Statistical analysis of MCC-IMS data for two group comparisons-an exemplary study on two devices.

The Multi-capillary-column-Ion-mobility-spectrometry (MCC-IMS) technology for measuring breath gas can be used for distinguishing between healthy and diseased subjects or between different types of diseases. The statistical methods for classifying the corresponding breath samples typically neglects potential confounding clinical and technical variables, reducing both accuracy and generalizability of the results. Especially measuring samples on different technical devices can heavily influence the results. We conducted a controlled breath gas study including 49 healthy volunteers to evaluate the effect of the variables sex, smoking habits and technical device. Every person was measured twice, once before and once after consuming a glass of orange juice. The two measurements were obtained on two different devices. The evaluation of the MCC-IMS data regarding metabolite detection was performed once using the software VisualNow, which requires manual interaction, and once using the fully automated algorithm SGLTR-DBSCAN. We present statistical solutions, peak alignment and scaling, to adjust for the different devices. For the other potential confounders sex and smoking, in our study no significant influence was identified.

Developmental venous anomaly in the newborn brain.

INTRODUCTION: Cerebral developmental venous anomaly (DVA) is considered a benign anatomical variant of parenchymal venous drainage; it is the most common vascular malformation seen in the adult brain. Despite its assumed congenital origin, little is known about DVA in the neonatal brain. We report here the first cohort study of 14 neonates with DVA. METHODS: Fourteen infants (seven preterm) with DVA diagnosed neonatally using cranial ultrasound (cUS) and magnetic resonance imaging (MRI) from three tertiary neonatal units over 14 years are reviewed. RESULTS: DVA was first detected on cUS in 6 and on MRI in 8 of the 14 infants. The cUS appearances of DVA showed a focal fairly uniform area of increased echogenicity, often (86 %) adjacent to the lateral ventricle and located in the frontal lobe (58 %). Blood flow in the dilated collector vein detected by Doppler ultrasound (US) varied between cases (venous flow pattern in ten and arterialized in four). The appearance on conventional MRI was similar to findings in adults. Serial imaging showed a fairly constant appearance to the DVAs in some cases while others varied considerably regarding anatomical extent and flow velocity. CONCLUSIONS: This case series underlines that a neonatal diagnosis of DVA is possible with carefully performed cUS and MRI and that DVA tends to be an incidental finding with a diverse spectrum of imaging appearances. Serial imaging suggests that some DVAs undergo dynamic changes during the neonatal period and early infancy; this may contribute to why diagnosis is rare at this age.

Muscle activity during running in water and on dry land: matched physiology.

We investigated muscle activity during deep water running (DWR) and treadmill running on dry land (TMR) at similar physiological responses. 9 subjects (30.7±10.4 years) participated in this study. The baseline conditions consisted of TMR at 3 ratings of perceived exertion (RPE) level (RPE 11, 13, and 15) with heart rate (HR) recorded during each condition. The target HR for each level of DWR condition was determined by the HR recorded during the TMR. Muscle activity from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and gastrocnemius (GA) were measured. As originally planned, HR was not different between modes (P>0.05) and was different between exercise intensities (P<0.001). Only TA muscle activity was influenced by the interaction of mode and intensity (P<0.05). Muscle activity from the GA during DWR was significantly lower than that of TMR (a 34-48% decrease; P<0.05), although muscle activity from the remaining tested muscles were not influenced by modes of exercise (P>0.05). These observations suggest that matching HR can be recommended to produce similar magnitude of lower extremity muscle activity during DWR to that of TMR, with the exception of the GA.

Severe neonatal complication of transverse lie after preterm premature rupture of membranes.

Both transverse lie and preterm premature rupture of membranes (PPROM) are associated with neonatal morbidity and mortality. We present a neonate born at 29 weeks gestation with severe birth trauma after PPROM and transverse lie. The patient had extensive swelling and areas of desquamated and necrotic skin of the right lower limb. Neonatal compartment syndrome (NCS) was suspected. Perfusion of the limb improved after decompressing subcutaneous incisions. A fetus in transverse lie may be mechanically damaged in the case of PPROM, especially at an early gestational age. Early recognition is of great interest in the management and prognosis of NCS.

