The effect of homeopathically prepared thyroxine on highland frogs: influence of electromagnetic fields.

BACKGROUND: Previous experiments show that amphibian larvae are responsive to homeopathically prepared thyroxine. METHODS: We studied the effect of a highly diluted and agitated thyroxine solution exposed to various electromagnetic fields on metamorphosis in highland Rana temporaria. The devices tested were: microwave oven, mobile phone, airport X-ray, and a red light barcode scanner. Animals were treated either with homeopathically prepared thyroxine (10(-30) parts by weight, 10(-35) in the water in which the animals were kept), or analogously prepared blank solution, or analogously prepared thyroxine exposed to the electromagnetic field of one of the devices tested. Solutions were administered at 48h intervals according to a standardized protocol. RESULTS: Animals treated with the standard test solution thyroxine 10(-30) metamorphosed more slowly than the control animals, ie the effect of the homeopathically prepared thyroxine was opposed to the usual physiological effect of molecular thyroxine. The cumulative number of test animals that had reached the four-legged stage at defined points in time was smaller in the group treated with homeopathically prepared thyroxine at most of the points in time. This was found independently by all three research teams involved. In contrast, this effect did not occur when the thyroxine solution had been exposed to the field of the early model microwave oven, or mobile phone. There was no difference between aqueous or alcoholic solutions were used, and there was, if any, only a small protective effect from aluminum foil. Airport X-ray and red light barcode scanning did not diminish the effect of the homeopathic solution.

Prostaglandin E(1) does not influence plasmatic coagulation, hepatic synthesis, or postoperative blood loss in patients after coronary-artery bypass grafting.

STUDY OBJECTIVE: To assess whether postoperatively administered prostaglandin E1 (PGE1) might prevent bleeding in patients after coronary artery bypass grafting (CABG). DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: University-affiliated hospital. PATIENTS: 49 patients scheduled for elective CABG surgery. INTERVENTIONS: The PGE1 group received intravenous PGE(1) up to 15 ng/kg/min for 72 hours after surgery, whereas the placebo group received isotonic saline for the same time period. MEASUREMENTS AND MAIN RESULTS: Nine patients (4 in the PGE1 group vs. 5 in the placebo group) had to be excluded because of hemodynamic instability, and 1 in the placebo group because of gastric bleeding. In the remaining 39 patients (20 vs. 19), no significant differences with regard to hemoglobin levels or platelet count could be observed. There was no significant difference between the groups concerning the amount of packed red blood cells, platelet concentrates, or fresh frozen plasma transfused. No significant differences could be observed regarding laboratory markers of coagulation activation or hepatic synthesis either. CONCLUSIONS: PGE1 did not prevent coagulation disturbances and blood loss when administered postoperatively in patients undergoing CABG. The absence of these expected effects might be explained by the concomitant administration of acetylsalicylic acid, whose antiaggregatory acivity seems to exceed the effects of PGE1.

Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit.

OBJECTIVE: To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. DESIGN: Retrospective cohort study. SETTING: ICU at a university cancer referral center. PATIENTS: A total of 414 cancer patients admitted to the ICU during a period of 66 months. INTERVENTIONS: None. MEASUREMENTS: Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. MAIN RESULTS: ICU survival was 53%, and 1-yr survival was 23%. The 1-yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long-term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. CONCLUSION: A combination of factors must be taken into account to estimate a critically ill cancer patient's prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.

[The difficult airway]. / Der schwierige Atemweg.

Management of the difficult airway has gained increasing interest, because hypoxia is one of the leading causes of death and of severe neurological sequelae related to anesthesia or resuscitation. The difficult airway algorithm of the American Society of Anesthesiologists as well as the guidelines of the European Resuscitation Council provide recommendations for the prevention of difficulties in tracheal intubation and/or mask ventilation. Especially preoperative patient evaluation is of major importance. Patients history, oral and maxillofacial anatomy, pharyngeal and laryngeal structures as well as cervical spine mobility have to be assessed and awake fiberoptic intubation has to be performed in all cooperative patients with indices pointing towards difficult airways. If problems in intubating the trachea are encountered after induction of anesthesia and mask ventilation is adequate, one must call for help and decide rapidly whether to awaken the patient or to proceed with alternative intubation techniques (e.g. different laryngoscope blades, flexible fiberoptic scope or other fiberoptic techniques, lighted wand, retrograde intubation or surgical airway). In the potentially life-threatening "cannot intubate--cannot ventilate" situation either transtracheal jet ventilation, laryngeal mask airway, the esophageal-tracheal Combitube or a surgical airway have to be performed or have to be inserted immediately. These alternative methods have to be appropriately taught and--as far as possible--to be trained under routine conditions in order to master emergency situations.

