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1.
Mult Scler J Exp Transl Clin ; 10(1): 20552173231226106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38222025

RESUMO

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

2.
ESMO Open ; 8(1): 100772, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36681013

RESUMO

BACKGROUND: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.


Assuntos
Neoplasias da Mama , Idoso , Feminino , Humanos , Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Volume Sistólico , Trastuzumab , Função Ventricular Esquerda
3.
Anaesthesia ; 77(7): 808-817, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35429334

RESUMO

This document provides practical guidance for the management of people with cardiac implantable electronic devices who are undergoing surgical intervention. Increasing numbers of people have cardiac device implants including pacemakers, implantable defibrillators and cardiac resynchronisation devices. During surgical procedures, exposure to electromagnetic interference may lead to inappropriate device function including withholding of pacing function or shock therapies. The guideline summarises key aspects of pre-operative assessment protocols to ensure that all people have their device clearly identified and have had appropriate device follow-up pre-operatively. It outlines general measures which can minimise the risk of potentially problematic electromagnetic interference in the surgical environment. It also includes detailed guidance according to the type of device, whether individuals are dependent on the pacing function of the device and the nature of the procedure they are undergoing. People identified as being at significant risk of harmful procedure-related inappropriate device function may require temporary alteration to the device programming. This may be carried out by a trained cardiac physiologist using a device programmer or, in some cases, can be achieved by clinical magnet application. Guidance on the safe use of magnets and emergency situations is included. Common diagnostic procedures and dental interventions are covered. The guidance aims to provide specific and pragmatic advice which can be applied to provide safe and streamlined care for people with cardiac implantable devices.


Assuntos
Desfibriladores Implantáveis , Marca-Passo Artificial , Eletrônica , Humanos
4.
Equine Vet J ; 51(6): 749-755, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30883892

RESUMO

BACKGROUND: Ulcerative keratitis with peripheral furrow formation is a poorly-described condition which has been associated with a grave prognosis due to rapid necrosis of the cornea. OBJECTIVE: To describe the infectious aetiologies associated with furrow-forming ulcerative keratitis, its overall clinical course and the efficacy of medical and surgical intervention in horses. STUDY DESIGN: Retrospective clinical case series. METHODS: Medical records of 72 horses which presented with furrow-forming ulcerative keratitis at the University of Florida between 1987 and 2015 were reviewed. RESULTS: Seventy-two horses (72 eyes) with furrow-forming ulcerative keratitis were treated at the University of Florida between 1987 and 2015. Of these, a definitive aetiologic diagnosis was available for 37 eyes. Ten of 37 eyes (27%) were diagnosed with fungal keratitis based on cytology of corneal scraping, culture, histopathology and/or fungal PCR. Fourteen of 37 eyes (38%) were diagnosed with a mixed fungal and bacterial keratitis. Thirteen of 37 eyes (35%) were diagnosed with bacterial keratitis. Overall, 26 of 72 total eyes were treated with medical therapy alone (36%). Forty-six of 72 eyes were treated medically and surgically (64%). Of the 26 eyes which received medical therapy, 20 healed with a positive visual outcome (77%) and 6 eyes were non-visual (23%). Of the 46 eyes which received surgical intervention, 40 healed with a positive visual outcome (87%), while six eyes were non-visual (13%). Altogether, 60 of 72 eyes healed with a positive visual outcome following medical or surgical treatment of furrow-forming ulcerative keratitis (83%). Twelve of 72 eyes failed treatment (17%), with six eyes requiring enucleation and six globes becoming phthisical after treatment. MAIN LIMITATIONS: Inconsistencies in available medical record data due to the large span of time (1987-2015) are inherent in this retrospective study, along with gradual evolution of corneal surgical techniques and medical therapies over the decades. CONCLUSIONS: Furrow-forming ulcerative keratitis was associated with a positive visual outcome in 83% of horses treated at the University of Florida between the years 1987 and 2015. Furrow formation may be associated with either fungal or bacterial infection.