Cranial ultrasound and MRI at term age in extremely preterm infants.

OBJECTIVES: Conventional MRI at term age has been reported to be superior to cranial ultrasound (cUS) in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in a previous study cUS was performed during the first 6 weeks only and not in parallel to MRI at term age. Therefore, the aim of the present work was to study brain injuries in preterm infants performing concomitant cUS and MRI at full-term age. METHODS: In a population-based cohort of 72 extremely low gestational age infants paired cUS and conventional MRI were performed at term age. Abnormalities on MRI were graded according to a previously published scoring system. On cUS images the lateral ventricles, the corpus callosum, the interhemispheric fissure and the subarachnoidal spaces were measured and the presence of cysts, grey matter abnormalities and gyral folding were scored. RESULTS: Moderate or severe WM abnormalities were detected on MRI in 17% of infants and abnormalities of the grey matter in 11% of infants. Among infants with normal ultrasound (n=28, 39%) none had moderate or severe WM abnormalities or abnormal grey matter on MRI. All infants with severe abnormalities (n=3, 4%) were identified as severe on MRI and cUS. CONCLUSIONS: All severe WM abnormalities identified on MRI at term age were also detected by cUS at term, providing the examinations were performed on the same day. Infants with normal cUS at term age were found to have a normal MRI or only mild WM abnormalities on MRI at term age.

Combined endovascular stent-graft repair and adjunctive visceral vessel reconstruction for complex thoracoabdominal aortic aneurysms.

AIM: This study demonstrates the therapeutic value of the hybrid open and endovascular procedure in anatomically challenging thoracoabdominal aortic aneurysms (TAAAs) in high-risk patients. METHODS: Between January 2000 and February 2006, 8 patients were treated with open visceral vessel revascularization and endovascular repair for TAAAs. Patient data were available from medical records. Pre- and postoperative physical examination, intra-arterial angiography, and spiral computed tomography scanning was performed in prearranged examinations. RESULTS: A total of 28 visceral bypasses were performed in the 8 patients: 6 patients with complete visceral vessel revascularization and 2 with an aorto-mesenteric-celiac bypass. Aneurysm exclusion was achieved through the deployment of in total 23 stent-grafts. Seven out of the 8 procedures were conducted electively and one under urgent conditions. The mean follow-up period was 21 months. We recorded one procedure-related death due to postoperative hemorrhage resulting from diffuse retroperitoneal bleeding with consecutive multiorgan failure. Moreover, one patient developed acute renal insufficiency, but returned to normal values after temporary hemodialysis. Major adverse events included 2 cases of pneumonia and one myocardial infarction. Two reoperations were performed due to one mesenteric bypass occlusion and one groin hematoma. No neurological complications were observed. CONCLUSION: The combined hybrid endovascular and open surgical approach in the treatment of complex TAAAs remains a feasible and effective operation technique. The less invasive character of the procedure and avoidance of aortic-cross clamping are clear advantages. Nevertheless, further study is mandatory to establish this alternative therapeutic option for complex TAAAs.

Vacuum assisted wound closure in postoperative periprosthetic groin infections: a new gold standard?

AIM: This study was designed to control the results of conservative treatment using vacuum assisted wound closure (VAWC) applied exclusively to cases of deep groin infections with involvement of alloplastic graft material. METHODS: During a 2 year period 10 patients with 11 deep inguinal infections involving alloplastic graft material were treated with supportive VAWC. Intraoperative management included extensive debridement, sartorius myoplastic and VAWC application. A retrospective case-note review was performed. Variables comorbidity, surgical management of the infection, microbiological results, complications and Doppler results were analysed. RESULTS: Six early graft infections (< 30 days after implantation) and 5 late infections were treated. In 3 cases (27.3%) the infected graft material was replaced by a silver-coated Dacron prosthesis. The mean duration of VAWC was 16+/-7.7 days; postoperative mean hospital stay was 25.3+/-8.5 days. Mean postoperative follow-up was 13.1 months with no procedure-related mortality. CONCLUSION: Even in the presence of synthetic vascular graft material, negative pressure therapy can greatly simplify challenging wound healing problems under maintenance of the alloplastic grafts. These preliminary results demonstrate the safety and effectiveness of VAWC for the treatment of deep alloplastic graft infections.

