Analysis of in-hospital analgesic pharmacotherapy costs and regimen and impact on postoperative pain-related function in degenerative lumbar intervertebral disc disease.

BACKGROUND: Pain medication may affect clinical and economic outcomes, and a detailed description of pain medication use is advocated in the literautre for better assessment of clinical outcomes of spine surgery, which otherwise clould be misleading. OBJECTIVES: To analyze the impact of in-hospital analgesic pharmacotherapy after spine surgery on subjective quality of life and pain relief in patients with degenerative lumbar intervertebral disc disease (DLIVD), and also to analyze pharmacotherapy costs. DESIGN: A single-center study included 50 patients with L5/S1 or L4/L5 DLIVD, eligible for spine surgery. INTERVENTION: Neurosurgery for DLIVD. MAIN ENDPOINTS: Outcomes in terms of postoperative pain and function were recorded prospectively using standardized questionnaires. Data for cost analysis and pharmcotherapy regimen were obtained retrospectively from case histories, doctors' request cards and hospital discharge summaries. RESULTS: Mean total pharmacotherapy cost amounted to €453.42±49.09. Mean pharmacotherapy cost amounted to €314.76±54.21 preoperatively, and €138.66±25.54 postoperatively. The greatest improvement in function and quality of life was in patients treated with non-opioids. CONCLUSION: This study supports the notion that analgesic pharmacotherapies could be differentiated in terms of overall impact on quality of life, and that pain-related distress might be the most relevant factor in this setting.

Multidomain intervention for the prevention of cognitive decline after stroke - a pooled patient-level data analysis.

BACKGROUND AND PURPOSE: The aim of this pooled patient-level data analysis was to test if multidomain interventions, addressing several modifiable vascular risk factors simultaneously, are more effective than usual post-stroke care for the prevention of cognitive decline after stroke. METHODS: This pooled patient-level data analysis included two randomized controlled trials using a multidomain approach to target vascular risk factors in stroke patients and cognition as primary outcome. Changes from baseline to 12 months in the trail making test (TMT)-A, TMT-B and 10-words test were analysed using stepwise backward linear mixed models with study as random factor. Two analyses were based on the intention-to-treat (ITT) principle using different imputation approaches and one was based on complete cases. RESULTS: Data from 322 patients (157 assigned to multidomain intervention and 165 to standard care) were analysed. Differences between randomization groups for TMT-A scores were found in one ITT model (P = 0.014) and approached significance in the second ITT model (P = 0.087) and for complete cases (P = 0.091). No significant intervention effects were found for any of the other cognitive variables. CONCLUSION: We found indications that multidomain interventions compared with standard care can improve the scores in TMT-A at 1 year after stroke but not those for TMT-B or the 10-words test. These results have to be interpreted with caution due to the small number of patients.

The influence of aripiprazole and venlafaxine on the antidepressant-like effect observed in prenatally stressed rats (animal model of depression).

Depression is a nosological entity which may appear alone or concomitantly (e.g. in schizophrenia). Analysis of data from both clinical and experimental studies allows a conclusion that atypical antipsychotics, such as aripiprazole (ARI), may also be effective in treating depression in addition to antidepressants. The aim of the studies was to determine antidepressant efficacy of ARI, venlafaxine (VEN) and combined therapy using both drugs, in prenatally stressed rats (animal depression model) and control group. In addition, this article was aimed at determining the effect of these drugs on locomotor activity of these animals. The effect of chronic stress used in pregnant rats and the use of drugs such as ARI (1.5 mg/kg) and VEN (20 mg/kg) were studied in forced swimming test (FST; antidepressant effect) and locomotor activity test. Performed tests confirmed the antidepressant effect of ARI, VEN and efficacy of combined drugs in FST in both prenatally stressed rats (effect present upon single administration and after 7, 14 and 21 days of testing) and control group rats (effect present upon single administration and 7 days of testing). Moreover, upon single administration of the used drugs to prenatally stressed rats, it was found sedative effect - reduced animals' locomotor activity. Study results have proven antidepressant and sedative efficacy of ARI, VEN and combined administration of these drugs. Due to the small amount of data on the above preparations, in particular in the context of animal depression models, further studies in this respect are recommended.

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

OBJECTIVES: The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. METHODS: The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. RESULTS: Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. CONCLUSION: Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness.

Neuroleptics and enrichment environment treatment in memory disorders and other central nervous system function observed in prenatally stressed rats.

