RESUMO
Calciprotein particles (CPP) are nanoscale mineralo-protein aggregates that help stabilize excess mineral in the circulation. We examined the relationship between CPP and bone mineral density in Fabry disease patients. We found an inverse correlation with total hip and femoral neck density, but none with lumbar spine. PURPOSE: Calciprotein particles (CPP) are colloidal mineral-protein complexes made up primarily of the circulating glycoprotein fetuin-A, calcium, and phosphate. They form in extracellular fluid and facilitate the stabilization, transport, and clearance of excess minerals from the circulation. While most are monomers, they also exist in larger primary (CPP-I) and secondary (CPP-II) form, both of which are reported to be raised in pathological states. This study sought to investigate CPP levels in the serum of patients with Fabry disease, an X-linked systemic lysosomal storage disorder that is associated with generalized inflammation and low bone mineral density (BMD). METHODS: We compared serum CPP-I and CPP-II levels in 59 patients with Fabry disease (37 female) with levels in an age-matched healthy adult cohort (n=28) and evaluated their association with BMD and biochemical data obtained from routine clinical review. RESULTS: CPP-I and CPP-II levels were higher in male Fabry disease patients than female sufferers as well as their corresponding sex- and age-matched controls. CPP-II levels were inversely correlated with BMD at the total hip and femoral neck, but not the lumbar spine. Regression analyses revealed that these associations were independent of common determinants of BMD, but at the femoral neck, a significant association was only found in female patients. CONCLUSION: Low hip BMD was associated with high CPP-II in patients with Fabry disease, but further work is needed to investigate the relevance of sex-related differences and to establish whether CPP measurement may aid assessment of bone disease in this setting.
Assuntos
Doença de Fabry , alfa-2-Glicoproteína-HS , Adulto , Densidade Óssea , Cálcio , Doença de Fabry/complicações , Feminino , Humanos , Masculino , Minerais/metabolismo , Fosfatos , Agregados Proteicos , alfa-2-Glicoproteína-HS/análiseRESUMO
Between 1971 and 1991, 845 patients were diagnosed as having IgA glomerulonephritis on renal biopsy performed. These patients were followed for a mean period of 53 months post biopsy (range 0-336 months). By the end of follow up 147 (17%) of patients have developed chronic renal failure (Cr > 0.2 mmol/l) or end-stage renal failure. Presenting creatinine > 0.12 mmol/l, hypertension, nephrotic range, age > 40 years and male gender, all correlated strongly on univariate analysis with the development of chronic renal failure or kidney disease (all p < 0.0001). However, a number of patients developing chronic renal failure or end-stage renal failure already had renal impairment (creatinine > 0.12 mmol/l at presentation). A separate comparison was performed of patients presenting with creatinine < 0.12 mmol/l and either developing chronic failure or end-stage renal failure within 5 years of biopsy (n = 18) and those with creatinine still < 0.12 mmol/l after 5 years follow up (n = 186). Of the 18 patients who deteriorated 6 (35%) were nephrotic at presentation and 9 (56%) had focal hyalinosis and sclerosis on renal biopsy. This compared with 5 (3%) patients with nephrotic range proteinuria and 16 (10%) patients with focal hyalinosis and sclerosis among the 186 patients who did not deteriorate (p < 0.0001). The sensitivity and specificity of the presence of either or both factors in predicting deterioration was calculated at 65% and 87% respectively. Thus in patients with normal renal function at presentation the presence of nephrotic range or focal hyalinosis and sclerosis are strong predictors of adverse clinical outcome.
