The effects of PEEP on arterial oxygenation

The effect of positive end expiratory pressure (PEEP) on arterial oxygenation depends on many factors. Two of the most important are the quality and the quantity of the physiological shunt. The quality depends on the mixed venous oxygen tension, and the quantity on the shunt fraction. Each of these factors may rise or fall with PEEP, depending on the pulmonary and circulatory state of the patient. Their ultimate balance influences the change in arterial oxygen tension.     

The activity of grepafloxacin in two murine models of <Emphasis Type="Italic">Mycobacterium avium</Emphasis> infection

The activity against Mycobacterium avium complex (MAC) of varying doses of grepafloxacin (GRE; 25mg/kg, 50mg/kg, 100mg/kg, and 200mg/kg) were compared to clarithromycin (CLA; 100mg/kg and 200mg/kg), ethambutol (EMB; 100mg/kg), and rifabutin (RBT; 10mg/kg) using an intranasal (IN) infection model compared to an intravenous (IV) infection model. Beige mice (C57BL6/J-Lyst bg J/+) were infected intranasally with about 10⁶ organisms and for the IV model about 10⁷ organisms. Treatment for both models was started 1 week postinfection and given by gavage 5 days/week for 4 weeks. At the initiation of therapy, an early control group was killed to determine the initial organism load. Three days following the completion of therapy, drug-treated groups of mice and the late control group were killed and the response to therapy measured. The most effective agents were CLA and RBT. GRE and EMB had modest activities in both the IN and the IV models. A matched comparison between IN and IV challenges for each of the agents used revealed greater suppression of MAC in the IN model compared to the IV model.     

Impact of Kendall,Hollon, Beck,Hammen, and Ingram (1987) on treatment of the continuity issue in “depression” research

The article, Issues and Recommendations Regarding Use of the Beck Depression Inventory (Kendall, Hollon, Beck, Hammen, & Ingram, 1987), has had a major impact on depression research. A majority of studies using only the BDI in nonclinical samples now refer to the construct measured as dysphoria rather than depression. This word change, however, is not always accompanied by other changes in research design and interpretation that would seem warranted by the concerns that initially prompted the dysphoria recommendation, such as the nonspecificity of high BDI scores to major depression. Researchers typically continue to derive hypotheses from depression theory, use only the BDI to measure dysphoria rather than purer markers of negative affectivity, cite as a limitation of their findings the danger of assuming continuity between subclinical and clinical depression, and sometimes lapse into depression terminology. Alternative suggestions are made for considering how the particular goals of a study might lead to various ways of handling the continuity issue.We are grateful to Tony Ahrens, Diane Arnkoff, and anonymous reviewers for feedback on earlier drafts.     

Immediate effects on depression of cognitive therapy interventions

The immediate effects on depression of exploring versus modifying depressive thoughts were compared in chronic moderately to severely depressed patients receiving cognitive behavioral therapy (CBT). Using a withinsubject design, it was found that periods of cognitive CBT consistently produced more change in belief in identified depressive thoughts than did similar periods devoted to exploring and obtaining more information relevant to the thoughts. The greater change in belief resulting from cognitive CBT was consistently accompanied by greater reduction in self-rated depressed mood than was obtained in the Thought Exploration condition. Differences in the effects of the two conditions on a measure of speech rate were not consistent. The results support a central prediction of the cognitive model of depression and suggest the specific therapeutic effectiveness of cognitive CBT techniques.This research was supported by the Medical Research Council of the United Kingdom. We are grateful to Peter Amies and Gillian Butler, who rated the recordings of the treatment interventions.     

