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1.
Res Vet Sci ; 105: 153-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27033925

ABSTRACT

The purpose of this pilot study was to evaluate the usefulness of selected echocardiographic parameters, NT-proBNP and cardiac troponin I (cTnI) in the detection of cardiotoxicity in dogs treated with doxorubicin for various malignancies. Echocardiographic studies and biomarker measurements were performed before each administration of doxorubicin, then 1 and 3 months after completion of therapy. Thirteen dogs were included, with a total cumulative dose of doxorubicin ranging from 30 to 150 mg/m(2). E/A ratio significantly decreased during doxorubicin administration (p=0.047). cTnI level was also significantly affected by treatment (p=0.046), increasing above normal at least at one time point in 11 of 13 dogs. The results of this pilot study suggest that monitoring of left ventricular diastolic function and cTnI level measurement might be useful in the early detection of cardiotoxic signs of doxorubicin therapy in dogs.


Subject(s)
Antibiotics, Antineoplastic/toxicity , Cardiotoxicity/veterinary , Doxorubicin/toxicity , Echocardiography, Doppler/veterinary , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin I/blood , Ventricular Function, Left , Animals , Biomarkers/blood , Cardiotoxicity/diagnosis , Diastole , Dogs , Echocardiography, Doppler/methods , Female , Male , Neoplasms/drug therapy , Pilot Projects , Prospective Studies
2.
J Vet Intern Med ; 28(5): 1498-503, 2014.
Article in English | MEDLINE | ID: mdl-24965966

ABSTRACT

BACKGROUND: Predicting subaortic stenosis (SAS) in adult Golden Retriever dogs (GRs) by evaluating them as puppies is hampered by the progressive expression of the SAS phenotype in youth. In some children who develop SAS as adults, an abnormal aortoseptal angle (AoSA) precedes development of stenosis. OBJECTIVES: To determine the normal AoSA in young adult GRs using echocardiography; to assess the value of AoSA in GR puppies for predicting development of the SAS phenotype. ANIMALS: Forty-eight 2- to 6-month-old GR puppies. METHODS: Prospective study. Puppies were recruited from clients and breeders. Puppies were evaluated with a physical examination and an echocardiogram, and this evaluation was repeated when they were 12-18-month-old adults. Puppies were classified as unaffected (WNL) or affected (SAS) retroactively, based on their results as adults. RESULTS: In WNL young adult GRs, mean ± SD AoSA was 152.3 ± 6.5°. Mean ± SD AoSA in SAS puppies (144.9 ± 8.6°) was significantly different from mean AoSA in WNL puppies (155.7 ± 8.8°, P < .01). No puppy with AoSA >160° had the SAS phenotype as a young adult; 93% (75.7-99.1%) of puppies with AoSA <145° had the SAS phenotype as young adults. Peak LVOT velocity increased significantly between evaluations (P < .0001) whereas AoSA did not (P = .45). CONCLUSION AND CLINICAL SIGNIFICANCE: A steep AoSA in GR puppies is associated with the SAS phenotype in young adulthood. Some GR puppies have an abnormal AoSA that persists in young adulthood and is detectable before peak LVOT velocity reaches levels consistent with SAS.


Subject(s)
Aorta/abnormalities , Dog Diseases/etiology , Heart Septal Defects/veterinary , Age Factors , Animals , Aorta/diagnostic imaging , Aortic Stenosis, Subvalvular/diagnostic imaging , Aortic Stenosis, Subvalvular/veterinary , Dog Diseases/diagnostic imaging , Dogs , Echocardiography/veterinary , Female , Heart Septal Defects/complications , Heart Septal Defects/diagnostic imaging , Male , Prospective Studies , Risk Factors
3.
J Vet Intern Med ; 27(6): 1441-51, 2013.
Article in English | MEDLINE | ID: mdl-24010489

ABSTRACT

BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.


