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M Haller

Publications and source records attributed to M Haller.

At least 37 records · Page 2Linked to original sources

Extraction and isolation of linear alkylbenzenesulfonate and its sulfophenylcarboxylic acid metabolites from fish samples.

Linear alkylbenzenesulfonate (LAS) is the most widely used synthetic surfactant. In fish, assessment of the environmental risk and investigation of the biotransformation behavior of LAS require compound-specific methods for extraction and isolation of LAS and its biotransformation products, sulfophenylcarboxylic acids (SPC). Matrix solid-phase dispersion (MSPD) extraction with subsequent ion-pair liquid-liquid (IP-LL) partitioning of the extract was a time-efficient sample preparation method for analysis of LAS. The recovery of parent LAS from spiked fish exceeded 70%, and the limit of quantitation ranged around 0.2 mg.kg-1 corresponding to 0.6 mumol.kg-1. In a simultaneous determination of LAS and SPC in fish, the analytes were MSPD extracted in different fractions. The target compounds were separated from the sample matrix by protein precipitation and subsequent isolation of (a) SPC by graphitized carbon black solid-phase extraction of the supernatant and (b) parent LAS by IP-LL partitioning of the pellet obtained after protein precipitation. The recoveries of the model compounds C12-2-LAS and C4-3-SPC were 84 +/- 6 and 65 +/- 11%, respectively. The use of C3-3-SPC as an internal standard corrected for the loss of the biotransformation product during sample workup. The suitability of both methods was demonstrated by analyzing fish containing LAS and SPC incurred during aqueous exposure.

Animals↗

Sensitivity and specificity of a screening test to document traumatic experiences and to diagnose post-traumatic stress disorder in ARDS patients after intensive care treatment.

OBJECTIVE: Many survivors of critical illness and intensive care unit (ICU) treatment have traumatic memories such as nightmares, panic or pain which can be associated with the development of posttraumatic stress disorder (PTSD). In order to simplify the rapid and early detection of PTSD in such patients, we modified an existing questionnaire for diagnosis of PTSD and validated the instrument in a cohort of ARDS patients after long-term ICU therapy. DESIGN: Follow-up cohort study. SETTING: The 20-bed ICU of a university teaching hospital. PATIENTS: A cohort of 52 long-term survivors of the acute respiratory distress syndrome (ARDS). INTERVENTIONS AND MEASUREMENTS: The questionnaire was administered to the study cohort at two time points 2 years apart. At the second evaluation, the patients underwent a structured interview with two trained psychiatrists to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The reliability and validity of the questionnaire was then estimated and its specificity, sensitivity and optimal decision threshold determined using receiver operating characteristic (ROC) curve analyses. RESULTS: The questionnaire showed a high internal consistency (Crohnbach's alpha = 0.93) and a high test-retest reliability (intraclass correlation coefficient alpha = 0.89). There was evidence of construct validity by a linear relationship between scores and the number of traumatic memories from the ICU the patients described (Spearman's rho = 0.48, p < 0.01). Criterion validity was demonstrated by ROC curve analyses resulting in a sensitivity of 77.0% and a specificity of 97.5% for the diagnosis of PTSD. CONCLUSIONS: The questionnaire was found to be a responsive, valid and reliable instrument to screen survivors of intensive care for PTSD.

APACHE↗

Effects of noninvasive positive pressure ventilatory support in non-COPD patients with acute respiratory insufficiency after early extubation.