Assuntos
Úlcera da Córnea/veterinária , Doenças dos Cavalos/patologia , Animais , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/patologia , Feminino , Doenças dos Cavalos/tratamento farmacológico , Cavalos , Masculino , Resultado do Tratamento
5.
Heart ; 101(22): 1800-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26269413

RESUMO

OBJECTIVE: Implantable cardioverter defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and the combination therapy (CRT-D) have been shown to reduce all-cause mortality compared with medical therapy alone in patients with heart failure and reduced EF. Our aim was to synthesise data from major randomised controlled trials to estimate the comparative mortality effects of these devices and how these vary according to patients' characteristics. METHODS: Data from 13 randomised trials (12 638 patients) were provided by medical technology companies. Individual patient data were synthesised using network meta-analysis. RESULTS: Unadjusted analyses found CRT-D to be the most effective treatment (reduction in rate of death vs medical therapy: 42% (95% credible interval: 32-50%), followed by ICD (29% (20-37%)) and CRT-P (28% (15-40%)). CRT-D reduced mortality compared with CRT-P (19% (1-33%)) and ICD (18% (7-28%)). QRS duration, left bundle branch block (LBBB) morphology, age and gender were included as predictors of benefit in the final adjusted model. In this model, CRT-D reduced mortality in all subgroups (range: 53% (34-66%) to 28% (-1% to 49%)). Patients with QRS duration ≥150 ms, LBBB morphology and female gender benefited more from CRT-P and CRT-D. Men and those <60 years benefited more from ICD. CONCLUSIONS: These data provide estimates for the mortality benefits of device therapy conditional upon multiple patient characteristics. They can be used to estimate an individual patient's expected relative benefit and thus inform shared decision making. Clinical guidelines should discuss age and gender as predictors of device benefits.


Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca/mortalidade , Terapia de Ressincronização Cardíaca/mortalidade , Dispositivos de Terapia de Ressincronização Cardíaca , Terapia Combinada/mortalidade , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume Sistólico/fisiologia
6.
Mitochondrion ; 13(4): 269-76, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23524250

RESUMO

Multiple Symmetrical Lipomatosis (MSL) is an unusual disorder characterized by the development of axial lipomas in adulthood. The pathoetiology of lipoma tissue in MSL remains unresolved. Seven patients with MSL were followed for a mean period of 12 years (8-20 years). All patients had cervical lipomas ranging from subtle lesions to disfiguring masses; six patients had peripheral neuropathy and five had proximal myopathy. Myoclonus, cerebellar ataxia and additional lipomas were variably present. All patients showed clinical progression. Muscle histopathology was consistent with mitochondrial disease. Five patients were positive for mtDNA point mutation m.8344A>G, three of whom underwent lipoma resection--all samples were positive for uncoupling protein-1 mRNA (unique to brown fat). Lipoma from one case stained positive for adipocyte fatty-acid protein-2 (unique to brown fat and immature adipocytes). This long-term study hallmarks the phenotypic heterogeneity of MSL's associated clinical features. The clinical, genetic and molecular findings substantiate the hypothesis that lipomas in MSL are due to a mitochondrial disorder of brown fat.


Assuntos
Tecido Adiposo Marrom/patologia , Lipomatose Simétrica Múltipla/etiologia , Lipomatose Simétrica Múltipla/patologia , Doenças Mitocondriais/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
Ann Oncol ; 24(3): 702-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23108952

RESUMO

BACKGROUND: Peri-operative chemotherapy and surgery is a standard treatment of localised oesophagogastric adenocarcinoma; however, the outcomes remain poor. PATIENTS AND METHODS: ST03 is a multicentre, randomised, phase II/III study comparing peri-operative ECX with or without bevacizumab (ECX-B). The primary outcome measure of phase II (n = 200) was safety, specifically gastrointestinal (GI) perforation rates and cardiotoxicity. RESULTS: Two hundred patients were randomised between October 2007 and April 2010. Ninety-one/101 (90%) ECX and 86/99 (87%) ECX-B patients completed pre-operative chemotherapy; 7 ECX and 9 ECX-B patients stopped due to toxicity. Gastrointestinal perforations (3 ECX, 1 ECX-B), cardiac events (1 ECX, 4 ECX-B) and venous thromboembolic events (VTEs, 8 ECX, 7 ECX-B) were uncommon. Arterial thromboembolic events (ATEs, myocardial infarction (MI) or cerebrovascular accident) were more frequent with ECX-B (5 versus 1 with ECX). Delayed wound healing, anastomotic leaks and GI bleeding rates were similar. More asymptomatic left ventricular ejection fraction (LVEF) falls (≥15% and/or to <50%) occurred with ECX-B (21.2% versus 11.1% with ECX). Clinically significant falls (≥10% to below lower limit of normal, LLN) occurred in (15.3%) and (8.9%) respectively, with no associated cardiac failure (median 22 months follow-up). CONCLUSIONS: Addition of bevacizumab to peri-operative ECX chemotherapy is feasible with acceptable toxicity and no negative impact on surgical outcomes.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Epirubicina/administração & dosagem , Neoplasias Esofágicas/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/fisiopatologia , Neoplasias Gástricas/cirurgia , Volume Sistólico/efeitos dos fármacos , Tromboembolia/induzido quimicamente , Tromboembolia/fisiopatologia , Resultado do Tratamento
8.
Equine Vet J Suppl ; (43): 115-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23447890

