Jan Žižka

Cytokine levels in healthy and allergic mothers and their children during the first year of life.

To assess the regulatory changes of immune system in children genetically pre‐disposed to allergic diseases and in their mothers, we tested cytokines IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, IFN‐γ and TGF‐β in 21 healthy and 21 allergic mothers (serum at the time of delivery, colostrum and milk throughout the suckling period) and their children (cord blood, venous blood and stool filtrates) up to 1 yr of age. Samples were taken at the time of delivery, 4 days post‐partum and then after 3, 6 and 12 months. Significant differences between the healthy and the allergic group were found in the levels of IL‐4, IL‐10, IL‐13 and IFN‐γ. The levels of IL‐4 in the allergic group were generally higher; the levels in the sera of children of allergic mothers during the post‐natal life decreased, reaching levels typical for the healthy group at 1 yr of age. Allergic mothers exhibited markedly higher IL‐10 levels in the serum at the time of delivery and in milk 3 months after delivery than healthy mothers while after 6 months the IL‐10 levels in all samples from the allergic group were very low. Children from allergic group had lower intestinal content of IL‐13 in comparison with the healthy counterparts. At 1 yr of age, the levels of IFN‐γ in sera and stool of children from the allergic group sharply increased. TGF‐β levels in the sera of both groups were high, while in the milk they were relatively low and substantially lower that in the childrens stool. TGF‐β of mammary secretions is therefore unlikely to exert a decisive regulatory influence on the childrens immunity. Long‐term clinical monitoring of the children will be performed to evaluate the potential prognostic significance of these changes for the future development of allergies.

Prevention of Allergy in Infants of Allergic Mothers by Probiotic Escherichia coli

Background: The objective is to study the effect of after-birth oral colonization by a probiotic Escherichia coli strain in infants of allergic mothers to reduce occurrence of allergy later in life. Methods: In a controlled clinical trial, 158 infants were randomly divided into groups of (i) 56 colonized infants of allergic mothers, (ii) 57 control infants of allergic mothers, and (iii) 45 control infants of healthy mothers. Incidence rates of bacterial pathogens in stool and levels of anti-E. coli immunoglobulins and some cytokines in serum were determined, and secretory IgA was monitored in stool filtrates and maternal milk. Clinical check-ups of infants aged 4 days, 3 and 6 months, 2, 3 and 5 years were carried out and clinical symptoms of allergy were monitored. One milliliter of the probiotic E. coli strain was administered to infants of allergic mothers at first within 48 h after birth and subsequently 3 times a week over a period of 4 weeks. Control infants of allergic and healthy mothers were monitored in these intervals as well. Results: Presence of the E. coli strain was monitored in stool samples throughout the study. At the conclusion of the study, allergy symptoms were found in 14 infants of control allergic mothers, 7 infants of healthy mothers, and in 2 colonized infants of allergic mothers. Colonization affected levels of several cytokines and specific anti-E. coli antibodies. Conclusions: After birth, targeted colonization of the intestine by a probiotic E. coli strain can be an effective means of allergy prevention in infants of allergic mothers.

Choroid plexus cyst of the left lateral ventricle with intermittent blockage of the foramen of Monro, and initial invagination into the III ventricle in a child

Abstract A cyst of the choroid plexus of the left lateral ventricle with intermittent blockage of the foramen of Monro and initially with invagination of the III ventricle in a child is described. In a 6-week-old boy a ventriculoatrial shunt was implanted for correction of an active asymmetrical hydrocephalus of unknown origin. When he was 3 months of age a water-soluble contrast CT ventriculography revealed a noncolloid cyst localised predominantly in the upper portion of the III ventricle. At that time the ventricular catheter obstructed with choroid plexus was removed; new bilateral catheters in a parieto-occipital region were implanted. In the course of the next 4 years, first the atrial catheter had to be extracted and then the peritoneal catheter was changed, in both cases because of obstruction. Periods of normal life alternated with periods of transient and intermittent symptoms of increased intracranial pressure, papilloedema, and myoclonic jerks. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) showed stabilised hydrocephalus with an enlarged left lateral ventricle. When the boy was 16 years old MRI revealed a choroid plexus cyst in the left lateral ventricle 2 cm in diameter, with a ball-valve type of obstruction of the foramen of Monro. CT stereoendoscopic resection of the wall of a large cyst filled with cerebrospinal fluid was performed, and two additional adnexal small cysts were coagulated using the bipolar coagulator, Diomed 25 laser and scissors; the symptoms then regressed, except for superior bilateral altitudinal anopsia. Light and electron microscopy of the cyst wall is reported. The cyst was composed of collagenic connective tissue lined with a basal lamina lacking in epithelial cells. The preoperative and postoperative MRI are presented. Choroid plexus cysts localised in the anterior part of lateral ventricles are very rare, and all reported cases have been in male patients. According to the literature our case is only the third ever described in a child.

