ABSTRACT
Orthostatic hypertension, defined by an increase of systolic blood pressure (SBP) of ≥20 mmHg upon standing, harbors an increased cardiovascular risk. We pooled data from two rigorously conducted head-down tilt bedrest studies to test the hypothesis that cardiopulmonary deconditioning and hypovolemia predispose to orthostatic hypertension. With bedrest, peak VO2 decreased by 6 ± 4 mlO2/min/kg (p < 0.0001) and plasma volume by 367 ± 348 ml (p < 0.0001). Supine SBP increased from 127 ± 9 mmHg before to 133 ± 10 mmHg after bedrest (p < 0.0001). In participants with stable hemodynamics following head-up tilt, the incidence of orthostatic hypertension was 2 out of 67 participants before bedrest and 2 out of 57 after bedrest. We conclude that in most healthy persons, cardiovascular deconditioning and volume loss associated with long-term bedrest are not sufficient to cause orthostatic hypertension.
Subject(s)
Bed Rest , Blood Pressure , Head-Down Tilt , Hypertension , Plasma Volume , Humans , Male , Female , Adult , Bed Rest/adverse effects , Middle Aged , Blood Pressure/physiology , Hypertension/physiopathology , Cardiovascular Deconditioning/physiology , Hypovolemia/physiopathology , Hypovolemia/complications , Hemodynamics/physiology , Oxygen Consumption/physiologyABSTRACT
The use of bioresorbable magnesium (Mg)-based elastic stable intramedullary nails (ESIN) is highly promising for the treatment of pediatric long-bone fractures. Being fully resorbable, a removal surgery is not required, preventing repeated physical and psychological stress for the child. Further, the osteoconductive properties of the material support fracture healing. Nowadays, ESIN are exclusively implanted in a non-transphyseal manner to prevent growth discrepancies, although transphyseal implantation would often be required to guarantee optimized fracture stabilization. Here, we investigated the influence of trans-epiphyseally implanted Mg-Zinc (Zn)-Calcium (Ca) ESIN on the proximal tibial physis of juvenile sheep over a period of three years, until skeletal maturity was reached. We used the two alloying systems ZX10 (Mg-1Zn-0.3Ca, in wt%) and ZX00 (Mg-0.3Zn-0.4Ca, in wt%) for this study. To elaborate potential growth disturbances such as leg-length differences and axis deviations we used a combination of in vivo clinical computed tomography (cCT) and ex vivo micro CT (µCT), and also performed histology studies on the extracted bones to obtain information on the related tissue. Because there is a lack of long-term data regarding the degradation performance of magnesium-based implants, we used cCT and µCT data to evaluate the implant volume, gas volume and degradation rate of both alloying systems over a period of 148 weeks. We show that transepiphyseal implantation of Mg-Zn-Ca ESIN has no negative influence on the longitudinal bone growth in juvenile sheep, and that there is no axis deviation observed in all cases. We also illustrate that 95 % of the ESIN degraded over nearly three years, converging the time point of full resorption. We thus conclude that both, ZX10 and ZX00, constitute promising implant materials for the ESIN technique.
Subject(s)
Magnesium , Zinc , Animals , Sheep , Magnesium/pharmacology , Calcium , Bone Nails , X-Ray MicrotomographyABSTRACT
Dysphagia is a clinically relevant problem in Parkinson's disease as well as in atypical Parkinsonian syndromes, such as multiple system atrophy and diseases from the spectrum of 4repeat tauopathies, which affect most patients to a varying degree in the course of their disease. This results in relevant restrictions in daily life due to impaired intake of food, fluids, and medication with a subsequent reduction in quality of life. This article not only gives an overview of the pathophysiological causes of dysphagia in the various Parkinson syndromes, but also presents screening, diagnostic and treatment procedures that have been investigated for the different diseases.
