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1.
Adv Physiol Educ ; 48(3): 639-647, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38932698

ABSTRACT

Science communication is a core skill for undergraduate science students to acquire in preparation for their future careers, but studies show that this skill is underdeveloped in science graduates. The aim of this study was to discover the resources and approaches undergraduate students use to effectively develop their science communication skills and how the use of these methods relates to academic performance on a communication task. Undergraduate students undertaking a second-year biomedical science course (n = 490) were asked which approaches and resources they used to aid the development of their science communication skills, and the frequency of their responses was correlated against their laboratory report mark, using multiple regression and relative weights analysis. Students' (n = 453) use of Communication Learning in Practice for Scientists (CLIPS; an open-access interactive website on science communication), resources provided by the university, interactions with university teaching staff, and engagement with the scientific literature significantly predicted the laboratory report mark. Students enrolled in a blended format or in remote online learning only, and in different programs, performed comparably in the written report and used similar approaches and resources, other than remote students reporting more use of other online resources and students in blended learning engaging more with university resources. Together, these findings provide insight into which strategies are most helpful for undergraduate students to engage with to improve their scientific communication skills. The findings highlight that the provision of well-designed interactive communication resources, guided assessment resources, and opportunities to engage with teaching staff can assist in the development of science communication skills.NEW & NOTEWORTHY This study identifies the approaches and resources that undergraduate science students use to develop their science communication skills. It reveals which of these approaches and resources predict improved academic performance in a written science communication assessment task. The findings point to the importance of explicit guidance, and engagement with teaching staff, in advancing the development of science communication skills.


Subject(s)
Communication , Students , Humans , Female , Male , Students/psychology , Universities , Young Adult , Science/education , Curriculum
2.
J Clin Monit Comput ; 36(3): 871-877, 2022 06.
Article in English | MEDLINE | ID: mdl-33991270

ABSTRACT

Patients with acute kidney injury who need continuous renal replacement therapy with locoregional citrate anticoagulation are at risk of citrate accumulation with disruption of the calcium balance. We aimed to evaluate the safety of detecting citrate accumulation and adjusting electrolyte disbalances during continuous venovenous hemodialysis (CVVHD) in critically ill patients with acute kidney injury using a blood sample frequency every 6 h. A prospective single center study in critically ill intensive care unit patients who suffered from acute kidney injury with the need of renal replacement therapy. We evaluated the deviations in pH, bicarbonate and calcium during CVVHD treatment with local regional citrate anticoagulation. Values indicate median and interquartile range. Severe hypocalcemia (below 1.04 mmol/L) or hypercalcemia (above 1.31 mmol/L) occurred in 10.5% and 4.8% respectively. During treatment changes of systemic ionized calcium, post-filter ionized calcium, pH and bicarbonate were corrected with protocolized adjustments. No arrhythmias or citrate accumulation were seen. The values stabilized after 42 h and after that no statistically significant changes were observed. After 42 h of citrate CVVHD, systemic ionized calcium, pH and bicarbonate levels stabilized. A blood sample frequency every 6 h is probably safe to detect citrate accumulation and to adjust the settings of electrolytes to avoid serious electrolyte disturbances in ICU patients without severe metabolic acidosis or severe liver failure.


Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Anticoagulants/therapeutic use , Bicarbonates , Calcium , Citrates , Citric Acid , Critical Illness , Electrolytes , Humans , Prospective Studies , Renal Dialysis , Renal Replacement Therapy
3.
Neoplasma ; 64(5): 762-769, 2017.
Article in English | MEDLINE | ID: mdl-28592129

ABSTRACT

Presented are updated results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 25 adult patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) after a reduced intensity conditioning (RIC) combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg or recently 4.0 mg/kg) followed by early initiation of reduction and withdrawal of prophylactic posttransplant immunosuppression. The median post-transplant follow-up was 32 (range, 4-87) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute graft versus host disease (GVHD) as well as the chronic one were equally observed in four cases (16%). Five patients (20%) relapsed with ALL in the median of 9 (range, 3-15) months after HSCT. During the above post-transplant follow-up, 4 recipients (16%) died. Disease progression and posttransplant complications were the cause of death in three (12%) and one (4%) of them, respectively. The probabilities of 2-year event-free (EFS) and overall survival (OS) were 70.3% (95% CI 51.9-88.7%) and 86.1% (95% CI 71.6-100%), respectively. Presented study confirmed our previously reported promising results and this approach may be considered as an alternative to traditional HSCTs performed in high-risk patients with ALL.


