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1.
J Pharm Biomed Anal ; 94: 180-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24598171

RESUMO

Convenient methods for testing drug candidates' lipophilicity and acidity are highly requested in modern pharmaceutical research and drug development strategies. Reversed-phase high-performance liquid chromatography (RP HPLC) might be particularly useful for the determination of both dissociation constant and the (pH-dependent) partition coefficient related parameters, applicable in high-throughput analysis of multi-component mixtures. The general theory of combined pH/organic modifier gradient has recently provided equations relating gradient retention time and pH of the mobile phase. The purpose of this work was to facilitate the identification of analytes in this technique by its transfer to RP HPLC coupled with time-of-flight mass spectrometry with electrospray ionization source (ESI-TOF-MS). The accuracy of the proposed methodology was assessed by analyzing a set of known drugs. The ammonium formate, ammonium acetate or ammonium bicarbonate buffers were used to control pH during chromatographic analysis. In result, the pKa and hydrophobicity parameters were determined and the accuracy of the estimated values was assessed by comparing them with literature data. The gradient RP HPLC coupled with ESI-TOF-MS methods allowed for the rapid determination of dissociation constant and hydrophobicity and was shown to be especially applicable for complex mixtures. The use of ESI-TOF-MS detection allowed to achieve the medium-throughput screening rate (100 compounds/day) and provided a simple approach to assess pharmacokinetically important physicochemical properties of drugs.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Espectrometria de Massas/métodos , Preparações Farmacêuticas/química , Soluções Tampão , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Força Próton-Motriz
3.
Circulation ; 101(14): 1693-7, 2000 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-10758052

RESUMO

BACKGROUND: QT dispersion, commonly measured in sinus beats (QTd-S), can also be calculated in premature ventricular beats (QTd-V). To date, no studies have addressed the relation between these 2 variables. METHODS AND RESULTS: In 148 patients with remote myocardial infarction and premature ventricular beats on a routine ECG, QT dispersion, defined as the difference between the maximum and the minimum QT interval across the 12-lead ECG, was calculated separately for the ventricular extrasystole and the preceding sinus beat. In the total group of patients, QTd-V was greater than QTd-S (83+/-33 versus 74+/-34 ms, respectively; P=0.001). During a follow-up period of 35+/-17 months, arrhythmic events (sustained ventricular tachycardia, ventricular fibrillation, or sudden death) were noted in 30 patients. A QTd-V of >/=100 ms was a stronger univariate marker of arrhythmic events than was a QTd-S of >/=100 ms, and multivariate analysis selected only prolonged QTd-V (hazard ratio 3.81, 95% CI 2.2 to 11.2) and low ejection fraction (hazard ratio 3.05, 95% CI 1.6 to 7.6) as independent predictors of arrhythmic events. CONCLUSIONS: The magnitude of QTd-V was greater than that of QTd-S in the total group of patients. Prolonged QTd-V is associated with a significantly increased risk for arrhythmic events in postinfarction patients, and the prognostic significance of QTd-V exceeds that of QTd-S.


Assuntos
Arritmias Cardíacas/etiologia , Complexos Cardíacos Prematuros/complicações , Complexos Cardíacos Prematuros/fisiopatologia , Frequência Cardíaca , Infarto do Miocárdio/complicações , Função Ventricular , Idoso , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Volume Sistólico
4.
Pol Merkur Lekarski ; 6(34): 192-3, 1999 Apr.
Artigo em Polonês | MEDLINE | ID: mdl-10391058

RESUMO

So far there is no unambiguous universally accepted standards for 24 ABPM. Aim of this study was to establish standard values of systolic and diastolic blood pressures, taking into account minimal night values, corresponding with basic biological activity. 1204 patients were tested. In 707 of them, (mean age 42.5 +/- 14.7 years), arterial hypertension was recognized. Basic on our results we determined borderline values (112/69 mmHg) which are diagnostic for arterial hypertension. Those norms eliminate influence of environmental factors on values of blood pressure. They correspond with homeostasis in hypertensive patients.