Subject(s)
Deglutition Disorders , Multiple System Atrophy , Parkinson Disease , Parkinsonian Disorders , Humans , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Quality of Life , Parkinsonian Disorders/complications , Parkinsonian Disorders/diagnosis , Parkinsonian Disorders/therapy , Parkinson Disease/complications , Parkinson Disease/diagnosis , Parkinson Disease/therapy , Multiple System Atrophy/complications , Multiple System Atrophy/diagnosis , Multiple System Atrophy/therapyABSTRACT
The Critically Endangered southern corroboree frog Pseudophryne corroboree is dependent upon captive assurance colonies for its continued survival. Although the captive breeding programme for this species has largely been successful, embryonic mortality remains high (40-90% per year). This study aimed to investigate the causes of mortality in P. corroboree embryos in the captive collection at Melbourne Zoo. During the 2021 breeding season, we investigated 108 abnormal embryos to determine the impact of infections and anatomical deformities on survival and used culture and molecular methods to identify microbes. Overall, 100% of abnormal embryos had fungal infections, and of these, 41.6% also had anatomical deformities. The mortality rate in abnormal embryos was 89.8%; however, we detected no difference in survival in any of the 3 observed fungal growth patterns or between deformed and non-deformed embryos. Sanger sequencing of the ITS region identified fungal isolates belonging to the genus Ilyonectria, the first record in a vertebrate host, and another as a Plectosphaerella sp., which is the first record of infection in an embryo. Dominant bacteria identified were of the genera Herbaspirillum and Flavobacterium; however, their role in the mortality is unknown. Fungal infection and deformities have a significant impact on embryo survival in captive-bred P. corroboree. In a species which relies on captive breeding, identifying and reducing the impacts of embryonic mortality can inform conservation efforts and improve reintroduction outcomes.
Subject(s)
Anura , Flavobacterium , Animals , SeasonsABSTRACT
Macrolides are one of the treatments of choice in community-acquired pneumonia, either when the clinical and/or biological elements suggest an infection by an intracellular bacteria (so-called atypical), or when the severity of the clinical picture justifies their empirical use. This work is a retrospective monocentric study carried out at the University Hospital of Liege on 25 consecutive patients hospitalized during the year 2019. It aims to specify whether the use of a particular macrolide, clarithromycin, actually meets the national recommendations both in terms of indication, dosage or duration. The results showed justified and adequate use in only 44 % of cases. Nevertheless, the indication was overwhelmingly mentioned in the medical record (96 %). Furthermore, the comparison with national data showed a much higher than average use at the University Hospital of Liege. An action plan is suggested to discuss these results within the Antibiotic Therapy Management Group and then communicate them to the prescribers who are concerned. The aim is to adapt the use of macrolides at the University Hospital of Liege to be more in line with national recommendations.
Les macrolides sont un des traitements de choix dans les pneumopathies communautaires, soit lorsque les éléments cliniques et/ou biologiques suggèrent une infection par une bactérie intracellulaire (dite atypique), soit lorsque la sévérité du tableau clinique justifie d'emblée leur usage empirique. Ce travail est une étude rétrospective monocentrique réalisée au CHU de Liège sur 25 dossiers consécutifs de patients hospitalisés durant l'année 2019. Il vise à préciser si l'usage d'un macrolide particulier, la clarithromycine, répond effectivement aux recommandations nationales, tant en matière d'indication, de posologie ou de durée. Les résultats ont montré un usage justifié et adéquat dans 44 % des cas seulement. Néanmoins, l'indication était très majoritairement mentionnée dans le dossier médical (96 %). Par ailleurs, la comparaison avec les données nationales a montré un usage bien supérieur à la moyenne au CHU de Liège. Un plan d'action est suggéré afin de discuter ces résultats au sein du Groupe de Gestion de l'Antibiothérapie pour, ensuite, les communiquer aux prescripteurs concernés. Cette stratégie est proposée afin d'adapter l'usage des macrolides au CHU de Liège pour qu'il s'accorde davantage avec les recommandations nationales.
