Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator.

OBJECTIVES Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. METHODS The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. RESULTS Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. CONCLUSIONS We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator

Gebiet: Chirurgie Biomedizintechnik Biophysik Transplantationsmedizin Kardiologie Abstract: OBJECTIVES: – Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. – – METHODS: – The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. – – RESULTS: – Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. – – CONCLUSIONS: – We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion. – – © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Progenitor cell recruitment during individualized high-flow, very-large-volume apheresis for autologous transplantation improves collection efficiency

BACKGROUND: Individual adaptation of processed patient's blood volume (PBV) should reduce number and/or duration of autologous peripheral blood progenitor cell (PBPC) collections. STUDY DESIGN AND METHODS: The durations of leukapheresis procedures were adapted by means of an interim analysis of harvested CD34+ cells to obtain the intended yield of CD34+ within as few and/or short as possible leukapheresis procedures. Absolute efficiency (AE; CD34+/kg body weight) and relative efficiency (RE; total CD34+ yield of single apheresis/total number of preapheresis CD34+) were calculated, assuming an intraapheresis recruitment if RE was greater than 1, and a yield prediction models for adults was generated. RESULTS: A total of 196 adults required a total of 266 PBPC collections. The median AE was 7.99 x 10(6), and the median RE was 1.76. The prediction model for AE showed a satisfactory predictive value for preapheresis CD34+ only. The prediction model for RE also showed a low predictive value (R2 = 0.36). Twenty-eight children underwent 44 PBPC collections. The median AE was 12.13 x 10(6), and the median RE was 1.62. Major complications comprised bleeding episodes related to central venous catheters (n = 4) and severe thrombocytopenia of less than 10 x 10(9) per L (n = 16). CONCLUSION: A CD34+ interim analysis is a suitable tool for individual adaptation of the duration of leukapheresis. During leukapheresis, a substantial recruitment of CD34+ was observed, resulting in a RE of greater than 1 in more than 75 percent of patients. The upper limit of processed PBV showing an intraapheresis CD34+ recruitment is higher than in a standard large-volume leukapheresis. Therefore, a reduction of individually needed PBPC collections by means of a further escalation of the processed PBV seems possible.

Delivery room management of very low birth weight infants in Germany, Austria and Switzerland--a comparison of protocols

Surveys from the USA, Australia and Spain have shown significant inter-institutional variation in delivery room (DR) management of very low birth weight infants (VLBWI, <1500g) at birth, despite regularly updated international guidelines.

Development of an ultra mini-oxygenator for use in low-volume, buffer-perfused preparations

Introduction: Small animal models are widely used in basic research. However, experimental systems requiring extracorporeal circuits are frequently confronted with limitations related to equipment size. This is particularly true for oxygenators in systems with limited volumes. Thus we aimed to develop and validate an ultra mini-oxygenator for low-volume, buffer-perfused systems. Methods: We have manufactured a series of ultra mini-oxygenators with approximately 175 aligned, microporous, polypropylene hollow fibers contained inside a shell, which is sealed at each of the two extremities to isolate perfusate and gas compartments. With this construction, gas passes through hollow fibers, while perfusate circulates around fibers. Performance of ultra mini-oxygenators (oxygen partial pressure (PO2 ), gas and perfusate flow, perfusate pressure and temperature drop) were assessed with modified Krebs-Henseleit buffer in an in vitro perfusion circuit and an ex vivo rat heart preparation. Results: Mean priming volume of ultra mini-oxygenators was 1.2±0.5 mL and, on average, 86±6% of fibers were open (n=17). In vitro, effective oxygenation (PO2=400-500 mmHg) was achieved for all flow rates up to 50 mL/min and remained stable for at least 2 hours (n=5). Oxygenation was also effective and stable (PO2=456±40 mmHg) in the isolated heart preparation for at least 60 minutes ("venous" PO2=151±11 mmHg; n=5). Conclusions: We have established a reproducible procedure for fabrication of ultra mini-oxygenators, which provide reliable and stable oxygenation for at least 60-120 min. These oxygenators are especially attractive for pre-clinical protocols using small, rather than large, animals.

Immune response of bovine milk somatic cells to endotoxin in healthy quarters with normal and very low cell counts