Assuntos
Ritmo Circadiano/fisiologia , Hipertensão/diagnóstico , Adulto , Feminino , Humanos , Masculino , Valores de Referência , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo
5.
Pol Merkur Lekarski ; 6(32): 73-5, 1999 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-10337175

RESUMO

The estimation of microcirculatory parameters in patients with essential hypertension and in normotensic control group was the aim of this study. The study group consisted of 14 patients with essential hypertension confirmed by 24-hours ABP. 10 healthy patients served as control group. The flow in the skin microcirculation was measured by laser-Doppler flowmeter (PF-3, PERIMED) on dorsal part of the palm. Microcirculatory indices were registered in resting conditions, during one-minute occlusion reaction and during reactive hyperemia. The following indices were calculated: resting flow, biological zero, maximal flow, time to maximal flow, ratio of maximal to resting flow, ratio of resting flow to biological zero and ratio of maximal flow to biological zero. Skin microcirculation was highly disturbed in patients with essential hypertension. It was expressed by significantly higher biological zero and longer time to maximal flow.


Assuntos
Hipertensão/diagnóstico , Fluxometria por Laser-Doppler/métodos , Pele/irrigação sanguínea , Adulto , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade
6.
Pol Arch Med Wewn ; 99(5): 382-9, 1998 May.
Artigo em Polonês | MEDLINE | ID: mdl-9816887

RESUMO

The link between left ventricular dysfunction and arrhythmogenesis is commonly known. However, so far, only the systolic left ventricular dysfunction has been evaluated. Because of the controversial results of those studies, we decided to assess if is there a link between late potentials (LP) and left ventricular diastolic dysfunction. Our material consisted of 56 patients: 11 women and 45 men, mean age was 61.12 +/- 10.07 years. Signal averaged ECG and ECHO were performed in each patient, 2-3 months after myocardial infarction. For high pass filter of 40 Hz, LP were defined as 2 or 3 abnormal SAECG variables (the averaged QRS > 114 ms, the low amplitude signal duration LAS > 38 ms and root mean square voltage of the terminal 40 ms RMS40 < 20 microV). During ECHO study, we assessed E and A waves E/A ratio, left ventricular end-diastolic volume (LVEDV), ejection fraction (EF), acceleration (AT) and deceleration times (DT). The patients were divided into 2 groups: group I-30 patients LP positive and group II-26 patients LP negative. There were no significant differences between the groups in terms of age, EF, and heart rate. We presented significant differences between group I and II in terms of E wave velocity (0.75 +/- 0.19 vs 0.64 +/- 0.19 p < 0.03) E/A ratio (2.13 +/- 1.56 vs 1.0 +/- 0.5 p < 0.05) respectively. We did not confirm significant differences as regards A wave velocity, AT, isovolumetric time (IVRT) and LVEDV between both tested groups. In group I we revealed a significant correlation between E wave (r = 0.45), E/A ratio (r = 0.62), AT (r = -0.42) E/A ratio (r = 0.56), DT (r = 0.55) and QRS, as well as DT and LPD (r = 0.40) and between IVRT and RMS40 (r = -0.43). The results of our study suggest that in patients after myocardial infarction: 1/incidence of LP depends on the degree of left ventricular filling pattern like in impaired relaxion, quite well correlated with filtered QRS time 3/in LP positive patients there was predominance of restrictive left ventricular filling pattern, quite well correlation with RMS40 amplitude.


Assuntos
Diástole , Infarto do Miocárdio/etiologia , Disfunção Ventricular Esquerda/diagnóstico , Adulto , Idoso , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/epidemiologia
7.
Pol Merkur Lekarski ; 3(14): 57-60, 1997 Aug.
Artigo em Polonês | MEDLINE | ID: mdl-9480175

RESUMO

The aim of the study was to evaluate the importance of time and frequency domain analysis of P-wave signal averaging, left atrium size measured echocardiographically and time of P.-wave assessed in II lead of standard ECG in patients with different frequency of atrial fibrillation events. The material consisted of 110 pts (81 men and 29 women), mean age 60.44 +/- 10.73 with atrial fibrillation events concomitant coronary heart disease and/or primary hypertension documented in standard ECG or Holter monitoring. The positive correlation, statistically significant between the frequency of atrial fibrillation events and the time of filtered P-wave vector, the time of filtered P-wave in X, Y, Z leads and differences between times of filtered P-wave vector and times of P-wave in II ECG lead was confirmed. Additionally the negative correlation, statistically significant between frequency of atrial fibrillation events and RMS10, RMS20 and RMS30 was confirmed. There was no correlation between frequency analysis of P-wave averaging or left size and frequency of atrial fibrillation events.


