ABSTRACT
INTRODUCTION: Greenlight XPS-180W® (AMS, San José, USA) photoselective vaporisation of the prostate (PVP) is considered as an alternative to transurethral resection of the prostate. The objective of this study was to assess the effect of energy density applied on adenoma during PVP treatment for benign prostate hyperplasia (BPH) on postoperative outcomes. METHODS: A single-centre retrospective study has been conducted in the department of Urology of Colmar Hospital, in patients with symptomatic BPH, treated by PVP, between January 2016 and January 2019. Patients were stratified into two groups according to energy delivered and prostate volume as determined preoperatively: Low density (<4kJ/mL) and high density (>4kJ/mL). Perioperative complications, PSA evolution and functional outcomes (International Prostate Symptom Score, quality of life, maximum urinary flow rate, post-void residual urine volume) were compared with a minimal delay of 6 months. The retreatment rate was similar in the two groups. RESULTS: A total of 215 patients were included with median follow-up of 25 months. High energy density was associated with less glandular volume. There were no statistically significant differences between the two groups concerning the perioperative complications and the functional outcomes. The postoperative reduction of the PSA level was more significant in the high-energy group (41% vs. 28%, P=0.03). CONCLUSION: The perioperative complications and functional outcomes of PVP with Greenlight XPS-180W® laser are equivalent depending on the energy density delivered. The greater decrease in postoperative PSA for high-energy density could nevertheless suggest better quality tissue destruction. LEVEL OF PROOF: 3.
Subject(s)
Laser Therapy , Prostatic Hyperplasia , Transurethral Resection of Prostate , Humans , Lasers , Male , Prostate/surgery , Prostatic Hyperplasia/surgery , Quality of Life , Retrospective Studies , Treatment Outcome , VolatilizationABSTRACT
Pasture-based and small-scale livestock farming systems are the main source of livelihood in the mountain primary sector, ensuring socioeconomic sustainability and biodiversity in rural communities throughout Europe and beyond. Mountain livestock farming (MLF) has attracted substantial research efforts from a wide variety of scientific communities worldwide. In this study, the use of text mining and topic modelling analysis drew a detailed picture of the main research topics dealing with MLF and their trends over the last four decades. The final data corpus used for the analysis counted 2â¯679 documents, of which 92% were peer-reviewed scientific publications. The number of scientific outputs in MLF doubled every 10â¯years since 1980. Text mining found that milk, goat and sheep were the terms with the highest weighed frequency in the data corpus. Ten meaningful topics were identified by topic analysis: T1-Livestock management and vegetation dynamics; T2-Animal health and epidemiology; T3-Methodological studies on cattle; T4-Production system and sustainability; T5-Methodological studies; T6-Wildlife and conservation studies; T7-Reproduction and performance; T8-Dairy/meat production and quality; T9-Land use and its change and T10-Genetic/genomic studies. A hierarchical clustering analysis was performed to explore the interrelationships among topics, and three main clusters were identified: the first focused on sustainability, conservation and socioeconomic aspects (T4; T6 and T9), the second was related to food production and quality (T7 and T8) and the last one considered methodological studies on mountain flora and fauna (T1; T2; T3; T5 and T10). The 10 topics identified represent a useful and a starting source of information for further and more detailed analysis (e.g. systematic review) of specific research or geographical areas. A truly holistic and interdisciplinary research approach is needed to identify drivers of change and to understand current and future challenges faced by livestock farming in mountain areas.
