A New Perfusion Circuit for the Newborn with Lung Immaturity: Extracorporeal CO2 Removal via an Umbilical Arteriovenous Shunt During Apneic O2 Diffusion

In spite of improved prophylaxis and therapy, the respiratory distress syndrome is still a major cause of morbidity and mortality in premature babies. Owing to the fact that a number of patients are unresponsive to other methods of neonatal care, an increasing number of perinatal centers have started to treat this group of patients with extracorporeal membrane oxygenation successfully. To make the extracorporeal gas exchange more practicable for the neonate directly after birth, a modification of this method using an umbilical arteriovenous shunt for CO2 removal in apneic premature lambs as an animal model was evaluated. A miniaturized low-resistance extracorporeal circuit that is totally incorporated in a regular intensive care baby incubator was developed. The benefit of using extracorporeal CO2 removal in very low birth weight newborns could be a conditioning of the premature lung during a short period of bypass, after which ventilation at nontraumatic pressures and nontoxic O2 concentrations would become possible.     

β2-Microglobulin and Low-Flux SyntheticDialyzers

Abstract: The aim of this study was to compare the effect on β₂-microglobulin (β₂-M) plasma levels of dialyzers with 3 low-flux synthetic membranes and regenerated cellulose (Cuprophan) in 12 chronic dialysis patients. The synthetic membrane materials chosen were low-flux polymethylmethacrylate (PMMA), low-flux polysulfone (PS 400), and polycarbonate-polyether (Gambrane). Adequate and comparable removal of small solutes was provided by dialyzers with all 4 membrane materials used under similar conditions. A significant reduction of β₂-M plasma levels was seen only with Gambrane while the other 2 synthetic membrane materials gave rise to increases similar to those known to occur with Cuprophan. After correction for the hemoconcentration caused by ultrafiltration, dialysis with Gambrane showed a 24% lower plasma β₂-M level while the β₂-M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in β₂-M removal was able to significantly lower the predialysis plasma β₂-M levels after only 5 dialysis sessions. The hemocompatibility of the 3 synthetic low-flux membranes as judged by the white blood cell (WBC) count and complement activation was similar and therefore cannot be used to explain the different β₂-M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of β₂-M in dialysis patients, a worthwhile approach may be to use a low-flux membrane such as Gambrane which combines removal with protection against potential activating factors in the dialysis fluid.     

Differential response to transforming growth factors-β1 and β2: connective tissue deposition in animal models

The ability of transforming growth factor (TGF)-beta(1) and TGF-beta(2) to promote connective tissue deposition were compared in different animal models. A single subcutaneous injection of TGF-beta(2) in collagen/heparin gel carrier promoted markedly more extensive development of connective tissue than TGF-beta(1) at the site of injection in both neonatal and adult mice. Both TGF-beta(1) and TGF-beta(2) promoted deposition of dense and well-vascularized connective tissue matrix infiltrated with macrophages and fibroblasts. However, the results of immunohistochemical analyses suggested that TGF-beta(2) promoted an accumulation of more macrophages in the connective tissue than TGF-beta(1). Similar differences in the extent of connective tissue development were observed in neonatal mice when these factors were administered as a solution, without the collagen/heparin gel carrier. TGF-beta(2) was also more potent than TGF-beta(1) in domestic pigs. However, in guinea pigs, TGF-beta(1) promoted more extensive connective tissue development than TGF-beta(2). These results suggest that the differential connective tissue response to TGF-beta(1) and TGF-beta(2) is species dependent. However, the differences in the physical and chemical properties of these factors may account in part for the differential response as well.     

Use of Neoral C2 monitoring: a European consensus

Large-scale clinical trials using C(2) monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard-exposure or low-exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C(2) monitoring significantly reduces the severity and incidence of acute rejection compared with C(0) monitoring, without adverse consequences in terms of renal function or tolerability. Different C(2) targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1-2 weeks post-transplant, and this should be taken into account to avoid overshooting C(2) target range. A patient with a low C(2) value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C(2) monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C(2) monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single-center trials have evaluated Neoral C(2) monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.     

