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1.
Sci Rep ; 13(1): 20415, 2023 11 21.
Article in English | MEDLINE | ID: mdl-37990118

ABSTRACT

Habitat selection studies facilitate assessing and predicting species distributions and habitat connectivity, but habitat selection can vary temporally and among individuals, which is often ignored. We used GPS telemetry data from 96 Gray wolves (Canis lupus) in the western Great Lakes region of the USA to assess differences in habitat selection while wolves exhibited resident (territorial) or non-resident (dispersing or floating) movements and discuss implications for habitat connectivity. We used a step-selection function (SSF) to assess habitat selection by wolves exhibiting resident or non-resident movements, and modeled circuit connectivity throughout the western Great Lakes region. Wolves selected for natural land cover and against areas with high road densities, with no differences in selection among wolves when resident, dispersing, or floating. Similar habitat selection between resident and non-resident wolves may be due to similarity in environmental conditions, when non-resident movements occur largely within established wolf range rather than near the periphery or beyond the species range. Alternatively, non-resident wolves may travel through occupied territories because higher food availability or lower human disturbance outweighs risks posed by conspecifics. Finally, an absence of differences in habitat selection between resident and non-resident wolf movements may be due to other unknown reasons. We recommend considering context-dependency when evaluating differences in movements and habitat use between resident and non-resident individuals. Our results also provide independent validation of a previous species distribution model and connectivity analysis suggesting most potential wolf habitat in the western Great Lakes region is occupied, with limited connectivity to unoccupied habitat.


Subject(s)
Wolves , Humans , Animals , Ecosystem , Territoriality , Movement , Great Lakes Region
2.
Sci Rep ; 12(1): 13556, 2022 08 08.
Article in English | MEDLINE | ID: mdl-35941166

ABSTRACT

Using existing data can be a reliable and cost-effective way to predict species distributions, and particularly useful for recovering or expanding species. We developed a current gray wolf (Canis lupus) distribution model for the western Great Lakes region, USA, and evaluated the spatial transferability of single-state models to the region. This study is the first assessment of transferability in a wide-ranging carnivore, as well as one of few developed for large spatial extents. We collected 3500 wolf locations from winter surveys in Minnesota (2017-2019), Wisconsin (2019-2020), and Michigan (2017-2020). We included 10 variables: proportion of natural cover, pastures, and crops; distance to natural cover, agriculture, developed land, and water; major and minor road density; and snowfall (1-km res.). We created a regional ensemble distribution by weight-averaging eight models based on their performance. We also developed single-state models, and estimated spatial transferability using two approaches: state cross-validation and extrapolation. We assessed performance by quantifying correlations, receiver operating characteristic curves (ROC), sensitivities, and two niche similarity indices. The regional area estimated to be most suitable for wolves during winter (threshold = maximum sensitivity/specificity) was 106,465 km2 (MN = 48,083 km2, WI = 27,757 km2, MI = 30,625 km2) and correctly predicted 88% of wolf locations analyzed. Increasing natural cover and distance to crops were consistently important for determining regional and single-state wolf distribution. Extrapolation (vs. cross-validation) produced results with the greatest performance metrics, and were most similar to the regional model, yet good internal performance was unrelated to greater extrapolation performance. Factors influencing species distributions are scale-dependent and can vary across areas due to behavioral plasticity. When extending inferences beyond the current occurrence of individuals, assessing variation in ecology such as habitat selection, as well as methodological factors including model performance, will be critical to avoid poor scientific interpretations and develop effective conservation applications. In particular, accurate distribution models for recovering or recovered carnivores can be used to develop plans for habitat management, quantify potential of unoccupied habitat, assess connectivity modeling, and mitigate conflict, facilitating long-term species persistence.


