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Vol 12, No 6 (2021)

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Editorial

Vitamin D deficiency in young children. The realities of today

Sergeev Y.S., Arsentev V.G., Shabalov N.P., Antsiferova E.S.

Abstract

The article presents a review of the literature on the clinical aspects of assessing vitamin D deficiency in young children by the concentration of 25(OH)D (hydroxycalciferol) in blood serum. The purpose of the review was to familiarize pediatric specialists with the real state of affairs in assessing the clinical significance of diagnosing vitamin D status, its relationship with the prevention of deficient rickets, ways of correcting and choosing the dose of calciferol. A daily dose of 400 IU of vitamin D for young children is effective and safe in preventing deficient rickets. Higher subsidized doses of calciferol have not been shown to be more effective. In addition, they can potentially lead to toxic levels of vitamin D metabolites in the blood. When using lower daily doses (less than 400 IU), an adequate prophylactic effect may not be achieved. Determination of the level of circulating serum hydroxycalciferol, which characterizes the status of vitamin D in the body, is not recommended for routine examination and as a standard for diagnosing deficient rickets in young children. Calciferol has multilateral effects, modulates not only phosphorus-calcium metabolism, but also affects other systems and functions of the body, in particular, ontogenesis and the immune system. According to foreign literature, all infants should receive vitamin D for the prevention of rickets, treatment from the age of one month. This is most reliably identified for children, probably at risk. Convincing data indicating a positive protective effect on diabetes mellitus D on unforeseen pathology, for example, the frequency of exclusion of pneumonia, infectious diarrhea, atopic dermatitis in infancy, has not yet been obtained.

Pediatrician (St. Petersburg). 2021;12(6):5-14
pages 5-14 views

Original studies

Quantitative assessment of regional pulmonary perfusion using three-dimensional ultrafast dynamic contrast-enhanced magnetic resonance imaging: pilot study results in 10 patients

Zakharova A.V., Prits V.V., Pozdnyakov A.V.

Abstract

Background. Currently there is a high demand in reliable noninvasive diagnostic technique assessing the physiological parameters of the lungs. We are exploring the three-dimensional ultrafast MRI sequence as a novel diagnostic modality allowing the assessment of regional quantitative perfusion parameters in pulmonary tissue.

Aim. To assess regional differences in quantitative pulmonary perfusion parameters in 10 volunteers with no evidence of interstitial lung disease by computed tomography, clinical, and laboratory data.

Materials and methods. 10 volunteers with no signs of interstitial lung disease were examined by three-dimensional ultrafast dynamic contrast-enhanced MR imaging using 3D T1-weighted images. The values of pulmonary blood flow (PBF), mean transit time (MTT), and pulmonary blood volume (PBV) for the targeted regions of interest were calculated based on the dynamic image series. For calculations, arterial input function (AIF) was used, as well as the time-intensity curves.

Results. The values of PBF, MTT, and PBV showed statistically significant differences between central and peripheral sections of lungs. Provided model can be implemented for quantitative assessment of regional pulmonary perfusion allows it to be used to determine the reliability of PBF, MTT and PBV values.

Conclusions. Three-dimensional ultrafast MRI sequence is a novel diagnostic modality allowing the assessment of regional quantitative pulmonary perfusion parameters in pulmonary tissue, regardless of physiological features of blood supply mechanisms in different lung regions.

Pediatrician (St. Petersburg). 2021;12(6):15-26
pages 15-26 views

Proton magnetic resonance spectroscopy in children with delayed mental and speech development associated with focal temporal lobe epilepsy

Sergeev A.M., Pozdnyakov A.V., Grechaniy S.V., Atamanova E.E., Pozdnyakova O.F., Shokin O.V., Polishchuk V.I.

Abstract

Background. The delays in mental and speech development are caused by epilepsy, and a special place among the forms of which is focal temporal epilepsy. The study of biomarkers of the considered pathological condition using proton magnetic resonance spectroscopy as indicators amenable to objective assessment and measurement determines the practical relevance of this work.

Aim. The aim of the study was to determine the role and place of proton magnetic resonance spectroscopy in clinical practice in children with mental and speech retardation associated with temporal lobe epilepsy.