Evaluation of ß2-Microglobulin Removal with High-Performance Hemodiafiltration

Several lines of evidence suggest that beta 2-microglobulin (beta 2M) accumulation in long-term hemodialysis (HD) patients results in so-called dialysis-associated amyloidosis (DAA), which is clinically manifested by carpal tunnel syndrome, osteoarthropathy, and the other organ involvements. For the purpose of preventing the beta 2M accumulation, the efficiency of beta 2M removal during (HPM), hemofiltration (HF), HD, and charcoal hemodiafiltration (HDF) with high-performance membranes (HPM), hemofiltration (HF), HD, and charcoal hemoperfusion was evaluated. Among 27 patients treated with these methods, significant beta 2M removal was noted in HDF with HPM and HD with polyacrylonitril (PAN) membrane. However, treatment of HDF with HPM for more than 6 months caused no remarkable improvement in clinical symptoms of patients, and serum beta 2M levels decreased in only two out of 15 patients. These results imply that beta 2M might be most effectively removed by HDF with HPM and HD with PAN membrane, but further long-term studies will be necessary to conclude whether these procedures could become successful therapeutic regimen for DAA.     

H2 antagonists and bupivacaine clearance

The effect of the H2 receptor antagonists cimetidine and ranitidine on bupivacaine clearance was assessed in women scheduled to undergo elective Caesarean section under epidural anaesthesia. Thirty-six women were randomly allocated to receive either no medication, cimetidine 400 mg or ranitidine 150 mg on the night prior to and on the morning of surgery. No significant difference was found between the peak bupivacaine levels: the mean (SD) values were 0.74 (0.17) microgram/ml, 0.81 (0.38) microgram/ml and 0.70 (0.24) microgram/ml in the control, cimetidine and ranitidine groups, respectively. Similarly, the H2 receptor antagonists did not alter the plasma bupivacaine against time curves, half-life or bupivacaine clearance in the three groups studied.     

CO2 production after suxamethonium and diazepam

The CO2-production and degree of relaxation after increasing doses of suxamethonium were measured in seven patients undergoing alloplastic surgery of the hip. The study indicates that the CO2-production rises following the injection of increasing doses of suxamethonium. Another group of patients received diazepam 0.1 mg kg-1 before the injection of suxamethonium 1 mg kg-1. CO2-production was significantly reduced compared to CO2 production when suxamethonium was not preceded by diazepam. It is suggested that diazepam in doses larger than 0.1 mg kg-1 might be effective in preventing fasciculations and postoperative muscle pains before the injection of suxamethonium in a dose of 0.5 mg kg-1.     

The Effects of PGI2 Analog (OP-41483) on Perfused Porcine Liver

The effects of a prostacyclin analog OP-41483 on energy metabolism were studied in an isolated porcine liver perfused with human blood for 8 h. OP-41483 was administered intravenously at a rate of 0.3 microgram/kg/min during the procurement and into the perfusate at a rate of 1.0 microgram/min during perfusion. Acetoacetate, beta-hydroxybutyrate, lactate, and pyruvate were measured before perfusion and at 1, 2, 3, 5, and 8 h after perfusion, from which values the ketone body ration (acetoacetate/beta-hydroxybutyrate, KBR), reflecting the redox state of liver mitochondria, was calculated. In the OP-41483 group, KBR increased rapidly from 0.34 to 0.95, 1.61, 1.51, 2.35, and 2.04, and lactate decreased rapidly from 9.81 to 6.30, 4.51, 3.22, 2.39, and 1.33 mmol/L at the respective hours after perfusion. There were significant differences after 3 h of perfusion as compared with the control group (p less than 0.05). These results suggest that administration of OP-41483 causes an increase in mitochondrial NAD+/NADH ratio (oxidized and reduced forms of free nicotinamide-adenine dinucleotides), leading to an enhancement of the metabolic capacity of the perfused liver.     

Intra-arterial and extra-arterial pH, PCO2 and PO2 monitors

In vitro blood gas analysers inherently limit the frequency of serial blood gas measurements because of blood loss and cost. In vivo blood gas monitors eliminate an inherent cost and blood loss associated with measurement. Optode microsensing is a technology that can be readily adapted to in vivo measurement of pH, PCO₂ and PO₂. Optode-based intra-arterial devices that display continuous values have been developed that are practical for routine use but consistent performance remains a problem; an extra-arterial device that provides intermittent values has been shown to be consistent but is not yet available for routine use. The transfer of blood gas measurements from laboratory analysers to the combination of point-of-care analysers and monitors should have as profound an impact on acute respiratory care as did the introduction of laboratory-based blood gas analysers over 30 years ago. However, we must be sure these devices are reliable, consistent and cost beneficial in order to avoid widespread adoption of yet another technology that provides more data, more cost, and questionable patient benefit.     

