For continuous variables, normal distribution was analysed by the

For continuous variables, normal distribution was analysed by the Shapiro-Wilk test. To detect differences between the patient groups, either the Student’s t-test or the Mann-Whitney U test was performed, depending on the underlying distribution. For categorical selleck kinase inhibitor variables, Fisher’s exact test was used. Statistics were calculated using IBM SPSS Statistics 18 (SPSS Inc., Chicago, IL, USA).ResultsIn the fibrinogen-PCC group, 80 of 353 patients treated in the STC between 2005 and 2009 fulfilled the inclusion criteria. Between 2005 and 2008 (data for 2009 were not available at the time of analysis), 21,263 patients were included in the TR-DGU. Of 21,263 patients, 2,582 fulfilled the general inclusion criteria. At this step, most cases were lost due to missing base deficit values.

After applying the specific haemostatic therapy criteria (Table (Table1),1), 601 patients could be included in the FFP group.Demographic data and trauma scores were available for all patients included in the study. As intended, the two groups were comparable with regard to demographic parameters as well as the overall magnitude of injury sustained and probability of survival assessed by the TRISS and RISC scores (Table (Table2).2). With regard to the pattern of injury, patients in the FFP group had sustained head and thoracic injuries of higher magnitude, whereas fibrinogen-PCC patients had sustained more severe abdominal injuries. Patients in the fibrinogen-PCC group also appeared to be less haemodynamically stable upon arrival at the ER. Standard laboratory coagulation data were available for at least 90% of the patients included in the study.

A significantly more prolonged prothrombin time (PT) was observed in the fibrinogen-PCC group (P = 0.0001; Table Table3);3); this difference was apparent upon arrival at the ICU as well as the ER. The base deficit also differed between the groups (6.4 �� 3.4 in the fibrinogen-PCC group and 6.9 �� 4.5 mmol/L in the FFP group), but this difference did not reach statistical significance.Table 2Patient demographic and clinical dataTable 3Standard laboratory parametersRBC transfusion data for treatment in the ER and during surgery were available for all patients. Complete avoidance of RBC transfusion was observed in 3% of patients in the FFP group and 29% of patients in the fibrinogen-PCC AV-951 group (P< 0.0001; Figure Figure1).1). In the FFP group, 583 of 601 patients (97%) received RBC transfusion (number of units ranging between 1 and 64), compared with 57 of 80 patients (71%) in the fibrinogen-PCC group (range: 1 to 28 units). Information on platelet concentrate transfusion for treatment in the ER and during surgery was available for 371 of the 601 patients in the FFP group, and for all patients in the fibrinogen-PCC group.

No Isl1-immunoreactive elements were distinguishable before St29-

No Isl1-immunoreactive elements were distinguishable before St29-30. From the onset of the appearance of Isl1 expression in the retina (St29-30), immunoreactivity appeared progressively following central-to-peripheral and vitreal-to-scleral gradients. From St42 Carfilzomib manufacturer onwards all retinal cell types were fully differentiated and the Isl1 expression pattern did not change significantly.3.1. Isl1 Expression in the X. laevis Differentiated RetinaThe Isl1 expression pattern in fully differentiated retinas will be reported first so as to establish a set of referents with which to compare developmental stages. Thus, at St53, the retina is almost fully developed, exhibiting complete lamination as determined from DAPI-stained cryosections (Figure 2(a)).

Anti-Isl1 antibody stained most of the cells located in the ganglion cell layer (GCL) (Figures 2(b), 2(c), 2(e), 2(f), 2(h), and 2(i)). Furthermore, different populations of Isl1-containing cells located in the inner nuclear layer (INL) could be distinguished by both morphological and topographical features: (i) a small population of cells with the major axis oriented parallel to the vitreal surface, lying at the border between the outer plexiform layer (OPL) and the INL, in the horizontal cell layer (Figures 2(b) and 2(c)); (ii) a population of cells located in the middle of the INL, in the bipolar cell layer (Figures 2(b), 2(c), 2(e), 2(f), 2(h), and 2(i)); and (iii) a small population of cells located at the inner edge of the INL, in the region where the amacrine cells are normally found (Figures 2(b), 2(c), 2(e), 2(f), 2(h), and 2(i)).