Comparison of conventional surgical versus Seldinger technique emergency cricothyrotomy performed by inexperienced clinicians.

BACKGROUND: Cricothyrotomy is the ultimate option for a patient with a life-threatening airway problem. METHODS: The authors compared the first-time performance of surgical (group 1) versus Seldinger technique (group 2) cricothyrotomy in cadavers. Intensive care unit physicians (n = 20) performed each procedure on two adult human cadavers. Methods were compared with regard to ease of use and anatomy of the neck of the cadaver. Times to location of the cricothyroid membrane, to tracheal puncture, and to the first ventilation were recorded. Each participant was allowed only one attempt per procedure. A pathologist dissected the neck of each patient and assessed correctness of position of the tube and any injury inflicted. Subjective assessment of technique and cadaver on a visual analog scale from 1 (easiest) to 5 (worst) was conducted by the performer. RESULTS: Age, height, and weight of the cadavers were not different. Subjective assessment of both methods (2.2 in group 1 vs. 2.4 in group 2) and anatomy of the cadavers (2.2 in group 1 vs. 2.4 in group 2) showed no statistically significant difference between both groups. Tracheal placement of the tube was achieved in 70% (n = 14) in group 1 versus 60% (n = 12) in group 2 (P value not significant). Five attempts in group 2 had to be aborted because of kinking of the guide wire. Time intervals (mean +/- SD) were from start to location of the cricothyroid membrane 7 +/- 9 s (group 1) versus 8 +/- 7s (group 2), to tracheal puncture 46 +/- 37s (group 1) versus 30 +/- 28s (group 2), and to first ventilation 102 +/- 42s (group 1) versus 100 +/- 46s (group 2) (P value not significant). CONCLUSIONS: The two methods showed equally poor performance.

Dexamethasone inhibits leukocyte migration through endothelial cells towards smooth muscle cells.

Leukocyte interactions with endothelial cell monolayers (ECM) and smooth muscle cells (SMC) play an important role during inflammatory processes. Several studies describe an inhibitory effect of dexamethasone on polymorphonuclear leukocytes (PMNL), endothelial cell function, and interleukin-1 (IL-1) release. Aim of the current study was to investigate the influence of dexamethasone on leukocyte migration through an endothelial cell monolayer towards SMC-layers stimulated by tumor necrosis factor-alpha (TNF-alpha). Using a recently developed triple chamber migration system, SMC-layers were cultured on the bottom of a 24-well plate. On the upper surface of the first filter, ECM were cultured, the second filter was a collecting filter. The amount of leukocyte migration through ECM towards TNF-alpha-stimulated smooth muscle cell layers with and without dexamethasone-pretreatment was measured using a fluorescence technique. The pretreatment of SMC-layers with dexamethasone reduced the amount of leukocyte migration down to 92 +/- 8.8% (0.001 mM, p=n.s.), to 67 +/- 5.7% (0.01 mM, p<0.05), to 53 +/- 4.6% (0.1 mM, p<0.05), and to 41 +/- 5.0% (1 mM, p<0.05). In conclusion, dexamethasone treatment of smooth muscle cell layers inhibits leukocyte migration through ECM towards smooth muscle cell layers. The inhibition seems to be due to a decrease in IL-1 release. Treatment of all cell types, PMNL, endothelial cells, as well as smooth muscle cell layers, simulating an in-vivo situation, seems to have an additive effect.

Leukocyte migration: a new triple migration chamber assay allows investigation of various cell interactions simultaneously.

Examination of the interactions between various cells of the vascular wall and blood components are essential for understanding different pathophysiological processes. Such investigations require appropriate techniques. Several groups have attempted to establish different methods. In all blood vessels except capillaries, endothelial cells (EC) and smooth muscle cells (SMC) coexist and interact very closely. The current study describes a new 3-dimensional triple chamber migration assay, studying leukocyte migration through human endothelial cell monolayers (ECM) towards human SMC layers simultaneously. To test the new assay, SMC-layers were prestimulated with different concentrations of tumor necrosis factor alpha (TNF-alpha, 1 ng/ml, 10 ng/ml, 100 ng/ml) over 6 hours. Then, two microporous membranes, a collecting membrane and a third membrane with cultured ECM, were inserted. Freshly isolated peripheral blood mononuclear cells (PBMNC) were seeded on the ECM and transmigrated cells were measured after further 3 hours incubation. The migration against non stimulated SMC-layers was used as control. Prestimulated SMC-layers led to a dose dependent increase of PBMNC migration into the subendothelial cell space. Antibodies against interleukin-1 reduced the PBMNC migration. In conclusion, this assay allows to study cell migration into the subendothelial space and interactions between different vascular cells. Moreover, this assay can also be used for studies on other cell-cell interactions in man.

