RESUMO
OBJECTIVE: We sought a shortened MOTHER neonatal abstinence syndrome (NAS) and Finnegan score that would retain comparable performance characteristics of the full instrument. STUDY DESIGN: Retrospective cohort. RESULTS: In total, 124,170 MOTHER NAS scores between August 2007 and May 2016 from 775 infants (≥36 weeks) were examined. Classification and regression tree model identified the most important subsets of the scored variables. A 9-element shortened scale yielded >90% sensitivity and specificity to predict clinical endpoints based on the full 19-element MOTHER NAS score. Conversion of the data sets to the Finnegan score, and applying the same procedure resulted in a nine-element score with similar performance characteristics. CONCLUSION: Shortened scoring instruments were identified with the high-predictive power for clinical endpoints based on the 19-element full MOTHER NAS score. There was no substantial variation in performance for age, supporting the current practice of utilizing a single scoring tool regardless of postnatal age.
Assuntos
Síndrome de Abstinência Neonatal , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Mães , Síndrome de Abstinência Neonatal/diagnóstico , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Neonatal abstinence syndrome is defined by signs and symptoms of withdrawal that infants develop after intrauterine maternal drug exposure. All infants with documented in utero opioid exposure, or a high pre-test probability of exposure should have monitoring with a standard assessment instrument such as a Finnegan Score. A Finnegan score of >8 is suggestive of opioid exposure, even in the absence of declared use during pregnancy. At least half of infants in most locales can be treated without the use of pharmacologic means. For this reason, symptom scores will drive the decision for pharmacologic therapy. Nevertheless, all infants, regardless of initial manifestations, should be first be managed with non-pharmacologic approaches which in turn, should not be considered as the sole alternative to drug therapy, but rather, as the base upon which all patients are treated. Those who continue to have symptoms despite supportive care should be pharmacologically treated, which in the most severe cases, is life-saving.
Assuntos
Analgésicos Opioides/efeitos adversos , Aleitamento Materno , Síndrome de Abstinência Neonatal/terapia , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Humanos , Recém-Nascido , Metadona/uso terapêutico , Morfina/uso terapêutico , Síndrome de Abstinência Neonatal/tratamento farmacológicoRESUMO
Vancomycin use is often associated with nephrotoxicity. It remains uncertain, however, to what extent vancomycin is directly responsible, as numerous potential risk factors for acute kidney injury frequently coexist. Herein, we critically examine available data in adult patients pertinent to this question. We review the pharmacokinetics/pharmacodynamics of vancomycin metabolism. Efficacy and safety data are discussed. The pathophysiology of vancomycin nephrotoxicity is considered. Risk factors for nephrotoxicity are enumerated, including the potential synergistic nephrotoxicity of vancomycin and piperacillin-tazobactam. Suggestions for clinical practice and future research are given.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Vancomicina/efeitos adversos , Injúria Renal Aguda/fisiopatologia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Humanos , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/análogos & derivados , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Fatores de Risco , Vancomicina/administração & dosagem , Vancomicina/farmacocinéticaRESUMO
The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration-time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log-likelihood criterion, goodness of fit plots, and scientific plausibility. Identification of covariates was done using a full covariate model approach. The pharmacokinetics of vancomycin was adequately described with a two-compartment model. Parameters included clearance of 2.83 L/hr, limited central volume of distribution 24.2 L, and low residual variability 0.67%. Findings from the analysis suggest that standard dosing recommendations for vancomycin in non-ECMO patients are adequate to achieve therapeutic trough concentrations in ECMO patients. This further shows that ECMO minimally affects the PK of vancomycin in adults including in higher-weight patients.
Assuntos
Antibacterianos/sangue , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Modelos Biológicos , Dinâmica não Linear , Vancomicina/sangue , Adulto , Idoso , Antibacterianos/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Estudos Prospectivos , Vancomicina/farmacocinéticaRESUMO
The effect of the protease-activated receptor-1 (PAR-1) antagonist vorapaxar on human bleeding time is not known. This was a randomized, two-period, open-label trial in healthy men (n = 31) and women (n = 5). In period 1, subjects received 81 mg aspirin q.d. or a vorapaxar regimen achieving steady-state plasma concentrations equivalent to chronic 2.5 mg q.d. doses, for 7 days. In period 2, each group added 7 days of the therapy alternate to that of period 1 without washout. Bleeding time and platelet aggregation using arachidonic acid, ADP, and TRAP agonists were assessed. Bleeding time geometric mean ratio (90% CI) for vorapaxar/baseline was 1.01 (0.88-1.15), aspirin/baseline was 1.32 (1.15-1.51), vorapaxar + aspirin/vorapaxar was 1.47 (1.26-1.70), and vorapaxar + aspirin/aspirin was 1.12 (0.96-1.30). Unlike aspirin, vorapaxar did not prolong bleeding time compared with baseline. Bleeding time following administration of vorapaxar with aspirin was similar to that following aspirin alone.