To further characterize Isl1-expressing cells, a double labeling with antibodies against calbindin-D28k (CB) and calretinin (CR) was also performed. In the developing and adult X. laevis retina, CB labels cones and subpopulations of bipolar, amacrine, and ganglion cells [35, 45]. Some of the CB-immunoreactive bipolar cells also expressed Isl1 (Figures 2(d)�C2(f)). CR labels subsets of horizontal, bipolar, amacrine, and ganglion cells [35]. Some of the CR-expressing horizontal, bipolar, and ganglion cells also expressed Isl1 (Figures 2(g)�C2(i)).Figure 2Morphological features and expression patterns of Isl1 and other cell differentiation markers in the St53 Xenopus laevis central retina. (a)�C(c) DAPI fluorescence combined with Isl1 immunofluorescence.

DAPI staining showed well-organized retinal …3.2. Isl1 Expression in the X. laevis Developing RetinaBy St29-30, although the lumen of the ventricle was still observed, the most distal part of the vesicle wall had invaginated to Brefeldin_A form a two-layered optic cup (Figure 3(a)). The neural retina was composed of a neuroblastic layer (NbL) (Figure 3(a)), and weak Isl1 immunoreactivity was first observed in sparse nuclei located near the vitreal surface of the central retina (Figure 3(b)). Similar morphological features and staining patterns were observed at St31 (Figures 3(c) and 3(d)).

Ten other patients also received ECLS, including two after the re

Ten other patients also received ECLS, including two after the restoration of spontaneous circulation following a brief period of asystole, selleck chem during refractory shock. The mean duration of external cardiac massage was 101 �� 55 minutes.Table 2Baseline characteristics at the time of ECLS implantation*Before the initiation of ECLS support, a severe decrease in cardiac contractility was documented by echocardiography in 14 cases. All patients were mechanically ventilated and received vasopressor. Four patients needed temporary external transthoracic electrostimulation. Six patients required continuous venovenous hemofiltration or conventional dialysis for acute renal failure before or immediately after ECLS implantation. Before connection to ECLS, the median arterial pH was 7.37 (7.34 to 7.

41), partial presure of arterial oxygen/fraction of inspired oxygen ratio was 239 (180 to 261), serum bicarbonate concentration was 19.0 mmol/L (17.7 to 20.6), plasma lactate concentration was 5.9 mmol/L (3.7 to 9.7), and serum creatinine concentration was 160 ��mol/L (114 to 204).ECLS feasibilityECLS feasibility, assessed with respect to time from admission to ECLS initiation, and the percentage of successful procedures (i.e. flow rate > 2.5 L/m2 and mean blood pressure > 60 mmHg) is shown in Table Table3.3. Time from hospital admission to initiation of ECLS was 6.4 �� 7.0 hours, and the time to ECLS implant was 58 �� 11 minutes. The mean ECLS flow rate was 3.45 �� 0.45 L/min. The average ECLS duration was 4.5 �� 2.4 days. In one patient (no.

17), an atrial balloon septostomy was performed to accomplish mechanical decompression of the left heart.Table 3ECLS feasibility, duration and complicationsECLS complicationsSignificant cannulation-related injuries of femoral vessels were reported in 10 patients: six patients with limb ischemia requiring urgent revascularization in three cases, one femoral thrombus, one cava inferior thrombus, and two cases of severe bleeding at the site of cannulation Dacomitinib requiring a surgical revision.Clinical outcomeFifteen patients were weaned off ECLS support and two patients withdrawn from support because of refractory multiorgan failure and cerebral death (Table (Table3).3). Thirteen patients survived and were discharged to hospital without significant cardiovascular or neurological sequelae (CPC 1 n = 9 and CPC 2 n = 4). Two patients died of septic shock and cerebral death during the hospital stay.DiscussionWe report one of the largest series of drug-induced cardiac arrest and refractory shock managed with ECLS. The high survival rate (76%) reported in this setting supports ECLS as an efficient rescue treatment in a subset of patients with drug-induced circulatory failure not responding to optimal conventional treatment.

