Potential impact on mental health in patients with treatment-resistant schizophrenia - clozapine augmentation with long-acting parenteral antipsychotics: a case series.

INTRODUCTION: The rate of pharmacoresistance among in patients diagnosed with schizophrenia is around 30%. Clozapineis the drug of choice for these patients; however, an adequate response to treatment doesn't always occur. One of the possible augmentation approaches, specifically for non-adherent patients, is the administration of long-acting parenteral antipsychotics. Our goal was to evaluate previous experiences of administering a combination of the atypical antipsychotic clozapine and long-acting injectable antipsychotics to pharmacoresistant patients at the Department of Psychiatry the Czech Republic and to assess the safety and effectiveness of such administration. METHODS: A retrospective evaluation of patient case studies was conducted for those who were hospitalized in the Ward for the therapy of Psychotic disorders between 2016 and 2020 and had a medication history of combining clozapine and depot antipsychotics. RESULTS: Over half of the patients had no illness relapses during the observed period. The clinical manifestation of adverse effects from combination therapy appears low in our patient sample, primarily involving mild and pharmacologically manageable side effects (tachycardia). Only one of the cases recorded neutropenia, which led to discontinuation of clozapine; the patient was maintained on long-acting injectable antipsychotics medication. CONCLUSION: From our findings, it can be inferred that augmenting clozapine with depot antipsychotics is a potential therapeutic intervention that pharmacoresistant patients could benefit from. However, it is essential to emphasize that this therapeutic approach should only be administered after carefully considering the patient's existing treatment. It should be strictly individualized based on the treating physician's or clinical pharmacist's sufficient professional experience.

Immunotherapy for cancer treatment.

BACKGROUND: Immunotherapy is an effective way to treat many diseases associated with disorders of the immune system by modulating immune response. It involves several ways of manipulating the immune system, which either suppress the immune response or, on the contrary, stimulates it. Immunotherapy is currently of immense importance not only in the context of the treatment of autoimmune diseases and immunodeficiencies, but it is also a promising method for treating cancer. Efforts to use the bodys own anti-tumor response have led to the discovery of alternative treatments for cancer. PURPOSE: The aim of this paper is to provide a literature review focused on the current possibilities of cancer immunotherapy. In addition to classical procedures such as chemotherapy and radiotherapy, treatments consisting of adoptive cell therapy and blockade of immune checkpoints are being increasingly indicated. The latest form of adoptive cell therapy is the use of T-lymphocytes expressing chimeric antigen receptors. This type of treatment is indicated for hematological cancers. In recent years, a new approach to the treatment of cancer has emerged using blockade of immune checkpoints by monoclonal antibodies. At present, antitumor therapy focuses on blocking of inhibitory molecules - cytotoxic T-lymfocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1). Administration of anti-CTLA-4 receptor specific monoclonal antibodies blocks binding between CTLA-4 receptors and B7 ligands, thereby preventing inhibition of activated cytotoxic T cells. Another type of checkpoints of the immune response include PD-1 molecules expressed on the surface of T-lymphocytes, B-lymphocytes, but also on the surface of myeloid cells. Blockade of PD-1 receptors and PD-L1 ligands prevents the inhibition of T-lymphocytes by tumor cells, leading to an increase in the immune systems ability to recognize tumor cells and subsequently destroy them. Blockade of PD-1 receptors and PD-L1 ligands prevents the inhibition of T-lymphocytes by tumor cells, leading to an increased immune response to the recognition of tumor cells and their subsequent destruction. An alternative form of tumor treatment is the administration of tumor vaccines and tumor-specific monoclonal antibodies (mAbs). The use of mAbs to kill tumors requires the expression of tumor-specific antigens on the surface of tumor cells. Through these receptors, mAb targets cytotoxic cells, toxins, drugs, or radioisotopes to tumor cells and thereby destroys them. Also, mAbs are able to block angiogenesis, which is crucial in tumor cell proliferation.

Alveolar Echinococcosis of the Liver with a Rare Infiltration of the Adrenal Gland.

