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Biomedical subjects

M Haller

Publications and source records attributed to M Haller.

At least 55 records · Page 3Linked to original sources

[The effects of aprotinin. Blood loss and coagulation parameters in orthotopic liver transplantation: A clinical-experimental, prospective and randomized double-blind study].

The effect of aprotinin (2,000,000 IU as a bolus +500,000 JU/h until the end of the operation) on transfusion requirements and coagulation parameters in orthotopic liver transplantation (study group: n = 9; placebo group: n = 9) was investigated in a randomised, double-blind study. Coagulation parameters were monitored intraoperatively using a mobile laboratory. In contrast to the published results, no effect on transfusion requirements could be demonstrated. However, aprotinin showed a positive effect on some coagulation parameters in the reperfusion phase. The mechanism appeared to be inhibition of the contact activation of the intrinsic system with less thrombin generation in the study group.

Aprotinin↗

[ARDS and Wegener granulomatosis].

UNLABELLED: Wegener's granulomatosis is a distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tract and glomerulonephritis. This disease can present as a clinical picture which resembles sepsis and adult respiratory distress syndrome (ARDS). Wegener's disease requires immunosuppression which can have detrimental consequences when used in sepsis. The following case report illustrates the diagnostic difficulties encountered by intensive care physicians treating severe pulmonary failure and multiple organ dysfunction in Wegener's granulomatosis appearing as ARDS with sepsis. CASE REPORT: A 19-year-old female patient had developed acute respiratory and renal failure after a prolonged period (many months) of antibiotic resistant otitis, sinusitis and mastoiditis. The patient had required intubation at another hospital and there was a history of tension pneumothorax and cardiopulmonary resuscitation during mechanical ventilation. Emergency extracorporeal membrane oxygenation (ECMO) for acute hypercapnic and hypoxic respiratory failure was instituted and the patient was transported to our institution while on ECMO. The patient was treated empirically for suspected pulmonary and systemic infection and received hydrocortisone (0.18 mg/kg/h) as part of a protocol-driven treatment of septic shock in addition to antibiotic and antimycotic regime. The use of ECMO was required for 10 and mechanical ventilation for another 50 days after admission. After successful extubation, central nervous system dysfunction became evident with a somnolent and generally unresponsive patient. When the hydrocortisone dose was gradually tapered, the clinical status of the patient further deteriorated, pulmonary gas exchange worsened and she developed renal failure with proteinura and hematuria. A renal biopsy was performed demonstrating vasculitis and focal segmental glomerulonephritis, a systemic granulomatous vasculitis was suspected; the serum was tested for anti-proteinase 3 antibodies (PR3-ANCA) and turned out to be positive (17.5 U/ml; normal range < 7 U/ml). The morphologic findings from renal biopsy, the positive test for antiproteinase 3 antibodies and the pulmonary-renal involvement with evidence of multisystem disease established the diagnosis of Wegener's granulomatosis. Immunosuppressive therapy with cyclophosphamide and prednisolone was instituted resulting in rapid improvement with recovery of pulmonary, renal and central nervous system function within two weeks. The use of ECMO in this patient served as a life-saving immediate measure usefull to "buy time" until a definite diagnosis could be established. ARDS represents an uniform pulmonary reaction to a large number of different noxious stimuli and disease entities. This case demonstrates that intensive care physicians caring for critically ill patients with ARDS should include even rare causes of pulmonary injury into their differential diagnosis.

Acute Kidney Injury↗

A case-based consiliarius for therapy recommendation (ICONS): computer-based advice for calculated antibiotic therapy in intensive care medicine.

We report here on the system ICONS which utilizes case-based reasoning for medical decision support. As an application domain we have chosen the medical field of 'calculated antibiotic therapy' in an intensive care medicine setting. The system ICONS which runs on a personal computer suggests adequate antibiotic therapy regimen satisfying medical and economic conditions. To speed up the process of finding an adequate antibiotic therapy for a current patient, case-based reasoning is used for finding previously documented similar cases and for modifying them according to the requirements of the current patient. To reduce the memory capacity for the documentation of cases, collections of similar cases are clustered to prototypes. Medical knowledge is represented within a hierarchy of such prototypes and cases and an additional context-sensitive background knowledge-base. A knowledge acquisition tool was programmed that allows revisions of the background medical knowledge-base by simple and comprehensive methods. In addition to the advantage of producing site-specific and time-dependent knowledge, case-based reasoning is a practical method for speeding-up the process of generating and evaluating hypotheses in medical classification tasks.