3 mmHg; MAP quartile II = 74 3 to 77 8 mmHg; MAP quartile III = 7

3 mmHg; MAP quartile II = 74.3 to 77.8 mmHg; MAP quartile III = 77.8 to 82.1 Palbociclib FDA mmHg; …MAP or MAP quartiles were not associated with the total number of disease-related events (linear regression model; MAP: standardized Beta-Coefficient, -0.052; P = 0.36; MAP quartiles: standardized Beta-Coefficient, -0.035; P = 0.55) or the occurrence of any single disease-related event. These associations were not influenced by age or pre-existent arterial hypertension. However, the mean vasopressor load was significantly associated with the total number of disease-related events (standardized Beta-Coefficient, 0.225; P < 0.001). Figure Figure22 presents the predicted number of total disease-related events by MAP and mean vasopressor load quartiles as predicted by the adjusted logistic regression model.

The mean vasopressor load (per ln unit) was associated with the occurrence of acute circulatory failure (RR, 1.64; 95% CI, 1.28 to 2.11; P < 0.001), metabolic acidosis (RR, 1.79; 95% CI, 1.38 to 2.32; P < 0.001), renal failure (RR, 1.49; 95% CI, 1.17 to 1.89; P = 0.001) and thrombocytopenia (RR, 1.33; 95% CI, 1.06 to 1.68; P = 0.01) in single adjusted logistic regression models. Study patients still had a significantly lower mean and maximum vasopressor load during the shock period when compared with the 68 patients excluded from the analysis (mean vasopressor load, 0.64 �� 1.92 vs. 2.31 �� 6.56 ��g/kg/min, P = 0.003; maximum vasopressor load, 1.19 �� 3.54 vs. 3.06 �� 7.4 ��g/kg/min, P = 0.01) [Figure S1 in Additional data file 1].

Figure 2Number of DRE by MAP and mean vasopressor load quartiles as predicted by the adjusted logistic regression model. Mean arterial blood pressure (MAP) quartile I = 70 to 74.3 mmHg; MAP quartile II = 74.3 to 77.8 mmHg; MAP quartile III = 77.8 to 82.1 mmHg; …The mean heart rate during the shock period was associated with 28-day mortality in the adjusted logistic regression model (RR 1.029; 95% CI, 1.01 to 1.047; P < 0.001) [Table S3 in Additional data file 1]. Mean heart rates in the highest sixtile (>122 bpm) were associated with a significantly higher 28-day mortality than heart rates in the lowest sixtile (<92 bpm). Again, the mean vasopressor load revealed the strongest association with 28-day mortality.DiscussionThe results of this post hoc analysis confirmed our study hypothesis that MAP levels exceeding 70 mmHg were not associated with 28-day mortality or the occurrence of disease-related events in patients with septic shock.

In contrast, any increase of MAP over 70 mmHg achieved by an increase of vasopressor dosages appears to be associated with the number of disease-related events and mortality.A limitation Cilengitide of our study is that analysed data were collected more than a decade ago and it can be argued that hemodynamic management of septic shock has changed since then. Specifically, the recent Surviving Sepsis Campaign recommended maintaining a minimum MAP of 65 mmHg as opposed to 70 mmHg in this trial.

