Prone and ECMO - a contradiction per se?

Acute respiratory distress syndrome (ARDS) still represents a serious problem in clinical routine and is associated with a high mortality. Several concepts are known for special treatment, but, in some instances, the application of an extracorporeal membrane oxygenation (ECMO) is necessary for both the improvement of oxygenation and the elimination of carbon dioxide (CO(2)). One basic aspect in lung protective ventilation in this context is alveolar recruitment, which can be achieved by different approaches, such as "the open lung concept", according to Lachmann, or by additional kinetic therapy. The most exposed feature of this entity is 'prone', which may be quite challenging in patients requiring extracorporeal support or organ replacement therapy under ongoing critical illness. We report two outstanding cases of prone under conditions of a veno-venous ECMO therapy which improved significantly under this position. Furthermore, we reflect critically possible risk factors and adverse events of such procedures and afford a current view from the literature.

German Registry for Acute Aortic Dissection Type A (GERAADA)--new software design, parameters and their definitions.

BACKGROUND: The working group for aortic surgery and interventional vascular surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) initiated the web-based German Registry for Acute Aortic Dissection type A (GERAADA). It is the project's aim to collect standardized data from a large pool of patients with acute aortic dissections type A (AADA) to gain a deeper insight and knowledge to improve surgical therapies and perioperative management for these patients in the future. METHODS: In addition to new medical insights, the working group has gained more experience over the last 4 years in how to collect valid and high-quality data. This experience led us to revise the database completely. In this article we describe the new version of GERAADA, providing an overview as well as defining the parameters, and explaining the new features. This overview fulfills a request by the users of GERAADA in the participating centers. RESULTS: Since its inception, 50 cardiac centers in Germany, Austria and Switzerland have provided over 2000 records and the first statistical results have been published. CONCLUSION: GERAADA's new design allows it to stay abreast of changes in medicine and to focus on the essentials necessary for statistically relevant results, while keeping the work load low for the data providers at each cardiac center.

[German Registry for Acute Aortic Dissection Type A (GERAADA): initial results]. / Deutsches Register für akute Aortendissektion Typ A (GERAADA): Erste Ergebnisse.

BACKGROUND: The working group "Aortic Surgery and Interventional Vascular Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) set up the German registry for acute aortic dissection type A (GERAADA) in July 2006. This web-based database was developed to record data of patients who had undergone surgery for aortic dissection type A (AADA). The aim of GERAADA is to learn from analyzing the data of AADA patients how to improve the perioperative management and surgical treatment of patients with AADA and to identify possible parameters affecting patient risk and outcome. PATIENTS AND METHODS: Between July 2006 and June 2009 (2010), 1558 (2137) patients with AADA were enrolled in the multi-center, prospective GERAADA database by 50 cardiac surgery centers in German-speaking countries in Europe. Data on patients' preoperative and intraoperative status, postoperative complications, midterm results and circumstances of death were recorded. Data were analyzed to identify risk factors influencing the outcome of these patients. The Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) in Mainz performed the statistical analyses. RESULTS: Analyses from GERAADA reveal a thirty-day mortality of 17% in 2137 AADA patients. Only short interventions in aortic arch surgery are safe during hypothermic circulatory arrest even without selective cerebral perfusion. If circulatory arrest times of over 30 min. are anticipated, antegrade cerebral perfusion is strongly recommended during the entire arch intervention using cardiopulmonary bypass. Surgical strategy in terms of isolated ascending aortic replacement versus ascending aortic replacement combined with aortic arch repair had no statistical relevant influence on 30-day mortality. AADA surgical results in elderly patients are more encouraging than those treated without surgery. Surgery is even feasible in octogenarians with a 35% mortality rate. CONCLUSION: The aim of this registry is to optimize AADA patients' medical care, thereby reducing their morbidity and mortality. AADA treatment should always involve open surgery. Initial analyses from GERAADA provide clinically relevant insights concerning patients with AADA, and may enable therapeutic recommendations for improving perioperative and surgical management. Our latest study detected significant influencing risk factors for the outcome of AADA patients and may contribute to a consensus in setting guidelines for standard medical treatment. PERSPECTIVE: A European Registry of Aortic Diseases ("EuRADa") is being established this year under the leadership of the "Vascular Domain" of the European Association for Cardio-Thoracic Surgery (EACTS). This database will collect parameters on all aortic diseases, dissection types A and B, aneurysms, perforating ulcer (PAU), intramural wall hematoma (IMH), traumatic aortic ruptures, and all potential treatment strategies (medical treatment, open surgical and endovascular).

