Diastolic deceleration area in the fetal MCA: a new Doppler parameter.

Objective: Doppler velocimetry has been widely used throughout the years as a valuable tool in the follow-up and prognosis of various pregnancy complications. Numerous Doppler indices have been introduced to qualitatively describe fetal blood flow. Currently, the Pulsatility index (PI) is the most widely used index for this purpose. In current clinical practice, middle cerebral artery (MCA) PI measurement is commonly used to assess fetal well-being, especially in late-onset fetal growth restriction (FGR). However, existing evidence suggests that MCA PI alone is inferior to the ratio between MCA and umbilical artery (UA) pulsatility indices in predicting adverse perinatal and neonatal outcomes. When comparing normal and abnormal MCA Doppler waveforms, it is evident that most changes appear in the diastolic part of the heart cycle. Therefore, the PI, which contains elements from both systole (peak systolic velocity-PSV) and diastole (end-diastolic velocity), may not be the most effective tool for quantifying fetal brain sparing (BS).Methods: We hypothesize that another measurement modality that focuses predominantly on the diastole could be more efficient for evaluating the amount of vasodilatation. In ultrasound velocimetry of larger blood vessels, there is a well-known phenomenon called "dicrotic notch" (DN), which appears on the declining part of each Doppler waveform and can be used to precisely pinpoint the end of systole and the start of diastole. We hypothesized that the extent of cerebral vasodilation can be more accurately assessed by measuring the area between the dicrotic notch (DN) and the end-diastolic velocity (which we refer to as the "diastolic deceleration area-DDA"). In this study, we introduced a new Doppler parameter along with a rationale for DDA measurement in the fetal MCA. We also defined third-trimester nomograms and provided a preliminary assessment of the correlation between DDA and fetal oxygen deficiency.Results: Our findings suggest that the DDA may serve as an independent instrument for identifying hypoxia during late pregnancy, either on its own or in conjunction with other Doppler and cardiotocography modalities.Conclusion: However, before incorporating DDA into clinical practice, it is crucial to conduct further research and validation studies with larger sample sizes and more diverse populations. This would help assess the generalizability of the results and establish optimal cutoff points for DDA in various clinical settings. It is also important to prospectively study the role of DDA in early- and late-onset fetal growth restriction (FGR), Rh-isoimmunization/anemia, preeclampsia, gestational diabetes, and other pregnancy complications. In fact, we believe that the concept of measuring specific areas in arterial Doppler velocimetry indices could have significant implications not only in fetal medicine and obstetrics, but also in other areas of human and veterinary medicine.

Dynamics of structural relaxation in bioactive 45S5 glass.

Kinetics of physical aging in archetypic 45S5 bioactive silicate glass composition with different types of phase separation are studied in situ below the glass transition temperature (T g). The qualitative nature of aging is found to be almost independent of the structural differences on the micrometer scale. A well-expressed step-like behavior in the enthalpy recovery kinetics is observed for aging temperatures T a ∼ 0.90T g and T a ∼ 0.85T g, which, however, disappears when the aging occurs at T a ∼ 0.95T g. The overall kinetics are described by a stretched-exponential function with stretching exponent close to 3/7 at T a ∼ 0.95T g, and 1/3 when the aging temperature drops to ∼0.90T g and below. The values correlate well with the predictions of Phillips' diffusion-to-traps and percolating fractals models. Appearance of step-like behavior at larger departure from T g is attributed to the hierarchical scheme of approaching equilibrium based on an alignment-shrinkage mechanism of physical aging proposed earlier for chalcogenide glasses.

[Hepatitis C virus - related cryoglobulinemic vasculitis with renal involvement current possibilities of diagnostic and treatment].

The extrahepatic manifestations of HCV infections, which include mixed cryoglobulinemia (MC), are important for prognosis and determination of the treatment options of these patients. Currently, mixed MC type II is considered as a specific marker of chronic HCV infection. Kidney damage is one of the severe, often determining a prognosis of extrahepatic manifestation of HCV-associated cryoglobulinemic vasculitis. The review discusses the current diagnostic approaches to cryoglobulinemic GN, as well as perspectives for improving antiviral and pathogenetic therapy.

The first experience of non-interferon therapy of HCV infection in patients with Wilson-Konovalov's disease.

