microm; gas ventilation-treatment group, 19.9 +/- 1.4 microm; p = .0022). CONCLUSIONS: Partial liquid ventilation is associated with notable improvement in gas exchange and with a reduction in the histologic and morphologic changes observed in an oleic acid model of acute lung injury.

Animals↗

White blood cell counts and plasma C3a have synergistic predictive value in patients at risk for acute respiratory distress syndrome.

OBJECTIVE: To investigate and select nonassociated variables with predictive value for acute respiratory distress syndrome (ARDS) in patients at risk. DESIGN: Prospective, observational study. SETTING: A university hospital intensive care unit. PATIENTS: Twenty-four critically ill patients with different risk factors for ARDS. INTERVENTIONS: Arterial and mixed venous blood, as well as urine samples, were collected. Invasive hemodynamic measurements were performed. MEASUREMENTS AND MAIN RESULTS: Fifty-nine variables pertaining to the cardiorespiratory, hepatic, immunologic, and renal systems and including plasma complement activation products C3a and SC5b-9 and polymorphonuclear elastase, were determined every 6 hrs for 3 days in patients at risk for ARDS. Associations among variables were investigated and the predictive value of nonassociated variables for ARDS was determined. Patients who developed ARDS (n=8) had lower white blood cell counts at the time they entered the study (p=.006) and during the first 24 hrs thereafter (p=.032). Also, plasma C3a concentrations were markedly higher during the first 24 hrs in patients who developed ARDS (p=.006). Plasma C3a had better predictive value than did white blood cell counts for cutoff points set by discriminant analysis at 1075 ng/mL (1.075 x 10(-3) g/L) and 5700 cells/mL, respectively. The combination of both variables in a discriminant function improved the predictive value for ARDS. CONCLUSIONS: The most notable and nonassociated alterations observed in patients who developed ARDS were lower white blood cell counts and higher plasma C3a concentrations compared with counts and concentrations in patients who did not develop ARDS. Plasma C3a concentrations showed better predictive value than white blood cell counts. The combination of white blood cell counts with plasma C3a concentrations synergistically improved the predictive value for ARDS. This combination may prove useful for identifying subpopulations at highest risk for ARDS and may contribute to make treatment at an early stage of the syndrome possible.

Adolescent↗

Rapid active internal core cooling for induction of moderate hypothermia in head injury by use of an extracorporeal heat exchanger.

OBJECTIVE: Moderate hypothermia (32 degrees C) may limit postischemic neuronal damage and is increasingly used clinically in head injury and stroke. For the use of hypothermia as a neuroprotective agent in the prevention of ischemic damage, it is necessary to induce it as soon as possible after the insult and to keep it at the lowest safe level. Active core cooling using an extracorporeal heat exchanger may circumvent the rather slow induction speed and temperature drifts experienced with surface cooling techniques. METHODS: In eight patients with severe head injuries (Glasgow Coma Scale score, 4-5), a venovenous extracorporeal circulation was established via a percutaneously introduced double-lumen cannula in the femoral vein. A heat exchanger was connected via a pressure-controlled roller pump. In addition to standard parameters, brain white matter temperature was continuously recorded as the target temperature. Cooling was initiated as early as possible with an extracorporeal temperature of 30 degrees C and maintained at a 32 degrees C brain temperature for 48 hours, and then gradual rewarming for 24 hours. RESULTS: Cooling was able to be initiated within 6 hours and 48 minutes +/- 3 hours and 47 minutes (mean +/- standard deviation) after trauma. A brain temperature of 32 degrees C was reached within 1 hour and 53 minutes +/- 1 hour and 21 minutes after induction of cooling with a cooling speed of 3.5 degrees C per hour. Brain temperature was able to be controlled within 0.1 degrees C intervals, which was especially helpful in gradual rewarming. No cardiac abnormalities or statistically significant changes in coagulation parameters occurred. Mean platelet count decreased to 89,614+/-42,090 on Day 3 after treatment. No clinical bleeding complications or problems resulting from extracorporeal circulation occurred. Moderate hypothermia was a helpful tool for managing increased intracranial pressure; however, five patients of this series died either of their intracranial abnormalities (n = 4) or of a delayed septic shock after pneumonia (n = 1) at various points in time during therapy. The three survivors experienced either an excellent or a good recovery. CONCLUSION: The results of this investigation suggest that the use of an extracorporeal heat exchanger to achieve active core cooling is suitable for fast and accurately controllable induction, maintenance, and reversal of moderate hypothermia in emergency situations with reliable control of temperature. In this small series of highly selected patients with severe head injuries, we did not note a beneficial effect of hypothermic therapy on outcome.