Subject(s)
Clarithromycin , Community-Acquired Infections , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/drug therapy , Hospitals , Humans , Macrolides , Retrospective StudiesABSTRACT
PURPOSE: Although three-dimensional conformal radiotherapy (3D-CRT) remains the gold standard as a curative treatment for NSCLC when surgery is not possible, intensity modulated radiotherapy (IMRT) is increasingly used routinely. The purpose of this study was to assess the clinical (immediate toxicities) and dosimetric impact of IMRT compared to 3D-CRT in the treatment of locally advanced (stages IIIA to IIIC) non-small cell lung cancer (NSCLC) treated with concomitant radiochemotherapy, while IMRT in lung cancer was implemented in the radiotherapy department of the Jean-Perrin Center. PATIENTS AND METHODS: Between March 2015 and October 2019, 64 patients treated with concomitant radiochemotherapy were retrospectively included. Thirty-two received 3D-CRT and 32 IMRT. The radiotherapy prescription was 66Gy in 33 fractions of 2Gy. RESULTS: IMRT has improved coverage of target volumes (V95 increased by 14.81% in IMRT; P<0.001) without increasing doses to OARs and reducing dysphagia (RR=0.67; P=0.027). Low doses to the lung were not significantly increased in IMRT (pulmonary V5 increased by 7.46% in IMRT). CONCLUSION: Intensity modulated radiotherapy, compared with the standard RC3D technique, improve the coverage of target volumes without increasing the dose to the OARs. It also improves the immediate tolerance of the treatment by reducing the number of dysphagia.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Organs at Risk/radiation effects , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Dose Fractionation, Radiation , Esophagus/radiation effects , Humans , Lung/radiation effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Middle Aged , Radiotherapy, Conformal/adverse effects , Radiotherapy, Conformal/methods , Radiotherapy, Conformal/statistics & numerical data , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/statistics & numerical data , Retrospective Studies , Skin/radiation effectsABSTRACT
BACKGROUND: Reference intervals for haematology and serum biochemistry parameters were developed for free-ranging Lumholtz's tree-kangaroo (Dendrolagus lumholtzi) using 35 samples from 12 female and 15 male free-ranging animals. Captive tree-kangaroos (n = 12) were also sampled for comparison. Differences were found between free-ranging and captive animals in white blood cell and neutrophil counts, and levels of aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, phosphate, triglycerides and lipase. These differences may be attributed to diet, activity, capture methods or age group. Reference intervals generated may be used for both free-ranging and captive Lumholtz's tree-kangaroos. This study provides a valuable tool for the assessment of health in rescued and captive tree-kangaroos and will aid in investigations into population health and disease in free-ranging Lumholtz's tree-kangaroos. OBJECTIVE: To develop reference intervals (RIs) for haematology and serum biochemistry parameters in Lumholtz's tree-kangaroos. METHODS: Haematological and serum biochemical RIs were determined using 35 samples from 27 clinically healthy Lumholtz's tree-kangaroos from the Atherton Tablelands region of Queensland examined between 2014 and 2019. Haematology and serum biochemistry parameters were measured from 16 samples from 12 captive animals for comparison. RESULTS: Reference intervals based on 35 samples from free-ranging animals showed higher mean and standard deviation values for white blood cell and neutrophil counts, and levels of aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, phosphate, triglycerides and lipase than results for 16 samples from captive animals. Captive individuals showed higher mean values than free-ranging individuals for albumin, protein, creatinine as well as Hb, MCV, MCH and MCHC. CONCLUSION: The haematological and serum biochemistry RIs developed for Lumholtz's tree-kangaroos in this study will provide a valuable tool during clinical examination and investigations into disease and population health by veterinarians and researchers. The differences in parameters between free-ranging and captive animals are consistent with differences in diet, age cohort, activity or capture methods. Reference intervals generated from free-ranging animals should also be valid for captive Lumholtz's tree-kangaroos.
Subject(s)
Macropodidae , Trees , Animals , Blood Chemical Analysis/veterinary , Creatinine , Female , Queensland , Reference ValuesABSTRACT
Alzheimer's Disease (AD) is a neurodegenerative progressive disorder for which there is currently no cure. Recent research demonstrates a robust correlation between type-2 diabetes mellitus (T2DM) and the development of MCI and AD, now referred to as type-3 diabetes. Both AD and T2DM, as metabolic pathologies, can be traced to the level of mitochondrial function. The metabolic hypothesis suggests that the cause of AD might be rooted in mitochondrial dysfunction accompanied by fuel shortage in the brain. Although glucose is known to be the deferred source of fuel for cells, ketone bodies have been observed to provide metabolically compromised brain cells with an alternative fuel source, bypassing deficiencies in GLUT transport due to increased insulin resistance. By keeping glucose and insulin levels low to allow for the production of ketones, there is evidence that mitochondrial function will be restored and cognition/memory improved. Further, visible red or near-infrared (NIR) light has been shown to heal and stimulate damaged tissue by interacting with the mitochondria to restore function. This case study evaluates the effects of a 10-week clinically prescribed ketogenic nutrition protocol combined with transcranial photobiomodulation (PBM) with a 59-year-old male, heterozygous ApoE4 carrier, with a dual diagnosis of mild AD and an 11 year history of insulin dependent type 2 diabetes (T2DM). Statistically significant results reflect an 83% reduction in HOMA-IR; 64% decrease in the triglyceride/HDL ratio; HgA1c reduction from 9.44% to 6.4%; 57% decrease in VLDL and triglycerides; and normalized cognition as measured via the MoCA (Montreal Cognitive Assessment), 26/30 post intervention.