Materials and methods. 37 children aged 2 to 10 years were studied. Of these, 15 children with a diagnosis of “mental and speech development delay, structural focal temporal epilepsy” were included in the first comparison group. The second comparison group consisted of 12 children without CNS pathology undergoing 1H-MRI examination to exclude somatic diseases. The third comparison group consisted of 10 children with “structural focal temporal epilepsy”, without mental and speech development delay.

Discussion. Multivoxel proton magnetic resonance spectroscopy (method PRESS) was used to determine the concentration of neurometabolites in the brain tissues of patients. In patients with mental and speech development delay associated with temporal epilepsy, a decrease in the ratio of NAA/Cr concentrations (p < 0.05) was revealed in the postcentral gyrus on the right, temporal lobe on the right and hippocampus and inner capsule on both sides, due to a decrease in the concentration of N-acetylaspartate; an increase in the ratio of Cho/Cr concentrations (p < 0.05) in the prefrontal cortex, postcentral gyrus and inner capsule on both sides, due to an increase in the concentration of choline. Two patients also showed lipid peaks on the lesion side when compared with EEG data.

Conclusions. The revealed metabolic changes in patients with delayed mental and speech development associated with temporal lobe epilepsy may be useful as an additional method of differential diagnosis with other forms of mental and speech development delay.

Pediatrician (St. Petersburg). 2021;12(6):27-34
pages 27-34 views

The effect of acute mental stress on the exchange of monoamines in the mesocortical and nigrostriatal systems of the rat brain

Bychkov E.R., Karpova I.V., Tsikunov S.G., Krytskaya D.V., Lebedev A.A., Tissen I.Y., Pyurveev S.S., Shabanov P.D.

Abstract

Background. Мesocortical and nigrostriatal dopaminergic systems are highly sensitive to stressful events. One of the most adequate models of acute psychogenic stress in animals is the death of a partner upon presentation of a predator.

Aim. To study the content of dopamine (DA), serotonin and their metabolites: dioxyphenylacetic (DOPAC), homovanillic and 5-hydroxyindoleacetic (5-HIAA) acids in the prefrontal cortex, striatum, and ventral tegmental area in rats on days 3, 7, and 14 after the acute psychogenic stress of the death of a partner upon presentation of a predator.

Materials and methods. 28 male Wistar rats were studied. Acute single psychotraumatic situation was used. A group of rats was placed in a tiger python terrarium. One animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. The content of monoamines in the brain structures was carried out by high performance liquid chromatography with electrochemical detection.

Results. Changes in the content of monoamines in the prefrontal cortex, striatum, and ventral tegmental area were found on the 7 and 14 days after the presentation of the predator. In the ventral tegmental area on the 7 day, there was an increase in the DOPAC/DA ratio and an increase in the serotonin metabolite 5-HIAA, which reflects an increase in the activity of dopamine and serotonin. In the prefrontal cortex on the 14 day, the DOPAС content and the DOPAС/DA index decreased. The 5-HIAA content in the prefrontal cortex and the 5-HIAA/5-HT value also significantly decreased.

Conclusions. Changes in the metabolism of monoamines after presentation of a predator develop gradually: increase of the dopamine and serotonin activity in the ventral tegmental area was noted on the 7 day after presentation of the predator, decrease in their activity in the striatum and prefrontal cortex only on the 14 day, reflecting the development of depressive states and post-traumatic stress disorder.

Pediatrician (St. Petersburg). 2021;12(6):35-42
pages 35-42 views

Dynamics of resistance to antibiotics in nosocomial staphylococci from multidisciplinary hospital

Gladin D.P., Kozlova N.S., Korolyuk A.M., Barantsevich N.E., Baranov I.A., Khairullina A.R., Barantsevich E.P.

Abstract

Background. Staphylococci are still the leading causative agents of infections associated with healthcare, and the study of their antibiotic resistance is still relevant.

Aim. The research is aimed at study of antibiotic resistance of hospital strains of staphylococci in dynamics.

