Current Treatment Possibilities Research Articles

Perinatal hypophosphatasia

Hypophosphatasia, also known as alkaline phosphatase deficiency, is a rare congenital metabolic disorder characterised by early bone and dental defects. First reports on hypophosphatasia date back to 1950s. The prevalence of the disorder in Europe is 1:300,000 births; data on the prevalence in Poland is missing. An abnormal structure of the region coding for the ALPL gene, which is responsible for producing tissue-nonspecific alkaline phosphatase, is the main cause of clinical symptoms. Consequently, there is a significant deficiency in the activity or even absence of this enzyme. Due to the heterogeneous clinical expression of hypophosphatasia, multiple clinical forms of the disorder, which vary in their mode of inheritance and prognosis, have been described, including rare and sporadically reported perinatal forms. There are ongoing studies on the aetiology, diagnosis and treatment of different clinical forms of hypophosphatasia. We present a case report of perinatal hypophosphatasia diagnosed in the Department of Neonatology at the University Clinical Hospital in Wroclaw, with particular focus on the implemented diagnostic-therapeutic process and possible complications in the affected child during the stay in the neonatal intensive care unit. We also performed a literature review to present a wider picture of the disorder belonging to the group of the so-called rare diseases. We described current diagnostic and treatment possibilities in hypophosphatasia, based on the latest clinical trials, as well as the costs of treatment using Strensiq, the only alkaline phosphatase analogue available on the market.

Detergent properties as the basis of the dimexide therapeutic effect in AA-amyloidosis infectious nature (clinical case analysis)

The article discusses the current possibilities of postinfectious AA-amyloidosis treatment with dimexide on the example of clinical observation, discribes in detail the problem of functional amyloid and debates the prospects of the principle of amyloid resorption in the treatment of systemic amyloidosis. The history of the use of dimexide in medical practice is given, thenecessary dataon the pharmacology of dimexide are presented.

Hereditary transthyretin amyloidosis

Hereditary transthyretin amyloidosis is described in this review, including the TTR gene structure and mutation spectrum, the transthyretin protein structure and functions, the main clinical manifestations of transthyretin amyloidosis. Also the problems of differential diagnosis are discussed, the history of the spread of the disease among various ethnic groups is examined, information is provided on the current possibilities of pathogenetic and etiological treatment of the disease.

Merkel cell carcinoma (MCC) – neuroendocrine skin cancer

Merkel cell carcinoma (MCC) is a rarely occurring skin cancer of high malignancy. It develops, most probably, from the neuroendocrine cells (Merkel’s cells). The most frequent location of this cancer is the skin of the head and neck (44–48% of cases), and then in the skin of the upper limbs (about 19% of cases) and then the lower limbs (16–20% of cases). The aetiology of this cancer is unknown, yet some role in its pathogenesis is played by ultraviolet light and immunosuppression. The basis of therapy in cases with locoregional spread is surgical intervention, whilst in more advanced cases, an effective systemic treatment is possible with the use of molecularly targeted therapies. This paper presents the current treatment possibilities in patients with Merkel cell carcinoma.

Novos Avanços no Tratamento da Onicomicose

O tratamento da micose do aparelho ungueal permanece um desafio nos dias de hoje. O foco infecioso encontra-se retido numa estrutura anatómica específica onde não se consegue por vezes uma resolução permanente, o que significa que a onicomicose se torna frequentemente uma condição crónica que retoma o estado ativo no intervalo de vários anos. A prioridade nos recentes desenvolvimentos da farmacoterapia da onicomicose foi atribuída à monoterapia tópica com o intuito da sua utilização em doentes que não toleram a medicação oral ou preferem um fármaco tópico e, com a vantagem adicional, de combiná-los com fármacos orais e/ou dispositivos médicos para expandir as possibilidades de tratamento atuais. Esta revisão engloba as opções terapêuticas da onicomicose no status quo. Dois novos fármacos tópicos, efinaconazol e tavaborol, foram aprovados no ano 2014 pela entidade reguladora competente Food and Drug Administration (FDA).

Current Possibilities of Gynecologic Cancer Treatment with the Use of Immune Checkpoint Inhibitors.