Subject(s)
Benzazepines/pharmacology , Cardiotonic Agents/pharmacology , Dog Diseases/physiopathology , Heart Failure/veterinary , Heart Valve Diseases/veterinary , Mitral Valve/physiopathology , Pyridazines/pharmacology , Animals , Benzazepines/therapeutic use , Blood Pressure/physiology , Body Temperature/physiology , Cardiotonic Agents/therapeutic use , Dog Diseases/diagnostic imaging , Dog Diseases/drug therapy , Dogs , Echocardiography/veterinary , Female , Heart Failure/diagnostic imaging , Heart Failure/drug therapy , Heart Failure/physiopathology , Heart Rate/physiology , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/drug therapy , Heart Valve Diseases/physiopathology , Hematocrit/veterinary , Kaplan-Meier Estimate , Longitudinal Studies , Male , Mitral Valve/diagnostic imaging , Mitral Valve/drug effects , Prospective Studies , Pyridazines/therapeutic use , Quality of Life , Single-Blind Method , Sodium/blood
4.
Hypertens Pregnancy ; 29(1): 21-37, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20132021

ABSTRACT

OBJECTIVE: Preeclampsia is a complex obstetrical syndrome characterized by hypertension and proteinuria. This syndrome is associated with oxidative stress, antioxidant imbalance and impaired production of vasoactive eicosanoids such as thromboxane A(2) (TXA(2)), a potent vasoconstrictor, and prostacyclin (PGI(2)), a well-known vasodilator. We hypothesized that there was a relationship between antioxidant vitamins, such as vitamin E and coenzyme Q(10) (CoQ(10)), and the production of vasoactive eicosanoids- PGI(2) and TXA(2)-potentially regulated by pro-oxidants and antioxidants in preeclampsia. METHODS: Therefore, the plasma levels of vitamin E, CoQ(10), TXA(2) and PGI(2) in normotensive (n = 30) and preeclamptic (n = 29) pregnancies were evaluated. Reduced and oxidized forms of vitamin E and CoQ(10) in blood were measured using a HPLC coupled to electrochemical detection. The levels of TXB(2) and 6-keto-PGF(1alpha), stable metabolites of TXA(2) and PGI(2) respectively, were measured by ELISA. RESULTS: The CoQ(10) oxidized/reduced ratio was significantly higher in preeclamptic compared to normotensive pregnancies (p = 0.04). A strong correlation between plasma levels of reduced vitamin E and CoQ(10), corrected for apolipoprotein B, was observed only in preeclampsia (r = 0.69, p < 0.0001). The 6-keto-PGF(1alpha)/TXB(2) ratio was higher in preeclampsia than in controls (p = 0.02), and this ratio was correlated to the oxidized/reduced ratio of both, vitamin E and CoQ(10) in all pregnancies (p <0.023). CONCLUSION: The data indicated that CoQ(10) is a sensitive marker of oxidative stress in preeclampsia. The correlation between vitamin E and CoQ(10) suggested a coordinated defense mechanism against oxidation. Furthermore, the higher 6-keto-PGF(1alpha)/TXB(2) ratio that strongly correlated with oxidative stress markers, suggests a mechanism developed by the maternal cardiovascular system to counteract hypertension during preeclampsia.


Subject(s)
Hypertension/physiopathology , Oxidative Stress , Pre-Eclampsia/physiopathology , Adult , Chromatography, High Pressure Liquid , Enzyme-Linked Immunosorbent Assay , Epoprostenol/blood , Fatty Acids/blood , Female , Humans , Patient Selection , Pre-Eclampsia/blood , Pregnancy , Thromboxane A2/blood , Ubiquinone/analogs & derivatives , Ubiquinone/blood , Vitamin E/blood
5.
J Vet Intern Med ; 23(2): 258-63, 2009.
Article in English | MEDLINE | ID: mdl-19143935

ABSTRACT

BACKGROUND: Pimobendan (PIMO) is a novel inodilator that has shown promising results in the treatment of advanced mitral valve disease (MVD), but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring MVD. HYPOTHESIS: The addition of pimobendan to treatment decreases the regurgitant fraction (RF) in dogs with asymptomatic MVD. ANIMALS: Twenty-four client-owned dogs affected by International Small Animal Cardiac Health Council class Ib MVD. METHODS: Prospective, blinded, and controlled clinical trial. Dogs were assigned to a PIMO treatment group (n = 19) (0.2-0.3 mg/kg q12h) or a control group (n = 5). Echocardiographic evaluations were performed over a 6-month period. RESULTS: The addition of PIMO to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period (P= .85). There was a significant increase in the ejection fraction of the PIMO treated dogs at 30 days (80.8 +/- 1.42 versus 69.0 +/- 2.76, corrected P= .0064), and a decrease in systolic left ventricular diameter (corrected P= .011) within the PIMO group compared with baseline. However, this improvement in systolic function was not sustained over the 6-month trial period. CONCLUSION AND CLINICAL IMPORTANCE: This study did not identify beneficial long-term changes in the severity of mitral regurgitation after addition of PIMO to angiotensin converting enzyme inhibitor treatment of dogs with asymptomatic MVD.