Anti-Bacterial Agents↗

Red cell transfusion therapy in the critical care setting.

According to our own experience and published reports the frequency of red cell transfusion in intensive care units is in the range of 0.2 to 0.4 units per patient per day and is dependent upon the local strategy, the patients involved and the kind of surgery performed. The rationale for red cell transfusion is to maintain or restore the oxygen carrying capacity of the blood to avoid tissue hypoxia which occurs when oxygen delivery drops below a certain critical value. Besides bleeding, phlebotomy is also a significant source of blood loss in critically ill patients. According to several recent reviews and consensus articles there is no basis for a fixed indicator for transfusion, such as a haemoglobin concentration of < 100 gL-1. The decision to transfuse has to be made according to the patients individual status. The major adaptive mechanism in response to acute anaemia is an increase in cardiac output and hence blood flow to tissues. As a consequence even moderate degrees of acute anaemia may not be tolerated by patients with cardiac disease, whilst marked anaemia carries a considerable risk of ischaemia in patients with brain lesions or cerebral arterial stenoses. In critically ill patients it has been postulated that supply dependency of oxygen consumption occurs over a wide range of oxygen delivery, far above the critical values of oxygen delivery seen under normal conditions. Maximising oxygen delivery was therefore formulated as a goal in these patients. However, whether pathological supply dependency of oxygen delivery really exists in critically ill patients is still under discussion and recent studies found no benefit in maximising oxygen delivery to this patient group. However, individualised triggers for red blood cell transfusion are adequate for critically ill patients considering their co-morbidities and severity of disease. Finally, the decision to transfuse must also take into account the potential risks (infectious and non-infectious), as well as benefits for the individual patient. In the future, the level of transfusions may be reduced by using blood sparing techniques such as blood withdrawal in closed systems, bedside microchemistry, intravascular monitors, or autotransfusion of drainage blood in intensive care units.

Adaptation, Physiological↗

Laboratory markers of veno-occlusive disease in the course of bone marrow and subsequent liver transplantation.

Plasminogen activator inhibitor 1 (PAI-1) and amino-propeptide of type III procollagen (PIIINP) have been described as markers of hepatic veno-occlusive disease (VOD) after bone marrow transplantation (BMT). We determined these parameters in two patients undergoing BMT and subsequent liver transplantation due to VOD. Previously normal PAI-1 levels (maximum 30.0 ng/ml in patient 1, 23.7 ng/ml in patient 2) were elevated for the first time in both patients at the time of clinically diagnosed VOD on days 40 and 20, respectively (patient 1: 317.5 ng/ml; patient 2: 317.2 ng/ml). Levels remained elevated until liver transplantation was performed on days 79 and 41, respectively. Baseline levels (day -8) of aminopropeptide of type III collagen (patient 1: 4.44 microg/l; patient 2: 8.1 microg/l) peaked at the time of BMT in both patients (155.0 microg/l and 108.3 microg/l). After an intermittent decrease at the time of discharge on day 32, a second elevation was observed in patient 1 when she was readmitted and presented with typical signs of VOD on day 40. In patient 2, PIIINP levels remained high until VOD was diagnosed (day 20) and liver transplantation was performed. After liver transplantation, PAI-1 levels normalized in both patients and PIIINP levels declined. Both patients died due to infectious complications and multiorgan failure on days 141 and 101, respectively. Whereas the early rise of PIIINP did not correlate with the clinical onset of VOD, the results emphasise the relevance of PAI-1 for diagnosing VOD.

Acute Disease↗

[Surgical interventions in extracorporeal membrane oxygenation (ECMO)].

Extracorporeal membrane oxygenation is a suitable technique for short-term treatment of resistant respiratory failure with a comparably low mortality rate of 32%. However, pulmonary complications are quite often encountered during ECMO therapy making thoracic interventions necessary. The most frequent of these complications is hemorrhage followed by lung fistula, which remain resistant to conventional therapy. The indication for operative lung resection during ECMO treatment must remain restricted to selected cases, since these procedures have a high morbidity.