Positionspapier zur Qualifikation und Zertifizierung von Untersuchern in der Echokardiographie

Ohne ZusammenfassungKonsensus der Kommission Zertifizierung Echokardiographie     

Ultrasonography in Crohn's disease

Eighteen patients with acute and subacute Crohn's disease were examined by ultrasound. In 7, ultrasound was the initial screening procedure leading to the diagnosis of Crohn's disease. This diagnosis was subsequently proved by results of barium studies. The most frequent ultrasonographic finding was conglomeration: an irregular mass containing scattered echodense and sonolucent areas that represented matted inflamed bowel loops. Some of the conglomerations showed a fine diffuse echo pattern with ill-defined posterior borders due to poor transmission. These areas denoted mesenteric fat covering the matted loops (fatty conglomeration). Other ultrasonographic findings were the target or bull's eye sign, abscess formation, and fluid in the cul-de-sac.     

Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling

In patients with infection, improving the probability of positive treatment outcomes depends on optimizing the interactions between the host, pathogen, and drug. In this setting, optimal regimens must be utilized which not only maximize effectiveness in a specific patient, but also minimize the development of microbial resistance. The probability of achieving a specifically targeted antimicrobial exposure can be assessed using Monte Carlo simulation, a technique which integrates an agents in vitro potency distribution (i.e., minimum inhibitory concentrations [MICs]) with the pharmacokinetic profile. The targeted pharmacodynamic parameters assessed by this technique include the ratio of peak concentration (C_max) to MIC (C_max:MIC); the ratio of the area under the plasma concentration-time curve (AUC) to MIC (AUC:MIC), and the time the drug concentration exceeds the MIC (T MIC). Some antimicrobials, e.g., the aminoglycosides, are most effective/bactericidal when they have a high C_max:MIC ratio; others, e.g., the fluoroquinolones, are more effective when the AUC:MIC ratio is high. In both of these scenarios, organism eradication is concentration-dependent, and the therapeutic goal is to maximize drug exposure. Like the fluoroquinolones, the efficacy of telithromycin, a newly developed ketolide, is most related to the AUC:MIC ratio. Outcome for other agents, such as the -lactams, is best predicted by the T MIC; in this case, organism eradication is time-dependent, and the therapeutic goal is to optimize the duration of antimicrobial exposure. This article discusses how the use of currently available antimicrobials can be optimized through an appreciation of pharmacodynamic profiling.     

Patient assessment of a combined medical and nursing preparation to cytotoxic chemotherapy

At Auckland hospital there is a combined medical and nursing preparation for patients receiving cytotoxic chemotherapy. The aim of the current study was to assess whether patients felt that this combined approach had prepared them adequately for chemotherapy. Patients were asked to complete three questionnaires anonymously at different times in their treatment programme: Immediately prior to chemotherapy, after three cycles of chemotherapy and 2 months after completion of chemotherapy. A high level of satisfaction with the programme was demonstrated: 68% of patients thought the orientation programme had prepared them very well, 32% adequately and none poorly for their chemotherapy. Separate interviews with medical and nursing staff were thought a good idea by 86% of patients and only 1 of 100 medical and 100 nursing interviews was assessed as not worthwhile. This study suggests that a combined medical and nursing preparation is a worthwhile practice in preparing patients for cytotoxic chemotherapy.     

New aspects of pulmonary mechanics: ‘slowly” distensible compartments of the respiratory system,identified by a PEEP step maneuver

