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Biomedical subjects

F Del Greco

Publications and source records attributed to F Del Greco.

At least 19 recordsLinked to original sources

Failure of deferoxamine to improve iron overload in chronic hemodialysis patients.

We prospectively studied the in vivo dialytic clearance of iron after deferoxamine (DFO) administration in four stable iron-overloaded chronic hemodialysis patients by quantifying iron concentration in blood entering and leaving the dialyzer and in dialysate after infusions of DFO. No significant arteriovenous iron differences were demonstrated. The mean ratio of venous to arterial iron approached identity at 1.005. All dialysate concentrates used contained large amounts of iron (300-610 micrograms/dl). No changes in efferent versus afferent dialysate iron concentration could be demonstrated. We conclude (a) iron removal during dialysis with DFO was not demonstrated; (b) the dialysate concentrate tested contained large amounts of iron; (c) in view of potentially significant toxicity, and lack of demonstrable therapeutic benefit, caution in prescribing DFO chelation therapy for iron overload is recommended.

Deferoxamine

Stimulation of erythrocyte and renal Na+,K+-adenosine triphosphatase activity by antidigoxin antibody in normal rats.

1. A circulating ouabain-like factor which inhibits the Na+,K(+)-pump has been implicated in volume-expanded states. To assess the role of this putative factor in normovolaemic rats, we measured erythrocyte and renal Na+,K(+)-adenosine triphosphatase activity after the infusion of a mixture of high-affinity digoxin-binding Fab fragments (Digibind) capable of removing digoxin from pump sites. 2. Compared with either saline (vehicle) or sheep immunoglobin G, infusion of the antidigoxin antibody caused a moderate increase of Na+,K(+)-adenosine triphosphatase activity in the erythrocyte (saline 348 +/- 12; immunoglobulin G 339 +/- 16; antidigoxin antibody 432 +/- 22 nmol h-1 mg-1; P less than 0.005 by analysis of variance) and a larger increase in the renal cortex (saline 9.7 +/- 0.9; immunoglobulin G 9 +/- 1.4; antidigoxin antibody 24.3 +/- 1.8 mumol h-1 mg-1; P less than 0.0005 by analysis of variance) without a change in blood pressure. 3. These results are consistent with the presence of a digoxin-like inhibitor of the Na+,K+-pump in normal rats.

Animals

Effect of treatment with hydrochlorothiazide on the red cell Na,K-adenosine triphosphatase in men with hypertension.

We studied the effect of hydrochlorothiazide, 50 mg daily, on Na,K-adenosine triphosphatase (ATPase) activity in the red cells of 10 black men with hypertension. We also examined net sodium and potassium movement in sodium-loaded, potassium-depleted, red cells. Treatment with hydrochlorothiazide resulted in a significant increase in mean ouabain-sensitive ATPase activity (+/- SEM) from 118.4 +/- 14.6 to 158.1 +/- 15.3 nmol phosphate released per milligram of protein (P = 0.0004). Ouabain-resistant ATPase did not change. Net sodium extrusion rose significantly, from 1.62 +/- 0.27 to 2.32 +/- 0.33 mmol/L/hr (P = 0.0275). We postulate that the enhanced activity of the Na,K pump results from the volume contraction induced by the diuretic. This interpretation is consistent with the concept that the Na,K pump is inhibited in volume expansion and volume-expanded hypertension. The finding of enhanced pump activity in subjects given treatment with hydrochlorothiazide suggests a possible mechanism of the antihypertensive action of diuretic therapy.

Adult

Na-K-adenosine triphosphatase and cation content in the erythrocyte in essential hypertension.

