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1.
Theriogenology ; 93: 33-39, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28257864

RESUMO

Benign prostatic hyperplasia (BPH) is an age-related disorder in the intact male dog that is associated with an increase in the prostatic size. Ultrasonography gives a reliable estimate of the prostatic size, but a method for screening the prostate size using a serum sample has advantages, such as requiring less expensive equipment. The primary aim of the study was to study the association between the concentration of the circulating biomarker canine prostate specific esterase (CPSE) and prostatic size. Seventy-nine dogs that were four years old or older were included in the study. Ultrasonography was used for calculating the volume of the prostate. The calculated volume was divided by an estimate of the normal prostatic volume in dogs aged one to four years, to determine the relative prostatic size: the size of the prostate in relation to the normal size in dogs 1-4 years old (Srel). CPSE was analyzed from serum samples. Multiple linear regression analysis was used for studying associations between variables. Prediction intervals for the relative prostatic size based on CPSE concentrations were calculated, as were receiver operating curves for CPSE concentrations predicting Srel. The concentration of CPSE was associated with the relative size and contour of the prostate (P < 0.001). All dogs with clinical signs of BPH had an Srel ≥ 2.5. A CPSE concentration of 200 ng/mL predicted Srel to 2.5 (95% P.I: 1.2-4.8). Based on ROC analysis, the optimal discrimination threshold for CPSE concentration for Srel ≥ 2.5 was estimated as 90 ng/mL (95% confidence interval: 50-140), with a sensitivity of 85% and a specificity of 72%. Screening for CPSE is of potential value in the aging intact male dogs. Although many dogs with an Srel ≥ 2.5 show no clinical signs, the insidious nature of BPH supports further investigations of the prostate in these dogs, corresponding to a CPSE concentration of approximately 90 ng/mL or higher.


Assuntos
Doenças do Cão/patologia , Esterases/sangue , Próstata/enzimologia , Próstata/patologia , Hiperplasia Prostática/veterinária , Envelhecimento , Animais , Biomarcadores/sangue , Doenças do Cão/enzimologia , Cães , Masculino , Tamanho do Órgão , Próstata/diagnóstico por imagem , Hiperplasia Prostática/enzimologia , Hiperplasia Prostática/patologia , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia/veterinária
2.
Eur J Pediatr ; 176(2): 279-283, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28039508

RESUMO

We present a patient with poikiloderma, severe osteoporosis and a mild intellectual disability. At the age of 9 years, this patient was proposed to suffer from a novel disease entity designated as calcinosis cutis, osteoma cutis, poikiloderma and skeletal abnormalities (COPS) syndrome. At the age of 35, he was diagnosed with Hodgkin's lymphoma. Recently, biallelic pathogenic variants in the RECQL4 gene were detected (c.1048_1049delAG and c.1391-1G>A), confirming a diagnosis of Rothmund-Thomson syndrome (RTS). In the brother of this patient, who had a milder phenotype, a similar diagnosis was made. CONCLUSION: We conclude that COPS syndrome never existed as a separate syndrome entity. Instead, osteoma cutis may be regarded as a novel feature of RTS, whereas mild intellectual disability and lymphoma may be underreported parts of the phenotype. What is new: • Osteoma cutis was not a known feature in Rothmund-Thomson patients. • Intellectual disability may be considered a rare feature in RTS; more study is needed. What is known: • RTS is a well-described syndrome caused by mutations in the RECQL4 gene. • Patients with RTS frequently show chromosomal abnormalities like, e.g. mosaic trisomy 8.


Assuntos
Síndrome de Rothmund-Thomson/diagnóstico , Adulto , Doenças Ósseas Metabólicas/diagnóstico , Osso e Ossos/anormalidades , Calcinose/diagnóstico , Cromossomos Humanos Par 8 , Diagnóstico Tardio , Humanos , Deficiência Intelectual/diagnóstico , Linfoma não Hodgkin/diagnóstico , Masculino , Ossificação Heterotópica/diagnóstico , Osteoporose/diagnóstico , Dermatopatias Genéticas/diagnóstico , Síndrome , Trissomia
3.
Haemophilia ; 22(3): 453-61, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26635073

