Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss.

Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

Detection of cytomegalovirus in infant cerebrospinal fluid by conventional PCR, nested PCR and PCR-Digene.

The possibility of amplification of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid (CSF) for the diagnosis of HCMV central nervous system (CNS) infection in infants was studied. Single-step PCR, nested PCR and PCR-Digene were used to assay CSF specimens from 37 patients. Criteria for patient inclusion in the study were: 1. clinical manifestations suggesting CMV neuroinfection such as seizures, hypertonia, hypotonia, intracranial calcification, microcephaly, chorioretinitis; 2. any of the following symptoms: anaemia, hepetomegaly, prolonged cholestatic jaundice, or hepatitis, splenomegaly, thrombocytopenia, intrauterine hypotrophy; 3. serologic presentation, and/or positive results for CMV infection obtained by single-step PCR and PCR-Digene in urine and/or blood. PCR-Digene results were positive in 6 CSF samples. Four CSF samples were positive by nested PCR and 1 CSF sample by single step PCR. We found that the double PCR was about ten or more times more sensitive than single PCR and the PCR-Digene was only three times more sensitive than nested-PCR. The results were correlated with serology. Thirty-three out of 37 examined patients were seropositive (ELISA IgG); ELISA IgM gave positive results in 9 patients. In control studies, cells infected with other members of the herpes virus family were negative with these methods, which suggest that amplification combined with primers from the IE and the L-region of CMV is specific. In conclusion, nested-PCR seems to be the best method for early diagnosis of CMV infection in CSF due to an absence of false positive results and its high specificity and sensitivity.

[Use of the PCR technique for diagnosis of symptomatic congenital toxoplasmosis based on own observations]. / Zastosowanie techniki PCR w diagnostyce objawowej toksoplazmozy wrodzonej w badaniach wlasnych.

UNLABELLED: The aim of our study was to determine the usefulness of PCR technique in postnatal diagnosis of congenital toxoplasmosis in 17 infants aged from 1 week to 10 months. In 13 cases the diagnosis was established. The diagnostic procedures involved: clinical examinations, serological tests, nested-PCR method and neuroimaging examinations. RESULTS: In almost all children (except one) a high level of toxoplasmatic IgG antibodies was found; in 1/3 we identified antibodies IgM and IgA. In 14 cases the PCR test from CSF was positive. In 4 infants the suspicion of congenital toxoplasmosis was ruled out; in 2 of them PCR from CSF was negative, in 2 - a false positive result was stated. CONCLUSIONS: PCR is a valuable technique for diagnosis of congenital toxoplasmosis. Because of the possibility of false positive and negative results - it should be combined with other laboratory methods.

Risk factors for cerebral palsy in very low-birthweight infants in the 1980s and 1990s.

One-hundred twenty-nine very low-birthweight infants were treated in Newborn and Infant Care Department of Children's Memorial Health Institute between 1985 and 1994; 89 were taken to prospective neurodevelopmental care. The newborns were divided into two groups. Group I had 38 preterm infants born from 1985 to 1989 and followed up at 7 to 11 years of age. Group II had 51 very low-birthweight infants treated from 1990 to 1994 and followed up at 2 to 5 years of age. Complicated, multiple pregnancy, normal delivery, and extremely low birthweight were significantly more frequent in group II. Very low-birthweight infants were frequently born by cesarean section in severe asphyxia. Only four (7.8%) newborns received surfactant therapy. From 1990 to 1994, respiratory distress syndrome III and IV, and a longer respiratotherapy period were significantly more frequent. From 1985 to 1994, the frequency of sepsis, periventricular leukomalacia, and normal ultrasonography was constant. Intraventricular hemorrhage I, II, and IV were frequently present in the 1990s, and intraventricular hemorrhage III was frequent in the 1980s. Cerebral palsy was diagnosed in 11 (28.9%) children in group I and 18 (35.2%) in group II (not statistically different). Multiple and complicated pregnancy, cesarean section, severe asphyxia, and respiratory distress syndrome did not increase the risk of cerebral palsy in very low-birthweight infants. Periventricular leukomalacia has a more predictive value for cerebral palsy in these infants than did intraventricular hemorrhage.