RESUMO

REASONS FOR PERFORMING STUDY: We wanted to investigate the visual outcome of horses presented with iris prolapse and treated with corneal transplantation. OBJECTIVE: To evaluate the visual outcome of horses with iris prolapse treated with penetrating keratoplasty alone and penetrating keratoplasty in combination with overlying conjunctival or amniotic membrane grafting. METHODS: A retrospective medical records study of horses presented to the University of Florida Veterinary Medical Center for iris prolapse and treated with penetrating keratoplasty in the period of 1998-2010. Data collected from the medical records included signalment, clinical descriptions of ocular lesions, treatments, and therapeutic outcome. RESULTS: Iris prolapses in this study were caused by corneal ulcers with keratomalacia (n = 37). All horses were treated medically for infection, hyperproteinase activity and iridocyclitis, and then surgically treated with either penetrating keratoplasty alone (n = 9) or penetrating keratoplasty with either a conjunctival pedicle flap (n = 22), amniotic membrane transplant (n = 5) or amnion membrane and conjunctival pedicle flap (n = 1). The eyes were visual postoperatively in a majority of the cases (n = 24; 64.9%). Limited vision was noted in 6 eyes (16.2%), 3 eyes became phthisical (8.1%) and 4 globes were enucleated (10.8%). Graft rejection manifested as some degree of donor corneal graft opacification in all cases. Anterior synechiae were present in 48.6% of the eyes. Wound dehiscence and aqueous humour leakage were also common as post operative problems. CONCLUSION: Penetrating keratoplasty alone or in combination with an overlying graft of conjunctiva or amniotic membrane can achieve a successful visual outcome in a high percentage of horses with iris prolapse.


Assuntos
Lesões da Córnea , Transplante de Córnea/veterinária , Doenças dos Cavalos/cirurgia , Doenças da Íris/veterinária , Transtornos da Visão/veterinária , Animais , Doenças da Córnea/complicações , Doenças da Córnea/veterinária , Úlcera da Córnea/complicações , Úlcera da Córnea/veterinária , Feminino , Cavalos , Doenças da Íris/cirurgia , Masculino , Resultado do Tratamento , Transtornos da Visão/etiologia
10.
Clin Neurophysiol ; 121(10): 1726-39, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20457537

RESUMO

OBJECTIVE: Assess the clinical utility of non-invasive distributed EEG source modelling in focal epilepsy. METHODS: Interictal epileptiform discharges were recorded from eight patients - benign focal epilepsy of childhood (BFEC), four; mesial temporal lobe epilepsy (MTLE), four. EEG source localization (ESL) applied 48 forward-inverse-subspace set-ups: forward - standardized, leadfield-interpolated boundary element methods (BEMs, BEMi), finite element method (FEMi); inverse - minimum norm (MNLS), L1 norm (L1), low resolution electromagnetic tomography (LORETA), standardized LORETA (sLORETA); subspace- whole volume (3D), cortex with rotating sources (CxR), cortex with fixed sources (CxN), cortex with fixed extended sources (patch). Current density reconstruction (CDR) maxima defined 'best-fit'. RESULTS: From 19,200 CDR parameter results and 2304 CDR maps, the dominant variables on best-fit were inverse model and subspace constraint. The most clinically meaningful and statistically robust results came with sLORETA-CxR/patch (lower Rolandic in BFEC, basal temporal lobe in MTLE). Computation time was inverse model dependent: sub-second (MNLS, sLORETA), seconds (L1), minutes (LORETA). CONCLUSIONS: From the largest number of distributed ESL approaches compared in a clinical setting, an optimum modelling set-up for BFEC and MTLE incorporated sLORETA (inverse), CxR or patch (subspace), and either BEM or FEMi (forward). Computation is efficient and CDR results are reproducible. SIGNIFICANCE: Distributed source modelling demonstrates clinical utility for the routine work-up of unilateral BFEC of the typical Rolandic variety, and unilateral MTLE secondary to hippocampal sclerosis.