Subject(s)
Antilymphocyte Serum/therapeutic use , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Melphalan/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Vidarabine/analogs & derivatives , Adult , Humans , Immunosuppressive Agents , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome , Vidarabine/therapeutic use
4.
Neoplasma ; 62(1): 146-51, 2015.
Article in English | MEDLINE | ID: mdl-25563379

ABSTRACT

UNLABELLED: Acute promyelocytic leukemia is a unique entity among acute leukemias. Introduction of all-trans retinoic acid and, subsequently, arsenic trioxide in its treatment has markedly improved treatment outcomes for this once frequently fatal disease. Improved outcomes have also been observed in elderly patients, including those in whom standard intensive therapy is contraindicated because of comorbidities.In our center, a total of 60 APL patients were treated in 1993-2013, of whom 9 were aged 60 or more years. Although most of them had significant comorbidities at the time of diagnosis, eight achieved complete remission. At the time of the analysis, six patients were alive and in long-term remission; two patients died of causes other than APL. The median follow-up was 59 months.Included is case report of a patient with a high comorbidity score whose treatment was markedly reduced and individualized.Our experience shows that, in APL patients a curative approach is generally tolerated and should always be attempted regardless of age and comorbidities. KEYWORDS: APL - elderly patients - comorbidity.

5.
Neoplasma ; 62(5): 805-11, 2015.
Article in English | MEDLINE | ID: mdl-26278139

ABSTRACT

Presented are results of allogeneic hematopoietic stem cell transplantations (HSCTs) in 13 patients with high-risk acute lymphoblastic leukemia (ALL) in the first complete remission after a reduced intensity conditioning combining fludarabine (150 mg/m2) and melphalan (140 mg/m2) with thymoglobulin (4.5 mg/kg). The immunosuppressive effect of T-cell depletion reducing the risk of graft-versus-host disease (GVHD) and non-relapse mortality was compensated by early initiation of reduction and withdrawal of prophylactic immunosuppression aimed at maintaining effective immunological antileukemic control. The median post-transplant follow-up was 23 (range, 10-65) months. Stable engraftment of donor's hematopoiesis was achieved in all patients. Acute GVHD was observed in two cases (15.4%); the chronic form was not noted. Two patients (15.4%) relapsed with ALL at 3 and 16 months after transplantation. During the above post-transplant follow-up, all 13 recipients were alive, with a probability of 2-year disease-free survival of 76.9% (95% CI 51-100%). Although the results were obtained with a small pilot study group it may be assumed that, given the prognostic risk of most patients and the nearly 2-year median post-transplant follow-up, the approach may be considered as an alternative to HSCTs after traditional myeloablative or reduced conditioning regimens with standard GVHD prophylaxis.

6.
Unfallchirurg ; 115(12): 1123-5, 2012 Dec.
Article in German | MEDLINE | ID: mdl-23052701

ABSTRACT

The aim of this article was to raise the awareness of the difficulties physicians face in the diagnosis and treatment of esophageal perforation following blunt thoracic trauma. We present a case of esophagus perforation following blunt chest trauma in the course of a motorcycle accident. Within 24 h the patient was admitted to the University hospital, and presented with progressive pain, subfebrile temperature, leukocytosis and pneumomediastinum. Emergency surgery revealed extensive esophageal lesions. A two-stage surgical approach was chosen with initial resection and temporary closure of the esophagus. After 2 months the integrity of the esophagus could be restored without complications.