Objective The aims of the present study were 1) to evaluate a method for identification of slowly distensible compartments of the respiratory system (rs), which are characterized by long mechanical time constants (RC) and 2) to identify slowly distensible rs-compartments in mechanically ventilated patients.Design Prospective studyon a physical lung model.Setting Intensive Care Unit, University Hospital, Tübingen.Patients and participants 19 patients with severe lung injury (acute respiratory distress syndrome, ARDS) and on 10 patients with mild lung injury.Measurements and results Positive end-expiratory pressure (PEEP)-increasing and-decreasing steps of about 5 cmH₂O were applied and the breath-by-breath differences of inspiratory and expiratory volumes (V) were measured. The sequence of Vs were analyzed in terms of volume change in the fast compartment (V_fast), the slow compartment (V_slow), total change in lung volume (VL) and mechanical time constant of the slow compartment (RC_slow). Thirty-eight measurements in a lung model revealed a good correlation between the preset V_slow/VL and V_slow/VL measured: r²=0.91 The V_slow/VL measured amounted to 0.94±0.15 of V_slow/VL in the lung model. RC_slow measured was 0.92±0.43 of the RC_slow reference. Starting from a PEEP level of 11 cmH₂O PEEP-increasing and PEEP-decreasing steps were applied to the mechanically ventilated patients. Three out of ten patients with mild lung injury (30%) and 7/19 patients with ARDS (36.8%) revealed slowly distensible rscompartments in a PEEP-increasing step, whereas 15/19 ARDS patients and 1/10 patients with mild lung injury showed slowly distensible rs-compartments in a PEEP-decreasing step (78.9% vs 10%,P<0.002, chi-square test).Conclusions The gas distribution properties of the respiratory system can be easily studied by a PEEP-step maneuver. The relative contribution of the slow units to the total increase of lung volume following a PEEP step could be adequately assessed. Slowly distensible rs-compartments could be detected in patients with severe and mild lung injury, however significantly more ARDS patients revealed slow rs-compartments in PEEP-decreasing steps. The influence of slowly distensible rs-compartments on pulmonary gas exchange is unknown and has yet to be studied.The work was performed at the Klinik für Anaesthesiologie und Transfusionsmedizin der Universität Tübingen     

Pharmacokinetics of panipenem/betamipron in patients with end-stage renal disease

Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of panipenem/betamipron. In this study, the pharmacokinetics of panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of panipenem/betamipron (500mg/500mg). The in vitro extraction ratios of panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of panipenem in patients were 9.53 ± 1.26l/h with hemodialysis, and 2.92 ± 0.238l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643l/h and 0.615 ± 0.511l/h, respectively. The clearance of panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500mg/500mg of panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.     

A new method for the diagnosis of acute hemorrhagic-necrotizing pancreatitis using contrast-enhanced CT

Twenty-eight consecutive patients with a first attack of alcohol-induced pancreatitis were studied using contrast-enhanced CT. The findings on CT were then related to the course of the disease. The patients with acute hemorrhagic-necrotizing pancreatitis showed significantly lower enhancement values of the pancreatic parenchyma than those with milder forms of the disease.The next 20 patients with severe pancreatitis were scanned using a slightly modified procedure. The enhancement values were calculated and plotted on the graphs for the 2 former groups.Two categories of pancreatic enhancement were found: low enhancement and high enhancement. In all 10 patients with low-enhancement values surgery revealed hemorrhagic-necrotizing pancreatitis. In the 10 patients with highenhancement values conservative treatment was continued, and the clinical course was nonfulminant in all of them.     

Learning about new anesthetics using a model driven,full human simulator

Objective.New pharmacological agents are introduced into medical practice at an ever-increasing pace. Teaching how to use new medications in the clinical setting presents educational challenges and puts patients at risk. Methods.Patients and clinical settings in which remifentanil might provide clinical advantages over existing anesthetics were identified. A simulator curriculum was developed to demonstrate the use of remifentanil in the sample cases. The simulation was designed to highlight the clinical advantages and potential side effects of remifentanil. A screen displaying the concentrations of remifentanil in plasma and in the hypothetical effector site was developed. A simulator was modified (addition of an infusion pump and a pharmacokinetic screen display) and transported to several cities in the U.S.A. An instructor guided small groups of anesthesiologists and anesthetists through a structured program that enabled participants to observe drug effects in simulated patients. Results.There were 836 participants in the remifentanil program, which was offered in 58 cities in the U.S.A. Surveys were completed by 574 anesthesiologists. There was a significant difference in comfort level for using remifentanil after the session compared to before (Chi-square, p< 0.001.) The statement: Clinical simulation experience is a means to learn about new agents like remifentanilwas rated as excellent by 81% and as good by 19% of participants. No participant found the experience to be not useful. Conclusions.Patient simulation is a novel method of introducing new drugs to the medical community and is perceived by anesthesia providers as a valuable addition to available teaching methods.     