Assuntos
Mapeamento Encefálico , Diagnóstico por Computador/métodos , Eletroencefalografia , Epilepsias Parciais/patologia , Couro Cabeludo/fisiopatologia , Adolescente , Córtex Cerebral/fisiopatologia , Criança , Epilepsias Parciais/fisiopatologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
11.
J Clin Neurophysiol ; 27(3): 141-62, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20461016

RESUMO

The aim of this study is to characterize and compare dipole and distributed EEG source localization (ESL) of interictal epileptiform discharges (IEDs) in focal epilepsy. Single and averaged scalp IEDs from eight patients-four with benign focal epilepsy of childhood with centrotemporal spikes (BFEC) and four with mesial temporal lobe epilepsy (MTLE)-underwent independent component analysis (ICA) from IED onset to peak. The boundary element method forward model was applied to one of four inverse models: two dipolar-moving regularized, rotating nonregularized and two distributed-standardized low-resolution electromagnetic tomography with rotating cortical sources or with fixed extended sources. Solutions were studied at IED onset, midupswing, peak; ESL strength maxima; ESL residual deviation minima (best fit). From 11,040 ESL parameter points and 960 ESL maps, best-fit dipole and distributed solutions fell at the IED midupswing in BFEC and MTLE when the dominant ICA component typically peaked, localizing to the lower Rolandic sulcus in BFEC and to basolateral or anterior temporal cortex in MTLE. Single-to-averaged ESL variability was high in MTLE. Dipole and distributed ESL are complementary; best-fit solutions for both occupy the IED midupswing and not the IED peak. ICA, a "blind" statistical operation, aids clinical interpretation of ESL fit quality. Single-to-averaged IED localization discordance can be high, a problem warranting further scrutiny if ESL is to earn a place in routine epilepsy care.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/patologia , Eletrodos , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Adolescente , Criança , Epilepsias Parciais/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Análise de Componente Principal
12.
QJM ; 102(7): 485-90, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19474111

RESUMO

BACKGROUND: A recent UK audit showed that a significant proportion of patients who received pacemakers had pacing indications previously overlooked, leading to significant delays to pacemaker implantation. AIM: To investigate the reasons for, and morbidity associated with, overlooked pacing indications. DESIGN: Prospective observational study in a UK regional pacing centre and its referring district hospitals. METHODS: Hospital records from referring and implanting centres were reviewed for 95 consecutive patients undergoing first pacemaker implant to determine symptoms, investigations and hospitalisations occurring after documentation of a pacing indication. RESULTS: Thirty-three of ninety-five patients (35%) had a pacing indication overlooked, which was Class I in 14 patients and Class IIa in 19. Reasons for not making a pacing referral in these patients included: failure to recognize the indication in 14, making adjustments to potentially culprit medication in 15 and requesting additional 'confirmatory' tests in 4. Twenty-six patients (79%) with missed indications experienced adverse events after documentation of an indication, and before receiving a pacemaker: 23 had ongoing symptoms (including one cardiac arrest), three received temporary pacing wires and 18 were hospitalized with symptoms related to cardiac rhythm. Twenty-seven patients (82%) had a total of 38 additional specialist investigations after documentation of a pacing indication. CONCLUSION: Documentation of an indication for pacing failed to trigger referral for permanent pacing in 35% of patients. This failure led to significant delays, morbidity and use of health service resource, which may have been avoided if timely recognition of the pacing indication had prompted referral. Failure to recognize pacing indications and reassessing symptoms and repeating investigation after changes to medication, often required for the management of associated tachyarrhythmias or other medical conditions, contribute to these delays, perhaps unnecessarily.