Subject(s)
Esophagus/injuries , Esophagus/surgery , Thoracic Injuries/complications , Thoracic Injuries/surgery , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/surgery , Adolescent , Esophagus/diagnostic imaging , Humans , Male , Radiography , Thoracic Injuries/diagnostic imaging , Treatment Outcome , Wounds, Nonpenetrating/diagnostic imaging
7.
Zentralbl Chir ; 137(5): 430-5, 2012 Oct.
Article in German | MEDLINE | ID: mdl-23136103

ABSTRACT

INTRODUCTION: True aneurysms of the deep femoral artery (APFA) are rare and are usually presented as case reports. Recommendations for diagnostics and therapy of APFAs are based on low-level evidence only. The purpose of this paper was to summarise the existing world experience with APFA. MATERIAL/METHODS: On the occasion of our own case a systematic review of the literature was performed for diagnostics and therapy for true APFA. Publications retrieved from PubMed, EMBASE, and the Cochrane Collaboration as well as by hand search from their references were reviewed. RESULTS: From 2002 onwards 25 papers on true APFAs were published in the English and German literature. Apart from two retrospective studies over a longer period of time these were exclusively case reports. A total of 55 true APFAs were reported in 47 patients with a mean age of 63 years. Therapeutic intervention was due to a rupture in 10 cases (18 %). The mean maximal diameter of APFA at presentation was 5.4 cm (2-18 cm). APFAs that were not ruptured presented frequently as a painful pulsatile mass in the groin and thigh. Therapeutic options for APFA included, apart from surgical resection with or without reconstruction of the deep femoral artery, the endovascular repair. DISCUSSION: Symptoms of swelling and pain in the presence of a mass at the proximal thigh should raise the suspicion of an APFA. Surgical therapy should be performed electively in APFAs with a diameter of more than 2 cm or in cases of rapid progression as well as in all symptomatic or ruptured cases. The endovascular approach should be considered as an alternative option in all cases.


Subject(s)
Aneurysm/surgery , Femoral Artery/surgery , Aged , Aged, 80 and over , Aneurysm/diagnosis , Aneurysm, Ruptured/surgery , Angioplasty/methods , Blood Vessel Prosthesis , Child , Diagnostic Imaging , Embolization, Therapeutic/methods , Humans , Leg/blood supply , Middle Aged , Prosthesis Design , Retrospective Studies , Sensitivity and Specificity , Stents
8.
Neuron ; 56(4): 621-39, 2007 Nov 21.
Article in English | MEDLINE | ID: mdl-18031681

ABSTRACT

Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (sez-6) null mutant mice, that Sez-6 is required for normal dendritic arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity.


Subject(s)
Cerebral Cortex/abnormalities , Cerebral Cortex/cytology , Dendrites/ultrastructure , Gene Expression Regulation, Developmental/genetics , Nerve Tissue Proteins/genetics , Pyramidal Cells/cytology , Animals , Cell Differentiation/genetics , Cell Membrane/genetics , Cell Membrane/metabolism , Cells, Cultured , Cerebral Cortex/metabolism , Cognition Disorders/genetics , Cognition Disorders/metabolism , Cognition Disorders/physiopathology , Dendrites/metabolism , Dendritic Spines/metabolism , Dendritic Spines/ultrastructure , Disks Large Homolog 4 Protein , Excitatory Postsynaptic Potentials/genetics , Female , Guanylate Kinases , Intracellular Signaling Peptides and Proteins/metabolism , Male , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Nervous System Malformations/genetics , Nervous System Malformations/metabolism , Nervous System Malformations/physiopathology , Neural Pathways/abnormalities , Neural Pathways/cytology , Neural Pathways/metabolism , Organ Culture Techniques , Patch-Clamp Techniques , Pyramidal Cells/metabolism , Synaptic Transmission/genetics
9.
Neoplasma ; 58(3): 263-70, 2011.
Article in English | MEDLINE | ID: mdl-21395368

