RESUMO
We have studied dissociative electron attachment (DEA) between low energy (≤0.6 eV) longitudinally polarized electrons and gas-phase chiral targets of 3-bromocamphor (C_{10}H_{15}BrO), 3-iodocamphor (C_{10}H_{15}IO), and 10-iodocamphor. The DEA rate depends on the sign of the incident electron helicity for a given target handedness, and it varies with both the atomic number (Z) and location of the heaviest atom in the molecule. While simple dynamic mechanisms can account for the asymmetry dependence on Z, they fail to explain the large asymmetry variation with the heavy atom location.
RESUMO
PURPOSE: To test the peripheral arterial vasodilation hypothesis of sodium retention in cirrhosis. This states that sodium retention is triggered by arterial underfilling and predicts that development of sodium retention will be associated with significant and related declines in indices of arterial filling that reverse when sodium retention resolves. DESIGN: Longitudinal evaluation of a cohort of patients with alcoholic liver disease. PATIENTS AND METHODS: Eighteen men, 8 of whom were studied twice, 3 three times, 2 four times, and 5 five times (40 between-study comparisons). Between 23 studies, the patients were ascites-free (Group NN). Ascites spontaneously disappeared between seven studies (Group YN), appeared between six studies (Group NY), and remained present between four studies (Group YY). Between-study changes in blood volume, arterial blood pressure, cardiac output, systemic vascular resistance, left atrial volume, left ventricular diastolic diameter, aortic root diameter, aortic blood velocity, plasma norepinephrine and atrial natriuretic factor concentrations, plasma renin activity, and urinary sodium excretion were evaluated by paired t-tests. These changes were also compared among groups by analysis of variance. In addition, correlations among the changes were sought. RESULTS: Systolic, diastolic, and mean arterial pressures, left ventricular diastolic diameter, aortic root diameter, stroke volume, cardiac output, plasma norepinephrine concentration, and systemic vascular resistance were unchanged between studies. Left atrial volume increased between studies in Group NY. Pulse pressure fell more in Group NY than in Groups NN and YN, principally as a result of a decline in systolic blood pressure. Plasma norepinephrine concentration, plasma renin activity, and blood volume rose more in Group NY than in Groups NN, YN, and YY. Changes in both systolic and pulse pressures were directly correlated with the change in sodium excretion but unrelated to the change in plasma norepinephrine concentration. Changes in plasma norepinephrine concentration and plasma renin activity were unrelated to changes in blood pressure, systemic vascular resistance, and urinary sodium excretion. CONCLUSIONS: None of the indices of arterial filling tested except pulse pressure were related to sodium retention. Reduced pulse pressure is inconsistent with arterial underfilling, as peripheral vasodilation instead increases pulse pressure by increasing diastolic run-off. These data do not support the hypothesis that arterial underfilling is the stimulus for sodium retention in alcoholic cirrhosis.