Subject(s)
Dog Diseases/diagnostic imaging , Dog Diseases/drug therapy , Echocardiography, Doppler/drug effects , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/veterinary , Pyridazines/pharmacology , Vasodilator Agents/pharmacology , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Dog Diseases/physiopathology , Dogs , Echocardiography, Doppler/veterinary , Female , Heart Rate/drug effects , Heart Rate/physiology , Male , Mitral Valve Insufficiency/drug therapy , Mitral Valve Insufficiency/physiopathology , Prospective Studies , Single-Blind Method
6.
J Vet Intern Med ; 22(5): 1103-10, 2008.
Article in English | MEDLINE | ID: mdl-18700858

ABSTRACT

BACKGROUND: Hyperthyroid cats are at risk of developing azotemic chronic kidney disease (CKD) and diagnostic tools currently used to screen for CKD in hyperthyroid cats are either unreliable or impractical. HYPOTHESIS: Urine N-acetyl-beta-D-glucosaminidase index (NAG(i)) is a good biomarker for azotemic CKD in hyperthyroid cats. ANIMALS: Twenty-four newly diagnosed nonazotemic hyperthyroid cats and 10 healthy cats. METHODS: All cats were evaluated for hyperthyroidism at baseline. Hyperthyroid cats were treated with methimazole and reevaluated once euthyroid. At the end of the study, cats were divided into 3 groups: healthy cats, nonazotemic, and azotemic euthyroid cats. Baseline group characteristics were compared to predict azotemic CKD. The influence of treatment on NAG(i) was evaluated. RESULTS: Baseline NAG(i) was significantly different among groups (P= .004). Azotemic cats had a higher median value (13.12 U/g) when compared with healthy cats (1.38 U/g). With NAG(i) >2.76 U/g, negative and positive predictive values for development of azotemia were 77.7 and 50%, whereas the combination of a urine specific gravity (USG) 7.80 microg/dL enhanced predictive values to 88.9 and 83.3%, respectively. NAG(i) values decreased significantly over time in treated nonazotemic cats. CONCLUSIONS AND CLINICAL RELEVANCE: Baseline NAG(i) did not differentiate azotemic from nonazotemic euthyroid cats. NAG(i) could be used to assess renal function during medical therapy allowing the clinician to adjust methimazole dosage accordingly. The combination of USG and T(4) could optimize identification of appropriate candidates for permanent treatment of hyperthyroidism.


Subject(s)
Acetylglucosaminidase/blood , Biomarkers/blood , Cat Diseases/metabolism , Hyperthyroidism/veterinary , Kidney Failure, Chronic/veterinary , Animals , Cat Diseases/blood , Cats , Chronic Disease , Hyperthyroidism/blood , Hyperthyroidism/complications , Hyperthyroidism/metabolism , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/metabolism
7.
J Vet Intern Med ; 22(5): 1124-35, 2008.
Article in English | MEDLINE | ID: mdl-18638016

ABSTRACT

BACKGROUND: Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. HYPOTHESIS: Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. ANIMALS: Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. METHODS: A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. RESULTS: Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.