FFP is collected in citrate-containing anticoagulation solution,

FFP is collected in citrate-containing anticoagulation solution, frozen within 8 hours and stored at -30��C for up to 1 year. FFP contains all sellckchem of the clotting factors, fibrinogen (400 to 900 mg/unit), plasma proteins (particularly albumin), electrolytes, physiological anticoagulants (protein C, protein S, antithrombin, tissue factor pathway inhibitor) and added anticoagulants [1,2].Plasma frozen within 24 hours of collection is termed frozen plasma (PF24), containing 15 to 20% lower factor VIII levels than FFP [23,24]. PF24 is common in countries using the buffy-coat method, in which RBC and plasma are extracted after hard spin from whole blood and platelets recovered after a second soft spin within 24 hours of collection. PF24 has similar clinical indications as FFP [2,23,24].

FFP is commonly thawed in a water bath over 20 to 30 minutes, but US Food and Drug Administration-approved microwaves can thaw 2 units of plasma in 2 to 3 minutes [1]. After thawing, the activity of labile clotting factors such as factor V and factor VIII decline gradually, and most countries recommend FFP use within 24 hours [25,26]. In some countries, FFP is used up to 5 days after thawing. The consequences of transfusing stored, thawed 5-day-old plasma is not completely understood, but the activity of factor VIII is expected to drop by >50%, and the activity of factor V and factor VII drops to about 20% 5 days after thawing [27].Photochemically treated FFP and solvent detergent FFP are approved methods of inactivating pathogens in some jurisdictions. Both methods cause loss of clotting factors, particularly factor VIII.

Some solvent detergent FFP preparations have reduced activity of protein S and ��2-antiplasmin, and have been associated with thrombo-embolic complications [28,29]. These solvent detergent preparations are extensively used in some European countries, while solvent detergent FFP was withdrawn in North America due to concerns of Parvovirus transmission [1].RisksFFP can transmit infectious diseases, albeit rarely. Screen ing and pathogen inactivation reduced transmission rates of HIV to 1:7.8 million, of hepatitis C virus to 1:2.3 million and of hepatitis B virus to 1:153,000 units transfused [30]. In the UK, concerns over Creutzfeldt-Jakob disease – a rare but rapidly progressive spongiform encephalopathy – led to leukocyte depletion in all blood products and recommendations to use FFP from areas of low epidemicity [31,32].

Other important complications relate to blood immunogenicity, increasingly recognized over the past two decades, particularly transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload [33,34]. TRALI is the commonest cause of transfusion-related death [33,34]. Two mechanisms have mostly been implicated in TRALI. Donor plasma antibodies react with human leukocyte antigens, causing complement AV-951 activation, endothelial damage, neutrophil activation and lung capillary leak.

1 fracture

1 fracture treated with cemented fenestrated screw and kyphoplasty. In one case, the fracture stabilization was associated with a minimally invasive endoscopic-assisted discectomy and interbody fusion for a preexisting symptomatic degenerative disc-disease at the same level. In another case where T11, T12, and L3 type A fractures were associated with L1 and L2 type B fractures, we performed a percutaneous stabilization from T10 to L4 and an L1-L2 arthrodesis with a miniopen approach (Figure 2). Figure 2 T11, T12, and L3 type A fractures associated with L1 and L2 type B fractures. Percutaneous stabilization from T10 to L4 and L1-L2 arthrodesis with a miniopen approach. In no other case fusion was associated to the MIS. To monotrauma patients with type A1, A2, and A3.

1 fractures without significant stenosis of the spinal canal, a conservative option consisting of cast and bed rest was also offered but was rejected in 85% of cases. In all cases, the impairment of the spinal canal was less than 30%, and local kyphosis was less than 20�� except in one case. All patients underwent plain radiographs and CT scan preoperatively and immediately postoperatively and were followed over time with systematic clinical and radiographic controls at 1, 3, 6, 12, and 24 months after surgery. 3. Results The average surgical time was 113 minutes (range 35 to 240 minutes), and it was directly related to the number of screws implanted: the average time, reduced to 106 minutes using 4 pedicle screws, becomes 144 minutes with 6 screws and 171 minutes with 8 screws. Blood losses were not assessable intraoperatively.