Subject(s)
Wolves , Animals , Conservation of Natural Resources/methods , Data Collection , Ecosystem , Seasons
3.
J. cardiothoracic vasc. anest ; 34(2): 1-9, Feb., 2020. tab, graf
Article in English | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1052870

ABSTRACT

ABSTRACT:This article reviews fellowship training in adult cardiac, thoracic, and vascular anesthesia and critical care from the perspective of European program initiators and educational leaders in these subspecialties together with current training fellows. Currently, the European Association of Cardiothoracic Anaesthesiology (EACTA) network has 20 certified fellowship positions each year in 10 hosting centers within 7 European countries, with 2 positions outside Europe (São Paulo, Brazil). Since 2009, 42 fellows have completed the fellowship training. The aim of this article is to provide an overview of the rationale, requirements, and contributions of the fellows, in the context of the developmental progression of the EACTA fellowship in adult cardiac, thoracic, and vascular anesthesia and critical care from inception to present. A summary of the program structure, accreditation of host centers, requirements to join the program, teaching and assessment tools, certification, and training requirements in transesophageal electrocardiography is outlined. In addition, a description of the current state of EACTA fellowships across Europe, and a perspective for future steps and challenges to the educational program, is provided. (AU)


Subject(s)
Critical Care , Anesthesia, Cardiac Procedures , Anesthesia
4.
Eur J Paediatr Dent ; 16(4): 272-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26637248

ABSTRACT

AIM: To identify the ideal timing of first permanent molar extraction to reduce the future need for orthodontic treatment. MATERIALS AND METHODS: A computerised database and subsequent manual search was performed using Medline database, Embase and Ovid, covering the period from January 1946 to February 2013. Two reviewers (JE and ME) extracted the data independently and evaluated if the studies matched the inclusion criteria. Inclusion criteria were specification of the follow-up with clinical examination or analysis of models, specification of the chronological age or dental developmental stage at the time of extraction, no treatment in between, classification of the treatment result into perfect, good, average and poor. The search was limited to human studies and no language limitations were set. RESULTS: The search strategy resulted in 18 full-text articles, of which 6 met the inclusion criteria. By pooling the data from maxillary sites, good to perfect clinical outcome was estimated in 72% (95% confidence interval 63%-82%). Extractions at the age of 8-10.5 years tended to show better spontaneous clinical outcomes compared to the other age groups. By pooling the data from mandibular sites, extractions performed at the age of 8-10.5 and 10.5-11.5 years showed significantly superior spontaneous clinical outcome with a probability of 50% and 59% likelihood, respectively, to achieve good to perfect clinical result (p<0.05) compared to the other age groups (<8 years of age: 34%, >11.5 years of age: 44%). CONCLUSION: Prevention of complications after first permanent molars extractions is an important issue. The overall success rate of spontaneous clinical outcome for maxillary extraction of first permanent molars was superior to mandibular extraction. Extractions of mandibular first permanent molars should be performed between 8 and 11.5 years of age in order to achieve a good spontaneous clinical outcome. For the extraction in the maxilla, no firm conclusions concerning the ideal extraction timing could be drawn.


Subject(s)
Molar/surgery , Tooth Extraction , Humans , Mandible/surgery , Maxilla/surgery , Time Factors
5.
Mol Psychiatry ; 20(6): 727-34, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25155880

ABSTRACT

Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hyperactivity disorder (ADHD) delivered in a large New England health-care system were identified from electronic health records (EHR), and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and EHRs to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1377 children diagnosed with ASD and 2243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression (odds ratio (OR) 1.10 (0.70-1.70)). Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression (OR 1.81 (1.22-2.70)). These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression.


Subject(s)
Antidepressive Agents/adverse effects , Attention Deficit Disorder with Hyperactivity/epidemiology , Autism Spectrum Disorder/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Prenatal Exposure Delayed Effects/etiology , Case-Control Studies , Child , Child, Preschool , England , Female , Humans , Logistic Models , Male , Mother-Child Relations , Pregnancy , Risk Factors
6.
Eur Arch Paediatr Dent ; 15(6): 443-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25001360

ABSTRACT

BACKGROUND: Generalised aggressive periodontitis (AP) in the prepubescent age is an exceptionally rare disease in the primary dentition of otherwise healthy children. Characteristics of AP are gingival inflammation, deep periodontal pockets, bone loss, tooth mobility and even tooth loss. The most common way of treating this disease is the extraction of all the involved primary teeth. CASE REPORT: A 4-year-old girl presented with signs of severe gingival inflammation. Clinical examination revealed deep pockets, increased tooth mobility and bone loss. Microbiological testing revealed the presence of a typical periopathogenic flora consisting of Aggregatibacter actinomycetemcomitans and the typical members of the red complex (Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola). The patient underwent tooth extraction of all primary teeth except the primary canines, followed by thorough root debridement and treatment with systemic antibiotics (amoxicillin plus metronidazole). FOLLOW-UP: Regular clinical and microbiological examinations over 4 years showed no signs of recurrence of a periodontitis, even in the erupted permanent teeth. CONCLUSION: Early diagnosis and consequent early treatment of aggressive periodontitis can stop the disease and therefore avoid the development of a periodontal disease in the permanent dentition. A close collaboration between specialists of different disciplines is required for a favourable outcome.