[Chronic, infantile, neurologic, cutaneous and articular syndrome (CINCA) in an infant]. / Syndrome chronique, infantile, neurologique, cutané et articulaire (CINCA) chez un nourrisson.

BACKGROUND: CINCA syndrome is a clinical syndrome of unclear etiology, characterized by a chronic multi-organ inflammatory process unsusceptible to treatment. CASE REPORT: An 18-month-old boy was admitted because he suffered, since the age of 2 months, from cutaneous, articular and neurological changes, lymphadenopathy, hepatosplenomegaly, choroiditis and psychosomatic development retardation. These clinical symptoms were unsusceptible to anti-inflammatory and antihistaminic drugs. Rehabilitation was not effective either. CONCLUSION: A long-term clinical observation is required before sustained multi-organ changes beginning in early childhood and exclusion of other chronic inflammatory diseases enable the diagnosis of CINCA syndrome.

[Application of polymerase chain reaction (PCR) for the detection of DNA-HCMV in cerebrospinal fluid of neonates and infants with cytomegalovirus infection]. / Wykorzystanie polimerazowej reakcji lancuchowej (PCR) do wykrywania DNA-HCMV w plynie mózgowo-rdzeniowym noworodków i niemowlat z zakazeniem wirusem cytomegalii.

The goal of the work was to prove the usefulness of PCR for detection of DNA-HCMV in cerebrospinal fluid of the infected newborns and infants and to compare our results with clinical diagnosis. The studied group consisted of 24 newborns and infants with HCMV infection (presence of DNA-HCMV in urine and blood, presence of specific IgM, IgG antibodies in serum, and clinical symptoms). Among 12 children with symptoms from central nervous system, DNA-HCMV was detected in CSF of 11 patients. Additionally DNA-HCMV was found in cerebrospinal fluid of 2 children IgM, IgG anti CMV positive but without CNS symptoms. Extraction of DNA from pellet was the most effective method of DNA preparation from CSF for PCR reaction. Final results were obtained approximately 7-8 hours after taking the samples for examination. Our results suggest that PCR technique as a highly specific method is very helpful for the detection of DNA-HCMV in CSF of children with CNS symptoms of disease.

[Human cytomegalovirus infection in the pre- and postnatal period with special regards to routes of infection]. / Zakazenie ludzkim wirusem cytomegalii (HCMV) w okresie przed i po urodzeniu ze szczególnym uwzglednieniem dróg zakazenia. uwzglednieniem dróg zakazenia.

The clinical course of HCMV infection in newborns and infants was discussed. Different routes and sources of infection were analyzed, especially acquired infection from the mother excreting the virus in breast milk. The usefulness of modern laboratory techniques (PCR to detect HCMV DNA and detection of antigen in leucocytes) and the importance of simultaneous tests performed in children and their mothers in stating the diagnosis was also evaluated.

[Persistent pulmonary hypertension in newborns]. / Przetrwale nadcisnienie plucne u noworodków.

One of the most critical problems of neonatology persistent pulmonary hypertension in the newborn, is discussed. This syndrome is characterized by increased resistance in pulmonary vessels leading to hypertension in pulmonary arteries and a recurrence of R > L shunting at the ductus arteriosus and foramen ovale. This leads to deep hypoxia and hypoxemia. It is most important to rule out a congenital cyanotic heart defect in the differential diagnosis. The aim of the treatment is to establish normal ventilation and intrapulmonary shunting as well as to control the symptoms leading to pulmonary hypertension that persist over time. The goal preceding treatment should be to determine the initial cause of the persistent pulmonary hypertension.

Development conditions and principles for identification of cow's milk protein hypersensitivity in infants.