Subject(s)
Agriculture , Livestock , Animals , Cattle , Data Mining , Europe , Farms , SheepABSTRACT
PURPOSE: Breast cancer continues to be the most commonly diagnosed cancer among Canadian women, with as many as 25-60% of women suffering from chronic neuropathic pain (CNP) as a pervasive consequence of treatment. While pharmacological interventions have shown limited efficacy for the management of CNP to date, psychological interventions, such as mindfulness-based stress reduction (MBSR), may be a promising alterative for improving pain-related problems. The purpose of this study was to use brain imaging methods to investigate this potential. METHODS: Resting-state fMRI was used in female breast cancer survivors with CNP before and after an 8-week MBSR course (n = 13) and compared with a waitlist control group (n = 10). RESULTS: Focusing on the default mode network, the most significant results show greater posterior cingulate connectivity with medial prefrontal regions post-MBSR intervention. Moreover, this change in connectivity correlated with reduced pain severity for the MBSR group. CONCLUSIONS: These results provide empirical evidence of a change in the brain following MBSR intervention associated with changes in the subjective experience of pain. IMPLICATIONS FOR CANCER SURVIVORS: This study gives hope for a non-invasive method of easing the struggle of CNP in women following breast cancer treatment.
Subject(s)
Breast Neoplasms , Cancer Survivors , Mindfulness , Neuralgia , Brain , Breast Neoplasms/complications , Breast Neoplasms/therapy , Canada , Female , Humans , Magnetic Resonance Imaging , Neuralgia/therapy , Stress, PsychologicalABSTRACT
We report the first isolation of Acinetobacter kookii from a Rothschild's giraffe calf (Giraffa camelopardalis rothschildi) that had severe polyarthritis. The isolate was resistant to more than one representative of each of four classes of antibiotics (penicillins, macrolides, lincosamides and tetracyclines). As A. kookii has not been previously associated with disease in humans or animals, it may be an emerging opportunistic pathogen posing a threat to immunocompromised patients. Furthermore, as transmission of Acinetobacter spp. with similar patterns of antimicrobial resistance has been previously reported in human and animal populations, special care should be taken when handling infected animals.
Subject(s)
Acinetobacter , Arthritis/veterinary , Giraffes , Acinetobacter/drug effects , Acinetobacter/isolation & purification , Acinetobacter Infections/drug therapy , Acinetobacter Infections/pathology , Acinetobacter Infections/veterinary , Animals , Animals, Zoo/microbiology , Anti-Bacterial Agents/therapeutic use , Arthritis/microbiology , Communicable Diseases, Emerging/veterinary , Drug Resistance , Giraffes/microbiology , MaleABSTRACT
BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Cancer, Regional Perfusion/mortality , Colorectal Neoplasms/mortality , Cytoreduction Surgical Procedures/mortality , Hyperthermia, Induced/mortality , Mutation , Peritoneal Neoplasms/mortality , ras Proteins/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Prognosis , Retrospective Studies , Survival RateABSTRACT
Tendons and ligaments are crucial structures inside the musculoskeletal system. Still many issues in the treatment of tendon diseases and injuries have yet not been resolved sufficiently. In particular, the role of estrogen-like compound (ELC) in tendon biology has received until now little attention in modern research, despite ELC being a well-studied and important factor in the physiology of other parts of the musculoskeletal system. In this review we attempt to summarize the available information on this topic and to determine many open questions in this field.