Adult↗

Protein C, protein S and antithrombin III levels in the course of bone marrow and subsequent liver transplantation due to veno-occlusive disease.

Veno-occlusive disease (VOD) of the liver is one of the most frequent fatal complications after bone marrow transplantation (BMT). A decrease of natural anticoagulants, in particular protein C (PC), has been assumed to be involved in the pathogenesis of the disease. We determined PC and antithrombin III (AT III) levels in two patients undergoing BMT and subsequent liver transplantation due to VOD. Additionally, in one of the patients protein S (PS) levels were also measured. Normal baseline (day-8) PC levels (86 and 89%) were markedly reduced in both patients at the time of VOD manifestation on day 20 and 40, respectively (26 and 31%). PS levels lay within the normal range from day-8 (before myeloablative chemotherapy) until one week after clinical onset of VOD when substitution therapy with fresh frozen plasma (FFP) was initiated. AT III levels decreased moderately during the second and third posttransplant week, but were normal in the patient with a late clinical manifestation of VOD. In both patients PC and PS levels lay within the normal range after liver transplantation which was performed on day 41 and 79, respectively. AT III was substituted several times. Both patients died due to infectious complications on day 141 and 101, respectively. The data confirm previous reports that a decrease of PC is observed in BMT recipients and can be associated with hepatic vein occlusion. Whereas the relevance of AT III is uncertain, PS does not seem to be involved in the pathogenesis of VOD. Liver transplantation lead to normalization of PC levels, but its significance remains to be discussed in terms of ethical justifiability, medical feasibility and costs.

Acute Disease↗

Evoked otoacoustic emissions and auditory selective attention.

The auditory system has an extensive peripheral efferent innervation. The question addressed in this paper is whether the olivocochlear bundle (OCB) efferent system innervating the outer hair cells (OHC) of the cochlea plays a role in selective attention. As evoked otoacoustic emissions (EOAE) provide a measure of the active micromechanical properties of OHCs, they can be used to assess the role of the efferent system in attention. Six experiments using tone-pip EOAEs are reported. In each experiment, EOAEs generated by 1 or 2 kHz tone pips when they were attended were compared with EOAEs to the same stimuli when they were unattended. In three experiments (1-4), a non-linear stimulus difference method was used to record a pure cochlear component of EOAEs. In Exps. 1-5, 1 and 2 kHz tone pips were delivered to the same ear and the difficulty of the subjects' task was manipulated in order to produce a more focussed attentional state or contralateral noise was presented to determine whether attention effects are dependent upon having an already activated efferent system. In Exp.6, the 1 and 2 kHz stimuli were delivered to opposite ears. A total of 70 subjects participated in the six experiments. There were no effects of attention on EOAEs in any of the experiments in the direction of previously reported effects. The results of these first six experiments employing simple attention switches between fixed auditory objects do not support active cochlear involvement in selective attention.

Acoustic Stimulation↗

Sarcoidosis recurrence following lung transplantation.

Sarcoidosis is a rare indication for lung transplantation. In this article, our experiences with recurring sarcoidosis following lung transplantation are described. Literature concerning recurrence of the disease in kidney, liver, heart and lung transmission of sarcoidosis via transplanted organs are discussed.

Humans↗

A comparison of the adrenocortical response during septic shock and after complete recovery.

OBJECTIVE: To compare the adrenocortical response to corticotropin during septic shock and after complete recovery. DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: 20 consecutive patients surviving septic shock. All patients met the American College of Chest Physicians/Society of Critical Care Medicine criteria for septic shock. In addition, the presence of high-output circulatory failure with a cardiac index > 41/min per m2 was a criterion for enrollment in the study. Complete recovery from septic shock was defined as discontinuation of any supportive therapies. Severity of illness during septic shock and after recovery was graded using the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system. INTERVENTIONS: In each patient, two short corticotropin stimulation tests were done during septic shock and after recovery. MEASUREMENTS AND RESULTS: Basal cortisol levels recorded during septic shock and after recovery did not differ (medians: 18.8 vs 18.9 micrograms/dl). However, the response to corticotropin was significantly attenuated during septic shock when compared with the response after recovery (medians: 7.7 vs 14.7 micrograms/dl; p = 0.02). After recovery, patients' stress response was less, as indicated by a reduction in APACHE II scores (medians: 21 vs 5 points; p < 0.01). CONCLUSIONS: Adrenocortical response to corticotropin is attenuated in patients with septic shock and high-output circulatory failure compared to the response in the much less stressful condition after recovery. The attenuated adrenocortical responsiveness may be explained by effects of circulating mediators from the systemic inflammatory response.