Despite the ongoing progress in cancer research, the global cancer burden has increased to 18.1 million new cases and 9.6 million deaths in 2018. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, considerably contribute to global cancer burden, leading to $5,862.6, $2,945.7, and $1,543.9 million of annual costs of cancer care, respectively. Thus, the development of effective therapies against gynecological cancers is still a largely unmet medical need. One of the novel therapeutic approaches is to induce anti-cancer immunity by the inhibition of the immune checkpoint pathways using monoclonal antibodies. The molecular targets for monoclonal antibodies are cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1). The rationale for the use of immune checkpoint inhibitors in patients with gynecological cancers was based on the immunohistological studies showing high expression levels of PD-1 and PD-L1 in those cancers. Currently available immune checkpoint inhibitors include nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab. The efficacy and safety of these inhibitors, used as monotherapy and with combination with chemotherapy, is being currently evaluated in several clinical studies. As the results are promising, more clinical trials are being planned, which may lead to the development of efficient therapies for gynecological cancer patients.

Current possibilities of complex diagnosis and treatment of the consequences of traumatic brain injury

Article is devoted to topical issues of complex diagnosis and treatment of the consequences of traumatic brain injury (TBI) in children, adolescents and adults. Craniocerebral trauma is one of the most important problems of modern neurology, due to the high frequency and severity of disability. In recent years, there has been a steady increase in effects of TBI, a significant part of which are asthenic, autonomic, cognitive, emotional and motor disorders. Factors affecting the severity of the consequences of TBI are: the severity of the injury, the age, at which the injury occurred, the time elapsed since the injury, the localization of the lesion. After mild TBI, the structure of cognitive impairment is dominated by memory and attention disorders (75%), visual-motor coordination, as well as asthenic disorders (88%), chronic headaches (95%). After moderate and severe TBI, there are more pronounced impairment of cognitive and motor functions accompanied by pathological neurological symptoms in 94-100% of children, which leads to difficulties in learning, self-service and has a negative impact on social adaptation. The article describes in detail the modern methods of complex diagnosis, as well as pathogenetically justified methods of drug therapy of cognitive disorders in patients with the consequences of TBI. The high efficacy of the modern cytoprotective drug Cytoflavin in the treatment of the effects of TBI is shown.

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.

Cognitive impairment in patients with metabolic syndrome. The current treatment possibilities

To study the effect of therapy with cytoflavin on cognitive function in patients with metabolic syndrome (MS). The randomized controlled open study included 156 patients with MS. The mean age was 41.27±5.16 years. The duration of observation was 16 weeks. The main group of patients (n=78) received cytoflavin in the dose of 2 tablets 2 times a day. Patients in the control group (n=78) received basic therapy. All patients underwent neuropsychological testing at baseline, after 2 months and at the end of the study. Cognitive evoked potentials (Р300) were recorded to assess cognitive functions. The levels of plasma glucose and lipid profile were measured. Cytoflavin improved cognitive functions. Two months after treatment, the results of neuropsychological testing and electrophysiological study were better in the main group compared to the control group.

Current possibilities of diagnosis and combined treatment in patients with locally advanced nasopharyngeal carcinoma

Current possibilities of diagnosis and combined treatment in patients with locally advanced nasopharyngeal carcinoma

Enthesitis: from pathophysiology to treatment

Entheses are the insertion sites of tendons and ligaments to the bone surface and are essential structures for locomotion. Inflammation of the entheses (enthesitis) is a key feature of psoriatic arthritis and spondyloarthritis. To date, our conceptual understanding of enthesitis remains limited. This Review provides an insight into the pathophysiology of enthesitis, addressing the role of biomechanics, prostaglandin E2-mediated vasodilation and the activation of innate immune cells in the initiation phase of enthesitis, as well as the role of entheseal IL-23-responsive cells that augment inflammation by producing pro-inflammatory mediators such as IL-17A, IL-22 and TNF. In addition, the molecular steps that translate inflammation into resident tissue responses, resulting in new bone formation, are discussed. The second part of the article summarizes the clinical features of enthesitis, and the role of clinical and imaging instruments in detecting enthesitis are discussed together with their challenges and limitations. Finally, the Review summarizes the current treatment possibilities for enthesitis based on the aforementioned pathophysiological concepts, focusing on the role of cytokine-blocking agents.

Treatment Possibilities for Psychosis in Parkinson's Disease with An Emphasis on the Newly Approved Drug: Pimavanserin.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with prominent motor and non-motor symptoms. Psychosis develops in over 40% of PD patients and it is one of the most distressing symptoms for patients and caregivers alike. Until recently, atypical antipsychotics, clozapine and quetiapine were used to treat psychotic symptoms, but treatment was associated with substantial concerns for side-effects of clozapine and unfounded efficacy for quetiapine. Extensive research has shown that the antipsychotic effect of these drugs could be attributed to serotonin 2a receptor (5-HT2A) triggered mechanisms. A selective 5-HT2A inverse agonist, pimavanserin, has been developed, investigated and has gained approval in April 2016 in the US for the treatment of hallucinations and delusions in PD. In this review we primarily focus on psychosis in PD, the current treatment possibilities and the new, emerging therapy, pimavanserin, a selective 5-HT2A inverse agonist. All articles were reviewed in this topic and indexed in PubMed with keywords: Parkinson's disease psychosis, serotonin 2a receptor inverse agonist, clozapine, quetiapine, pimavanserin.