Adult↗

Computer tomographic assessment of perfluorocarbon and gas distribution during partial liquid ventilation for acute respiratory failure.

The average in vivo chest computed tomographic (CT) attenuation number (air = -1,000, soft tissue = 0, perflubron = +2,300 Hounsfield units [HU]) of 10 ventrodorsal-oriented lung segments was calculated to assess the distribution of gas and perflubron in 14 oleic acid lung-injured adult sheep during partial liquid ventilation (PLV, n = 7) or gas ventilation (GV, n = 7). Partial liquid ventilation was associated with a significant decrease in shunt fraction (PLV = 40 +/- 12%, GV = 76 +/- 12%, p = 0.004). Computed tomographic attenuation data during expiration (HUexp) demonstrated minimal gas aeration in GV animals in the dependent (segments 6-10) lung zones (HUexp = -562 +/- 108 for segments 1-5, HUexp = -165 +/- 104 for segments 6-10, p = 0.015). During PLV, perflubron was predominantly distributed to the dependent lung regions (HUexp = 579 +/- 338 for segments 1-5, HUexp = 790 +/- 149 for segments 6-10, p = 0.04). The ratio of the inspiratory to expiratory HU (HUinsp/exp) was greater in dependent than nondependent regions (mean HUinsp/exp segments 1-5 = 0.56, segments 6-10 = 0.81, p = 0.01), indicating that during inspiration relatively more gas than perflubron was distributed to the nondependent lung regions. We conclude that during PLV in this lung injury model, (1) gas exchange is improved when compared with gas ventilation, (2) perflubron is distributed predominantly to the dependent regions of the lung, and (3) although gas is distributed throughout the lung with each inspiration, more gas than perflubron goes to the nondependent lung regions.

Acute Disease↗

Partial carbon dioxide rebreathing: a reliable technique for noninvasive measurement of nonshunted pulmonary capillary blood flow.

OBJECTIVE: To determine the validity and clinical utility of the partial CO2 rebreathing technique for measurement of nonshunted pulmonary capillary blood flow and cardiac output. DESIGN: Prospective, controlled animal laboratory investigation and clinical trial. SETTINGS: Animal research facility and intensive care unit of a university hospital. SUBJECTS: Fifteen adult sheep, weighting 58 to 78 kg. PATIENTS: Mechanically ventilated patients with different underlying diseases (n = 12) and with adult respiratory distress syndrome (ARDS) (n = 8). INTERVENTIONS: CO2 elimination rate (VCO2) was measured breath-by-breath with a system developed for the study and also by gas collection (validation procedure in patients with different underlying diseases). Partial CO2 rebreathing maneuvers, cardiac output by thermodilution, and blood gas analysis were performed in sheep with lung atelectasis and in patients with ARDS. MEASUREMENTS AND MAIN RESULTS: The degree of correlation between VCO2 measured with the system developed and gas collection was very good (r2 = .95, p < .0001), and bias and precision calculations (1 +/- 9 mL/min) showed close agreement between methods. The overall degree of correlation between partial CO2 rebreathing measurements and cardiac output was moderate (r2 = .54, p < .0001), the noninvasive method tending to underestimate cardiac output, as shown by bias and precision calculations (-1.69 +/- 1.90 L/min). In contrast, the overall degree of correlation between partial CO2 rebreathing measurements and nonshunted pulmonary capillary blood flow was good (r2 = .73, p < .0001). Bias and precision calculations (0.25 +/- 0.83 L/min) showed a tendency for the partial CO2 rebreathing technique to slightly overestimate pulmonary capillary blood flow. Variance differences between partial CO2 rebreathing measurements and cardiac output could be mostly explained by intrapulmonary right-to-left shunt fraction (r2 = .51, p < .0001). CONCLUSIONS: Our results support the use of the system developed for breath-by-breath VCO2 measurements. The lack of agreement between partial CO2 rebreathing measurements and cardiac output was mostly explained by intrapulmonary right-to-left shunt, suggesting that this technique may not be appropriate for monitoring cardiac output in patients with increased venous admixture. In contrast, our results demonstrate that the partial CO2 rebreathing technique is reliable for measurement of the effective nonshunted pulmonary capillary blood flow. This technique may prove useful to guide ventilatory therapy adjustments in an attempt to optimize nonshunted pulmonary capillary blood flow.