RESUMO

BACKGROUND: Haemophilia A and B are treated with FVIII and FIX replacement therapy. Treatment may be complicated by inhibitory antibodies that require bypass therapy such as FEIBA(®) in which prothrombin (FII) is suggested to be the main active component. METHODS: To evaluate the effect of FII on haemophilia recombinant human (rh) FII (MEDI8111) or plasma-derived human FII (pdhFII) was given as single doses to anaesthetized haemophilia A and B mice 3 min before tail transection and rhFVIII or rhFIX was used for comparison. After tail transection, automatic bleeding registration was used to continuously measure blood loss (BL) and bleeding time (BT). Thrombin generation and plasma concentrations of human FVIII, FIX, FII and thrombin-antithrombin complex (TAT) were measured. RESULTS: Blood loss and BT were dose-dependently decreased by rhFVIII or rhFIX. The concentrations that decreased BL and BT for rhFVIII by 50% (EC50) were 0.06 and 0.01 IU mL(-1) and for rhFIX 0.07 and 0.07 IU mL(-1) , respectively. Administration of rhFVIII and rhFIX dose-dependently increased thrombin generation potential but did not affect TAT. MEDI8111 and pdhFII dose-dependently decreased BL and BT in haemophilia A mice, EC50 37 and 87 and 100 and 155 mg L(-1) respectively. In haemophilia B mice given MEDI8111 EC50 was for BL 56 mg L(-1) and for BT 67 mg L(-1) . TAT and thrombin generation increased dose-dependently for MEDI8111 and pdhFII. CONCLUSION: MEDI8111 dose-dependently decreased bleeding and increased procoagulant activity in haemophilia A and B mice and suggest that MEDI8111 may be useful for preventing bleeding in patients with haemophilia A and B.


Assuntos
Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Protrombina/uso terapêutico , Animais , Coagulantes/uso terapêutico , Modelos Animais de Doenças , Fator IX/genética , Fator IX/metabolismo , Fator IX/uso terapêutico , Fator VIII/genética , Fator VIII/metabolismo , Fator VIII/uso terapêutico , Hemorragia/prevenção & controle , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Protrombina/genética , Protrombina/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento
4.
Equine Vet J ; 48(1): 57-64, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25290785

RESUMO

REASONS FOR PERFORMING STUDY: Validated noninvasive detection methods for early osteoarthritis (OA) are required for OA prevention and early intervention treatment strategies. OBJECTIVES: To evaluate radiography and low-field magnetic resonance imaging (MRI) for the detection of early stage OA osteochondral lesions in equine centrodistal joints using microscopy as the reference standard. STUDY DESIGN: Prospective imaging of live horses and imaging and microscopy of cadaver tarsal joints. METHODS: Centrodistal (distal intertarsal) joints of 38 Icelandic research horses aged 27-29 months were radiographed. Horses were subjected to euthanasia approximately 2 months later and cadaver joints examined with low-field MRI. Osteochondral joint specimens were classified as negative or positive for OA using light microscopy histology or scanning electron microscopy. Radiographs and MRIs were evaluated for osteochondral lesions and results compared with microscopy. RESULTS: Forty-two joints were classified OA positive with microscopy. Associations were detected between microscopic OA and the radiography lesion categories; mineralisation front defect (P<0.0001), joint margin lesion (P<0.0001), central osteophyte (P = 0.03) and the low-field MRI lesion categories; mineralisation front defect (P = 0.01), joint margin lesion (P = 0.02) and articular cartilage lesion (P = 0.0003). The most frequent lesion category detected in microscopic OA positive joints was the mineralisation front defect in radiographs (28/42 OA positive joints, specificity 97%, sensitivity 67%). No significant differences were detected between the sensitivity and specificity of radiography and low-field MRI pooled lesion categories, but radiography was often superior when individual lesion categories were compared. CONCLUSIONS: Early stage centrodistal joint OA changes may be detected with radiography and low-field MRI. Detection of mineralisation front defects in radiographs may be a useful screening method for detection of early OA in centrodistal joints of young Icelandic horses.