Time course of immunological markers in patients with the systemic inflammatory response syndrome: evaluation of sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and TGF-beta 2.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) is viewed as a system-wide inflammatory response. Up until now, no parameter has been available for predicting the development of septic shock. In the present study, we evaluated the usefulness of serum levels of CD14, vascular cells adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), macrophage inflammatory protein (MIP) 1 alpha and transforming growth factor beta 2 (TGF-beta 2) as early markers of outcome in patients with SIRS. METHODS: A group of 28 SIRS patients (13 survivors/15 non-survivors) was compared with a healthy control group and with patients with local inflammation. Blood samples were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and anti-inflammatory parameters such as TGF-beta 2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: At the beginning, all evaluated proinflammatory immunological parameters with the exception of sVCAM-1 were significantly increased in patients with SIRS compared with the healthy control group. However, no significant difference could be observed for all immunological parameters comparing survivors and non-survivors, with the exception of interleukin (IL) 6 at day 7. CONCLUSION: All evaluated proinflammatory parameters were increased in patients with SIRS during the course of the disease. However, the parameters have no correlation with outcome and prognosis of SIRS patients.

Diagnostic validity of pulmonary artery catheterization for residents at an intensive care unit.

OBJECTIVE: To assess the amount of additional information provided by measurements derived from pulmonary artery catheter (PAC) use beyond that derived from clinical evaluation by intensive care residents. METHODS: One hundred forty-nine consecutive patients undergoing right-heart catheterization were prospectively included in the study. Before inserting a PAC, physicians had to predict pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), cardiac index (CI), mixed venous oxygen saturation (SvO2), oxygen delivery (DO2), oxygen consumption (VO2), and pulmonary shunt fraction (Qs/Qt) by selecting a given option on a questionnaire. Ranges of options were chosen to create clear clinical differences among them. RESULTS: The correct value was predicted in a median of 50% of cases (range, 45-63%). PAP was predicted correctly in 55%, PCWP in 46%, SVRI in 63%, CI in 62%, SvO2 in 45%, DO2 in 45%, VO2 in 51%, and Qs/Qt in 51%. A significant difference was found between estimated and measured values for all parameters (p < 0.01). No significant differences were detected between more and less experienced physicians. There was no significant difference between estimated and measured values with respect to the different courses of intensive care unit admissions or the different indications for PAC insertion. CONCLUSION: In a selected group of critically ill patients, the PAC adds valuable and clinically relevant information to clinical assessment in about 50% of cases. Its use should not be withheld in patients with unclear hemodynamic and metabolic profiles.

Cytokine profile and correlation to the APACHE III and MPM II scores in patients with sepsis.

In 35 patients fulfilling the criteria of systemic inflammatory response syndrome (SIRS) of infectious origin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), tumor necrosis factor-soluble receptor (TNF-sR), and interleukin-12 (IL-12), C-reactive protein (CRP) levels and the Acute Physiology, and Chronic Health Evaluation III score (APACHE III) were determined on days 1 to 7, 14, 21, and 28. The Mortality Probability Models (MPM) II sepsis score was assessed at the time of admission into the study. The MPM II sepsis score correlated with IL-6 plasma levels on day 1. The APACHE III scores correlated with plasma levels of TNF-sR on days 2-7, with IL-6 levels on days 3-7, and with CRP levels on days 4-7 (p < 0.01). The MPM II sepsis score, the APACHE III score, and the IL-6, TNF-sR, and CRP levels were significantly different between survivors and nonsurvivors and between patients with and without shock (p < 0.05). A significant decrease of the APACHE III scores, IL-6, and CRP levels was observed over the study period in the survivor group only (p < 0.05), while neither the dynamics of TNF-alpha nor IL-12 plasma levels contributed to the risk estimation of mortality.

Bronchoscopy via a redesigned Combitube in the esophageal position. A clinical evaluation.