Effect of breast milk of healthy and allergic mothers on in vitro stimulation of cord blood lymphocytes

Maternal milk has beneficial effects on the development and function of the newborns immune system. Whether the milk of allergic mother has the same effects as the milk of healthy mothers is not yet quite clear. To contribute to the characterization of its immunomodulatory action, we tested the effect of milk of healthy and allergic mothers on the proliferation and immunoglobulin formation in cultures of cord blood mononuclear leucocytes (CBML) of newborns of healthy and allergic mothers. CBML proliferation was tested by 3H‐thymidine incorporation, IgM, IgG and IgA production by reverse ELISPOT. CBML response was examined in unstimulated cultures and after stimulation with polyclonal activators in the presence or absence of colostrum or milk. The cells of children of allergic mothers have a significantly higher proliferative activity than those of children of healthy mothers. Maternal colostrum/milk in high doses markedly suppresses cell proliferation after stimulation with polyclonal activators, whereas lower milk doses in the cultures have no such effect and exert a rather stimulatory action. Immunoglobulin production by cord blood lymphocytes is also different in the two groups of children. Low basal immunoglobulin formation is increased after stimulation with a strong polyclonal activator of B cells –Bacillus firmus, CBML of children of allergic mothers produce more IgA than those of children of healthy mothers. The stimulated production of all immunoglobulin classes in cells of children of healthy mothers is still enhanced by colostrum/milk. Children of allergic mothers show a markedly increased production of only IgM and IgA. The effect of healthy and allergic colostrum and milk on cell proliferation and immunoglobulin production is similar. The lymphocytes of children of allergic mothers differ from the lymphocytes of children of healthy mothers in their proliferative activity and the ability to form immunoglobulin already at birth.

Mature sacrococcygeal teratoma containing the lower half of a human body

Twins were diagnosed by ultrasound in a 29-year-old woman. The cesarean delivery revealed at first a mature girl with a large benign sacrococcygeal teratoma and then a healthy boy. X-ray and CT examinations of the teratoma showed pelvic and lower limb bones. A mature teratoma-tridermona (weight 475 g) containing the underdeveloped lower half of a human body was confirmed during surgery and verified morphologically. The fraternal twins, i.e., the girl operated upon and her brother, have been followed for 5 years and are without any complaints. They have normal neurological function.

COMPARISON OF DUPLEX ULTRASONOGRAPHY AND MAGNETIC RESONANCE IMAGING IN THE DETECTION OF SIGNIFICANT RENAL ARTERY STENOSIS

OBJECTIVE The aim of our study was to evaluate duplex ultrasonography (DUS) and magnetic resonance angiography (MRA) in detection of haemodynamically significant renal artery stenosis (RAS). METHODS The study included patients with high clinical suspicion of renovascular hypertension (RVH). The imaging of renal arteries was performed by DUS, MRA and digital subtraction angiography (DSA). Significant RAS was defined as maximum systolic velocity > or =180 cm/sec (DUS) or as 60% reduction of the endoluminal arterial diameter (MRA, DSA). The results of DUS and MRA were assessed in respect to the results of DSA. RESULTS Arterial supply of 186 kidneys in 94 patients was evaluated. DSA revealed significant RAS in 61 kidneys evaluated. DUS was not able to examine arterial supply in 18 kidneys of 13 patients. In the detection of significant RAS, DUS was characterized by sensitivity and specificity of 85% and 84%. MRA achieved satisfactory imaging quality in all but one kidney evaluated. The sensitivity and specificity of MRA in the detection of significant RAS was 93% and 93%, respectively. CONCLUSION In patients with high clinical probability of RVH, MRA proved to be more reliable and superior in both sensitivity and specificity to DUS in the detection of significant RAS.

Perinatal period cytokines related to increased risk of future allergy development.