Assuntos
Doenças dos Cavalos/diagnóstico , Imageamento por Ressonância Magnética/veterinária , Osteoartrite/veterinária , Animais , Cadáver , Feminino , Doenças dos Cavalos/diagnóstico por imagem , Cavalos , Imageamento por Ressonância Magnética/métodos , Masculino , Osteoartrite/diagnóstico , Osteoartrite/diagnóstico por imagem , Radiografia , Tarso Animal/diagnóstico por imagem , Tarso Animal/patologia
6.
J Thromb Haemost ; 13(7): 1293-300, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25944555

RESUMO

BACKGROUND: The present study was carried out to investigate the impact of FII levels, and their increase, on the hemostatic potential in plasma from hemophilia A and B patients with and without inhibitors. METHOD: Recombinant human factor (F) II (rhFII) was added ex vivo to plasma from 68 patients with hemophilia A and B, with or without inhibitors. The hemostatic potential as measured by thrombin generation (calibrated automated thrombogram [CAT]) was focused on the endogenous thrombin potential (ETP) as it has been shown to correlate with the clinical phenotype of bleeding in hemophilia patients and has also been used to guide bypassing therapy in hemophilia patients with inhibitors before elective surgery. The factor eight inhibitor bypassing agent (FEIBA(®) ) was used as a reference to the clinical situation. RESULTS: The study shows that rhFII concentration-dependently increased ETP by a similar magnitude in hemophilia A and B, both with and without inhibitors. Compared with FEIBA, rhFII showed a shallower concentration-response curve. In both types of hemophilia 100 mg L(-1) of rhFII roughly doubled the ETP. A corresponding response was obtained by 0.5 U mL(-1) of FEIBA. CONCLUSION: These data support the theory that FII is one of the major components responsible for the efficacy of FEIBA. The data also indicate that rhFII may be useful, alone or in combination with other coagulation factors, in some of the conditions for which FEIBA is used today, although more data are needed to substantiate this.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Coagulantes/farmacologia , Hemofilia A/sangue , Hemofilia B/sangue , Protrombina/farmacologia , Trombina/metabolismo , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Autoanticorpos/sangue , Fatores de Coagulação Sanguínea/farmacologia , Testes de Coagulação Sanguínea , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Fator VIII/imunologia , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Hemofilia A/imunologia , Hemofilia B/diagnóstico , Hemofilia B/tratamento farmacológico , Hemofilia B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
7.
Int J Lab Hematol ; 37(3): 357-64, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25212252

RESUMO

INTRODUCTION: When investigating coagulation assays to measure the effect of infused prothrombin (FII) in in vivo coagulopathy models, we found that addition of FII, plasma-derived human FII (pd-hFII) or recombinant human FII (r-hFII), to normal plasma resulted in a concentration-dependent increase in prothrombin time (PT) initiated with Innovin(®) . METHODS: The effect on PT by addition to plasma of either pd-hFII or r-hFII, using different commercial PT reagents, was studied both by turbidimetry and viscometry. RESULT: Addition of FII to plasma resulted in increased PT when initiated with Innovin(®) : PT increased with 20% by doubling the concentration. The prolongation of PT became more pronounced with 2-6000 times diluted Innovin(®) . However, by adjustment of the final free Ca(2+) concentration in the assay with diluted Innovin(®) from 8.3 to 1.3 mmol/L, no FII-dependent increase in PT was found. In contrast, no prolongation of PT was found with other commercial PT reagents. A KM = 3 nmol/L was obtained with pd-hFII, respectively, r-hFII with FII-depleted plasma using Thromborel(®) to initiate PT. CONCLUSION: At normal plasma concentration of FII, addition of FII should not have an effect on PT. The prolonged PT with Innovin(®) , but not with other PT reagents, at supranormal FII concentration is an artefact.


Assuntos
Proteínas Sanguíneas , Tempo de Protrombina , Protrombina/farmacologia , Proteínas Recombinantes , Cálcio/farmacologia , Humanos , Protrombina/administração & dosagem , Proteínas Recombinantes/farmacologia , Tromboplastina/farmacologia
8.
J Thromb Haemost ; 12(10): 1678-86, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25142753