OBJECTIVE: To investigate the effects of noninvasive positive pressure ventilation (NPPV) on pulmonary gas exchange, breathing pattern, intrapulmonary shunt fraction, oxygen consumption, and resting energy expenditure in patients with persistent acute respiratory failure but without chronic obstructive pulmonary disease (COPD) after early extubation. DESIGN: Prospective study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: 15 patients after prolonged mechanical ventilation (> 72 h) with acute respiratory insufficiency after early extubation. INTERVENTIONS: Criteria for early extubation were arterial oxygen tension (PaO2) > or = 40 mm Hg (fractional inspired oxygen 0.21), arterial carbon dioxide tension (PaCO2) < or = 55 mm Hg, pH > 7.32, respiratory rate < or = 40 breaths per min, tidal volume (VT) > or = 3 ml/kg, rapid shallow breathing index < or = 190 and negative inspiratory force > or = 20 cmH2O. After extubation, two modes of NPPV were applied [continuous positive airway pressure (CPAP) of 5 cmH2O and pressure support ventilation (PSV) with 15 cmH2O pressure support]. MEASUREMENTS AND MAIN RESULTS: Oxygenation and ventilatory parameters improved during both modes of NPPV (p < 0.05): increase in PaO2 of 11 mm Hg during CPAP and 21 mm Hg during PSV; decrease in intrapulmonary shunt fraction of 7% during CPAP and 12% during PSV; increase in tidal volume of 1 ml/kg during CPAP and 4 ml/kg during PSV; decrease in respiratory rate 6 breaths/min during CPAP and 9 breaths/min during PSV. Oxygen consumption (15% during CPAP, 22% during PSV) and resting energy expenditure (12% during CPAP, 20% during PSV) were reduced (p < 0.05). PaCO2 decreased, whereas minute ventilation and pH increased during PSV (p < 0.05). The median duration of NPPV was 2 days. Two patients had to be reintubated. CONCLUSIONS: In non-COPD patients with persistent acute respiratory failure after early extubation, NPPV improved pulmonary gas exchange and breathing pattern, decreased intrapulmonary shunt fraction, and reduced the work of breathing.

APACHE↗

Evaluation of a new continuous thermodilution cardiac output monitor in cardiac surgical patients: a prospective criterion standard study.

OBJECTIVE: To evaluate the accuracy of a new continuous cardiac output monitor in critically ill patients. DESIGN: Criterion standard study. SETTING: Cardiac surgery intensive care unit in a university hospital. PATIENTS: Twenty cardiac surgical patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac output was monitored continuously with a modified pulmonary artery catheter that has a heating filament on the outside of the catheter. Four modes of data processing with different response times ("Normal," "Fast," "FastFilter," and "Urgent" modes) used by the monitoring system. A total of 240 determinations of cardiac output were performed using conventional bolus thermodilution technique; these results were compared with those obtained using three of the four continuous measuring modes available ("Normal," "FastFilter," and "Urgent"). Cardiac output ranged from 3.47 to 15.77 L/min (bolus thermodilution). The mean (bias) +/- SD of differences (precision) for all measurements was 0.40+/-1.26 L/min in the Normal mode (cardiac output <10 L/min: 0.34+/-0.66 L/min), 0.53+/-1.27 L/min in the FastFilter-mode (cardiac output <10 L/min: 0.60+/-0.75 L/min), and 0.63+/-1.34 L/min in the Urgent mode (cardiac output <10 L/min: 0.57+/-0.82 L/min). CONCLUSIONS: Continuous cardiac output measurement using the thermodilution technique is reasonably accurate, reliable, and applicable in routine clinical practice. The values obtained using the Normal mode of the monitor agreed significantly better with the conventional thermodilution method than the results of the two other modes studied (FastFilter and Urgent). In addition, measurements in two patients with cardiac output values of >10 L/min did not agree with the results of the bolus thermodilution method.

Adult↗

Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study.

OBJECTIVE: To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock. DESIGN: Prospective, randomized, double-blind, single-center study. SETTING: Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital. PATIENTS: Forty consecutive patients who met the ACCP/SCCM criteria for septic shock. An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of >4 L/min/m2 after fluid resuscitation (pulmonary capillary wedge pressure: 12-15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopressor support (norepinephrine or epinephrine in any dose, dopamine > or = 6 microg/kg/min). Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome (MODS). The severity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MODS was described by the Sepsis-related Organ Failure Assessment score. INTERVENTIONS: All eligible patients were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr. When septic shock had been reversed, the dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to >155 mmol/L, the hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic saline solution was the placebo. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline data at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo. Hydrocortisone significantly reduced the time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1st and 3rd Quartiles, 1 and 6 days) in the hydrocortisone-treated group and 7 days (1st and 3rd Quartiles, 3 and 19 days) in the placebo group (p = .005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group. CONCLUSIONS: Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions. Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study.