Subject(s)
Alzheimer Disease/therapy , Apolipoprotein E4/metabolism , Diabetes Mellitus, Type 2/therapy , Low-Level Light Therapy/methods , Alzheimer Disease/complications , Alzheimer Disease/diet therapy , Alzheimer Disease/radiotherapy , Blood Glucose , Cognitive Dysfunction , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/radiotherapy , Diet, Ketogenic , Glycated Hemoglobin , Humans , Ketosis , Lipids/blood , Male , Mental Status and Dementia Tests , Middle AgedABSTRACT
The Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) spacecraft landed successfully on Mars and imaged the surface to characterize the surficial geology. Here we report on the geology and subsurface structure of the landing site to aid in situ geophysical investigations. InSight landed in a degraded impact crater in Elysium Planitia on a smooth sandy, granule- and pebble-rich surface with few rocks. Superposed impact craters are common and eolian bedforms are sparse. During landing, pulsed retrorockets modified the surface to reveal a near surface stratigraphy of surficial dust, over thin unconsolidated sand, underlain by a variable thickness duricrust, with poorly sorted, unconsolidated sand with rocks beneath. Impact, eolian, and mass wasting processes have dominantly modified the surface. Surface observations are consistent with expectations made from remote sensing data prior to landing indicating a surface composed of an impact-fragmented regolith overlying basaltic lava flows.
ABSTRACT
PURPOSE: To determine whether the interactive visualisation of patient-specific virtual 3D models of the renal anatomy influences the pre-operative decision-making process of urological surgeons for complex renal cancer operations. METHODS: Five historic renal cancer patient pre-operative computed tomography (CT) datasets were retrospectively selected based on RENAL nephrectomy score and variety of anatomy. Interactive virtual 3D models were generated for each dataset using image segmentation software and were made available for online visualisation and manipulation. Consultant urologists were invited to participate in the survey which consisted of CT and volume-rendered images (VRI) for the control arm, and CT with segmentation overlay and the virtual 3D model for the intervention arm. A questionnaire regarding anatomical structures, surgical approach, and confidence was administered. RESULTS: Twenty-five participants were recruited (54% response rate), with 19/25 having > 5 years of renal surgery experience. The median anatomical clarity score increased from 3 for the control to 5 for the intervention arm. A change in planned surgical approach was reported in 19% of cases. Virtual 3D models increased surgeon confidence in the surgical decisions in 4/5 patient datasets. There was a statistically significant improvement in surgeon opinion of the potential utility for decision-making purposes of virtual 3D models as compared to VRI at the multidisciplinary team meeting, theatre planning, and intra-operative stages. CONCLUSION: The use of pre-operative interactive virtual 3D models for surgery planning influences surgical decision-making. Further studies are needed to investigate if the use of these models changes renal cancer surgery outcomes.