Antibiotics modulate the stimulated cytokine response to endotoxin in a human ex vivo, in vitro model.

BACKGROUND: Sepsis may lead to the suppression of stimulated cytokine release after Gram-negative stimuli, correlating with a fatal outcome. Treatment of sepsis includes adequate therapy with antibiotics. The aim of this study was to investigate the role of antibiotics in the modulation of the lipopolysaccharide (LPS)-stimulated cytokine response of human monocytes. METHODS: In this ex vivo, in vitro study, whole blood samples were taken from 10 healthy volunteers, stimulated with LPS in the presence or absence of various antibiotics (penicillin, amoxicillin, cefuroxime, ceftazidime, cefotaxime, piperacillin/tazobactam, imipenem/cilastatin, gentamicin, netilmicin, ciprofloxacin, vancomycin) and cultured for 24 h. Thereafter, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, CD14 and HLA-DR expression on monocytes was assessed using flow cytometry. RESULTS: All cephalosporins decreased LPS-stimulated IL-10 release. Cefuroxime and cefotaxime also decreased the expression density of the LPS recognition molecule CD14 on monocytes. An increase in LPS-stimulated IL-10 release was observed with vancomycin. A suppression of LPS-stimulated TNF-alpha and IL-10 release was observed in the presence of ciprofloxacin. CONCLUSION: These results indicate a modulation of the expression density of CD14 on monocytes, together with a shift from a balanced to an inflammatory cytokine release pattern, by cefuroxime and cefotaxime. Vancomycin changes the response to an anti-inflammatory release pattern. After ciprofloxacin, a profound unresponsiveness of immune-competent cells to LPS stimulation is observed. Because of the critical role of a balanced innate immune response, these data may be of importance for the selection of antibiotics in septic patients.

[Standard procedures in hemodialysis shunt surgery]. / Standardverfahren in der Hämodialyse-Shuntchirurgie.

Native arteriovenous (AV) fistula are the first choice for primary hemodialysis access. It is essential to save as much vein as possible, and therefore distal AV shunts should be tried first. In patients with diabetes, primary brachiocephalic shunts are indicated and show better results than distal AV fistulae. The major complication of AV fistulae is shunt thrombosis. Immediate surgical repair is necessary, with the aim of preserving enough puncture sites to allow prompt continuation of the hemodialysis therapy. It is important to avoid central venous catheters, because these cause infectious complications more frequently. Shunt infections occur more often in polytetrafluoroethylene grafts than in native AV fistulae and represent a life-threatening situation for dialysis patients.

Ginkgo biloba special extract EGb 761 in the treatment of peripheral arterial occlusive disease (PAOD)--a review based on randomized, controlled studies.

OBJECTIVE: The present review gives an overview and evaluation of clinical studies proving the efficacy of EGb 761 in patients with PAOD. METHODS: Relevant original papers and reports on this topic were identified by means of a literature search. Only randomized, double-blind, placebo-controlled clinical trials in patients with the indication peripheral arterial occlusive disease in stage II according to Fontaine were included (only treatment with the oral form of EGb 761). For the selected studies the ratio theta of the walking distance between EGb 761 and placebo was calculated and a test for relevant superiority of EGb 761 was performed (according to the guidelines of the Deutsche Gesellschaft für Angiologie (German Society of Angiology) [Heidrich et al. 1996]). Furthermore, a pooled estimation of the ratio was carried out. RESULTS: Nine studies complied with the criteria. The methodological quality and design of the trials were heterogeneous. In the majority of the studies, there was an advantage of EGb 761 in the increase of pain-free walking distance compared to placebo. For 7 studies, the advantage was found to be statistically significant. Testing the relevant superiority showed a significant result in 6 of the selected studies. The pooled estimator of the ratio amounts to theta = 1.23 (95% CI: 1.16, 1.31) and demonstrates the efficacy of EGb 761 over placebo as well. CONCLUSIONS: This review confirms the efficacy of Ginkgo biloba special extract EGb 761. It demonstrates not only the statistical significance of the difference with respect to placebo but also the clinical relevance for the treatment of patients with PAOD.

