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Biomedical subjects

L Blendis

Publications and source records attributed to L Blendis.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effects of insulin on renal function, sympathetic nervous activity and forearm blood flow in normal human subjects.

OBJECTIVE: To assess fully the vasodilatory and sodium-retaining effects of insulin. DESIGN: Prospective physiologic study using a dose-response protocol. SETTING: Clinical investigation unit of a tertiary referral hospital. PARTICIPANTS: Six normal, healthy men. INTERVENTIONS: Subjects were given increasing doses of insulin intravenously from 10 to 1200 mU/m2 per minute, using the euglycemic "clamp" technique. OUTCOME MEASURES: Urinary sodium excretion, systemic and renal hemodynamics, plasma norepinephrine levels and forearm blood flow after each dose. RESULTS: Low doses of insulin (up to 20 mU/m2 per minute) produced a significant antinatriuresis (0.18 [SEM 0.05] v. 0.37 mmol per minute at baseline, p < 0.01) and antidiuresis (2.53 [SEM 0.67] v. 6.21 [SEM 1.66] mL per minute, p < 0.01) with no associated changes in renal hemodynamics or sympathetic nervous activity. Subsequent higher doses of insulin improved urinary volume and sodium excretion to above baseline levels associated with renal and forearm vasodilatation, although mean arterial pressure remained unaltered. CONCLUSIONS: Hyperinsulinemia initially causes an antinatriuresis and antidiuresis through a direct action on the renal tubule. The subsequent phenomenon of escape from renal sodium retention may serve as a regulatory mechanism on sodium homeostasis in conditions associated with hyperinsulinemia and sodium retention.

Adult↗
PubMed1996

Access to adult liver transplantation in Canada: a survey and ethical analysis.

OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and because the primary limiting factor is organ supply, increased organ acquisition efforts are needed.

Adult↗
PubMed1996

Hyperinsulinemia in preascitic cirrhosis: effects on systemic and renal hemodynamics, sodium homeostasis, forearm blood flow, and sympathetic nervous activity.

Insulin has been shown to be vasodilatory and antinatriuretic and to stimulate sympathetic nervous activity independent of hypoglycemia in healthy normal subjects. It is hypothesized that hyperinsulinemia, which is commonly observed in cirrhosis, may in part be responsible for the systemic vasodilatation, sympathetic activation, and sodium retention in these patients. The aims of this study, in preascitic cirrhotics, were as follows: (1) to document baseline hyperinsulinemia and its effects on sodium handling, forearm and renal circulations, and sympathetic nervous activity; (2) to determine if pharmacological increases in plasma insulin levels would result in an exaggeration of these physiological effects. Seven male, nonobese, well-compensated, preascitic cirrhotic patients were studied, after being maintained on a 150 mmol sodium per day diet for 7 days, firstly at baseline level, followed by increasing doses of insulin from 10 to 1,200 mU/m2/min using the euglycemic clamp technique. Systemic and renal hemodynamics, urinary sodium excretion, plasma norepinephrine, and forearm blood flow (FBF) were measured at the end of baseline and each hyperinsulinemic period. Baseline measurements in the cirrhotics, when compared with our laboratory standards obtained from a comparable group of male healthy normals, showed significant hyperinsulinemia (P=.01), associated with significantly higher FBF (P=.02), and glomerular filtration rate (GFR) (P=.02), as well as significantly reduced urinary volume (P=.04) and fractional excretion of sodium (P=.04). Insulin infusions in the cirrhotics produced no further sodium retention, but further forearm vasodilatation occurred at doses > or = 10 mU/m2/min. In contrast, there was no further renal vasodilatation except at very high pharmacological levels of insulin together with an unchanged GFR, natriuresis, and diuresis. Hyperinsulinemia produced no significant effects on the sympathetic nervous activity. In conclusion, these results suggest that hyperinsulinemia may be implicated in the glomerular hyperfiltration and sodium retaining tendency of preascitic cirrhotic patients with glucose intolerance. The ability of the kidneys to escape from the sodium retaining effects may serve as an in-built physiological regulatory mechanism on sodium homeostasis.

Adult↗
PubMed1996

The effect of posture on central blood volume in patients with preascitic cirrhosis on a sodium-restricted diet.