Assuntos
Hemodinâmica/fisiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/fisiopatologia , Sódio/metabolismo , Adulto , Idoso , Análise de Variância , Artérias/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Cirrose Hepática/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Pressorreceptores/fisiologia , Sódio/sangue , Resistência Vascular/fisiologia , Vasodilatação/fisiologiaRESUMO
PURPOSE AND PATIENTS AND METHODS: The relationship of plasma renin activity (PRA) to indices of circulatory filling and other possible determinants of renin secretion was studied in 31 men with alcoholic liver disease. Characteristics of patients with normal and increased PRA values were examined. Significant differences guided subsequent simple and multiple regression analysis. RESULTS: Supine PRA was increased (greater than 2.4 ng/mL/h on a 200 mEq/d intake of sodium, ranging as high as 33 ng/mL/h) in 14 of 57 studies. Nonascitic patients with elevated PRA values were significantly younger than those with normal PRA values. Among patients without ascites, the plasma atrial natriuretic factor concentration correlated inversely with PRA. Ascitic patients with elevated PRA values had a significantly reduced serum sodium concentration, urinary sodium excretion, creatinine clearance, and arterial pressure. Systemic vascular resistance, plasma norepinephrine and caffeine concentrations, and left atrial volume were similar in patients with and without increased PRA values. Univariate followed by multiple regression analysis identified age and plasma atrial natriuretic factor concentration as significant independent correlates of PRA in patients without ascites (R2 = 0.54). Serum sodium concentration and urinary sodium excretion were significant correlates of PRA in patients with ascites (R2 = 0.80). CONCLUSION: The associates of PRA in alcoholic liver disease are diverse and potentially complex. Age and plasma atrial natriuretic factor concentration are important in patients without ascites. In patients with ascites, tubular delivery of sodium to the macula densa, as modified by the filtered load and proximal reabsorption, appeared to be a principal association of PRA. Indices of circulatory filling did not emerge as clearly independent associations of PRA. Increased PRA values in patients with ascites may be an effect of sodium retention rather than part of its cause.
Assuntos
Hepatopatias Alcoólicas/enzimologia , Renina/sangue , Adulto , Idoso , Ascite/enzimologia , Ascite/metabolismo , Fator Natriurético Atrial/sangue , Cafeína/metabolismo , Creatinina/metabolismo , Hemodinâmica , Humanos , Rim/fisiopatologia , Fígado/metabolismo , Fígado/fisiopatologia , Circulação Hepática , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Análise de Regressão , Renina/metabolismo , Sódio/metabolismo , SupinaçãoRESUMO
Less complex methods of measuring hepatic metabolic capacity are needed. A simplified caffeine clearance test was evaluated in 23 patients with stable alcoholic liver disease. First, saliva caffeine concentrations were measured over a 24-h caffeine-free interval. Clearance was calculated from the rate of elimination of caffeine and an assumed volume of distribution and compared with the results of a formal clearance test using sequential plasma and saliva samples following a 300 mg oral dose. The simplified method was then assessed in 11 hospitalized patients with cirrhosis. Saliva caffeine concentrations remained measurable over the interval of study in 82% of patients. Caffeine clearance as determined by the simplified method did not differ from plasma caffeine clearance after an oral dose. Application of this method was achieved in 11 of 12 patients hospitalized for complications of severe liver disease, and revealed markedly diminished clearance. Thus, caffeine clearance can be accurately estimated in patients with severe liver disease using two or more samples of either saliva or plasma. This simplified determination of caffeine elimination rate provides a more practical assessment of hepatic metabolic capacity than a formal clearance test.
Assuntos
Cafeína/farmacocinética , Cirrose Hepática Alcoólica/metabolismo , Fígado/metabolismo , Adulto , Bilirrubina/sangue , Cafeína/sangue , Jejum , Feminino , Meia-Vida , Encefalopatia Hepática/metabolismo , Humanos , Masculino , Taxa de Depuração Metabólica , Saliva/metabolismo , Albumina Sérica/análiseRESUMO
A pathological state of arterial vasodilation has been postulated to cause the increased cardiac output commonly observed in cirrhosis. Further, subsequent arterial underfilling has been proposed as the stimulus to sodium retention and ascites formation. Left ventricular size during the cycle of a cardiac contraction is predictably altered by a decrease in afterload. Specifically, increased systolic emptying should be observed. The relationship of left ventricular size during the cardiac cycle to systemic hemodynamic indices and urinary sodium retention was investigated in patients with alcoholic cirrhosis to test these hypotheses. Echocardiographic studies were performed on 24 male patients with alcoholic cirrhosis and compared with the results obtained in 10 age-matched male controls. Patients with cirrhosis had increased cardiac output and heart rate and decreased arterial pressure compared with normal subjects, confirming the presence of a hyperdynamic circulation. Patients with cirrhosis had enlarged left ventricular diameter at both end diastole (0.08 +/- 0.01 vs. 0.07 +/- 0.007 cm/kg dry body wt; P less than 0.001) and end systole (0.06 +/- 0.01 vs. 0.05 +/- 0.005 cm/kg; P less than 0.05). Left ventricular end-diastolic diameter was directly related to blood volume (r = 0.56, P less than 0.005). No significant differences in cardiac output, arterial pressure, or systemic resistance were found between patients with and patients without ascites. Increased cardiac output in cirrhosis occurs in conjunction with an enlarged ventricle throughout the cardiac cycle. The increase in left ventricular end-systolic diameter indicates that diminished afterload is not responsible for the increase in cardiac output. As the diameter of the ventricle during diastolic filling correlates with vascular volume, cardiac output in cirrhosis may be primarily determined by an increase in vascular volume.