Subject(s)
Clinical Competence , Decision Making , Imaging, Three-Dimensional , Kidney Neoplasms/diagnosis , Nephrectomy/methods , Surgeons/standards , Tomography, X-Ray Computed/methods , Female , Humans , Kidney/diagnostic imaging , Kidney/surgery , Kidney Neoplasms/surgery , Male , Retrospective Studies , Tumor BurdenABSTRACT
Fracture treatment in children needs new implant materials to overcome disadvantages associated with removal surgery. Magnesium-based implants constitute a biocompatible and bioresorbable alternative. In adults and especially in children, implant safety needs to be evaluated. In children the bone turnover rate is higher and implant material might influence growth capacity, and the long-term effect of accumulated particles or ions is more critical due to the host's prolonged post-surgery lifespan. In this study we aimed to investigate the degradation behavior of ZX00 (Mg-0.45Zn-0.45Ca; in wt.%) in a small and a large animal model to find out whether there is a difference between the two models (i) in degradation rate and (ii) in bone formation and in-growth. Our results 6, 12 and 24â¯weeks after ZX00 implantation showed no negative effects on bone formation and in-growth, and no adverse effects such as fibrotic or sclerotic encapsulation. The degradation rate did not significantly differ between the two growing-animal models, and both showed slow and homogeneous degradation performance. Our conclusion is that small animal models may be sufficient to investigate degradation rates and provide preliminary evidence on bone formation and in-growth of implant materials in a growing-animal model. STATEMENT OF SIGNIFICANCE: The safety of implant material is of the utmost importance, especially in children, who have enhanced bone turnover, more growth capacity and longer postoperative lifespans. Magnesium (Mg)-based implants have long been of great interest in pediatric orthopedic and trauma surgery, due to their good biocompatibility, biodegradability and biomechanics. In the study documented in this manuscript we investigated Mg-Zn-Ca implant material without rare-earth elements, and compared its outcome in a small and a large growing-animal model. In both models we observed bone formation and in-growth which featured no adverse effects such as fibrotic or sclerotic encapsulation, and slow homogeneous degradation performance of the Mg-based implant material.
Subject(s)
Absorbable Implants , Implants, Experimental , Magnesium/pharmacology , Animals , Bone Screws , Bone and Bones/drug effects , Bone and Bones/physiology , Female , Models, Animal , Osseointegration/drug effects , Osteogenesis/drug effects , Rats, Sprague-Dawley , Sheep , X-Ray MicrotomographyABSTRACT
OBJECTIVE: To describe characteristics and long-term outcomes of the rare symptomatic lower-limb giant-cell arteritis (LL-GCA). METHODS: Retrospective analysis of 8 patients (6 women; mean±SD age, 63.6±10.9 years; follow-up, 137.3±57.3 months). RESULTS: Four patients satisfied≥3 American College of Rheumatology (ACR) GCA-classification criteria; 4 had<3 criteria and histological LL-GCA proof or associated typical upper-limb involvement. Patients had 2.1±1.1 vascular risk factors. Bilateral and rapidly progressive arterial claudication was the first LL sign; 2 had rest ischemia. Imaging-visualized most-to-least frequent inflammatory lesion localizations were: superficial femoral, popliteal, tibiofibular trunk, posterior tibial arteries. All received corticosteroids for 132±76.2 months; 2 required immunosuppressive agent adjunction. Only 3 required 1-6 revascularizations: twice during the first month post-diagnosis and twice later. Thromboendarterectomy and endovascular procedures did not work while bypasses were successful. LL-claudication regressed for 7 (10.5±12.1 months) and disappeared for 5 (16.8±9.8 months). Three patients stopped corticosteroids (26-90 months), 1 restarted 45 months later. Every patient relapsed once (23.9±26.7 months, mean corticosteroid dose: 0.28±0.30mg/kg/day). LL-GCA caused only 1 of the 4 deaths. CONCLUSION: Symptomatic LL-GCA attributable long-term mortality seems to be low despite frequent relapses and corticosteroid-dependence.
Subject(s)
Giant Cell Arteritis , Lower Extremity/blood supply , Adult , Aged , Female , Giant Cell Arteritis/diagnosis , Giant Cell Arteritis/therapy , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: Intensity modulated radiotherapy for prostate cancer involves daily monitoring of the positioning of the prostate, possible with cone beam CT (CBCT). It allows increased accuracy compared to readjustments but induces an increase in the time dedicated to these medical checks. The aim of the study was to evaluate the possibility of delegation of this task to the radiation therapists by comparing their readjustments to the doctors. PATIENTS AND METHODS: Five consecutive patients treated with radiation for prostate cancer (76Gy) were analysed. All had a daily CBCT for position control. The movements of the prostate relative to the bony part, the positional variations of the prostate measured by the radiation therapists and the doctors and medical time required to analyse imagery (filling of the rectum and bladder and perform a recalibration) were measured. RESULTS: One hundred seventy-six CBCT were analysed or 980 steps in the three axes. The movements of the prostate relative to bony part were respectively at least 5mm in 19%, 7% and 3% in the anterior-posterior, upper-lower and right-left axes. Changes readjustments between radiation therapists and doctors were in 95% of cases at the most 4mm in the anterior-posterior and upper-lower axis, and 3mm in the left-right axis. The time for medical use of the CBCT averaged 8min 40 [4 to 22min]. CONCLUSION: The daily readjustment on the prostate using CBCT may be delegated to radiation therapists with acceptable concordance of less than 4mm for 95% of measurements. An initial and ongoing training will ensure treatment safety.