Human alveolar echinococcosis (AE) is a silently-progressing disorder that has become a threat in many countries. Since 2000, when the first case was recorded, the number of human AE patients in Slovakia is on continuous raise. The article presents a rare case of alveolar echinococcosis with infiltration in the adrenal gland and discusses the problems associated with differential diagnosis of the disease. In 2016, abdominal ultrasound performed due abdominal pain complaint showed the presence of cystic lesions in the right liver lobe of 54-year old female patient. During surgery, another lesion in the right adrenal gland was found, and neoplastic processes or echinococcosis were considered in the differential diagnosis. Due to unclear correlation between radiology, serology and histopathology results and endemic situation in Slovakia, molecular examination was recommended. Subsequently E. multilocularis was confirmed as etiological agent of infection. Alveolar echinococcosis is considered as a rare disease, with very few patients referred to clinicians or hospitals that sometimes have almost none existing experience with the diagnosis and treatment of the disease. Therefore, the establishment of networks or reference centres specialized on management of the disease would be suitable way to provide the patients with the best care and improve the disease diagnosis, treatment and prognosis.

Survey on the diagnosis and treatment of Clostridium difficile infection.

BACKGROUND: The toxigenic strains of Clostridioides (Clostridium) difficile is the most common pathogen of nosocomial and antibiotic-related diarrhoea in healthcare facilities. Lately, there has been an increase in the incidence of C. difficile infection (CDI) cases in Slovakia. MATERIALS AND METHODS: Retrospective analysis of the CDI appearance was carried out in the Zilina region. Additionally, an electronic survey focused on the diagnosis and treatment management of C. difficile infection was conducted among leading clinicians of the wards where CDI was present. RESULTS: Eighty percent of clinicians reported that they were following the recommendations for diagnosis and treatment of C. difficile infection in their everyday practice. The majority of leading physicians were from internal medicine wards (50 %). Most respondents stated that the laboratory results correlated with the clinical symptoms of patients. The first-choice treatment of C. difficile infections was reported to be oral vancomycin (in 21.7 %) and oral metronidazole (in 47.8 %). The estimate of first-choice treatment success rate was 80 %, while the recurrence rate and severe course was observed in 20%. Vancomycin was the standard treatment for recurrent infection. It was administered orally either alone (31 %) or combined with metronidazole (38 %) or fidaxomicin (31 %). CONCLUSION: The results of the survey showed that recommendations for the diagnosis and treatment were implemented in the wards of hospitals and showed the awareness of the necessity of rapid diagnosis and early treatment of C. difficile infection in patients (Fig. 4, Ref. 30).

Ribotypes in isolates and testing algorithm of C. difficile infections in the studied sample.

BACKGROUND: Clostridium (Clostridioides) difficile is the most common pathogen of nosocomial and antibiotic-related diarrhea in health-care facilities. The aim of the analysis was to show the testing algorithm and to identify hypervirulent strains (suspected RT 027). METHODS: The retrospective analysis of patient samples suspected on CDI was carried out by a two-step algorithm. Biological specimens were analysed by GDH or culture, immunoenzymatic assay on toxins A/B and selected samples also by a real-time PCR. RESULTS: In 1006 specimen suspected on CDI, 202 specimens were evaluated as positive in the two-step algorithm. Conflicting results (64 C. difficile isolates) were tested in a three-step algorithm by a real-time PCR and revealed 59 toxigenic and non RT 027 ribotypes. Statistically significant dependence among the independent variables, such as: diagnostic parameters and length of hospitalization (p = 0.175) and C. difficile (suspected RT027) ribotypes was not found. CONCLUSION: The results of PCR ribotyping showed a high prevalence of hypervirulent and toxigenic ribotypes in the studied sample. A resistance to vancomycin was found in one isolate. The PCR method contributed to the rapid laboratory diagnosis and thus treatment of high risk patients or was used as a third step in in the case of unclear results of standard diagnostic methods(Tab. 1, Fig. 4, Ref. 18). Text in PDF www.elis.sk.

What is the optimal number of library plans in ART for locally advanced cervical cancer?