ABSTRACT

Antibody (rituximab) dependent cellular cytotoxicity is a key mechanism in killing CD20+ lymphoma cells. FcγRIIIA-158 V/F gene polymorphism results in expression of 3 variants of the FcγRIIIA receptor (FcγRIIIA) on cytotoxic lymphocytes with different receptor affinity. We studied 102 patients with newly diagnosed FL to assess whether the FcγRIIIA genotype influences outcome in patients treated with risk-adapted immunochemotherapy. The median age was 52 years (31-84); 90% of the patients had advanced (III/IV) clinical stages. The Follicular Lymphoma International Prognostic Index (FLIPI) scores were as follows: low 18.9%, intermediate 33.7% and high 47.4%. The front-line treatment was stratified according to the commonly used risk factors (FLIPI, beta-2-microglobuline and serum-Tyrosine-Kinase levels, bulky disease) into 3 treatment groups: (1) patients with FLIPI 0-1 treated with (R)-CHOP (51%), (2) patients under 60 (65) years of age with intermediate-risk disease (FLIPI 2) indicated for an intensive protocol (ProMACE-CytaBOM or sequential chemotherapy) (21%), and (3) patients under 60 (65) years with high-risk disease (FLIPI ≥3) treated with intensive chemotherapy plus autologous stem cell transplantation (28%). Rituximab was added to front-line chemotherapy in 59% of the patients. Generally, complete remission (CR) or unconfirmed CR was achieved in 85% of the patients, 11% had partial remission and 4% stable disease. Molecular CR (CRm) was achieved in 67.4% of 86 evaluable patients. Overall survival (OS) at 5 years reached 84% (95% CI 0.74-0.93); event-free survival (EFS) at 5 years was 58% (95% CI 0.45-0.71). The frequencies of FcγRIIIA-158 gene polymorphisms V/V, V/F and F/F were 8%, 50% and 42%, respectively. The FLIPI score distribution was not different in F/F patients as compared to V/F+V/V carriers (chi-square, P=0.7). The treatment modalities (treatment arm or rituximab administration) had the same distribution in V/V+V/F vs F/F patients (chi-square, P=0.16 and P=0.62, respectively). The CRm rates were similar in both subgroups of V/V+V/F vs F/F patients (chi-square, P=0.92). Survival curves for OS and EFS were not significantly different when comparing the subgroups of V/V+V/F vs F/F patients (P=0.28 and P=0.57, respectively). We found no difference in the quality of treatment response or survival after front-line immunochemotherapy between FcγRIIIA subgroups. FcγRIIIA polymorphism have no influence on the outcome of patients treated with risk-adapted chemotherapy with or without rituximab.


Subject(s)
Lymphoma, Follicular/therapy , Receptors, IgG/genetics , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Genotype , Hematopoietic Stem Cell Transplantation , Humans , Lymphoma, Follicular/genetics , Lymphoma, Follicular/mortality , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
10.
Neoplasma ; 58(3): 256-62, 2011.
Article in English | MEDLINE | ID: mdl-21395367

ABSTRACT

Tyrosine kinase inhibitors (TKI) have completely changed the prognosis of patients with Ph+ chronic myeloid leukemia (CML). The occurrence of a second malignancy (SM) in CML patients successfully treated with TKI may significantly affect their prognosis. In a retrospective study of 1,038 patients with CML treated at 10 centers in the Czech Republic and Slovakia between 2000 and 2009, SM was detected in 35 (3.37%) patients after TKI therapy was initiated. The median intervals from the diagnosis of CML and from the start of TKI therapy to the diagnosis of SM were 58 months (range 2 - 214) and 32 months (range 1 - 102), respectively. The observed age-standardized incidence of SM after the start of TKI therapy was 8.95 / 1,000 person-years. Comparison of the incidence of SM in CML patients with population data was performed only for patients from the Czech Republic. The age-standardized incidence rate of all malignant tumors except non-melanoma skin cancers was 6.76 (95% CI: 6.74; 6.78) / 1,000 person-years in 2000 - 2007 while the incidence rate of SM in 708 CML patients from the Czech Republic treated with TKI was 9.84 (95% CI: 6.20; 13.48) / 1,000 person-years, i.e. 1.5-fold higher, although the difference was statistically insignificant. The distribution of SM types in CML patients treated with TKI was similar to that in the age-standardized general Czech population. The median overall survival (OS) of patients treated with TKI who also developed SM (57 months) was shorter than the OS of patients treated with TKI but not suffering from SM (median OS not reached, log rank test p < 0.001. Prospective long-term population-based studies in CML patients treated with TKI as first-line therapy are needed to determine the relationship of SM to KTI therapy.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Neoplasms, Second Primary/epidemiology , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Adolescent , Adult , Aged , Aged, 80 and over , Czech Republic/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Slovakia/epidemiology
11.
Klin Onkol ; 34(2): 153-162, 2021.
Article in English | MEDLINE | ID: mdl-33906365