Assuntos
Glomerulonefrite por IGA/diagnóstico , Glomerulosclerose Segmentar e Focal/epidemiologia , Glomérulos Renais/patologia , Proteinúria/epidemiologia , Adulto , Biópsia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite por IGA/urina , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Valor Preditivo dos Testes , Proteinúria/patologia , Fatores de Risco , Sensibilidade e Especificidade , Fatores de TempoRESUMO
Escherichia coli were grown on 14.3% uniformly 13C-labeled glucose as the sole carbon source and challenged anaerobically with 90% 13C-labeled formaldehyde. The major multiply labeled metabolites were identified by 13C NMR spectroscopy to be glycerol and 1,2-propanediol, and a minor metabolite was shown to be 1,3-propanediol. In each case, formaldehyde is incorporated only into the C1 position. A novel form of 13C NMR isotope dilution analysis of the major products reveals that all the 1,2-diol C1 is formaldehyde derived but that about 40% of the glycerol C1 is derived from bacterial sources. Glycerokinase converted the metabolite [1-13C]glycerol to equal amounts of [3-13C]glycerol 3-phosphate and [1-13C]glycerol 3-phosphate, demonstrating that the metabolite is racemic. When [13C]formaldehyde incubation was carried out in H2O/D2O mixtures, deuterium incorporation was detected by beta- and gamma-isotope shifts. The 1,3-diol is deuterium labeled only at C2 and only once, while the 1,2-diol and glycerol are each labeled independently at both C2 and C3; C3 is multiply labeled. Deuterium incorporation levels are different for each metabolite, indicating that the biosynthetic pathways probably diverge early.
Assuntos
Escherichia coli/metabolismo , Formaldeído/metabolismo , Glicerol/biossíntese , Propilenoglicóis/metabolismo , Deutério , Glicerol Quinase/metabolismo , Espectroscopia de Ressonância Magnética , Propilenoglicol , SolventesRESUMO
13C NMR has been used to demonstrate the metabolism of dilute solutions of labeled formaldehyde by Escherichia coli to methanol, formate, carbon dioxide, and several other unidentified metabolites which contain labeled CH2 groups. Aeration of bacterial suspensions within the spectrometer dramatically increased the rate of oxidation to formate and carbon dioxide. Deoxygenation with nitrogen gas virtually abolished all metabolism, as did the exposure of bacteria to very high formaldehyde concentrations. Deuterium NMR of whole cells in deuterium-depleted water further demonstrated the conversion of formaldehyde-d2 to methanol-d2, ruling out a formaldehyde dismutase as an important species. Two-dimensional proton-carbon chemical shift correlation was used to reveal the chemical shifts of the protons attached to 13C labels in metabolites. The results indicate that formaldehyde is efficiently detoxified by the bacterial cell through a route or routes which do not appear to involve tetrahydrofolate. This detoxification may be in competition with the lethal antibacterial processes associated with formaldehyde.
Assuntos
Escherichia coli/metabolismo , Formaldeído/metabolismo , Isótopos de Carbono , Deutério , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Formaldeído/toxicidade , Cinética , Espectroscopia de Ressonância MagnéticaRESUMO
Non-excretor cirrhotic patients, defined by their inability to normally excrete a standard water load, display variable responses to head-out water immersion. The hemodynamic, hormonal, and renal functional status of fifteen such patients were analyzed relative to water excretion during head-out water immersion. Group 1 patients (N = 7) all excreted less than 40% of the water load during immersion, whereas excretion was greater than 40% in all eight patients in Group 2. Group 1 patients, when compared with Group 2, had more ascites, more diuretic resistance, lower serum sodium concentration (125 +/- 2 vs. 130 +/- 1 mEq/liter, P less than 0.05), and more impaired baseline water excretion (12.9 +/- 1.2 vs. 35.9 +/- 5.9% of water load in 5 hr, P less than 0.005). Systemic hemodynamic responses to water immersion were similar in both groups. Glomerular filtration rate and renal plasma flow were significantly more impaired in Group 1 patients (inulin clearance 28 +/- 6 vs. 62 +/- 9 ml/min/1.73 m2, P less than 0.05; para-aminohippurate clearance 212 +/- 35 vs. 357 +/- 37 ml/min, P less than 0.05). Concentrations of plasma vasopressin (1.7 +/- 0.5 vs. 0.8 +/- 0.1 pg/ml, P less than 0.05), renin (8.6 +/- 1.7 vs. 3.8 +/- 0.9 ng/ml/hr, P less than 0.05), aldosterone (82 +/- 14 vs. 39 +/- 10 ng/dl, P less than 0.05) and norepinephrine (1155 +/- 183 vs. 603 +/- 126 pg/ml, P less than 0.05) were all significantly higher in Group 1 than Group 2 patients during water immersion.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diurese , Imersão/fisiopatologia , Rim/fisiopatologia , Cirrose Hepática Alcoólica/fisiopatologia , Adulto , Volume Sanguíneo , Feminino , Hemodinâmica , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , ÁguaRESUMO