Subject(s)
Benzazepines/therapeutic use , Dog Diseases/drug therapy , Heart Failure/veterinary , Mitral Valve Insufficiency/veterinary , Pyridazines/therapeutic use , Animals , Benzazepines/adverse effects , Cardiotonic Agents/adverse effects , Cardiotonic Agents/therapeutic use , Dogs , Female , Heart Failure/complications , Heart Failure/mortality , Male , Mitral Valve Insufficiency/complications , Mitral Valve Insufficiency/drug therapy , Multivariate Analysis , Proportional Hazards Models , Pyridazines/adverse effects
8.
Neurology ; 68(6): 451-6, 2007 Feb 06.
Article in English | MEDLINE | ID: mdl-17283322

ABSTRACT

OBJECTIVE: To determine whether survival motor neuron (SMN) expression was stable over time. METHODS: We developed a multiplex real-time reverse transcriptase (RT)-PCR assay to quantify SMN transcripts in preclinical blood samples from 42 patients with spinal muscular atrophy (SMA) drawn for three time points per patient; most blood samples were shipped to a centralized laboratory. RESULTS: We obtained a sufficient amount (9.7 +/- 5.6 microg) of good-quality total RNA, and RNAs were stable for up to a 3-year interval. This allowed RNA samples collected during a 9- to 12-month period to be analyzed in a single run, thus minimizing interexperimental variability. SMN expression was stable over time; intersample variability for baseline measures, collected during a 17-month interval, was less than 15% for 38 of 42 SMA patients analyzed. This variability was well below the 1.95-fold increase in full-length SMN (flSMN) transcripts detected in SMA fibroblasts treated with 10 mM valproic acid. CONCLUSION: Real-time quantification of SMN messenger RNA expression may be a biomarker that is amenable to multicenter SMA clinical trials.


Subject(s)
Cyclic AMP Response Element-Binding Protein/analysis , Cyclic AMP Response Element-Binding Protein/genetics , Muscular Atrophy, Spinal/diagnosis , Muscular Atrophy, Spinal/genetics , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/genetics , RNA, Messenger/analysis , RNA, Messenger/genetics , RNA-Binding Proteins/analysis , RNA-Binding Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Biomarkers , Cohort Studies , Computer Systems , Genetic Predisposition to Disease/genetics , Humans , Pilot Projects , Reproducibility of Results , SMN Complex Proteins , Sensitivity and Specificity
9.
J Vet Intern Med ; 15(5): 430-7, 2001.
Article in English | MEDLINE | ID: mdl-11596729

ABSTRACT

To evaluate the usefulness of the Doppler-derived effective orifice area (EOA) in assessing the hemodynamic severity of subaortic stenosis (SAS) in dogs, 2-dimensional and Doppler echocardiographic examinations were performed in 16 dogs with SAS, 22 normal adult dogs, and 22 normal puppies. The EOA was calculated by the continuity equation using the stroke volume determined in the right ventricular outflow tract. The EOA was significantly lower (P < .001 ) in the SAS dogs (0.76+/-0.45 cm2) and in the normal puppies (1.58+/-1.00 cm2) than in the normal adult dogs (2.34+/-0.78 cm2). The EOA indexed for body surface area (IEOA) was significantly lower (0.89+/-0.48 cm2/m2) in SAS dogs than in the normal puppies (2.42+/-0.85 cm2/m2) or adults (2.22+/-0.76 cm2/m2). The normal dogs (adults and puppies) had an IEOA of > or =1.25 cm2/m2. Among the demographic and echocardiographic parameters measured in this study, only the indexed EOA was significantly associated (P = .03) with the occurrence of adverse events (eg, syncope, episodic weakness, ventricular arrhythmias). This study demonstrates the usefulness and feasibility of the indexed EOA as measured by Doppler echocardiography for noninvasive assessment of SAS severity in dogs.


Subject(s)
Aortic Stenosis, Subvalvular/veterinary , Dog Diseases/diagnostic imaging , Dog Diseases/physiopathology , Animals , Animals, Newborn , Aortic Stenosis, Subvalvular/diagnostic imaging , Aortic Stenosis, Subvalvular/physiopathology , Blood Flow Velocity/veterinary , Body Surface Area/veterinary , Case-Control Studies , Dogs , Echocardiography, Doppler/standards , Echocardiography, Doppler/veterinary , Female , Male , Predictive Value of Tests , Severity of Illness Index , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/veterinary
10.
J Biomed Mater Res ; 58(5): 467-77, 2001.
Article in English | MEDLINE | ID: mdl-11505420