Two Bankrobbers With “Antisocial” and “Schizoid/Avoidant” Personality Disorders, Comorbid With Partial Seizures: Temporal Lobe Epilepsy and Limbic Psychotic Trigger Reaction, Respectively

Diagnostic overshadowing is illustrated by two cases of unplanned, motiveless bank robbery, initially merely attributed to antisocoial or schizoid/avoidant (loner) personality disorder, respectively. Both disorders, however, were comorbid with their potentially unobservable counterparts, with brief partial seizures, supported by both men's abnormal scalp-EEG's, their symptomatology with psychosis, and their histories of closed head injury in childhood. Such injuries are known to render particularly the temporo-limbic brain system susceptible to later partial seizure: Mr. A. had temporal lobe epilepsy (TLE) with stereotypic auditory command hallucinations and clouding of consciousness. (His past antisocial aggressive behavior might also have reflected TLE-related inter-ictal events.) Mr. B. had the symptomatology proposed as limbic psychotic trigger reaction (LPTR). Mr. B., a social loner, typically ruminated on past intermittent moderate stresses, a specific precondition of seizure kindling, ultimately elicited by a specific stimulus, resembling his past hurts. As is typical for LPTR, Mr. B. had no clouding of consciousness and no amnesia for his atavistically regressive acts, committed with flat affect, nausea, and fleeting delusions of grandeur (being gifted, like Rembrandt).     

Komplexitätstheorie und Manualmedizin

Zusammenfassung  Ausgehend von Fallbeobachtungen wird dargestellt, dass die teils sehr unterschiedlichen Effekte manueller Therapie (MT) am besten verständlich sind, wenn man 2 unterschiedliche Wirkungsweisen unterscheidet. Diese Differenzierung in robuste und subtile MT ermöglicht es, beide Behandlungstypen effizienter einzusetzen. Komplexitätstheoretische Konzepte und die Theorie des intelligenten Organismus werden zur Erklärung dieser Effekte erläutert und diskutiert.

Elevated serum bleomycin-detectable iron concentrations in patients with sepsis syndrome

Objective To determine serum bleomycin-detectable free iron in patients with septic shock and to relate these findings to both outcome and a marker of free radical damage.Design A prospective observational study.Setting A nine-bed intensive care unit in a university teaching hospital.Patients Sixteen consecutive patients with septic shock, defined as: (1) Clinical evidence of acute infection; (2) hypo- or hyperthermia (<35.6° or >38.3°C); (3) tachypnoea (>20 breaths/min or ventilated); (4) tachycardia (>90 beats min); (5) shock (systolic pressure <90 mmHg) or on inotropes. Fourteen patients also had secondary organ dysfunction.Measurements and results Bleomycin-detectable iron concentrations were elevated in all patients (37.2±11.0 mol/l vs 5.1±3.3 mol/l in healthy subjects,P<0.0001), but there was no difference between patients who died and those who survived (39.2±9.3 and 36.2±12.3 mol/l, respectively). Thiobarbituric acid reactive substances 9an index of lipid peroxidation) were higher in those who died (3.33±2.29 mol/l) than in the surviving patients (0.99±0.14 mol/l,P<0.01) or healthy subjects (0.92±0.39 mol/l,P<0.01). Free iron did not correlate with thiobarbituric acid-reactive substances. However, a significant correlation was found between lipid peroxidation and clinical severity (APACHE II) score (r=0.54,P<0.05).Conclusions The present study provides evidence of lipid peroxidation in patients who die with septic shock. The data suggest that ironcatalysed hydroxyl radical generation does not form an important contribution to this lipid peroxidation in patients with sepsis.     

Chronic daily headache: recent insights from functional imaging

Abstract New imaging technology allows us to study neurologic disorders that have had no previous structural basis. There have been recent reports on the involvement of nociceptive pathways in daily headache. A systematic review was performed using key words chronic daily headache and imaging. This paper reviews the literature on imaging studies performed on daily headache with emphasis on the new imaging technology.     