RESUMO

BACKGROUND: Corn trypsin inhibitor (CTI), an inhibitor of FXIIa, is used to prevent plasma coagulation by contact activation, to specifically investigate tissue factor (TF)-initiated coagulation. OBJECTIVE: In the present work the specificity of CTI for factor (F) XIIa is questioned. METHODS AND RESULTS: In the commercial available plasma coagulation assays CTI was found to double activated partial thromboplastin time (APTT) at a plasma concentration of 7.3 ± 1.5 µm CTI (assay concentration 2.4 µm). No effect was found on the prothrombin time (PT) when high TF concentrations were used. Also, with specific antibodies for FXIIa and for FXIa only APTT was found to be extended but not PT. With specific enzyme assays using chromogenic substrates CTI was shown to be a strong inhibitor of FXIIa and a competitive inhibitor of FXIa with Ki  = 8.1 ± 0.3 µm, without effect on the coagulation factors FVIIa, FIXa, FXa and thrombin. In thrombin generation and coagulation (free oscillation rheometry, FOR) assays, initiated with low TF concentrations, no effect of CTI (plasma concentrations of 4.4 and 13.6 µm CTI, 25 resp. 100 mg L(-1) in blood) was found with ≥ 1 pm TF. At ≤ 0.1 pm TF in the FOR whole blood assay the coagulation time (CT) concentration dependently increased while the plasma CT became longer than the observation time. CONCLUSION: To avoid inhibition of FXIa and the thrombin feedback loop we recommend that for coagulation assays the concentration of CTI in blood should be below 20 mg L(-1) (1.6 µm) and in plasma below 3 µm.


Assuntos
Testes de Coagulação Sanguínea , Coagulação Sanguínea/efeitos dos fármacos , Fator XIIa/química , Fator XIa/química , Proteínas de Plantas/química , Anticorpos Monoclonais/química , Ligação Competitiva , Calibragem , Fator XIIa/imunologia , Fator XIa/imunologia , Hematócrito , Humanos , Oscilometria , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Trombina/química
9.
Eur Cell Mater ; 27: 213-36; discussion 234-6, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24668595

RESUMO

Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.


Assuntos
Calcinose/veterinária , Doenças dos Cavalos/patologia , Cartilagem Hialina/patologia , Articulações/patologia , Osteocondrose/veterinária , Tarso Animal/patologia , Animais , Calcinose/patologia , Cavalos , Osteocondrose/patologia
10.
J Vet Intern Med ; 27(6): 1452-62, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24128373

RESUMO

BACKGROUND: Pimobendan and benazepril are frequently used with diuretics to treat dogs in congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). AIM: To compare the short-term effects of pimobendan versus benazepril on pump function, heart size, and neuroendocrine profile in dogs with CHF caused by MMVD. ANIMALS: Sixteen client-owned dogs. MATERIAL AND METHODS: Seven-day prospective single-blinded study of dogs stabilized on furosemide monotherapy, randomized to pimobendan (0.4-0.6 mg/kg/day) or benazepril (0.25-1.0 mg/kg/day). Dogs had first-pass radionuclide angiocardiography, and heart size was measured by radiography and echocardiography. Circulating neuroendocrine hormones were measured. RESULTS: Baseline variables did not differ between treatment groups. Greater decreases in the pimobendan than in the benazepril group were found for heart rate (P = .001), heart rate-normalized pulmonary transit time (P = .02), left atrial size (P = .03), and systolic and diastolic left ventricular diameters (P < .001 and P = .03, respectively) and volumes (P < .001 and P = .02, respectively), whereas ejection fraction increased more (P = .02) in the pimobendan group. Of the neuroendocrine hormones, only N-terminal proatrial natriuretic peptide (NT-ProANP) differed (P = .04) between groups. Within groups, plasma aldosterone increased (P = .01), and NT-proANP (P = .01) and NT-proB-type (P = .02) natriuretic peptide decreased in the pimobendan group, and NT-proANP (P = .02) and plasma vasopressin (P = .01) decreased in the benazepril group. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan improves short-term cardiac function more than benazepril in dogs with CHF caused by MMVD. Pimobendan treatment enables the heart to work at smaller end-systolic and diastolic dimensions while maintaining adequate forward stroke volume. Some of the treatment responses found in neuroendocrine profile might have therapeutic relevance.


Assuntos
Benzazepinas/farmacologia , Cardiotônicos/farmacologia , Doenças do Cão/fisiopatologia , Insuficiência Cardíaca/veterinária , Doenças das Valvas Cardíacas/veterinária , Valva Mitral/fisiopatologia , Piridazinas/farmacologia , Aldosterona/sangue , Animais , Fator Natriurético Atrial/sangue , Benzazepinas/uso terapêutico , Cardiotônicos/uso terapêutico , Diuréticos/farmacologia , Diuréticos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Cães , Ecocardiografia/veterinária , Feminino , Furosemida/farmacologia , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/fisiologia , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/fisiopatologia , Masculino , Valva Mitral/efeitos dos fármacos , Peptídeo Natriurético Encefálico/sangue , Tamanho do Órgão/fisiologia , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Precursores de Proteínas/sangue , Piridazinas/uso terapêutico , Volume Sistólico/fisiologia , Vasopressinas/sangue
11.
J Vet Intern Med ; 25(6): 1312-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22092622