Postoperative analgesia was performed in all cases with a 36-hour lasting elastomeric pump containing an opioid and an NSAID. All monotrauma patients recovered the standing position in the second postoperative day on the average and were discharged on the fifth day. In polytrauma patients has been granted an immediate mobilization in the bed. The mean followup was 38 months, with a minimum of 6 months and a maximum of 72 months. All the cases, except one, have been considered healed after a 6-month control. Radiological examinations confirmed good spontaneous reconstruction of the anterior and posterior columns. Radiographic evaluation was performed through the measurement of the segmental kyphosis and the wedging deformity of the involved vertebral body [6].

Back pain, evaluated by VAS scale was 1.9 points at FU. Clinical evaluation was performed by subjective evaluation of the final results by patients themselves, and every patient was satisfied of surgical procedure. Radiographic evaluation showed a real improvement in the postoperative period (segmental kyphosis: 4.1 preop, ?2.2 postop, and 2.7FU kyphosis of the fractured vertebral segment: 12.2 preop, 5.9 postop, and 8.7 FU), but also a worsening of the segmentary kyphosis in the cases treated with CD Horizon Longitude (6.4 preop, 3.5 postop, and 7.8 FU) if implanted Cilengitide with multiaxial screws.

5 3 Cost of the Device Initial installation

5.3. Cost of the Device Initial installation cost ranges from 1.5 to 2.5 million dollars (US) depending on the model, along with an approximately 100,000 dollars annual maintenance fee and 2000 dollars per instrument (each instrument has a ten use lifespan); the da Vinci robotic system is one of the most expensive operating tools available, making it impractical for many institutions. 5.4. New Technology and Unproven Benefit Stronger studies are needed to assess the real cost-benefit of this technology compared to other techniques. 6. Surgical Set-Up The description below applies to the TORS procedures, although not all procedures in the head and neck region use this approach. (Other approaches are commented on in each procedure description.

) Transoral Robotic Surgery (TORS) is defined as surgery performed via the oral cavity that uses a minimum of three robotic arms and allows bimanual manipulation of tissues [21]. It was first developed by Weinstein and O’Malley, who have assessed the feasibility of this technique using the da Vinci Robotic System [13, 22�C27]. To minimize obstruction and maximize the communication between the surgeon and his/her assistants in TORS surgery, the surgeon’s cart should be located at the end of the operating room, allowing free space to maneuver the surgical cart that is placed on the right side of the patient, opposite to the surgeon. The support staff and instrument carts are located on the side of the patient, opposite the surgeon as well. The anesthesia machine and anesthesiologist are at the patient’s foot (Figure 1).

Anesthesia induction is usually done without moving the patient; this technique is described in detail by Chi et al. [28]. According to Chi et al., this method of organization slightly complicates the induction, but vastly simplifies setup for procedure, saving 15�C20 minutes per case. Performing the induction across from the anesthesia unit does not require the disconnection/reconnection of IV lines, monitor devices, or the anesthesia circuit, avoiding entanglement with the robotic equipment. Next, with the patient in supine position, the airway is secured via standard endotracheal intubation and the tube is appropriately secured. Safety goggles and a molded dental guard are used to protect the patient. Following induction, the robotic cart is brought in to the right of the patient, and the endoscopy tower and scrub table are brought in to the left.

The surgeon then places a retractor in the patient’s mouth to gain surgical exposure, and the 3 sterilely draped robotic arms are placed in surgical position (Figures (Figures22 and and33). Figure 2 Patient-side cart and robotic arms positioning. (Courtesy of Intuitive Surgical Inc., 2010.) Entinostat Figure 3 Robotic arms positioning in the oral cavity. Laryngeal reconstruction in pediatric patient. (Courtesy of Dr. Rahbar, 2007.) 7.