Assuntos
Aspirina/farmacologia , Voluntários Saudáveis , Lactonas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Piridinas/farmacologia , Difosfato de Adenosina/farmacologia , Adulto , Ácido Araquidônico/farmacologia , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Tempo de Sangramento , Testes de Coagulação Sanguínea , Quimioterapia Combinada , Feminino , Humanos , Lactonas/administração & dosagem , Lactonas/sangue , Lactonas/farmacocinética , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/sangue , Piridinas/farmacocinética , Receptores de Trombina/agonistas , Adulto JovemRESUMO
It was hypothesized that the four-factor prothrombin complex concentrate (4F-PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two-period crossover, assessor-blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four-factor prothrombin complex concentrate (4F-PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP-reagent and PPP-reagent low, anti-Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F-PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F-PCC and saline in anti-Xa assessment at 30 min or later time points.
Assuntos
Anticoagulantes/farmacologia , Fatores de Coagulação Sanguínea/farmacologia , Voluntários Saudáveis , Pirazóis/farmacologia , Piridonas/farmacologia , Adulto , Determinação de Ponto Final , Fator Xa/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Placebos , Tempo de Protrombina , Trombina/metabolismoRESUMO
The dual enrolling of phase I volunteers is a potential risk to subjects. It can also distort study results, threaten study validity, and possibly cause harm to future patients. Existing subject registries differ in structure, funding, and governance. Although the choice of the ideal system is driven by the scope of the risk and the funding mechanism, and is ultimately a value judgment of freedom versus paternalism, none of the registries significantly impinges on the tenets of ethically based research.
Assuntos
Ética em Pesquisa , Sistema de Registros/ética , Sujeitos da Pesquisa/provisão & distribuição , Altruísmo , Custos e Análise de Custo , Humanos , Motivação , Autonomia Pessoal , Sujeitos da Pesquisa/psicologia , Medição de RiscoRESUMO
BACKGROUND/AIMS: This study characterized the safety and pharmacological properties of AVI-005, a novel glycosylated recombinant human interferon-alpha2b produced from the egg whites of chickens transfected with human cDNA. METHODS: 18 healthy volunteers received single subcutaneous rising doses (0.5, 1.66 or 5 million international units, MIU) of AVI-005. A randomized parallel comparator group of 10 subjects received 5 MIU of unglycosylated IFN-alpha2b (Intron A). The pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-24h, Vd, and clearance were compared between AVI-005 and unglycosylated IFN-alpa2b. RESULTS: At equipotent doses, AVI-005 had a larger AUC0-24h than the control interferon. Pharmacodynamic markers ofneopterin and beta2-microglobulin for the two treatments were similar. These markers were increased by AVI-005 in a dose-dependent manner. Pharmacodynamic responses to treatment with AVI-005 were shown by the change in mRNA expression for interferon inducible protein kinase and 2'5'-oligoadenylate synthetase. Adverse events in the two groups were qualitatively and quantitatively similar. CONCLUSION: AVI-005 demonstrates biological activity and pharmaco-kinetic properties in humans that support further development.
Assuntos
Interferon-alfa/farmacologia , Proteínas Recombinantes/farmacologia , 2',5'-Oligoadenilato Sintetase/genética , Adulto , Animais , Animais Geneticamente Modificados , Galinhas , Feminino , Glicosilação , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Interferon-alfa/farmacocinética , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Proteínas Quinases/genética , RNA Mensageiro/biossíntese , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Equivalência Terapêutica , Microglobulina beta-2/sangueRESUMO
Governmental agencies overseeing pharmaceutical products use a risk/benefit approach to analyse data and make regulatory decisions. Comprehensive public dissemination of the safety profile of pharmaceutical products is part of an overall strategy for reducing risk associated with the use of any medical product. In the US, reports of postmarketing surveillance of approved drugs are in the public domain. Some, but not all, of the information in drug interaction studies is available to the public through the Freedom of Information Act (FOIA). However, there are concerns over the misuse of these data for commercial or other gain. The need to protect intellectual property and foster innovation in drug development, and concerns of legal liability are often cited as reasons to limit full public access to data from drug development studies. In contrast, intellectual freedom. public safety, and a mandate for transparent decision-making processes by regulatory agencies are issues that support open access to these data. Ultimately. concern for the public safety justifies open access to postmarketing surveillance data, and to a lesser degree, data regarding drug interactions in marketed products, and should outweigh the potential loss of competitive advantage by pharmaceutical companies.