RESUMO

BACKGROUND: In canine mitral regurgitation (MR) the rate of heart enlargement increases in the last year before congestive heart failure (CHF). Measurement of heart size and its rate of increase may be useful tests for CHF in MR. OBJECTIVES: To determine the value of vertebral heart scale (VHS) and its rate of increase (∆VHS units/month) for diagnosing the presence and predicting the onset of CHF. ANIMALS: Longitudinal study of 94 Cavalier King Charles Spaniels (CKCS). METHODS: VHS was measured at intervals before CHF. ∆VHS/month was calculated from sequential pairs of VHS measurements and the interval between them. Diagnostic accuracy and utility were determined by the areas under receiver operating characteristic plots (AUROC), and likelihood ratios (LR). RESULTS: AUROC for VHS at the onset of CHF was 0.93 (95% CI, 0.96-0.90), to predict CHF 1-12 months before CHF was 0.74 (95% CI, 0.81-0.66), and for ∆VHS/month at CHF was 0.98 (95% CI, 0.99-0.96). Interval LRs and their cutoff values for CHF were for VHS: 13 (95% CI, 20-7.3) at ≥12.7; 1.2 (95% CI, 2.0-0.68) between 12.7 and 12.0; 0.04 (95% CI, 0.18-0.01) at ≤12.0, and for ∆VHS/month: 15 (95% CI, 30-7.7) at ≥0.08; 0.72 (95% CI, 2.0-0.25) between 0.08 and 0.06; and 0.05 (95% CI, 0.13-0.02) at ≤0.06. CONCLUSIONS AND CLINICAL IMPORTANCE: Under the conditions of this study, VHS and particularly ∆VHS/month are useful measurements for detecting onset of CHF in CKCS with MR.


Assuntos
Doenças do Cão/diagnóstico por imagem , Insuficiência Cardíaca/veterinária , Coração/diagnóstico por imagem , Insuficiência da Valva Mitral/veterinária , Miocárdio/patologia , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Feminino , Coração/anatomia & histologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/patologia , Masculino , Insuficiência da Valva Mitral/patologia , Tamanho do Órgão , Radiografia
12.
J Thromb Haemost ; 9(4): 729-37, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21255250

RESUMO

BACKGROUND: This study was conducted to assess whether newly developed recombinant clotting factor concentrates enable the reversal of dilutional coagulopathy. METHODS: In 50 anesthetized pigs, ~60% of the blood volume was withdrawn and replaced with hydroxyethyl starch. Pigs were randomized to receive either 200 mg kg(-1) fibrinogen (n = 10), fibrinogen and 35 IU kg(-1) prothrombin complex concentrate (PCC) (n = 10), fibrinogen and 4 mg kg(-1) recombinant human factor II (rhFII) concentrate (n = 10), fibrinogen and a three-factor combination (3F) of 4 mg kg(-1) rhFII, 0.006 mg kg(-1) recombinant human FVIIa and 0.32 mg kg(-1) recombinant human FX (n = 10), or saline (n = 10). Thereafter, a standardized liver laceration was performed to induce uncontrolled hemorrhage. Survival time and blood loss were determined, and standard coagulation tests and thrombelastometry were performed. RESULTS: Fibrinogen combined with rhFII or PCC improved survival. Blood loss was significantly decreased in all groups as compared with the animals receiving saline. Clotting time was significantly shortened in the animals treated with fibrinogen and PCC, as well as in those treated with fibrinogen and 3F. One animal died after administration of fibrinogen and PCC. CONCLUSION: Following hemodilution, a combination of fibrinogen and PCC, rhFII or 3F enhances coagulation and final clot strength. Mortality was reduced statistically significantly only in the animals treated with fibrinogen and rhFII or PCC, whereas administration of the combination of fibrinogen and PCC caused a fatal thromboembolic complication. The combination of fibrinogen and rhFII might be effective in reversing dilutional coagulopathy and may reduce blood loss in cases of dilutional coagulopathy.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Fator X/farmacologia , Protrombina/farmacologia , Animais , Fator X/uso terapêutico , Protrombina/uso terapêutico , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Suínos
13.
Clin Genet ; 79(1): 71-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20486941