Kinetics of 131I-β2 Microglobulin in Hemodialysis Patients: Assessment Using Total Body Counting

Abstract: The kinetics of ¹³¹I-β₂-microglobulin (β₂-M) were studied using external total body gamma counting in a low noise chamber after administration of trace doses of radioactivity (4 μCi) in 14 uremic patients treated by either hemodialysis or hemofiltration. Data were collected over a 1 week period that included 3 dialysis sessions. The following artificial membranes were used: Cuprophan, polyacrylonitrile AN69, polysulfone, polymethylmethacrylate (PMMA), and polyamide. Radiolabeled β₂-M excretion by an extrarenal route was nearly nonexistent. The ¹³¹I-β₂-M half-life was between 2.4 and 8 days, shorter in patients with residual diuresis. A mean removal of 153 ± 33 mg/L of β₂-M was obtained per dialysis session with a highly permeable membrane. A hemofiltration session (25 L exchange per session) was slightly more efficient in removing β₂-M than a 4 h hemodialysis session with the same AN69 highly permeable membrane. The amounts of ¹³¹I-β₂-M binding on the membranes, expressed as β₂-M equivalents, were 0, 16, 54, 58, and 59 mg/m² for Cuprophan, polysulfone, polyacrylonitrile AN69, polyamide, and PMMA, respectively. In conclusion, the decrease of total body gamma counting directly reflected the β₂-M breakdown and removal in hemodialysis patients. Intact β₂-M was removed by convection with synthetic, highly permeable membranes. In addition, membrane adsorption accounted for 15% (polysulfone) to near 100% (PMMA) of the β₂-M removal per session. Adsorption was of the same magnitude regardless of the dialysis technique in use, indicating a membrane saturability process. None of the currently available dialysis procedures based on a 3 sessions per week schedule can balance β₂-M generation.     

Transcutaneous Po2 Monitoring During Treatment with Continuous Positive Airway Pressure in Infants with Idiopathic Respiratory Distress Syndrome

During a 20-month period, 20 infants with idiopathic respiratory distress syndrome (IRDS) were treated with continuous positive airway pressure (CPAP) when they required at least 40% inspired oxygen. The infants were allocated to monitoring with either repeated blood-gas determinations according to the usual practice or continuous transcutaneous Po₂ measurements supplemented by blood-gas measurements only when judged necessary. The groups were comparable with regard to birth weight and gestational age, and did not differ significantly with regard lo effectiveness or duration of the CPAP treatment, survival rates (90 versus 80%) or number of complications. None developed retrolental fibroplasia. However, Ptco₂ monitoring resulted in significantly less hypo- and hyperoxaemia and the number of blood-gas analyses performed during CPAP therapy amounted to only 0.6 per infant per day in the transcutaneously monitored group as against 5.3 in the other group. We propose that Ptco₂ monitoring should now be the method of choice and that the use of umbilical artery catheterization should be restricted to selected groups of very low birth-weight infants and to infants in need of ventilator therapy.     

Measurement of transcutaneous P±o2, Pco2 and skin blood flow at different probe temperatures using mass spectrometry

Transcutaneously measured partial pressures of oxygen and carbon dioxide (PtcO2, PtcCO2) approximate the corresponding arterial values at a probe temperature of 44 degrees C. The temperature-dependent increase of PtcO2 and PtcCO2 is caused by an increased skin perfusion, a decrease in the mean diffusion path, a change of skin metabolism, a decrease of tissue solubility of oxygen and carbon dioxide and a right shift of the oxygen and carbon dioxide binding curves of blood. Seven healthy volunteer test subjects participated in the study. A transcutaneous probe connected to a mass spectrometer was placed on the earlobe of the test subject. Four measurements of the transcutaneous PO2, PCO2 and skin blood flow (from the washout kinetics of argon) were determined on each test subject. The first measurement was made with a transcutaneous probe temperature of 37 degrees C. The probe temperature was then increased to 44 degrees C before the next determination. Finally, two determinations were made at 37 degrees C, separated by a time interval of 1 h. The PtcO2 and skin blood flow increased when the probe temperature increased from 37 degrees C to 44 degrees C. However, when the probe temperature was decreased again from 44 degrees C to 37 degrees C, the estimated skin blood flow returned to the initial value while the PtcO2 remained unchanged. It required a further 1 h before the PtcO2 returned to the initial value at 37 degrees C. The most likely explanation of the experimental results is that heating of the skin to 44 degrees C causes a reversible decrease in the skin metabolism.     

