Absence Of Clinical Effects Research Articles

New topical combinations in acne therapy

Introduction. Therapeutic treatment modalities for acne involve both topical and oral medications. Fixed-dose combinations that affect all components of the pathogenesis of acne vulgaris are given preference among topical medications.Aim. To evaluate the efficacy and tolerability of Metrogyl® a topical drug, containing adapalene and metronidazole, which is used as topical therapy in patients with mild to moderate acne.Materials and methods. A prospective, open-label, randomized, single-centre comparative study was conducted in 2022. A total of 60 patients were subjected to the Mir-O-Med clinic-based observation (Krasnodar): 19 men and 41 women aged 18 to 45 years with mild to moderate acne. Group 1 received a fixed-dose combination of adapalene 1.0 mg and metronidazole10.0 mg (Metrogyl® A); Group 2 – a fixed-dose combination of adapalene 0.1% and clindomycin phosphate 1%; Group 3 – a fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel; Group 4 – adapalene 0.1%. Group 5, a separately created group, included patients from Group 1, who continued therapy for another 3 months.Results. After therapy, 6 (40%) patients from Group 1 archived clinical remission, and 9 (60%) patients found significant improvement. No deterioration in patients’ condition or absence of clinical effects was observed during therapy. The combination of adapalene and metronidazole (Metrogyl® A) to treat mild to moderate acne is comparable in terms of efficacy to the combination of adapalene and benzoyl peroxide, 10% more efficient than topical adapalene therapy and 30% more efficient than topical antibiotics combination.Conclusion. The obtained results showed high therapeutic efficacy, good tolerability and safety of Metrogyl® A, which allows to use it as monotherapy and as part of combination with other agents in patients with mild to moderate acne.

Systemic Thrombolysis and Post-stroke Epilepsy

Systemic thrombolysis is a highly effective treatment for ischemic stroke. The effect of thrombolysis on the development of post-stroke epilepsy (PSE) remains a subject of scientific debate. The aim of this study was to clarify the clinical and neuroimaging features of PSE in patients with ischemic stroke, who underwent systemic thrombolysis. . A total of 46 patients after ischemic stroke were examined, including 33 men and 13 women aged 28 to 80 years. Group I consisted of 9 patients with PSE after systemic thrombolysis with rtPA (alteplase) at a dose of 0.9 mg/kg. Group II included 8 patients without PSE after systemic thrombolysis. Group III consisted of 29 patients with PSE, who received standard drug therapy. Comparative group analysis took into account the medical history, clinical and neuroimaging data. . Patients with PSE were characterized by the absence of clinical effect after systemic thrombolysis (p = 0.026); infarcts extending to the frontal and insular lobes (p = 0.038), insular lobe and basal nuclei (p = 0.026); development of a hemorrhagic component in the cerebral cortex (p = 0.005), as well as in the territory of the deep and terminal branches of the middle cerebral artery (MCA) (p = 0.006). Development of PSE is associated with ineffective systemic thrombolysis and the appearance of extensive and large cerebral infarcts with a hemorrhagic component.

Increased indoleamine 2,3-dioxygenase activity and expression in prostate cancer following targeted immunotherapy.

We previously found that PD-L1 expression is increased on tumor cells following vaccination treatments that lead to increased tumor-specific T cells that secrete IFNγ. Indoleamine 2,3-dioxygenase (IDO) is another IFNγ inducible gene that has potent immunosuppressive effects. There have been reports of IDO expression in prostate cancer; however, it is unknown whether IDO expression might similarly increase in prostate tumors following T-cell-based immunotherapy. Blood samples from normal male blood donors (n = 12) and patients with different stages of prostate cancer (n = 89), including patients with metastatic, castration-resistant prostate cancer treated with a DNA vaccine and/or pembrolizumab, were evaluated for IDO activity by kynurenine and tryptophan levels. Metastatic tissue biopsies obtained pre- and post-treatments were evaluated for IDO expression. IDO suppression of vaccine-induced T-cell function was assessed by ELISPOT. Overall, IDO activity was increased in patients with more advanced prostate cancer. This activity, and IDO expression as detected immunohistochemically, increased following treatment with either a DNA vaccine encoding the prostatic acid phosphatase (PAP) tumor antigen or PD-1 blockade with pembrolizumab. Increased IDO activity after treatment was associated with the absence of clinical effect, as assessed by lack of PSA decline following treatment. Increased antigen-specific T-cell response, as measured by IFNγ release, to the vaccine target antigen was detected following in vitro stimulation of peripheral blood cells with 1-methyltryptophan. These findings suggest that IDO expression is a mechanism of immune evasion used by prostate cancer and that future clinical trials using T-cell-based immune strategies might best include IDO inhibition.