Subject(s)
Aggressive Periodontitis/diagnosis , Tooth, Deciduous , Aggressive Periodontitis/microbiology , Alveolar Bone Loss/diagnosis , Anti-Bacterial Agents/therapeutic use , Child, Preschool , Female , Follow-Up Studies , Gingivitis/diagnosis , Gingivitis/microbiology , Humans , Periodontal Debridement/methods , Periodontal Pocket/diagnosis , Periodontal Pocket/microbiology , Tooth Extraction/methods , Tooth Mobility/diagnosis
7.
Ger Med Sci ; 8: Doc12, 2010 Jun 15.
Article in English, German | MEDLINE | ID: mdl-20577643

ABSTRACT

Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery (Deutsche Gesellschaft für Thorax-, Herz- und Gefässchirurgie, DGTHG) and the German Society for Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin, DGAI) made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess the available monitoring methods with regard to indication, procedures, predication, limits, contraindications and risks for use. The differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilatators, inodilatators and calcium sensitizers and the use of intra-aortic balloon pumps will also be addressed. The guideline has been developed following the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).


Subject(s)
Cardiac Surgical Procedures , Critical Care/standards , Monitoring, Physiologic/standards , Postoperative Care/standards , Practice Guidelines as Topic , Blood Volume , Critical Care/methods , Germany , Hemodynamics , Humans , Monitoring, Physiologic/methods , Postoperative Care/methods , Vasoconstrictor Agents/therapeutic use
8.
Eur J Echocardiogr ; 11(5): 387-93, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20530602

ABSTRACT

Every perioperative transoesophageal echo (TEE) study should generate a written report. A verbal report may be given at the time of the study. Important findings must be included in the written report. Where the perioperative TEE findings are new, or have led to a change in operative surgery, postoperative care or in prognosis, it is essential that this information should be reported in writing and available as soon as possible after surgery. The ultrasound technology and methodology used to assess valve pathology, ventricular performance and any other derived information should be included to support any conclusions. This is particularly important in the case of new or unexpected findings. Particular attention should be attached to the echo findings following the completion of surgery. Every written report should include a written conclusion, which should be comprehensible to physicians who are not experts in echocardiography.


Subject(s)
Echocardiography, Transesophageal , Perioperative Care , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/pathology , Heart Valves/diagnostic imaging , Heart Valves/pathology , Hemodynamics , Humans , Prognosis
9.
Anaesthesist ; 58(8): 764-78, 780-6, 2009 Aug.
Article in German | MEDLINE | ID: mdl-19669105

ABSTRACT

A regular hydration status and compensated vascular filling are targets of perioperative fluid and volume management and, in parallel, represent precautions for sufficient stroke volume and cardiac output to maintain tissue oxygenation. The physiological and pathophysiological effects of fluid and volume replacement mainly depend on the pharmacological properties of the solutions used, the magnitude of the applied volume as well as the timing of volume replacement during surgery. In the perioperative setting surgical stress induces physiological and hormonal adaptations of the body, which in conjunction with an increased permeability of the vascular endothelial layer influence fluid and volume management. The target of haemodynamic monitoring in the operation room is to collect data on haemodynamics and global oxygen transport, which enable the anaesthetist to estimate the volume status of the vascular system. Particularly in high risk patients this may improve fluid and volume therapy with respect to maintaining cardiac output. A goal-directed volume management aiming at preventing hypovolaemia may improve the outcome after surgery. The objective of this article is to review the monitoring devices that are currently used to assess haemodynamics and filling status in the perioperative setting. Methods and principles for measuring haemodynamic variables, the measured and calculated parameters as well as clinical benefits and shortcomings of each device are described. Furthermore, the results for monitoring devices from clinical studies of goal-directed fluid and volume therapy which have been published will be discussed.