Subject(s)
Estrogen Receptor Modulators/pharmacology , Ligaments/drug effects , Phytoestrogens/pharmacology , Tendon Injuries/drug therapy , Tendons/drug effects , Animals , Collagen Type I/genetics , Collagen Type I/metabolism , Estrogen Receptor alpha/chemistry , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/chemistry , Estrogen Receptor beta/genetics , Estrogen Receptor beta/metabolism , Female , Gene Expression/drug effects , Hormone Replacement Therapy/methods , Humans , Ligaments/injuries , Ligaments/metabolism , Menopause/genetics , Ovariectomy , Pregnancy , Structural Homology, Protein , Tendon Injuries/genetics , Tendon Injuries/metabolism , Tendon Injuries/pathology , Tendons/metabolism , Tendons/pathologyABSTRACT
The objective of this review was to evaluate morbidity, mortality and survival outcomes of elderly patients with peritoneal carcinomatosis. A systematic literature search and standardized data collection of primary research publications until June 2016 on morbidity, mortality and survival outcomes in adults aged 65 and older with peritoneal carcinomatosis treated with cytoreduction and HIPEC was performed, using PubMed, EMBASE, Scopus, ClinicalTrials.gov and Cochrane. Bibliographies of relevant reports were also hand-searched to identify all potentially eligible studies. Nine studies were included. Severe morbidity of all elderly patients ranges from 17% to 56% in centers with high experience. In-hospital and 30-day mortality ranges from 0% to 8%. In only two studies were the differences in morbidity and mortality statistically significant related to the control group. However, older adults undergoing cytoreductive surgery and HIPEC consistently had lower survival rates across all study settings and procedure types than younger individuals. In studies that stratified for elderly patients, PCI, completeness of cytoreduction, tumor histology and albumin levels were predictive factors of survival. None of these studies examined quality of life, which precludes including functional outcomes in this review. Differences in exposures, outcomes, and data presented in the studies did not allow for quantification of association using a meta analysis.
Subject(s)
Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Peritoneal Neoplasms/therapy , Adult , Aged , Chemotherapy, Cancer, Regional Perfusion , Combined Modality Therapy , Humans , Quality of LifeABSTRACT
Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by deficiency of frataxin protein, with the primary sites of pathology being the large sensory neurons of the dorsal root ganglia and the cerebellum. FRDA is also often accompanied by severe cardiomyopathy and diabetes mellitus. Frataxin is important in mitochondrial iron-sulfur cluster (ISC) biogenesis and low-frataxin expression is due to a GAA repeat expansion in intron 1 of the FXN gene. FRDA cells are genomically unstable, with increased levels of reactive oxygen species and sensitivity to oxidative stress. Here we report the identification of elevated levels of DNA double strand breaks (DSBs) in FRDA patient and YG8sR FRDA mouse model fibroblasts compared to normal fibroblasts. Using lentivirus FXN gene delivery to FRDA patient and YG8sR cells, we obtained long-term overexpression of FXN mRNA and frataxin protein levels with reduced DSB levels towards normal. Furthermore, γ-irradiation of FRDA patient and YG8sR cells revealed impaired DSB repair that was recovered on FXN gene transfer. This suggests that frataxin may be involved in DSB repair, either directly by an unknown mechanism, or indirectly via ISC biogenesis for DNA repair enzymes, which may be essential for the prevention of neurodegeneration.
Subject(s)
Friedreich Ataxia/therapy , Genetic Therapy , Genomic Instability , Iron-Binding Proteins/genetics , Animals , Cells, Cultured , DNA Breaks, Double-Stranded , Fibroblasts/metabolism , Humans , Iron-Binding Proteins/metabolism , Lentivirus/genetics , Mice , Recombinational DNA Repair , FrataxinABSTRACT
3D organoids using stem cells to study development and disease are now widespread. These models are powerful to mimic in vivo situations but are currently associated with high variability and low throughput. For biomedical research, platforms are thus necessary to increase reproducibility and allow high-throughput screens (HTS). Here, we introduce a microwell platform, integrated in standard culture plates, for functional HTS. Using micro-thermoforming, we form round-bottom microwell arrays from optically clear cyclic olefin polymer films, and assemble them with bottom-less 96-well plates. We show that embryonic stem cells aggregate faster and more reproducibly (centricity, circularity) as compared to a state-of-the-art microwell array. We then run a screen of a chemical library to direct differentiation into primitive endoderm (PrE) and, using on-chip high content imaging (HCI), we identify molecules, including regulators of the cAMP pathway, regulating tissue size, morphology and PrE gene activity. We propose that this platform will benefit to the systematic study of organogenesis in vitro.
