Stage Of Clinical Manifestations Research Articles

Milwaukee Protocol — from idea to implementation

Despite the fact that rabies in the modern world is a rare sporadic disease, the relevance of its methods of treatment is beyond doubt, since in the absence of timely prevention, it is characterized by 100% mortality. As of 2020, there are about 70 cases of experimental rabies treatment protocols according to the Milwaukee Protocol Rabies Registry. The very idea that the human body can cope with the virus itself has been around for a long time. Even before the advent of the Milwaukee protocol, there were attempts at treatment at the stage of clinical manifestations. The first was Michael Huttwick of the Center for Infectious Disease Control in Atlanta, although the scientific community is still arguing whether it was really rabies. The essence of this protocol is the introduction of a patient into an artificial coma, the introduction of antiviral drugs, symptomatic therapy (anticolvusants, mechanical ventilation, etc.). At the moment, there is the sixth version of the Milwaukee Protocol (from 2018), which provides general recommendations for its maintenance, since the material base is too small to draw any general conclusions.

Features of intestinal microbiota biodiversity in patients with inflammatory intestinal diseases and metabolic disorders (literature review)

Relevance. Pathology of non-infectious genesis is currently playing a leading role in the structure of overall morbidity of the population. The incidence of inflammatory bowel diseases increases all over the world. The severity of inflammatory bowel diseases complicates the presence of comorbid pathology, metabolic disorders, which lead to disability and the risk of premature death. Currently available diagnostic measures allow to detect disorders at the stage of clinical manifestations. There are several factors causing the development of pathological changes at the early stage including the peculiarities of intestinal microbiome formation and the predominance of certain microorganism clusters with the subsequent formation of a biotype, which may allow diagnosing the disease at a latent stage.Aim: To evaluate the role of the intestinal microbiota in the formation of inflammatory bowel diseases and metabolic disorders according to the data of national and foreign literature.Material and Methods. The review of literature on this topic was carried out based on the analysis of data obtained from the publications indexed in PubMed, Web of Science, Scopus, Google Academy, and eLibrary.ru databases over the past 10 years.Results. Data on the role of intestinal microbiota in the development of changes in patients with inflammatory bowel diseases and metabolic disorders (obesity, impaired glucose tolerance, and diabetes mellitus) were revealed. New potential mechanisms for the development of type 2 diabetes mellitus were identified, and the features of the generic composition of the flora in patients with comorbid pathology were described.Conclusion. The obtained results suggest that further research is required to improve understanding of this pathology and to create the methods for correcting the gut microbiota in case of abnormal findings.

The Effectiveness of Local Conservative Therapy after Panretinal Laser Coagulation against the Background of Diabetic Neuropathy

Background: Panretinal photocoagulation (PRP) (also called scatter laser treatment) remains one of the effective methods of treatment, and it can help to prevent blindness and low vision in diabetic retinopathy (DR). The aim of this study was to investigate the efficacy of local prolonged conservative therapy after PRP and the effect of somatic polymorbidity on visual functions in patients with diabetic neuropathy (DN) at the stage of clinical manifestations based on monitoring the clinical, functional and morphometric parameters of the macular region of the retina. Methods and Results: The study included 78 patients with type 2 diabetes (T2D) who underwent PRP for DR using a VISULAS® 532s solid-state laser (ZEISS). The patients were divided into two groups depending on the presence or absence of DN. Group 1 (n=60, 120 eyes) included patients with DN (stage of clinical manifestations), Group 2 (n=18, 36 eyes) included patients without DN. All patients underwent standard ophthalmological examination: visometry, tonometry, perimetry, biomicroscopy of the anterior segment of the eye and vitreous body, and fundus ophthalmoscopy. Thickness map of the retina was obtained using the RTVue-100 OCT (Optovue, Fremont, CA) EMM5 scan protocol and the Stratus OCT (Carl Zeiss Meditec, USA) radial scan protocol. After laser treatment, all patients, regardless of the treatment stage, were prescribed topically Broxinac® ( Bromfenac ophthalmic solution 0.09%), 1 drop twice a day for a month. In the presence of macular edema, a carbonic anhydrase inhibitor (Dorzolamide 2% solution) was added to the Broxinac® solution (1 drop twice a day) for up to 1 month after each PRP stage. The dynamics of CVA parameters and the retinal thickness of the macular region were assessed before PRP and 3 months after the complex treatment. Based on the monitoring of the clinical, functional and morphometric parameters of the macular region of the retina after PRP in T2D patients, we found a local, prolonged, 3-month conservative therapy to be effective, using the instillation of Broxinac® supplemented with Dorzolamide 2% solution in the presence of macular edema. Conversely, there is a negative effect of somatic polymorbidity (stage 3 chronic kidney disease), aspartate aminotransferase >40U/L) on corrected visual acuity (CVA) and morphometric parameters of the macular region of the retina during PRP in T2D patients with DN at the stage of clinical manifestations.