It is believed that the most effective method of treatment in schizophrenia is pharmacotherapy, in particular, the use of atypical neuroleptics like aripiprazole (ARI) and olanzapine (OLA). Moreover, studies of many authors have shown that enriched living conditions and tobacco smoke exposure can also affect the cognitive functions that are disturbed in the course of schizophrenia. The aim of the study was to find whether tobacco smoke and enrichment living conditions have the influence on cognitive functions in the newborn offspring of prenatally stressed rats and whether drugs such as ARI (1.5 mg/kg intraperitoneally (i.p.)) and OLA (0.5 mg/kg ip) in single and chronic treatment modify those functions (Morris water maze). The study (in the same conditions) also analyses immobility time (Porsolt test) and motor activity of animals that received ARI and OLA. It has been shown that ARI and OLA as well as enriched environment reduce cognitive function disorders and modify cognitive functions in rats exposed to tobacco smoke. In turn, current research has shown that nicotine has increased cognitive function disorders compared to the previous study (animals without tobacco smoke exposure).

Sodium molybdate - an additive of choice for enhancing the performance of AC/AC electrochemical capacitors in a salt aqueous electrolyte.

Sodium molybdate (Na2MoO4) has been used as an additive to 1 mol L(-1) lithium sulfate electrolyte for electrochemical capacitors based on activated carbon (AC) electrodes, in order to reduce the corrosion of stainless steel current collectors. We demonstrate that the MoO4(2-) anions improve the overall capacitance owing to pseudofaradaic processes. In a two-electrode cell, capacitance values of 121 F g(-1) have been achieved up to 1.6 V using 1 mol L(-1) Li2SO4 + 0.1 mol L(-1) Na2MoO4, as compared to 103 F g(-1) when 1 mol L(-1) Li2SO4 is used. Further, by using a two-electrode setup equipped with a reference electrode, we could demonstrate that, at 1.6 V, the positive electrode potential reaches a value of 0.96 V vs. NHE in 1 mol L(-1) Li2SO4, crossing the thermodynamic potential limit of oxygen evolution (Eox = 0.846 V vs. NHE), and the pitting potential, Epit = 0.95 V vs. NHE. By contrast, in 1 mol L(-1) Li2SO4 + 0.1 mol L(-1) Na2MoO4, the pseudofaradaic contribution occurring at -0.05 V vs. NHE due to MoO4(2-) anions drives the positive electrode to reach only 0.798 V vs. NHE. Hence, the oxidation of the AC and corrosion of the stainless steel current collector at the positive electrode are unlikely in Li2SO4 + Na2MoO4 when the capacitor operates at 1.6 V. During potentiostatic floating of the capacitor at 1.6 V for 120 hours in Li2SO4 + Na2MoO4, the capacitance and resistance remain constant at 125 F g(-1) and ~1.0 Ω, respectively, while the resistance increases from 1.4 Ω to 3.1 Ω in Li2SO4. Overall, the addition of MoO4(2-) anions to Li2SO4 aqueous electrolyte allows the capacitance to be enhanced, corrosion of the positive stainless steel current collector to be inhibited and the AC/AC electrochemical capacitor to demonstrate stable performance up to 1.6 V.

Human de novo papillary renal-cell carcinomas in a kidney graft: evidence of recipient origin with adenoma-carcinoma sequence.

Papillary renal-cell carcinoma (pRCC) is unusual for its occurrence in kidneys with chronic dysfunction, for its frequent multifocality and for its common association with papillary adenoma, a benign renal lesion morphologically indistinguishable from pRCC. Concomitant development of papillary adenoma and pRCC in five transplanted kidneys, where donor and recipient characteristics are well established, provided a unique opportunity for molecular studies of de novo pRCC carcinogenesis. We aimed to study this tumor type to determine whether or not the different papillary tumors have the same origin, and whether or not papillary adenomas are precursor lesions of pRCC. We performed XY-FISH in sex-mismatched kidney transplants, and polymorphic microsatellite DNA and high-resolution melting of mitochondrial DNA analyzes in all five patients on laser-microdissected tumor cells, then compared these molecular profiles to donor and recipient profiles. This study (i) identified the recipient origin of de novo papillary adenomas and pRCCs in a kidney transplant, (ii) demonstrated an identical origin for precursor cells of papillary adenomas and pRCCs and (iii) showed additional genetic alterations in pRCCs compared to papillary adenomas. This molecular approach of papillary tumors developed in transplanted kidney identified successive steps in carcinogenesis of human de novo papillary renal-cell carcinoma.

Increased apoptosis is linked to severe acute GVHD in patients with Fanconi anemia.