Assuntos
Estimulação Cardíaca Artificial , Cardiopatias/mortalidade , Marca-Passo Artificial , Encaminhamento e Consulta , Estimulação Cardíaca Artificial/mortalidade , Erros de Diagnóstico , Cardiopatias/terapia , Humanos , Auditoria Médica , Estudos Prospectivos , Fatores de Tempo
13.
Br J Cancer ; 100(5): 684-92, 2009 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-19259090

RESUMO

More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associated with anthracyclines) led to the development of cardiac guidelines for adjuvant trials, which are used to monitor patient safety in clinical practice. Clinical experience has shown that the trial protocols are not truly applicable to the breast cancer population as a whole, and exclude some women from receiving trastuzumab, even though they might benefit from treatment without long-term adverse cardiac sequelae. Consequently, five oncologists who recruited patients to trastuzumab trials, some cardiologists with whom they work, and a cardiovascular lead general practitioner reviewed the current cardiac guidelines in the light of recent safety data and their experience with adjuvant trastuzumab. The group devised recommendations that promote proactive pharmacological management of cardiac function in trastuzumab-treated patients, and that apply to all patients who are likely to receive standard cytotoxic chemotherapy. Key recommendations include: a monitoring schedule that assesses baseline and on-treatment cardiac function and potentially reduces the overall number of assessments required; intervention strategies with cardiovascular medication to improve cardiac status before, during, and after treatment; simplified rules for starting, interrupting and discontinuing trastuzumab; and a multidisciplinary approach to breast cancer care.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/prevenção & controle , Monitorização Fisiológica/métodos , Algoritmos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/fisiopatologia , Feminino , Diretrizes para o Planejamento em Saúde , Coração/fisiopatologia , Cardiopatias/etiologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/fisiopatologia , Humanos , Trastuzumab , Reino Unido , Função Ventricular Esquerda/efeitos dos fármacos
14.
Ann Oncol ; 20(5): 816-27, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19153118

RESUMO

Anthracyclines are considered to be among the most active agents for the treatment of breast cancer. However, their use is limited by cumulative, dose-related cardiotoxicity. Such cardiotoxicity results in a permanent loss of cardiac myocytes and a progressive reduction in cardiac function following each subsequent dose of anthracycline. Initially, damage to the heart is subclinical; however, increasingly impaired cardiac function can result in cardiovascular symptoms, with serious cardiac injury resulting in chronic heart failure. Since the early detection and treatment of cardiotoxicity can reduce its clinical effects, it is important that oncologists are aware of these adverse effects and manage them appropriately. This review examines the risk factors for anthracycline-associated cardiotoxicity and offers recommendations on strategies to reduce the cardiotoxicity of anthracyclines in the management of patients with advanced breast cancer.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/induzido quimicamente , Neoplasias da Mama/patologia , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Cardiopatias/patologia , Cardiopatias/prevenção & controle , Humanos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Medição de Risco , Fatores de Risco
16.
Vet Ophthalmol ; 11 Suppl 1: 35-43, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19046268

RESUMO

OBJECTIVE: To describe and evaluate a surgical technique utilized for the therapy of deep corneal stromal abscesses (DSA) in horses. The DSA is excised and replaced with a partial thickness corneal lamellar allograft. METHODS: A retrospective clinical study describing the indications for the surgical technique utilized and the outcomes of this procedure in 10 eyes of 10 horses. RESULTS: Each affected eye had a discrete DSA within the posterior stroma. An initial partial thickness semicircular corneal incision was made at the limbus, followed by anterior stromal lamellar dissection over the lesion. After excision of the DSA and replacement with a larger diameter split-thickness donor button, the anterior stroma was replaced into its original position and the initial corneal incision was repaired. All of the animals that underwent deep lamellar endothelial keratoplasty (DLEK) procedure healed appropriately and with subjectively less postoperative scarring and complications than previously described surgical approaches to DSA. CONCLUSIONS: This procedure is an effective technique for surgical removal of DSA in horses and, in most cases, results in a visual and cosmetically acceptable globe. The advantages of this technique compared to other surgical approaches to DSA are the peripheral location of the incision, shortened anesthesia times, the resultant minimal scarring and shorter healing times associated with DLEK.