Ранняя диагностика нарушения функции почек у детей при острых кишечных инфекциях

In recent years, significant breakthroughs have been made in the study of etiology, pathogenesis, and the development of accessible diagnostic methods, as well as in the treatment of acute intestinal infections, resulting in a significantly lower frequency of their severe course and adverse outcomes and in reducing the frequency and duration of hospitalization. At the same time, the emergence of modern biochemical markers of injury of different organs and systems makes it possible to investigate new pathological conditions that were previously detected in the stage of clinical manifestations. These include the problem of early diagnosis of acute kidney injury in children, the frequency and timing of which have not yet been studied. Objective. Comparative evaluation of the diagnostic value of glomerular filtration rate and serum cystatin C levels for early diagnosis of kidney failure in children with acute intestinal infections (AII). Patients and methods. This study included 80 children with acute intestinal infection who were hospitalized in G.N.Speransky Children’s Clinical Hospital No 9. In all cases the course of disease was moderate-to-severe without developing hemolyticuremic syndrome. To assess kidney function in the acute period of intestinal infection, we studied glomerular filtration rate (GFR) by the “bedside” Schwartz equation, as well as serum cystatin C levels. Results. In the acute period of AII in children under 3 years of age, GFR was 98.56 ± 2.84 mL/min/1.73 m2 according to the “bedside” Schwartz equation of 2009. In the group of children over 3–7 years of age, these values were 108.85 ± 3.84 mL/min/1.73 m2, differences are statistically significant (p < 0.001). High (>950 ng/mL) serum cystatin C levels were found in 22% of patients. In other patients, cystatin C levels remained within or below the normal range. The analysis showed that 10% of children in the age group of 1–3 years and 2.5% of children in the age group of 3–7 years were at risk of developing acute kidney injury in AII, according to the GFR estimation based on the Schwartz “bedside” equation and cystatin C-based equation. When assessing the risk of developing acute kidney injury according to the GFR estimation using the cystatin C-based equation, the proportion of such patients in the age group of 1–3 years was 20% and in the age group of 3–7 years – 22%, and when assessing GFR according to the Schwartz “bedside” equation only, the proportion of children was 7.5% and 7.5%, respectively. Conclusion. Determination of cystatin C levels in children in the early period of acute intestinal infections of moderate severity is an earlier and more accurate marker of acute kidney injury, regardless of age and sex of patients, in comparison with the evaluation of glomerular filtration rate. Inclusion of cystatin C in laboratory test plan allows timely identification of patients who are in the risk group of developing acute kidney injury. Key words: children, kidney failure, acute intestinal infection, acute kidney injury, cystatin C, glomerular filtration rate

ПОРУШЕННЯ МЕТАБОЛІЗМУ ЖИРНИХ КИСЛОТ ЯК ОДИН З ЕТІОПАТОГЕНЕТИЧНИХ МЕХАНІЗМІВ ФОРМУВАННЯ ХОЛЕЛІТІАЗУ У ДІТЕЙ ТА МОЖЛИВІ ШЛЯХИ КОРЕКЦІЇ ВИЯВЛЕНИХ ПОРУШЕНЬ.