RESUMO

Studies to identify copy number variants (CNVs) on the X-chromosome have revealed novel genes important in the causation of X-linked mental retardation (XLMR). Still, for many CNVs it is unclear whether they are associated with disease or are benign variants. We describe six different CNVs on the X-chromosome in five male patients with mental retardation that were identified by conventional karyotyping and single nucleotide polymorphism array analysis. One deletion and five duplications ranging in size from 325 kb to 12.5 Mb were observed. Five CNVs were maternally inherited and one occurred de novo. We discuss the involvement of potential candidate genes and focus on the complexity of X-chromosomal duplications in males inherited from healthy mothers with different X-inactivation patterns. Based on size and/or the presence of XLMR genes we were able to classify CNVs as pathogenic in two patients. However, it remains difficult to decide if the CNVs in the other three patients are pathogenic or benign.


Assuntos
Duplicação Cromossômica , Cromossomos Humanos X , Deficiência Intelectual Ligada ao Cromossomo X , Inativação do Cromossomo X/genética , Southern Blotting , Dosagem de Genes , Humanos , Cariotipagem , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/genética , Deficiência Intelectual Ligada ao Cromossomo X/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos , Deleção de Sequência
14.
J Vet Intern Med ; 24(6): 1393-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20958790

RESUMO

BACKGROUND: Pulmonary edema and venous congestion are well-recognized signs of congestive heart failure (CHF) in advanced canine chronic mitral regurgitation (MR). However, little is known about pulmonary blood volume (PBV), blood pulmonary transit time (PTT), and the regulation of these. OBJECTIVES: To measure and evaluate the relationships of PBV, forward stroke volume (FSV), and heart rate normalized blood pulmonary transit time (nPTT) in healthy dogs and dogs with MR. ANIMALS: Thirty-three Cavalier King Charles Spaniels; 11 healthy, 4 in modified New York Heart Association (NYHA) class I, 11 in class II, and 7 in CHF. METHODS: Heart rate normalized PTTs were measured by radionuclide angiocardiography. Left ventricular end diastolic and systolic diameter, left atrial/aortic root ratio, and FSV were measured by echocardiography. PBV and pulmonary blood volume index (PBVI) were calculated by established formulas. RESULTS: PBVI was 308±56 (mean±SD) mL/m2 for healthy dogs, 287±51 mL/m2 in NYHA class I, 360±66 mL/m2 in Class II, and 623±232 mL/m2 in CHF (P=.0008). Heart rate normalized PTT, not FSV, was a predictor of PBV (r=0.92 and 0.02, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased PBV, not decreased FSV, is the main cause of increased nPTT in MR. Increased nPTT can be used as an indicator of abnormal cardiopulmonary function in dogs with MR.


Assuntos
Doenças do Cão/fisiopatologia , Pulmão/fisiopatologia , Insuficiência da Valva Mitral/veterinária , Edema Pulmonar/veterinária , Animais , Volume Sanguíneo , Cães , Feminino , Masculino , Insuficiência da Valva Mitral/classificação , Insuficiência da Valva Mitral/fisiopatologia , Edema Pulmonar/fisiopatologia
15.
Cytogenet Genome Res ; 128(4): 245-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20431279

RESUMO

Here we report the clinical and cytogenetic results of a family carrying a cryptic translocation involving chromosome 3pter and 21qter detected by single nucleotide polymorphism array and subtelomeric fluorescent in situ hybridisation analysis. The index patient, with mild mental retardation in combination with minor dysmorphic features, inherited the derivative chromosome 21 resulting in a partial trisomy of the short arm of chromosome 3 and a partial monosomy of the long arm of chromosome 21. Her apparently healthy brother inherited the derivative chromosome 3 resulting in a terminal deletion of the short arm of chromosome 3 and a terminal duplication of the long arm of chromosome 21. We discuss the different phenotypes for the 2 genotypes and argue for the importance of reporting these imbalances to achieve accurate genetic counseling in prenatal and postnatal diagnosis.