Assuntos
Abscesso/veterinária , Doenças da Córnea/veterinária , Transplante de Córnea/veterinária , Endotélio Corneano/transplante , Doenças dos Cavalos/cirurgia , Abscesso/cirurgia , Animais , Doenças da Córnea/cirurgia , Substância Própria , Transplante de Córnea/métodos , Feminino , Sobrevivência de Enxerto , Cavalos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
17.
QJM ; 101(12): 955-60, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18820315

RESUMO

BACKGROUND: Regional variation in permanent pacemaker (PPM) implantation rates is well described, the reasons for which are unclear. Significant delays to PPM implantation in UK practice were described 20 years ago, but contemporary data are lacking. AIM: To investigate delays to PPM implantation and their causes. DESIGN: Prospective observational study in a UK regional pacing centre and its referring district hospitals. METHODS: A total of 95 consecutive patients receiving first PPM implant for bradycardia indications from 1 June 2006 to 31 August 2006 were included. Hospital records from the referring and implanting centres were reviewed to determine the timings of: symptom onset; first hospital contact; documented pacing indication (defined by 2002 ACC/AHA/NASPE guidelines); referral to implanter; and PPM implantation. RESULTS: Forty-eight patients (51%) were referred for pacing urgently; median delay from symptoms to PPM 15 days (range 0-7332 days). Forty-seven patients (49%) were referred electively; median delay from symptoms to PPM 380 days (range 33-7505 days), P < 0.0001. Twenty-three of the 47 elective patients (49%) had previous hospitalization with symptoms suggestive of bradycardia. Thirty-three of the 95 patients (35%) had a Class I or IIa pacing indication which did not trigger a pacing referral. CONCLUSION: There are significant delays to PPM implantation in the United Kingdom, longer in those treated electively than those managed as emergencies. Some delays are due to 'process' problems including waiting lists, but a substantial proportion of patients had delays due to failure to refer for pacing once a pacing indication was documented.


Assuntos
Marca-Passo Artificial , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Implantação de Prótese/métodos , Encaminhamento e Consulta , Fatores de Tempo , Reino Unido , Listas de Espera
18.
Vet Ophthalmol ; 11(4): 228-33, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18638348

RESUMO

OBJECTIVE: To evaluate a new procedure for fixation of prolapsed nictitans glands to the cartilage of the nictitans that will not interfere with the mobility of the nictitating membrane. METHODS: A prospective clinical trial utilizing a nonabsorbable suture to anchor the prolapsed gland to the cartilage of the third eyelid was undertaken. Fifteen eyes of 10 dogs were included in the study. A 4-0 nylon suture was passed from the anterior surface of the third eyelid through the base of the cartilage to the posterior aspect and then tunneled circumferentially beneath the conjunctiva over and around the prolapsed gland. The suture was then passed through the cartilage again to the anterior face of the third eyelid. The gland was replaced into its normal position as the suture was slowly tightened and then tied on the anterior aspect of the nictitans. RESULTS: Over a period of several weeks, the glands reduced in size and took on a normal appearance. All glands but one remained in place for the length of follow-up, which ranged from 2 weeks to 33 months. CONCLUSIONS: This procedure results in acceptable cosmetic effects with the return of the gland to its normal position posterior to the nictitating membrane. The advantage of this technique over traditional tacking to the orbital rim is that the third eyelid retains its normal mobility and, thus, its protective functions. The procedure once mastered is very quick and can be performed in less time than many of the traditional replacement techniques.


Assuntos
Doenças do Cão/cirurgia , Cães/cirurgia , Glândulas Exócrinas/cirurgia , Doenças Palpebrais/veterinária , Membrana Nictitante/cirurgia , Técnicas de Sutura/veterinária , Animais , Doenças do Cão/patologia , Glândulas Exócrinas/patologia , Doenças Palpebrais/complicações , Doenças Palpebrais/patologia , Doenças Palpebrais/cirurgia , Feminino , Seguimentos , Masculino , Órbita/cirurgia , Periósteo/cirurgia , Prolapso , Estudos Prospectivos , Distribuição Aleatória , Lágrimas/metabolismo , Resultado do Tratamento
19.
Vet Ophthalmol ; 11(4): 234-41, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18638349