German registry for acute aortic dissection type A (GERAADA)--lessons learned from the registry.

A German registry for acute aortic dissection type A (GERAADA) was initiated by the Working Group for Aortic Surgery and Interventional Vascular Surgery of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) in July 2006. This web-based database was developed to record the data of patients who had undergone surgery for aortic dissection type A. From analyzing the data, we aim to learn how to improve surgical treatment and to identify parameters affecting patient outcome. In the beginning, 33 cardiac centers participated via online access to the registry on the GSTCVS' homepage. Since then, 43 centers in Germany, Switzerland and Austria have begun entering data on the pre- and intraoperative status of their patients, postoperative complications, mid-term results and circumstances of death. We have succeeded in interpreting the initial results and trends from the registry now available to all of the participating centers, which benefit from this shared pool of analyzed data by optimizing their therapy regimes and comparing their success with that in the other centers.

Synergistic antiproliferative effect of human recombinant interferons and retinoic acid in cultured breast cancer cells.

A combination of retinoic acid (RA) and human recombinant DNA-derived interferon-gamma (Hu-IFN-gamma) was tested with respect to the growth inhibitory action on several human mammary carcinoma cell lines (ZR-75.1, 734-B, MCF-7, and BT-20), a human lung carcinoma cell line (CCL-185), and a human laryngeal carcinoma cell line (HEP-2). The mammary carcinoma cell lines were all sensitive to Hu-IFN-gamma, and 2 of them (ZR-75.1 and 734-B) were also affected by RA. The combination of both substances led to a pronounced synergistic amplification of growth inhibition in ZR-75.1 and 734-B cells. RA also increased the antiproliferative activity of Hu-IFN-gamma in the RA-resistant BT-20 cells and to a less pronounced degree in MCF-7 cells. In contrast to these findings, no synergistic effects were observed between Hu-IFN-gamma and RA in CCL-185 and HEP-2 cells. Human recombinant DNA-derived interferon-alpha 2 amplified the action of RA only in BT-20 cells, but it did not act synergistically with RA in the other cell lines tested.

Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells.

Retinoids and gamma-interferon (IFN-gamma) have been demonstrated to synergistically amplify growth inhibition in cultured breast cancer cells. Since IFN-gamma enhances effects mediated by retinoids more than vice versa, we focused our investigations on the mRNA expression of cellular retinoic acid-binding proteins (CRABPs) and retinoic acid receptors (RARs), since these are the key molecules that mediate retinoid action. Synergistic inhibition of cell proliferation under treatment with 9-cis-retinoic acid and IFN-gamma was detected in the three breast cancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cells. RAR-alpha and RAR-gamma mRNA were observed in all cell lines, whereas RAR-beta was not detectable. CRABP I message was expressed in MCF-7 cells only, but CRABP II was found in all three breast cancer cell lines. IFN-gamma (10 ng/ml) increased RAR-gamma expression but had no influence on RAR-alpha, whereas RAR-beta was not detectable in any of the cell lines. RA (1 microM)-mediated CRABP II increase was suppressed by IFN-gamma (10 ng/ml). These observations indicate that IFN-gamma-mediated increase in RAR-gamma and suppression of RA-mediated CRABP II activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.

Modulation of ovarian carcinoma tumor marker CA-125 by gamma-interferon.