The status of the central blood volume in cirrhosis is controversial. A combination of sodium restriction and upright posture, which redistributes intravascular volume to dependent parts of the body should further aggravate a contracted central blood volume reduction. The aim of this study was to determine the effect of upright posture and sodium restriction on central blood volume (CBV) in preascitic cirrhotic patients, compared with controls. Eight male, preascitic, alcoholic cirrhotic subjects and eight healthy male controls were studied while on a 20-mmol/d sodium diet. Measurements of CBV by radionuclide angiography, and neurohumoral factors were performed on day 7 in both supine and erect positions and cardiac output and systemic vascular resistance (SVR) was calculated. Sodium restriction resulted in less weight loss in the cirrhotic patients (P = .03), with significantly lower plasma renin activity (P = .001). Similar central blood volumes and systemic hemodynamics were observed in both groups in the supine posture. In contrast to the cirrhotic patients, in the control subjects, upright posture resulted in a significant reduction in cardiac output (P = .002) and increase in SVR (P = .005), associated with a decrease in all blood volumes which were significantly less than in the cirrhotic patients. Mean arterial pressure was maintained in both groups in both postures. In conclusion, with sodium restriction, preascitic cirrhotic patients have less intravascular volume contraction than control patients. Erect posture results in redistribution of this relatively expanded intravascular volume to the CBV. Therefore, a low-sodium diet can be safely administered in preascitic cirrhotic patients.

Adult↗
PubMed1996

The effect of varying sodium intake on blood volume, forearm blood flow and vascular responsiveness to sympathetic stimulation in pre-ascitic cirrhosis.

OBJECTIVES: To assess, in patients with well-compensated pre-ascitic cirrhosis, (1) the extent of vasodilatation, if any, in the forearm circulation and (2) the effect of sodium status on its response to reflex sympathetic stimulation. DESIGN: Case-control study. SETTING: Clinical investigation unit of the Toronto Hospital, a tertiary referral hospital. PATIENTS: Eight male, alcoholic patients with pre-ascitic cirrhosis and 10 age- and sex-matched controls. INTERVENTIONS: Patients and controls were given a diet containing 20 mmol of sodium per day for 7 days, then a diet containing 200 mmol of sodium per day for the subsequent 7 days. On the seventh day of each diet, systemic hemodynamics, forearm circulation and effective arterial blood volume were assessed. A cold pressor test was performed after both diets to assess the response of the forearm circulation to reflex sympathetic stimulation. OUTCOME MEASURES: Heart rate, mean arterial pressure, forearm blood flow, forearm vascular resistance, central venous pressure, atrial natriuretic factor concentrations and neurohumoral pressor levels (plasma renin activity, aldosterone and plasma norepinephrine levels). RESULTS: No forearm vasodilatation was evident in the patients with pre-ascitic cirrhosis; their forearm blood flow and forearm vascular resistance were similar to those of the controls. Sodium loading did not influence baseline forearm blood flow. Cold pressor stimulus resulted in a significant decrease in forearm blood flow and a significant increase in forearm vascular resistance, mean arterial pressure, heart rate and plasma norepinephrine levels in both groups after the low-sodium diet. High sodium intake resulted in significantly greater reduction in forearm blood flow (-19%, standard error of the mean [SEM] 3% v. -8%, SEM 3%; p < 0.05) and significantly greater increase in forearm vascular resistance (+46%, SEM 7% v. +25%, SEM 8%; p < 0.05) in the patients with cirrhosis than in the controls. CONCLUSIONS: Well-compensated pre-ascitic cirrhotic patients do not have forearm vasodilatation. Sodium loading does not increase baseline forearm blood flow in these patients, but it does lead to a heightened response to reflex sympathetic stimulation. Sodium loading, with the associated sympathetic hyper-responsiveness, may therefore contribute to further sodium retention in these patients.

Adult↗
PubMed1995

Transjugular intrahepatic portosystemic stent shunt: effects on hemodynamics and sodium homeostasis in cirrhosis and refractory ascites.