Fanconi anemia (FA) patients have an increased risk of acute GVHD (aGVHD) after hematopoietic SCT, with hypersensitivity to DNA-cross-linking agents and defective DNA repair. MicroRNA-34 and p53 can induce apoptosis after DNA damage.Here we assessed epithelial cell apoptosis, and studied TP53 and miR-34a expression in the skin and gut biopsies in five non-transplanted FA patients, in 20 FA patients with aGVHD and in 25 acquired aplastic anemia patients (AA). Epithelial apoptosis was higher in FA than in acquired AA patients in both the skin and gut biopsies, though they had a similar preparative regimen. Further study on gut biopsies in FA patients showed that this deleterious effect was not linked to TP53 gene overexpression. As, among p53-independent signaling pathways of apoptosis, the microRNA-34 family mimics p53 apoptotic effects in response to DNA damage, we studied miR-34a expression in the same series of FA patients' gut biopsies. MiR-34a expression level was higher in severe aGVHD compared with non-aGVHD subjects or non-transplanted patients, and significantly related to apoptotic cell numbers across the three groups of FA patients. Thus, in FA patients, increased apoptosis occurs in target epithelial cells of severe aGVHD, and this deleterious effect is linked to overexpression of miR-34a but not TP53.

The effect of ethyl alcohol on the function of spatial memory in rats.

Alcoholism is a mental disease in the course of which depression, anxiety, and cognitive function deficits may appear, and these symptoms can be aggravated by comorbid schizophrenia.The aim of this study was to find whether spatial memory (Morris Water Maze) function impairment is found in prenatally stressed rats (PSG) (prenatal stress paradigm - animal model of schizophrenia) and whether aripiprazole ARI and olanzapine OLA modify these functions. It was also important to study the effect of ethyl alcohol administered to rats.Behavioural tests showed that ARI and OLA improved spatial memory in the non-stressed control group (NSCG) and in the PSG. Moreover, spatial memory in the non-stressed alcohol group (NSAG) improved significantly compared to the NSCG, while in the prenatally stressed alcohol group (PSAG) spatial memory improved both in comparison to the NSCG and PSG. No statistically significant differences were found by comparing groups which received ethyl alcohol (NSAG, PSAG).

Endothelial cell apoptosis in severe drug-induced bullous eruptions.

BACKGROUND: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are characterized by extensive keratinocyte apoptosis mediated by cytotoxic proteins. Similar features have been found in another severe dysimmune syndrome, allogeneic acute graft-versus-host disease, where endothelial cell apoptosis has been recently characterized. OBJECTIVES: To determine whether endothelial cell apoptosis occurs in dermal vessels of TEN and SJS, and whether it is linked to expression of cytotoxic proteins. METHODS: Skin biopsies of eight patients with severe drug-induced bullous eruptions (four TEN, four SJS), eight with drug-induced urticaria and eight healthy controls were compared. Blood vessel damage was studied by electron microscopy and quantified by CD31 immunostaining. Apoptotic cells, characterized by electron microscopy, were quantified on terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay. Immunohistochemistry was also used to characterize and quantify inflammatory cells and granzyme B, tumour necrosis factor (TNF)-alpha and Fas ligand (FasL) expression. RESULTS: Endothelial cell apoptosis was observed in all TEN and SJS cases: it occurred in 85% of the vessel sections. It occurred in one case of drug-induced urticaria, in 5% of vessel sections, but not in healthy controls. Numbers of CD68+ macrophages and CD8+ T lymphocytes were significantly higher in TEN and SJS compared with both other groups; granzyme B and TNF-alpha but not FasL were expressed. CONCLUSIONS: Characterization of endothelial cell apoptosis in TEN and SJS is important to assess a factor worsening skin damage, with possible extension to other organs. It may also be useful for the development of novel therapeutic strategies.

Ocular manifestations in oculodentodigital dysplasia resulting from a heterozygous missense mutation (L113P) in GJA1 (connexin 43).

PURPOSE: To characterize the ophthalmic findings, intrafamilial variability, and molecular genetic basis of oculodentodigital dysplasia (ODDD; MIM no. 164200). METHODS: Ophthalmic examination included best-corrected visual acuity, slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, Goldmann applanation tonometry and A-scan ultrasonography. Blood samples were taken for DNA extraction and mutation screening of GJA1 (connexin 43). RESULTS: All three affected individuals had characteristic features of ODDD. The ophthalmic features were epicanthus, microcornea, and the presence of glaucoma. The ocular phenotype resulted from a heterozygous T>C transition at nucleotide 338 in GJA1 (L113P) that was not detected in 120 chromosomes of unaffected individuals. The L113P mutation results in a nonconservative substitution in the cytoplasmic loop of Cx43 (GJA1) and is predicted to disrupt the high-order structure of Cx43. CONCLUSIONS: This report describes the ocular phenotype in a molecularly characterized ODDD syndrome family. The ocular features in this family highlight the key role Cx43 plays in eye development and in the development of glaucoma. L113P represents a pathogenic mutation in GJA1 (Cx43) and results in ODDD with marked intrafamilial variation in glaucoma type and severity.

A new, recurrent mutation of GJB3 (Cx31) in erythrokeratodermia variabilis.