Adult↗

The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder and health-related quality of life in survivors.

OBJECTIVES: The exposure to intense physical and psychological stress during intensive care can result in posttraumatic stress disorder (PTSD) in survivors. Cortisol is a biological stress mediator that can have a protective effect during severe stress. The administration of stress doses of hydrocortisone during treatment in the intensive care unit could theoretically result in a lower incidence of PTSD. We tested this hypothesis in survivors of septic shock. DESIGN: A retrospective case-controlled analysis. SETTING: A 20-bed multidisciplinary intensive care unit of a tertiary-care university hospital. PATIENTS: We identified 27 patients who received standard therapy for septic shock. These patients served as controls and were compared with an equal number of patients who received hydrocortisone in addition to standard treatment. These patients were selected from our database with regard to age (+/-4 yrs), gender, and cause of septic shock to be as similar as possible with control patients. INTERVENTIONS: Patients from the hydrocortisone group had received stress doses of hydrocortisone (100 mg bolus, followed by 0.18 mg/kg/hr) in addition to standard treatment. Patients from the control group received standard protocol-driven treatment only. PTSD was diagnosed with the Posttraumatic Stress Syndrome-10 inventory, a self-report scale for diagnosis of PTSD. Health-related quality of life was measured using the Medical Outcomes Study Short-Form Survey (Medical Outcomes Trust, Boston, MA), which consists of 36 questions. MEASUREMENTS AND MAIN RESULTS: Patients who received hydrocortisone during septic shock had a significantly lower incidence of PTSD than patients who received standard treatment only (5 of 27 vs. 16 of 27; p = .01) and had significantly higher scores on the mental health index of the Medical Outcomes Study Short-Form health-related quality-of-life questionnaire (68 vs. 44 points; p = .009). CONCLUSIONS: Data from this study support the hypothesis that the administration of stress doses of hydrocortisone in doses equivalent to the maximal endocrine secretion rate during septic shock reduces the incidence of PTSD and improves emotional well-being in survivors. This hypothesis should be tested in a prospective randomized trial.

APACHE↗

Hypoxia activates ATP-dependent potassium channels in inspiratory neurones of neonatal mice.

1. The respiratory centre of neonatal mice (4 to 12 days old) was isolated in 700 micro(m) thick brainstem slices. Whole-cell K+ currents and single ATP-dependent potassium (KATP) channels were analysed in inspiratory neurones. 2. In cell-attached patches, KATP channels had a conductance of 75 pS and showed inward rectification. Their gating was voltage dependent and channel activity decreased with membrane hyperpolarization. Using Ca2+-containing pipette solutions the measured conductance was lower (50 pS at 1.5 mM Ca2+), indicating tonic inhibition by extracellular Ca2+. 3. KATP channel activity was reversibly potentiated during hypoxia. Maximal effects were attained 3-4 min after oxygen removal from the bath. Hypoxic potentiation of open probability was due to an increase in channel open times and a decrease in channel closed times. 4. In inside-out patches and symmetrical K+ concentrations, channel currents reversed at about 0 mV. Channel activity was blocked by ATP (300-600 microM), glibenclamide (10-70 microM) and tolbutamide (100-300 microM). 5. In the presence of diazoxide (10-60 microM), the activity of KATP channels was increased both in inside-out, outside-out and cell-attached patches. In outside-out patches, that remained within the slice after excision, the activity of KATP channels was enhanced by hypoxia, an effect that could be mediated by a release of endogenous neuromodulators. 6. The whole-cell K+ current (IK) was inactivated at negative membrane potentials, which resembled the voltage dependence of KATP channel gating. After 3-4 min of hypoxia, K+ currents at both hyperpolarizing and depolarizing membrane potentials increased. IK was partially blocked by tolbutamide (100-300 microM) and in its presence, hypoxic potentiation of IK was abolished. 7. We conclude that KATP channels are involved in the hypoxic depression of medullary respiratory activity.

Adenosine Triphosphate↗

[Health-related quality of life. Long-term survival in patients with ARDS following extracorporeal membrane oxygenation (ECMO)].