Interferons are known to modulate several cellular functions by the induction of different proteins. In our study a gamma-interferon-mediated presentation of one of the most important ovarian tumor markers (CA-125) on the cell surface was demonstrated using two ovarian carcinoma cell lines in vitro (HTB-77 and SKOV-3). This induction was found to be dependent on an intact protein biosynthesis. The gamma-interferon effect reached a maximum on the third day of treatment. Under such conditions the CA-125 concentration was increased intracellularly, on the cell surface, and in the supernatant culture medium. The surface antigen was shed rapidly with a half-life of 1 day. The addition of dexamethasone to gamma-interferon treated HTB-77 cells improved CA-125 expression synergistically. HLA-DR and CA-125 expression was found to be regulated by interferons in different ways. The demonstration of CA-125 expression provides an important insight into the potential regulatory mechanism governing this tumor marker. Since interferons are naturally occurring substances as well as therapeutically administered agents, it seems necessary to pay attention to possible tumor marker modulation.

Neopterin as a prognostic indicator in patients with carcinoma of the uterine cervix.

In vitro, neopterin, a pyrazinopyrimidine compound, is excreted by human monocytes-macrophages after induction by supernatants from activated T-lymphocytes or by recombinant gamma-interferon. In vivo, it represents a noninvasive test for activation of cellular immune reactions. To evaluate the prognostic value of pretherapeutic urinary neopterin levels and of serial neopterin measurements during follow-up in women with cervical cancer, 1088 urine specimens from 186 consecutive patients were analyzed. Clinical assessments were made without knowledge of the results of neopterin assays (a "blinded" assessment). During the observation period (June 1980 to March 1984), 27 relapses, 18 metastases, and 26 deaths were seen. The prognostic significance of pretherapeutic neopterin and other possible prognostic clinical and laboratory parameters was tested by the univariate and multivariate Cox proportional hazards model using a stratification according to stage and surgical treatment. The combination of age at diagnosis, pretherapeutical hemoglobin, leukocyte count, and neopterin was found to predict survival best. On the basis of this result, risk groups were identified exhibiting markedly different survival behavior. A highly significant association was found between serial neopterin measurements and the risk for a relapse, metastasis, or death. The data suggest that urinary neopterin levels might be a useful adjuvant parameter in monitoring women with cervical cancer.

Paclitaxel- and docetaxel-dependent activation of CA-125 expression in human ovarian carcinoma cells.

Taxanes represent a new class of antineoplastic agents that are being evaluated in several malignant tumors; they have been shown to induce a high remission rate and to prolong survival in ovarian cancer patients. However, CA-125 has been suggested to be an unreliable marker for monitoring response to paclitaxel therapy. Therefore, we were interested in whether taxanes may directly modulate CA-125 expression. Human ovarian carcinoma cell lines OVCAR-3, HOC-7, SKOV-6, 2780, 2774, and HTB-77 were treated with paclitaxel or docetaxel. Secreted, surface-associated, and cytosolic CA-125 were estimated by means of a sandwich solid-phase RIA or by immuno-flow cytometry. In addition to in vitro antiproliferative activity, paclitaxel and docetaxel augmented the expression of the tumor marker CA-125 in the three ovarian carcinoma cell lines, OVCAR-3, HOC-7, and SKOV-6, constitutively expressing this tumor marker. The three CA-125-negative cell lines, 2780, 2774, and HTB-77, did not respond to taxane treatment by expressing this tumor marker, although their proliferation was markedly inhibited. The taxane-mediated induction of CA-125 was found to be dependent on intact protein and RNA biosynthesis. However, CA-125 concentration was increased in the supernatant medium only and not on cell surface or cytosol. Our results demonstrate an in vitro activation of ovarian carcinoma cells in terms of CA-125 secretion by taxanes. This may explain the CA-125 fluctuations observed in vivo under paclitaxel treatment and may indicate that CA-125 is not a reliable tumor marker during taxane chemotherapy.

Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer.