ABSTRACT

BACKGROUND: Oral cavity injuries are very significant complications in the treatment of oncological and hemato-oncological patients. Preventive and curative interventions and patient education reduce the risk of complications and their consequences. A working group of authors from professional groups prepared recommendations for care. PURPOSE: A basic summary of recommended interventions to prevent and treat oral cavity injuries in daily practice, defined on the basis of expert societies guidelines, trials, literature data and proven practice and on the consensus opinions of the authors group members. RESULTS: Preventive measures and patient education are essential in the approach to dealing with oral injuries in chemotherapy, radiotherapy, risky targeted treatment and osteonecrosis of the jaw. Local care products are an important element of care, in case of infections, their antimicrobial action is essential, in case of graft-versus-host disease or in connection with targeted oncological therapy, corticoids are used. CONCLUSION: The recommended procedures contribute to the reduction of the development, severity and consequences of oral complications in oncological and hemato-oncological patients.


Subject(s)
Mouth Diseases/therapy , Neoplasms/therapy , Humans , Mouth Diseases/etiology , Patient Education as Topic
12.
J Physiol ; 588(Pt 8): 1281-92, 2010 Apr 15.
Article in English | MEDLINE | ID: mdl-20194128

ABSTRACT

Synaptic activity in the medial prefrontal cortex (mPFC) is fundamental for higher cognitive functions such as working memory. The present study shows that small conductance (SK) calcium-activated potassium channels attenuate excitatory synaptic transmission at layer 2/3 and layer 5 inputs to layer 5 pyramidal neurons in the mPFC. SK channels are located postsynaptically at synapses where they are activated during synaptic transmission by calcium influx through NMDA receptors, L-type calcium channels, R-type calcium channels and by calcium release from IP(3)-sensitive stores. Removal of the SK channel-mediated shunt of synaptic transmission reveals significant NMDA receptor-mediated activation during basal synaptic transmission, which is greater at layer 5 inputs (approximately 30%) than at layer 2/3 inputs (approximately 20%). These findings show that interactions between NMDA receptors, SK channels and voltage-gated calcium channels play a critical role in regulating excitatory synaptic transmission in layer 5 pyramidal neurons in the mPFC.


Subject(s)
Potassium Channels, Voltage-Gated/physiology , Prefrontal Cortex/physiology , Receptors, N-Methyl-D-Aspartate/physiology , Small-Conductance Calcium-Activated Potassium Channels/physiology , Synapses/physiology , Animals , Calcium/metabolism , Calcium Channels, L-Type/physiology , Calcium Channels, R-Type/physiology , Cell Communication , Female , Male , Models, Animal , Pyramidal Cells/cytology , Pyramidal Cells/physiology , Rats , Rats, Wistar , Synaptic Transmission/physiology
13.
Neoplasma ; 57(4): 355-9, 2010.
Article in English | MEDLINE | ID: mdl-20429627

ABSTRACT

Dasatinib is effective second line treatment for patients with chronic myeloid leukemia (CML) resistant or intolerant to imatinib. We report here the first experiences with dasatinib therapy in 71 CML patients resistant or intolerant to imatinib from the real clinical practice of 6 hematological centers in the Czech Republic. Dose 100 mg daily and 70 mg twice daily was administered to patients with chronic phase (CP) and advanced phases (AP) CML. In chronic phase (n=46), complete hematological reponse (CHR) was achieved in 97%, major cytogenetic reponse (MCgR) in 77% and complete cytogenetic response (CCgR) in 67%. Major molecular reponse (MMR) was achieved in 19/31 patients in median of 10 months. In advanced phase (n=25), CHR was attained in 77%, MCgR in 39%, CCgR in 33% and MMR in 2/18 patients. Eleven different baseline mutations were followed up in 15 patients. Dasatinib eliminated mutations in most of the patients, but 3 patients acquired a new one. Novel mutations were detected under dasatinib therapy in 2 patients. Dasatinib was well tolerated, cytopenias were common and was managed by dose modification. The estimated progression free survival (PFS) at 12 months was 97+/-3% in CP and 62+/-21% in AP. The median time to treatment failure was 605 days in AP while it was not reached in CP patients. Our clinical experiences, described here, confirmed that dasatinib is associated with high response rates especially in imatinib resistant or intolerant CML patients in chronic phase.