Breast sarcomas. A review of the possible treatment modalities

Background. Breast sarcomas (BS) are rare tumors which origin within the connective tissue of the breast. A clear delimitation from breast carcinoma should be established because the management and evolution and prognosis are different. BS can develop “de novo” – primary BS or can be related to a previously treated malignant breast tumor – for example after breast conservative surgery and adjuvant radiotherapy. Aim. Owing to the rarity of this tumor type, there is limited evidence with regard to the optimal treatment possibilities. The information comes primary from small retrospective studies so that the treatment principles resemble that of primary mesenchymal malignancies arising in other parts of the body (e.g. leiomyosarcoma, angiosarcoma or liposarcoma). We aimed to make a review of the current treatment possibilities of the BS emphasizing on the type and extent of the surgical treatment, the utility of the axillary lymph node (LN) dissection and the feasibility and benefit of an adjuvant chemotherapy. Method. We performed an online research on Pubmed using the following key words: “sarcoma”, “radiotherapy”, “surgery”, “chemotherapy”. We tried to select the data referring to sarcoma developing with the connective tissue of the breast as well as the information of BS developing after irradiation of the breast in women previously diagnosed with breast cancer (BC) who received adjuvant radiotherapy. We further looked for reports about the role of an adjuvant treatment, namely chemotherapy. Conclusion. The only treatment proved to have a benefit on the prognosis is the surgical treatment with the achievement of a wide, radical, complete resection (R0-resection). For angiosarcomas, either primary or therapy-related, the margins of resection should be more than 1 cm for small tumors and more than 3 cm for larger tumors. Adjuvant chemotherapy has limited benefits and should be applied in selected cases.

Homeopathy and allergology – from the beginnings until today

Exploration of the homeopathic literature regarding description and treatment of allergies with a comparison to the current treatment strategies and possibilities.

Некоторые сведения о распространенности и современных возможностях лечения весеннего кератоконъюнктивита

Некоторые сведения о распространенности и современных возможностях лечения весеннего кератоконъюнктивита

Smartphones, Research and Development and Corporation Tax: Current Treatment and Future Possibilities

The object of this article is to summarize the parts of UK corporation tax law relevant to businesses that contribute to the research and development (R&D) of smartphones, and to propose future improvements. From 1 July 2016, English statute concerning the UK Patent Box regime mirrors the existing or expected requirements of all European Union (EU) Member States Patent Box laws and Organisation for Economic Co-operation and Development (OECD) standards, so the legal analysis is relevant to many other jurisdictions. The article then proposes some future corporation tax law enhancements relevant to lawmakers globally. These proposals require imagination, and aim to simultaneously encourage more R&D investment by businesses and increase the total long-term amount of corporate tax raised.

Neurological presentations of bacterial meningitis in children: current possibilities of diagnosis and treatment

To improve clinical/laboratory diagnosis of bacterial meningitis (BM) in children. Fifty-seven patients, aged from 4 months to 12 years, with BM were examined. Bacteriological study of the mucus from the nasopharynx, sterility tests of blood and cerebrospinal fluid (CNF), clinical and biochemical tests, serological study of paired samples of plasma - indirect hemagglutination test, latex agglutination assay, immunological study of plasma and CNF with the determination of interferon -α, -β and -γ, interferon procalcitonin and neopterin with ELISA were performed at admission and after CNF remediation. Molecular-genetic study of the blood serum and CNF using PCR, neurosonography, computed tomography and MRI of the brain were done as well. Most of the patients had generalized meningococcus infection (64,9%). Hib-meningitis, pneumococcus meningitis and other forms were less frequent. Characteristics of neurological presentations of BM depending on the etiology, somatic complications and time from the manifestation of symptoms were described. Clinical/biochemical criteria of BM and correlations between procalcitonin, neopterin and interleukin-8 in the CNF and blood of the patients and disease severity as well as between the level of inflammatory reactions in the CNF and the BM form were established. These results are important for the development of informative biomarkers for the prognosis of BM course and outcome.