PURPOSE: The clinical impact of endogenous cytokines supplied with deterministic properties in the generation of either T helper (Th)1 -type or Th2-type immune response was investigated in patients with ovarian cancer. Whereas interleukin (IL)- 12 initiates the differentiation of naive Th0 cells toward Th1 phenotype, IL-4 and IL-10 mediate the development of Th2-type immunity. PATIENTS AND METHODS: Cytokines were determined before treatment by means of enzyme-linked immunosorbent assay (ELISA) in ascites fluid and serum of 76 patients with ovarian cancer. Cytokine levels were compared with each other and with standard clinicopathologic parameters. A stepwise logistic regression was calculated to rule out interdependence in the associations of the various variables. Survival analyses were performed with the Kaplan-Meier method and differences in survival were examined according to Mantel and Breslow. Cox proportional hazards analysis was used to identify independent prognostic factors. RESULTS: Whereas IL-10 and IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only 43% of the specimens. With the exception of neopterin, macrophage colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels were significantly elevated in ascites fluid compared with serum (P < .01). In univariate analyses, high ascitic-fluid concentrations of either neopterin, tumor necrosis factor-alpha (TNF-alpha), or IL-12 were associated with poor disease-free (P < .005) and overall (P < .01) survival. Multivariate Cox regression analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable that retained independent prognostic significance (P < .03 for disease-free and P < .01 for overall survival), together with residual disease, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO)-stage, and patient age. CONCLUSION: In ovarian cancer, high ascitic-fluid IL-12 levels, which may indicate a local Th1-generated immune response, are associated with disease progression.

The prognostic value of nuclear roundness and neopterin in ovarian cancer.

The prognostic value of clinical factors, morphometric features and neopterin, a marker for macrophage activation, was investigated retrospectively in 68 ovarian carcinoma patients. Nuclear roundness was a good predictor of patient survival. About 50% of our patients showed neopterin concentrations above the cut-off level of 275 mumol/mol creatinine. Interestingly, those patients with elevated urinary neopterin concentration, and thus displaying a sign of activation of cell-mediated immunity, had a shorter survival than those with normal concentration. Applying a multivariate Cox regression analysis, the only independent parameters predicting patient survival were FIGO stage, residual disease, nuclear roundness and neopterin.

Human interferon-gamma increases adhesion of cultured carcinoma cells to the substratum.

Effects of human recombinant-DNA derived interferon-gamma and -alpha 2 on the adhesion of cultured breast cancer cells (BT-20, ZR-75.1, MCF-7, 734-B and Hs-578-T), larynx carcinoma cells (HEP-2), epidermoid carcinoma cells (KB), lung carcinoma cells (CCL 185), and ovarian carcinoma cells (1847) to the surface of cell culture plastic dishes were studied. Layered cells were detached after a 3-day treatment with interferon either by trypsin-EDTA, trypsin, protease or cooling to 4 degrees C. Treatment with interferon-gamma (500 unit/ml) significantly increased the incubation time for trypsin-EDTA, EDTA and at 4 degrees C necessary to bring cells into suspension for the 4 cell lines BT-20, ZR-75.1, MCF-7 and HEP-2. Interferon-alpha 2 was not able to induce a similar effect. Reattachment of interferon-gamma treated ZR-75.1 cells was not increased after harvesting by trypsinization or EDTA action. Decreased adhesion of cultured cells is associated with transformation and the effects of interferon-gamma may be explained by reinforced normal phenotype. Interferon-gamma induced adhesion was not associated with other interferon effects especially the anti-proliferative activity or modulation of surface antigens.

Inhibition of the estradiol-induced growth of cultured human breast cancer cells by the anti-estrogens tamoxifen, desmethyl-tamoxifen, 4-hydroxy-tamoxifen and enclomiphene.

The growth effects of tamoxifen (T), desmethyl-tamoxifen (dMeT), 4-hydroxy-tamoxifen (OHT) and enclomiphene (Clo) on cultured human breast cancer cell lines have been related to published binding affinities for the estrogen receptor. Only in cells which were stimulated by estrogens did these anti-estrogens markedly inhibit growth. In both estrogen sensitive cell lines tested, 734 B and ZR 75.1, the anti-estrogen activity showed the identical rank: OHT much greater than Clo approximately equal to T = dMeT; this anti-proliferative potency agrees with reported affinities of these compounds for the estrogen receptor. In culture media containing defined amounts of estradiol we observed that a 10,000-fold molar excess of OHT was required to inhibit the estradiol-induced growth, but the estradiol-independent proliferation was not affected.

