Domokos Boda

Blood glutathione redox ratio as a parameter of oxidative stress in premature infants with IRDS

Oxygen toxicity is thought to play an important pathogenic role in several neonatal diseases, including idiopathic respiratory distress syndrome (IRDS). Therefore, the development of a reliable measure of the actual oxidative stress status of patients would be of great clinical significance. In order to obtain information about the oxidative stress during the first week of life in premature infants with IRDS, the blood concentrations of oxidized and reduced glutathione, as well as their molar ratios, were determined by a highly sensitive, specific enzymic assay. The fractional inspired oxygen concentrations needed to maintain adequate arterial oxygen tension and the arterio-alveolar oxygen ratios were chosen as parameters indicating the severity of illness in premature infants at a given time. There was a highly significant positive correlation between the glutathione redox ratios and the fractional inspired oxygen concentrations. A maturity-related difference was also found; the oxidized glutathione concentrations were the highest in the least mature infants, accompanied by a pronounced compensatory rise in the reduced glutathione concentrations as well. A significant negative correlation was found between the arterio-alveolar oxygen ratio and the glutathione redox ratio: i.e., an improvement in oxygenation was accompanied by a decrease in the glutathione redox ratio. The efficient recycling of reduced glutathione in erythrocytes providing antioxidant protection for premature infants, permits the use of the blood glutathione redox ratio as a noninvasive measure of in vivo oxidative stress.

Surface Tension, Glutathione Content and Redox Ratio of the Tracheal Aspirate Fluid of Premature Infants with IRDS

Objective: Determination of the surface tension (ST), the total glutathione (GL) content and the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) in the tracheal aspirate (TA) of newborn infants with IRDS. Methods: The ST of the TA was determined by monitoring the fluid level pulsated in a capillary glass tube by means of a digitalized videocomputerized picture analysis program, a technique developed in our laboratory. The concentrations of GSSG and total GL in the TA were determined enzymatically with glutathione reductase. All results of laboratory tests were referred to the total phospholipid (PL) concentration. Patients, Experimental Material: TA samples were collected from 32 intubated premature and newborn infants admitted to the NICU with IRDS during the first 2 weeks of their lives. Control samples were obtained from 11 children prior to elective surgery. Results: The ST relative to the PL content (surface tension index, STI) was significantly lower in the newborns with IRDS than in the control group, and the concentration of GSH in the TA was also markedly decreased in all IRDS infants studied. The concentration of GSSG and the ratio of GSSG to GSH were significantly higher in the severe cases and in those with an unfavourable prognosis. Surfactant treatment had a protective effect against oxidative stress, it induced a decrease in both the GSSG concentration and in the GL redox ratio (GSSG/GSH) in the TA. There was a close correlation between the GSH content and the STI value of the samples studied. Conclusion: Oxidation and consequent depletion of GSH in the TA may be an aggravating factor in the development of the insufficient surface activity in intubated newborns with IRDS.

Measurement of surface tension in biological fluids by a pulsating capillary technique

Ever since the discovery of the antiatelectatic function of the pulmonary surfactant, the measurement of surface tension (ST) has been of increasing importance in respiration physiology and clinical research. For the determination of ST, the elevation of the level of a fluid artificially pulsated in a capillary glass tube was monitored, and ST was calculated with the digitalized video-computerized picture analysis program Surftens. The biological relevance of the method is given by the Gibbs-Thomson principle, according to which surface-active lipids stream towards the surface by an adsorptive process; on pulsation of the fluid in a capillary glass tube, therefore, ST is gradually decreased to a minimal value. ST values of 60 amniotic fluid samples collected from pregnancies with different gestation times were determined. A multiple regression analysis of the results, including other parameters (total protein content, total lipid content, phospholipid content and microviscosity), indicated that this method may enhance the precision of the determination of gestation time. Precision analysis of various samples proved that this technique gives well-reproducible results under the given standardized conditions. The main field of application of the method may be in clinical practice and in studies on as yet inadequately known factors affecting the ST of biological fluids.

