Changes in respiratory mechanics and gas exchange during the acute respiratory distress syndrome

BACKGROUND: The time course of impairment of respiratory mechanics and gas exchange in the acute respiratory distress syndrome (ARDS) remains poorly defined. We assessed the changes in respiratory mechanics and gas exchange during ARDS. We hypothesized that due to the changes in respiratory mechanics over time, ventilatory strategies based on rigid volume or pressure limits might fail to prevent overdistension throughout the disease process. METHODS: Seventeen severe ARDS patients {PaO2/FiO2 10.1 (9.2-14.3) kPa; 76 (69-107) mmHg [median (25th-75th percentiles)] and bilateral infiltrates} were studied during the acute, intermediate, and late stages of ARDS (at 1-3, 4-6 and 7 days after diagnosis). Severity of lung injury, gas exchange, and hemodynamics were assessed. Pressure-volume (PV) curves of the respiratory system were obtained, and upper and lower inflection points (UIP, LIP) and recruitment were estimated. RESULTS: (1) UIP decreased from early to established (intermediate and late) ARDS [30 (28-30) cmH2O, 27 (25-30) cmH2O and 25 (23-28) cmH2O (P=0.014)]; (2) oxygenation improved in survivors and in patients with non-pulmonary etiology in late ARDS, whereas all patients developed hypercapnia from early to established ARDS; and (3) dead-space ventilation and pulmonary shunt were larger in patients with pulmonary etiology during late ARDS. CONCLUSION: We found a decrease in UIP from acute to established ARDS. If applied to our data, the inspiratory pressure limit advocated by the ARDSnet (30 cmH2O) would produce ventilation over the UIP, with a consequent increased risk of overdistension in 12%, 43% and 65% of our patients during the acute, intermediate and late phases of ARDS, respectively. Lung protective strategies based on fixed tidal volume or pressure limits may thus not fully avoid the risk of lung overdistension throughout ARDS.

Acute stress reactions in the first 3 weeks postpartum: A study of 219 parturients

OBJECTIVES: There is increasing research on posttraumatic stress (PS) 4-6 weeks and 3 months postpartum, but, there are no data on acute stress reactions (ASR) in the first 3 weeks postpartum, i.e. the potential precursors of PS. However, ASR may have long-term effects, e.g., on a subsequent pregnancy without having manifested as PS in the meantime. We propose: (i) to describe the patterns of ASR after childbirth, (ii) to explore differences between women with normal and traumatogenic ASR, and (iii) to provide data on the early detection of traumatogenic ASR 2 and 3 weeks postpartum. STUDY DESIGN: Intra-event variables (relationship with caregivers, overall birth experience, and dissociative experiences, as well as obstetric variables) were assessed 48-96h. postpartum, as were ASR (by means of the Impact-of-Event Scale IES) in weeks 1, 2, and 3 postpartum. According to research on PS the upper 33%-range of ASR in weeks 2 and 3 was defined as 'traumatogenic'. RESULTS: Normal ASR in week 1 are at a level which in non-obstetric trauma-situations is considered as the upper range of low stress or lower range of medium distress. ASR decline constantly from week 1 to week 3. However, high ASR in week 1 do not drop faster than do low ones, thus indicating a prolonged stress reaction in women with high ASR in week 1. Low ASR (IES-scores <10) and high ASR (IES-scores >20) in week 1 are highly predictive for normal ASR, and traumatogenic ASR in weeks 2 and 3, respectively. Medium ASR (IES-scores 10-20) in week 1 are of uncertain predictive value for stress reactions in weeks 2 and 3 and have to be re-assessed at that time. CONCLUSIONS: Clinical screening for ASR appears to be helpful in detecting women with a compromised ability to process childbirth-related stress. The association between ASR and long-term development should be further explored.

Bacterial profile and burden of periodontal infection in subjects with a diagnosis of acute coronary syndrome

BACKGROUND: Periodontitis has been identified as a potential risk factor in cardiovascular diseases. It is possible that the stimulation of host responses to oral infections may result in vascular damage and the inducement of blood clotting. The aim of this study was to assess the role of periodontal infection and bacterial burden as an explanatory variable to the activation of the inflammatory process leading to acute coronary syndrome (ACS). METHODS: A total of 161 consecutive surviving cases admitted with a diagnosis of ACS and 161 control subjects, matched with cases according to their gender, socioeconomic level, and smoking status, were studied. Serum white blood cell (WBC) counts, high- and low-density lipoprotein (HDL/LDL) levels, high-sensitivity C-reactive protein (hsC-rp) levels, and clinical periodontal routine parameters were studied. The subgingival pathogens were assayed by the checkerboard DNA-DNA hybridization method. RESULTS: Total oral bacterial load was higher in the subjects with ACS (mean difference: 17.4x10(5); SD: 10.8; 95% confidence interval [CI]: 4.2 to 17.4; P<0.001), and significant for 26 of 40 species including Porphyromonas gingivalis, Tannerella forsythensis, and Treponema denticola. Serum WBC counts, hsC-rp levels, Streptococcus intermedius, and Streptococcus sanguis, were explanatory factors to acute coronary syndrome status (Nagelkerke r2=0.49). CONCLUSION: The oral bacterial load of S. intermedius, S. sanguis, Streptococcus anginosus, T. forsythensis, T. denticola, and P. gingivalis may be concomitant risk factors in the development of ACS.