Subject(s)
Antineoplastic Agents/therapeutic use , Drug Resistance, Neoplasm , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Salvage Therapy , Thiazoles/therapeutic use , Adult , Aged , Benzamides , Dasatinib , Female , Fusion Proteins, bcr-abl/genetics , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Mutation/genetics , Protein-Tyrosine Kinases/antagonists & inhibitors , Survival Rate , Treatment Outcome , Young Adult
14.
J Neurosci ; 28(43): 10803-13, 2008 Oct 22.
Article in English | MEDLINE | ID: mdl-18945888

ABSTRACT

Emotionally arousing events are particularly well remembered. This effect is known to result from the release of stress hormones and activation of beta adrenoceptors in the amygdala. However, the underlying cellular mechanisms are not understood. Small conductance calcium-activated potassium (SK) channels are present at glutamatergic synapses where they limit synaptic transmission and plasticity. Here, we show that beta adrenoceptor activation regulates synaptic SK channels in lateral amygdala pyramidal neurons, through activation of protein kinase A. We show that SK channels are constitutively recycled from the postsynaptic membrane and that activation of beta adrenoceptors removes SK channels from excitatory synapses. This results in enhanced synaptic transmission and plasticity. Our findings demonstrate a novel mechanism by which beta adrenoceptors control synaptic transmission and plasticity, through regulation of SK channel trafficking, and suggest that modulation of synaptic SK channels may contribute to beta adrenoceptor-mediated potentiation of emotional memories.


Subject(s)
Amygdala/cytology , Excitatory Postsynaptic Potentials/physiology , Long-Term Potentiation/physiology , Pyramidal Cells/physiology , Receptors, Adrenergic, beta/physiology , Small-Conductance Calcium-Activated Potassium Channels/metabolism , Adrenergic Agents/pharmacology , Animals , Animals, Newborn , Apamin/pharmacology , Egtazic Acid/analogs & derivatives , Egtazic Acid/pharmacology , Electric Stimulation/methods , Endocytosis/drug effects , Enzyme Activators/pharmacology , Enzyme Inhibitors/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Long-Term Potentiation/drug effects , Long-Term Potentiation/radiation effects , Membrane Potentials/drug effects , Membrane Potentials/physiology , Membrane Potentials/radiation effects , Organ Culture Techniques/methods , Patch-Clamp Techniques/methods , Protein Transport/drug effects , Protein Transport/physiology , Pyramidal Cells/drug effects , Rats , Rats, Wistar , Transfection
15.
Neoplasma ; 56(1): 76-83, 2009.
Article in English | MEDLINE | ID: mdl-19152250