Practical experiences and in vitro and in vivo validation studies with a new gastric tonometric probe in human adult patients

PURPOSE This study provides practical experiences with a new, simple, balloon-free gastric tonometric probe (probe) and reports the results of simultaneous in vitro and in vivo measurements with a conventional, ballooned gastric air tonometer (catheter) and the new device. MATERIALS AND METHODS Ten healthy volunteers and 50 anesthetized surgical patients with different American Society of Anesthesiologists (ASA) scores, scheduled for neurologic, orthopedic, trauma, and cardiac operations, were enrolled in the study. The values of 60 in vitro and, in 12 surgical patients, 101 in vivo paired Pco(2) measurements--performed simultaneously with the new tonometric probe and the catheter that was connected to a Tonocap monitor--were compared. The tolerability of the measurement with the new probe was examined, and the results of gastric tonometry and, in surgical cases, the gastric tonometric, end-expiratory, and arterial Pco(2) values were registered. The results were evaluated by analysis of variance test. The data of the in vivo paired measurements were evaluated by Bland-Altman analysis. RESULTS The use of the probe proved to be well tolerated and easily applicable in the studied cases. The results of 20 measurements obtained in healthy volunteers and those of 520 measurements in the surgical cases correspond to the data obtained with the classical methods published in the medical literature. During in vitro paired measurements, there was a good agreement between the data obtained with the 2 methods; however, in the in vivo studies, the results of measurements performed with the probe were mostly higher. CONCLUSIONS The differences between the results obtained with the 2 methods might have been caused by the quicker equilibration property of the probe and by the fundamental differences between the 2 methods. The new probe seems to be applicable for routine human measurements.

The founding and early history of the European Society for Paediatric Nephrology (ESPN)

The founding of the European Society for Paediatric Nephrology (ESPN) in 1967 was the milestone for pediatric nephrology in Europe. Now, at the beginning of the 21st century, more than 2,000 European pediatricians in 46 European countries work in the field of pediatric nephrology, and approximately 500 of these meet regularly at the annual ESPN meetings. Half of these 2,000 pediatricians work in about 200 specialized pediatric nephrology centers in tertiary care units, whereas the other half work in secondary pediatric care, with a special interest in common renal diseases. In this article the founding and early years of the ESPN are outlined and include the structure of the first ten annual ESPN meetings from 1967–1976. Historical reports are given by five pioneers who were first-hand witnesses of the development of pediatric renal care in Europe.

A Newly Developed Sublingual Tonometric Method for the Evaluation of Tissue Perfusion and Its Validation In Vitro and in Healthy Persons In Vivo and the Results of the Measurements in COPD Patients

Introduction. Since its first publication in the medical literature, an extremely large number of references have demonstrated that the tonometric measurement of tissue perfusion is a reliable indicator of the actual condition of critically ill patients. Later a new method was developed by the introduction of sublingual tonometry for the determination of tissue perfusion. In comparison with gastric tonometry, the new method was simpler and could even be used in awake patients. Unfortunately, at present, because of severe failures of manufacturing, the device is withdrawn from commerce. Materials and Methods. In this study, we present a new method using a newly developed tool for the PslCO2 measurement in sublingual tonometry as well as the data for its validation in vitro and in vivo and the results of 25 volunteers and 54 COPD patients belonging to different GOLD groups at their hospitalization due to the acute exacerbation of the disease but already in a stable condition at the time of the examination. Results and Conclusion. The results of the performed examinations showed that the method is suitable for monitoring the actual condition of the patients by mucosal perfusion tonometry in the sublingual region.

Intraoperative gastric tonometric examinations in children and infants with a new probe, combined with measurement of the endtidal PCO2.