APACHE↗

[Venovenous extracorporeal membrane oxygenation (ECMO) with a heparin-lock bypass system. An effective addition in the treatment of acute respiratory failure (ARDS)].

Mortality of severe acute respiratory distress syndrome (ARDS) in Germany is about 60%. Respiratory therapy can make the lung injury worse by high positive airway pressures, high tidal volumes and high inspiratory oxygen concentrations. Extracorporeal membrane oxygenation (ECMO) was employed to reduce aggressive mechanical ventilation, but it has not been proved to be superior to conventional ventilation. However, encouraged by recently developed improvements in the technique and concept of ECMO, we introduced this therapy into our program for the treatment of ARDS. PATIENTS AND METHODS. All patients with severe ARDS (lung injury score > 2.5) admitted to our multidisciplinary intensive care unit from March 1992 to March 1995 were evaluated prospectively. After admission, the patients first underwent a conventional therapeutic approach, including pressure-controlled inverse-ratio ventilation, permissive hypercapnia, changes in body position (in particular, the prone position), negative fluid balance, anti-biotics, and low-dose hydrocortisone infusion. ECMO via a covalently heparin-coated, venovenous bypass-system with a vortex pump and two membrane lungs was performed if ARDS did not improve after 24-96 h of conventional therapy and if two of three of the slow-entry criteria for ECMO were fulfilled: (1) PaO2/FiO2 < 150 mmHg at PEEP > 5 mbar; (2) semistatic compliance < 30 ml/mbar; (3) right-left shunt > 30%. Only in cases of life-threatening hypoxemia (PaO2 < 50 mmHg at FiO2 1.0 and PEEP > 5 mbar for > 2 h (fast-entry criteria) was ECMO instituted immediately. RESULTS. Sixty patients fulfilled the entry criteria for our study. Thirty-nine patients were treated with a conventional protocol, 37 after improvement of ARDS and 2 who had not improved but in whom there were contraindications to the use of ECMO. ECMO was performed in 10 patients who had not improved, but who fulfilled the slow-entry criteria and in 11 primarily hypoxemic patients who fulfilled the fast-entry criteria. The survival rate was 30/39 (77%) for the conventional therapy group, 6/10 (60%) for the slow-entry group, and 11/11 (100%) for the fast-entry group. The onset of ECMO allowed a significant decrease in peak and mean airway pressures, tidal volume, ventilatory rate, minute volume and inspiratory oxygen concentration. Sufficient gas exchange was provided, and pulmonary artery pressures significantly decreased on bypass. The most frequent complications on bypass were pneumothorax (15/21 patients) and bleeding (7/21 patients). CONCLUSION. In comparison with the historical results at our own institution, the present study demonstrates an improvement in the survival rate from 56% to 78% since ECMO has become available. We conclude that venovenous ECMO with a heparin-bonded bypass circuit is an effective additional option for the treatment of patients with severe ARDS.

Adolescent↗

Perioperative mucosal pH and splanchnic endotoxin concentration in orthotopic liver transplantation.