UNLABELLED: Treatment of severe acute respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) can be lifesaving but requires maximal use of intensive care resources over prolonged periods of time, resulting in high costs. Little is known about the health-related quality of life (HRQL) in long-term survivors. This case-controlled retrospective study was designed to assess the health-related quality of life in long-term survivors of ARDS and ECMO-therapy. METHODS: 14 long-term survivors of ARDS (APACHE II score = 24, Lung Injury Score = 3.25, median values) treated using ECMO between 1992 and 1995 (median time interval between data collection and discharge from the ICU 16 months) and 14 ARDS-patients conventionally treated during the same period (group I) were identified and completed the SF-36 Health Status Questionnaire (Medical Outcome Trust, Boston, USA). 14 healthy subjects (group II) were drawn at random from a large data base generated to provide normal values for the SF-36 in a German population. All three groups were comparable with respect to sex and age. RESULTS: Long-term survivors of ECMO-therapy reported significant reductions in physical functioning when compared with patients treated by mechanical ventilation alone (group I, -12.5%, p < 0.05) and with healthy controls (group II, -50%, p < 0.05) and showed a higher incidence of chronic physical pain (+5% and +24%, respectively, p < 0.05). There were no differences with regard to the mental health dimensions of the SF-36 (e.g. vitality, mental health index or social functioning) between ECMO-patients and all controls. Nine patients (64.3%) from the ECMO group versus all patients treated conventionally (group I) had full-time employment (p = 0.46, Chi2 test). CONCLUSIONS: The majority of long-term survivors of ECMO-treatment show good physical and social functioning, including a high rate of employment. The more aggressive approach of ECMO-therapy and a possibly more severe underlying disease process may explain impairments in health-related quality of life outcomes after ECMO-treatment. Despite these limitations, long-term survivors of ECMO-therapy are able to reach a highly satisfactory health-related quality of life.

APACHE↗

[Retrospective analysis of transpulmonary and pulmonary arterial measurement of cardiac output in ARDS patients].

OBJECTIVES: To investigate the agreement (and its potential dependency on extra-vascular lung water) between transpulmonary (TPID) and standard pulmonary artery (PAID) thermodilution cardiac output measurements. METHODS: One hundred and sixty simultaneous cardiac output measurements using transpulmonary and pulmonary artery thermodilution techniques were retrospectively compared in 18 patients with acute respiratory distress syndrome. In addition, extravascular lung water was determined using a double indicator technique (temperature and indocyanine green). RESULTS: Mean (+/- SD) difference ("bias") was 0.03 L/min (+/- 1.04 L/min), linear regression analysis resulted in TPID = 0.87 PAID + 1.16 (r = 0.91). Mean extra vascular lung water was 1625 mL (minimum-maximum: 403-3266 mL) and therefore markedly elevated as could have been expected in patients with ARDS. Bias (PAID-TPID) was not dependent on extravascular lung water. CONCLUSIONS: Transpulmonary and pulmonary artery thermodilution methods can be used interchangeably. The results demonstrate for the first time in humans that transpulmonary thermodilution provides valid cardiac output values in patients with markedly increased fluid content of the lungs.

Adult↗

Group A streptococcal toxic shock syndrome with severe necrotizing fasciitis following hysterectomy--a case report.

In the last 10 years an increasing number of cases of group A streptococcal toxic shock syndrome have appeared in various clinical settings. The manifestation of this syndrome includes rapidly progressive multiorgan failure and soft-tissue necrosis. This report presents a case of streptococcal toxic shock syndrome caused by Streptococcus pyogenes with severe necrotizing fasciitis of the abdominal wall following hysterectomy. Aggressive surgical intervention with debridement of all necrotic tissue necessitated resection of the complete abdominal wall (skin, subcutaneous tissue, muscle and peritoneum). The abdominal wall defect was covered with free myocutaneous flaps and split-skin grafts. Optimal treatment, including adequate antibiotic therapy and radical surgical intervention, is an indispensable prerequisite of successful outcome.

Fasciitis, Necrotizing↗

Inhaled nitric oxide (NO) for the treatment of early allograft failure after lung transplantation. Munich Lung Transplant Group.