Assuntos
Acesso à Informação/legislação & jurisprudência , Interações Medicamentosas , Vigilância de Produtos Comercializados/métodos , Gestão de Riscos , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMO
Gap junction number and size vary widely in cardiac tissues with disparate conduction properties. Little is known about how tissue-specific patterns of intercellular junctions are established and regulated. To elucidate the relationship between gap junction channel protein expression and the structure of gap junctions, we analyzed Cx43 +/- mice, which have a genetic deficiency in expression of the major ventricular gap junction protein, connexin43 (Cx43). Quantitative confocal immunofluorescence microscopy revealed that diminished Cx43 signal in Cx43 +/- mice was due almost entirely to a reduction in the number of individual gap junctions (226 +/- 52 vs. 150 +/- 32 individual gap junctions/field in Cx43 +/+ and +/- ventricles, respectively; P < 0.05). The mean size of an individual gap junction was the same in both groups. Immunofluorescence results were confirmed with electron microscopic morphometry. Thus when connexin expression is diminished, ventricular myocytes become interconnected by a reduced number of large, normally sized gap junctions, rather than a normal number of smaller junctions. Maintenance of large gap junctions may be an adaptive response supporting safe ventricular conduction.
Assuntos
Conexina 43/biossíntese , Junções Comunicantes/ultraestrutura , Ventrículos do Coração/ultraestrutura , Miocárdio/ultraestrutura , Animais , Caderinas/análise , Conexina 43/análise , Fáscia/ultraestrutura , Imunofluorescência , Ventrículos do Coração/metabolismo , Heterozigoto , Processamento de Imagem Assistida por Computador , Camundongos , Camundongos Mutantes , Microscopia Confocal , Microscopia Eletrônica , Miocárdio/metabolismo , Músculos Papilares/ultraestruturaRESUMO
BACKGROUND: Currently normal or pathologic conditions are documental by color slides, photos or videotape. However, it is more difficult to manage large numbers of images and to recall specific pictures or videos at any time. Digital record archives may be a solution for this problem. MATERIAL AND METHODS: We present a digital video and photographic archive that controls documents with a picture archive software designed for use in ENT examination units. RESULTS: Working on this digital unit we have developed a software program that allows the creation and administration of digital pictures and videos using only one program. To avoid mistakes manual recording of data was reduced to a minimum. Filing is done automatically and similar results can be found via self-explained criteria. Due to the pro-user computer software, less trained persons are not afraid to use the system. Hence, the number of documented diagnoses has increased. Present experience shows that material and videos make it easier to work with patients and clinical confidence is increased. Additionally, the physician is protected indirectly. When many persons work with one system, digital photographic archives increase the clinician's ability to refind documents, even after a period of years. The need for quality assurance in medicine will help find more use for a digital archive in ENT.