Hemodynamic and hormonal factors were monitored in nine patients with nephrotic syndrome who were evaluated relative to their capacity to excrete a 20-mL/kg water load (normal greater than 80%). In five "nonexcretor" patients (37% of water load excreted in five hours), as compared to four normal excretors (105% of water load excreted in five hours; P less than .01 v nonexcretors), neither BP (131/88 v 119/79 mm Hg), pulse (74 v 77 beats/min), cardiac index (3.7 v 3.1 L/min/m2), pulmonary wedge pressure (9.3 v 7.3 mm Hg), systemic vascular resistance (1537 v 1254 dynes-sec-cm-5), nor plasma volume (41.3 v 40.1 mL/kg) were different. Similarly, plasma renin activity (2.6 v 3.7 ng/mL/h), plasma aldosterone (12 v 10.9 ng/dL), and plasma norepinephrine (403 v 312 pg/mL) were not different between nonexcretor v excretor patients with nephrotic syndrome. Plasma vasopressin concentrations were also similar both before (3.1 +/- 0.8 v 2.4 +/- 1.2 pg/mL) and during the water load (0.9 +/- 0.3 v 1.0 +/- 0.4 pg/mL). Inulin clearances, however, were lower in the nonexcretor v the excretor nephrotic patients (37 v 78 mL/min/1.73 m2; P less than .02) and correlated with water excretion (r = .68; P less than .05). Head-out water immersion increased sodium (40 to 110 microEq/min; P less than .01) and water excretion (37% to 82%; P less than .025) in the nonexcretors; the improvement correlated with the increase in inulin clearance during immersion (r = .70; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Água Corporal/metabolismo , Taxa de Filtração Glomerular , Síndrome Nefrótica/fisiopatologia , Sódio/urina , Adolescente , Adulto , Aldosterona/sangue , Arginina Vasopressina/sangue , Feminino , Hemodinâmica , Humanos , Imersão , Inulina/metabolismo , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/sangue , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/urina , Norepinefrina/sangue , Volume Plasmático , Renina/sangueRESUMO
Candida infection of joint replacements is a rare but increasingly reported phenomenon. A case of Candida parapsilosis prosthetic knee joint infection occurring in the UK is described. Cure followed removal of the prosthesis and treatment, first with a combination of amphotericin and 5-fluorocytosine, then ketoconazole.
Assuntos
Candidíase/etiologia , Prótese Articular/efeitos adversos , Infecções Relacionadas à Prótese/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
Hyaluronic acid (HA) is a ubiquitous component of extracellular matrix. After tissue injury, HA appears in greater abundance during the inflammatory response and the phase of clearance of cell and matrix debris, before collagen production and matrix degradation. The aim of this study was to examine whether normal rat renal fibroblasts were capable of HA synthesis and to determine the effect of HA on in vitro collagen production in a series of normal rat cortical fibroblast cultures. Fibroblast cultures from both renal cortex and medulla were established from adult Sprague-Dawley rats. HA synthesis was measured by radioimmunoassay, and incorporation of (3)H-proline into collagen was used to determine collagen synthesis. Fibroblasts were defined on the basis of morphology and alpha smooth muscle actin immunohistochemistry. HA synthesis was measured in both renal cortical and medullary fibroblasts at passage 3 for both 24 and 48 h in 5 animals and expressed as a fraction of protein content. HA was synthesized by both cortical and medullary fibroblasts; however, cortical fibroblasts produced less HA than medullary fibroblasts at both 24 h (p = 0.05) and 48 h (p = 0.02). In normal cortical fibroblasts, exogenous HA suppressed overall total (cell and media) collagen production after a 22-hour labelling period (p = 0.002 compared to controls). Decreased collagen production was also found individually in cell (p = 0.02) and media fractions (p = 0.01). Both cortical and medullary fibroblasts are capable of synthesizing HA in vitro. Furthermore, the findings in this study suggest that HA may be an important mediator in reducing renal cortical fibroblast collagen production and may play an important role in limiting renal interstitial scarring.