Assuntos
Fibrilação Atrial/diagnóstico , Eletrocardiografia , Idoso , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Pol Merkur Lekarski ; 3(14): 65-7, 1997 Aug.
Artigo em Polonês | MEDLINE | ID: mdl-9480177

RESUMO

UNLABELLED: We evaluated effects of perindopril (Prestarium-SERVIER) in the treatment of the primary hypertension in 41 patients (mean age 41.6) in the I or II degrees WHO using 24 ambulatory blood pressure measurement and echocardiography. Investigation were performed before and after 3 and 6 months of the treatment. Initially 4 mg of perindopril was given and individually was increased after 3 months to 8 mg according to 24 ambulatory blood pressure measurement results. We obtained significant decrease of blood pressure in 3 (134.6/86.6 mm Hg) and in 6 (135/88, 9 mm Hg) months of treatment in comparison to baseline values (141.8/91.1 mm Hg), decrease of left ventricular mass to 244.4 g in 3 and 248.8 g after 6 months (baseline 258.5 g), as well as index of left ventricular mass, wall thickness and left ventricular end diastolic volume. There was no significant differences in: ejection, heart rate, left ventricular inflow on the successive investigations. Good effect of perindopril we observed in 31 patients (75.6%) after 6 months of treatment. We did not observe any serious side effects of perindopril. CONCLUSION: Perindopril in treatment hypertension effectively reduces the level of blood pressure (systolic, diastolic and mean) without any effect on heart rate. Prestarium reduces left ventricular mass, intraseptal wall thickness and left ventricular end diastolic volume. There is no influence on inflow to the left ventricle as well as on ejection fraction.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Indóis/uso terapêutico , Adulto , Anti-Hipertensivos/farmacologia , Cardiomegalia/tratamento farmacológico , Ecocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/diagnóstico por imagem , Indóis/farmacologia , Masculino , Pessoa de Meia-Idade , Perindopril
9.
Pol Arch Med Wewn ; 95(4): 299-306, 1996 Apr.
Artigo em Polonês | MEDLINE | ID: mdl-8755835

RESUMO

The aim of this study was to assess if amiodarone hydrochloride administered intravenously influenced signal-averaged electrocardiogram and if this effect can be used in diagnosing patients prone to sustained ventricular tachycardia (sVT). Two hundred thirty seven patients were divided into 3 groups: group K--58 patients with no apparent heart disease, group W--121 patients with remote myocardial infarction and group C-58 patients with remote myocardial infarction and at least one episode of sVT. Signal-averaged electrocardiograms (SAECG) were assessed in time domain (QRS, LPD, RMS40) and frequency domain analysis logarhythmically (40 D, 60 A) and linearly [formula: see text] for windows lasting 120 and 140 ms, and starting 20, 40, 80 ms before the end and 60 ms after the beginning of QRS complex. Amiodarone hydrochloride increased frequency of late potentials (LP) in all groups especially in group C (K 5.2%-9.1%, W 33.9%-41.4%, C 75.9% -90.9%. Amiodarone hydrochloride prolonged total activation time--QRS (K -4.27 ms, W -6.06 ms, C -5.82 ms), time of low amplitude signals LPD (K -2.64 ms, W -2.87 ms, C -5.39 ms) and decreased the amplitude of RMS40 (K -2.12 mV, W -4.67 mV, C -5.0 mV). In group C the influence of amiodarone hydrochloride was found the strongest in the terminal part of the QRS complex whereas its influence on total activation time of QRS complex was weaker. We concluded that in patients prone to sVT amiodarone hydrochloride most strongly influenced the terminal part of QRS complex which suggested predominant influence on the zone of delayed conduction and amiodarone hydrochloride non significantly influenced on the results of frequency domain analysis.


Assuntos
Amiodarona/farmacologia , Eletrocardiografia/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Adulto , Idoso , Amiodarona/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia
10.
Kardiol Pol ; 39(10): 273-7; discussion 278-9, 1993 Oct.
Artigo em Polonês | MEDLINE | ID: mdl-8246355