Adult↗

[The role of extracorporeal membrane oxygenation (ECMO) in current neonatology].

Two hundred term or near-term neonates were referred to an ECMO center for severe PPHN associated diseases. In 2 time periods from 1987 to 1991 and from 1992 to December 1995 alternative treatment modes were tried in an attempt to obviate ECMO. During the first time period patients underwent a trial of high-frequency oscillatory (HFOV) ventilation before ECMO. In the second time period patients first received inhaled NO followed by HFOV in non-responders. If this also failed HFOV was combined with iNO. In both time periods about 40% of the patients were spared ECMO treatment by these alternative treatment modalities. INO only benefited 15% of the ECMO candidates who apparently had fared just as well on HFOV alone in the preceding time period. While patients who were improved by iNO were spared HFOV with its potential severe complications, i.e. air leaks and cardiocirculatory instability. More extended long-term studies will have to show which of these 2 treatment modalities (iNO or HFOV) should be given-first priority in an attempt to avoid ECMO in neonates with severe respiratory failure.

Extracorporeal Membrane Oxygenation↗

[Clinical significance of cytokines Il-6, Il-8 and C-reactive protein in serum of patients with acute pancreatitis].

The detection of cytokines may elucidate the pathophysiological mechanisms that produce early systemic complications in acute interstitial (i) or necrotizing (n) pancreatitis (AP). The increase in the level of cytokines in the blood of patients with AP may correlate with the severity of the disease. In a prospective clinical trial from October 1992 to August 1993, 23 patients with AP were recruited and blood samples taken for cytokine detection by commercially available Elisa kits and C-reactive protein (CRP) by laser nephelometry. Six of 11 patients with nAP died either early (n = 1) or of late septic complications. None died of iAP. The peak of cytokine and CRP level in the first 3 days of hospitalization was used for calculation. The IL-6 concentration in the blood reached up to 2600 pg/ml in the 1st few days, depending on the severity of AP, and dropped to almost zero in the next days, independently of the clinical course. The differentiation of i- versus nAP, using a cut-off line of 600 pg/ml, was correct in 20 patients [87%, sensitivity (SE): 82%, specificity (SP): 91%, P < 0.001]. The blood levels of IL-8 reached a maximum of 1381 pg/ml in the 1st few days, depending on the severity of AP, and showed a correlation with the clinical course in the following days. The peak of IL-8 blood levels indicated correctly the severity of AP in 18 out of 23 patients using a cutoff level of 200 pg/ml (accuracy: 78%, SE: 82%, SP: 75%, P < 0.01). The CRP levels increased up to a maximum of 535 mg/l and indicated the course of AP correctly in 18 out of 22 patients (SE and SP 82%, P < 0.01). There was no correlation between cytokine blood levels and mortality. In the blood samples of five patients with i- or nAP, no TNF-alpha was detectable. The blood levels of IL-6, and to a lesser extent of IL-8 and CRP, can predict the severity and early systemic complications of AP. The excessive rise in cytokines can be explained by the stimulation of immunological cells (macrophages, lymphocytes and endothelial cells) in the course of AP, inducing early systemic complications.

Acute Disease↗