PURPOSE: Library-of-plans ART is used to manage daily anatomy changes in locally advanced cervical cancer. In our institute, the library contains 2 VMAT plans for patients with large cervix-uterus motion. Increasing this number could be beneficial for tissue sparing, but is burdensome while the dosimetric gain is yet unclear. This study's aim is to determine the optimal number of plans at an individual patient level. MATERIAL AND METHODS: Data of 14 treated patients were analyzed. Plan libraries were created containing 1-4 VMAT plans. Pre-treatment extent of uterus motion was defined by the 99th percentile of the Hausdorff distance (HD99). For dosimetric evaluations, OARs were contoured in daily CBCT scans, plan selection was simulated, and the V45Gy and V40Gy parameters were recorded. RESULTS: Moderate to strong correlations were found between HD99 and the volume of spared OARs. All patients benefitted from adding a 2nd plan, as is the clinical practice. For patients with a HD99 between 30 and 50mm, a 3-plan library reduced the composite V40Gy with 11-21ml compared to a 2-plan library. CONCLUSION: Patients with large uterus motion (HD99>30mm) would benefit from an extension of the plan library to 3. HD99 is an easy-to-implement criteria to select those patients pre-treatment.

Identification of Mycobacterium Species by MALDI-TOF Mass Spectrometry.

Matrix-assisted laser desorption ionization - time-of-flight (MALDI-TOF) mass spectrometry enables to identify microorganisms by comparison of the protein content with reference spectra in the database. The aim of this study was to evaluate the efficacy of phenotypic identification of mycobacteria by MALDI-TOF mass spectrometry in laboratory practice. Seventy five isolates of mycobacteria were identified by molecular and phenotypic method, and the results were compared by MALDI-TOF. For MALDI-TOF, material was processed according to the Bruker Daltonics protocol and Mycobacterial Library database version 2.0, with 313 reference mycobacteria spectra. All except one of the 72 isolates agreed with regard to the species and genus by both methods. Forty three isolates were identified as the M. tuberculosis complex by MALDI-TOF. Thirty one isolates of nontuberculous mycobacteria were consistently identified by both methods to the species level. We conclude that MALDI-TOF mass spectrometry is an accurate method of bacterial identification. Simplicity, speed, and economic availability of the method makes it suitable for mycobacteria identification in a routine laboratory.

Importance of GOLD Guidelines for Chronic Obstructive Pulmonary Disease.

In December 2011, a major revision of GOLD 2011 guidelines was published based on the evidence-based medicine. The goal of GOLD 2011 is to determine the severity of the disease, its impact on the patient's health, and the risk of future events; all of which eventually guide therapy. A combined COPD assessment according to GOLD 2011 considers the patient's level of symptoms, spirometry abnormalities, risk of exacerbation, and the presence of comorbidities. GOLD 2011 stratifies patients into four basic groups labeled A, B, C, and D. The aim of the present study was to assess the importance of updated GOLD guidelines for the diagnosis, treatment, and prevention of COPD. We found that the multicomponent 2011 guidelines offer a significant advantage over the previous mono-component COPD assessment according to GOLD 2006 in terms of disease control and therapy management, with patients enjoying better spirometry values and a higher arterial oxygen content considered the primary outcomes of interest.

Microbiologic Methods in the Diagnostics of Upper Respiratory Tract Pathogens.

Upper respiratory tract infection (URI) is a nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, and larynx above the vocal cords. The aim of this study was to provide a summary of the most common pathogens of URI and to compare advantages and disadvantages of traditional and new rapid microbiological tests used to identify them. Blood samples were simultaneously examined by the enzyme-linked immunosorbent assay (ELISA) and by the FilmArray Respiratory Panel for eight different pathogens in a total of 15 tests performed in nasopharyngeal swabs. The ELISA method is unable to identify the pathologic agent until the host's immune system elicits a response. The method is readily available in many laboratories at a low cost, which puts less strain on economic resources. The FilmArray® Panel, on the other hand, is more expensive, but it is fast and exact in the identification of a broad spectrum etiologic agents. Nonetheless, since most repiratory tract infections are viral in origin and there is no treatment available, the diagnosis provided by the FilmArray Panel does not provide any additional clinical benefit and thus should be used only whenever necessary on the individual basis.