Activation of non-ischemic, hypoxia-inducible signalling pathways up-regulate cytoprotective genes in the murine liver

BACKGROUND/AIMS: We investigated the molecular response of a non-ischemic hypoxic stress in the liver, in particular, to distinguish its hepatoprotective potential. METHODS: The livers of mice were subjected to non-ischemic hypoxia by clamping the hepatic-artery (HA) for 2h while maintaining portal circulation. Hypoxia was defined by a decrease in oxygen saturation, the activation of hypoxia-inducible factor (HIF)-1 and the mRNA up-regulation of responsive genes. To demonstrate that the molecular response to hypoxia may in part be hepatoprotective, pre-conditioned animals were injected with an antibody against Fas (Jo2) to induce acute liver failure. Hepatocyte apoptosis was monitored by caspase-3 activity, cleavage of lamin A and animal survival. RESULTS: Clamping the HA induced a hypoxic stress in the liver in the absence of severe metabolic distress or tissue damage. The hypoxic stimulus was sufficient to activate the HIF-1 signalling pathway and up-regulate hepatoprotective genes. Pre-conditioning the liver with hypoxia was able to delay the onset of Fas-mediated apoptosis and prolong animal survival. CONCLUSIONS: Our data reveal that hepatic cells can sense and respond to a decrease in tissue oxygenation, and furthermore, that activation of hypoxia-inducible signalling pathways function in part to promote liver cell survival.

Internal iliac artery embolization before endovascular repair of aortoiliac aneurysms with a nitinol vascular occlusion plug

PURPOSE: To evaluate the acute and midterm effectiveness of a novel vascular occlusion device for embolization of the internal iliac artery (IIA) before endovascular repair of aortoiliac aneurysms. MATERIALS AND METHODS: Between March 2005 and April 2006, nine men (mean age, 75 years +/- 5; range, 66-83 y) with aortoiliac aneurysms underwent bifurcated endovascular stent-graft procedures. All these patients were referred specifically for embolization. Pre- and perioperatively, eight patients underwent unilateral embolization and one underwent bilateral embolization of the IIA to prevent type II endoleak. Via a contralateral femoral approach with a 6-F or 8-F sheath, the embolization procedure was performed with an Amplatzer Vascular Plug, a self-expandable cylindrical device consisting of a nitinol-based wire mesh. Technical success, clinical outcome, and complications were evaluated. Follow-up at 3, 6, and 12 months was performed with clinical and radiologic examinations. RESULTS: IIA embolization was technically successful in all cases and no procedure-related complications occurred. Imaging at discharge and at 3-, 6-, or 12-month follow-up was accomplished in all nine patients. Control computed tomography and magnetic resonance angiography did not reveal retrograde perfusion of the aneurysmal sac, ie, type II endoleak. Three of nine patients (33.3%) reported symptoms of buttock claudication that did not resolve completely. Clinical symptoms such as bowel ischemia or sexual dysfunction were not observed. CONCLUSIONS: The midterm results of this study suggest that preoperative IIA embolization with a nitinol vascular occlusion plug during endovascular treatment of aortoiliac aneurysms is safe and effective.

Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial

BACKGROUND: Coronary stents improve immediate and late results of balloon angioplasty by tacking up dissections and preventing wall recoil. These goals are achieved within weeks after angioplasty, but with current technology stents permanently remain in the artery, with many limitations including the need for long-term antiplatelet treatment to avoid thrombosis. We report a prospective multicentre clinical trial of coronary implantations of absorbable magnesium stents. METHODS: We enrolled 63 patients (44 men; mean age 61.3 [SD 9.5 years]) in eight centres with single de novo lesions in a native coronary artery in a multicentre, non-randomised prospective study. Follow-up included coronary angiography and intravascular ultrasound at 4 months and clinical assessment at 6 months and 12 months. The primary endpoint was cardiac death, non-fatal myocardial infarction, or clinically driven target lesion revascularisation at 4 months FINDINGS: 71 stents, 10-15 mm in length and 3.0-3.5 mm in diameter, were successfully implanted after pre-dilatation in 63 patients. Diameter stenosis was reduced from 61.5 (SD 13.1%) to 12.6 (5.6%) with an acute gain of 1.41 mm (0.46 mm) and in-stent late loss of 1.08 mm (0.49 mm). The ischaemia-driven target lesion revascularisation rate was 23.8% after 4 months, and the overall target lesion revascularisation rate was 45% after 1 year. No myocardial infarction, subacute or late thrombosis, or death occurred. Angiography at 4 months showed an increased diameter stenosis of 48.4 (17.0%). After serial intravascular ultrasound examinations, only small remnants of the original struts were visible, well embedded into the intima. Neointimal growth and negative remodelling were the main operating mechanisms of restenosis. INTERPRETATION: This study shows that biodegradable magnesium stents can achieve an immediate angiographic result similar to the result of other metal stents and can be safely degraded after 4 months. Modifications of stent characteristics with prolonged degradation and drug elution are currently in development.

ECG-triggered muscular counterpulsation for treatment of low cardiac output

BACKGROUND: Skeletal muscular counterpulsation (MCP) has been used as a new noninvasive technique for treatment of low cardiac output. The MCP method is based on ECG-triggered skeletal muscle stimulation. The purpose of the present study was to evaluate acute hemodynamic changes induced by MCP in the experimental animal. METHODS: Eight anaesthetized pigs (43+/-4 kg) were studied at rest and after IV â-blockade (10 mg propranolol) before and after MCP. Muscular counterpulsation was performed on both thighs using trains (75 ms duration) of multiple biphasic electrical impulses with a width of 1 ms and a frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was used to synchronize stimulation to a given time point. LV pressure-volume relations were determined using the conductance catheter. After baseline measurements, MCP was carried out for 10 minutes at low and high stimulation amplitude. The optimal time point for MCP was determined from LV pressure-volume loops using different stimulation time points during systole and diastole. Best results were observed during end-systole and, therefore, this time point was used for stimulation. RESULTS: Under control conditions, MCP was associated with a significant decrease in pulmonary vascular resistance (-18%), a decrease in systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops showed a leftward shift with a decrease in end-systolic volume. After â-blockade, cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%). CONCLUSIONS: In the animal model, ECG-triggered skeletal muscular counterpulsation is associated with a significant improvement in cardiac function at baseline and after IV â-blockade. Thus, MCP represents a new, non-invasive technique which improves cardiac function by diastolic compression of the peripheral arteries and veins, with a decrease in systemic vascular resistance and increase in cardiac output.

EEG reactivity and EEG activity in never-treated acute schizophrenics, measured with spectral parameters and dimensional complexity

Our approaches to the use of EEG studies for the understanding of the pathogenesis of schizophrenic symptoms are presented. The basic assumptions of a heuristic and multifactorial model of the psychobiological brain mechanisms underlying the organization of normal behavior is described and used in order to formulate and test hypotheses about the pathogenesis of schizophrenic behavior using EEG measures. Results from our studies on EEG activity and EEG reactivity (= EEG components of a memory-driven, adaptive, non-unitary orienting response) as analyzed with spectral parameters and "chaotic" dimensionality (correlation dimension) are summarized. Both analysis procedures showed a deviant brain functional organization in never-treated first-episode schizophrenia which, within the framework of the model, suggests as common denominator for the pathogenesis of the symptoms a deviation of working memory, the nature of which is functional and not structural.

Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer's disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

The synergistic action of a VEGF-receptor tyrosine-kinase inhibitor and a sensitizing PDGF-receptor blocker depends upon the stage of vascular maturation

OBJECTIVE: To investigate the effects of tyrosine-kinase inhibitors of vascular endothelial growth factor (VECF) and platelet-derived growth factor (PDCF)-receptors on non-malignant tissue and whether they depend upon the stage of vascular maturation. MATERIALS AND METHODS: PTK787/ZK222584 and CGP53716 (VEGF- and PDGF-receptor inhibitor respectively), both alone and combined, were applied on chicken chorioallantoic membrane (CAM). RESULTS: On embryonic day of CAM development (E)8, only immature microvessels, which lack coverage of pericytes, are present: whereas the microvessels on E12 have pericytic coverage. This development was reflected in the expression levels of pericytic markers (alpha-smooth muscle actin, PDGF-receptor beta and desmin), which were found by immunoblotting to progressively increase between E8 and E12. Monotherapy with 2 microg of PTK787/ZK222584 induced significant vasodegeneration on E8, but not on E12. Monotherapy with CGP53716 affected only pericytes. When CGP53716 was applied prior to treatment with 2 microg of PTK787/ZK222584, vasodegeneration occurred also on E12. The combined treatment increased the apoptotic rate. as evidenced by the cDNA levels of caspase-9 and the TUNEL-assay. CONCLUSION: Anti-angiogenic treatment strategies for non-neoplastic disorders should aim to interfere with the maturation stage of the target vessels: monotherapy with VEGF-receptor inhibitor for immature vessels, and combined anti-angiogenic treatment for well developed mature vasculature.