ABSTRACT

We processed data of 79 patients (pts) with malignant lymphoma from the National Registry of haematopoietic stem cell transplants conducted between 1997 and 2006. The haematopoietic stem cell donor in 48 pts was an HLA matched relative, and in 30 pts an unrelated volunteer. Sixty (77%) pts were transplanted with reduced intensity conditioning (RIC), eleven (23%) pts with myeloablative conditioning (MC). Acute graft-versus-host disease (aGVHD) was recorded in 26 (33%) pts. Chronic GVHD was diagnosed in 19 (36%) of the 53 assessable pts. Transplant-related mortality (TRM) in the first 100 days, 1 year and 3 years for the whole group was 26%, 33% and 33%. Twenty (26%) of the pts relapsed. During the median follow-up of 26 months the overall survival (OS) was 44%, the progression free survival (PFS) was 54% and cumulative incidence of relapse was 45%. Pts with chemoresistant disease had significantly worse results (OS at 3 years 22% vs. 56%, p=0.002). We did not find any correlation between the incidence of GVHD and the frequency of relapse. Similarly, we did not observe any difference in survival between patients following MC vs. RIC. Survival of pts transplanted from related donors did not differ statistically from unrelated donors. Key words: Lymphoma, allogeneic, transplantation, GVHD.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Lymphoma/therapy , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Adult , Czechoslovakia , Female , Graft vs Host Disease/epidemiology , Graft vs Host Disease/prevention & control , Humans , Kaplan-Meier Estimate , Lymphoma/mortality , Male , Middle Aged , Registries
16.
Nat Neurosci ; 8(5): 635-41, 2005 May.
Article in English | MEDLINE | ID: mdl-15852010

ABSTRACT

At glutamatergic synapses, calcium influx through NMDA receptors (NMDARs) is required for long-term potentiation (LTP); this is a proposed cellular mechanism underlying memory and learning. Here we show that in lateral amygdala pyramidal neurons, SK channels are also activated by calcium influx through synaptically activated NMDARs, resulting in depression of the synaptic potential. Thus, blockade of SK channels by apamin potentiates fast glutamatergic synaptic potentials. This potentiation is blocked by the NMDAR antagonist AP5 (D(-)-2-amino-5-phosphono-valeric acid) or by buffering cytosolic calcium with BAPTA. Blockade of SK channels greatly enhances LTP of cortical inputs to lateral amygdala pyramidal neurons. These results show that NMDARs and SK channels are colocalized at glutamatergic synapses in the lateral amygdala. Calcium influx through NMDARs activates SK channels and shunts the resultant excitatory postsynaptic potential. These results demonstrate a new role for SK channels as postsynaptic regulators of synaptic efficacy.


Subject(s)
Amygdala/physiology , Calcium Signaling/physiology , Neuronal Plasticity/physiology , Potassium Channels, Calcium-Activated/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Synaptic Transmission/physiology , Animals , Calcium/antagonists & inhibitors , Calcium/metabolism , Calcium Signaling/drug effects , Chelating Agents/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Female , Long-Term Potentiation/drug effects , Long-Term Potentiation/physiology , Male , Neuronal Plasticity/drug effects , Organ Culture Techniques , Patch-Clamp Techniques , Potassium Channel Blockers/pharmacology , Potassium Channels, Calcium-Activated/antagonists & inhibitors , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Small-Conductance Calcium-Activated Potassium Channels , Synaptic Membranes/drug effects , Synaptic Membranes/metabolism , Synaptic Transmission/drug effects
17.
Klin Mikrobiol Infekc Lek ; 15(3): 95-8, 2009 Jun.
Article in Sk | MEDLINE | ID: mdl-19637140

ABSTRACT

Toxoplasmosis is a parasitic disease associated with high mortality in immunocompromised patients. It may lead to life-threatening conditions, usually neuroinfections, pneumonia or disseminated disease. It may be potentially dangerous, especially for patients with prolonged lymphopenia or those treated with immunosuppressive drugs. In our centre, we have observed 3 cases of toxoplasmosis in patients after allogeneic haematopoietic stem cell transplantation (HSCT) (2.6% of 116 allo-HSCT patients since 2000) and one case after autologous HSCT (0.3% of 395 auto-HSCT patients since 1997). Toxoplasmosis is manifested by neurological symptoms including hemiparesis and paraparesis, cerebral salt-wasting syndrome (hyponatraemia and hypoosmolality), psychoorganic syndrome and signs of respiratory infection. The diagnosis was made by combining clinical signs and results of PCR and CT examinations. The patients were treated with high-dose pyrimethamine, clindamycin, co-trimoxazole and folic acid. Three of the four patients have survived with no signs of the disease. One patient died prior to treatment. The increasing use of highly immunosuppressive chemotherapy and conditioning regimens (including rituximab, fludarabine and anti-thymocyte globulin) is associated with a significant risk of toxoplasmosis. Variable manifestations, non-specific results of MRI or CT examinations and possibility of PCR negativity are the main obstacles to successful diagnosis.