ABSTRACT

In 1984, low-density polyethylene (LDPE) and polymethylsiloxane (PDMS), two primary reference materials (PRM), were made available by the National Heart, Lung, and Blood Institute (NHLBI) as discriminatory tools for the validation of standardized and novel in vitro and in vivo tests in the evaluation of biomaterials. This article reviews the results and conclusions obtained by several studies investigating the hemocompatibility, in vitro biocompatibility, inflammatory response, and in vivo tissue reactions of these two reference materials. Variable results obtained with LDPE and PDMS in ex vivo hemocompatibility studies were attributed to the type of animal model used, the flow velocity of the circulating blood, the time of exposure, and the methodology used to measure blood cell adhesion or activation at the surface of the materials. In contrast, both the LDPE and PDMS appeared to be suitable reference materials when used in in vitro biocompatibility, inflammatory response, and in vivo studies. However, caution must be taken when interpreting the results, because gamma sterilization of these two materials as well as their origin (for example PDMS) are two critically important factors. In conclusion, we see a definite need for standardized hemocompatible parameters and better high-quality hemocompatibility studies on PRM. This review also suggests other materials as potential PRM candidates, namely, Biomer and Intramedic polyethylene.


Subject(s)
Biocompatible Materials/chemistry , Coated Materials, Biocompatible/pharmacology , Dimethylpolysiloxanes/pharmacology , Inflammation/chemically induced , Polyethylene/pharmacology , Silicones/pharmacology , Animals , Blood Coagulation/physiology , Blood Platelets/physiology , Hemolysis/physiology , Humans , Reference Standards
11.
Artif Organs ; 24(11): 879-88, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11119076

ABSTRACT

Membranes made from 4 commercial poly(carbonate urethanes): Carbothane (CB), Chronoflex (CF), Corethane 80A (CT80), and Corethane 55D (CT55), and from 2 poly(ether urethanes): Tecoflex (TF) and Tecothane (TT) were prepared by solution casting and sterilized by either ethylene oxide (EO) or gamma radiation. Their biocompatibility was evaluated in vitro in terms of proliferation, cell viability, and adhesion characteristics of human umbilical veins (HUVEC), monocytes (THP-1), and skin fibroblasts, and by measuring complement activation through the generation of the C3a complex. Their hemocompatibility was determined by measuring the level of radiolabeled platelet, neutrophil, and fibrin adhesion in an ex vivo arteriovenous circuit study in piglets as well as via an in vitro hemolysis test. The results of this study showed no endothelial cell proliferation on any of the materials. The cell viability study revealed that the CB, CF, and TF membranes sterilized by EO maintained the highest percentage of monocyte viability after 72 h of incubation (>70%) while none of the gamma-sterilized membranes displayed any cell viability. The fibroblast adhesion and C3a generation assays revealed that none of the materials supported any cell adhesion or activated complement, regardless of the sterilization method. The hemolysis test also confirmed that the 4 poly(carbonate urethanes) were hemolytic while none of the poly(ether urethanes) were. Finally, the ex vivo study revealed that significantly more platelets adhered to the CB and CT55 membranes while the levels of neutrophil and fibrin deposition were observed to be similar for all 6 materials. In conclusion, the study identified the CF and TF membranes as having superior biocompatibility and hemocompatibility compared to the other polyurethanes.


Subject(s)
Biocompatible Materials , Heart, Artificial , Membranes, Artificial , Polyurethanes , Animals , Biocompatible Materials/chemistry , Blood , Cell Adhesion , Cell Division , Cell Survival , Complement Activation , Complement C3a/analysis , Fibrin , Fibroblasts/physiology , Heart Ventricles , Hemolysis , Humans , Monocytes/physiology , Neutrophils/physiology , Platelet Adhesiveness/physiology , Polycarboxylate Cement/chemistry , Polyurethanes/chemistry , Prosthesis Design , Skin/cytology , Sterilization , Swine , Umbilical Veins/cytology
12.
J Am Anim Hosp Assoc ; 35(6): 507-9, 1999.
Article in English | MEDLINE | ID: mdl-10580911

ABSTRACT

An unusual case of multiple lymphangiomas with lymph node involvement is described. A seven-month-old, spayed female golden retriever was presented with a myriad of cystic masses in the inguinal and caudal mammary regions. She was diagnosed with congenital lymphangiomas (i.e., lymphatic hamartomas). As in human lymphangiomas, lymphatic endothelial cells expressing factor VIII-related antigen and smooth muscle were present in this case. A literature search did not identify similar characteristics in other reported canine lymphangiomas. The dog was treated surgically and had a recurrence. Following a second surgical intervention, she is now disease-free.