RESUMO

OBJECTIVE: To compare aqueous humor myocilin protein levels in dogs with the primary glaucomas to those with the secondary glaucomas, primary cataracts, and diabetic cataracts. MATERIALS AND METHODS: Four groups were selected, based on diagnosis by the attending veterinary ophthalmologists and included: primary glaucoma (primary open-angle glaucoma (POAG) and primary closed angle glaucoma (PCAG); n = 155); secondary glaucoma (n = 94); primary (presumed inherited) cataract (n = 142), and diabetic cataract (n = 83). A total of 474 samples (187 males, 263 females, 24 unreported) with average ages of 117 months for the males and 101 months for the females were analyzed. Myocilin protein was measured using the Coomassie staining and Western blot methods relative to a myocilin control. RESULTS: Differences were seen between nonglaucomatous (cataractous) and glaucomatous dogs with myocilin levels in glaucomatous eyes being many times higher than those in the cataractous dogs. Primary glaucomatous dogs were found to have an aqueous humor myocilin protein level of 17.30 +/- 1.03 units. Secondary glaucomas had the highest level of myocilin in the aqueous humor with 19.27 +/- 1.41 units. Diabetic cataractous dogs had the lowest levels of myocilin reported with 6.60 +/- 0.88 (mean +/- SEM) units. Normal (cataractous) dogs had a myocilin level in the aqueous humor of 8.05 +/- 0.86 units. CONCLUSION: Aqueous humor protein levels were elevated, relative to the myocilin control, in both the primary and secondary glaucoma groups compared to the cataract and diabetic cataract groups. Like in the Beagle POAG, aqueous humor myocilin protein levels are increased. Further studies are indicated to investigate the exact role of the aqueous humor myocilin protein in the genesis in increased IOP in these primary glaucomatous breeds.


Assuntos
Humor Aquoso/metabolismo , Catarata/veterinária , Proteínas do Citoesqueleto/metabolismo , Doenças do Cão/metabolismo , Proteínas do Olho/metabolismo , Glaucoma/veterinária , Glicoproteínas/metabolismo , Animais , Estudos de Casos e Controles , Catarata/genética , Catarata/metabolismo , Proteínas do Citoesqueleto/análise , Doenças do Cão/genética , Cães , Proteínas do Olho/análise , Feminino , Predisposição Genética para Doença , Glaucoma/genética , Glaucoma/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/veterinária , Glicoproteínas/análise , Masculino
20.
Vet Ophthalmol ; 11(2): 123-33, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18302577

RESUMO

OBJECTIVE: To evaluate the visual outcome of three techniques of corneal transplantation surgery in treating severe inflammatory keratopathies in the horse. DESIGN: Retrospective medical records study. ANIMALS STUDIED: Medical records of 206 horses that received corneal transplantation surgery at the University of Florida Veterinary Medical Center from 1993 to 2007 were reviewed. PROCEDURE: Data collected from the medical records included signalment, types of ocular lesions, type of transplant surgery performed, length of follow-up, complications, and visual outcomes. RESULTS: Full thickness penetrating keratoplasty (PK) was performed in 86 horses for melting ulcers, iris prolapse/descemetoceles, and medically nonresponsive full thickness stromal abscesses (SA). Posterior lamellar keratoplasty (PLK) and deep lamellar endothelial keratoplasty (DLEK) are split thickness penetrating keratoplasties that were utilized for medically nonresponsive deep stromal abscesses (DSA) in 54 and 66 eyes, respectively. The most common postoperative surgical complication was graft rejection and varying degrees of graft opacification. Wound dehiscence and aqueous humor leakage was also a common postoperative problem. A positive visual outcome was achieved for PK, PLK, and DLEK in 77.9%, 98.1%, and 89.4%, respectively. CONCLUSIONS: Corneal transplantation is a tectonically viable surgery in the horse with an overall success rate of 88.5% in maintaining vision when treating vascularized and infected corneal disease in the horse.


Assuntos
Doenças da Córnea/veterinária , Transplante de Córnea/veterinária , Doenças dos Cavalos/terapia , Acuidade Visual/fisiologia , Animais , Doenças da Córnea/terapia , Transplante de Córnea/métodos , Feminino , Rejeição de Enxerto/veterinária , Cavalos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
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