Assuntos
Cromossomos Humanos Par 21 , Cromossomos Humanos Par 3 , Duplicações Segmentares Genômicas , Deleção de Sequência , Translocação Genética , Criança , Pré-Escolar , Face/anormalidades , Família , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Trissomia
16.
J Small Anim Pract ; 51(4): 210-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20406369

RESUMO

OBJECTIVES: The objective of the study was to examine the changes in vertebral heart scale, and left atrial and ventricular dimensions before and at onset of congestive heart failure in cavalier King Charles spaniels with mitral regurgitation. METHODS: Records and radiographs from 24 cavalier King Charles spaniels with mitral regurgitation were used. Vertebral heart scale (24 dogs), and left atrial dimension and left ventricular end diastolic and end systolic diameters (18 dogs) and their rate of increase were measured at intervals over years to the onset of congestive heart failure. They were plotted against time to onset of congestive heart failure. RESULTS: Dimensions and rates of change of all parameters were highest at onset of congestive heart failure, the difference between observed and chance outcome being highly significant using a two-tailed chi-square test (P<0.001). CLINICAL SIGNIFICANCE: The left heart chambers increase in size rapidly only in the last year before the onset of congestive heart failure. Increasing left ventricular end systolic dimension is suggestive of myocardial failure before the onset of congestive heart failure. Rate of increase of heart dimensions may be a useful indicator of impending congestive heart failure.


Assuntos
Doenças do Cão/fisiopatologia , Insuficiência Cardíaca/veterinária , Coração/anatomia & histologia , Insuficiência da Valva Mitral/veterinária , Animais , Cães , Feminino , Insuficiência Cardíaca/fisiopatologia , Masculino , Insuficiência da Valva Mitral/fisiopatologia , Linhagem , Índice de Gravidade de Doença
17.
J Small Anim Pract ; 50 Suppl 1: 44-53, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19765219

RESUMO

OBJECTIVES: To measure accuracy and variability of diagnosis by radiography of heart enlargement (HE) and heart failure (HF) in mitral regurgitation (MR). METHODS: Sixteen readers representing four levels of experience evaluated 50 sets of radiographs with varying severity of MR for presence or absence of HE, left atrial enlargement (LAE) and HF. The performance of the readers was compared with a reference standard, using area under the curve (AUC) of receiver operating characteristic (ROC) curves. The interreader agreement value kappa (K) was calculated. A subset of difficult cases of HF was analysed before and after removing an outlying reader from each group. RESULTS: AUC for HE was 0.89, for LAE it was 0.93 and for HF it was 0.92. Experience increased certainty of diagnosis but not accuracy. K ranges were HE, 0.53 to 0.67; LAE, 0.61 to 0.69 and HF, 0.49 to 0.58. When only difficult cases of HF were read, accuracy decreased and experienced readers performed better than inexperienced. When outlying readers were excluded, the differences between experienced and inexperienced readers increased. CLINICAL SIGNIFICANCE: LAE, not HE, should be used to evaluate the heart size and indirectly the severity of MR on radiographs. For HF, agreement among individual readers was only moderate. Studies of reader accuracy should consider the effects of interreader variability.


Assuntos
Doenças do Cão/diagnóstico por imagem , Insuficiência da Valva Mitral/veterinária , Variações Dependentes do Observador , Animais , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/veterinária , Cães , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/veterinária , Insuficiência da Valva Mitral/diagnóstico por imagem , Curva ROC , Radiografia , Padrões de Referência
18.
Acta Radiol ; 50(2): 181-93, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19169917

RESUMO

BACKGROUND: In diagnosing acute pulmonary embolism (PE) in azotemic patients, scintigraphy and magnetic resonance imaging are frequently inconclusive or not available in many hospitals. Computed tomography is readily available, but relatively high doses (30-50 g I) of potentially nephrotoxic iodine contrast media (CM) are used. PURPOSE: To report on the diagnostic quality and possible contrast-induced nephropathy (CIN) after substantially reduced CM doses to diagnose PE in azotemic patients using 80-peak kilovoltage (kVp) 16-row multidetector computed tomography (MDCT) combined with CM doses tailored to body weight, fixed injection duration adapted to scan time, automatic bolus tracking, and saline chaser. MATERIAL AND METHODS: Patients with estimated glomerular filtration rate (eGFR) <50 ml/min were scheduled to undergo 80-kVp MDCT using 200 mg I/kg, and those with eGFR >or=50 ml/min, 120-kVp MDCT with 320 mg I/kg. Both protocols used an 80-kg maximum dose weight and a fixed 15-s injection time. Pulmonary artery density and contrast-to-noise ratio were measured assuming 70 Hounsfield units (HU) for a fresh clot. CIN was defined as a plasma creatinine rise >44.2 micromol/l from baseline. RESULTS: 89/148 patients (63/68 females) underwent 80-/120-kVp protocols, respectively, with 95% of the examinations being subjectively excellent or adequate. Mean values in the 80-/120-kVp cohorts regarding age were 82/65 years, body weight 66/78 kg, effective mAs 277/117, CM dose 13/23 g I, pulmonary artery density 359/345 HU, image noise (1 standard deviation) 24/21 HU, contrast-to-noise ratio 13/13, and dose-length product 173/258 mGy x cm. Only 1/65 and 2/119 patients in the 80- and 120-kVp cohorts, respectively, with negative CT and no anticoagulation suffered non-fatal thromboembolism during 3-month follow-up. No patient developed CIN. CONCLUSION: 80-kVp 16-row MDCT with optimization of injection parameters may be performed with preserved diagnostic quality, using markedly reduced CM doses compared with common routine practice, which should be to the benefit of patients at risk of CIN.