Effect of doxapram on cerebral blood flow velocity in preterm infants.

BACKGROUND: Doxapram is used to treat apnea of prematurity when there is an insufficient response to methylxanthine treatment. As an unwanted side effect, reduced cerebral perfusion has been seen in methylxanthine-treated infants while effects of doxapram on the cerebral perfusion have not been studied yet. PATIENTS AND METHODS: Fifteen preterm infants treated with doxapram were included in the study. Birth weight ranged from 380 g to 1150 g (median 740 g), gestational age from 24 to 27 weeks (median 26 weeks). Infants received a doxapram loading dose (2.5 mg/kg) over a 30-minute period, followed by a continuous infusion of 0.5 mg/kg/h. Using Doppler sonography, blood flow velocities and the resistance index were measured in the anterior cerebral artery. Measurements were performed at baseline and 30 and 120 minutes after the start of doxapram. RESULTS: Maximal systolic blood flow velocity (V(max)) decreased significantly after the infants had received the loading dose (V(max) baseline: 40.7 cm/s +/- 6.9 [mean +/- SD]; V(max) 30 min: 35 cm/s +/- 8.9; p = 0.0017) but returned to near baseline values at 120 min (38.5 +/- 9.0, p = 0.22). End-diastolic, time-averaged, and time-averaged maximal velocities did not change significantly at 30 or 120 min. CONCLUSIONS: Doxapram induced a significant decrease in maximal cerebral blood flow velocity. Further studies are needed to assess whether this decrease may be critical to cerebral white matter perfusion in the vulnerable preterm infant.

[Comparison of effects of endotracheal suction and surfactant administration on hemodynamics and oxygenation of premature infants--a near infrared spectroscopy study]. / Vergleich der Effekte von endotrachealem Absaugen und Surfactantapplikation auf Hämodynamik und Oxygenierung Frühgeborener--Eine Nahinfrarotspektroskopie-Studie.

BACKGROUND: Aim of this study was to assess whether the decrease in heart rate and oxygen saturation occurring acutely after bolus administration of surfactant is different from the effect of endotracheal suctioning and whether there are effects on cerebral haemodynamics and oxygenation. METHODS: Twelve premature infants, birth weight 720-1560 g (Median 935 g), gestational age 25-30 weeks (Median 28 weeks), were investigated during surfactant administration (Curosurf) as a single bolus and a preceding endotracheal suctioning procedure. Using near infrared spectroscopy changes in cerebral blood volume and cerebral oxygenation index were assessed. Heart rate, arterial oxygen saturation, PCO2, and arterial blood pressure were registered continuously. Data were compared at 30, 60 and 120 seconds after the beginning of suctioning and surfactant administration. RESULTS: Endotracheal suctioning and surfactant administration induced a similar decrease in heart rate (-29/min, SD 25, p < 0.01 and -30/min, SD 23, p < 0.001) during the first 30 seconds and in oxygen saturation at the 30 seconds datapoint (-3%, SD 2, p < 0.01 and -3%, SD 6, p < 0.05). The decrease in oxygen saturation persisted at 60 seconds after the start of suctioning (-4%, SD 5, p < 0.05). In contrast, oxygen saturation was no longer different from baseline levels 60 seconds after surfactant administration (+1%, SD 6, p = 0.5). After suctioning, cerebral oxygenation index had decreased significantly from baseline levels at 30, 60, and 120 seconds. In contrast, after surfactant administration, no significant difference from baseline was noted at 30 and 60 seconds and a significant increase occurred at 120 seconds. Mean arterial blood pressure, PCO2, and cerebral blood volume did not change significantly during endotracheal suctioning and during surfactant administration. CONCLUSIONS: Acute decreases in heart rate and oxygen saturation during bolus administration of surfactant are equal to effects occurring during endotracheal suctioning. However, the decrease in oxygen saturation is shorter and more importantly, no decrease in cerebral oxygenation occurs.