Materials and methods. Susceptibility to 16 antimicrobial agents was studied in 554 Staphylococcus strains, isolated from patients in a multidisciplinary medical centre. The method of serial microdilutions was used.

Results. Antibiotic-resistant strains prevailed (85.4%). Methicillin-resistance and multy-resistance were found to be more typical for coagulase-negative strains – 75.2% and 74.1% respectively, than for Staphylococcus aureus – 14.2% and 15.4% respectively. Methicillin-resistance and poly-resistance in S. aureus was found to decrease – it was 11.1% and 12.8% in 2015–2016 (17.1% and 17.9% respectively in 2011–2012). On the contrary, methicillin-resistance in coagulase-negative staphylococci strains during the same period increased 1.5 times. Totally, methicillin-resistant strains composed a half of the isolates – 48.7%. The studied Staphylococcus strains were susceptible to vancomycin, daptomycin, tigecycline. Resistance to linezolid and amikacin was 2.2% and 2.7% respectively. S. aureus strains were all susceptible to linezolid, fusidic acid, rifampicin, trimethoprim-sulfamethoxazole. Minimum inhibitory concentrations (MIC) of antibiotics for staphylococci varied in wide ranges from 0.06 to ≥128 mg/l. For S. aureus and S. epidermidis, the MIC50 and MIC90 of only five drugs (benzylpenicillin, tigecycline, vancomycin, linezolid, and daptomycin) were the same, while the MIC50 and MIC90 of most of the other studied drugs against S. epidermidis were significantly higher compared to S. aureus.

Conclusion. The variability of resistance of staphylococci to antimicrobial drugs in a multidisciplinary hospital confirms the need for continuous monitoring of their antibiotic resistance.

Pediatrician (St. Petersburg). 2021;12(6):43-53
pages 43-53 views

Maternal body estrogen exposure influences the mice offspring ovaries’ morphology

Sulaymanova R.T., Khayrullin R.M., Lebedeva A.I., Sulaymanova L.I., Askhabova E.D.

Abstract

Background. The question of the effect of female sex hormones and their analogues on humans and experimental animals is of great interest in medicine.

Aim. The aim of the work was to study the morphological features of the ovaries of the offspring of laboratory mice during the administration of estrogens to the maternal body.

Materials and methods. Female laboratory mice after fertilization were divided into groups: two control and two experimental, which at the stage of development of gestation E11.5 underwent intramuscular, single administration of experimental doses of estrogens. The first experimental group was injected with the synthetic drug synestrol in the form of a 2% oil solution at a total dose of 50 mcg / kg (n = 5; S-50), the first control group was injected with olive oil at a dose of 0.2 μm/kg (n = 5). The second experimental group was injected with a 0.4 ml 0.0005% fulvestrant oil solution at a dose of 100 mcg/kg (n = 5; F-100), the second control group (n = 5) received sterile castor oil at a dose of 0.8 μm/kg.

Results. Persistent morphological changes are observed in the ovaries of the offspring of the first experimental group S-50: an increase in the average area of the cortical substance, a decrease in the area of the medulla, an increase in the average number of yellow bodies, an increase in the average number of luteal cells in the yellow body, a decrease in the total number of follicles and atretic bodies, indicating a violation of the folliculogenesis process, an increase in the average diameter of blood vessels demonstrating increased blood circulation. With the introduction of the drug fulvestrant 100 mcg / kg in the second experimental group F-100, morphological changes in the form of an increase in the average area of the cortical substance, a decrease in the average area of the medulla, sclerosis of the stromal component, accompanied by a restructuring of the vascular network with signs of atresia and cystic degeneration of the follicular epithelium in secondary and tertiary follicles are considered on a slice of the ovaries of the offspring.

Conclusions. The obtained results of the study confirm the urgency of the problem of implementing complex measures aimed at limiting the effects of estrogenetic drugs introduced into the maternal body during pregnancy, in order to prevent adverse effects on the development of the ovaries of offspring.

Pediatrician (St. Petersburg). 2021;12(6):55-62
pages 55-62 views

Reviews

Epidemiological and clinical and laboratory features of COVID-19 in pediatric patients

Belykh N.A., Solovyova O.A., Anikeeva N.A.