OBJECTIVE: To assess the effects of transjugular intrahepatic portosystemic shunt (TIPS) on systemic and renal hemodynamics, neurohumoral factors, and sodium homeostasis in patients with cirrhosis and refractory ascites. DESIGN: Prospective study with 1-year follow-up. SETTING: Tertiary referral center and university-affiliated hospital. PATIENTS: 7 patients with cirrhosis and refractory ascites had metabolic studies done while receiving a 22 mmol/d sodium, 1 L/d fluid diet. INTERVENTION: TIPS insertion. MEASUREMENTS: Urinary sodium excretion, systemic and renal hemodynamics, hormonal profile, and central blood volume were measured before, at day 1 after, and at 1 month after TIPS insertion. RESULTS: Immediately after TIPS insertion, mean corrected sinusoid pressure decreased from 18.2 +/- 2.2 mm Hg to 7.7 +/- 1.3 mm Hg (P < 0.001); mean cardiac output increased from 6.83 +/- 0.68 L/min to 8.62 L/min (P = 0.005); and mean systemic vascular resistance decreased from 1018 +/- 103 dyne.s.cm-5 to 762 +/- 46 dyne.s.cm-5 (P = 0.011). Mean plasma renin activity, serum aldosterone levels, and 24-hour urinary sodium excretion (5.8 +/- 0.7 mmol/d before TIPS insertion compared with 6.0 +/- 1.8 mmol/d 1 day after insertion) were unchanged; mean elevated plasma norepinephrine levels significantly increased. By 1 month after insertion, mean proximal tubular reabsorption of sodium had decreased, and this had led to a mean natriuresis of 15.1 +/- 3.1 mmol/d (P = 0.02 compared with baseline), which was associated with a decrease in plasma renin activity and aldosterone levels to within the normal range. CONCLUSIONS: Our results suggest that natriuresis associated with TIPS is delayed and occurs in the presence of increased systemic vasodilatation at 1 month after insertion and that TIPS insertion should not be done in any patients with refractory ascites without careful attention to cardiac and renal status. However, in carefully selected patients, TIPS is a safe and effective means of managing refractory ascites.

Adult↗
PubMed1995

Pattern of sodium handling and its consequences in patients with preascitic cirrhosis.

BACKGROUND/AIMS: The initial abnormalities in the renal sodium handling in patients with cirrhosis before developing ascites remain unknown. The aim of this study is to further characterize sodium metabolism and the effects of sodium loading in preascitic cirrhosis. METHODS: Eight male, preascitic patients with cirrhosis and 6 volunteers had their daily urinary sodium excretion level measured while on a strictly metabolically controlled diet, first consisting of 20 mmol then of 200 mmol sodium per day each for 7 days. Central blood volume, plasma norepinephrine, and atrial natriuretic factor levels were measured during each diet. RESULTS: Preascitic patients with cirrhosis had significantly less daily urinary sodium excretion on both diets. Volume expansion in the patients with cirrhosis was indicated by significantly greater weight gain and higher atrial natriuretic factor levels for each diet. Patients with cirrhosis had central blood volume expansion (1725 +/- 54 mL/m2) compared with controls (1495 +/- 81 mL/m2; P = 0.03) on a low-sodium diet. This increased significantly in the controls (1864 +/- 164 mL/m2; P = 0.04) on a high-sodium diet, associated with suppression of plasma norepinephrine, but not in the patients with cirrhosis (1679 +/- 107 mL/m2; P > 0.05). CONCLUSIONS: Failure of further central blood volume expansion in the patients with cirrhosis on high-sodium diet in the presence of significant weight gain suggests maldistribution away from the effective arterial blood volume. This study provides further reasons why preascitic patients with cirrhosis might benefit from sodium restriction.

Adult↗
PubMed1995

Effects of sodium status on the venous response to noradrenaline infusion in pre-ascitic cirrhosis.