Prophylactic urgent revascularization of the internal carotid artery in the symptomatic patient.

BACKGROUND: The symptomatic patient showing a string sign or ulcerative stenosis of the internal carotid artery (ICA) is subject to a high risk of arterial thrombosis or persisting intracranial embolization during the waiting period before operative revascularization. PATIENTS AND METHODS: During one year 186 operative revascularization procedures of the ICA were performed on the symptomatic patient. 26 of them fulfilled the prophylactic urgency criteria: symptoms of the cerebrovascular insufficiency and a string sign or ulcerative stenosis of the ICA with ulceration greater than 2 mm in depth. These results were compared to the control group of the 157 procedures under elective circumstances. RESULTS: Mean clamping time of the urgency and the elective patients were 23.8 min vs. 24.5 min and operation time 50.1 min vs. 54.3 min. None of our urgency patients presented new neurological defects in the postoperative phase, while this occurred in 3.8% in the elective group. Mortality rate in the elective group was 2.7% and 0% in the urgency group. Furthermore, there were fewer local complications in the urgency group. CONCLUSION: The urgent indication for the desobliteration of the ICA showing a symptomatic string sign or ulcerative stenosis can be recommended. Early thrombosis or neurological defects during the waiting period may be prevented without increasing complication rates.

[Small premature infants do not tolerate axillary temperature measurement any better than rectal measurement. Study of the effect of axillary and rectal temperature measurement on vital parameters and cerebral hemodynamics and oxygenation]. / Kleine Frühgeborene tolerieren die axilläre Temperaturmessung nicht besser als die rektale. Untersuchung zum Effekt von axillärer und rektaler Temperaturmessung auf Vitalparameter und zerebrale Hämodynamik und Oxygenierung.

BACKGROUND: Aim of this study was to assess, by use of monitoring parameters and near infrared spectroscopy (NIRS), whether premature infants tolerate axillary temperature measurement better than rectal. METHODS: Twenty-one infants were studied. Birth weight was 540-1680 g (median 840 g), weight at the time of investigation 470-1500 g (Median 920 g), gestational age 24-31 weeks (median 29 weeks), age at time of investigation 4-25 days (median 11 days). Four pairs of axillary/rectal temperatures were taken in every infant. Heart rate and oxygen saturation were monitored. Using NIRS cerebral oxygenated and deoxygenated hemoglobin were measured and total cerebral hemoglobin and the cerebral oxygenation index were calculated. RESULTS: Mean heart rate increased slightly but significantly from baseline during axillary and rectal temperature measurement (axillary: +6/min (+/- 7); p < 0.0001; rectal: +4/min (+/- 6); p < 0.0001). Peak increase in heart rate was significantly higher during axillary than during rectal temperature measurement (axillary: +18/min (+/- 10); rectal: +14/min (+/- 8); axillary versus rectal: p = 0.02). There was no difference in the number of measurements during which oxygen saturation dropped intermittently below 88% (rectal: 21% of measurements; axillary: 20% of measurements). NIRS parameters were not significantly different between axillary and rectal measurements: cerebral oxygenated hemoglobin and the oxygenation index showed a decrease in cerebral oxygenation during both, axillary and rectal measurement. CONCLUSIONS: Axillary temperature measurement is not better tolerated than rectal in premature infants.

Umbilical artery catheter blood sampling decreases cerebral blood volume and oxygenation in very low birthweight infants.

