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Biomedical subjects

J Golej

Publications and source records attributed to J Golej.

28 records · Page 2Linked to original sources

Extracorporeal membrane oxygenation discontinuation despite technically successful reoperation: A case report.

Death remains a probable outcome of pediatric cardiac extracorporeal membrane oxygenation (ECMO) despite increasing efforts to improve the results. On venoarterial ECMO, in an obviously hopeless situation, the decision to withdraw a life supporting measure resulting in the sudden death of a child places a heavy burden on the team. After valvulotomy of critical aortic stenosis in a prenatally diagnosed term neonate, ECMO had to be installed during postoperative resuscitation. Despite technically successful homograft implantation while on ECMO complicated by postoperative bleeding, advancing multiorgan failure resulted in ECMO withdrawal. As shown in this case report, exact termination criteria are lacking but are necessary to prevent increasing team and resource related conflicts in pediatric cardiac ECMO.

Aortic Valve↗

Oral administration of methylglyoxal leads to kidney collagen accumulation in the mouse.

Methylglyoxal (MG) is a physiological substrate of the glyoxalase system which is impaired in the diabetic state and implicated in the development of diabetic complications. Like other reactive aldehydes in diabetes mellitus (DM) this carbonyl can bind to and modify proteins which may lead to changes of biochemical and biophysical properties of connective tissue proteins, a hallmark of diabetes mellitus. As previous studies on MG effects were confounded by other aldehydes found in DM, we decided to administer MG to 10 healthy, female OF-1 mice for a period of five months, at a level of 50 mg/kg body weight per day using 10 healthy untreated litter mates as controls. The left kidneys were taken for the determination of total kidney collagen, fluorescence, acid solubility of collagen and the right kidneys were used for the determination of glomerular basement membrane thickness. Total kidney collagen was significantly higher in the MG treated mice compared to control mice. Only about half the amount of collagen could be extracted from kidneys of MG treated animals indicating reduced solubility. Fluorescence in proteins from extracted kidneys of MG treated animals was about twice that of untreated animals. Glomerular basement membrane thickness was significantly higher in MG treated animals. Our findings indicate that MG can increase glomerular basement membrane thickness and the suggested underlying mechanism may be decreased solubility by increased cross linking as reflected by elevated protein fluorescence and decreased acid salt extraction. The involvement of MG in the development of diabetic complications postulated by others is herewith clearly supported by our findings.

Administration, Oral↗

A simple neonatal mock circulation enabling pulsatility and different hemodynamical states for neonatal ECMO research: application to assess the effect of a centrifugal pump operated neonatal ECMO system on the circulation.

In neonates, extracorporeal membrane oxygenation (ECMO) is increasingly used for circulatory support, e.g., after cardiac surgery. For training purposes and for research, animal experiments are usually required, complicated by increasing social issues, high costs, and limited reproducibility. Therefore, we designed a mechanical neonatal mock circulation (NMC) model enabling pulsatility and various hemodynamic conditions commonly occurring in neonates. Connected to a flow and pressure reading interface, a computer assisted data management system was installed. A nonocclusive roller pump combined with stiff and elastic tubing segments (for aortic pressure regulation and venous capacity) as well as constant and variable resistance (and optionally a patent duct) are essential features of the NMC system. To show the investigational potential, we studied the influence of venoarterial and venovenous ECMO on the NMC performance during normal circulation, hypovolemia, high arterial resistance, the combination of both, and in low cardiac output. By assessing the significant effects of ECMO on the circulatory function of the NMC, its feasibility and investigational properties could be demonstrated.

Blood Pressure↗

Preoperative ECMO in congenital cyanotic heart disease using the AREC system.