Assuntos
Colágeno/biossíntese , Ácido Hialurônico/biossíntese , Córtex Renal/metabolismo , Medula Renal/metabolismo , Animais , Células Cultivadas , Fibroblastos/metabolismo , Ácido Hialurônico/farmacologia , Córtex Renal/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Infections are an important cause of mortality and morbidity in renal transplant recipients. To study the impact of anti-rejection therapy on the timing of infections, the records of 599 consecutive renal transplants, performed prior to 31 December 1996 at the Royal Melbourne Hospital, were reviewed. Patients were grouped according to acute rejection (AR) episode and treatment during the first 6 months after transplantation. Group 1 [n = 168 (35%)] patients did not experience any episode of AR. Group 2 [n = 169 (35%)] patients had one or more episodes of AR and received high doses of steroids. Group 3 [n = 141 (30%)] patients had more than one episode of AR and received anti-lymphocyte antibodies in addition to high doses of steroids. Infections were more common in Groups 2 and 3 but only cytomegalovirus (CMV) disease occurred earlier in patients treated with lympholytics. Given the high incidence and early onset of CMV disease in patients receiving lympholytics and considering that an effective prophylactic protocol remains undetermined, pre-emptive treatment with ganciclovir in this high risk group appears justified.
Assuntos
Infecções por Citomegalovirus/etiologia , Rejeição de Enxerto/tratamento farmacológico , Hospedeiro Imunocomprometido , Transplante de Rim , Doença Aguda , Adulto , Soro Antilinfocitário/uso terapêutico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Muromonab-CD3/uso terapêutico , Infecções Oportunistas/imunologia , Infecções Oportunistas/prevenção & controle , Prednisolona/uso terapêutico , Pré-Medicação , Fatores de Risco , Fatores de TempoRESUMO
Myofibroblasts, cells with both fibroblastic and smooth muscle cell features, have been implicated in renal scarring. In addition to synthetic properties, contractile features and integrin expression may allow myofibroblasts to rearrange and contract interstitial collagenous proteins. Myofibroblasts from normal rat kidneys were grown in cell-populated collagen lattices to measure cell generated contraction. Following detachment of cell populated collagen lattices, myofibroblasts progressively contracted collagen lattices, reducing lattice diameter by 42% at 24 h. Alignment of myofibroblasts, rearrangement of fibrils and beta(1) integrin expression were observed within lattices. We postulate that interstitial myofibroblasts contribute to renal scarring through manipulation of collagenous proteins.
Assuntos
Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Rim/citologia , Músculo Liso/citologia , Animais , Células Cultivadas , Integrina beta1/biossíntese , Queratinas/biossíntese , Masculino , Microscopia Confocal , Ratos , Ratos Sprague-Dawley , CicatrizaçãoRESUMO
Clinical data in 244 patients with IgA nephropathy and biopsy findings in 519 biopsies (107 patients had at least two biopsies) were analysed. Males predominated (73 per cent) and had more severe disease and a worse prognosis than females. The most frequent symptom was macroscopic haematuria, often with associated loin pain; however, this was typical only in young males. Hypertension was the major presenting feature in 23 per cent of patients. Urinary erythrocyte counts correlated with the presence of crescents on biopsy (p less than 0.0001). Serum IgA levels wer elevated in only 21 per cent, while IgM levels were raised in 43 per cent of patients. Two hundred and seventeen patients were followed for at least one year (mean 59.7 months, range 12-255 months). In 82 patients five-year follow-up and in 33 patients ten-year follow-up data were available. Five- and 10-year survival figures were 91.5 and 87.5 per cent respectively. Clinical resolution occurred in only 6 per cent of patients but in those who had biopsies following clinical resolution, diffuse mesangial cell proliferation and IgA deposits persisted in all. The rate of clinical deterioration correlated with proteinuria, hypertension, impaired renal function, crescents and sclerosed glomeruli on biopsy. Continuing high urinary erythrocyte counts were the strongest predictor of a progressive course.