Efficacy of RNA interference knockdown using aerosolized short interfering RNAs bound to nanoparticles in three diverse aphid species.

RNA interference (RNAi) has emerged as a promising method for validating gene function; however, its utility in nonmodel insects has proven problematic, with delivery methods being one of the main obstacles. This study investigates a novel method of RNAi delivery in aphids, the aerosolization of short interfering RNA (siRNA)-nanoparticle complexes. By using nanoparticles as a siRNA carrier, the likelihood of cellular uptake is increased, when compared to methods previously used in insects. To determine the efficacy of this RNAi delivery system, siRNAs were aerosolized with and without nanoparticles in three aphid species: Acyrthosiphon pisum, Aphis glycines and Schizaphis graminum. The genes targeted for knockdown were carotene dehydrogenase (tor), which is important for pigmentation in Ac. pisum, and branched chain-amino acid transaminase (bcat), which is essential in the metabolism of branched-chain amino acids in all three aphid species. Overall, we observed modest gene knockdown of tor in Ac. pisum and moderate gene knockdown of bcat in Ap. glycines along with its associated phenotype. We also determined that the nanoparticle emulsion significantly increased the efficacy of gene knockdown. Overall, these results suggest that the aerosolized siRNA-nanoparticle delivery method is a promising new high-throughput and non-invasive RNAi delivery method in some aphid species.

Experimental model of allergic asthma.

The aim of the study was to prepare and evaluate the experimental model of allergic asthma. Changes in chough reflex, bronchoconstriction and the degree of inflammation were studied in ovalbumin (OVA) sensitized guinea pigs after 0, 7, 14, 21 days of exposure. The cough reflex was induced by citric acid inhalation in conscious animals in a double chamber body plethysmograph. Tracheal smooth muscle reactivity was assessed by examining the in vitro response to histamine (H) (10(-8)-10(-3) mol/l) and in vivo to H nebulization (10(-6) mol/l). BALF levels of IL-4, IL-5 and the eosinophil count were used as parameters of airway inflammation. After 7 days of OVA sensitization, there was an increase in tracheal smooth muscle contractility in vitro to cumulative concentration of H and an increase in cough parameters. After 14 days of OVA sensitization, there was a further increase in tracheal smooth muscle contractility to H, an increase in airway resistance, and a small increase in cough parameters. After 21 day of OVA sensitization, cough parameters were significantly reduced, airway resistance after H inhalation was increased, and there were significant increases in IL-4, IL-5, and eosinophils in BALF. In conclusion, progress in asthmatic inflammation during 21-day OVA sensitization caused a gradual increase in inflammatory mediators, a decline in cough reflex, and enhanced bronchoconstriction. This experimental model of allergic asthma can be used for pharmacological modulations of defense reflexes and inflammation.

Polyphenols and their components in experimental allergic asthma.

The aim of the study was to investigate the potential anti-inflammatory effects in -experimental allergic asthma of natural polyphenolic compounds or their single major components. The experiment was performed after 21-days sensitization of guinea pigs with ovalbumin suspension. Changes in airway reactivity after the long-term treatment with the polyphenolic compounds Provinol and Flavin-7 and their single major components quercetin and resveratrol during were assessed using a whole body plethysmography. Reactivity of tracheal smooth muscle was studied in vitro in response to cumulative doses of the bronchoconstrictive mediators histamine and acetylcholine. Furthermore, concentrations of the inflammatory cytokines IL-4 and IL-5 were measured in bronchoalveolar lavage fluid. The results demonstrate significant anti-inflammatory effects of Provinol and Flavin-7 exerted in the airways. In contrast, chronic treatment with quercetin and resveratrol, single components of the two polyphenols, did not show such activity. We conclude that polyphenolic compounds are more effective in the anti-inflammatory effects in the airways than their separate components.