Very few studies reported the duration and radiation exposure res

Very few studies reported the duration and radiation exposure resulting from X-ray selleck and fluoroscopy. Authors who did report this data found that MI-TLIF had greater duration of radiation exposure for patients undergoing the procedure [3, 5, 7]. Due to the relative recent adoption of MI-TLIF use, the long-term effects of increased radiation exposure have not been evaluated. The development of 2D computer assisted fluoroscopy systems as well as the O-arm is a modern means to decrease this exposure risk. Further, careful attention to radiation safety in the operating room is critical. 4.2. Studies of Note Following data collection and the literature review, it is clear that there is a paucity of data comparing MI-TLIF and open TLIF. To our knowledge, there remains no high-class studies that directly compare these two techniques.

However, smaller studies, both prospective and retrospective in nature, have shown promise in regards to novel MI techniques for TLIF. Scheufler et al. compared percutaneous transforaminal lumbar interbody fixation (pTLIF) with mini-open transforaminal lumbar interbody fixation (oTLIF) while utilizing the Wiltse method [10]. They found at 8 month and 16 month follow-up, overall clinical outcome did not differ between the two techniques. However, in terms of pain following the operation, pTLIF resulted in significantly lower levels of pain (P < 0.01). Though the study showed no decreased advantages due to the percutaneous approach, a longer prospective study would be needed to further discern the success and functionality of each multilevel fusion.

In a study examining 42 patients with mean follow-up time of 29 months, Dhall et al. compared mini-open and open TLIF [4]. The authors found that mean estimated blood loss for mini-open (194mL) was significantly lower (P < 0.01) than the open-group (505mL). The length of stay was decreased for mini-open patients by on average, 2.5 days (P < 0.01). However, there were complications of neurologic nature in 2 patients, while 2 other patients required further revision. All 42 patients displayed fusion, and the authors felt that the mini-open technique was a possible substitute to open TLIF. Schwender et al. performed one of the earlier studies (2001-2002) on 49 patients who had MI-TLIF. Majority of patients in the study either had degenerative disc disease with herniated nucleus pulposus (HNP) or spondylolisthesis [14].

45 of 49 cases were completed at the L4-L5 or L5-S1 levels. Mean operative times were approximately 240 minutes, approximate blood loss was 140mL, and hospital stays averaged 1.9 days. Complications were limited to four patients, two of which required screw repositioning while two others developed radiculopathy following Carfilzomib the procedure. VAPS changed on average from 7.2 to 2.

However, their disadvantages included femoral CPB cannulation, li

However, their disadvantages included femoral CPB cannulation, ligation of the right internal thoracic artery, occasional chest wall instability, and difficult conversion to full sternotomy. In 1997, Cohn et al. [7] presented 84 minimally invasive cases (41 aortic and 43 mitral) using a right parasternal incision and excising the third and fourth costal cartilages. Interestingly, greater patient satisfaction, a decrease in postoperative atrial fibrillation (AF), and overall lower costs were found [7]. Later, Greelish et al. [20] primarily used a lower mini-sternotomy for mini-MVS with excellent results. Chitwood et al. [21] designed a new aortic clamp that allows transthoracic aortic occlusion. Video assistance has also been used for mini-MVS through small thoracotomies [9, 16, 17].

Although there are highly encouraging results using a right thoracotomy, several disadvantages exist, including peripheral CPB cannulation, the potential need for a double-lumen endotracheal tube, and occasional difficulty with MV exposure [16]. In contrast to this, the Leipzig Group has shown excellent results with their 5-6cm right lateral minithoracotomy under video assistance with peripheral femoral cannulation (Figure 2), direct transthoracic aortic clamping and with single endotracheal tube (Figure 3), and use of cannulation of right internal jugular vein for concomitant tricuspid valve procedures [22, 23]. Several groups strongly advocate for intra-aortic balloon occlusion for minimally invasive and robotic mitral surgery [24�C27]. Most commonly these devices are introduced as retrograde through the femoral artery.