Subject(s)
Hemodynamics/physiology , Monitoring, Intraoperative/methods , Perioperative Care/methods , Blood Volume/physiology , Cardiac Output/physiology , Catheterization, Peripheral , Echocardiography, Transesophageal , Fluid Therapy , Humans , Hypovolemia/diagnosis , Hypovolemia/therapy , Lithium , Monitoring, Intraoperative/instrumentation , Perioperative Care/instrumentation , Stroke Volume/physiology
10.
Gesundheitswesen ; 69(10): 560-4, 2007 Oct.
Article in German | MEDLINE | ID: mdl-18040964

ABSTRACT

On the basis of a representative sample (N=546) of adolescents of the city of Stuttgart (class levels 8 and 9) this article explores the extent to which the self-evaluation of body weight deviates from the classification of weight recommended by the German Arbeitsgemeinschaft Adipositas im Kindes- und Jugendalter (AGA, Working Committee on Obesity in Children and Adolescents). The analysis revealed that 47.7% of the girls and 38.2% of the boys do not correspond with the body mass index-based classification recommended by the AGA. This is particularly related to adolescents who are underweight or have normal weight. Concerning the self-evaluation of body weight, great gender differences were exposed: boys are likely to underestimate their weight {OR=1.85 CI (95%): [1.06-3.13]}, whereas girls tend to overestimate their body weight {OR=2.08 CI (95%): [1.38-3.14]}. The findings are displayed in the context of current national and international research results. In conclusion, the role of public health services in terms of promoting healthy body weight is discussed.


Subject(s)
Body Image , Body Weight , Obesity/epidemiology , Obesity/psychology , Self Concept , Adolescent , Body Mass Index , Female , Germany/epidemiology , Humans , Male
11.
Thorac Cardiovasc Surg ; 55(2): 130-48, 2007 Mar.
Article in German | MEDLINE | ID: mdl-17377871

ABSTRACT

Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors, are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery and the German Society for Anaesthesiology and Intensive Care Medicine made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess available monitoring methods and their risks as well as the differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilators, inodilators and calcium-sensitizers and the use of intra-aortic balloon pumps. The guideline has been developed according to the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).


Subject(s)
Cardiac Surgical Procedures/methods , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/therapy , Critical Care/methods , Monitoring, Physiologic/methods , Vascular Surgical Procedures/methods , Anesthesiology/standards , Cardiac Surgical Procedures/standards , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/surgery , Critical Care/standards , Germany , Humans , Monitoring, Intraoperative/methods , Monitoring, Physiologic/standards , Vascular Surgical Procedures/standards
12.
Acta Anaesthesiol Scand ; 51(3): 347-58, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17096667

ABSTRACT

BACKGROUND: In Germany, more than 100,000 patients are monitored and treated in 80 intensive care units (ICUs) following cardiac surgery each year. The controversies concerning the different methods of hemodynamic monitoring and the appropriate agents for volume therapy and inotropic support are well known. However, little is known about how monitoring and treatment are currently performed. METHODS: A questionnaire with 39 questions was sent to the leading physicians of 80 ICUs in Germany, treating patients after cardiac surgery. The questions to be answered covered the current practice of hemodynamic monitoring, volume replacement, inotropic/vasopressor support and transfusions in patients after cardiac surgery. RESULTS: Sixty-nine per cent of the questionnaires were completed and returned. All ICUs used basic monitoring as recommended by the societies. The use of advanced hemodynamic monitoring included the pulmonary artery catheter (58.2%), transesophageal echocardiography (38.1%) and transpulmonary dilution techniques (13%). Crystalloids (21.2%) and colloids (73%) were used for volume replacement. Epinephrine (41.8%) and dobutamine (30.9%) were the first-choice inotropic drugs for the treatment of low cardiac output syndrome, followed by phosphodiesterase inhibitors (14.5%). Second-choice drugs for the treatment of low cardiac output syndrome were enoximone (29%), milrinone (25%) and dobutamine (25%). A written transfusion protocol and a transfusion threshold for red blood cells existed in 59% and 79% of ICUs, respectively. CONCLUSION: Hemodynamic monitoring and the variability in clinical practice with regard to volume replacement, transfusion triggers and the use of vasopressors/inotropes in cardiac surgery patients tend to follow the results of traditional experience rather than current scientific knowledge. Guidelines are therefore necessary to help to improve the standards of intensive care after cardiac surgery and thus the outcome of patients.