Subject(s)
Hematopoietic Stem Cell Transplantation , Immunocompromised Host , Toxoplasmosis/etiology , Transplantation Conditioning/adverse effects , Adult , Female , Humans , Male , Middle Aged , Toxoplasmosis/immunology
18.
Int J Immunogenet ; 35(4-5): 401-3, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18976446

ABSTRACT

Interleukin-6 (IL-6) is an important pro-inflammatory mediator implicated in immune-mediated complications of allogeneic haematopoietic stem cell transplantation (aHSCT). In accord with previous reports, this preliminary study on 56 donor-recipient pairs revealed IL-6-174 single nucleotide polymorphisms as a risk factor for the development of acute graft-versus-host disease and decreased survival after aHSCT.


Subject(s)
Graft vs Host Disease/genetics , Hematopoietic Stem Cell Transplantation/adverse effects , Interleukin-6/genetics , Polymorphism, Genetic/genetics , Transplantation, Homologous/immunology , Adolescent , Adult , Alleles , Czech Republic , Female , Gene Frequency , Genotype , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Hematopoietic Stem Cell Transplantation/mortality , Humans , Interleukin-6/immunology , Male , Middle Aged , Polymorphism, Genetic/immunology , Polymorphism, Single Nucleotide/genetics , Young Adult
19.
Neoplasma ; 55(3): 215-21, 2008.
Article in English | MEDLINE | ID: mdl-18348654

ABSTRACT

Improved survival has been observed in poor-risk diffuse large B-cell lymphoma (DLBCL) patients treated with high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in first complete remission. Retrospective studies have suggested that HDT with ASCT can improve survival also in partial responders but some doubts about the advantage of intensive therapy in such patients still remain. We evaluated retrospectively the results of HDT and ASCT in 55 patients with confirmed DLBCL treated between May 1999 and July 2006. Thirty-six patients (65%) showed partial remission (PR) and 19 patients (35%) reached complete remission (CR) after induction treatment with (44%) or without (56%) concomitant rituximab (R) immunotherapy. After HDT and ASCT, 69% of patients fulfilled the criteria of CR, 22% had unconfirmed CR (CRu), 7% remained in PR and 1 patient (2%) relapsed. Twenty patients in PR after the induction treatment reached CR after ASCT, 12 other PR patients achieved CRu. The 5-year event-free survival (EFS) of the 55 transplanted patients was 76% (95% confidence interval /CI/, 63% to 89%) and the 5-year overall survival (OS) was 85% (95% CI, 73% to 97%). The EFS and OS rates differed significantly only between patients younger than 40 years and older groups (p=0.022 and p=0.046, respectively). On univariate analysis of prognostic factors, EFS and OS were not affected by any of the following: age, sex, stage, subtype of DLBCL, initial lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase levels, International Prognostic Index (IPI) and age-adjusted IPI scores, induction treatment with or without rituximab and type of primary therapeutic response (CR vs PR). These results show that first-line HDT and ASCT for adults up to the age of 65 years with poor-risk DLBCL is a feasible and effective treatment option even in the era of R-chemotherapy in CR as well as for patients in PR.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse/therapy , Adult , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Male , Middle Aged , Prognosis , Remission Induction , Retrospective Studies , Survival Rate , Transplantation, Autologous
20.
Vnitr Lek ; 54(12): 1174-84, 2008 Dec.
Article in Czech | MEDLINE | ID: mdl-19140527

ABSTRACT

National working group representing clinicians (hematologists, oncologists, infection diseases and ICU specialists), microbiologists, and different special medical societies and working groups prepared evidence-based guidelines for the treatment established fungal infection--invasive candidiasis in the adult hematology and ICU patients. These guidelines updated those published in the Czech Republic in 2003-2004. Evidence criteria of the Infectious Diseases Society of America (IDSA) were used for assessing the quality of clinical trials, and EORTC/MSG Consensus Group for definitions of invasive fungal disease.


Subject(s)
Candidiasis/drug therapy , Humans
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