1. This study assesses the effects of sodium status on venous responsiveness to noradrenaline and the neurohumoral profile in pre-ascitic cirrhotic patients. Eight cirrhotic patients and ten control subjects were studied after both a low (20 mmol/day) and a high (200 mmol/day) sodium diet. Venous responsiveness to increasing doses of noradrenaline in a dorsal hand vein and various plasma hormone levels were measured. Maximal response (Rmax.) and the dose of noradrenaline that yielded 50% of Rmax. (ED50) were then calculated. 2. A significantly smaller dorsal hand vein diameter was observed in the control subjects on a low sodium (2.23 +/- 0.14 mm) compared with a high sodium (2.57 +/- 0.15 mm; P = 0.04) diet, but not in the cirrhotic patients. Rmax. was not significantly different in either group on both diets. With low sodium intake, ED50 was similar in the two groups. However, on high sodium intake, control subjects had a significantly higher ED50 (34.4 +/- 7.4 ng/min) than the cirrhotic patients (5.03 +/- 0.86 ng/min; P < 0.003). Plasma noradrenaline in the control subjects fell significantly with the change from a low (1.29 +/- 0.11 nmol/l) to a high (0.68 +/- 0.09 nmol/l; P < 0.001) sodium diet, but remained elevated in the cirrhotic patients. Cirrhotic patients had significantly higher atrial natriuretic factor levels and lower plasma renin activity than the control subjects on both diets. 3. In conclusion, pre-ascitic cirrhotic patients show no evidence of venodilatation. Their sympathetic nervous activity is not suppressible by volume expansion. Relative hyper-responsiveness of the peripheral venous circulation to adrenergic stimulation with high sodium intake is present.

Adult↗
PubMed1995

Systemic hemodynamic, forearm vascular, renal, and humoral responses to sustained cardiopulmonary baroreceptor deactivation in well-compensated cirrhosis.

The aim of this study was to assess baroreceptor function in well-compensated cirrhosis by determining the forearm vascular, renal, and humoral responses to sustained baroreceptor deactivation. The effect of sodium status on baroreceptor function was also assessed. Eight cirrhotic patients and 10 age- and sex-matched controls were studied twice after a 20 mmol and 200 mmol of sodium/d diet for 7 days. Systemic and renal hemodynamics, renal sodium handling, forearm blood flow, and neurohumoral factors were assessed before, during, and after the application of lower body negative pressure (LBNP) for 1 hour. Controls and cirrhotic patients had similar baseline mean arterial pressure, heart rate, forearm and renal hemodynamics. High-sodium intake resulted in suppression of sympathetic nervous activity in the controls (plasma norepinephrine, 1.06 +/- 0.11 nmol/L on low vs. 0.76 +/- 0.08 nmol/L on high sodium; P = 0.01) but not in the cirrhotic patients (1.35 +/- 0.22 nmol/L on low vs. 1.26 +/- 0.11 nmol/L on high sodium; P > 0.05). Both groups responded to LBNP with significant further increases in plasma norepinephrine, resulting in significant decreases in forearm blood flow on both sodium diets. Controls also responded with a significant worsening of renal hemodynamics on low-sodium diet only, but this was not observed in the cirrhotic patients on either diet. Therefore, in well-compensated cirrhotic patients: (1) sympathetic activation occurs despite an adequate, effective arterial filling, and this may contribute to sodium retention; and (2) baroreceptor function is normal. Apparent end organ unresponsiveness within the renal circulation may account for the lack of renal hemodynamic changes to reflex sympathetic stimulation.

Adult↗
PubMed1994

Prostaglandin E in the treatment of recurrent hepatitis B infection after orthotopic liver transplantation.

While orthotopic liver transplantation (OLT) has become the treatment of choice for most irreversible end-stage liver diseases, its role in patients with hepatitis B (HBV) infection is controversial. A high risk of reinfection of the transplanted graft, associated with significant morbidity and mortality, has been reported. Although passive and active immunization can delay reappearance of the virus in the allograft, there is not yet an effective therapy for recurrent HBV infection in liver transplant recipients. Between October 1985 and March 25, 1991, 28 OLT in 25 patients with acute and chronic HBV infections were performed. Twelve of the patients were HBV DNA-negative, six were HBV DNA-positive, and seven were not tested prior to transplantation. Only the 19 patients surviving more than 100 days after transplantation were considered to have sufficient duration of follow-up (mean 734 days; range 500-1545) to include in analysis of recurrence. Five (26%) were free of recurrent disease at the time of last follow-up (mean 1031 days, range 526 to 1770 days. Recurrent HBV in the allograft, as defined by positive immunoperoxidase stains of biopsy sections for viral antigens, was detected in 74% (13 male, 1 female; 7 Asian, 7 white) at a mean of 134 days posttransplantation. Histological changes of viral hepatitis, first appearing an average of 157 days (range 95-326) posttransplantation, were evident in 13 of 14 with positive immunostaining. Twelve of the 14 patients were treated, on an open trial basis, with intravenous and oral prostaglandin E (PGE) because of deteriorating clinical condition. Eleven of the twelve responded to PGE with an initial drop in serum transaminases, improvement in coagulopathy and resolution of encephalopathy. One patient failed to respond and died of a myocardial infarction within 9 days of institution of therapy. Three of the eleven patients with an initial response relapsed and died in liver failure as a direct result of recurrent HBV after 13, 16, and 37 days of treatment in association with generalized sepsis. Eight of the 12 patients (67%) had a sustained favorable response to PGE therapy (mean follow-up 737 days, range 403-1545). All patients with a sustained response had accompanying improvement in histology and reduction in viral antigen staining in hepatocytes. Treatment with PGE appeared to be of benefit in recurrent HBV infection of the transplanted liver with an initial response rate of 92% and a sustained response rate of 67%.