Testing of cytokine levels in colostrum, cord blood and amniotic fluid of healthy and allergic mothers and their newborns (using protein microarrays and quantitative analysis by ELISA) revealed differences in the levels of IL-5, IL-10, TGF-β, TNF-α, EGF and eotaxin between healthy and allergic groups. Significantly higher concentration of IL-5 and IL-10 in the colostrum of allergic mothers and cord blood of their children and also tendency to a higher level of IL-4 found at allergic mothers and their children (but without statistical significance) indicate a bias to TH2 response in this group. The higher level of TGF-β in the colostrum of healthy mothers should be involved in beneficial immunological tuning of their children including enhanced IgA formation and better intestine maturation. In amniotic fluid, concentration of TGF-β was higher in children of allergic mothers. A significantly higher level of EGF was proved in the colostrum of healthy mothers and in cord blood of their children in comparison with allergic group. EGF deficiency in the allergic group could impair or delay intestine maturation and support thus allergy development.

Cytokine expression in cord blood cells of children of healthy and allergic mothers

To determine some early signs connected with the increased risk of future allergy development, gene expression and production of selected cytokines were tested in children of allergic mothers and compared with newborns of healthy mothers. Expression of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, TNF-α, TGF-β and EGF was tested in cord blood cells using real-time PCR and production of these cytokines was evaluated in cord sera by ELISA. Gene expression of IL-2, IL-4, IL-8, IFN-γ, IL-1β, TNF-α and TGF-β was decreased and that of IL-10, IL-13 and EGF increased in children of allergic mothers in comparison with those of healthy mothers. Significant differences in sera of healthy and allergic groups were only in IL-10 and EGF. Different relationship among serum cytokine levels reflects the fact that the cytokines are not produced only by blood cells. Significantly decreased production of EGF in newborns of allergic mothers could negatively influence maturation of mucosal membranes of these children and support thus their easier allergization. Allergic phenotype pointing to the bias to TH2 response and to possibly impaired intestine maturation was apparent already on the level of cord blood and could serve as a predictive sign of increased allergy risk.

Contrast-enhanced MR angiography utilizing parallel acquisition techniques in renal artery stenosis detection

Significant renal artery stenosis (RAS) is a potentially curable cause of renovascular hypertension and/or renal impairment. It is caused by either atherosclerosis or fibromuscular dysplasia. Correct and timely diagnosis remains a diagnostic challenge. MR angiography (MRA) as a minimally invasive method seems to be suitable for RAS detection, however, its diagnostic value widely differs in the literature (sensitivity 62-100% and specificity 75-100%). The aim of our prospective study was to compare the diagnostic value of contrast-enhanced MRA utilizing parallel acquisition techniques in the detection of significant RAS with digital subtraction angiography (DSA). A total of 78 hypertensive subjects with suspected renal artery stenosis were examined on a 1.5 Tesla MR system using a body array coil. Bolus tracking was used to monitor the arrival of contrast agent to the abdominal aorta. The MRA sequence parameters were as follows: TR 3.7 ms; TE 1.2 ms; flip angle 25 degrees; acquisition time 18s; voxel size 1.1 mm x1.0 mm x 1.1 mm; centric k-space sampling; parallel acquisition technique with acceleration factor of 2 (GRAPPA). Renal artery stenosis of 60% and more was considered hemodynamically significant. The results of MRA were compared to digital subtraction angiography serving as a standard of reference. Sensitivity and specificity of MRA in the detection of hemodynamically significant renal artery stenosis were 90% and 96%, respectively. Prevalence of RAS was 39% in our study population. Contrast-enhanced MRA with high spatial resolution offers sufficient sensitivity and specificity for screening of RAS.

IgE against food and respiratory allergens in healthy and allergic mothers and their children

IgE against mixtures of common food or respiratory allergens were determined by ELISA in healthy (n = 38) and allergic (n = 62) mothers and their children. Significantly higher level of IgE against respiratory allergens was found in sera of allergic mothers and in cord blood of their children. No correlation between antibody level in maternal and newborn’s sera was found; this argues against the transfer of IgE from mother to fetus and points rather to offspring’s intrauterine sensitization. Specific IgE level in cord blood was higher in children who developed later allergy than in children who did not. Specific IgE level in colostrum was low both in healthy and allergic mothers; there was no correlation between high concentration of IgE against respiratory allergens in sera of allergic mothers and their colostrum, which does not support the idea of IgE transport from blood to mammary gland. Only slightly increased colostral IgE was detected in allergic mothers whose children manifested allergy later. Allergy of the mother and high level of anti-allergen IgE in her serum and in cord blood are the main predictive factors of future occurrence of allergy in the offspring. A combination of several predictive factors could have higher prognostic value.