BACKGROUND: In cyanotic congenital heart disease, oxygen delivery is impaired either by reduced pulmonary perfusion or by limited entry of oxygenated blood into the systemic circulation. Additional impairment of oxygen delivery (eg, in pulmonary hypertension) leads to hypoxic cerebral damage. Preoperative extracorporeal membrane oxygenation enables oxygenation in otherwise untreatable cases. METHODS: In 3 neonates suffering from cyanotic congenital heart disease (1 with tricuspid atresia and 2 with transposition of the great arteries) with arterial desaturation despite application of prostaglandins, balloon atrioseptostomy, and eventually inhaled nitric oxide during intermittent positive-pressure ventilation with an inspired oxygen fraction of 1, oxygenation could only be established by means of preoperative extracorporeal membrane oxygenation. We used a venovenous single-lumen cannula tidal-flow extracorporeal membrane oxygenation system described by Chevalier and associates that has previously been used for extracorporeal lung support. In this system, called AREC (assistence respiratoire extra-corporelle), alternating clamps and a nonocclusive roller pump were used. RESULTS: All 3 survived. CONCLUSIONS: We conclude that the AREC system enables sufficient preoperative oxygenation in patients with cyanotic congenital heart disease and hypoxia in spite of all conventional therapeutic means. This provides a stable preoperative condition for elective palliation or correction.

Cyanosis↗

The transcription of the XRCC1 gene in spleen following ionizing irradiation in radiosensitive and radioresistant mice.

The XRCC1 gene was described to play a role for the sensitivity of mammalian cell lines towards ionizing irradiation. Cells with a mutation of this gene present with decreased single strand break repair, reduced recombination repair, show increased double strand breaks and sister chromatid exchange is increased up to tenfold. The goal of our study was to investigate the transcription of this gene in the spleen following ionizing irradiation in the mouse. Furthermore, we intended to examine whether radiation sensitive (RS) mice would show a transcriptional pattern different from radiation resistant (RR) mice. Radiation sensitive BALB/c/J Him mice and radiation resistant C3H He/Him mice were untreated or whole body irradiated with X-ray at 4 and 6 Gy and sacrificed 5, 15 and 30 min after irradiation. mRNA was isolated from the spleen and hybridized with probes for XRCC1 and beta-actin as a house keeping gene control. Transcription of XRCC1 was not different in unirradiated or 4 Gy-irradiated mouse RR or RS mouse strains. When irradiated at 6 Gy, RR mice showed an approximately threefold increase of mRNA XRCC1/mRNA beta actin as early as 15 min after irradiation. We conclude that radiation resistant mice show a higher transcription level for the XRCC1 gene in the spleen early after high dose X-ray whole body irradiation. This finding is the first in vivo study on XRCC1 of this kind and may in part explain the differences in the radiation sensitivity between the two strains studied.

Animals↗

Single needle venovenous extracorporeal membrane oxygenation using a nonocclusive roller pump for rescue in infants and children.

In 1993, J.Y. Chevalier described a single needle venovenous extracorporeal membrane oxygenation (ECMO) system using a nonocclusive roller pump and alternating clamps for pulmonary support in neonates. We modified this system to use it in older children as well and for additional indications. Introducing a double raceway and 2 different sizes of tubing sets and performing percutaneous approach, we treated 21 children (age 1 day to 49 months) using this system. Indications for treatment were hypoxia and hypoxic induced myocardial dysfunction resulting from pulmonary failure, sepsis, and congenital defects. Of the children treated for neonatal indications, 7/9 survived. For 2 children ECMO was terminated because of intraventricular hemorrhage (IVH). In the pediatric group 5/7 of the children could be weaned from ECMO, and 2 children died after more than 30 days on ECMO. Two of the children who had been almost completely weaned died later because of therapy withdrawal following a brain death diagnosis. In the cardiac group, 3/5 of the children survived. We conclude that the described system is an effective venovenous ECMO system that reduces invasivity and expenditure.

Anticoagulants↗

Extracorporeal membrane oxygenation in neonates.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO), originally developed as an artificial replacement for respiratory assistance, is decreasingly used in neonates with respiratory failure. Nevertheless, there is a constant need for this invasive and expensive neonatal treatment modality. INTERVENTION: Review of our experience (80 recent ECMO performances because of circulatory failure) and the literature. RESULTS: In contrary to reduced ECMO performances out of respiratory insufficiency in neonates, ECMO as circulatory support is increasingly used. Neonatal sepsis, pre- and postoperative cardiac failure, combined circulatory and respiratory failure after resuscitation and with congenital diaphragmatic hernia result in a permanent need for ECMO, whenever there are fewer ECMO treatments per year. Nonocclusive pumps, portable devices, small priming volumes and tapered anticoagulation protocols enable survival through ECMO even in virtually hopeless hemodynamic conditions. Special efforts in investigation and prevention of permanent neurological impairment, especially after severe pre-ECMO hypoxia seem to be mandatory. CONCLUSION: ECMO remains an important tool in neonatal and pediatric intensive care. However, the number of ECMO therapies was reduced due to respiratory therapeutic progress, but indications and ECMO technology have changed.