Low somatic cell count (SCC) is a reliable indicator of high-quality milk free of pathogenic microorganisms. Thus, an important goal in dairy practice is to produce milk with low SCC. Selection for cows with low SCC can sometimes lead to extremely low SCC in single quarters. The cells in milk are, however, predominantly immune cells with important immune functions. To investigate the mammary immune competence of quarters with very low SCC, healthy udder quarters of cows with normal SCC of (40-100) x 10(3) cells/ml and very low SCC of < 20 x 10(3) cells/ml were challenged with lipopolysaccharide (LPS) from Escherichia coli. In the first experiment, SCC and cell viability after a challenge with 50 ng of LPS/quarter was investigated. In the second experiment, tumour necrosis factor alpha (TNF-alpha) concentration and lactate dehydrogenase (LDH) activity in milk, and mRNA expression of various innate immune factors in milk cells were measured after a challenge with 100 mug LPS/quarter. LPS challenge induced an increase of SCC. SCC levels reached were higher in quarters with normal SCC and maximum SCC was reached 1 h earlier than in very low SCC quarters. The increase of TNF-alpha concentrations in milk in response to LPS challenge was lower in quarters with very low SCC than in quarters with normal SCC. The viability of cells and the LDH activity in milk increased in response to LPS challenge, however, without a difference between the groups. The mRNA expression of IL-1beta and IL-8 was increased in milk cells at 12 h after LPS challenge, whereas that of TNF-alpha and lactoferrin was not increased at the measured time points (12, 24 and 36 h after LPS challenge). No differences of mRNA expression of measured immune factors between normal and very low SCC samples were detected. The study showed that udder quarters with very low SCC responded with a less marked increase of SCC compared with quarters with normal SCC. This difference corresponded with simultaneously lower TNF-alpha concentrations in milk. However, the immune competence of the cells themselves based on mRNA expression of TNF-alpha, IL-8, IL-1beta, and lactoferrin, did not differ. The results may indicate that very low SCC can impair the immune competence of udder quarters, because the immune response in udder quarters with lower SCC is less efficient as fewer cells contribute to the production of immunoregulators.

Adequacy of an early arterial phase low-volume contrast protocol in 64-detector computed tomography angiography for aortoiliac aneurysms

PURPOSE: This retrospective study was conducted to determine whether a low-volume contrast medium protocol provides sufficient enhancement for 64-detector computed tomography angiography (CTA) in patients with aortoiliac aneurysms. METHODS: Evaluated were 45 consecutive patients (6 women; mean age, 72 +/- 6 years) who were referred for aortoiliac computed tomography angiography between October 2005 and January 2007. Group A (22 patients; creatinine clearance, 64.2 +/- 8.1 mL/min) received 50 mL of the contrast agent. Group B (23 patients; creatinine clearance, 89.4 +/- 7.3 mL/min) received 100 mL of the contrast agent. The injection rate was 3.5 mL/s, followed by 30 mL of saline at 3.5 mL/s. Studies were performed on the same 64-detector computed tomography scanner using a real-time bolus-tracking technique. Quantitative analysis was performed by determination of mean vascular attenuation at 10 regions of interest from the suprarenal aorta to the common femoral artery by one reader blinded to type and amount of contrast agent and compared using the Student t test. Image quality according to a 4-point scale was assessed in consensus by two readers blinded to type and amount of contrast medium and compared using the Mann-Whitney test. Multivariable adjustments were performed using ordinal regression analysis. RESULTS: Mean total attenuation did not differ significantly between both groups (196.5 +/- 33.0 Hounsfield unit [HU] in group A and 203.1 +/- 44.2 HU in group B; P = .57 by univariate and P > .05 by multivariable analysis). Accordingly, attenuation at each region of interest was not significantly different (P > .35). Image quality was excellent or good in all patients. No significant differences in visual assessment were found comparing both contrast medium protocols (P > .05 by univariate and by multivariable analysis). CONCLUSIONS: Aortoiliac aneurysm imaging can be performed with substantially reduced amounts of contrast medium using 64-detector computed tomography angiography technology.

Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a stable isotope study

Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P < 0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P < 0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P < 0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P < 0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P < 0.01). The total cholesterol concentration (P < 0.02), the low density lipoprotein cholesterol concentration (P < 0.02), and the VLDL cholesterol/VLDL apoB ratio (P < 0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P < 0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P < 0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.

Abnormalities of very low density lipoprotein apolipoprotein B-100 metabolism contribute to the dyslipidaemia of adult growth hormone deficiency

Increased cardiovascular mortality in adult growth hormone deficiency (GHD) may be, in part, explained by the dyslipidaemia associated with this condition. It is possible that abnormalities of very low density lipoprotein apolipoprotein B-100 (VLDL apoB) metabolism contribute to this dyslipidaemia. To test this hypothesis, we measured VLDL apoB kinetics in adult GH deficient patients (4 females, 3 males; age 50.1 +/- 4.7 yr (mean +/- SEM); BMI 28.2 +/- 1.1 kg/m2; total cholesterol (TC) 6.6 +/- 0.3 mmol/l; triglyceride (TG) 2.8 +/- 0.6 mmol/l; HDL cholesterol 1.1 +/- 0.1 mmol/l) and in control subjects (4 females, 3 male; age 47.0 +/- 4.7 yr; BMI 27.0 +/- 2.6 kg/m2; TC 5.0 +/- 0.4 mmol/l; TG 0.9 +/- 0.2 mmol/l; HDL cholesterol 1.4 +/- 0.1 mmol/l). [1-(13)C] leucine was administered by a primed (1 mg/kg), constant intravenous infusion (1 mg/kg/hr) and VLDL apoB enrichment with 13C leucine was determined using gas-chromatography mass-spectrometry. The GHD patients had a significantly higher hepatic secretion rate of VLDL apoB (15.5 +/- 1.8 mg/kg/day vs 9.4 +/- 0.6 mg/kg/day p = 0.007) and reduced catabolism ofVLDL apoB (metabolic clearance rate; 12.3 +/- 1.7 ml/min vs 24.3 +/- 4.8 ml/min p < 0.05) compared with control subjects. These findings suggest that GH is integrally involved in the regulation of VLDL apoB metabolism.