BACKGROUND: The esophageal-tracheal Combitube (Kendall-Sheridan Catheter Corp., Argyle, NY) is an effective device for providing adequate gas exchange. However, tracheal suctioning is impossible with the Combitube placed in the esophageal position. To eliminate this disadvantage, the Combitube was redesigned by creating an enlarged hole in the pharyngeal lumen that allows fiberoptic access, tracheal suctioning, and tube exchange over a guide wire. METHODS: The two anterior, proximal perforations of regular Combitubes were replaced by a larger, ellipsoid-shaped hole. After the study was approved by the institutional review board, 20 patients with normal airways (Mallampati I or II) were studied. During general anesthesia, patients were esophageally intubated with the Combitube. A flexible bronchoscope was inserted and guided via the modified hole and glottic opening down the trachea. For the replacement procedure, a J tip guide wire was introduced through the bronchoscope. The bronchoscope and the Combitube were removed and a standard endotracheal tube was advanced over a guide catheter. RESULTS: Bronchoscopic evaluation of the trachea and guided replacement of the Combitube by an endotracheal tube was successful in all 20 study patients. The average time needed to perform airway exchange was 90 +/- 20 s (mean +/- SD). Arterial oxygen saturation and end-tidal carbon dioxide levels remained normal in all patients. No case of laryngeal trauma was observed during intubation or the airway exchange procedure. CONCLUSIONS: The redesigned Combitube enables fiberoptic bronchoscopy, fine-tuning of its position in the esophagus, and guided airway exchange in patients with normal airways. Further studies are warranted to demonstrate its value in patients with abnormal airways.

Prostaglandin E1 inhibits platelet decrease after massive blood transfusions during major surgery: influence on coagulation cascade?

BACKGROUND: A plunge in platelet count if often observed after massive blood transfusions during major surgery. This study was designed to assess whether the prophylactic administration of prostaglandin E1 (PGE1) might prevent this drop in platelet count. METHODS: Forty-five patients receiving massive transfusions of packed red blood cells (> 10 units) during major orthopedic surgery were enrolled in a prospective, randomized, double-blind, placebo-controlled study and divided into two groups: group 1 (therapy group) received intravenous PGE1 up to 30 ng/kg/min for 72 hours after surgery, and group 2 (placebo group) received a placebo during the same time period. RESULTS: The patients in group 1 suffered no reduction in platelet count and thus required no platelet concentrate transfusions. In contrast, a significant postoperative drop in platelet count (p < 0.05) was observed in the placebo group between days 3 and 5 after surgery when compared to the therapy group, necessitating transfusions of platelet concentrates in this group. Similarly, red blood cell count and hemoglobin were far more stable in the therapy group, which required fewer transfusions of red blood cells than did the placebo group (p < 0.05). There seemed to be a tendency toward a consumptive coagulation disorder in the placebo group as indicated by a decrease of fibrinogen levels, prothrombin time, and antithrombin III activity, and an increase of partial thromboplastin time. The incidence of adult respiratory distress syndrome was slightly lower in the therapy group. Last but not least, the length of intensive care unit stay was significantly shorter in the therapy group (p < 0.05). CONCLUSION: In our study, the administration of PGE1 prevented a reduction in platelet count. Furthermore, measurements of clotting activity furnished the possibility that PGE1 might inhibit transfusion-induced coagulation disturbances. We recommend that PGE1 should be considered in patients requiring massive transfusion during major surgery.

Influence of pentoxifylline on cytokine levels and inflammatory parameters in septic shock.

OBJECTIVE: To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock. DESIGN: Prospective study comparing a therapy group to a matched control group. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty four patients fulfilling the criteria of septic shock were included in this study. Twelve patients received PTX (therapy group) and 12 patients matched for diagnosis, age and gender served as the control group. INTERVENTIONS: Pentoxifylline at 1 mg/kg per hour over 24 h in the therapy group. MEASUREMENTS AND RESULTS: Cytokine levels [tumor necrosis factor-alpha (TNF)], soluble TNF receptor [TNF-R], and interleukin-6 [IL-6] and inflammatory proteins [C-reactive protein, alpha-1-antitrypsin (AAT), fibronectin, and haptoglobin], as well as hemodynamic parameters and the APACHE III score were evaluated before initiation of therapy and 24 h-later. After 24 h, TNF levels were significantly lower in the therapy group (p = 0.013), while IL-6 levels were significantly higher in the therapy group (p = 0.030). Within the 24 h TNF declined significantly in the therapy group (p = 0.006), while IL-6 showed a significant increase (p = 0.043). AAT and the APACHE III score tended to differ significantly after 24 h between the groups [AAT levels higher in the therapy group (p = 0.05), APACHE III score lower (p = 0.05)]. In the therapy group, the systemic vascular resistance index was significantly higher after 24 h (p = 0.0026) whereas the cardiac index declined (p = 0.035). CONCLUSIONS: PTX does influence TNF levels in septic shock patients. Nevertheless, inhibiting a single mediator in severe septic shock cannot stop the inflammatory overreaction.