Administration, Oral↗
PubMed1994

Toxic effects of intravenous and oral prostaglandin E therapy in patients with liver disease.

BACKGROUND: Prostaglandins are cytoprotective agents that have been shown to benefit patients with a variety of acute and chronic liver diseases. Few data exist on the frequency of adverse effects of prostaglandins in these patients. METHODS: We retrospectively studied 105 patients with liver disease who were treated with either intravenous (i.v.) or oral prostaglandin E (PGE). Forty-four patients with primary nonfunction after liver transplantation and 36 patients with fulminant hepatic failure received i.v. PGE1 for 4.5 +/- 2.6 and 12.6 +/- 10.9 days, respectively. Twenty-five patients with recurrent hepatitis B viral infection after liver transplantation received oral PGE1 for 105 +/- 94 days or PGE2 for 464 +/- 399 days. RESULTS: Twenty-six of 80 patients (33%) receiving i.v. PGE1 developed gastrointestinal and/or cardiovascular side effects and 8% developed arthritis. Twenty-three of 25 patients (92%) who received high-dose oral PGE1 or PGE2 incurred arthritis and/or gastrointestinal adverse effects. Twenty-five patients received prolonged PGE therapy (oral > 60 days; i.v. > 28 days). Of this group, 23 (92%) developed clubbing and cortical hyperostosis resembling hypertrophic osteoarthropathy. All adverse effects were dose related and resolved with reduction or cessation of therapy. CONCLUSION: PGE therapy resulted in a wide spectrum of multisystem adverse effects which were reversible with reduction or cessation of therapy. Although the administration of PGE was safe and generally well tolerated, close medical supervision is necessary to avoid serious side effects.

Administration, Oral↗
PubMed1994

Central blood volume in cirrhosis: measurement with radionuclide angiography.

In patients with cirrhosis a diminished effective central arterial blood volume associated with systemic arterial vasodilation has been proposed as the mechanism that initiates renal sodium retention. Furthermore, total central blood volume has recently been reported as reduced in cirrhosis, and the controversy over the stimulus for sodium retention in cirrhosis remains. The aim of this study was to assess the central blood volume with radionuclide angiography to determine whether there is effective arterial underfilling in cirrhosis. Twenty-nine patients (13 with and 16 without ascites) and 10 age- and sex-matched control subjects were studied under metabolic conditions. Radionuclide ventricular volume and total central blood volume were determined from gated images, taking into account the 99Tc count activity per milliliter of blood volume and attenuation. The pulmonary volumes were similarly derived.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Oral iron chelation with 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron loaded thalassemia patients.

Despite the successes of deferoxamine (DFO) in the treatment and prevention of iron overload, an effective orally available iron chelating drug is needed, since erratic compliance with irritating, cumbersome parenteral infusions still results in fatal iron accumulation in many patients. Disorders of increased iron absorption should also benefit from the development of safe and effective iron chelating agents. Individuals with non-transfusion-dependent thalassemia (thalassemia "intermedia"), exhibit excessive dietary iron absorption that can lead to serious iron loading by the second or third decade of life. An orally effective iron-chelating drug would have major therapeutic advantages for all these patients.

Administration, Oral↗
PubMed1992

Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia.

In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron-chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13-40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1-weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted.

Adult↗