Subject(s)
Allied Health Personnel , Cone-Beam Computed Tomography , Patient Positioning , Prostate/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated/methods , Aged , Efficiency , Humans , Male , Middle Aged , Organs at Risk , Physician's Role , Radiotherapy Dosage , Time FactorsABSTRACT
AIMS: To describe the gross and light microscopic characteristics of skin lesions observed on the ventral skin of captive Archey's frogs (Leiopelma archeyi) between 2000 and 2012, and to investigate their occurrence, possible aetiology and association with survival. METHODS: Postmortem skin samples were obtained for histological evaluation from 37 frogs, with and without skin lesions, that died while in captivity at Auckland Zoo between 2000 and 2012. Four frogs with skin lesions were biopsied under general anaesthesia and samples used for both light and transmission electron microscopy. The records of 94 frogs held at the University of Otago and Auckland Zoo between 2000-2012 were reviewed, which included some frogs recently collected from the wild. Information about the occurrence of skin lesions, and mortality associated with skin lesions was collated. RESULTS: Grossly the skin lesions varied in appearance; most were circular, pale grey papules, which measured from <0.5-1.5â mm in diameter with no umbilication. The overlying epidermis was not fragile and there was no associated inflammation. Contents often appeared clear or semi-transparent. Lesions were located predominantly on ventral surfaces including trunk, thighs, lower legs and forearms, and gular region, but not on digits. The number ranged from single to multiple, often confluent lesions covering the entire ventral surface of the frog. Histologically the lesions consisted of enlarged proliferating mucous glands that expanded the dermis and elevated the epidermis. They were semi-organised, solid or occasionally cavitated acinar structures with central lumina which sometimes contained mucus. Nuclei showed moderate anisokaryosis and mitotic figures were uncommon. Transmission electron microscopy did not show any infectious agents. Between 2000 and 2012, skin lesions were recorded in 35/94 (37%) frogs. The size and location of skin lesions varied over time, with some resolving and sometimes reappearing. Skin lesions were not associated with an increased risk of death. CONCLUSIONS: The skin lesions had the gross and microscopic characteristics of adenomatous hyperplasia of the dermal mucous glands. CLINICAL RELEVANCE: The aetiology of this adenomatous hyperplasia is unknown, but factors associated with the captive environment are the most likely cause. This is the first description of adenomatous hyperplasia of the cutaneous mucous glands in amphibians.
Subject(s)
Anura , Hyperplasia/veterinary , Skin Diseases/veterinary , Animals , Hyperplasia/pathology , Skin/ultrastructure , Skin Diseases/mortality , Skin Diseases/pathologyABSTRACT
Intensity modulated radiation therapy (IMRT) and brachytherapy are standard techniques for the irradiation of oral cavity cancers. These techniques are detailed in terms of indication, preparation, delineation and selection of the volumes, dosimetry and patient positioning control.
