Chronic Low Back Pain: Current Pharmacotherapeutic Therapies and a New Biological Approach.

Chronic low back pain (CLBP) syndrome represents one of the leading causes of long-term disability worldwide. The prevalence of CLBP has been rising significantly in relation to increasing average life expectancy. CLBP results from chronification of acute low back pain. There are many factors contributing to the CLBP crisis; common etiopathogenetic factors include e.g., functional blockage of intervertebral joints. The treatment of CLBP is complex. An important part of treatment consists of pain pharmacotherapy, for which several groups of drugs are used. The problem lies in the side effects of many of these traditionally used medications. Therefore, new and safer treatment methods are being sought. Innovative options for CLBP pharmacology include injections containing collagen, which can be combined with other traditionally used drugs, which helps reduce dosages and increase the overall safety of CLBP therapy.

[A Development and Overview of the Use of Chemotherapy and the Role of Radiotherapy and Surgery in Patients with Newly Diagnosed Pancreatic Tumor and Cancer in the Current 5-year Center Practice]. / Vývoj a prehled vyuzití chemoterapie a role radioterapie a chirurgie u pacientu s nove diagnostikovaným tumorem a karcinomem pankreatu v bezné 5leté praxi centra.

BACKGROUND: Chemotherapy (CHT), surgery and radiotherapy (RT) are essential modalities in the treatment of pancreatic malignancies. Their use in practice may be influenced by a number of factors. PATIENTS AND METHODS: Retrospective analysis of CHT, surgery and RT indications and CHT results in patients reported with pancreatic tumor in Pilsen in 2012-2016. RESULTS: A total of 348 patients with median age 68 (19-89) years with newly diagnosed pancreatic tumor, resp., with histology/cytology verified carcinoma in 74.5% cases, with v. s. carcinoma without verification in 21% and with other malignancy not further analyzed here in 4.5% (mostly neuroendocrine tumor). In patients with generalized malignancy (n = 195), exploratory laparotomy was performed in 23% to get tissue samples or verify staging - palliative anastomoses were done in 25% of operated patients, CHT was performed in 29% of the generalized tumors, palliative RT of tumor was performed in 1 patient, and RT of metastases in 3 patients. In patients with local or regional nodal affection (n = 137) laparotomy was done in 59%, R0 resection in 34 (42%) of 81 operated, R1 in 6%, palliative anastomoses were done in 17% and irreversible electroporation in one patients, CHT or radiochemotherapy after R0 and R1 resections was provided in 61% operated patients. The most commonly used CHT was monotherapy with gemcitabine or FOLFIRINOX. The indication of CHT in cytology/histology verified generalized cancers and with excluding patients refusing CHT was proposed in 2012 to 16%, in 2014 to 49% and in 2016 to 84% of patients. In the case of a local or regional nodal involvement the CHT was proposed to 40, 55 and 86% of patients. Median overall survival in generalized tumor patients receiving CHT (n = 137) vs. not-receiving CHT (n = 56) was 2 vs. 8 months (p = 0.0001), and in the local or regional nodal involvement patients receiving CHT (n = 74) vs. not-receiving CHT (n = 62) was 5 vs. 16 months (p = 0.0001). CONCLUSION: CHT and surgery are the dominant treatment modalities. There has been a marked increase in the CHT and histology/cytology verifications indications, with a major factor being a clinician evaluation of a patient to be fit for CHT and its benefit or to complete pancreatic tumor verification. With still very limited results in pancreatic cancer treatment, a careful assessment of each patients indication, respecting patients desire, is always required, knowing that even in the case of advanced disease, CHT can bring benefit, albeit limited.Key words: pancreas - carcinoma - chemotherapy The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. This study was supported by the grant of Ministry of Health of the Czech Republic - Conceptual Development of Research Organization (Faculty Hospital in Pilsen - FNPl, 00669806).Submitted: 13. 3. 2018Accepted: 18. 4. 2018.

[Everolimus in Daily Clinical Practice Focusing to Oral Mucosa Damage Issues - Single Oncology Centre Experience within the Course of the Year 2016]. / Everolimus v denní klinické praxi se zamerením na problematiku postizení sliznice dutiny ústní - zkusenost onkologického centra v prubehu roku 2016.