WITHDRAWN: The efficiency of polyphenolic compounds on allergen induced hyperreactivity of the airways.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.bionut.2010.09.002. The duplicate article has therefore been withdrawn.

Effects of flavin7 on allergen induced hyperreactivity of airways.

Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4), and interleukin 5 (IL-5) in bronchoalveolar lavage fluid (BALF). Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

[Identification of blockers of adrenergic beta-receptors by thin layer chromatography]. / Prukaz blokátoru adrenergních receptoru beta chromatografií na tenké vrstve.

Blockers of adrenergic beta-receptors (beta-blockers) are commonly administered in cardiology for coronary heart disease, arrhythmias, hypertension and some cardiopathic treatment. They have been also approved as a therapy of chronic heart failure recently. From pharmacological point of view, cardioselective and non selective beta-blockers (with or without intrinsic sympathomimetic activity) are distinguished. New drugs like celiprolol, carvedilol or sotalol have been developed and so the range of the group still continues to widen out. In toxicological routine practice we meet beta-blockers either in acute intoxication cases or in a control of patient's adherence to prescribed therapy. Dizziness, nausea, weakness, vasoconstriction and bradycardia are their usual undesirable effects, whilst in grave cases of a drug overdose bronchoconstriction, coronary spasms, hypotension and even cardiac insufficiency may occur. The article deals with the possibility of detection and identification of beta-blockers and their metabolites in urine by thin layer chromatography.

The role of non-critical health-care tools in the transmission of nosocomial infections.

The authors performed the cultivation of swabs taken from membranes of 110 stethoscopes of physicians, medical students and shared stethoscopes from ward consultant rooms. In addition to that, 24 random samples from other non-invasive health-care tools and the hospital environment were taken. In order to find out about the disinfection habits and knowledge of medical students, 97 of them were addressed in an anonymous questionnaire. Out of 110 stethoscopes, microbial colonisation was not present only in nine cases (8 %). Staphylococcus sp. was present on 94 stethoscopes (85 %), out of which 19 (20 %) were methicillin-resistant staphylococci of various species. S. aureus was found in 16 cases (14 %), out of which MRSA made 12 % (two cases). Cultivation of 24 additional samples discovered methicillin-resistant staphylococci in four cases--two of them were MRSA present on the esmarch and a blood-presure cuff. The questionnaire revealed that only six (6 %) addressed medical students have ever disinfected their stethoscopes in the past. Disinfection of non-critical tools should become an integral part of under-graduate and postgraduate education (Tab. 1, Fig. 2, Ref. 7).

Incidence and etiological agents of bacterial meningitis among children <5 years of age in two districts of Romania.

To expand upon the limited comprehensive population-based data for childhood bacterial meningitis in Eastern Europe, the present study was conducted in the Iasi and Constanta districts of Romania. From March 2000 through March 2002, children <5 years of age hospitalized for bacterial meningitis were enrolled in a prospective surveillance study. A total of 56 cases of bacterial meningitis were identified, including 37 due to Neisseria meningitidis (22 per 100,000 per year), 13 due to Haemophilus influenzae type b (7.6 per 100,000 per year), and six due to Streptococcus pneumoniae (3.5 per 100,000 per year). Of the 31 meningococcal isolates that were serotyped, 12 were serogroup A, eight were serogroup B, and 11 were serogroup C. Among all cases of bacterial meningitis, 25 occurred in children <1 year of age, including those due to meningococci (n=14), H. influenzae type b (n=7), pneumococci (n=3), and Klebsiella pneumoniae (n=1). In Romania the incidence of H. influenzae type b meningitis is similar to that found in other areas of Southern and Eastern Europe during the pre-vaccination era, and the incidence of meningococcal meningitis is one of the highest yet found in Europe. An unexpectedly high proportion of these meningococcal meningitis cases is due to serogroup A. Disease burden could be substantially reduced through the introduction of H. influenzae type b conjugate vaccine and, when available, meningococcal conjugate vaccine protective against serogroups A, B and C.