The authors studied a group of 153 infants presenting pneumonia and/or bronchitis suspected to be immunized to cow's milk proteins (cow's milk allergy). The diagnosis was confirmed in 96 children (62.7%), which is 20.8% of hospitalized infants presenting respiratory tract diseases. Factors influencing the occurrence of family cow's milk intolerance and the type of infant feeding were analyzed thoroughly. Our own principles of diagnosing hypersensitivity to cow's milk proteins, considering the family history suggesting the possibility of cow's milk hypersensitivity, the occurrence of recurrent wheezy bronchitis and symptoms of the gastrointestinal tract were established. The diagnostic usefulness of LMIT with cow's milk allergens was assessed.

[Clinical characteristics of infections with cytomegalovirus in infants from personal observations]. / Charakterystyka kliniczna zakazen wirusem cytomegalii u niemowlat na podstawie wlasnych obserwacji.

An infection with cytomegaly virus had been diagnosed in 13 infants (including 4 neonates examined up to 2 weeks of life) out of 960 infants hospitalized within 3 years. Clinical examination most frequently revealed hepato- and splenomegaly, pneumonia and neurological disorders, and during a further stage of the clinical course psychomotoric retardation was noted in 7 out of 13 infants, and hearing loss in 5 out of 13 infants. A specific immunoglobulin G preparation (Cytotect) has been successfully used in all children, producing recovery or clinical improvement together with serologic improvement.

[Studies on the occurrence of systemic manifestations during first eruption of teeth in children]. / Badania nad wystepowaniem objawów ogólnoustrojowych w przebiegu pierwszego zabkowania u dzieci.

The aim of the study was establishing whether systemic symptoms and signs appearing in children during first eruption of teeth are connected with this process, and what is the correlation between the studied features and eruption of individual milk teeth. The study involved 55 generally healthy infants aged 3-4 months, and the observation was continued up to the age of 36 months. The study on the development of teeth was carried out in two Regional Paediatric Dental Clinics in Warsaw, at 6-week intervals in the first year of life, and at 10-week intervals in the 2nd and 3rd years. The systemic symptoms and signs were recorded by mothers, and the obtained data were stored on computer cards. The results were subjected to statistical analysis considering finally these systemic manifestations which were present in at least 25% of children. The manifestations connected with teeth eruption included: profuse salivation, biting of hard, things, restlessness, appetite loss and sleep disturbances. These symptoms were most pronounced at the time of milk incisors eruption, less evident during eruption of first molars, and were absent during eruption of second molars. Canine teeth eruption was connected particularly with restlessness and sleep disturbances. Such signs as raised body temperature, skin changes, gastrointestinal disturbances were only weakly connected with teeth eruption.

[Coexistence of Toxoplasma gondii and Cytomegalovirus infections in infants]. / Wspóøistnienie zarazen pierwotniakiem Toxoplasma gondii i wirusem cytomegalii u niemowlat.

Coexistence of Toxoplasma gondii and Cytomegalovirus infection in 3 dystrophic newborns is discussed. Also the not very characteristic course of the infection is stressed.

[Congenital toxoplasmosis--in prospective studies]. / Toxoplazmoza wrodzona--w badaniach prospektywnych.

In the action of prevention of congenital toxoplasmosis prospective studies were carried out of women at reproductive age for detection of antibodies to Toxoplasma gondii. Women seronegative before pregnancy were subjected during pregnancy to three tests for the presence of these antibodies in the 1st, 2nd and 3rd trimester. After development of seroconversion in pregnancy further observation was conducted which made possible the diagnosis of active primary infection in pregnancy in 12 cases. Prophylactic treatment of the mothers was administered and the newborns were observed for the consequences of intrauterine infection.

[Long-term clinical observation of children with passively acquired anti-Toxoplasma antibodies]. / Dlugotrwala obserwacja kliniczna dzieci z biernym przeniesieniem przeciwcial przeciwtoksoplazmowych.

A group of 20 children born to mothers, suspected of active toxoplasma infection during gestation, was analysed. Multispecialist examinations carried out in children for the period of 2-3 years have shown that the specific antibodies were acquired transplacentally. This enabled to exclude an active infectious process in children.