Evaluation of cerebral metabolism and quantitative electroencephalography after hypothermic circulatory arrest and low-flow cardiopulmonary bypass at different temperatures.

Although widely used for repair of complex cardiovascular pathologic conditions, long intervals of hypothermic circulatory arrest and low flow cardiopulmonary bypass may both result in cerebral injury. This study examines cerebral hemodynamics, metabolism, and electrical activity to evaluate the risks of cerebral injury after 60 minutes of hypothermic circulatory arrest at 8 degrees C, 13 degrees C, and 18 degrees C, compared with 60 minutes of low flow cardiopulmonary bypass at 18 degrees C. Thirty-two puppies were randomly assigned to one of four experimental groups and centrally cooled to the appropriate temperature. Serial evaluations of quantitative electroencephalography, radioactive microsphere determinations of cerebral blood flow, calculations of cerebral oxygen consumption, cerebral glucose consumption, cerebral vascular resistance, cerebral oxygen extraction, systemic oxygen metabolism, and systemic vascular resistance were done. Measurements were obtained at baseline (37 degrees C), at the end of cooling, at 30 degrees C during rewarming, and at 2, 4, and 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. At the end of cooling, cerebral vascular resistance remained at baseline levels in all groups, but systemic vascular resistance was increased in all groups. Cerebral oxygen consumption became progressively lower as temperature was reduced: it was only 5% of baseline at 8 degrees C; 20% at 13 degrees C; and 34% and 39% at 18 degrees C. Quantitative electroencephalography was silent in the 8 degrees C and 13 degrees C groups, but significant slow wave activity was present at 18 degrees C. Systemic vascular resistance and cerebral oxygen consumption returned to baseline values in all groups by 2 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass, but cerebral vascular resistance remained elevated at 2 and 4 hours, not returning to baseline until 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. All but two of the long-term survivors (27 of 32) appeared neurologically normal; after hypothermic circulatory arrest at 8 degrees and 18 degrees C two animals had an unsteady gait. Comparison of quantitative electroencephalography before operation and 6 days after operation showed a significant increase in slow wave activity (delta activity) after hypothermic circulatory arrest and low flow cardiopulmonary bypass at 18 degrees C, a change that suggests possible cerebral injury. Although undetected after operation by simple behavioral and neurologic assessment, significant differences in cerebral metabolism, vasomotor responses, and quantitative electroencephalography do exist during and after hypothermic circulatory arrest and low flow cardiopulmonary bypass at various temperatures and may be implicated in the occurrence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantitative electroencephalography: a method to assess cerebral injury after hypothermic circulatory arrest.

Although hypothermic circulatory arrest and low-flow cardiopulmonary bypass are routinely used for surgical correction of congenital cardiac anomalies, use of long durations of arrest, often required for more complex repairs, raises serious concerns about cerebral safety. Searching for an intraoperative assessment that can reliably predict cerebral injury, we have found an excellent correlation between changes in quantitative electroencephalography intraoperatively and immediately postoperatively after prolonged hypothermic arrest, and neurologic and behavioral evidence of cerebral injury. After epidural placement of four recording electroencephalographic electrodes and baseline neurologic/behavioral and electroencephalographic assessment, 32 puppies were randomly assigned to one of four groups: hypothermic controls in which cooling to 18 degrees C was followed immediately by rewarming, 30 minutes of hypothermic circulatory arrest at 18 degrees C, 90 minutes of arrest at 18 degrees C, and 90 minutes of low-flow cardiopulmonary bypass at 25 ml/kg per minute at 18 degrees C. An electroencephalogram was recorded at baseline, after cooling, during rewarming, and at 2, 4, and 8 hours after the start of rewarming, as well as before the operation and 1 week after the operation. Postoperative neurologic and behavioral outcome was assessed 24 hours after cardiopulmonary bypass and daily for 1 week by means of a graded scale in which 0 is normal and 12 and 13 indicate severe neurologic injury (coma and death). Thirty animals survived the experimental protocol: two animals in the 90-minute hypothermic arrest group died before neurologic evaluation could be completed, and the remainder exhibited various degrees of neurologic and behavioral impairment, more severe on day 1 than on day 6. No animal in the remaining groups had a significant neurologic deficit. Quantitative electroencephalographic analysis shows marked differences between the 90-minute arrest group and the controls in the percent electroencephalographic silence during rewarming and at 2 hours, and in the percent recovery of baseline power at 2, 4, and 8 hours. At 2 hours after the start of rewarming, a correlation between electroencephalographic amplitude and neurologic/behavioral score on day 1 was carried out, which predicts with great certainty (p < 0.00001) that if electroencephalographic power at this time is less than 500 microV2, overt neurologic injury will subsequently become apparent. In addition, a significant shift from higher to lower frequency in the day 6 postoperative electroencephalogram compared with baseline occurs only in the 90-minute arrest group.(ABSTRACT TRUNCATED AT 400 WORDS)