Subject(s)
Drug Evaluation, Preclinical/methods , Embryoid Bodies/cytology , Embryoid Bodies/drug effects , High-Throughput Screening Assays/methods , Microtechnology/methods , Temperature , Animals , Cell Aggregation/drug effects , Cell Line , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Enzyme Activation/drug effects , Gene Expression Regulation, Enzymologic/drug effects , Kinetics , Mice , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Reproducibility of ResultsABSTRACT
According to previous studies, plasma erythropoietin (EPO) may decrease after hyperbaric oxygen exposure due to oxidative stress. It is hypothesized that the decrease of EPO can be attenuated by oxygen free radical scavengers.The aim of the present study was to evaluate whether EPO plasma levels can be influenced by oral application of vitamin C and E before repeated hyperbaric oxygen exposure during diving. 16 healthy male police task force divers performed 3 morning dives on oxygen within a regular diving schedule on 3 consecutive days. They were randomized into either the placebo group or the vitamin group, receiving 1 g ascorbic acid and 600 IU D-α-tocopherol orally 60 min before the dive. Blood samples for EPO measurement were taken on days 1, 2, and 3 at T1, T3 and T5 60 min before and at T2, T4 and T6 60 min after each dive, respectively. A moderate decrease of EPO was observed beginning at T3 until T6 in the placebo group. The EPO concentrations in the vitamin group did not show relevant variations compared to baseline. Radical scavenging vitamins C and D may counteract hyperbaric oxygen related mechanisms reducing EPO production in hyperbaric oxygen exposure during diving.
Subject(s)
Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Diving/physiology , Erythropoietin/blood , Hyperbaric Oxygenation , alpha-Tocopherol/administration & dosage , Administration, Oral , Humans , MaleABSTRACT
UNLABELLED: Fracture Liaison Services are the best model to prevent secondary fractures. The International Osteoporosis Foundation developed a Best Practice Framework to provide a quality benchmark. After a year of implementation, we confirmed that a single framework with set criteria is able to benchmark services across healthcare systems worldwide. INTRODUCTION: Despite evidence for the clinical effectiveness of secondary fracture prevention, translation in the real-world setting remains disappointing. Where implemented, a wide variety of service models are used to deliver effective secondary fracture prevention. To support use of effective models of care across the globe, the International Osteoporosis Foundation's Capture the Fracture® programme developed a Best Practice Framework (BPF) tool of criteria and standards to provide a quality benchmark. We now report findings after the first 12 months of implementation. METHODS: A questionnaire for the BPF was created and made available to institutions on the Capture the Fracture website. Responses from institutions were used to assign gold, silver, bronze or black (insufficient) level of achievements mapped across five domains. Through an interactive process with the institution, a final score was determined and published on the Capture the Fracture website Fracture Liaison Service (FLS) map. RESULTS: Sixty hospitals across six continents submitted their questionnaires. The hospitals served populations from 20,000 to 15 million and were a mix of private and publicly funded. Each FLS managed 146 to 6200 fragility fracture patients per year with a total of 55,160 patients across all sites. Overall, 27 hospitals scored gold, 23 silver and 10 bronze. The pathway for the hip fracture patients had the highest proportion of gold grading while vertebral fracture the lowest. CONCLUSION: In the first 12 months, we have successfully tested the BPF tool in a range of health settings across the globe. Initial findings confirm a significant heterogeneity in service provision and highlight the importance of a global approach to ensure high quality secondary fracture prevention services.