Subject(s)
Cardiac Surgical Procedures , Cardiotonic Agents/therapeutic use , Epinephrine/therapeutic use , Vasoconstrictor Agents/therapeutic use , Blood Transfusion/standards , Cardiac Output, Low/drug therapy , Germany , Health Care Surveys , Humans , Hydroxyethyl Starch Derivatives/therapeutic use , Hypovolemia/drug therapy , Monitoring, Physiologic/methods , Monitoring, Physiologic/statistics & numerical data , Postoperative Care , Practice Guidelines as Topic , Serum Albumin/therapeutic use , Surveys and Questionnaires
13.
J Am Soc Echocardiogr ; 14(6): 595-600, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11391288

ABSTRACT

BACKGROUND: The echocardiographic contrast agent Optison may be useful in patients undergoing cardiac surgery. This study investigates its effects on hemodynamics, cardiac performance, and oxygenation in this group of patients. METHODS: Parameters of hemodynamic stability, cardiac performance, and oxygenation were measured in 57 patients by transesophageal echocardiography, electrocardiography, invasive arterial blood pressure and central venous pressure monitoring, capnography, pulsoximetry, and pulmonary artery catheter before and 5 and 10 minutes after an intravenous bolus of 0.3 mL of Optison. RESULTS: No statistically significant differences in ST-segment changes, heart rate, arterial and central venous pressure, peripheral oxygen saturation, cardiac index, left ventricular ejection fraction, and regional wall motion were seen 5 and 10 minutes after injection of Optison compared with baseline parameters. CONCLUSIONS: Optison did not cause clinically important changes in parameters of hemodynamic stability, cardiac performance, and oxygenation in our patients. The intraoperative use of intravenous Optison appears to be safe in patients undergoing cardiac surgery, including in the use of cardiopulmonary bypass.


Subject(s)
Albumins/pharmacology , Cardiac Surgical Procedures , Contrast Media/pharmacology , Fluorocarbons/pharmacology , Heart/drug effects , Adult , Aged , Aged, 80 and over , Blood Pressure/drug effects , Cardiopulmonary Bypass , Heart Rate/drug effects , Hemodynamics/drug effects , Humans , Intraoperative Period , Middle Aged , Stroke Volume/drug effects
14.
Benefits Q ; 17(2): 30-2, 2001.
Article in English | MEDLINE | ID: mdl-11372472

ABSTRACT

This article discusses the voucher--also called defined contribution--health care benefits model in terms of its features, the impetus for its development, obstacles to its implementation and the challenges it creates for employers. Although employers appear to have little current interest in health benefit vouchers, the author argues that a serious economic downturn could renew employers' interest in this promising concept.


Subject(s)
Community Participation , Health Benefit Plans, Employee/trends , Cost Sharing , Forecasting , Health Benefit Plans, Employee/organization & administration , Health Maintenance Organizations , Humans , Medical Savings Accounts , Models, Organizational , United States
15.
N Z Vet J ; 48(4): 111-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-16032135

ABSTRACT

AIMS: To assess the effects of external thermal manipulation on the soft-tissue and vascular perfusion of the equine digit using nuclear scintigraphy and documented tissue temperatures. METHODS: Six horses were used in a randomised crossover design. Each horse was treated with external heat (47 degrees C) or external cold (4 degrees C) applied to a digit for 30 minutes. The opposite front foot was untreated and used for control measurements. Nuclear scintigraphy was performed before, during, and after therapy to assess vascular and soft-tissue perfusion to the digit in response to therapy. Dorsal hoof wall laminar-tissue temperatures were recorded before, during, and after therapy using a thermistor. RESULTS: Treatment with topical cold therapy significantly decreased soft-tissue perfusion of the digit to 80.5% of the pre-cooled values. Conversely, the application of external heat significantly increased soft-tissue perfusion of the digit 25.1% above the pre-heated values. Vascular perfusion showed similar, but not statistically significant trends. External cold application to the digit caused a significant mean decrease in laminar-tissue temperatures of 11.6 degrees C during therapy, while external heat application to the digit caused a significant mean increase in laminar-tissue temperatures of 3.9 degrees C. CONCLUSION: The external application of heat and cold to the normal equine foot could effectively alter soft-tissue perfusion and laminar-tissue temperatures within 30 minutes of treatment. The application of hot water and ice water to the digit was a safe, well-tolerated, and economical therapy. CLINICAL RELEVANCE: Cooling the foot could decrease enzymatic reactions associated with laminitis, and warming could increase local perfusion when desired.