In the article we present three clinical observations demonstrating that HCV infection in patients with remission of Wilson disease causes an recrudescence of the disease, in one of the observations - decompensation of liver cirrhosis. In this study we first describe on the successful treatment of HCV infection with direct antiviral drugs in patients with Wilson disease. Establishment of all factors of liver damage and successful treatment (elimination of the virus, adequate lifelong medical treatment) allow to expect a favorable prognosis in patients with a combination of Wilson disease and HCV infection.

[Hepatitis C virus-associated cryoglobulinemic vasculitis: A 20-year experience with treatment]. / Krioglobulinemicheskii vaskulit, assotsiirovannyi s virusom gepatita S: 20-letnii opyt lecheniia.

AIM: To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV). SUBJECTS AND METHODS: Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients' survival was studied; multivariate logistic regression analysis was carried out. RESULTS: 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91). CONCLUSION: HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

Micro-Raman spectroscopy as an enabling tool for long-term intracellular studies of nanomaterials at nanomolar concentration levels.

Given the importance of nanomaterials for medicine, health and biological sciences, a method for reliable intra-cellular tracking of nanocarbon materials at ultra-low concentrations was investigated. Namely, hyperspectral imaging of DNA-functionalized single-walled carbon nanotubes inside neural stem cells was demonstrated, over several mitosis cycles, also in a 3D z-stacking mode.

[WILSON-KONOVALOV'S DISEASE IN TWO SISTERS: DIFFERENCES IN THE CLINICAL PICTURE AND SUCCESSFUL THERAPY].

Wilson-Konovalov's disease is a rare genetic pathology of copper metabolism that in the first place affects liver and CNS. Due to autosomal-recessive inheritance of this condition, it most frequently occurs in sibs. We report a case of Wilson-Konovalov's disease in two sisters differing in its clinical course: severe abdominal variant in the younger sister and largely neurologic form in the elder one. This observation demonstrates clinical variability of Wilson-Konovalov's disease, the possibility of its late clinical manifestation (at the age 45 years), the necessity of examination of all sibs of a proband regardless of age, and the possibility of radical improvement of prognosis even when the disease is diagnosed at the stage of decompensated liver cirrhosis.

[Dynamics of elements distribution in blood, depending on age, by example of Moscow Region residents].

Elemental status of a person determines the qualitative and quantitative content of chemical elements in the human body. This marker allows us to estimate the level of imbalance of chemical elements and therefore health risks. The method for simultaneous quantitative and qualitative analysis of 67 elements in biomaterials has been proposed. The detailed elemental analysis of whole blood samples of 1711 healthy people (age range 0-100 years) of Moscow Region has been performed. A number of patterns of age-related changes of the element status conditionally healthy people has been estimated. Na content in the samples increased with the age of the person. Presumably, this result reflects the studied populations nutrition disorders associated with immoderate consumption of table salt. The maximum content of Ca was observed in blood samples of people age range 0-20 years (66-69 mg/kg), the Ca content in the blood samples of people age range 26-85 years was significantly lower (59-62 mg/kg). The maximum decrease of Ca was detected in blood samples of people age range of 85-100 years (57-59 mg/kg). Thisreductionin the concentration of Ca, apparently due to age-related changes of Ca balance, correlates with decrease of bone mineral density and bone mass. Iron content decreased in the blood samples of people age range 10-100 years from 480 to 390 mg/kg. Selenium content in blood of people age range 0-25 years linearly increased, remained stable high in the blood of people age range 25-55 years (0,13-0,136 mg/kg) and then gradually decreased. A graph of As content dependence from a person's age is a mirror image of the graph of Se content dependence from a person's age, which is evidence of the antagonistic effects of these elements. Graphic changes in the content of rare earth elements Eu and Ho reflect the unidirectional trend of these elements accumulation. The maximum content of these elements was observed in blood samples of people age range of 25-65 years. Perhaps a reduction of Eu and Ho in the age range 65-100 years age reflects a downward trend in bone mineral density and decrease in bone mass, which correlates with the Ca content in the blood depending on the age of people. The data obtained showed a significant increase of U and V in the blood of people age range of 85-100 years. The compounds of vanadium and uranium normally relatively easily filtered by the kidneys and excreted in the urine. This result seems to demonstrate age-related deterioration in the functioning of the excretory system. A list of recommendations for nutrition correction of elemental imbalance of the observed population has been proposed.

[Wilson-Konovalov disease in 3 sisters: a radical change in prognosis if timely diagnosed].