The occlusive balloon is usually positioned under echocardiographic guidance just above the sinotubular junction, and balloon has the potential hazard of migration either into the arch with neurological complications or to the left ventricle with resultant ventricular dysfunction. Balloon occlusion may be advantageous compared to the transthoracic clamp method when there is limited access to the aorta. Aortic dissection is a feared complication of using the endoballoon, but experience with this technique dramatically reduces the risk of this adverse event. However, some group demonstrated increased morbidity, cost, and operative/cross-clamp time when the endoballoon technique was used for mitral valve surgery [28].

Telemanipulators, robotics that allow a hand-like mechanism to be controlled by a human operator, were first used in Paris, France, by Carpentier et al. [8] and Falk et al. [12] in Leipzig, Germany. Telemanipulator-supported operations, which involve femoral cannulation and direct or endoluminal aortic clamping, have Anacetrapib been used and propagated by Chitwood et al. [9, 18] and others [29, 30], who claim that this technique could be safely and effectively used [7].

Stabilization of HIF 1a and EpoR expression levels in hNPCs The i

Stabilization of HIF 1a and EpoR expression levels in hNPCs The induction of HIF 1a, a key molecule of hypoxia, is a well characterized cellular response to lowered oxygen. Therefore dilution calculator HIF 1a expression in hNPCs cultured at 3% oxygen over a time course of 1 h, 3 h, 1 d, 2 d, 3 d and 4 d of differentiation was measured using western blot analysis. EPO treatment did not influence the expression levels of the protein. Although an early up regulation of HIF 1a could not be quantified, the consis tent expression of HIF 1a demonstrated that the system is HIF 1a sensitive. Western blot analysis of the EpoR were performed with proliferating as well as EPO treated cells differentiated for 3 days.

The quantifica tion of the data showed that the signal intensity is identi cal in all conditions tested, with no significant differences in the EpoR expression levels, indicating that any effect of EPO would not be mediated by an upregula tion of the EpoR, but by EPO itself. Influence of low oxygen and EPO on the proliferation rate of hNPCs To determine the effect of hypoxia on the proliferation, hNPCs were expanded either at 20% or 3% O2. In addi tion, EPO was added to proliferating cells at different concentrations and cell samples were collected every 24 h to verify the number of cells. At an oxygen level of 20%, EPO did not enhance cell proliferation of hNPCs compared to control cells. Consis tently, EPO did not change the proliferation levels of hNPCs at 3% oxygen. To investigate the effect of hypoxia on the proliferation of hNPCs, untreated cells from both conditions were compared and the number of cells ml was determined.

The prolif eration curves showed very similar results with no increase of the proliferation rate under hypoxic condi tions. The comparison of the doubling times of treated and untreated cells under normoxic and hypoxic conditions revealed no significant difference. Untreated cells cultured at 20% O2 showed a doubling time of 19. 48 1. 34 h and cells cultured at 3% O2 a doubling time of 20. 45 1. 53 h. In addition, no sig nificant difference of doubling times between the two groups could be detected with EPO treatment, 10 IU ml, 11. 76 2. 08 h versus 15. 12 1. 94 h, 50 IU ml, 17. 46 1. 78 h versus 19. 28 1. Dacomitinib 99 h, 100 IU ml, 18. 77 1. 57 h versus 19. 69 4. 15 h, 300 IU ml, 26. 38 5. 86 h versus 20. 57 2. 41 h. To verify the action of EPO, HCD 57 cells, an EPO dependent erythroleukemia cell line, were used. This cell line needs to be cultured with EPO for regular proliferation and stops proliferation when cultured with out EPO. The application of EPO resulted in a continuous proliferation of the cells, while the withdrawal of EPO stopped it.