THE SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI) AS TREATMENT OF DEPRESSION IN PATIENTS WITH EPILEPSY

The current possibilities of treatment of depression in epilepsy were represented. Depression is one of the most frequent psychiatric comorbidities in epilepsy. The prevalence of depression ranges from 10 to 80%, and most often found in patients with focal epilepsy resistant to antiepileptic therapy. Depression in patients with epilepsy are not often diagnosed and therefore not treated. A number of common epilepsy and depression pathogenetic mechanisms, such as impaired metabolism of certain neurotransmitters in the central nervous system, especially serotonin was descripted. Based on this, the most promising drugs in the treatment of depression in epilepsy are now the selective serotonin reuptake inhibitor (SSRI), such as escitalopram. Objective. The primary objectives were to evaluate the efficacy and safety of escitalopram in treating depressive symptoms. Materials and methods. The study involved 68 patients aged 19-69 years with cryptogenic and focal epilepsy and different disease duration (from 5 to 21 years), different types of seizures and suffering depression interictal (between 2 and 5.5 years). Depression Rating Scale of Montgomery-Asberg (MADRS) was used. To assess the severity of the patient ’s condition at the time of the survey, a global assessment of disease severity (CGI-S) and the global assessment of the mental state (CGI-I) were used. While taking escitalopram (10-20 mg per day.), all patients received basic anticonvulsant therapy. Results. During follow-up the patients with epilepsy who took escitalopram, proconvulsant effect were not denoted. In assessing depressive symptoms improved markedly. Against the background of escitalopram no deterioration was marked, no sedation, addiction to the drug was observed, minimum drug interactions with anticonvulsants was registered. Conclusion. The results described observation program suggests a safe and effective treatment of escitalopram epilepsy patients with depression, it is well tolerated, low drugdrug interactions, as well as improve the quality of life of patients.

Current Possibilities of Treatment in Pelvic-Perineal Floor Dysfunctions

To support through personal experience the use on a large scale of the modern techniques of correction of the pelvic floor disorders by using polypropylene prosthetic devices. Objectives: To specify the technical details regarding the correct placement of prostheses in feminine genital prolapse. Show the personal casuistry in order to highlight the indications techniques and results of these types of surgeries. Plead for expending the modern techniques in pelvic-perineal floor dysfunctions. Material and Methods: The study was performed between July 2007 and July 2013, in the second surgical Clinic St.Spiridon Hospital Iasi, on 138 cases with different pelvic floor dysfunctions. Different procedures were practiced, isolated or associated, on the patients in the lot, depending on symptoms, the prolapse type and degree, age, local anatomical situation and the existence or absence of sexual life. Thus they were performed: strip urethrocystopexy or “hammock” device, with four arms transobturator - 68 cases; The sacrosciatic posterior colposuspension or the anal levator floor restoration–29 cases; abdominal colpopexy in 41 cases, 18 of which with hysterectomy or resection of residual cervix. In 5 cases a polypropylene mesh implant has been associated with this procedure at anal levator level; and in 11 cases the doctors used a suburethral transobturator vaginal strip for stress urinary incontinence (SUI). The abdominal approach allows the correct path of skeletonization of the internal genitalia and also of the vagina which is turned inside-out like a glove finger, avoiding damage on the ureters and bladder. The vaginal vault is secured to the promontory with a polypropylene device and it ensures the results maintain in time. Results: The treatment of the different pelvic-perineal floor disorders that are associated or not with stress urinary incontinence has benefited lately from new indications and techniques by using different prosthetic devices made of polypropylene, which are especially conceived and placed through minimally invasive procedures. Generally, all the cases had an immediate simple postoperatory evolution with only two haematomas that required surgical evacuation and 3 cases of vaginal mucosa necrosis, one of them requiring the removal of the device implanted. The anatomical and functional results were good. Conclusions: The use of strips, nets and polypropylene devices in correcting different pelvic floor disorders, shows certain advantages, as it is relatively easy tom implement, the hospitalization period is shortened and there are very good results that pass the test of time.

Current possibilities of treatment of generalized convulsive seizures

Current possibilities of treatment of generalized convulsive seizures are presented. Progress in the field of pharmacotherapy of epilepsy allowed to introduce new antiepileptic drugs (AED). Some of them are modified AED with higher efficacy or better tolerability and others represent a generation of new drugs with different mechanisms of action. Perampanel, an agonist of AMPA-receptors, is a new drug approved in more than 40 countries, including Russia. At present, the use of some AED is limited by the high risk of sudden death (sudden unexpected death in epilepsy (SUDEP)). SUDEP is a common cause of death directly associated with epilepsy, with the highest frequency in patients with active epilepsy. Subtherapeutic concentrations of SED in the serum of SUDEP patients may be the consequence of inadequate treatment and low compliance to treatment that causes the development of pseudoresistant seizures and, hence, the higher risk of SUDEP. At the same time, AED per se play an important role in the modification of functions of the autonomic nervous system and may induce disturbances of heart rate and conductivity.