Wilson-Konovalov disease is a rare autosomal recessive genetic disorder in which copper accumulates in the liver, brain and other target organs. The paper describes a family case of the abdominal form of the disease in three sisters, the eldest of them died from fulminant liver failure at the age of 18 years. The second sister aged 16 years was diagnosed as having the disease at the stage of decompensated liver cirrhosis; her treatment with D-penicillamine resulted in complete disease remission. The youngest sister was diagnosed with the disease at the preclinical stage, which could expect its good prognosis. However, the patient's refusal of treatment led to death from liver failure. This case demonstrates the importance of timely diagnosis and the possibility of dramatic improvement in prognosis even at the stage of decompensated liver cirrhosis.

[Successful treatment of severe HCV-cryoglobulinemic vasculitis with the use of CD20 monoclonalantibodies and antiviral agents].

This paper reports a case of successfuid treatment of severe HCV-cryoglobulinemic vasculitis with ulcerative necrotic skin lesions, digital necrosis, cryoglobulinemic glomnerulonephritis and sensorimotor neuropathy. Possibilities for the change of prognosis in the patients with HCV-cryoglobulinemic vasculitis are discussed along with the prospects for the improvement of antiviral and pathogenetic therapy.

[Hepatitis C virus-related cryoglobulinemic vasculitis with renal involvement: current possibilities of treatment].

The paper considers the specific features of renal involvement developing in chronic infection caused by hepatitis C virus (HCV) and the current possibilities of treatment. It details the clinical and morphological manifestations of HCV-related cryoglobulinemic glomerulonephritis, and criteria for its diagnosis and prognosis. The author discuss new approaches to treating (severe cryoglobulinemic vasculitis with renal involvement in particular)--antiviral therapy (pegylated interferon-alpha/ribavirin) in combination with biological agents (anti-CD monoclonal antibodies, such as rituximab) to achieve clinical, virological, immunological remissions and a response at a molecular level--to eliminate oligo- and monoclonal B lymphocyte proliferation.

[Current possibilities for treatment for hepatitis C virus-induced cryoglobulinemic vasculitis and B-cell lymphoma].

The paper presents a detailed review of the data available in the literature on the treatment of cryoglobulinemic vasculitis and some forms of B-cell non-Hodgkin lymphoma caused by hepatitis C virus. It shows treatment successes associated with the use of current combined antiviral therapy (interferon-alpha and ribavirin) and its combination with anti-CD20 monoclonal antibodies (rituximab). The combined therapy with rituximab and antiviral drugs allows a radical improvement of prognosis in nearly 50% of patients. Remaining treatment problems and new drug prospects are discussed.

[Possibilities provided by personalized therapy of chronic hepatitis C (case conference at E.M.Tareev Clinic of Nephrology, Internal and Occupational Diseases)].

The presented clinical case gave rise to discussion of the main mechanisms and factors behind the progress of chronic hepatitis C. Special emphasis is laid on the currently available possibilities of antiviral therapy and its future prospects. The efficacy of personalized treatment and approaches to its improvement are considered based on the proper preventive measures and correction of factors responsible for poor responsiveness to the treatment, in the first place metabolic disorders (obesity, hepatic steatosis).

[Successful rituximab therapy of HCV-cryoglobulinemic vasculitis with severe ulcerative and necrotic lesions of the skin].

This clinical observation demonstrates successful rituximab therapy of HCV-cryoglobulinemic vasculitis with severe ulcerative and necrotic lesions of the skin on the lower extremities. Vasculitis recurred 3 years after the persistent virological response had been achieved and complete clinical remission resulted from antiviral therapy. Possible causes of vasculitis relapses in the absence of HCV viremia are discussed with reference to the difficulties encountered in managing this condition.

[Hepatitis virus genotype structure in patients with chronic hepatitis C].