Subject(s)
Brachytherapy/methods , Mouth Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Brachytherapy/adverse effects , Brachytherapy/standards , Dose Fractionation, Radiation , Humans , Lymphatic Irradiation/methods , Lymphatic Metastasis , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/therapy , Organs at Risk , Patient Positioning , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Image-Guided , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/standardsABSTRACT
Three experiments evaluated the effects of ractopamine hydrochloride (RAC) dose and duration on growth performance and carcass characteristics of feedlot steers. In total, 1,509 crossbred steers (530 kg initial BW [SD 22]) were used in a randomized complete block design using a 3 × 3 factorial treatment structure. Treatments consisted of RAC dose (0, 100, or 200 mg/steer daily) and duration (28, 35, or 42 d) of RAC feeding prior to harvest. Initiation of RAC dose was staggered (7 d apart) based on RAC duration, which resulted in common days on feed among treatments. Data from the 3 experiments were combined for statistical analyses. There were no RAC dose × duration interactions ( ≥ 0.85) for growth performance. Live final BW was not different ( ≥ 0.24) as RAC dose increased. Dry matter intake linearly decreased ( < 0.01) as RAC dose increased. Live ADG and G:F linearly increased ( ≤ 0.01) as RAC dose increased. Carcass-adjusted ADG and G:F linearly increased ( ≤ 0.02) as RAC dose increased. Compared with steers fed 0 mg RAC/steer daily, G:F was improved by 5.0 and 13.0% when steers were fed 100 ( = 0.31) and 200 ( = 0.01) mg RAC/steer daily, respectively. Hot carcass weight tended ( = 0.10) to linearly increase as RAC dose increased, with carcasses from steers fed 100 ( = 0.38) and 200 ( = 0.10) mg RAC/steer daily being 2.2 and 4.1 kg heavier, respectively, than carcasses from steers fed 0 mg RAC/steer daily. Increasing RAC dose linearly ( < 0.01) increased LM area and linearly ( = 0.02) decreased marbling score. Live final BW was not different ( ≥ 0.60) among RAC durations. Carcass-adjusted final BW, ADG, and G:F were not different ( ≥ 0.41) as RAC duration increased. Carcass traits did not differ ( ≥ 0.18) among RAC duration. Feeding 200 mg RAC/steer daily improved ADG, feed efficiency, and HCW. Increasing the feeding duration of RAC had no effect of growth performance or carcass characteristics. These data indicate that feeding 200 mg RAC/steer daily for 28 d improves steer growth performance.
Subject(s)
Body Composition/drug effects , Cattle/growth & development , Phenethylamines/pharmacology , Adrenergic beta-Agonists/administration & dosage , Adrenergic beta-Agonists/pharmacology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Diet/veterinary , Dose-Response Relationship, Drug , Male , Phenethylamines/administration & dosage , Weight Gain/drug effectsABSTRACT
The permeable nature of frog skin presents an alternative route for the delivery of therapeutic chemicals to treat disease in frogs. However, although therapeutic chemicals are often topically applied to the skin of frogs, their pharmacokinetics have rarely been reported. To provide evidence to guide both candidate drug and formulation selection, we highlight factors expected to influence percutaneous absorption through frog skin, including the anatomy and physiology of the skin and the physicochemical properties of applied therapeutic chemicals. Importantly, we also highlight the effects of the formulation on percutaneous absorption, especially the inclusion of potential penetration enhancers as excipients. Finally, we collate empirical data on the topical application of various therapeutic chemicals in postmetamorphic frogs and show that, in contrast to mammalian species, even large chemicals (i.e. >500 Da) and those with a wide range of log P values (-4 through +6) are likely to be absorbed percutaneously. Topical application in frogs thus promises a convenient and effective method for delivering systemic treatments of a diverse range of chemicals; however, further experimental quantification is required to ensure optimal outcomes.
Subject(s)
Animal Diseases/drug therapy , Anura , Pharmaceutical Preparations/administration & dosage , Skin/drug effects , Administration, Topical , Animals , Skin Physiological PhenomenaABSTRACT
Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel.
Subject(s)
Induction Chemotherapy , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/therapy , Paclitaxel/administration & dosage , Salvage Therapy , Disease-Free Survival , Female , Humans , Male , Survival Rate , Young AdultABSTRACT
In early 2015, an outbreak of 10 confirmed measles cases occurred in Toronto, Ontario. As part of the outbreak response, the Toronto Public Health staff conducted both traditional and supplementary case investigation activities. Despite this extensive effort, and unlike many previous measles outbreaks in Canada, neither the source case nor any confirmed epidemiologic links between cases were identified. The outbreak investigation brought to light potential gaps in the current measles surveillance and suggested approaches to future investigations: routine use of social media and other time-stamped resources to enhance case investigation; early and repeated targeted communication with primary care partners to improve case detection; and continued efforts to increase and maintain sufficient immunization coverage to interrupt transmission.