EFFECT OF PROPRANOLOL ON AEROBIC-HEMODYNAMIC SUPPORT OF PHYSICAL ACTIVITY IN PATIENTS WITH EFFORT ANGINA, POSITIVE ANTIANGINAL ACTION AND THE ABSENCE OF CLINICAL EFFECT AFTER PROPRANOLOL-BASED TREATMENT

Aim. To analyze the changes in the aerobic-hemodynamic parameters during physical exercise in patients with effort angina administered with reference non-selective beta-blocker propranolol (Obsidan) with positive antianginal action and the absence of clinical effect after the drug intake.Material and Methods. A total of 58 patients (mean age of 54.2 [48.5; 59.5] years) with effort angina of functional class II–IV were examined with spiro-veloergometry tests before and after administration of propranolol (Obsidan: manufactured by Isis Pharma GmbH, Germany) at a dose of 40 mg. At threshold physical activity the following parameters were assessed: oxygen consumption (VO2 ), specific oxygen consumption, cardiac index (CI), rate pressure product (RPP); total peripheral vascular resistance (TPVR), arteriovenous oxygen difference (a-vDО2 ) and mechanical work of the heart (HW).Results. The efficacy of single-dose obsidian was observed in 58.6% of patients with angina (group 1); in this, tolerance to physical exercise increased from 50.0 [25.0; 75.0] W to 75.0 [50.0; 100.0] W. In the rest of patients (group 2), no antianginal effect was registered. At the first stage (at initial threshold physical activity level), administration of propranolol was characterized by saving pattern of heart function: statistically significant decrease in the heart rate, mean arterial pressure, CI and HW. This naturally resulted in reduction of myocardial oxygen demand (decrease in RPP from 163.0 [134.5; 218.5] U to 102.0 [90.0; 142.5] U; p<0.001) and predetermined the drug anti-ischemic action. At the second stage (maximum physical effort), an increase in the physical activity, caused by increase in VO2 from 738.0 [604.5; 1148.0] mL/min to 972.0 [774.5; 1458.0] mL/min, occurred due to higher oxygen extraction from peripheral blood (a-vDО2 increase; p<0.002). In group 2, despite the absence of an increase in tolerance to physical exercise, administration of propranolol was characterized by low RPP threshold i.e. the physical effort similar to the initial level was performed at a lower cardiac energy consumption.Conclusion. Therefore, anti-ischemic effect of Obsidan was due to a decrease in theenergy expenditure of the cardiac function along with a limitation in the hemodynamic productivity efficiently compensated by an increase in the oxygen extraction from circulating blood during physical activity.

EFFECT OF PROPRANOLOL ON AEROBIC-HEMODYNAMIC SUPPORT OF PHYSICAL ACTIVITY IN PATIENTS WITH EFFORT ANGINA, POSITIVE ANTIANGINAL ACTION AND THE ABSENCE OF CLINICAL EFFECT AFTER PROPRANOLOL-BASED TREATMENT

Aim. To analyze the changes in the aerobic-hemodynamic parameters during physical exercise in patients with effort angina administered with reference non-selective beta-blocker propranolol (Obsidan) with positive antianginal action and the absence of clinical effect after the drug intake.Material and Methods. A total of 58 patients (mean age of 54.2 [48.5; 59.5] years) with effort angina of functional class II–IV were examined with spiro-veloergometry tests before and after administration of propranolol (Obsidan: manufactured by Isis Pharma GmbH, Germany) at a dose of 40 mg. At threshold physical activity the following parameters were assessed: oxygen consumption (VO2 ), specific oxygen consumption, cardiac index (CI), rate pressure product (RPP); total peripheral vascular resistance (TPVR), arteriovenous oxygen difference (a-vDО2 ) and mechanical work of the heart (HW).Results. The efficacy of single-dose obsidian was observed in 58.6% of patients with angina (group 1); in this, tolerance to physical exercise increased from 50.0 [25.0; 75.0] W to 75.0 [50.0; 100.0] W. In the rest of patients (group 2), no antianginal effect was registered. At the first stage (at initial threshold physical activity level), administration of propranolol was characterized by saving pattern of heart function: statistically significant decrease in the heart rate, mean arterial pressure, CI and HW. This naturally resulted in reduction of myocardial oxygen demand (decrease in RPP from 163.0 [134.5; 218.5] U to 102.0 [90.0; 142.5] U; p<0.001) and predetermined the drug anti-ischemic action. At the second stage (maximum physical effort), an increase in the physical activity, caused by increase in VO2 from 738.0 [604.5; 1148.0] mL/min to 972.0 [774.5; 1458.0] mL/min, occurred due to higher oxygen extraction from peripheral blood (a-vDО2 increase; p<0.002). In group 2, despite the absence of an increase in tolerance to physical exercise, administration of propranolol was characterized by low RPP threshold i.e. the physical effort similar to the initial level was performed at a lower cardiac energy consumption.Conclusion. Therefore, anti-ischemic effect of Obsidan was due to a decrease in theenergy expenditure of the cardiac function along with a limitation in the hemodynamic productivity efficiently compensated by an increase in the oxygen extraction from circulating blood during physical activity.