We measured ouabain-sensitive and ouabain-resistant Na-K-adenosine triphosphatase (ATPase) activity in the red cells of 25 normotensive (average mean blood pressure [BP] 90.2 +/- 1.27 mm Hg) and 29 hypertensive subjects (average mean BP 115.3 +/- 2.45 mm Hg). Intracellular Na and K content were measured in 13 of the normotensive and 19 of the hypertensive subjects. All subjects were male, black, of comparable weight, and had not received antihypertensive medications for at least 30 days. Ouabain-sensitive ATPase activity was found significantly lower in the hypertensive than in the control group (140.2 +/- 11 and 97.6 +/- 7.6 nmol/mg/hr, respectively, P = 0.0008), whereas no significant difference in ouabain-insensitive ATPase was observed. Intracellular Na concentration was higher (9.47 vs. 7.24 mmol/L, P = 0.0144), and intracellular K concentration lower (82.8 vs. 88.8 mmol/L, P = 0.0425) in the hypertensive subjects. These results are consistent with diminished activity of the Na-K pump in black males with essential hypertension who have received no treatment.

Blood Pressure

Reduction in slow intercompartmental clearance of urea during dialysis.

The kinetics of urea and inulin were analyzed in five anesthetized dogs during sequential 2-hour periods before, during, and after hemodialysis. The distribution of both compounds after simultaneous intravenous injection was characterized by three-compartment models, and the total volumes of urea (0.66 +/- 0.05 L/kg) and inulin (0.19 +/- 0.01 L/kg) distribution were similar to expected values for total body water and extravascular space, respectively. Intercompartmental clearances calculated before dialysis were used to estimate blood flows to the fast and slow equilibrating compartments. In agreement with previous results, the sum of these flows was similar to cardiac output, averaging 101% of cardiac output measured before dialysis (range 72% to 135%). Dialysis was accompanied by reductions in the slow intercompartmental clearances of urea (81%) and inulin (47%), which reflected a 90% attenuation in blood flow supplying the slow equilibrating compartments. This was estimated to result in a 10% average reduction in the efficiency with which urea was removed by dialysis (range 2.0% to 16.4%). Mean arterial pressure fell by less than 5% during dialysis, but total peripheral resistance increased by 47% and cardiac output fell by 35%. In the postdialysis period, total peripheral resistance and cardiac output returned toward predialysis values, but blood flow to the slow equilibrating peripheral compartment was still reduced by 80%. These changes parallel activation of the renin-angiotensin system, but further studies are required to establish causality.

Animals

The clinical course of end-stage renal disease in systemic lupus erythematosus.

Despite treatment advances, renal failure still develops in patients with systemic lupus erythematosus (SLE). With the common use of long-term maintenance hemodialysis, this complication is no longer fatal. In order to evaluate factors that contribute to the outcome of patients with SLE receiving long-term hemodialysis, we retrospectively analyzed the clinical course of 14 patients with SLE receiving hemodialysis for more than three months, and compared them with 62 patients receiving long-term hemodialysis who did not have SLE. While receiving long-term hemodialysis, SLE activity was minimal, with most manifestations involving the CNS or synovitis. Five-year survival was significantly lower in the SLE than in the non-SLE group (58.6% v 88.5%), but no deaths were directly attributable to SLE activity. Morbidity in the SLE group was primarily due to infection and vascular access problems.

Adult

Renal osteodystrophy in patients on hemodialysis as reflected in the bony pelvis.

Roentgen studies in a group of 131 patients on maintenance hemodialysis reveal renal osteodystrophy in 25 patients (19 per cent). In 24 patients of the latter group (98 per cent), the various manifestations of renal osteodystrophy appear in the bony pelvis. These include: osteomalacia; osteitis fibrosa; osteosclerosis; dialysis osteopenia; and extraosseous calcifications. Some of the changes, i.e., bending of bone, Looser's lines, metaphyseal fractures and dialysis osteopenia, are due, at least in part, to the weight bearing nature of the bony pelvis. These findings are ararely, if ever, seen in the digits or in other non-weight bearing bones. It is therefore proposed to evaluate the bony pelvis, together with the magnification digital roentgenogram, when a less costly and less time consuming skeletal survey is needed in hemodialized patients.

Adolescent