Abstract

The article presents up-to-date data on the main pathogenetic mechanisms and features of the new coronavirus infection caused by the SARS-CoV-2 virus. The review highlights the main epidemiological features of infection with SARS-CoV-2 in children at various age periods, features of the immune response and variants of the course of the disease with lung damage, as well as other organs and systems. The clinical and laboratory features of the course of a new coronavirus infection in children are highlighted. It was found that children are less likely to develop severe COVID-19 than adults. More than 95% of all cases of the disease range from asymptomatic course to clinical manifestations of mild and moderate severity. About 2% of children’s patients need hospitalization, including in the intensive care unit and ventilator. However, extrapulmonary manifestations are registered in children more often than in adults, especially from the gastrointestinal tract and circulatory organs. According to numerous authors, the features of the clinical and laboratory course of COVID-19 in pediatric patients are probably associated with a number of factors, among which age-related features of the immune response, the functioning of angiotensin-converting enzyme-2 (ACE-2) used by coronaviruses as a cellular receptor are indicated. Understanding the role of the child population in the dynamics of transmission of infection is important, since children significantly affect the rate of infection spread.

Pediatrician (St. Petersburg). 2021;12(6):63-76
pages 63-76 views

Is psoriasis therapy an art based on experience?

Zaslavsky D.V., Chuprov I.N., Nasyrov R.A., Krasnogorskaya O.L., Bolshakova E.S., Manylova E.S., Mineeva O.K., Drozdova L.N., Shternliht K.V., Sidikov A.A., Kovalenko K.A., Brazhnikova A.P., Kozlova D.V.

Abstract

Psoriasis is a chronic immune-associated skin disease of a multifactorial nature with phenotypic diversity in the general population, as well as a large number of comorbid diseases in patients. The generalized pustular psoriasis, historically was considered one of the variants of the course of psoriasis. Today some authors classify it as a genetically different condition combined with a plaque psoriasis. The selected tactics of psoriasis therapy can become a trigger for the manifestation of a pustular form. Despite the availability of modern data on the immunopathogenesis of the disease, there are no standardized methods of treatment that can take into account the individual characteristics of patients, which is doubly important in pediatric practice, since the arsenal of drugs approved for use is limited. We demonstrate the clinical case of a patient with progressive plaque psoriasis, earlier getting systemic and topical corticosteroids for a long time. This therapy did not allowed to take the course of the disease under control, even more it caused appearance of complications. Our clinical example from practice allows us to focus on the problem of complications of classical therapy for psoriasis and the intricacies of prescribing both topical and systemic drugs. Systemic therapy requires the development of algorithms based on objective diagnostic criteria and the results of studies on the effectiveness and safety of modern drugs in pediatric practice.

Pediatrician (St. Petersburg). 2021;12(6):77-88
pages 77-88 views

Clinical observation

Combination of tuberculosis of the intra thoracic lymph nodes and acute lymphoblastic leukemia in a child

Lozovskaya M.E., Yarovaya Y.A., Vasilieva E.B., Klochkova L.V., Malysheva E.A., Noskova O.M.

Abstract

According to scientific research, malignant neoplasms in children are biomedical risk factors for the development of tuberculosis (TB). On the contrary, the occurrence of oncological disease in a child against the background of an existing tuberculous process is extremely rare. The combination of malignant neoplasm and tuberculosis creates difficulties in differential diagnosis, treatment of diseases, prevention of exacerbations and relapses. This article presents a clinical observation – the development of acute lymphoblastic leukemia (ALL) in a 6-year-old child against the background of TB of the intrathoracic lymph nodes during treatment. TB proceeded favorably despite multiple family contact in the child and resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs in adult relatives of the patient. At the onset of ALL, bilateral pulmonary infiltrates and pleural effusion were observed, which were not associated with TB. Specific polychemotherapy for ALL and continued chemotherapy for TB led to the cure of two diseases. Supportive cytostatic and immunosuppressive therapy for ALL required periodic courses of anti-relapse anti-tuberculosis therapy for 5 years. After 10 years of observation, the child is healthy. Thus, the possibility of a rare in clinical practice combination of TB and ALL in children should be taken into account in the diagnosis and treatment of these diseases. During courses of immunosuppressive therapy for ALL, there is a risk of reactivation of TB. It is necessary to recommend long-term observation of such children by a phthisiatrician and an oncologist to prevent recurrence of both diseases.