Typical errors in therapy of gastroesophageal reflux disease

To analyze compliance of doctors with the clinical guidelines for the management of patients with gastroesophageal reflux disease (GERD) under outpatient clinic conditions. An anonymous questionnaire study involving 104 general practitioners was undertaken. The questionnaires included items concerning lifestyle modifications, the use of proton pump inhibitors (PPI), dosage and time of their administration, combined therapy and endoscopic control. The analysis of the filled questionnaires demonstrated that 15,6% of the doctors always discuss the necessity changing lifestyle with GERD patients, 75% of the doctors discuss it but occasionally, and 9,4% never hold such discussions. 56,7% of the doctors begin treatment from double doses of proton pump inhibitors regardless of the endoscopic stage of esophagus damage. The mode of PPI administration is at variance with that recommended by the instruction in 61,5% of the cases. The basic course of erosive esophagitis treatment lasts 4, 2, and 8 weeks in 45,2%, 9,6%, and 45,2% of the cases. Treatment of GERD starts from combined therapy in 14,4% of the cases. Monotherapy with PPI is inefficient in 85,6% of the cases. Endoscopic control of erosive esophagitis is practiced by 51,9% of the doctors, 48,1% of the respondents recommend this diagnostic procedure only in the absence of clinical effect. Our analysis revealed typical mistakes in the treatment of patients with GERD, demonstrated the importance of expert control and support of training physicians, and introduction of modern quality standards into the practical management of patients with this pathology.

AB0370 Association of Clinical Efficacy with Serum Level of Adalimumab (ADA) and Anti- Adalimumab Antibody Levels in Patients with Early Rheumatoid Arthritis (RA)

BackgroundADA is effective and safe drug for the treatment of RA. Application of ADA can be accompanied by formation anti-adalimumab antibody (anti-ADA Ab) influencing on efficiency of therapy and the...

Digital Analytic Cardiography (DACG), a New Method for Quantitative Trophism Assessment of the Myocardium

Digital Analytic Cardiography (DACG), a New Method for Quantitative Trophism Assessment of the Myocardium Background: At present, none of the available ischemic heart disease (IHD) diagnostic methods can reveal the disease with 100% certainty. Methods and Results:DACG, a new method of ECG signal processing, has been utilized to calculate the criteria. We observed 5 groups of patients: 2 control without IHD; one group with IHD, 8 of whom were observed before and after using nitrates; and 2 patients with syndrome X.There were authentic augmentations of all worked-out criteria (G, L, S) in the ischemia zone of the myocardium in relation to the non-ischemic zones (from 2 to 7). In the control, all criteria oscillate from 0 to 1.5. The value of the G criterion has a strict correlation with the functional classification of IHD. We observed a strong correlation between the clinical effect by nitrates and our criteria. The absence of a clinical effect by nitrates correlated with no dynamics in all criteria. The combination of the absence of criteria and clinical effect by nitrates with elevated L criteria led to acute myocardial infarction in a few hours. We developed non-locality in the ischemic process in patients with syndrome X with significant augmentation of the G and L criteria in all zones of the myocardium. Conclusions:The proposed DACG method allows for authentically diagnosing IHD and its functional class impartially, as well as localizing the ischemic process and qualifying its depth quantitatively.

The efficacy of psychological interventions for infertile patients: a meta-analysis examining mental health and pregnancy rate

Psychological interventions for infertile patients seek to improve mental health and increase pregnancy rates. The aim of the present meta-analysis was to examine if psychological interventions improve mental health and pregnancy rate among infertile patients. Thus, controlled studies were pooled investigating psychological interventions following the introduction of assisted reproductive treatments (ART). The databases of Medline, PsycINFO, PSYNDEX, Web of Science and the Cochrane Library were searched to identify relevant articles published between 1978 and 2007 (384 articles). Included were prospective intervention studies on infertile patients (women and men) receiving psychological interventions independent of actual medical treatment. The outcome measures were mental health and pregnancy rate. A total of 21 controlled studies were ultimately included in a meta-analysis comparing the efficacy of psychological interventions. Effect sizes (ES) were calculated for psychological measures and risk ratios (RR) for pregnancy rate. The findings from controlled studies indicated no significant effect for psychological interventions regarding mental health (depression: ES 0.02, 99% CI: -0.19, 0.24; anxiety: ES 0.16, 99% CI: -0.10, 0.42; mental distress: ES 0.08, 99% CI: -0.10, 0.51). Nevertheless, there was evidence for the positive impact of psychological interventions on pregnancy rates (RR 1.42, 99% CI: 1.02, 1.96). Concerning pregnancy rates, significant effects for psychological interventions were only found for couples not receiving ART. Despite the absence of clinical effects on mental health measures, psychological interventions were found to improve some patients' chances of becoming pregnant. Psychological interventions represent an attractive treatment option, in particular, for infertile patients who are not receiving medical treatment.