Assuntos
Mesângio Glomerular/imunologia , Imunoglobulina A/análise , Nefropatias/imunologia , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Mesângio Glomerular/patologia , Glomerulonefrite/complicações , Hematúria/complicações , Humanos , Hipertensão/complicações , Nefropatias/mortalidade , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/complicaçõesRESUMO
C3b receptor mediated clearance by the reticuloendothelial system (RES) was tested in vivo using autologous C3b coated, technetium labelled erythrocytes in patients with rheumatoid arthritis (RA) and rheumatoid vasculitis. Diminished C3b mediated erythrocyte clearance was found in all patients with rheumatoid vasculitis and some patients with active RA. Normal C3b mediated clearance was found in some patients with previous vasculitis, in remission when tested. These results are consistent with the hypothesis that acquired dysfunction of RES C3b receptors is implicated in the pathogenesis of rheumatoid vasculitis.
Assuntos
Artrite Reumatoide/fisiopatologia , Complemento C3b/fisiologia , Sistema Fagocitário Mononuclear/fisiopatologia , Vasculite/fisiopatologia , Adolescente , Adulto , Artrite Reumatoide/metabolismo , Complemento C3b/metabolismo , Eritrócitos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Fagocitário Mononuclear/metabolismo , Fagocitose , Vasculite/metabolismoRESUMO
Sodium excretion in 13 patients with decompensated cirrhosis was measured under baseline conditions of water loading (n = 13) and during conditions designed to improve effective blood volume including: head-out water immersion alone (n = 13); norepinephrine infusion alone (n = 6), and combined norepinephrine and head-out water immersion (n = 6). All 13 patients were in positive sodium balance under baseline conditions, with a mean plasma aldosterone concentration of 78.7 +/- 15.6 ng per dl. In only four patients was plasma aldosterone less than 50 ng per dl. During head-out water immersion alone, 5 patients achieved negative sodium balance and, in all 5, plasma aldosterone was less than 50 ng per dl (mean = 23.0 +/- 5.3 ng per dl). However, the mean plasma aldosterone during head-out water immersion in the eight patients who remained in positive sodium balance during this maneuver was 64.0 +/- 11.9 ng per dl (p less than 0.01). During norepinephrine alone, positive sodium balance was maintained in all patients, and plasma aldosterone was not significantly different from baseline. Combining norepinephrine and head-out water immersion resulted in the largest and most consistent negative sodium balance. The mean plasma aldosterone concentration was decreased significantly (78.7 +/- 15.6 to 32.6 +/- 9.9 ng per dl (p less than 0.05). Regardless of the maneuver performed, no patient in whom aldosterone exceeded 50 ng per dl achieved negative sodium balance. Furthermore, only in those studies utilizing head-out water immersion, with or without norepinephrine, was negative sodium balance seen.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aldosterona/sangue , Volume Sanguíneo , Cirrose Hepática/fisiopatologia , Sistema Renina-Angiotensina , Sódio/metabolismo , Equilíbrio Hidroeletrolítico , Humanos , Imersão/fisiopatologia , Rim/fisiopatologia , Cirrose Hepática/metabolismo , Natriurese/efeitos dos fármacos , Norepinefrina/farmacologiaRESUMO
BACKGROUND: Expression of the beta1 family of integrins allows dermal fibroblasts in wounds to contribute to the healing process through migration, adhesion, synthesis, and rearrangement of extracellular matrix. To date the ability of human renal fibroblasts to reorganize collagens and the role of cell surface receptors in this process remain unknown. METHODS: Renal fibroblasts were grown from the cortical tissue of surgically removed human kidneys. The ability of human renal fibroblasts to reorganize interstitial collagen I was examined in vitro using solidified collagen I lattices. Integrin function was blocked by incubating fibroblasts with isotype-specific antibodies prior to addition to collagen I lattices. RESULTS: Human renal fibroblasts embedded in collagen I lattices progressively decreased lattice diameter to 60.6+/-11.4% of initial diameter at 48 h post-release (P:<0.01). Fibroblasts incubated in the presence of antibody to beta1 integrin failed to contract collagen I lattices, whilst fibroblasts incubated with non-specific antibody reduced lattice diameter to 60.1+/-12.4% of initial diameter at 48 h post-release (P:<0.01). Further characterization of integrin alpha subunits showed that blocking alpha2beta1 integrin prevented lattice contraction (P:<0.05, alpha2beta1 integrin antibody vs non-specific antibody), whilst blocking of alpha5beta1, alpha3beta1 and alpha1beta1 integrins did not influence this process. CONCLUSIONS: We postulate that collagen I fibril rearrangement by human renal fibroblasts in vitro appears to be an integrin-mediated process involving the alpha2beta1 integrin.