Subject(s)
Benchmarking , Osteoporotic Fractures/prevention & control , Secondary Prevention/standards , Delivery of Health Care, Integrated/organization & administration , Delivery of Health Care, Integrated/standards , Health Care Surveys , Hip Fractures/epidemiology , Hip Fractures/prevention & control , Humans , Osteoporotic Fractures/epidemiology , Practice Guidelines as Topic , Secondary Prevention/organization & administration , Spinal Fractures/epidemiology , Spinal Fractures/prevention & controlABSTRACT
This study evaluated the theoretical clinical outcome of three marbofloxacin posology regimens in two groups of pigs (weaners and fatteners) for the treatment of Actinobacillus pleuropneumoniae (App) and Haemophilus parasuis (Hp) infection and the appearance of resistant bacteria due to the antibiotic treatment. The probability of target attainment (PTA) for pharmacokinetic/pharmacodynamics (PK/PD) ratios associated with clinical efficacy and with the appearance of antimicrobial resistance for fluoroquinolones at each minimum inhibitory concentration (MIC) or mutant prevention concentration (MPC) were calculated, respectively. The cumulative fraction of response (CFR) was calculated for the three posology regimens against App and they ranged from 91.12% to 96.37% in weaners and from 93% to 97.43% in fatteners, respectively. In the case of Hp, they ranged from 80.52% to 85.14% in weaners and from 82.01% to 88.49% in fatteners, respectively. Regarding the PTA of the PK/PD threshold associated with the appearance of antimicrobial resistance, results showed that marbofloxacin would prevent resistances in most of the animals up to the MPC value of 1 µg/mL.
Subject(s)
Actinobacillus Infections/veterinary , Actinobacillus pleuropneumoniae/drug effects , Anti-Bacterial Agents/pharmacokinetics , Fluoroquinolones/pharmacokinetics , Haemophilus Infections/veterinary , Haemophilus parasuis/drug effects , Swine Diseases/drug therapy , Actinobacillus Infections/drug therapy , Age Factors , Animals , Animals, Newborn/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Biological Availability , Drug Resistance, Bacterial , Fluoroquinolones/pharmacology , Fluoroquinolones/therapeutic use , Haemophilus Infections/drug therapy , Microbial Sensitivity Tests , Monte Carlo Method , Swine/metabolism , Swine Diseases/microbiology , Treatment OutcomeSubject(s)
Algorithms , Antibodies, Monoclonal/therapeutic use , Critical Pathways/standards , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Practice Guidelines as Topic , Rheumatology/standards , Diagnosis, Differential , Evidence-Based Medicine , Germany , HumansABSTRACT
OBJECTIVE: This chapter aims to evaluate current knowledge of the burden of systemic lupus erythematosus (SLE) on individual patients, with a particular focus on health-related quality of life (HRQoL), activities of daily living (ADLs), individual symptoms, such as fatigue and pain, work disability and employment. METHODOLOGY: A literature search was performed in Medline (PubMed) and a qualitative analysis was done of all publications relating to the burden of SLE (January 2000 to May 2010, updated in June 2013) matching the following inclusion criteria: prospective studies involving ≥100 patients with SLE; studies focussing on QoL, ADL, function/disability, patient perceptions/experience of their illness, physical/psychological/social impact, unmet needs, work disability/employment status or specific signs/symptoms expected to impact on HRQoL/ADL; studies predominantly involving patients of Caucasian ethnicity; and studies based in Europe, North America or Australia. Studies in juvenile patients; studies of the impact of obesity; studies of non-pharmacological interventions, dietary supplements or alternative medicines; and health-economic analyses were excluded. RESULTS/CONCLUSIONS: The present literature analysis showed that SLE has a considerable impact on the HRQoL of patients and their ability to carry out normal daily activities, resulting in a high prevalence of disability. The HRQoL of patients with SLE is consistently lower than that of matched healthy control subjects or patients with other chronic diseases. Predictors of poor HRQoL in patients with SLE include older age, fatigue and the presence of co-morbid neurological or psychiatric disorders, particularly depression or anxiety. Conversely, clinical measures of disease activity and organ damage are poor indicators of patients' HRQoL. Even though current evidence gives an insight into the HRQoL in patients with SLE, there are still many areas where results need to be confirmed or clarified and therefore there is the need to conduct further studies including trials with HRQoL as a primary objective.