The Quality of the Evidence According to GRADE Is Predominantly Low or Very Low in Oral Health Systematic Reviews

OBJECTIVES The main objective was to assess the credibility of the evidence using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) in oral health systematic reviews on the Cochrane Database of Systematic Reviews (CDSR) and elsewhere. STUDY DESIGN AND SETTING Systematic Reviews or meta-analyses (January 2008-December 2013) from 14 high impact general dental and specialty dental journals and the Cochrane Database of Systematic Reviews were screened for meta-analyses. Data was collected at the systematic review, meta-analysis and trial level. Two reviewers applied and agreed on the GRADE rating for the selected meta-analyses. RESULTS From the 510 systematic reviews initially identified 91 reviews (41 Cochrane and 50 non-Cochrane) were eligible for inclusion. The quality of evidence was high in 2% and moderate in 18% of the included meta-analyses with no difference between Cochrane and non-Cochrane reviews, journal impact factor or year of publication. The most common domains prompting downgrading of the evidence were study limitations (risk of bias) and imprecision (risk of play of chance). CONCLUSION The quality of the evidence in oral health assessed using GRADE is predominantly low or very low suggesting a pressing need for more randomised clinical trials and other studies of higher quality in order to inform clinical decisions thereby reducing the risk of instituting potentially ineffective and/or harmful therapies.

Ultrasonographic guided axillary plexus blocks with low volumes of local anaesthetics: a crossover volunteer study

Our study group recently evaluated an ED(95) local anaesthetic volume of 0.11 ml.mm(-2) cross-sectional nerve area for the ulnar nerve. This prospective, randomised, double-blind crossover study investigated whether this volume is sufficient for brachial plexus blocks at the axillary level. Ten volunteers received an ultrasonographic guided axillary brachial plexus block either with 0.11 ('low' volume) or 0.4 ('high' volume) ml.mm(-2) cross-sectional nerve area with mepivacaine 1%. The mean (SD) volume was in the low volume group 4.0 (1.0) and 14.8 (3.8) ml in the high volume group. The success rate for the individual nerve blocks was 27 out of 30 in the low volume group (90%) and 30 out of 30 in the high volume group (100%), resulting in 8 out of 10 (80%) vs 10 out of 10 (100%) complete blocks in the low vs the high volume groups, respectively (NS). The mean (SD) sensory onset time was 25.0 (14.8) min in the low volume group and 15.8 (6.8) min in the high volume group (p < 0.01). The mean (SD) duration of sensory block was 125 (38) min in the low volume group and 152 (70) min in the high volume group (NS). This study confirms our previous published ED(95) volume for mepivacaine 1% to block peripheral nerves. The volume of local anaesthetic has some influence on the sensory onset time.

Cognitive and behavioral aspects of executive functions in children born very preterm

This study investigated whether children aged between 8 and 12 years born very preterm (VPT) and/or at very low birth weight (VLBW) performed lower than same-aged term-born controls in cognitive and behavioral aspects of three executive functions: inhibition, working memory, and shifting. Special attention was given to sex differences. Fifty-two VPT/VLBW children (26 girls, 50%) born in the cohort of 1998-2003 and 36 same-aged term-born children (18 girls, 50%) were recruited. As cognitive measures, children completed tasks of inhibition (Color-Word Interference Test, D-KEFS; Delis, Kaplan, & Kramer, 2001 ), working memory (digit span backwards, HAWIK-IV; Petermann & Petermann, 2008 ), and shifting (Trail Making Test, number-letter-switching, D-KEFS; Delis et al., 2001 ). As behavioral measures, mothers completed the Behavior Rating Inventory of Executive Function (BRIEF; Gioia, Isquith, Guy, & Kenworthy, 2000 ). Scales of interest were inhibit, working memory, and shift. Analyses of the cognitive aspects of executive functions revealed that VPT/VLBW children performed significantly lower than controls in the shifting task but not in the working memory and inhibition tasks. Analyses of behavioral aspects of executive functions revealed that VPT/VLBW children displayed more problems than the controls in working memory in everyday life but not in inhibition and shifting. No sex differences could be detected either in cognitive or behavioral aspects of executive functions. To conclude, cognitive and behavioral measures of executive functions were not congruent in VPT/VLBW children. In clinical practice, the combination of cognitive and behavioral instruments is required to disclose children's executive difficulties.