RESUMO

In patients with unexplained syncope and documented nonsustained VT or complex premature ventricular beats indication for programmed ventricular stimulation (PVS) should be considered. However, the variables derived from noninvasive methods that predict diagnostic yield of PVS are incompletely defined. The purpose of this study was to elucidate the role of noninvasive testing variables in predicting inducible monomorphic sustained ventricular tachycardia (SVT) in 116 patients (pts) presenting with syncope. The study group consisted of 45 pts with remote Q wave myocardial infarction. 5 pts with non-Q wave myocardial infarction, 21 pts with another heart disease and 45 pts without organic heart disease. All pts underwent standard ECG, Holter monitoring, echocardiography, signal-averaged ECG and PVS with 1, 2 and 3 extrastimuli at three basic cycle lengths. Nonsustained VT, low ejection fraction, prolongation of QTc interval, abnormal Q waves in postinfarction pts (Q-MI) and late potentials (LP) indicate a greatly increased probability of inducible SVT. Inducible SVT was present in 15 of 45 (33%) pts with Q-MI. Although in the group of 71 pts without Q-MI, nonsustained VT on Holter monitoring was detected in 20 pts, LP in 16 pts, prolongation of QTc interval in 3 pts and low ejection fraction in 2 pts, the positive yield of PVS was documented in only one case (1%). The combination of Q-MI and LP best predicted inducible SVT showing a sensitivity of 75%, specificity of 93%, overall predictive accuracy of 91%, predictive value of positive response of 63% and negative response of 69% to identify pts who would have inducible SVT. Thus, the combination of Q-MI and LP variables was shown as the best predictor of inducible SVT in pts with unexplained syncope. In pts without Q-MI the noninvasive testing variables have considerably less value in selection of pts to PVS, because inducible SVT is very rare in this population.


Assuntos
Eletrofisiologia , Síncope/etiologia , Taquicardia Ventricular/diagnóstico , Adulto , Idoso , Ecocardiografia , Eletrocardiografia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taquicardia Ventricular/complicações
11.
Kardiol Pol ; 36(3): 131-5, 1992 Mar.
Artigo em Polonês | MEDLINE | ID: mdl-1351545

RESUMO

Exercise testing has been shown to be predictive for future cardiac events in patients with established diagnosis of coronary heart disease. Exercise test parameters associated with poor prognosis may be unreliable if patient is receiving beta adrenergic agents. The purpose of this study was: 1) to compare the results of exercise testing performed before and during beta blocking therapy, and 2) to determine the role of beta blockers in the prognostic significance of the ST-segment response recorded during exercise testing. The study population consisted of 518 patients (mean age 52 +/- 7 years) with coronary heart disease. The diagnosis was based on the presence of one of the following three criteria: 1) typical history and significant ST-segment depression on resting or exercise electrocardiogram, 2) history of myocardial infarction, 3) significant coronary angiographic abnormalities. In all patients symptom-limited exercise test was performed before and two weeks after the onset of beta blocker therapy. The data from the first and second tests were estimated for significance of differences between the mean values with following results: maximal heart rate--135 +/- 21 and 123 +/- 19 bpm (p less than 0.001), maximal work load achieved--98 +/- 43 and 109 +/- 44 W (p less than 0.001), maximal systolic blood pressure--171 +/- 28 and 163 +/- 26 mmHg (p less than 0.001). Occurrence of characteristic ST-segment depression was more frequent during the first than during the second test (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Doença das Coronárias/tratamento farmacológico , Eletrocardiografia/efeitos dos fármacos , Adulto , Idoso , Doença das Coronárias/mortalidade , Doença das Coronárias/fisiopatologia , Teste de Esforço/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
12.
Kardiol Pol ; 33(3): 151-7, 1990 Mar.
Artigo em Polonês | MEDLINE | ID: mdl-2082068

RESUMO

The purpose of the study was to describe the clinical picture in patients with ischemic heart disease (IHD) and verifying severity of ventricular arrhythmias. The study included 856 patients with IHD aged 23-88 years (mean = 55.3), including 659 men and 197 women. Holter monitoring was performed in all patients. Ventricular arrhythmias were graded according to Lown. The patients were divided into five groups: group 1-349 patients with Lown's grade 1 and 2; group 2-95 patients with grade 3; group 3-152 patients with grade 4a and 4b; group 4-11 patients with grade 5; group 5-507 patients (selected from groups 2, 3 and 4) with Lown's grade 3 and 4 or 5. Arterial hypertension was found in 17.1%, myocardial infraction in 66%, and syncope in 12.3% of the patients. The patients with complex ventricular arrhythmias versus Lown's grade 1 and 2 show significant differences especially in respect to: the frequency of previous anterior myocardial infraction, the incidence of pain at rest, loss consciousness, the frequency of ventricular tachycardia and fibrillation, anginal pain and exercise-related arrhythmias. The patients with Lown's ventricular arrhythmia grade 3-5 do not differ significantly in their clinical manifestations of IHD from the patients with ventricular arrhythmias grade from 3 to 5. The development of silent myocardial ischemia during exercise stress testing is typical also for the patients with complex ventricular arrhythmias. A decreased contractility index, ejection fraction and dyskinesis are significantly more frequent in the patients with complex ventricular arrhythmias.