Positive end-expiratory pressure: Implications for tidal volume changes in anesthesia machine ventilation

In clinical practice, the addition of positive end-expiratory pressure (PEEP) into a standard anesthesia circle circuit decreases the delivered tidal volume (DTV) to a patient. We studied the magnitude of the DTV/PEEP relationship in two commonly used anesthesia systems. In addition, the magnitude of the DTV/PEEP relationship varies with both pulmonary compliance and volume of gas contained in the patient's breathing system between the ventilator and PEEP valve site, and this was also evaluated. Routine monitoring of expired tidal volume should be used whenever PEEP is added to an anesthesia circuit.     

Cardiac output measurement by the thermodilution method: An in vitro test of accuracy of three commercially available automatic cardiac output computers

Objective To describe the accuracy and the reproducibility of the thermodilution flow measurements obtained using 3 commercially available cardiac output computers commonly used in intensive care units.Design An experimental in vitro study. Twelve different values of control flow (Qctr) were measured (Qmsr) using 3 different cardiac output computers (Abbott Critical Care System, Oximetrix 3 SvO₂/CO Computer, Baxter Oximeter/Cardiac Output Computer SAT-1^TM; American Edwards Laboratories, 9520 A Cardiac Output Computer). Standard equipment and techniques were employed, taking account of the specific weight and heat of warm water relative to blood. In addition, separate sets of measurements were performed in order to investigate the effect on Qmsr of some variables which may influence the indicator loss (time for injection, depth of immersion of the catheter, temperature of the injected fluid).Setting Our laboratory, inside the intensive care unit.Measurements and results The analysis of the linear regression of Qmsr versus Qctr (r values between 0.992 and 0.984; residual standard deviation values comprised between 0.24 and 0.49 l/min; intercepts and slopes not significantly different from identity line), the values of the percentage errors (PE=[Qctr–Qmsr]·100/Qctr; PE mean values 7.9, 5.0 and 13.1), and those of the coefficients of variability (CV=standard deviation mean value, %; CV mean values 5.4, 5.8 and 4.6), show a good level of accuracy and reproducibility of the measurements. Our data confirm previously reported results. Furthermore, the cumulative effect of variables capable of influencing the indicator loss, even if corrected according to the calculation constant the manufacturers provide, was found to result in statistically significant changes of Qmsr.Conclusion The accuracy and reproducibility of the automatic cardiac computers tested is sufficient for practical clinical purpose. It may also depend on the modality of injection of the cooling bolus, which may significantly influence the effective indicator losses.     

Reversible “locked-in” syndromes

Two young patients are described who made good recoveries from a locked-in syndrome presumed to be due to ventral pontine ischemia. The first patient recovered completely from quadriplegia and mutism. In the second patient the only permanent sequellae were slight dysarthria and mild spasticity. Since patients may recover nearly completely from a locked-in syndrome, aggressive supportive therapy seems justified during the initial weeks or months.     

Content dimensions of self-statements in assertive situations: A factor analysis of two measures

The individual and combined factor structures of two assertive self-statement inventories, the Assertive Self-Statement Test (ASST) and the Subjective Probability of Consequences Inventory (SPCI), were investigated. Both measures showed adequate internal reliability coefficients. Factor loadings for the ASST suggest that this scale may be more multidimensional in its negative and positive self-statement content than originally assumed, while loadings for the SPCI corresponded closely with Fiedler and Beach's (1978) original intentions. A second-order analysis performed on factor scores from the ASST and SPCI revealed two conceptual dimensions common to both inventories. These second-order factors were felt to reflect externally oriented concerns and internally oriented concerns when refusing unreasonable requests. Multiple regression analyses indicated that both separate scale factors and second-order factors were differentially predictive of subjects' degree of ability to formulate effective refusal responses. Results are discussed in terms of the increased clarity of assertive self-statement content afforded by the current methods.Appreciation is expressed to Randy L. Cale and John L. Rodman for their assistance in conducting this study.