Acute device-based blood pressure reduction: electrical activation of the carotid baroreflex in patients undergoing elective carotid surgery

Carotid sinus baroreceptors are involved in controlling blood pressure (BP) by providing input to the cardiovascular regulatory centers of the medulla. The acute effect of temporarily placing an electrode on the carotid sinus wall to electrically activate the baroreflex was investigated. We studied 11 patients undergoing elective carotid surgery. Baseline BP was 146+30/66+/-17 mm Hg and heart rate (HR) 72+/-7 bpm (mean +/- standard deviation). An electrode was placed upon the carotid sinus and after obtaining a steady state baseline of BP and HR, an electric current was applied and increased in 1-volt increments. A voltage dependent and highly significant reduction in BP was observed which averaged 18+/-26* and 8.0+/-12 mm Hg for systolic BP and diastolic BP, respectively. Maximal reductions occurred at 4.4+/-1.2 V: 23+/-24 mm Hg*, 16+/-10 mm Hg* and 7+/-12 bpm* for systolic BP, diastolic BP and HR, respectively ( = p <.05). Thus, electrical stimulation of the carotid sinus activates the carotid baroreflex resulting in a reduction in BP and HR. This presents a proof of concept for device based baroreflex modulation in acute BP regulation and adds to the available data which provide a rationale for evaluating this system in the context of chronic BP reduction in hypertensive patients.

Stenting of common iliac vein obstructions combined with regional thrombolysis and thrombectomy in acute deep vein thrombosis

OBJECTIVES: To evaluate the efficacy of stent placement after infrainguinal loco-regional thrombolysis and iliac thrombectomy (surgical TT) of acute deep vein thrombosis (DVT) in patients with May-Thurner-Syndrome. MATERIAL AND METHODS: We retrospectively analysed a group of 11 patients (9 women) (mean age 34 years, range 16-64 years) with surgical TT and additional intra-operative stenting due to compression of the common iliac vein. Patients underwent venography to demonstrate outflow patency after surgical TT, and to identify any obstruction at the level of the left-sided common iliac vein ("Beckenvenen-Sporn"). Obstruction at the level of arterial crossing was treated using Wallstents placed via an introducer sheath from the inguinal access site. Stents were fully deployed using balloons adjusted to the size of vein. Patients were treated with oral anticoagulants for 6 months, and followed using duplex ultrasonography. RESULTS: Technical success defined as complete vein patency and normal valve function was documented in all 11 patients. One patient needed early stent extension due to residual stenosis. At 6 months follow-up one patient (9%) had an asymptomatic occlusion of the stented common iliac vein. In all 11/11 (100%) patients the femoral segment was found to be patent, and in 1/11 (9%) there was mild reflux with few clinical symptoms of post-thrombotic syndrome. The calculated cumulative primary patency rate for venous iliac stents was 82%, and assisted patency rate was 91%, which remained unchanged over a mean follow-up of 22 months. CONCLUSION: Combining surgical TT and stenting of common iliac vein obstructions in DVT is safe, effective, and results in a acceptable venous patency.

Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection

BACKGROUND: CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. METHODOLOGY/PRINCIPAL FINDINGS: Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. CONCLUSIONS/SIGNIFICANCE: During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.

[Acute headache in a case of cerebral cavernomas]

We report a case of a 52-year-old female patient with known cerebral cavernomas and acute headache. A cranial CT scan excluded an intracranial bleeding. Cavernomas are rare vascular malformations of the venous blood system (synon. cavernous angiomas) with a slow blood flow. Clinical manifestation is presented between an age of 30-50 years with mostly unspecific neurological symptoms like headache, nausea, vomiting and dizziness, but also epileptic seizures and bleedings may occur. In general, therapy is symptomatic. In cases of seizures, however, anticonvulsive treatment is indicated. Operation can be discussed for peripheral localized cavernomas with bleeding or for refractory seizures. If antiplatelet or anticoagulation therapy is necessary due to other diseases (coronary heart disease, atrial fibrillation, thrombosis, pulmonary embolism), cerebral cavernomas are not considered as an absolute contraindication. The risk for an ischemic stroke under atrial fibrillation (5-20%), for example, is higher than the risk for bleeding of a cerebral cavernoma under anticoagulation therapy.