Gyula Tálosi

The role of complement in Streptococcus pneumoniae-associated haemolytic uraemic syndrome

BACKGROUND Atypical forms of haemolytic uraemic syndrome (aHUS) include HUS caused by defects in the regulation of alternative complement pathway and HUS linked to neuraminidase-producing pathogens, such as Streptococcus pneumoniae. Increasing data support a pathogenic role of neuraminidase in the development of S. pneumoniae-associated haemolytic uraemic syndrome (SP-HUS), but the role of complement has never been clarified in detail. Therefore, we aimed to investigate whether the pathologic complement profile and genetic risk factors of aHUS are present in patients with SP-HUS. METHODS Enrolling five patients with SP-HUS classical and alternative pathway activity, besides C3, C4, factors H, B, I and anti-factor H autoantibody levels were determined. The coding regions of CFH, CFI, CD46 (MCP), THBD, C3 and CFB genes were sequenced and the copy number of CFI, CD46, CFH and related genes were also analyzed. RESULTS We found that in the acute phase samples of SP-HUS patients, complement components C4, C3 and activity of the classical and alternative pathways were decreased, indicating severe activation and complement consumption, but most of these alterations normalized later in remission. Three of the patients carried mutations and risk haplotypes in complement-mediated aHUS associated genes. The identified mutations include a previously published CFI variant (P50A) and two novel ones in CFH (R1149X) and THBD (T44I) genes. CONCLUSIONS Our results suggest that severe complement dysregulation and consumption accompany the progress of invasive pneumococcal disease (IPD)-associated SP-HUS and genetic variations of complement genes may contribute to the development of this complication in a proportion of the affected patients.

Prostaglandin E1 treatment in patent ductus arteriosus dependent congenital heart defects.

Abstract Prostaglandin E1 (PGE1) treatment can be life saving in patients suffering from ductus dependent congenital heart defect. We analyzed the indications and side-effects of PGE1 therapy over a five-year period. The purpose of the study was also to examine whether a change in serum electrolyte levels could be detected. Forty-nine patients were treated with PGE1 during this period. PGE1 treatment was indicated by ductus dependent systemic circulation in 16 cases, ductus dependent pulmonary circulation in 17 cases, transposition of the great arteries in 13 cases and pulmonary hypertension (persistent fetal circulation) in three cases. As early side-effects of the treatment, fever occurred in 27/49 cases while apnoea was observed in 15 patients. In a one-week-old neonate with coarctation of the aorta grade III intraventricular hemorrhage developed. A mild decrease of sodium, potassium and chloride levels and a slight shift of pH levels toward metabolic alkalosis could be detected after one day and one week of PGE1 treatment. Because of these side-effects of PGE1 patients should be monitored in an intensive care unit. According to our observations electrolyte levels may exhibit a slight decrease; however, in the case of a short-term therapy extra salt supplementation is not necessary.

XANTHINE OXIDASE ACTIVATION IN MILD GESTATIONAL HYPERTENSION

Objective: We hypothesized that activation of the xanthine oxidase (XO) enzyme system is a potential source of free radicals in pregnancy-induced hypertension (PIH). Methods: A prospective observational study was carried out on 16 pregnant women who met the criteria of gestational hypertension [rise in blood pressure (BP) of 30 mm Hg systolic or 15 mm Hg diastolic after 20 weeks gestation or BP>140/90 mm Hg if earlier pressure is unknown] without proteinuria or any signs of renal impairment. Fourteen women with a clinically normal pregnancy matched for maternal age, parity, and gestational age acted as pregnant controls. Nonpregnant control women were members of the laboratory staff (n=15). Main Outcome Measures: Concentrations of free sulfhydryl (SH) groups, purine catabolites, lipid peroxidation products in plasma, and blood carboxyhemoglobin levels were used to follow oxidative stress and potential hemolysis. A noninvasive measurement of functional XO activity was carried out (i.e., the urinary ratio of the two metabolites of caffeine was estimated). Results: A pronounced oxidative stress was demonstrated in plasma samples of patients with hypertension by the elevated concentrations of uric acid and lipid peroxidation products. A reduced level of free sulfhydryl groups and an increased concentration of hypoxanthine (HX) were shown in normotensive pregnant individuals. The XO activity index was substantially higher in overweight pregnant subjects with mild hypertension [0.849±0.096 (p<0.01)] than in normotensive pregnant women or in age-matched nonpregnant subjects [0.596±0.105, 0.542±0.049 (means±SD), respectively]. Conclusions: Our study of mildly hypertensive pregnant subjects provides additional evidence of the putative role of XO activation as a source of free radicals in the early stage of endothelial dysfunction.