BACKGROUND: Erythrokeratodermia variabilis (EKV) is an autosomal dominant or recessive genodermatosis characterized by the coexistence of randomly occurring, transient, erythematous patches and hyperkeratosis of the skin. The disorder has been mapped to chromosome 1p35.1 but is genetically heterogeneous. EKV may be caused by pathogenic mutations in one of two neighbouring connexin genes, GJB3 and GJB4, encoding the gap junction proteins Cx31 and Cx30.3, respectively. Twelve distinct mutations identified to date cluster either at the cytoplasmic amino-terminus or in the four transmembrane domains. OBJECTIVES: To report a large family with EKV and an unrelated sporadic case. METHODS: DNA amplification and mutation analysis, followed by denaturing high-performance liquid chromatography to confirm the segregation of the mutations in the two families with EKV. RESULTS: A novel, recurrent GJB3 mutation (625C-->T; L209F) was identified in the family with EKV and in the unrelated sporadic case. CONCLUSIONS: This mutation is the first to affect a conserved residue in the cytoplasmic carboxy-terminus of any connexin gene with a cutaneous phenotype, emphasizing its structural and/or functional importance.

Deleterious mutations in SPINK5 in a patient with congenital ichthyosiform erythroderma: molecular testing as a helpful diagnostic tool for Netherton syndrome.

The congenital erythrodermas represent a heterogeneous group of inherited and acquired disorders often accompanied by systemic infections, impaired epidermal barrier function and concomitant life-threatening fluid and electrolyte imbalance. In the present report, we describe a patient who was considered to have congenital ichthyosiform erythroderma for 26 years until molecular testing led to the correct diagnosis of Netherton syndrome.

Extracellular matrix and cardiac remodelling.

Cardiac remodelling associated with primitive and secondary cardiomyopathy is generally associated with changes in the expression in extracellular matrix (ECM) proteins as well as their transmembrane receptors, the integrins. It emerges now that the ECM provides a structural, chemical, and mechanical substrate that is essential in cardiac function and responses to pathophysiological signals. This review will describe the various elements of the ECM, its modifications that are associated with cardiac hypertrophy and heart failure, and the molecular basis bringing a better insight into the dynamics of the ECM.

Activation of cardiac endothelium as a compensatory component in endotoxin-induced cardiomyopathy: role of endothelin, prostaglandins, and nitric oxide.

BACKGROUND: In view of growing evidence of an important endothelial paracrine regulation of cardiac function, the present study investigated the role of cardiac endothelium-derived endothelin-1 (ET-1), prostaglandins, and nitric oxide (NO) during endotoxin-induced cardiomyopathy in rabbits. METHODS AND RESULTS: Immunohistochemical studies showed a marked transient coinduction of the inducible isoforms of NO synthase (NOS-2) and cyclooxygenase (COX-2) in endocardial endothelium and coronary arteriolar endothelium of hearts 12 hours after intravenous administration of lipopolysaccharide (LPS+12h); staining for both isoforms was much weaker 24 hours later (LPS+36h). Nitrotyrosine localization was similar to that of NOS-2, suggesting a NOS-2-related endothelial formation of peroxynitrite in septic hearts. Contractile performance of papillary muscles was depressed in both LPS-treated groups. In the LPS+12h group, however, isometric twitches were significantly prolonged (482+/-14 versus 420+/-14 ms in the saline-treated group, P<0.005). This twitch prolongation was completely reversed by simultaneous administration of BQ-123 and indomethacin to block endogenous ET-1 and prostaglandins, respectively. In addition, in the LPS+12h group, myocardial inotropic responsiveness to exogenous ET-1 was enhanced (P<0.01). CONCLUSIONS: Cardiac endothelial activation and myocardial sensitization to endothelium-derived mediators may be part of an adaptive response in the early (12 hours) stages of septic cardiomyopathy.

[The use of color Doppler ultrasonography in the diagnosis of benign breast tumors]. / Zastosowanie techniki koloroweo Dopplera w diagnostyce Lagodnych schorzen gruczolu sutkowego.

The paper describes Color Doppler Velocity (CDV) technique with clinical implications in examinations of patients with benign breast lesions. Results suggest that CDV might be useful in differentiation of the breast lesions in routine clinical work.

[Evaluation of using the B-mode color system in sonomammography with computer analysis of images compared with conventional gray scale modalities]. / Ocena zastosowania systemu B-mode color w sonomammografii wraz z komputerowa analiza obrazów uzyskiwanych w tym systemie w porównaniu z konwencjonalna skala szarosci.

The paper describes B-mode color and B-tag modalities with clinical implications in breast examinations. New color techniques show increased sensitivity of the human eye to color pictures compared to gray scale levels. Computer analysis of pictures obtained in color mode and gray scale supports these findings.