Assuntos
Otolaringologia/instrumentação , Garantia da Qualidade dos Cuidados de Saúde , Sistemas de Informação em Radiologia/instrumentação , Gravação em Vídeo/instrumentação , Sistemas Computacionais , Alemanha , Humanos , Otorrinolaringopatias/diagnóstico , Neoplasias Otorrinolaringológicas/diagnóstico , SoftwareRESUMO
Penicillin-binding protein 2a (PBP2a) is the primary beta-lactam resistance determinant of methicillin-resistant Staphylococcus aureus (MRSA). MecA, the gene coding for PBP2a, was cloned with the membrane-anchoring region at the N-terminus deleted. The truncated protein (PBP2a) was overexpressed in Escherichia coli mostly in the soluble form accounting for approximately 25% of soluble cell protein and was purified to homogeneity. The purified protein was shown to covalently bind beta-lactams in an 1:1 ratio as determined by electrospray mass spectrometry. A novel method based on HPLC-elctrospray mass spectrometry has been developed to quantitatively determine the formation of the covalent adducts or acyl-PBP2a complexes. By using this method, combined with kinetic techniques including quench flow, we have extensively characterized the interactions between PBP2a and three beta-lactams and determined related kinetic parameters for the first time. The apparent first-order rate constants (ka) of PBP2a acylation by benzylpenicillin showed a hyperbolic dependence on the concentration of benzylpenicillin. This is consistent with the mechanism that the binding of the penicillin to PBP2a consists of reversible formation of a Michaelis complex followed by formation of the penicilloyl-PBP2a adduct, and allowed the determination of the individual kinetic parameters for these two steps, the dissociation constant Kd of 13.3 mM and the first-order rate constant k2 of 0.22 s-1. From these values, the second-order rate constant k2/Kd, the value reflecting the overall binding efficiency of a beta-lactam, of 16.5 M-1 s-1 was obtained. The fairly high Kd value indicates that benzylpenicillin fits rather poorly into the protein active site. Similar studies on the interaction between PBP2a and methicillin revealed k2 of 0.0083 s-1 and Kd of 16.9 mM, resulting in an even smaller k2/Kd value of 0.49 M-1 s-1. The rate constants k3 for deacylation of the acyl-PBP2a complexes, the third step in the interactions, were measured to be <1.5 x 10(-)5 s-1. These results indicate that the resistance of PBP2a to penicillin inactivation is mainly due to the extremely low penicillin acylating rate in addition to the low association affinity, but not to a fast rate of deacylation. Acylation of PBP2a by a high-affinity cephalosporin, Compound 1, also followed a saturation curve of ka versus the compound concentration, from which k2 = 0.39 s-1, Kd = 0.22 mM, and k2/Kd = 1750 M-1 s-1 were obtained. The 100-fold increase in the k2/Kd value as compared with that of benzylpenicillin is mostly attributable to the decreased (60-fold) Kd, indicating that the cephalosporin fits much better to the binding pocket of the protein.
Assuntos
Proteínas de Bactérias , Proteínas de Transporte/metabolismo , Hexosiltransferases , Meticilina/metabolismo , Muramilpentapeptídeo Carboxipeptidase/metabolismo , Peptidil Transferases , Staphylococcus aureus/metabolismo , beta-Lactamas/metabolismo , Acilação , Proteínas de Transporte/química , Proteínas de Transporte/genética , Clonagem Molecular , Escherichia coli/genética , Genes Bacterianos , Cinética , Substâncias Macromoleculares , Espectrometria de Massas/métodos , Proteínas de Membrana/metabolismo , Meticilina/farmacologia , Resistência a Meticilina/genética , Muramilpentapeptídeo Carboxipeptidase/química , Muramilpentapeptídeo Carboxipeptidase/genética , Penicilina G/metabolismo , Proteínas de Ligação às Penicilinas , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Análise de Sequência , Staphylococcus aureus/química , Staphylococcus aureus/genética , beta-Lactamas/químicaAssuntos
Doenças do Gato/patologia , Síndrome de Stevens-Johnson/veterinária , Administração Tópica , Corticosteroides/uso terapêutico , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Biópsia , Doenças do Gato/terapia , Gatos , Diagnóstico Diferencial , Exsudatos e Transudatos , Feminino , Necrose , Síndrome de Stevens-Johnson/patologia , Síndrome de Stevens-Johnson/terapiaRESUMO
This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems. Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones. Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase. Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump.
Assuntos
Carbapenêmicos/química , Carbapenêmicos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Quinolonas/química , Proteínas de Bactérias/efeitos dos fármacos , Carbapenêmicos/síntese química , Proteínas de Transporte/efeitos dos fármacos , Divisão Celular , Bactérias Gram-Negativas/enzimologia , Bactérias Gram-Positivas/enzimologia , Hexosiltransferases/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Complexos Multienzimáticos/efeitos dos fármacos , Muramilpentapeptídeo Carboxipeptidase/efeitos dos fármacos , Proteínas de Ligação às Penicilinas , Peptidil Transferases/efeitos dos fármacos , Relação Estrutura-Atividade , Inibidores da Topoisomerase IIAssuntos
Doenças do Cão/diagnóstico , Pâncreas/patologia , Pancreatite/veterinária , Doença Aguda , Animais , Diagnóstico Diferencial , Doenças do Cão/terapia , Cães , Masculino , Necrose , Pâncreas/diagnóstico por imagem , Pancreatite/diagnóstico , Pancreatite/terapia , Radiografia , Tripsina/metabolismo , UltrassonografiaRESUMO
Species specific diseases, e.g. idiopathic mucinosis of the Chinese Shar Pei are reported by use of 31 clinical cases and 140 biopsy samples. Idiopathic mucinosis is one of the most frequent diseases of this increasing breed in Germany, too. The disease is diagnosed by use of histologic examination of skin biopsies. Therapy is performed by application of corticosteroids and symptomatic treatment.