The natural history of thoracic aortic aneurysms.

Because improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 +/- 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 +/- 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (> 5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter)2.1; change in volume = 0.0356 (initial aortic volume)1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased plasma tryptophan in pregnancy.

OBJECTIVE: To examine levels of serum tryptophan and its degradation product kynurenine in uncomplicated pregnancy, according to the week of pregnancy and the concentrations of neopterin. METHODS: Plasma was analyzed from 45 healthy pregnant women (15 in each trimester), 15 healthy puerperas, and 20 nonpregnant controls. Tryptophan and kynurenine were measured by reverse-phase, high-performance liquid chromatography, and neopterin by radioimmunoassay. RESULTS: In healthy pregnant women, tryptophan values decreased (median first trimester: 72 mumol/L; second trimester: 51 mumol/L; third trimester: 46 mumol/L; P < .001) in a manner correlated with the duration of pregnancy (Spearman rank correlation coefficient ra = -0.771, P < .001) and normalized in the puerperium (median 60 mumol/L). No change in kynurenine, a tryptophan degradation product, was observed, but the ratio of kynurenine to tryptophan increased during pregnancy and correlated positively with gestational age (ra = 0.714, P < .001). In addition, an inverse correlation existed between neopterin and tryptophan concentrations (ra = -0.566, P < .001), as well as a positive one between neopterin and the kynurenine to tryptophan ratio (ra = 0.660, P < .001). CONCLUSION: Tryptophan levels decrease during normal pregnancy and the decrease may be related to immune activation phenomena.

Atrial natriuretic peptide-induced release of cyclic guanosine monophosphate by coronary bypass grafts.

BACKGROUND: Superior long-term patency rates of the internal mammary artery (IMA) versus saphenous vein (SV) after coronary artery bypass grafting are well documented. Higher production rates of vasodilating and platelet-inhibiting mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact on its long-term durability and resistance to coronary artery graft disease. For the right gastroepiploic artery (RGEA) marked release of protective mediators is reported as well. The vasodilating effect of cyclic guanosine monophosphate (cGMP) released after stimulation by atrial natriuretic peptide might serve as another graft protective system. The aim of the present study was to determine cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge. METHODS: Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was determined by 125-iodide radioimmunoassay. RESULTS: Basal cGMP production rates of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of atrial natriuretic peptide led to a statistically significant increase of cGMP release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3 fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05). CONCLUSIONS: From these data we conclude that the IMA in comparison with the RGEA and SV produces more extracellular cGMP when stimulated by atrial natriuretic peptide. This effect might support the cGMP-mediated protective properties of nitric oxide and could underline the extraordinary suitability of the IMA as a bypass conduit.

Aortic dissection involving a double aortic arch with a right descending aorta.

We report the successful surgical treatment of a 67-year-old man with a double aortic arch, right descending aorta, and a subacute dissection of the descending thoracic aorta using hypothermic circulatory arrest.