<p> Проведено обстеження 47 пацієнтів: 34 дівчинки та 13 хлопчиків віком 2-18 років (16 дітей мали холелітіаз у стадії клінічних проявів, 16 - холелітіаз у фізикохімічній стадіїнатлі обтяженоїспадковості). Контрольна група- 15дітей (8дівчатокта7хлопчиків). Діагностичний комплекс: клініко-анамнестичні дані, загальний та біохімічний аналіз крові (АЛТ, АСТ, загальний білокта білірубін, ЛФ, ГГТ, ліпідограма), визначення жирнокислотного складу ліпідів сироватки крові та жовчі методом газорідинної хроматографії, УЗД біліарного<br />тракту з функціональним навантаженням, дуоденальне зондування з мікроскопічним та біохімічним дослідженням жовчі.<br /><br /></p>

DIAGNOSIS OF PULMONARY HYPERTENSION IN SCLERODERMA SYSTEMATICA

Pulmonary hypertension (PH) associated with scleroderma systematica (SDS) is a menacing manifestation of this systemic disease of connective tissue, in which a rapid progression results in very poor outcomes. In SDS, PH is more frequently observed with the prolonged disease, circumscribed skin lesion, develops after a long benign course, and is one of the common causes of death. The early stage of PH can be identified by instrumental and not always accessible studies. The stage of clinical manifestations, which is frequently manifested only by dyspnea, requires a differential diagnosis from a wide range of conditions both caused by and concurrent with SDS. The need for differential diagnosis stems from the varying course and prognosis of the disease, as well as treatment policy.

Pathological Tau proteins of Alzheimer's disease as a biochemical marker of neurofibrillary degeneration

Paired Helical Filaments (PHF) accumulate in the degenerating neurons from the associative cortical brain areas during Alzheimer's disease. They are composed of a triplet of hyperphosphorylated microtubule-associated protein Tau, called Tau 55, 64, 69 or PHF-Tau. The distribution of PHF-Tau in the different brain areas corroborates neuropathological observations and specifies that: — the entorhinal cortex and hippocampus are vulnerable regions specifically affected by Alzheimer-type neurofibrillary degeneration during aging, — the temporal cortex is already affected at the very first stage of clinical manifestations, — almost the whole brain is concerned by neurofibrillary degeneration at the end-stages of the disease. Tau-PHF are also observed in the cortical areas from Parkinson patients with dementia, and more especially in the prefrontal cortex. Tau pathology for Progressive Supranuclear Palsy is significantly different, with a doublet of pathological Tau, namely Tau 64 and 69, in almost all cortical and subcortical areas. Therefore, the presence of pathological Tau proteins in several associative cortical areas is always associated with severe intellectual impairment. Finally, PHF-Tau are powerful biochemical markers of the degenerating process which could be used for setting up an early biological diagnosis test of Alzheimer's disease based upon the immunodetection of PHF antigens in the CSF, as well as for developing experimental models of neurodegeneration.

Prodromal Dysimmunity in Cancer

Instances of immune disorders which are apparently prodromic to the development of malignancy are described. These include one case of pulmonary granulomatous asbestosis ending in IgA myeloma, two cases of Sezary syndrome with lymphocytic lymphoma, one case of Duhring’s disease with lymphoma, and three cases of hepatobiliary diseases developing hepatoma and skin carcinomas. The pathophysiology is discussed in the light of the transition between the dysimmunity and the neoplasia. Postulates evolving from these observations are: (a) the existence of tissue or organ-oriented T-cell surveillors (histosophocytes), (b) obligatory antecedent dysimmunity in cancer, (c) therapy must be directed to the dysimmune situations rather than empirical augmentation of ‘cancer immunity’. All the transition syndromes presented four stages of immunologic evolution: (1) the initial stage of immune competence; (2) a stage of immune dysfunction, asymptomatic but when changes can be demonstrated; (3) a stage of overt, clinical, immunologic deficiency (prodromic, preneoplastic) when surveillance is inappropriate, and (4) a stage of clinical manifestations of the malignancy (immunodecadence) with persistence of the immunologic disorder (perineoplastic). Allogenic carcinogenesis and its potentiation by immunosuppression is recognized as a fourth category of carcinogenic agent next to chemicals, radiations and viruses.