[Detection of new antidepressive agents using thin-layer chromatography]. / Prukaz nekterých nových antidepresiv chromatografií na tenké vrstve.

Series of new antidepressants appeared in the treatment of central nervous system disorders in the last years. Into this group belong: 1. antidepressants of the 3rd generation which selectively inhibit serotonine reuptake; 2. thymoleptics--a group of compounds which have no anticholinergic effects and act as noradrenaline reuptake inhibitors or noradrenaline and serotonine reuptake inhibitors; 3. antipsychotics from the group of selective serotonine and dopamine antagonists. All they have less undesirable side-effects than classical tricyclic antidepressants of the first generation and thymoleptics of the second generation. Thus they are nowadays more often used as the drugs of the first choice and are therefore met more often in the biological material analyzed in toxicological laboratories. This contribution deals with the detection and identification of paroxetine, sertraline, venlafaxine, mirtazapine, tianeptine, risperidone and quetiapine in urine by thin layer chromatography.

[Analysis of bacterial meningitis in the Slovak Republic 1991-1998]. / Analýza bakteriálnych meningitíd v Slovenskej republike za roky 1991-1998.

The authors present the results of analyses of cases of notified bacterial meningitis in Slovakia in 1991-1998, focused on haemophilic meningitis. They demonstrate the ratio of different sources of infection on the development of disease--Haemophilus influenzae 214 cases (13.6%), Streptococcus pneumoniae 183 (11.6%), Neisseria meningitidis 343 (21.8%), other infectious agents 182 (11.5%) and negative cultivations 652 (41.4%). In children aged 0-5 years 668 cases were notified, i.e. 42.4% of the total number (1,574), in other age groups 906 cases, i.e. 57.6%. The mean notified morbidity of haemophil meningitis in 1991-1998 was 0.5/100,000 population. The highest age specific morbidity was in the group of children aged 0-5 years and varied from 2.5/100,000 in 1991 to 7.7/100,000 in 1998.

[Fatty acid composition and parameters of VLDL and LDL in persons with dyslipidemia]. / Slození mastných kyselin a parametry lipoperoxidace VLDL a LDL u osob s dyslipidémií.

BACKGROUND: Oxidatively modified LDL play an important role in the pathogenesis of endothelial dysfunction, initiation and development of atherosclerosis and stability of the atheromatous plaque. The increased oxidative stress is apparent from a number of deviations, which are part of the insulin resistance syndrome (hypertension, hypoalphacholesterolaemia, diabetes and hyperlipoproteinaemia). The objective of the work was to examine the degree of oxidation and oxidability of LDL and VDL in subjects with dyslipidaemia. METHODS AND RESULTS: In 40 subjects with dyslipidaemia, defined as a triglyceride concentration above 2.30 mmol/l and a drop of HDL cholesterol below 0.90 mmol/l, the authors assessed the fatty acid profile in plasma lipid classes and LDL by capillary gas chromatography. Lipoperoxidation in VLDL and LDL was examined by the method of kinetics of conjugated dienes according to Esterbauser. The results were compared with a group of healthy controls. The group of dyslipidaemic subjects had higher concentrations of NEFA, IRI, blood sugar and uric acid. In these subjects the concentration of conjugated dienes in VLDL was significantly higher and the lag stage in VLDL and LDL was reduced. Both groups differed as to the composition of VLDD and LDL. The group of dyslipidaemic subjects had a higher concentration of cholesterol, phospholipids, triglycerides and apolipoprotein B. A constant finding in the fatty acid profile of all lipid classes was a raised concentration of palmitoleic acid and reduced linoleic acid concentration. CONCLUSIONS: Dyslipidaemic subjects have, as compared with a control group, higher NEFA, IRI and uric acid concentrations. Furthermore they differed not only by the composition of VLDL and LDL but also by a higher degree of VLDL oxidation and reduced resistance to lipoperoxidation of VLDL and LDL particles. A consistent finding in the fatty acid profile was an increased level of palmitoleic acid in all plasma lipid classes and LDL and a drop of linoleic acid in phosphatidylcholine LDL and plasma cholesterolesters.