UNLABELLED: The aim of this study was to assess whether blood sampling from umbilical artery catheters reduces cerebral blood volume and cerebral oxygenation in very low birthweight infants. A total of 20 infants, median birthweight 890 g (530-1,500 g), median gestation age 26 +4 wk (range: 22 +5 to 30 +6 wk) were studied from 10 min before until 10 min after routine blood sampling from umbilical artery catheters placed in the high position. Using near infrared spectroscopy, changes in concentrations of cerebral oxygenated and deoxygenated haemoglobin were measured, and changes in cerebral blood volume and cerebral oxygenation index were calculated. Heart rate, oxygen saturation, transcutaneous PO2 and PCO2 were registered continuously. Mean arterial blood pressure was measured before and after sampling. Oxygenated haemoglobin decreased significantly from baseline during blood sampling, whereas deoxygenated haemoglobin did not change significantly. This resulted in a decrease in cerebral blood volume and cerebral oxygenation index. Heart rate increased slightly, but significantly, from baseline. Oxygen saturation, blood pressure, transcutaneous PO2 and PCO2 did not change significantly. CONCLUSION: Blood sampling from umbilical artery catheters induces a significant decrease in cerebral blood volume and cerebral oxygenation.

Carotid endarterectomy prior to major abdominal aortic surgery.

BACKGROUND: Major aortic surgery carries a high risk of stroke. Carotid artery occlusive disease (CAOD) has been identified as one of the contributing risk factors. Regarding the long-term prevention of stroke, carotid endartectomy (CEA) seems to be superior to the best medical treatment in patients with high-grade CAOD. However, the role of CEA prior to major aortic surgery has not been studied. DESIGN: Prospective study, observational design. SUBJECTS AND SETTING: 201 patients referred to a community hospital for major aortic surgery. INTERVENTION: The patients were non-invasively screened by continuous-wave and duplex Doppler ultrasonography for the presence of CAOD. In 41 patients with angiographically confirmed high-grade CAOD, CEA was performed prior to major aortic surgery. MAIN OUTCOME MEASURE: Combined mortality and major morbidity from CEA and abdominal aortic surgery. RESULTS: There was no mortality or morbidity related to CEA. Total perioperative mortality related to major aortic reconstruction was 3.5%. No new perioperative focal neurologic deficits occurred except for one fatal stroke in a patient in whom CEA had been judged not to be indicated. CONCLUSIONS: CEA can be performed safely prior to major aortic surgery resulting in excellent overall neurologic outcome in patients with high-grade CAOD. We propose that patients scheduled for major aortic surgery be screened for the presence of high-grade CAOD and that CEA be performed first, if indicated according to published guidelines.

Effect of surfactant administration on cerebral haemodynamics and oxygenation in premature infants--a near infrared spectroscopy study.

OBJECTIVES: The aim of this study was to assess changes in cerebral haemodynamics and oxygenation induced by surfactant administration using near infrared spectroscopy (NIRS). METHODS: Eighteen premature infants, mean birth weight 960 g (range 550-1560 g), mean gestation age 28 weeks (range 25-30 weeks), were studied during 27 surfactant administrations. Porcine surfactant was administered to treat respiratory distress syndrome in a bolus of 100 mg/kg. Manual bag ventilation was performed for one minute after instillation. Heart rate, arterial oxygen saturation measured by pulse oximetry, transcutaneous PO2 (TcPO2), and PCO2 (TcPCO2), blood pressure, and cerebral oxygenated (O2Hb), deoxygenated (HHb), and total haemoglobin (tHb) concentration changes obtained by NIRS were registered every second from 15 minutes before until 30 minutes after surfactant administration. RESULTS: During surfactant administration, there was a short-lasting but significant drop in heart rate and arterial oxygen saturation. NIRS parameters remained constant during and up to 1 minute after administration. One to three minutes after administration, heart rate, oxygen saturation, and TcPO2 increased significantly concomitantly with an increase in O2Hb and a decrease in HHb. In 10 cases, TcPO2 increased above 100 mmHg. tHb--indicative of cerebral blood volume--did not change significantly. Five to 30 minutes after surfactant administration there was no difference of monitoring data from baseline levels. TcPCO2 and blood pressure remained unchanged during the measurement period. CONCLUSION: Cerebral blood volume remained constant in very-low-birth-weight infants when surfactant was administered by bolus administration followed by manual ventilation according to our protocol. Attention should be directed towards rapid adaptation of inspiratory oxygen concentrations after surfactant administration to avoid hyperoxaemia.