Assuntos
Artérias/patologia , Débito Cardíaco Elevado/etiologia , Ventrículos do Coração/patologia , Cirrose Hepática Alcoólica/complicações , Adulto , Pressão Sanguínea , Volume Sanguíneo , Dilatação Patológica , Ecocardiografia , Frequência Cardíaca , Humanos , Cirrose Hepática Alcoólica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sódio/urina , Resistência VascularRESUMO
We present a case of collagenous colitis with evidence of terminal ileal involvement. The patient suffered from chronic watery diarrhea of three months' duration, and colonoscopy revealed a normal endoscopic appearance. Histologic examination of biopsies revealed a broad subepithelial band of collagen, with similar histologic findings in the terminal ileum. Additionally, the patient exhibited abnormalities of d-xylose and vitamin B12 absorption, although there were no clinical signs of malabsorption. Biopsy of the proximal small intestine was normal. The significance of these findings for the definition of the clinicopathologic entity of collagenous colitis and its pathogenesis are discussed.
Assuntos
Colite/patologia , Colágeno/análise , Colo/patologia , Ileíte/patologia , Íleo/patologia , Colite/complicações , Diarreia/etiologia , Feminino , Humanos , Ileíte/complicações , Mucosa Intestinal/patologia , Pessoa de Meia-IdadeRESUMO
We investigated the occurrence of alcoholic autonomic dysfunction in patients with alcoholic cirrhosis in order to define its prevalence and relationship to renal sodium retention. Forty-seven alcoholics and 16 age-matched normal subjects were evaluated. Thirty-seven patients had liver disease (13 with and 24 without ascites), and 10 patients had normal hepatic function. Autonomic nervous system function was ascertained by skin sudomotor responses and the response of blood pressure and plasma norepinephrine concentration to upright tilt (sympathetic nervous system function), and by heart rate responses to deep breathing, Valsalva maneuver, and upright tilt (parasympathetic and sympathetic nervous system function). Heart rate responses to deep breathing and Valsalva maneuver were diminished, and skin sudomotor responses were significantly worse, in alcoholics than in control subjects. Alcoholic patients also had significantly lower supine mean arterial pressure (93 +/- 10 vs. 116 +/- 8 mm Hg, p less than or equal to 0.0001), and significantly greater increases in arterial pressure during passive upright tilt, than control subjects (mean increase 6.5 +/- 6.6 vs. 0.1 +/- 1.6 mm Hg, p = 0.0003). All of these findings were present to similar degrees in patients with and without liver disease and in cirrhotic patients with and without ascites. Supine heart rates, however, differed among the groups evaluated. Heart rate was significantly greater in patients with cirrhosis than in alcoholic patients without liver disease (83 +/- 11 vs. 71 +/- 13 bpm, p = 0.006), and in patients with ascites than in patients without ascites (88 +/- 12 vs. 80 +/- 10 bpm, p = 0.04). Plasma norepinephrine concentration was elevated in most patients with cirrhosis and was significantly higher in patients with ascites than in patients without ascites (789 +/- 238 vs. 388 +/- 185 pg/ml, p less than 0.0001; nl range: 65-320 pg/ml). Autonomic nervous system function is similarly impaired in alcoholics with and without liver disease. Patients with cirrhosis also have increased heart rate and elevated plasma norepinephrine concentration, abnormalities that are most pronounced in patients with sodium retention. Their is uncertainty as to the stimulus for norepinephrine release, and its source, in these patients. However, the similarity of supine blood pressure in patients with and without ascites and the occurrence of orthostatic hypertension rather than orthostatic hypotension following upright tilt suggest that arterial underfilling is not responsible.