BACKGROUND: Oral mucositis, mTOR associated stomatitis, is a major complication in everolimus (EVE) treatment with an incidence of 44-64%. The management of it in the daily practice has not been described enough, so far. PATIENTS AND METHODS: Retrospective analysis of patients treated with EVE in 2016 at our center, n = 42 patients (69% female), median age 66 (37-81) years, breast cancer in 20 (48%) and renal cell carcinoma in 22 (52%), starting EVE dose of 10mg/day in 34 (81%) and 5mg/day in 8 (19%) patients. RESULTS: Discomfort and/or dysgeusia without mucosa defects (grade 1 NCI-CTC) was in 4/34 (12%) patients, mucosal defects without oral intake limitation (grade 2) in 6/34 (17.5%), mucosal defects limiting oral intake (grade 3) in 7/34 (20.5%) patients. ACTIONS TAKEN: in grade 1 EVE dose reduced to 5mg/day in 1/4 affected patients, in grade 2 locally administered dexamethasone solution recommended in 2/6, reduction of EVE to 5mg/day in 4/6 (in two cases the reduced dose left because of complications recurrences), in grade 3 locally administered dexamehasone solution recommended in 5/7, transient reduction of EVE to 5mg/day in 1/7, permanent reduction of EVE in 5/7 (recurrent aphthous lesions), EVE terminated in 1/7. In patients with EVE starting dose of 5mg/day there was one case (1/8, 12.5%) of grade 2 complication requiring no intervention. The complications developed within 2-20 weeks after EVE initiation (median of 8 weeks). CONCLUSION: The incidence of stomatitis and its severity in this cohort is comparable with published trials data, it confirms the significant incidence of damage affecting the quality of life, oral intake and anti-cancer treatment in daily practice. The interventions used in groups of similarly affected patients appears slightly heterogeneous, influenced by individual physician approach. There is tendency not to interrupt the EVE treatment and keep it either in a dosage of 10 or 5mg/day if the oral damage is tolerable. Local treatment with dexamethasone is not yet fully exploited.Key words: everolimus - stomatitis - mucositis - oral cavity Supported by the grant of Ministry of Health of the Czech Republic - Conceptual Development of Research Organization (Faculty Hospital in Pilsen - FNPl, 00669806) and National Sustainability Program I (NPU I) No. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 27. 2. 2017Accepted: 26. 3. 2017.

[Radiotherapy Indications in Patients with Hematological Malignancies During the Five Years Course of Modernized Center of Oncology and Radiotherapy Clinic in Pilsen]. / Indikace radioterapie u pacientu s hematologickými malignitami v prubehu peti let provozu modernizovaného centra Onkologické a radioterapeutické kliniky v Plzni.

Submitted: 27. 2. 2016.

[Correction of kyphotic deformity of the cervical spine in ankylosing spondylitis using pedicle subtraction osteotomy of the seventh cervical vertebra]. / Korekce kyfotické deformity krcní pátere pri ankylozující spondyloartritide pedikl subtrakcní osteotomií sedmého krcního obratle.

PURPOSE OF THE STUDY: The aim of the study is to present the technique of pedicle subtraction osteotomy (PSO) of the seventh cervical vertebra (C7) for correction of rigid kyphotic deformity of the cervicothoracic junction (C/Th) in patients with severe ankylosing spondylitis (AS).. MATERIAL AND METHODS: The PSO technique for correction of rigid deformity of the C/Th spine was used in five patients with the aim to restore their ability of horizontal vision. The follow-up in all patients lasted two years at least. Clinical assessment of treatment results was based on the patients' neurological status and their satisfaction with the correction achieved. Improvement in a vertical 2) line of sight was evaluated using the angle measured between the forehead-chin line and the vertical (FCv angle) in a lateral view photograph of the standing patient. The achieved correction of kyphotic deformity was assessed by comparing the pre-operative Cobb's angle between the second cervical and the fourth thoracic vertebra with the post-operative one. RESULTS: The average operative time was 4 hours (range, 3.5 to 5 h). The average blood loss was 1600 ml (range, 800 to 2100 ml). On the average, the FCv angle was reduced by 45.2° and Cobb's angle was corrected) by 54.6°. All patients were satisfied with the degree of correction achieved and reported alleviation of neck pain. none of the patients showed any significant loss of correction or neurological deterioration at two-year follow-up. DISCUSSION: The theoretical and technical principles of corrective osteotomy at the C7 level performed for rigid kyphotic deformity of the spine at the C/Th junction are presented in our group of patients. Our results give support to the superiority of instrumented PSO used currently over the previous techniques. In accordance with the relevant literature data, attention is drawn to a relatively higher risk of this procedure in comparison with corrective surgery performed at the other spinal levels. CONCLUSIONS: Corrective osteotomy of a rigid kyphotic deformity at the C/Th spine level in AS patients involves a complex reconstructive surgical procedure. The PSO technique reduces the risk of injury to the visceral structures ventral to the spine, and provides optimal conditions for bone healing at the site of vertebral body resection. If the patient heals well, a successful PSO procedure will markedly improve the quality of his/her life.

[Metazosin tablets (Kenosin) in the treatment of chronic congestive heart failure]. / Metazosin tabl. (Kenosin), pri lécbe chronického mestnavého srdecního selhávání.