Pediatrician (St. Petersburg). 2021;12(6):89-96
pages 89-96 views

Structural epilepsy in children who have suffered a hemorrhagic stroke

Fomina M.Y., Gumenik H.V., Korostovtsev D.D., Kovelenova M.V.

Abstract

The relevance of studying the consequences of hemorrhagic strokes in young children is due to the frequency of cerebrovascular pathology, the formation of persistent neurological deficits, including post-stroke epilepsy, and high mortality. It is known that hemorrhages are diagnosed in the first 28 days of life in 6-7 out of 100,000 infants, in children from the 28th day of life to 18 years of age from 0.7 to 5.1 cases per 100 thousand children. Mortality in hemorrhagic and ischemic strokes in children ranges from 7 to 28%. Epileptic seizures of the acute and acute period of stroke are prognostically unfavorable factors of the course of the disease. The article presents brief literature data on the etiology and localization of hemorrhagic strokes, their role in the formation of pharmacoresistant epilepsy. Special attention is paid to the role of late hemorrhagic disease of newborns, accompanied by intracranial hemorrhages, in the formation of structural epilepsy in the future. The paper describes own clinical observations of 25 patients suffering from epilepsy after a hemorrhagic stroke with a description of the clinical picture, features of paroxysmal states and their therapy, neuroimaging data, electroencephalographic phenomena. A clinical example is presented in which the clinical, anamnestic, electrophysiological data of a patient with pharmacoresistant epilepsy developed as a result of a hemorrhagic stroke on the background of late hemorrhagic disease of newborns are considered.

Structural epilepsy in children, formed after a hemorrhagic stroke, is accompanied by significant multi-regional damage, pronounced neurological deficit and is characterized by a pharmacoresistant course.

Pediatrician (St. Petersburg). 2021;12(6):97-106
pages 97-106 views

Наследственные болезни обмена

Lysosomal storage diseases. Mucopolysaccharidosis types IV, VI, and VII – Morquio, Maroto–Lamy and Sly syndrome

Gorbunova V.N., Buchinskaia N.V.

Abstract

The review is devoted to the clinical, biochemical, and molecular genetic characteristics of autosomal recessive mucopolysaccharidoses (MPS) types IV, VI, and VII. MPS IV type, or Morquio’s syndrome, is represented by 2 types – A and B. The cause of the most frequent MPS IVA is hereditary deficiency of galactose-6-sulfatase, due to the presence of inactivating mutations in the GALNS gene. The pathogenetic basis of the disease is associated with excessive accumulation in lysosomes, mainly of cartilage tissue of keratan sulfate and chondroitin-6-sulfate. Main clinical manifestations of MPS IVA are dwarfism and progressive deformity of the spine, sternum, and knees. The milder MPS IVB is due to hereditary β-galactosidase deficiency and is an allelic variant of GM1 gangliosidosis. The cause of MPS VI, or Maroto–Lamy syndrome, and MPS VII, or Sly syndrome, is hereditary deficiency of arylsulfatase B and β-glucuronidase, respectively. The pathogenesis of these diseases is due to the excessive accumulation of dermatan sulfate and, in the second case, additionally, heparan sulfate. Patients with type VI and VII MPS have a Hurler-like phenotype, but in the first case, intellectual deficiency are usually absent, while in Sly syndrome, moderate mental retardation is observed. The possibility of neonatal screening and early diagnosis of these MPS in order to increase the effectiveness of their prevention and treatment is discussed. The importance of experimental models for studying the molecular basis of the pathogenesis of these severe hereditary diseases and the development of various therapeutic approaches, such as bone marrow transplantation, enzyme replacement therapy and substrate-reducing therapy, is emphasized. Descriptions of clinical cases of MPS IVA and VI types are presented.

Pediatrician (St. Petersburg). 2021;12(6):107-125
pages 107-125 views

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