Subject(s)
Dog Diseases/diagnosis , Lymphangioma/veterinary , Mammary Neoplasms, Animal/diagnosis , Animals , Diagnosis, Differential , Dog Diseases/pathology , Dog Diseases/surgery , Dogs , Female , Lymphangioma/diagnosis , Lymphangioma/pathology , Lymphangioma/surgery , Lymphatic Metastasis , Mammary Neoplasms, Animal/pathology , Mammary Neoplasms, Animal/surgery , Neoplasm Invasiveness , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/veterinary , Reoperation/veterinary
14.
J Affect Disord ; 54(1-2): 39-48, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10403145

ABSTRACT

BACKGROUND: Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors. In a 12-week randomized, multicenter, double-blind trial, the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression. METHODS: A total of 203 patients were randomized to fixed doses (20 mg/day) of paroxetine or fluoxetine for the first six weeks of therapy. From week 7-12, dosing could be adjusted biweekly, as required (paroxetine 20-50 mg/day, and fluoxetine 20-80 mg/day). The mean prescribed doses were paroxetine 25.5 mg/day (range 20.0-40.2 mg/day), and fluoxetine 27.5 mg/day (range 20.0-59.5 mg/day). Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia. RESULTS: Both active treatments demonstrated comparable antidepressant efficacy (HAM-D, CGI). Anxiolytic activity of the two drugs (COVI, STAI, HAM-D) was also comparable. However, paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy (HAM-D Agitation item, p < 0.05; Psychic Anxiety item, p < 0.05), with no differences detected after week 2. The overall incidence of adverse effects was comparable in the two treatment groups. Constipation, dyspepsia, tremor, sweating and abnormal ejaculation were more common in paroxetine-treated subjects, whereas nausea and nervousness were more frequent in fluoxetine-treated patients. Weight loss was more common in the fluoxetine versus paroxetine group (11.88% versus 2.94%, respectively). ESRS scores for akathisia were low throughout the study and showed little change. LIMITATIONS: Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others. DISCUSSION: The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy. Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine.


Subject(s)
Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/psychology , Fluoxetine/adverse effects , Paroxetine/adverse effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Anxiety/chemically induced , Depressive Disorder, Major/diagnosis , Dose-Response Relationship, Drug , Female , Humans , Male , Psychiatric Status Rating Scales , Severity of Illness Index , Treatment Outcome
16.
Brain Res Dev Brain Res ; 105(1): 35-42, 1998 Jan 14.
Article in English | MEDLINE | ID: mdl-9497077

ABSTRACT

Neurotransmitters influence a wide variety of developmental processes. We hypothesize that N-methyl-D-aspartate (NMDA) glutamate receptors influence proliferation of populations of forebrain neurons. As our model, we use a subclass of GABAergic striatal interneurons that express the calcium binding protein parvalbumin (PV). To separate proliferative and post-proliferative effects of NMDA receptor antagonists on PV neurons, we first determined the birth-date of rat striatum PV neurons at the coronal level selected for analysis. Dividing striatal progenitor cells were marked by intraperitoneal injections of 5'-bromodeoxyuridine (BrdU) given to timed pregnant rats at selected time points between embryonic days (E) 12-22. Double immunohistochochemistry for BrdU and PV was used in adult progeny to determine the time course of neurogenesis of striatal PV neurons. The results of the neurogenetic analysis were then used for rational timing of treatment with competitive (CGS 19755) and non-competitive (MK-801) NMDA receptor antagonists. In comparison to pair-fed and vehicle-injected controls, gestational rats given CGS-19755 and MK-801 during the proliferative phase (E15-E18) showed a marked reduction of striatal PV neuron cell density as adults. In contrast, animals given NMDA antagonists during the post-proliferative period (E18-E21) showed no significant reduction in PV neuron cell density compared to pair-fed controls. These results suggest that glutamate influences cell proliferation of a population of striatal neurons by an NMDA-mediated mechanism, providing evidence for a novel role for excitatory amino acids in early forebrain development.