OBJECTIVE: Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantation. DESIGN: Prospective clinical dose-response study. SETTING: Anesthesiological intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2) of less than 13.3 kPa (100 mmHg). INTERVENTIONS: Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator. MEASUREMENTS AND RESULTS: Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p < 0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5(5.2/6.0) kPa at control to 5.1(4.7/5.6) kPa at 1 ppm, 4.9(4.3/5.3) kPa at 4 ppm, and to 4.7(4.1/5.1) kPa at 8 ppm. PaO2 increased from 12.7(10.4/17.1) to 19.2(12.4/26.0) kPa at 1 ppm NO, to 23.9(4.67/26.7) kPa at 4 ppm NO and to 24.5(11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO2), all were subject to long-term inhalation (1-19 days). All were successfully weaned from NO and were discharged from the intensive care unit. CONCLUSION: The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation.

Administration, Inhalation↗

Comparison of secretory responses as measured by membrane capacitance and by amperometry.

We have compared capacitance and amperometric measurements in bovine chromaffin cells when secretion was elicited by flash photolysis of caged-calcium or step depolarizations. Total amperometric charge depended linearly on the amount of capacitance increase in both types of experiments. Furthermore, the properties of resolvable amperometric spikes after flashes were comparable to those observed after depolarizations, and their timing was compatible with the rate of capacitance increase. For a more detailed comparison, we used Monte Carlo simulations of multiple amperometric events occurring randomly over the surface of a sphere and summing together, to generate a reference amperometric signal for a given measured capacitance increase. Even after correction for endocytotic processes, the time courses of the integrated experimental records lagged behind the integrated Monte Carlo records by approximately 50 ms in flash and depolarization experiments. This delay was larger by approximately 40 ms than what can be expected from the "pre-foot delay" or the foot duration. Possible sources for the remaining delay could be diffusional barriers like the patch-pipette and the chamber bottom, which are not taken into account in the model. We also applied a novel type of fluctuation analysis to estimate the relative quantum size of an amperometric event. On average the estimates from experimental amperometric traces, in both flash and depolarization experiments, were 3-5 times smaller than estimates from simulated ones. This discrepancy can be due to contributions to the amperometric current from small vesicles, preferred release from cellular regions orientated toward the chamber bottom, or abundance of "foot-only" events. In conclusion, amperometric signals in flash and depolarization experiments displayed similar delayed average time courses and a lower estimate for the relative quantum size compared to the modeled amperometric signals. However, individual amperometric spikes were in agreement with expectations derived from capacitance signals.

Adenosine Triphosphate↗

First clinical implications of perioperative red cell volume measurement with a nonradioactive marker (sodium fluorescein).

UNLABELLED: We measured red cell volume (RCV) with the nonradioactive marker sodium fluorescein (SoF) in 30 patients undergoing gynecological operations. Sixteen patients underwent preoperative isovolemic hemodilution (PIHD). RCV measurements were performed before and after PIHD and at the end of the operation. All RCVs were related to corresponding hematocrit (hct) levels. We report a simplified method for its clinical application by reducing the number of blood samples required. To validate our method, we compared RCV within the PIHD bags (bag RCV) with the difference of the patients' RCV before and after PIHD. Bag RCV obtained during PIHD (mean 399+/-81 mL) was measured with a precision of 4.2% by using SoF. There was a significant difference (mean 286+/-401 mL; P < 0.05) between intraoperatively estimated and measured blood loss. The blood loss tended to be underestimated and, in some cases, was underestimated or overestimated substantially. Preoperative and postoperative hct values only offered an imprecise estimation of the patients' RCV. We conclude that RCV measurement using SoF is a precise method for monitoring changes in RCV during PIHD and surgical operation. IMPLICATIONS: We measured red cell volume changes of 30 patients with the nonradioactive marker sodium fluorescein before and after hemodilution and postoperatively with a high precision. We frequently found large differences between intraoperatively estimated and measured blood loss. Preoperative hematocrit values offered an imprecise estimation of the patients' red cell volume.

Adult↗

Perioperative management of patients undergoing lung transplantation.