Thromboxane B2 Production During Erection

The effect of erection on 6-keto-PGF1 alpha and thromboxane B2 in penile blood during electrically evoked erection was studied in the chacma baboon. 6-keto-PGF1 alpha remained at a low concentration, but thromboxane B2 showed a statistically significant rise 8-10 minutes after commencement of erection. Elevated thromboxane B2 during erection may potentiate platelet aggregation and may be one of the key events in the pathogenesis of ageing impotence.     

Change in PaO2 During Artificial Ventilation With Added Dead Space

When patients during anaesthesia were ventilated with large tidal volumes which produced a mean PaCO₂ of 26 mm Hg, insertion of a 500 ml dead space increased PaCO₂ to 48 mm Hg, and was accompanied by a rise in PaO₂ from 172 mm Hg to 212 mm Hg, probably caused by an increase in cardiac output.
It is suggested that a state of normocapnia should be attempted when respiration and circulation are interfered with, as under anaesthesia.

ZUSAMMENFASSUNG

Wenn Patienten in Narkose mit so grossen Atemvolumina beatmet werden, dass ein durchschnittliches PaCO₂ von 26 mm Hg resultiert, kann man durch Zwischenschalten eines Totraumes von 500 ml das PaCO₂ wieder auf 48 mm Hg erhöhen. Dies ist von einem PaO₂-Anstieg von 172 mm Hg auf 212 mm Hg begleitet, der wahrscheinlich die Folge eines erhohten Herzminutenvolumens ist.
Es wird vorgeschlagen, einen Zustand der Normokapnie anzustreben, wenn, wie unter der Narkose, die Atem- und Kreislaufverhältnisse gestört sind.     

Estimation of Blood Flow in Transcutaneous PO2 Measurements

A method for estimation of the cutaneous blood flow in transcutaneous Po₂ measurements is presented. Recordings of electrode and skin temperature make it possible to compute the effect dissipated to the circulating blood. Eighteen measurements were performed on three healthy volunteers at electrode temperature settings from 37.0°C to 45.0°C. The blood-flow estimates ranged from 0.07 to 0.19 ml·cm^-2·min^-1. At an electrode temperature of 45.0°C the investigations showed a tc-Po₂ value as low as 7 mmHg (0.9 kPa) which, however, corresponded well to the lowest blood-flow estimate determined. The temperature-corrected (37°C) a-Po₂-tc-Po₂ gradient ranged from 50 mmHg to 95 mmHg (6.7–12.6 kPa). The investigations confirm the importance of simultaneous determinations of cutaneous blood flow, capillary temperature and cutaneous oxygen consumption in order to describe the connection between arterial and cutaneous oxygen tension. The cutaneous blood How seems in this connection to be the most important parameter.     

Purification and characterization of phospholipase A2 from bovine prostate

Phospholipase A2 (PLA2) was purified from bovine prostate by ammonium sulphate precipitation and fractionation by anion exchange chromatography, chromatofocusing and gel filtration. The purified enzyme was Ca(2+)-dependent and had a pH-optimum of 8.0. Ba2+, Fe2+, Hg2+, Mg2+, Pb2+, Sr2+ and Zn2+ as well as lysophosphatidylcholine, lysophosphatidylethanolamine and p-bromophenacyl bromide (p-BPB) inhibited the enzyme strongly. The enzyme had an estimated molecular weight of 12,000 +/- 1,000 daltons on SDS-PAGE. Isoelectric focusing showed one PLA2 activity-containing band at pl 5.3. The purified enzyme hydrolysed linoleic acid at the sn-2 position of phosphatidylcholine and phosphatidylethanolamine with high selectivity, compared to arachidonic acid.