Although impairment of splanchnic perfusion may induce mucosal hypoxia and endotoxaemia during orthotopic liver transplantation (OLT), little is known about the changes in mucosal oxygenation during and after the procedure. To study the effects of liver surgery itself on mucosal pH (pHi) and the response of pHi to acute changes in portal flow, we measured gastric pHi during six liver resections using tonometry: in two patients, after clamping of the hepatoduodenal ligament, pHi decreased within 30 min and recovered promptly after reperfusion. We then investigated gastric and sigmoid pHi (pHig, pHis) during the perioperative phase in 18 OLT. Median pHi values were low before surgery (pHig 7.28 (first/third quartiles 7.22/7.34); pHis 7.27 (7.12/7.36)). Although global oxygen delivery and haemodynamic variables remained constant and veno-venous bypass (VVB) was used to maintain portal flow, pHi declined during the anhepatic phase (pHig 7.19 (7.13/7.23), P < 0.01; pHis 7.13 (7.06/7.24), P < 0.05). After reperfusion of the graft, pHi recovered and did not differ from baseline values by the end of OLT. After operation pHig increased further, reaching the highest values 30 h after ICU admission (7.34 (7.26/7.38)). In the intraoperative period, no significant endotoxaemia was observed either in portal or systemic blood. The maximum reduction in pHi was related neither to the duration of VVB and OLT nor to the number of red cell units transfused. pHi after reperfusion did not correlate with graft viability or dysfunction of the lung or kidney. We conclude that pHi indicates mucosal ischaemia during OLT which is not necessarily associated with endotoxaemia, and intraoperative pHi monitoring does not appear to be a valuable predictor of postoperative graft failure and organ dysfunction.

Adult↗

Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome.

Inhalation of nitric oxide (NO) and prostacyclin (PGI2) may induce selective pulmonary vasodilation and-by improving ventilation-perfusion ratio in ventilated areas of the lung-increase Pao2 in patients with acute lung injury. To assess the therapeutic efficacy of both compounds, dose-response curves were established in patients with adult respiratory distress syndrome (ARDS). Patients received both PGI2 (doses of 1, 10, and 25 ng/kg/min) and NO (concentrations of 1, 4, and 8 ppm). Cardiorespiratory parameters were assessed at control, at each drug concentration, and after withdrawal of NO and PGI2. PGI2 resulted in a significant, dose-dependent and selective reduction of pulmonary artery pressure (PAP) from 35.1 +/- 6.3 mm Hg at control to 33.1 +/- 4.8 (1 ng/kg/min), 31.3 +/- 4.8 mm Hg (10 ng/kg/min) and 29.6 +/- 4.5 mm Hg (25 ng/kg/min), respectively. Inhaled NO reduced PAP from 34.5 +/- 5.6 to 32.1 +/- 5.9 mm Hg at 4 ppm, and to 31.8 +/- 6.1 mm Hg at 8 ppm, respectively, with no effect at 1 ppm. Pao2/Flo2 ratio increased from 105 +/- 37 to 125 +/- 56 mm Hg (range of increase: 0 to 57 mm Hg) at PGI2 10 ng/kg/min and to 131 +/- 63 mm Hg (range: -5 to 89 mm Hg) at 25 ng/kg/min with no effect at 1 ng/kg/min. NO improved Pao2 (e.g., from 116 +/- 47 to 167 +/- 86 mm Hg at 8 ppm) and reduced intrapulmonary shunt at all doses tested. We conclude that both inhaled PGI2 and NO may induce selective pulmonary vasodilation and increase Pao2 in severe ARDS.

APACHE↗

Risk factors for systemic fungal infections in liver transplant recipients.

The risk factors for systemic fungal infections were analysed retrospectively in 186 orthotopic liver transplant procedures performed in 152 patients between June 1985 and January 1993. The total incidence of systemic fungal infections was 16.5% (25/152). The incidence of disseminated candidiasis, aspergillosis, and combined candidiasis and aspergillosis was 6.5% (n = 10), 7.2% (n = 11) and 2.6% (n = 4), respectively. Mortality associated with systemic fungal infections was 80% (20 of 25 patients). There were ten cases of disseminated candidiasis, with 4 patients surviving, and 11 cases of invasive aspergillosis, with 1 patient surviving. All patients with combined systemic fungal infection died. To identify perioperative risk factors, 39 variables were used to compare patients with systemic fungal infections versus those without fungal infections. Fourteen variables were significantly associated with systemic fungal infections by univariate analysis. A consecutive logistic regression analysis revealed that the amount of fresh frozen plasma transfused due to poor initial function of the allograft and acute renal failure requiring hemofiltration were independently significant risk factors for systemic fungal infections. There was no statistical correlation between systemic fungal infections and the underlying liver disease, previous long-term corticosteroids and the postoperative immunosuppressive therapy. Risk factors identified in this study should be considered in the postoperative care of the individual liver transplant recipient. In our study a poor initial function of the hepatic allograft substantially increased the risk of systemic fungal infection.

Adult↗