16.
Bioorg Med Chem Lett ; 9(2): 291-4, 1999 Jan 18.
Article in English | MEDLINE | ID: mdl-10021947

ABSTRACT

The 4-oxospiro[benzopyran-2,4'-piperidine] ring system is contained within potent class III antiarrhythmic agents. We highlight how these agents can be chemically transformed into a new class of potent (< 1 nM) and selective (> 25-fold) alpha 1a-receptor subtype adrenergic antagonists.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists , Benzopyrans/pharmacology , Piperidines/pharmacology , Spiro Compounds/pharmacology , Animals , Anti-Arrhythmia Agents/chemical synthesis , Humans , Male , Prostatic Hyperplasia/drug therapy , Rats
19.
J Med Chem ; 41(12): 2146-63, 1998 Jun 04.
Article in English | MEDLINE | ID: mdl-9622556

ABSTRACT

The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors. Incorporation of a 5-fluoro substituent on the central benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo potency but was detrimental to the pharmacokinetic profiles of these compounds. Although lipophilic substitution around the pyridine ring of compound 30 gave higher affinity in vitro, such substituents were a metabolic liability and caused shortfalls in vivo. Two approaches to prevent this metabolism, addition of a cyclic constraint and incorporation of trifluoromethyl groups, were examined. The former approach was ineffective because of metabolic hydroxylation on the constrained ring system, whereas the latter showed improvement in plasma pharmacokinetics in some cases.


Subject(s)
Oxazines , Pyridines , Receptors, Oxytocin/antagonists & inhibitors , Administration, Oral , Animals , Biological Availability , Cell Line , Chromatography, High Pressure Liquid , Dogs , Female , Humans , Kidney/cytology , Kidney/embryology , Kidney/metabolism , Liver/metabolism , Male , Mass Spectrometry , Oxazines/chemical synthesis , Oxazines/metabolism , Oxazines/pharmacokinetics , Oxazines/pharmacology , Pregnancy , Pyridines/chemical synthesis , Pyridines/metabolism , Pyridines/pharmacokinetics , Pyridines/pharmacology , Rats , Receptors, Oxytocin/metabolism , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/metabolism , Spectrophotometry, Ultraviolet , Uterine Contraction/drug effects , Uterus/drug effects , Uterus/physiology
20.
Bioorg Med Chem Lett ; 8(18): 2467-72, 1998 Sep 22.
Article in English | MEDLINE | ID: mdl-9873563

ABSTRACT

Benign prostatic hyperplasia can be managed pharmacologically with alpha-1 adrenergic receptor antagonists. Agents that demonstrate selectivity for the alpha-1a receptor subtype may offer advantages in clinical applications with respect to hypotensive side effects. The N-alkylated saccharins reported here represent a new class of subtype selective alpha-1a adrenergic receptor antagonists which demonstrate potent effects on prostate function in vivo and are devoid of blood pressure side effects.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists , Adrenergic alpha-Antagonists/chemical synthesis , Drug Design , Saccharin/analogs & derivatives , Adrenergic alpha-Antagonists/pharmacology , Alkylation , Animals , Aorta/drug effects , CHO Cells , Cell Line , Cricetinae , Dogs , Finasteride/chemistry , Finasteride/pharmacology , Humans , In Vitro Techniques , Male , Models, Chemical , Prazosin/analogs & derivatives , Prazosin/chemistry , Prazosin/pharmacology , Prostate/drug effects , Rats , Receptors, Adrenergic, alpha-1 , Saccharin/chemical synthesis , Saccharin/pharmacology , Structure-Activity Relationship , Sulfonamides/chemistry , Sulfonamides/pharmacology , Tamsulosin
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