Eversion endarterectomy versus open thromboendarterectomy and patch plasty for the treatment of internal carotid artery stenosis.

OBJECTIVE: in 1996 we changed our treatment for stenosis of the internal carotid artery (ICA) from open thromboendarterectomy and PTFE-patch plasty (TEA) to eversion endarterectomy (EEA). DESIGN: retrospective study. METHODS: a total of 475 EEAs of the ICA were performed between 2/96 and 11/96. These results were compared to the results of TEA carried out between 2/94 and 11/94 (n=388). RESULTS: clamping and operation time were significantly shorter for EEA. Neurological complications included transient ischaemic attacks in 1. 0% in the EEA group versus 1.3% after TEA (p=0.72), minor strokes (0. 6% vs. 1.8%, p=0.10) and major strokes in 1.5% versus 1.1% (p=0.59). The rate of restenosis >50% was 2.5% after EEA and 10.2% after TEA. The only detectable difference of statistical significance in complication rates was in the lesions of the hypoglossal nerve (5.3% vs. 2.6%, p=0.04). CONCLUSIONS: EEA of the ICA is a safe procedure for carotid reconstruction with the additional advantages of short clamping time, possibility of simultaneous shortening of an elongated ICA, and no requirement for patching.

Low-dose iloprost infusions compared to the standard dose in patients with peripheral arterial occlusive disease Fontaine stage IV. DAWID Study Group.

BACKGROUND: Intravenous iloprost, titrated from 0.5 up to 2.0 ng/kg/min has been shown in patients with PAOD III/IV to significantly improve healing of trophic lesions, relief of rest pain, and reduce the rate of major amputation or death at 6 months as compared to placebo. The effect is considered related to improvement of the microcirculation. The aim of the present trial was to identify an optimum dose regarding treatment response and tolerability, by studying 4 doses of 25, 50, 75 and 100 micrograms iloprost daily. PATIENTS AND METHODS: 302 patients with PAOD IV were randomised via a double-blind fashion to one of the 4 doses. The primary endpoint was the responder rate at end of treatment. Responders were defined as patients with very good or good global efficacy, as judged by lesion healing and pain relief. Side effects were documented and a pre-defined benefit/risk index was calculated. RESULTS: No dose-dependency of iloprost regarding primary or secondary endpoints was observed. The rate of responders ranged between 48.7-53.5%. Side effects, mainly related to vasodilation, increased dose-dependently (p < 0.001, chi 2-test), with a significant decrease of the benefit/risk index from 2.19 +/- 1.19 to 1.64 +/- 0.97 (p = 0.012, ANOVA). Responders had a better outcome at 6 months than non-responders (2.6 fold higher rate of major amputation or death; life table analysis). CONCLUSIONS: It is concluded that iloprost should be titrated to the optimum rather than maximum tolerated dose, since a higher incidence of side effects not associated with an increased treatment response was observed at higher doses.

GPCRDB: an information system for G protein-coupled receptors.

The GPCRDB is a G protein-coupled receptor (GPCR) database system aimed at the collection and dissemination of GPCR related data. It holds sequences, mutant data and ligand binding constants as primary (experimental) data. Computationally derived data such as multiple sequence alignments, three dimensional models, phylogenetic trees and two dimensional visualization tools are added to enhance the database's usefulness. The GPCRDB is an EU sponsored project aimed at building a generic molecular class specific database capable of dealing with highly heterogeneous data. GPCRs were chosen as test molecules because of their enormous importance for medical sciences and due to the availability of so much highly heterogeneous data. The GPCRDB is available via the WWW at http://www.gpcr.org/7tm