This review focuses on recent developments in the perioperative management of patients undergoing lung transplantation. Relevant current literature and the experience of the Munich Lung Transplant Group were taken into consideration. Recent advances include the use of inhalational nitric oxide for the treatment of early graft dysfunction and the use of aerosolized cyclosporine for the treatment of recurrent and steroid-resistant acute rejection. Opportunistic infections remain a major source of morbidity and mortality in lung transplant recipients.

Journal Article↗

Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome.

OBJECTIVES: Despite considerable progress in intensive care management of the acute respiratory distress syndrome (ARDS), little is known about health-related quality of life in long-term survivors. In addition, intensive care treatment can be extremely stressful, and many survivors of ARDS report adverse experiences such as respiratory distress, anxiety, or pain during intensive care unit (ICU) treatment. This study was performed to assess health-related quality of life in survivors of ARDS and to test the hypothesis that adverse experiences during ICU treatment result in posttraumatic stress disorder (PTSD) and negative effects on health-related quality of life. DESIGN: Retrospective, cohort, case-controlled analyses. SETTING: A 12-bed multidisciplinary ICU of a tertiary care university hospital, capable of providing extracorporeal life support for adults with severe ARDS. PATIENTS: We studied 80 patients who were admitted to our hospital from 1985 to 1995 and who survived an episode of ARDS. ARDS was defined according to the criteria of the American-European Consensus Conference on ARDS. INTERVENTIONS: Health-related quality of life was measured using the Health Status Questionnaire of the self-administered Medical Outcomes Study Short Form Survey that consists of 36 questions (SF-36) and the German version of the Post Traumatic Stress Syndrome 10-Questions Inventory (PTSS-10), a self-report scale for the diagnosis of posttraumatic stress disorder based on the Diagnostic and Statistical Manual (Third Edition) criteria (American Psychiatric Association). The number of adverse experiences (anxiety, respiratory distress, pain, and nightmares) during intensive care was evaluated by means of a structured questionnaire. For each patient with ARDS, three age- and gender-comparable controls were randomly selected from databases providing normal values for the SF-36 and PTSS-10 scores in populations at risk for posttraumatic stress disorder. MEASUREMENTS AND MAIN RESULTS: Survivors of ARDS showed statistically significant impairments in all eight health dimensions of the SF-36 when compared with normal controls (median reduction 21.3%, p < .006) with maximal impairments in physical function (median reduction 28.9%, p = .000) and a 38% higher frequency of chronic pain (p = .0001). Three of 34 patients reporting none, or one, adverse experience had evidence of posttraumatic stress disorder vs. 19 of 46 patients remembering multiple traumatic episodes (p = .007). Patients reporting multiple adverse experiences described the lowest health-related quality of life, with maximal impairments in psychosocial functioning (p < .005) and only small limitations in physical function. CONCLUSIONS: Long-term survivors of ARDS describe a good overall health-related quality of life. Major impairments in mental health domains of health-related quality of life are associated with the development of posttraumatic stress disorder and are a possible result of traumatic experiences during ICU therapy.

Adolescent↗

Extra protein loss not caused by surgical bleeding in patients with ovarian cancer.

BACKGROUND: [corrected] Clinical experience in patients with ovarian cancer has shown special difficulties in maintaining cardiovascular stability during surgery. METHODS: To evaluate the causes for this observation, 15 patients with benign ovarian tumours (group I) and 13 patients with ovarian cancer (group II) were investigated perioperatively. Plasma volume (indocyanine green-dilution technique), haematocrit, plasma protein concentration, mean arterial pressure, heart rate, and central venous pressure were measured immediately before and after cytoreductive surgery. RESULTS: Normal values of blood-, plasma-, and red cell volume were determined preoperatively in both groups, and in relation to body surface area there were no intergroup differences of these parameters. In group I, the significant decrease in red cell volume of 313 ml postoperatively was compensated for by an increase in plasma volume of 371 ml (median values). In contrast to group I, the decrease in red cell volume of 328 ml in group II was not related to a significant increase in plasma volume, so that blood volume postoperatively was 483 ml lower than preoperatively, although the same standardized infusion regimen as in group I was applied. Patients of group II had a significantly higher loss of intravascular protein (49 g vs 13 g in group I), which left the intravascular space by another way than by surgical bleeding. This extra protein loss is termed Intraoperative Protein Shift (IPS). CONCLUSION: IPS could be an important quantity in perioperative fluid balance. We assume that different surgical procedures predispose to occurrence of differing amounts of IPS.