Management of acquired coagulation disorders in emergency and intensive-care medicine.

Coagulation disorders usually confront the emergency physician as bleeding episodes or as abnormalities of laboratory tests. Bleeding has to be treated aggressively, while pathological coagulation tests should be related to a more differentiated diagnosis at first. The most common causes of acquired coagulation disorders are liver disease, vitamin K deficiency, and disseminated intravascular coagulation (DIC). More rarely, inhibitors, external factors such as drugs or extracorporeal circulation, or other diseases such as amyloidosis are present. Since localized hemorrhage is the most common bleeding source in liver disease, endoscopic and surgical therapeutic measures, respectively, are warranted. Careful and balanced substitution therapy according to laboratory findings should be initiated simultaneously and should consist of fresh frozen plasma (FFP), which contains all components of the coagulation system physiologically balanced. Prothrombin complex concentrates should be used in emergency situations only, keeping their potential hazards in mind. Adequate vitamin K substitution is indicated in liver disease as well as in coagulopathy due to vitamin K deficiency. Management of DIC primarily consists of aggressive treatment of the underlying disease. Substitution therapy is difficult and should be carefully monitored by the adequate laboratory tests. FFP is the adequate source of both procoagulants and inhibitors but may cause certain problems. Heparin therapy can be beneficial but is not recommended generally. Antithrombin III substitution cannot be assumed as established therapy so far. Inhibitors can lead to bleeding, but the most common inhibitor, lupus anticoagulant, rather predisposes to thrombosis. In bleeding patients with inhibitors against single clotting factors, treatment consists of adequate substitution before initiating the diagnostic workup.

[Results of critical care management of patients after bone marrow transplantation]. / Ergebnisse der intensivmedizinischen Betreung von Patienten nach Knochenmarktransplantation.

In a retrospective study we investigated the clinical course of patients who required intensive care support after bone marrow transplantation. Out of 25 patients only 5 (20%) survived treatment in the intensive care unit (ICU) and this group showed a significantly lower age, lower APACHE III and organ-failure scores and higher serum albumin values, as well as a longer interval between bone marrow transplantation and admission to intensive care. However, no patient requiring mechanical ventilation primarily for pneumonia or other infections arising as a complication of bone marrow transplantation survived intensive care. All patients requiring ventilation for more than 24 hours died in hospital. Of the 5 patients surviving ICU treatment only 3 were eventually discharged from hospital and only one single patient was alive after 6 months. Hence, current intensive care management appears to be indicated in only a small group of patients after bone marrow transplantation.

Dexverapamil as resistance modifier in acute myeloid leukaemia.

In order to evaluate dexverapamil as a resistance modifier in acute myeloid leukaemia, we have added dexverapamil (4 x 300 mg/d orally) to DA chemotherapy (daunorubicin, cytosine arabinoside) in six patients with acute myeloid leukaemia. Two patients (1 first and 1 second relapse) achieved complete remission and two patients (1 refractory disease, 1 third relapse) showed some improvement. One patient in first relapse died due to disease progression and one drug-refractory patient remained refractory. The peak plasma levels of dexverapamil and nordexverapamil ranged from about 600 to 4100 ng/ml and from 450 to 1130 ng/ml, respectively. Major sideeffects were hypotension and sinus bradycardia. These results show the need for further evaluation of dexverapamil as a resistance modifier in acute myeloid leukaemia.

[Bronchiolitis obliterans organizing pneumonia with acute respiratory insufficiency]. / "Bronchiolitis obliterans organizing pneumonia" mit akuter respiratorischer Insuffizienz.

A 22-year-old woman was hospitalized because of fever of 39 degrees C and increasing dyspnoea. The chest radiograph demonstrated coarse confluent opacities bilaterally. Despite antibiotic treatment the condition deteriorated acutely after 2 days. All efforts to find an infectious agent, including immunological tests, were unsuccessful. Artificial ventilation became necessary because of increasing respiratory failure with an arterial oxygen partial pressure of 56 mm Hg, CO2 of 41 mm Hg and a respiratory rate of 60/min. Histological examination of a transthoracic lung biopsy revealed bronchiolitis obliterans organizing pneumonia, which was treated with prednisolone. The initial dose was 500 mg/d, gradually reduced to 12.5 mg/d over 2 weeks. The clinical and radiological findings improved markedly after 2 days and the patient discharged herself after 3 weeks and there was no follow-up.