Anticoagulants↗

[Acute respiratory failure (ARDS) in a young child after drowning accident: therapy with exogenous surfactant and high frequency oscillatory ventilation].

The adult respiratory distress syndrome (ARDS) in children has a very poor prognosis with a mortality risk of between 55 and 85%, in spite of improvements due to the introduction of positive endexpiratory pressure ventilation. We describe the clinical course of a not yet 3 year-old boy with severe ARDS following near-drowing. Treatment with exogenous surfactant and high frequency oscillatory ventilation, a well-established procedure in neonatology, was responsible for the favorable outcome. The high cost of surfactant therapy, however, is the main limiting factor for this kind of treatment in children beyond the neonatal period, but it may be the last therapeutic resort in the management of severe ARDS.

Child, Preschool↗

[Therapy refractory arterial hypotension after heart operation].

Adrenalin insufficiency associated with adrenal hemorrhage, is a rare complication after cardiac surgery in neonates. A boy suffering from transposition of the great arteries, who had an arterial switch-operation on day three of his life, acquired a bilateral adrenal hemorrhage. Clinically the situation resembled a septic shock. Despite large doses of catecholamines, he continued to have severe arterial hypotension, anuria, and kyperkalemia. The clinical condition did not change, although sepsis specific therapy was initiated. Consequently adrenal insufficiency, as a possible postoperative complication, was considered and prednisolon, initially in a dose of 15 mg/kg/d, was administered. The clinical condition improved dramatically. The diagnosis could be confirmed by ultrasound examination and determination of cortisol and ACTH plasma levels. Adrenal insufficiency was only transitory, adrenal sonography on day 135 returned to normal. The surgical procedure on heart-lung bypass, the obligatory anticoagulation and the perioperative stress have to be considered as pathogenetic factors.

Adrenal Insufficiency↗

L-arginine reduces kidney lipid peroxidation, glycoxidation and collagen accumulation in the aging NMRI mouse.

Collagen accumulation in organs is a main feature of the physiological aging process. There are two main theories for the responsible mechanisms, the free oxygen radical and the glycoxidation theory. Both lead to carbonyle-induced protein modification, increased collagen cross-linking and subsequently to the collagen accumulation. In previous studies we provided evidence for the blocking of reactive carbonyles by L-arginine in the diabetic state and present here data for this effect in the aging NMRI mouse. NMRI mice were fed L-arginine in tap water for a period of 6 months and compared to an untreated control group. Kidney collagen content of the treated group was significantly reduced (treated: 8.83 +/- 0.72 mg collagen/100 mg kidney weight; untreated: 11.95 +/- 0.98 mg collagen (100 mg kidney weight; p < 0.05). Using a colorimetric assay for lipid peroxidation products we found significantly reduced lipid peroxidation-derived aldehydes in the treated group (treated: 0.25 +/- 0.03 extinction; untreated: 0.36 +/- 0.04 extinction; p < 0.05). The parameter for glycoxidation, N-epsilon-carboxymethyllysine (CML) was significantly lower in the experimental group as well (treated: 2.3 +/- 0.5 nM CML/microM hydroxyproline; untreated: 4.3 +/- 0.52 nM CML/microM hydroxyproline; p < 0.05). No differences were observed for the biomarker of hydroxyradical attack, o-tyrosine. L-Arginine could have reduced collagen accumulation by blocking collagen glyc(oxidation) which is known to lead to increased collagen cross-linking, solubility and degradation as a strong correlation between both CML and collagen content (r2 = 0.654, p < 0.05) as well as between lipid peroxidation products and collagen content (r2 = 0.539, p < 0.05) was observed.

Aging↗