Background:  Important progress relating to the early prediction of postoperative complications was recently achieved through the combined use of endtidal PCO2 (PETCO2) and gastric tonometry. The aim of this article was to present results obtained with a new tonometric instrument, proving its feasibility and extending its use to the control of anesthetized infants and children.

A method for determination of the inhibition of xanthine oxidase activity in plasma during allopurinol treatment

SummaryA micromethod suitable for measuring the combined blood levels of allopurinol and alloxanthine has been developed. The two compounds display marked inhibition of xanthine oxidase activity (Ki=6.3×10−10 and 5.4×10−10 M), so the amounts found in 20 µl serum from allopurinol-treated patients can cause marked inhibition of xanthine oxidase activity in vitro under appropriate conditions. If the concentrations of compounds acting in an ‘allopurinol-like’ manner are expressed in terms of allopurinol, activity equivalent values are obtained which reflect the effective drug concentration during therapy. The procedure is simple and suitable for serial examinations. It also satisfies the demands of the clinician, in that it can reveal any disturbance in the absorption of allopurinol and in excretion of the drug and its active metabolite, alloxanthine.

Measurement of gastric-to-end-tidal carbon dioxide difference in neonates requiring intensive care

Objective: Gastric-arterial partial CO2 pressure gap (Pg-aCO2 gap) measured by gastric tonometry may detect the disturbance of splanchnic perfusion. As in the neonatal age it is very difficult to follow up the circulatory condition with frequent acid-base examinations, we wanted to compare the Pg-aCO2 gap with an alternative gap of PgCO2 – end-tidal carbon dioxide (Pg-ETCO2 gap). Methods: A prospective study was performed on ventilated neonates requiring intensive therapy (n = 44, weight: 1813 ± 977 g). PETCO2 and PgCO2 were measured with a side stream capnograph. We applied a newly developed gastric tonometric probe. Patients were divided into two groups: Group 1 of patients in stable condition (n = 35) and Group 2 of patients with severe condition (i.e. Clinical Risk Index for Babies [CRIB] score higher than 10; n = 9). For main statistical analysis a mixed model repeated measurements ANOVA, Bland–Altman analysis were applied. Results: Pg-ETCO2 gap was higher than Pg-aCO2 gap (11.40 ± 7.79 versus 3.63 ± 7.98 mmHg, p < 0.01). Both gaps were higher in Group 2 (8.71 ± 10.89 and 18.27 ± 10.49 versus 2.53 ± 6.78 and 9.92 ± 6.22 mmHg, p < 0.01 and p < 0.05). Bland–Altman analysis of the two gaps showed an acceptable correspondence. Conclusions: Pg-ETCO2 gap may be used as a method for continuous estimation of splanchnic perfusion and a prognostic index also in critically ill neonates. However, the Pg-aCO2 gap should not be abandoned.

Alterations of the placental circulation and of there activity of the umbilical artery in experimental hypoxia and asphyxia

In the first series of experiments exteriorization of foetuses was carried out in near-term guinea pigs. The experimental groups of exteriorized foetuses were: 1.Hypoxic /N2 in cap/, 2. asphyctic /temporary cord-clamping in utero/ and 3. controls. The spontaneous closure of the cord vessels, transplacental antipyrine transfer, acid-base balance and survival rate of the foetuses were followed. After induction of spontaneous breathing in the foetuses which remained connected with the placenta, the previousely closed vessels reopened and the placental circulation was restored under the effect of the N2- breathing. In postasphyctie foetuses the placental circulation persisted in spite of the breating of atmospheric air, resulting in a favorable effect on the survival rate. In the second series of experiments the reactivity of isolated human umbilical artery and rabbit central ear artery was studied. The ultrafiltrates of the serum of hypoxic newborns exerted a smaller pressor effect on the human umbilical artery than on the rabbit ear vessel, while the corresponding effect of the normal serum ultrafiltrate was higher on the umbilical artery. In conclusion, a humoral action of the blood of hypoxic-asphyctic newborns is assummed, which tends to preserve the placental circulation.