Subject(s)
Fatigue/complications , Lupus Erythematosus, Systemic/complications , Quality of Life/psychology , Activities of Daily Living/psychology , Fatigue/psychology , Health Status , Humans , Lupus Erythematosus, Systemic/psychology , Sickness Impact ProfileABSTRACT
The objective was to conduct a study to investigate if violative meat residues are detected in very young bob veal calves that are fed first-milking colostrum harvested from cows that were dry treated, on-label, with cephapirin benzathine. First-milking colostrum was collected from cows that were given intramammary treatment at dry off, on-label, with cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Newborn bull calves meeting study inclusion criteria were removed from their dams shortly after birth and before suckling, and assigned to 1 of 2 trials. For the first trial, 6 treated calves were fed 3.8L of fresh maternal colostrum and 1 control calf was fed 1.5 doses of a plasma-derived colostrum replacer (Secure Calf Colostrum Replacer, VitaPlus Inc., Madison, WI) within 1h after birth. For the second trial, 5 treated calves were fed 3.8L of fresh maternal colostrum and 1 control calf was fed 1.5 doses of Secure Calf Colostrum Replacer within 1h after birth. All calves were humanely euthanized at 24h (trial 1) or 48h (trial 2) of age, and tissues were harvested for antimicrobial residue testing. Samples of maternal colostrum and colostrum replacer were also submitted for antimicrobial residue testing. Kidneys collected from all study calves tested negative for cephapirin benzathine residues when using both the KIS assay (Charm Sciences, Lawrence, MA) and liquid chromatography-tandem mass spectrometry analysis. The potential transfer of cephapirin from cows treated on-label at dry off to calves via colostrum may not be a significant source of cephapirin residues in veal tissues.
Subject(s)
Anti-Bacterial Agents/analysis , Cephapirin/analysis , Colostrum/chemistry , Diet/veterinary , Food Contamination/analysis , Meat/analysis , Animals , Animals, Newborn , Anti-Bacterial Agents/administration & dosage , Cattle , Cephapirin/administration & dosage , Drug Residues/analysis , Ethylenediamines/analysis , Female , Kidney/chemistry , Mammary Glands, Animal/drug effectsABSTRACT
New approaches in Pharmacokinetic/Pharmacodynamic (PK/PD) integration suggested that marbofloxacin, a fluoroquinolone already licensed for the treatment of bovine respiratory disease at a daily dosage of 2 mg/kg for 3-5 days, would be equally clinically effective at 10 mg/kg once (Forcyl(®)), whilst also reducing the risk of resistance. This marbofloxacin dosage regimen was studied using mutant prevention concentration (MPC), PK simulation, PK/PD integration and an in vitro dynamic system. This system simulated the concentration-time profile of marbofloxacin in bovine plasma established in vivo after a single 10 mg/kg intramuscular dose and killing curves of field isolated Pasteurellaceae strains of high (minimum inhibitory concentration (MIC) MIC ≤ 0.03 µg/mL), average (MIC of 0.12-0.25 µg/mL) and low (MIC of 1 µg/mL) susceptibility to marbofloxacin. The marbofloxacin MPC values were 2- to 4-fold the MIC values for all Mannheimia haemolytica, Pasteurella multocida tested. Marbofloxacin demonstrated a concentration-dependent killing profile with bactericidal activity observed within 1 h for most strains. No resistance development (MIC ≥ 4 µg/mL) was detected in the dynamic tests. Target values for risk of resistance PK/PD surrogates (area under the curve (AUC) AUC(24 h) /MPC and T(>MPC) /T(MSW) ratio) were achieved for all clinically susceptible pathogens. The new proposed dosing regimen was validated in vitro and by PK/PD integration confirming the single-injection short-acting antibiotic concept.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Cattle/blood , Fluoroquinolones/pharmacology , Fluoroquinolones/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fluoroquinolones/administration & dosage , Fluoroquinolones/blood , Half-Life , Male , Mannheimia haemolytica/drug effects , Microbial Sensitivity Tests , Models, Biological , Pasteurellaceae/drug effectsABSTRACT