Assuntos
Azotemia/complicações , Meios de Contraste/administração & dosagem , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ácidos Tri-Iodobenzoicos/administração & dosagem , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos
19.
J Epidemiol Community Health ; 63(2): 166-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18977807

RESUMO

BACKGROUND: Different scales claim to measure the construct "Sense of Coherence". Results from these scales have been compared without knowing whether they measure the same construct. This article compares two versions of Antonovsky's original scale (SOC-13 and SOC-29), translated into Swedish, and a three-item scale (SOC-3) that claims to measure Sense of Coherence. METHODS: The data were analysed in a cross-sectional setting. The study consisted of university students studying social work (n = 395). RESULTS: The original scales had no distribution problems in differentiating Sense of Coherence. The SOC-3 had severe distribution problems. The two versions of the original Sense of Coherence scale had an acceptable reliability (Cronbach's alpha; SOC-29 = 0.93, SOC-13 = 0.89). The SOC-3 scale did not have an acceptable reliability (Cronbach's alpha = 0.39). SOC-29 and SOC-13 had a high intercorrelation (r = 0.96, p<0.001). The SOC-3 significantly correlated with SOC-29 (r = -0.72, p<0.001) and SOC-13 (r = -0.67, p<0.001), but the magnitude was significantly lower than the intercorrelation between SOC-29 and SOC-13 (Fisher's z-transformation, p<0.001). CONCLUSIONS: Because scales that claim to measure the same construct are not always interchangeable, researchers should make sure they compare results from studies that use the same scales.


Assuntos
Indicadores Básicos de Saúde , Saúde Mental , Adaptação Psicológica , Adulto , Atitude Frente a Saúde , Estudos Transversais , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
20.
J Environ Manage ; 86(3): 465-80, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17292530

RESUMO

The resulting impact of disasters on society depends on the affected country's economic strength prior to the disaster. The larger the disaster and the smaller the economy, the more significant is the impact. This is clearest seen in developing countries, where weak economies become even weaker afterwards. Deliberate strategies for the sharing of losses from hazardous events may aid a country or a community in efficiently using scarce prevention and mitigation resources, thus being better prepared for the effects of a disaster. Nevertheless, many governments lack an adequate institutional system for applying cost effective and reliable technologies for disaster prevention, early warnings, and mitigation. Modelling by event analyses and strategy models is one way of planning ahead, but these models have so far not been linked together. An approach to this problem was taken during a large study in Hungary, the Tisza case study, where a number of policy strategies for spreading of flood loss were formulated. In these strategies, a set of parameters of particular interest were extracted from interviews with stakeholders in the region. However, the study was focused on emerging economies, and, in particular, on insurance strategies. The scope is now extended to become a functional framework also for developing countries. In general, they have a higher degree of vulnerability. The paper takes northern Vietnam as an example of a developing region. We identify important parameters and discuss their importance for flood strategy formulations. Based on the policy strategies in the Tisza case, we extract data from the strategies and propose a framework for loss spread in developing and emerging economies. The parameter set can straightforwardly be included in a simulation and decision model for policy formulation and evaluation, taking multiple stakeholders into account.


Assuntos
Planejamento em Desastres/organização & administração , Desastres , Política Pública , Alocação de Recursos , Países em Desenvolvimento , Humanos , Medição de Risco , Gestão de Riscos , Vietnã , Populações Vulneráveis
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