Chromosome abnormalities without phenotypic consequences

Some changes in chromosome morphology, detected during cytogenetic analysis, are not associated with clinical defects. Therefore a proper discrimination of harmless variants from true abnormalities, especially during prenatal diagnosis, is crucial to allow precise counseling. In this review we described chromosome variants and examples of chromosome anomalies that are considered to be unrelated to phenotypic consequences. The correlation between the presence of marker chromosomes and a risk of clinical signs is also discussed. Structural rearrangements of heterochromatic material, satellite polymorphism, or fragile sites, are well-known examples of common chromosome variation. However, the absence of clinical effects has also been reported in some cases of chromosome abnormalities concerning euchromatin. Such euchromatic anomalies were divided into 2 categories: unbalanced chromosome abnormalities (UBCAs), such as deletions or duplications, and euchromatic variants (EVs). Recently so-called molecular karyotyping, especially whole-genome screening by the use of high-resolution array-CGH technique, contributed to revealing a high number of previously unknown small genomic variations, which seem to be asymptomatic, as they are present in phenotypically normal individuals.

Bone Marrow Mesenchymal Stem Cells Suppress Lymphocyte Proliferation In Vitro but Fail to Prevent Graft-versus-Host Disease in Mice

Several reports have suggested that mesenchymal stem cells (MSCs) could exert a potent immunosuppressive effect in vitro, and thus may have a therapeutic potential for T cell-dependent pathologies. We aimed to establish whether MSCs could be used to control graft-vs-host disease (GVHD), a major cause of morbidity and mortality after allogeneic hemopoietic stem cell transplantation. From C57BL/6 and BALB/c mouse bone marrow cells, we purified and expanded MSCs characterized by the lack of expression of CD45 and CD11b molecules, their typical spindle-shaped morphology, together with their ability to differentiate into osteogenic, chondrogenic, and adipogenic cells. These MSCs suppressed alloantigen-induced T cell proliferation in vitro in a dose-dependent manner, independently of their MHC haplotype. However, when MSCs were added to a bone marrow transplant at a MSCs:T cells ratio that provided a strong inhibition of the allogeneic responses in vitro, they yielded no clinical benefit on the incidence or severity of GVHD. The absence of clinical effect was not due to MSC rejection because they still could be detected in grafted animals, but rather to an absence of suppressive effect on donor T cell division in vivo. Thus, in these murine models, experimental data do not support a significant immunosuppressive effect of MSCs in vivo for the treatment of GVHD.

Autoimmune disease and pregnancy.

Autoimmune diseases are relatively common in women, and tend to occur in the childbearing years. These disorders fall broadly into two groups: (i) Multisystem diseases such as systemic lupus erythematosus (SLE) and related connective tissue disorders (CTD). This group includes the 'pre-clinical' antiphospholipid or lupus obstetric syndrome which may first manifest itself as a pregnancy disorder causing recurrent abortion, fetal death, fetal growth retardation and early onset severe pre-eclampsia. (ii) Tissue- or organ-specific disorders such as autoimmune thrombocytopaenic purpura (ATP), autoimmune thyroid disease (Graves' disease, Hashimoto's autoimmune thyroiditis, and post-postum thyroiditis), autoimmune haemolytic anaemia, and the very rare myasthenia gravis. The study of autoimmune diseases against the background of pregnancy as an experimental system of nature has provided important insights into the nature of the disease processes and the relevance or otherwise of circulating autoantibodies to pathological effects. Thus, for example, if neonatal manifestations of adult disease are causally related to the transfer of autoantibodies across the placenta, they will disappear over a time course consistent with the catabolism of IgG, providing no permanent damage is produced. Conversely, if autoantibodies are demonstrable in the neonate, in the absence of clinical effects, they may only be an epiphenomenon of the maternal disease. In addition, on occasions, disease manifestations may be seen in the baby when the mother shows none. This may occur when the mother is in remission, but still has circulating antibodies, or when she has an occult form of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)