Assuntos
Doenças do Cão/patologia , Mucinoses/veterinária , Pele/patologia , Corticosteroides/uso terapêutico , Fatores Etários , Animais , Biópsia , Doenças do Cão/epidemiologia , Doenças do Cão/terapia , Cães , Feminino , Alemanha/epidemiologia , Endogamia , Masculino , Mucinoses/epidemiologia , Mucinoses/patologia , Mucinoses/terapia , Especificidade da EspécieRESUMO
Altogether 11 cases of stings in dogs are reported. In at least nine cases, common vipers (Vipera berus) were identified to be the causes. The most frequently observed symptoms were haemorrhagic and oedematous inflammations of the area of the wounds, furthermore haemolysis and intense leukocytosis with relative and absolute neutrophilia and in some cases shock symptoms. One dog died 17 days after the accident from multiple organ insufficiencies, all the other dogs improved. As a therapy, bandage of the injured limb, quieting of the dog, snake antitoxin, corticosteroids, antihistaminics, antibiotics, and symptomatic therapy depending on the clinical signs are recommended.
Assuntos
Doenças do Cão , Mordeduras de Serpentes/veterinária , Corticosteroides/uso terapêutico , Animais , Antivenenos/uso terapêutico , Bandagens , Cães , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Inflamação , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Choque Hemorrágico/etiologia , Choque Hemorrágico/terapia , Mordeduras de Serpentes/fisiopatologia , Mordeduras de Serpentes/terapia , Venenos de Víboras , ViperidaeAssuntos
Doenças do Cão , Infestações por Ácaros/veterinária , Pioderma/veterinária , Dermatopatias Infecciosas/veterinária , Infecções Estafilocócicas/veterinária , Administração Oral , Administração Tópica , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Cães , Inseticidas/administração & dosagem , Inseticidas/uso terapêutico , Masculino , Infestações por Ácaros/complicações , Infestações por Ácaros/tratamento farmacológico , Pioderma/etiologia , Pioderma/microbiologia , Dermatopatias Infecciosas/tratamento farmacológico , Dermatopatias Infecciosas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Toluidinas/administração & dosagem , Toluidinas/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
The efficacy and safety of the angiotensin converting enzyme inhibitor enalapril in dogs with naturally acquired class III or class IV heart failure was evaluated in this study. Eighteen small-breed dogs with insufficiency of their mitral valves, but without other diseases were included in this study over a period of six months. When necessary due to massive pulmonary edema or high serum potassium concentrations, furosemide was added to the therapy with enalapril. No other drugs, including digitalis, were used in this study. The treatment was followed by anamnesis, clinical examinations, electrocardiography, radiography, echocardiography and laboratory diagnosis. Examinations were performed before treatment and after one week, after six weeks and after six months of treatment. 72% of the dogs improved in NYHA classification until the end of the study (p < 0.05). The incidence of seizures due to syncopes or severe respiratory distress decreased during this study (p < 0.01). For 28% of the dogs this treatment was not successful. In the electrocardiographic, radiographic and laboratory examinations statistically significant changes could not be recorded. The decrease in heart rate did not reach statistical significance. The echocardiographic investigation evaluated a significant decrease in fractional shortening and in the diastolic diameter of the left ventricular wall (p < 0.05 respectively p < 0.01), but no significant change in the diastolic or systolic diameter of the interventricular septum. The average oral dose of enalapril was 0.38 mg/kg body weight b.i.d., the average dose of furosemide was 0.37 mg/kg body weight b.i.d. in the first week of the study and was raised to 0.74 mg/kg body weight b.i.d. until the end of the study. Side effects like diarrhea, vomiting or reduced appetite did not increase during the course of the study. However one dog was excluded from the study because of repeated vomiting after six weeks of treatment. This study shows the beneficial clinical and hemodynamic effects and the security of the therapy with enalapril for dogs with heart failure due to mitral insufficiency.