Renal injury in perinatal hypoxia: ultrasonography and changes in renal function

Abstract We studied 12 hypoxaemic neonates (5 mature newborns, birth weight 2850–4200 g, gestational age 37–41 weeks; and 7 premature newborns, birth weight 770–1850 g, gestational age 27–34 weeks;) with repeated urine and blood chemistry on the 1st and 3rd days of life. Nephrosonographical examinations on the 1st, 3rd and 5–7th days of life were also performed. As controls, 12 healthy infants were examined (gestational age 36–42 weeks; birth weight 2450–4200 g). Hypoxic neonates had higher serum creatinine and blood urea nitrogen levels. Tubular markers also demonstrated renal tubular damage. Neonates in both hypoxic groups were hyperuricaemic and hyperuricosuric, and had higher urinary protein concentrations. All these infants exhibited an increased echogenicity of the renal cortex, and 11/12 showed the same finding in the medullary area. These findings disappeared within 1 week in all infants. Among the 12 healthy control infants, no cortical hyperechogenicity was found and only three of these infants displayed transient medullary renal hyperechogenicity. Conclusion Since the hypoxaemic infants demonstrated greatly increased urinary concentrations of uric acid and protein, we suggest that a temporary precipitation of these two agents may be responsible for the ultrasonographic findings. Circulatory redistribution might play a role in the phenomenon of cortical hyperechogenicity.

Side-effects of long-term prostaglandin E1 treatment in neonates

Background: In some neonates suffering from ductus arteriosus dependent congenital heart defect, a Prostaglandin E1 (PGE1) therapy longer than 2 weeks may be needed. However, PGE1 analogue compounds may produce several adverse effects.

Inhibitory effects of methylxanthines on the pre-eclamptic-like symptoms in ewes

OBJECTIVE Our objective was to determine whether two methylxanthines, pentoxifylline (PTX) and allopurinol, would have beneficial effects on experimental pregnancy-induced pre-eclampsia- like disease in ewes. STUDY DESIGN 20 animals at the gestational age of 130-135 days were divided into four groups (control; fasting; fasting, pentoxifylline-treated; and fasting, allopurinol-treated). The illness was provoked with a 4-day fasting period. Electrolytes, glucose, conventional parameters, plasma haem content, indirect bilirubin concentration and free thiol levels were measured. RESULTS Unlike in the fasting group, conventional signs of the disease, such as hypertension, kidney and liver injury and platelet count decrease, were all mitigated in the fasting, drug-treated animals. In the treated animals plasma haem content increased by a less significant level, while indirect bilirubin concentration showed a more rapid rise. CONCLUSIONS Both methylxanthines partly inhibited the pre-eclamptic-like symptoms in ewes. We speculate that the better induction of haem oxygenase might play an important role in this inhibitory effect on this particular animal model.

Chryseobacterium gleum – a novel bacterium species detected in neonatal respiratory tract infections

Abstract We report three patients with early neonatal infections. All patients had respiratory tract involvement with increased inflammation markers. Chryseobacterium gleum was cultured from the stomach content aspirated on arrival at the Neonatal intensive Care Unit and it was identified with the help of a Microflex™ MALDI Biotyper mass spectrometer (Bruker-Daltonik, Fremont, CA). Recovery could be achieved with ciprofloxacin treatment. We consider our cases a possible new clinical presentation of a rare human pathogen.

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.

Iatrogenic Skin Disorders and Related Factors in Newborn Infants

Recent technological advances and diagnostic and therapeutic innovations have resulted in an impressive improvement in the survival of newborn infants requiring intensive care. Consequently, with the use of modern invasive diagnostic and therapeutic procedures, the incidence of iatrogenic events has also increased. The aim of this study was to assess various iatrogenic complications in neonates requiring intensive care and determine possible contributing factors to the injuries.

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.