Assuntos
Colágeno , Fibroblastos/citologia , Integrinas/fisiologia , Córtex Renal/citologia , Adulto , Idoso , Técnicas de Cultura de Células/métodos , Células Cultivadas , Feminino , Fibroblastos/fisiologia , Humanos , Integrina alfa1beta1 , Integrina alfa3beta1 , Integrina beta1/fisiologia , Integrinas/análise , Córtex Renal/fisiologia , Masculino , Pessoa de Meia-Idade , Receptores de Colágeno , Receptores de Fibronectina/fisiologiaRESUMO
Plasma norepinephrine concentrations are elevated in patients with decompensated cirrhosis, and correlate inversely with urinary sodium and water excretion. Increased plasma norepinephrine concentrations may result from a decreased metabolic clearance rate or an increased secretion rate, possibly in response to a decreased "effective arterial blood volume." If the latter hypothesis is correct, plasma norepinephrine might be expected to be suppressed when central blood volume is expanded by head-out water immersion. In the present study, plasma norepinephrine secretion and clearance rates were determined by infusion of tritiated norepinephrine. Norepinephrine secretion rates were elevated in eight cirrhotic patients as compared to control subjects (1.50 +/- 0.25 vs. 0.26 +/- 0.08 micrograms/m2 per min, P less than 0.001), whereas clearance rates were similar (3.13 +/- 0.48 vs. 2.60 +/- 0.28 liters/min, NS). Baseline plasma norepinephrine concentrations were markedly elevated in the cirrhotic patients (830 +/- 136 vs. 185 +/- 12 pg/ml, P less than 0.001). Head-out water immersion significantly suppressed plasma concentrations of both norepinephrine (704 +/- 72 to 475 +/- 70 pg/ml, P less than 0.005) and epinephrine (121 +/- 33 to 57 +/- 10 pg/ml, P less than 0.05) in all seven patients studied. We conclude that the high circulating catecholamine concentrations in cirrhosis are secondary to increased secretion, rather than to decreased metabolic clearance, and are suppressible by central blood volume expansion.
Assuntos
Volume Sanguíneo , Cirrose Hepática/sangue , Norepinefrina/sangue , Adulto , Idoso , Feminino , Humanos , Imersão , Masculino , Pessoa de Meia-Idade , Norepinefrina/metabolismo , ÁguaRESUMO
The effect of head-out water immersion (HWI) in decompensated cirrhotic patients to correct sodium and water excretion has been found to be incomplete and variable. The explanation may be that the efficacy of HWI in correcting a decreased effective arterial blood volume (EABV) in decompensated cirrhotic patients is limited by an accompanying decrease in systemic vascular resistance (SVR) and thus a relative increase in arterial vascular holding capacity. The present studies were undertaken to examine this possibility by maintaining SVR (dynes X sec X cm-5) nearly constant during HWI with an exogenous infusion of norepinephrine (HWI + NE). In six decompensated cirrhotic patients, neither HWI nor NE infusion alone significantly increased sodium excretion (UNaV, 13 vs. 19 and 13 microEq/min, respectively), but each maneuver increased the excretion of a 20 ml/kg water load (28 to 60 and 61%, respectively, both P less than 0.05). The combination of HWI + NE, however, significantly increased UNaV to 70 microEq/min (P less than 0.05) and percentage of water excretion to 95 (P less than 0.001), values significantly greater than those achieved with either maneuver alone. These differences were not explained by any changes in inulin clearance. With HWI alone, cardiac index (CI) increased (4.2 to 5.3 liter/min/m2, P less than 0.01), but SVR decreased (872 to 613 dynes X sec X cm-5, P less than 0.001) and mean arterial pressure (MAP) remained constant (83 vs. 78 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)