Adult↗

Nucleotide hydrolysis-dependent conformational changes in p21(ras) as studied using ESR spectroscopy.

We have employed ESR spectroscopy using guanine nucleotides that contain a spin label at the 2',3'-position of the ribose to investigate structural changes in the proto-oncogene product p21(ras) that are dependent on nucleotide hydrolysis. The three nucleotide analogs used were 2',3'-(2,2,5, 5-tetramethyl-3-pyrroline-1-oxyl-3-carboxylic acid ester (SL) GTP, SL-GDP, and the non-hydrolyzable analog SL-guanylylimidodiphosphate. SL-GTP was hydrolyzed by p21 with rates similar to those for GTP hydrolysis and appears to be an excellent substrate analog. The ESR spectra of SL-GTP and SL-GDP in complex with p21 differ significantly when acquired at 0 degrees C or 5 degrees C indicating different environments (conformations) of the protein-bound radicals depending on the phosphorylation state of the bound nucleotide. We calculated the rate constant for the conformational change as deduced from the changes in the corresponding ESR spectra upon incubation of the p21.SL-GTP complex at 25 degrees C and compared it to the rate constant of hydrolysis of SL-GTP at the same temperature. The rate constant deduced from the ESR method was similar to that determined by a high performance liquid chromatography technique. The data are in agreement with the idea that a conformational change during GTP hydrolysis by p21 occurs simultaneously with the actual hydrolysis step.

Binding Sites↗

[Generalized gas gangrene infection with rhabdomyloysis following cholecystectomy].

We report a rare case of spontaneously developing generalised gas gangrene with massive rhabdomyolysis after a cholecystectomy and drainage of a hepatic abscess. On preoperative physical examination the patient appeared severely ill and was icteric and oliguric. Laboratory evaluation showed signs of systemic inflammation, elevated lactate levels, evidence of disseminated intravascular coagulation (DIC), and increased levels of serum creatine kinase (CK) activity. Abdominal ultrasound and endoscopic retrograde cholangiography showed a gallbladder perforation and a hepatic abscess. Cholecystectomy and drainage of the abscess was performed immediately and without technical problems. After postoperative admission to the intensive care unit, the patient showed evidence of generalised myonecrosis with subcutaneous gas formation and acute renal failure. Initially, there were few other signs of systemic toxicity; the patient was not hypotensive and the pulmonary gas exchange was normal. Within hours diffuse swelling of his right leg developed with cutaneous gangrene and a compartment syndrome. After fasciectomy and extensive surgical debridement, uncontrollable bleeding due to DIC developed from the fasciectomy site, which finally required exarticulation of the leg at the hip joint. At this point, multiple organ failure including severe adult respiratory distress syndrome was present. Two days after cholecystectomy, the patient died from hypoxic cardiocirculatory failure. Clostridium perfringens was repeatedly isolated from the wounds. Besides gas gangrene, the differential diagnosis of such infections includes localised clostridial cellulitis, nonclostridial anaerobic cellulitis caused by mixed aerobes and anaerobes, and type I or type II necrotising fasciitis. Patients with systemic necrotising infections should be treated with broad-spectrum antimicrobial regimens (penicillin G, 3rd generation cephalosporins, clindamycin, and aminoglycosides). An otherwise unexplained elevation of serum CK activity in the presence of acute cholecystitis may suggest haematologic spread of an aggressive myolytic agent and the beginning of myonecrosis. This should prompt immediate surgical exploration after establishing broad-spectrum antibiotic coverage. The role of hyperbaric oxygen treatment in this situation remains to be established. If hyperbaric oxygen is to be employed, it should neither delay surgical exploration nor jeopardize the patient with the hazards of an interhospital transport.

Cholecystectomy↗