The integrated pest management (IPM) premises claim for a joint use of beneficial organisms (parasitoids and predators) and selective pesticides. Botanical pesticides are being considered as selective pesticides. During the last 20 years of the 20th century, the plant family Meliaceae was identified as a promising source of compounds with insect-control properties. The Chinaberry tree, Melia azedarach L., is a deciduous tree native to Persia, India, and China, but has been cultivated in many countries including Africa, Australia, and the Americas. It is a source of tetranortriterpenoid compounds called meliatoxins, which have similar structures and insecticidal activities compared to azadirachtin. Eriopis connexa Germar (Coleoptera: Coccinelidae) is a native predator from the Neotropical Region. It is a beneficial organism associated to several agro-ecosystems, feeding on soft-bodies pest such as aphids, whiteflies and thrips. In horticultural crops, it has been observed to feed on worldwide important pest such as Bemisia tabaci Gennadius (Heteroptera: Aleyrodeidae) and Myzus persicae L. (Heteroptera: Aphididae), both of them considered as virus vectors. The objectives of this work were to evaluate the side-effects of M. azaderach (Meliaceas) extract on eggs, larvae and adults of Eriopis connexa. Extracts from unripe fruits (1%, w/w, obtained by the CEPROCOR, Cordoba-Argentina) were employed for ecotoxicological bioassays. The exposure method was by immersion for eggs and by ingestion of drinking water for adults. The botanical extract solutions were prepared using distilled water as solvent and a tensioactive (Tween 20) for topical application. The bioassays were carried out in the laboratory under controlled conditions: 23 +/- 0.5 degrees C temperature, 75 +/- 5% RH and 16:8 (L:D) photoperiod. Hatching, development time, adult emergence, pre-oviposition period, fecundity and fertility were evaluated as endpoints. No detrimental effects were observed in treated organisms irrespective of the exposure way and development stage. According to these preliminary results, M. azaderach fruit extracts can be compatible with E. connexa for pest control. However, future studies should be addressed to conclude about its toxicity on beneficial organisms.
Subject(s)
Coleoptera/drug effects , Insecticides/toxicity , Melia azedarach/chemistry , Plant Extracts/chemistry , Plant Extracts/toxicity , Animals , Insecticides/chemistry , Ovum/drug effects , Pest Control, Biological/methodsABSTRACT
BACKGROUND: Critical limb ischemia (CLI) is the end-stage of peripheral artery disease. Only about two thirds of patients with CLI can be revascularised, one third progresses to leg amputation with high associated morbidity and mortality. Therapeutic angiogenesis with bone marrow cells has shown promising improvement in less severe stages of peripheral ischemia. Our study evaluates the therapeutic value of bone marrow cell induced angiogenesis and arteriogenesis in severe, limb-threatening ischemia. PATIENTS AND METHODS: the BONe Marrow Outcome Trial in Critical Limb Ischemia (BONMOT-CLI) is a investigator-initiated, double-blinded, 1:1 randomized, placebo-controlled multi-centre study at 4 sites in Germany. Only patients with no option for revascularisation or after failed revascularisation will be included. A total of 90 patients is to be included. One arm with 45 subjects will be treated with a concentrate of autologous bone marrow cells which will be injected at 40 sites into the ischemic limb. In the placebo arm, study subjects will undergo a sham bone marrow punction and 40 saline injections. At three months, a combined primary endpoint of major amputation or persisting critical limb ischemia (no clinical or perfusion improvement) will be evaluated. Secondary endpoints are death, changes in perfusion, quality of life, walking distance, minor amputations, wound healing, collateral density and cancer incidence. Post-study follow-up is up to two years. CONCLUSIONS: The results of this first randomized placebo-controlled trial for autologous bone marrow cell therapy in CLI will clarify the value of this new therapeutic modality in a patient population with no other alternatives except major amputation.