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Rim/metabolismo , Cirrose Hepática Alcoólica/fisiopatologia , Sódio/urina , Ascite/complicações , Ascite/fisiopatologia , Pressão Sanguínea , Frequência Cardíaca , Humanos , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática Alcoólica/metabolismo , Masculino , Norepinefrina/sangue , Taquicardia/etiologiaRESUMO
We tested the hypothesis that increased plasma glucagon concentration resulting from portal-systemic shunting or liver dysfunction causes arterial vasodilation and thereby stimulates sodium retention in cirrhosis. Twenty-seven studies were performed in patients with alcoholic liver disease, 11 of whom had ascites. Liver function was quantitated as the elimination rate of antipyrine, caffeine, and stable isotopes of cholic acid administered both orally (2,2,4,4-2H) and intravenously (24-13C). Portal-systemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Cardiac output was measured by using Doppler echocardiography. Plasma glucagon concentration was increased in patients with ascites when compared with that in patients without ascites (474 +/- 180 pg/ml vs 245 +/- 120 pg/ml, p = 0.0007) but was unrelated to urinary sodium excretion, heart rate, mean arterial pressure, cardiac output, and systemic vascular resistance (r = -0.48, 0.35, -0.13, 0.18, and 0.22, respectively). Plasma glucagon concentration correlated with the half-lives of all model compounds (r = 0.58, p = 0.002; r = 0.62, p = 0.0008; r = 0.62, p = 0.001; and r = 0.64, p = 0.0005; for caffeine, antipyrine, oral and intravenous cholic acid, respectively) but not with shunt fraction (r = 0.14). Increased plasma glucagon concentration in cirrhosis is probably a result of diminished hepatic clearance. However, increased plasma concentration of glucagon does not appear to cause a hyperdynamic circulatory state or sodium retention.
Assuntos
Glucagon/sangue , Cirrose Hepática Alcoólica/sangue , Fígado/fisiopatologia , Natriurese , Sistema Porta/fisiopatologia , Resistência Vascular , Humanos , Cirrose Hepática Alcoólica/fisiopatologia , Masculino , Concentração OsmolarRESUMO
Plasma contains three forms of cyst(e)ine: cysteine, cystine, and protein-bound cysteine. The former is a thiol and the latter two are disulfides. The levels of all three types of cyst(e)ine, as well as the cysteinyl tripeptide glutathione, were measured in the plasma of 14 normal and 10 cirrhotic individuals. All subjects ate mixed foods. Some cirrhotic patients were studied during nasogastric hyperalimentation with Vivonex (Norwich Eaton Pharmaceuticals, Norwich, N.Y.) as well as during total parenteral nutrition with FreAmine III (American McGaw, Irvine, Calif.); neither formula contains cyst(e)ine. Regardless of the nature of the diet, cirrhotic patients had significantly subnormal values for cysteine, glutathione, and albumin. In addition, the following significant changes were found to be diet-dependent: (a) elevated methionine during Vivonex, (b) subnormal taurine during mixed foods and total parenteral nutrition, (c) depressed protein-bound cysteine during total parenteral nutrition, (d) depressed cyst(e)ine thiol/disulfide ratio during mixed foods, and (e) depressed total thiol during Vivonex and total parenteral nutrition. The data indicate multiple abnormalities in sulfur metabolism in cirrhosis.