Assuntos
Arritmias Cardíacas/etiologia , Doença das Coronárias/complicações , Adulto , Idoso , Arritmias Cardíacas/fisiopatologia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Kardiol Pol ; 33(7): 12-6, 1990.
Artigo em Polonês | MEDLINE | ID: mdl-2259059

RESUMO

The purpose of this study was to compare the relation of signal averaged variables of the QRS complex to spontaneous and to inducible sustained ventricular tachycardia. Signal averaging of the surface QRS complex was performed in 96 patients with coronary artery disease and ventricular arrhythmias. Twenty eight of them were evaluated by programmed electrical stimulation. Signal average variables were considered abnormal as: 1) the QRS duration as the time from the onset to end point of the QRS vector complex greater than 120 ms, 2) the maximal amplitude of the terminal 40 ms of the QRS vector complex less than 25 microV, 3) the duration of low (less than 40 microV) amplitude signal of QRS vector complex less than or equal to 40 ms. The ventricular late potentials were defined as the pressure of 2 or 3 abnormal averaged variables. Programmed electrical stimulation was performed using single and double extrastimuli at sinus rhythm and at ventricular pacing rates 100, 120, 140 bpm, followed by ventricular burst pacing (3 and 10 consecutive beats) at sinus rhythm. If stimulation of the right ventricular apex did not initiate ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation or two repetitive nonsustained ventricular tachycardias) right ventricular outflow tract stimulation was performed. Sustained ventricular tachycardia was defined as ventricular tachycardia lasting 30 s or requiring termination because hemodynamic compromise. Quantitative comparison of signal averaged variables was performed in patients with inducible versus noninducible ventricular tachycardia and in patients with spontaneous versus non-spontaneous ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Doença das Coronárias/fisiopatologia , Taquicardia/etiologia , Potenciais de Ação/fisiologia , Idoso , Doença das Coronárias/complicações , Estimulação Elétrica , Eletrocardiografia , Ventrículos do Coração/fisiopatologia , Humanos , Pessoa de Meia-Idade , Taquicardia/diagnóstico , Fatores de Tempo
14.
Kardiol Pol ; 33(5): 303-7, 1990.
Artigo em Polonês | MEDLINE | ID: mdl-2074626

RESUMO

This multicenter study comprised a group of 900 patients (207 females and 693 males, aged 23-68 years, mean 53) with ischaemic heart disease. Go medications other than nitrates, nifedipine and diuretics were administered at the time of study. In all patients a simultaneous standard 12-lead ecg and a phonocardiogram was registered. QT and QS2 intervals were then measured, and the QT/QS2 index calculated. QT/QS2 ratio 1.0 was considered as a normal one. A 24-h Holter ecg monitoring was performed in each patients, and ectopic ventricular activity was graded according to the Lown's classification. For patients with each class of arrhythmia the mean value of QT/QS2 was calculated. All means were similar, with values 1.0. Proportion of patients with abnormal values of QT/QS2 index was similar in patients showing different Lown classes of arrhythmia. Since a 24-hour monitoring does not give a full information about the arrhythmic events, patients with the history of VT/VF were analyzed separately. In this group an increase of QT/QS2 index was observed significantly more frequently than in other patients (37% vs 19%, p = 0.016). It is concluded that no close relationship exists between QT/QS2 index and the type of ventricular arrhythmia found on the Holter monitoring. However, pathologic QT/QS2 values seem to characterize the patients with increase risk of VT/VF.


Assuntos
Arritmias Cardíacas/fisiopatologia , Doença das Coronárias/fisiopatologia , Eletrocardiografia , Adulto , Idoso , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Cor Vasa ; 29(6): 456-62, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3436150

RESUMO

Out of 2000 patients examined by two-dimensional echocardiography 20 patients (1%) were chosen in whom rupture of chordae tendineae was demonstrated (19 in the left and 1 in the right ventricle). In this group, rupture was connected with myocardial infarction in 5 cases and no coexistent cardiovascular disease was found in 7 cases. In 5 cases rupture of multiple chordae was found, with severe signs of left ventricular failure. In the remaining 15 cases only single chordae were ruptured. In 8 cases of this group, no significant hemodynamic disturbances were observed. Two-dimensional ECHO makes possible diagnosis of the rupture of single or multiple chordae and evaluation of the cause and consequences of this complication.


Assuntos
Cordas Tendinosas , Ecocardiografia , Ruptura Cardíaca/diagnóstico , Adulto , Feminino , Ruptura Cardíaca Pós-Infarto/diagnóstico , Humanos , Masculino
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