BACKGROUND: Postsynaptic alpha 1 adrenoceptor blockers are considered suitable drugs for modern vasodilatatory treatment of chronic heart failure. Therefore new analogues of these substances with more favourable characteristics than those of their main representative, prazosin are sought. The objective of the present work was to evaluate the therapeutic effect and tolerance of the original alpha 1-adrenoceptor blocker metazosin developed in the Research Institute for Pharmacy and Biochemistry (VUFB). METHODS AND RESULTS: In a multicentre clinical trial metazosin (tablets à 10 mg), 10-20 mg/day, were added to standard treatment of 56 patients of both sexes suffering from chronic congestive heart failure, for a period of eight weeks. The administration of metazosin led to rapid improvement of subjective complaints (in particular dyspnoea) as well as objective symptoms of peripheral congestion, to a significant (p < 0.05) regression of X-ray signs of pulmonary congestion and a slight (but statistically significant--p < 0.05) increase of the ejection fraction and cardiac output. After two months treatment the functional degree of severity of insufficiency according to the NYHA classification decreased from 2.7 to 2.2. Metazosin did not induce tachycardia and was well tolerated by the patients. CONCLUSIONS: Metazosin (Kenosin) tablets is a suitable supporting drug in the comprehensive treatment of chronic cardiac failure, in particular if refractory to treatment.

[Pharmacology of a new antihypertensive agent, metazosin (Kenosin)]. / Farmakologie nového antihypertenzíva metazosinu (Kenosin).

Metazosin (KENOSIN) displaces 3H-prazosin from its bond to alpha-1 receptors of the cerebral cortex, antagonizes the effects of phenylephrin on spinal rats and on perfused peripheral vascular regions, which demonstrates that it is a blocker of alpha-1 adrenergic receptors. It does not affect the central alpha-2 adrenergic receptors. No peripheral antiserotonin effect was found. Metazosin decreases the blood pressure in normotensive and hypertensive animals. On intravenous administration, the decrease commences very rapidly after the onset of administration. In dogs, systolic and diastolic blood pressure, cardiac output, peripheral resistance and pressure in the pulmonary artery are decreased. In animals with experimentally increased pressure in the lesser circulation it produces a decrease in pressure. On the basis of hypotensively active doses in experimental animals, the administration of 5 mg was proposed as the clinica pose. Results of the 1st stage of clinical trials have demonstrated that this dose is effective in persons with the systolic pressure higher than 120 mm Hg. At present the effect of metazosin is tested on hypertonic patients.

Pharmacokinetics and pharmacodynamics of conventional and controlled-release formulations of metipranolol in man.

The pharmacokinetics and beta-adrenoceptor blocking effects of conventional and sustained-release metipranolol have been studied in 6 healthy male volunteers given a single oral dose of 40 mg. Plasma drug concentrations determined by TLC and a radioreceptor assay, and the inhibition of exercise-induced tachycardia, were monitored for 48 h. Relevant amounts of active metabolites other than deacetylmetipranolol were not found. Compared to conventionally formulated metipranolol, the controlled-release product had a prolonged mean residence time (10.7 vs 5.5 h), the peak drug concentration was halved and the time to peak drug concentrations was delayed. Relatively constant plasma concentrations (cideal = 6.5 ng/ml) and a clinically significant reduction of exercise-induced tachycardia were maintained throughout a 24 h dosing interval. An individual deacetylmetipranolol plasma concentration-effect relationship was evaluated using the Emax model. Mean parameters were Emax 26% and C50 2.9 ng/ml.

Terguride in parkinsonism. A multicenter trial.

Terguride is an ergoline derivative with mixed agonistic/antagonistic dopaminergic activity. This led to a paradoxical suggestion that it is effective in the treatment of both schizophrenia and parkinsonism. A total of 65 in- or outpatients with parkinsonism mostly of vascular or idiopathic etiology were included in a 4-week, open, multicenter trial. Terguride was administered under an increasing dose schedule which was leveled off according to the clinical response. Mostly because of nausea, vomiting, and lack of improvement 25% of inpatients and 61% of outpatients were removed from the study. The average daily dose at the end of the trial was 4.2 mg, ranging from 1.0 to 5.5 mg. The average Simpson and Angus scale total score and performance in the Spiral Drawing Task improved significantly during the trial by 20% and 38% respectively. The following adverse effects were noted most frequently throughout the study (including those who withdrew): constipation (occurred in 42% of all ratings performed during the trial) drowsiness and nausea (16% each). Adverse circulatory effects were negligible. Psychotic symptoms, including depression, confusion, hallucinations, and paranoid syndrome, each occurred in 1 patient, i.e., at a lower rate than with other dopaminergic drugs. Scotopic electroretinograms in a subsample of 7 patients showed a significant transitory decrease in the B-wave amplitude at the end of the 1st week and a subsequent return to pretreatment values.