Subject(s)
Interneurons/physiology , Neostriatum/physiology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , gamma-Aminobutyric Acid/physiology , Animals , Antimetabolites , Bromodeoxyuridine , Cell Count/drug effects , Cell Survival/drug effects , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Female , Immunohistochemistry , Male , Neostriatum/cytology , Parvalbumins/metabolism , Pipecolic Acids/pharmacology , Pregnancy , Rats , Rats, Sprague-Dawley
17.
Neuroscience ; 78(1): 259-70, 1997 May.
Article in English | MEDLINE | ID: mdl-9135106

ABSTRACT

In the embryonic CNS, preformed pathways precede the growth of axonal fasciculi [Katz M. J. and Lasek R. J. (1980) Cell Motil. 1, 141-157; Katz M. J. et al. (1980) Neuroscience 5, 821-833]. What are the developmental events that lead to the elaboration of these preformed pathways? To answer this question, we investigated the organization of the primitive neural tube and more particularly the arrangement of the early-generated cells using [3H]thymidine autoradiography or bromodeoxyuridine. Our data suggest that the position of early-generated cells might be involved in the setting of such pathways. In the brain stem of E12(0) (12 days and 0 h) and E12(15) rat embryos, the first-generated cells were organized into three longitudinal columns associated with glycoconjugate-rich extracellular spaces in the adjacent primitive marginal layer. Also, axons traced with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) were contiguous to the early-generated cellular columns and represented the primordium of the medial longitudinal fasciculus, the lateral longitudinal tract and the mesencephalic trigeminal tract. Our results show a correlation between the organization of early-generated cells, likely neurons, and the pattern of extracellular spaces in the marginal layer where axons grow. It has been reported in the literature that neurons produce elements of the extracellular matrix such as growth-modulating molecules or space-creating molecules. We therefore suggest that the position of early-generated neurons could be involved in the elaboration of a template for the setting of some major longitudinal tracts during embryonic development of the brainstem.


Subject(s)
Axons/physiology , Brain Stem/cytology , Brain Stem/embryology , Neurons/physiology , Animals , Antimetabolites , Bromodeoxyuridine , Carbocyanines , Female , Fluorescent Dyes , Histocytochemistry , Neural Pathways/cytology , Neural Pathways/embryology , Pregnancy , Rats , Rats, Sprague-Dawley , Thymidine/metabolism
18.
Article in English | MEDLINE | ID: mdl-8888111

ABSTRACT

1. The role of serotonin in the aetiology of obsessive compulsive disorder (OCD) has been established through considerable indirect evidence (Landry and Chouinard, 1990). The strongest evidence comes from the fact that drugs known to be serotonin-selective reuptake inhibitors (SSRIs) have been found to be useful in the pharmacotherapy of OCD (Landry and Chouinard, 1990). 2. The authors investigated a new treatment approach by adding an adrenal steroid suppressant to a SSRI, fluoxetine, in the case of a severe obsessive-compulsive patient who was drug-resistant to clomipramine and SSRIs. 3. We found that the combination of aminoglutethimide 250 mg qid and fluoxetine 40 mg die significantly improved the patient's condition. Moreover, during a four and a half year period, each time we tried to decrease either fluoxetine or the steroid suppressant, the patient started to relapse, suggesting that the adrenal steroid suppressant had a potentiating effect on the SSRI.


Subject(s)
Aminoglutethimide/therapeutic use , Drug Interactions , Fluoxetine/therapeutic use , Obsessive-Compulsive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/pharmacology , Humans , Male , Middle Aged , Psychiatric Status Rating Scales
19.
J Am Diet Assoc ; 96(4): 354-60, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8598436