AIM: Studies of hepatitis C virus (HCV) genotype and subtype structure in patients with chronic hepatitis C in 3 regions of the Central federal district of Russia. MATERIALS AND METHODS: Hepatitis C virus genotype and subtype structure was determined in patients with chronic HCV infection in Moscow (1993 - 1995 and 2005), Moscow region (2008) and Vladimir region (1993 -1995, 2005-2007). HCV genotype was determined by using A. Widell et al. (1994) technique, PCR (AmpliSens diagnostic kits), Genotype C test system. RESULTS: In all studied regions and during all the time periods the first position in rating belonged to HCV 1b subtype. In 1993 - 1995 and 2005 - 2007 period changes in HCV genotype and subtype structure were registered that consisted of relative weight of 1b subtype decrease and 3a subtype increase. Subtype 1b in females with chronic hepatitis C was registered more often than in males. In Vladimir region 3a subtype in males was detected more often than in females. In males older than 30 years the first rating position belongs to 1b subtype and in males younger than 30 years--subtype 3a. In females older than 30 years in Moscow region and Vladimir region, as well as in females younger than 30 years in Vladimir region subtype 1b was detected more often, while in Moscow region HCV subtypes 1b and 3a were detected with the same rate of 47.6%. CONCLUSION: Currently there is an urgent need to include mandatory monitoring of hepatitis C virus genetic variants into the system of hepatitis C epidemiologic control in Russia. This approach will allow for a significant increase in quality of hepatitis C serological diagnostics, and can be used in the prognosis of evolution of the epidemic process of this disease.

[B-cell lymphoma in a woman with chronic hepatitis C and mixed cryoglobulinemia of type 2].

A report is presented of a rare case of B-cell non-Hodgkin's lymphoma and severe exacerbation of cryoglobulinic vasculitis which developed in a female patient with chronic hepatitis C four years after achievement of a persistent virusological response to antivirus treatment. Causes of a specific course of the disease and development of the tumor in the absence of HCV in blood serum are discussed: latent HCV-infection in immune cells with persistent antigenic stimulation of B-lymphocytes, possibility of HCV-independent lymphoproliferation.

[Metabolic syndrome in patients with chronic hepatitis C genotype 1].

The aim of this prospective study was too asses the frequency and clinical significance of metabolic syndrome (MS), insulin resistance (IR) and hepatic steatosis in 114 patients with chronic hepatitis C (HCV) genotype 1. MS was found in 47% and IR in 50% of the cases. Diagnosis of IR in patients without MC and marked fibrosis supported the role of HCV in the development of metabolic abnormalities. Hepatic steatosis was found in 38% of the patients and the degree of steatosis significantly correlated with that of fibrosis. Obesity, IR, steatosis and liver cirrhosis were independent negative predictors of the response to the treatment with peginterferon alpha and ribavirin.

[Antiviral therapy in a patient with chronic hepatitis C, metabolic syndrome and interferon-induced depression].

A case of metabolic syndrome is reported in which its elimination before the onset of antiviral treatment of chronic hepatitis A and drug therapy of subsequent depression promoted successful outcome with a stable virological response. Modern approaches are discussed to enhancing efficiency of antiviral therapy by active correction of factors responsible for poor results of the treatment and its undesirable consequences.

[Metabolic syndrome and insulin resistance in patients with chronic hepatitis C].

AIM: To estimate the incidence and clinical value of metabolic syndrome, insulin resistance, and steatosis in patients with chronic hepatitis C (CHC) caused by its virus genotype 1. SUBJECTS AND METHODS: One hundred and fourteen patients (67 men and 47 women; mean age 44.9 +/- 13.3 years) were examined. RESULTS: There were high incidence rates of metabolic syndrome (47.2%) and insulin resistance (50%), in the genesis of which the host-virus interaction is discussed. There was an independent correlation of the insulin resistance and elevated leptin levels with abdominal obesity and hepatic steatosis; however, these indicators did not correlate with the stage of fibrosis. At the same time hepatic steatosis (found in 38% of the patients) and its degree correlated with the stage of fibrosis. Thirty-four of 66 (54.5%) patients receiving antiviral therapy achieved a stable virological response. CONCLUSION: Obesity, hyperglycemia, and significant insulin resistance along with the stage of hepatic cirrhosis are independent cofactors that determine no treatment response.

[Depressive disturbances during antiviral therapy in patients with type C hepatitis].

The article presents the results of a clinico-psychopathological study of depressive disorder (DD) in 91 patients with chronic C hepatitis and no psychiatric background during combined antiviral therapy (AVT) with interferon-alpha (IFN-alpha) and ribavirin. Depression developed in 39 or 43% of the patients. Moderate or severe depressions (46% and 31%, respectively) prevailed. Clinical features that were different in cases of IFNa-induced depression and endogenous DD were revealed. The severity of depression did not correlate with the severity of the underlying disease, the duration of AVT, and the type of used. The antidepressants and remeron proved to be effective in treatment of IFN-alpha-induced depressions. In all cases, treatment with antidepressants made it possible to carry out complete AVT.