Subject(s)
Bone Marrow Transplantation , Extremities/blood supply , Ischemia/surgery , Amputation, Surgical , Critical Illness , Double-Blind Method , Germany , Humans , Ischemia/mortality , Ischemia/physiopathology , Neovascularization, Physiologic , Quality of Life , Recovery of Function , Regional Blood Flow , Research Design , Time Factors , Transplantation, Autologous , Treatment Outcome , Walking , Wound HealingABSTRACT
Disturbances in cortico-cortical and cortico-subcortical circuits in schizophrenia have been described by previous neuroimaging and electrophysiological studies. Transcranial magnetic stimulation (TMS) provides a neurophysiological technique for the measurement of cortical excitability, especially of the motoneural system. Previous studies using paired-pulse TMS to investigate short-interval cortical inhibition (SICI) and intracortical facilitation (ICF), mainly involving chronic schizophrenia patients, have been inconsistent and only one study in first-episode patients has been conducted so far. We assessed SICI (interstimulus interval, ISI, 3 milliseconds, ms) and ICF (ISI 7 ms) in 29 first-episode schizophrenia patients (FE-SZ) with limited exposure to antipsychotic treatment against measures of 28 healthy controls (HC). Amplitudes of motor evoked potentials (MEPs) were measured from the left and right first dorsal interosseus muscle (FDI). The conditioning stimulus was set at 80% intensity of resting motor threshold (RMT) and the test stimulus (TS) was set at an intensity that produced an MEP amplitude of about 1 mV. For SICI conditions, FE-SZ demonstrated significantly higher MEP amplitudes from left motor cortex (right FDI) compared to HC, and for MEPs from right motor cortex (left FDI) a similar trend was observable (FE-SZ 41% vs. HC 21% of TS, p=0.017 for left motor cortex, and FE-SZ 59% vs. HC 31% of TS, p=0.059 for right motor cortex; Mann-Whitney U-test). No significant difference in MEPs could be detected for ICF on either hemisphere. In addition, there was no difference in left and right RMT comparing patients and control subjects. Our result of a reduced SICI in a large sample of well characterized first-episode schizophrenia patients suggests that a GABAergic deficit may be involved in schizophrenic pathophysiology, already early in the disease course, supporting the intracortical dysconnectivity hypothesis.
Subject(s)
Cerebral Cortex/physiopathology , Neural Inhibition/physiology , Schizophrenia/physiopathology , Adult , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Control Groups , Evoked Potentials, Motor/physiology , Female , Functional Laterality/physiology , Humans , Male , Motor Cortex/physiopathology , Motor Neurons/physiology , Neural Pathways/physiopathology , Reaction Time/physiology , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Transcranial Magnetic Stimulation/methods , gamma-Aminobutyric Acid/physiologyABSTRACT
BACKGROUND: The Genius dialysis system is increasingly used as an intermittent hemodialysis device in the setting of acute renal failure. Slow extended hemodialysis is preferred in the case of critical ill patients. In this study we established a safe and feasible citrate anticoagulation protocol for slow extended hemodialysis (SLED) with the Genius system. METHODS: We compared six anticoagulation protocols using SLED in 34 critically ill patients with acute renal failure. One group (A) received only citrate anticoagulation. Four groups (B - D) were treated with citrate and different additional systemic anticoagulation. Patients in the last group (F) were anticoagulated with heparin and were free of citrate anticoagulation. The total number of treatments was 103. A 4% sodium citrate solution was infused into the arterial line of the dialysis device for citrate anticoagulation. The dialysis solution contained one mmol/L of calcium. No additional calcium supplementation was done. We monitored electrolyte, acid-base and cardiovascular status prospectively. RESULTS: Hemodialysis was well tolerated hemodynamically. Electrolytes remained stable throughout hemodialysis in all groups. The decrease in ionized and total calcium was within the expected, clinically acceptable range. Bicarbonate and pH levels increased during dialysis, especially if citrate was used. CONCLUSIONS: Slow extended Genius hemodialysis with citrate is well tolerated and offers a safe and effective alternative to systemic anticoagulation.