ABSTRACT

OBJECTIVES: To investigate the basic dimensions of patient emotional experience of hospitalization; to identify the moderators of emotional experience in terms of individual characteristics and contextual factors; and to investigate the contribution of the dimensions of the patient emotional experience to satisfaction with foodservices. DESIGN: Survey questionnaire. SUBJECTS/SETTING: One hundred two hospitalized patients of a specialized, acute-care, urban hospital in Canada who required one or more overnight stays. Patients with notable physical, cognitive, or emotional limitations were excluded from the study. Patients admitted to the obstetrics department were also excluded because of the unique nature of their emotional experience of hospitalization. STATISTICAL ANALYSES PERFORMED: Factor analysis followed by orthogonal rotation (varimax), analyses of variance, and multiple regression analyses. RESULTS: Five dimensions represented the emotional experience of hospitalization: positive emotions, arousal emotions, and three negative dimensions structured on the basis of their possible causes (situation-, other-, or self-attributed negative emotions). Individual characteristics (gender, age, marital status, perceived health status) and contextual factors (perceived control over the situation, complexity of medical diagnosis, and admission procedures) significantly influenced patient emotions. Satisfaction with foodservices was structured in technical and interpersonal dimensions; the largest part of the common variance was accounted for by interpersonal aspects. The relationship between emotions and satisfaction was direct for positive emotions and, surprisingly, for situation-attributed negative emotions and self-attributed negative emotions. Other-attributed negative emotions and arousal emotions were negatively associated with satisfaction with foodservices. APPLICATIONS: Results suggest that dietitians' interventions should be adapted for subgroups of patients who experience different emotions. Results also provide insights on individual and contextual factors that can be used to identify or better understand the specific characteristics of these subgroups. The pattern of relationships between emotions and satisfaction demonstrates that the fine-tuning of dietitians' interventions as a function of patients' emotional states may be conducive to increased patient satisfaction with foodservices.


Subject(s)
Emotions , Food Service, Hospital/standards , Inpatients/psychology , Patient Satisfaction , Adult , Aging/psychology , Analysis of Variance , Arousal , Factor Analysis, Statistical , Female , Health Status , Humans , Male , Marital Status , Middle Aged , Quebec , Reproducibility of Results , Self Concept , Surveys and Questionnaires
20.
J Clin Psychiatry ; 57(1): 22-8, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8543543

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the prevalence of extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) in affective disordered patients treated with lithium and to study the association of these symptoms with medication and other factors. METHODS: This cross-sectional study was carried out in all consenting outpatients attending an affective disorders clinic in a psychiatric hospital. The study sample consisted of 130 stable outpatients: 110 with bipolar disorder, 18 with unipolar (major) depression, and 2 with atypical affective disorder. At the time of evaluation, 110 patients were receiving lithium, 37 in combination with antidepressants and 19 with neuroleptics, and 40 had a history of neuroleptic treatment during the previous 6 months. The patients were assessed with the Extrapyramidal Symptom Rating Scale (ESRS) for parkinsonism, akathisia, dystonia, and TD. The prevalence of these symptoms was calculated for all patients and by current lithium and neuroleptic intake. Multiple linear regression analysis was used to investigate the relationship between the ESRS subscale scores and gender, age, diagnosis, and medication type. RESULTS: The prevalence of tremor was 20.8%; hypokinetic parkinsonism, 7.7%; akathisia, 4.6%; dystonia, 3.8%; and TD, 9.2%. Tremor was associated with lithium and neuroleptic intake; hypokinesia was associated with neuroleptic treatment and age; and TD was associated with neuroleptic, lithium, and tricyclic intake and age. Seven of 51 patients taking lithium but without a history of neuroleptic treatment during the previous 6 months presented symptoms of TD. CONCLUSION: The combination of lithium and neuroleptics was associated with a high prevalence of EPS. The presence of TD in lithium-treated patients not treated with neuroleptics for at least 6 months is consistent with the hypothesis that lithium may exacerbate the vulnerability of affective disordered patients to dyskinesias.


Subject(s)
Dyskinesia, Drug-Induced/epidemiology , Lithium/therapeutic use , Mood Disorders/drug therapy , Parkinson Disease, Secondary/epidemiology , Adult , Aged , Ambulatory Care , Antipsychotic Agents/therapeutic use , Bipolar Disorder/drug therapy , Bipolar Disorder/psychology , Cross-Sectional Studies , Depressive Disorder/drug therapy , Depressive Disorder/psychology , Drug Therapy, Combination , Dyskinesia, Drug-Induced/etiology , Female , Humans , Lithium/adverse effects , Male , Middle Aged , Parkinson Disease, Secondary/chemically induced , Prevalence , Psychiatric Status Rating Scales , Regression Analysis , Treatment Outcome
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