[Uremic polyneuropathy. An uncertain etiopathogenesis].
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Biomedical subjects
Publications and source records attributed to L Migone.
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Glomerular hemodynamics were studied, by micropuncture, in Munich-Wistar rats submitted to 24-hour unilateral ureteral ligation (UUL). Glomerular capillary pressure (PG), intratubular pressure (PT) and pressure in the first-order peritubular capillaries (EAP) were measured with a servonulling device. Single nephron filtration fraction (SNIFF) was calculated fmom arterial and peritubular blood protein concentration. SNGFR was both measured by conventional micropuncture techniques and calculated from efferent arteriole blood flow (EABF) and SNFF. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent (Re) arterioles were calculated. Measurements were repeated 1 to 2 hours after the release of the ureter. Sham-operated rats were used as control. UUL caused a marked increase in Ra (from 4.9 +/- [SD] 2.4 to 12.7 +/- 5.1 dynes/sec/cm-5). The fall in SNGFR (from 111.9 +/- [SD] 23.9 to 34.4 +/- 23.1 nl/min/kg body wt) was secondary to a decrease in both PG and AABF. A further increase in Ra (16.0 +/- 6.7 dynes.sec.cm-5) occurred after releasing the ureter. SNGFR, however, was unaltered (33.7 +/- 16.6 nl/min/kg body wt) since PG decreased parallel to PT, but AABF did not significantly change. Conclusion. Ureteral obstruction determines, in 24 hours, a marked cortical ischemia that is not promptly reversed by ureteral release.
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The clinical experience obtained with 2 hours every other day recirculation dialysis, using 20-40 liters of dialysate, without sorbents, and standard cuprophane dialyzers of 1.0-1.5 sq.mt. is reported. So far, over 350 treatments in 8 patients have been performed. After 2 hours of treatment the removal of urea, creatinine, phosphate and uric acid, is similar to that obtained by 4-6 hours of haemofiltration. The alkalinazation of the patient through direct venous infusion of bicarbonate, makes predialysis acid-base significantly better than in standard haemodialysis and haemofiltration. Asymptomatic correction of severe fluid overload is easily obtained like in isolated ultrafiltration. The role of osmolality and vasopressors are discussed. A dry weight below the value obtained by previous dialysis treatment is achieved, and volume dependent hypertensions as in haemofiltration are corrected after 2-8 weeks. As an additional advantage, this method offers a highly semplified technical approach and a further reduction of the dialysis time.
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In order to study the effects of acute ureteral obstruction on glomerular hemodynamics, glomerular hydrostatic capillary pressure (PG), pressure in the first-order peritubular capillaries (EAP), and intratubular pressure (PT) were directly measured in superficial nephrons on Munich-Wistar rats by micropuncture with a servo-nulling device, in control conditions and one to two hours after ureteral ligation. Single nephron filtration fraction (SNFF) was calculated from arterial and peritubular blood protein concentration. SNGFR was measured by conventional micropuncture techniques in control conditions and was calculated from efferent arteriole blood flow (EABF) and SNFF during ureteral obstruction. EABF was obtained by timed complete collection of blood from superficial efferent arterioles. Afferent arteriole blood flow (AABF) and resistance of afferent (Ra) and efferent arterioles (Re) were calculated from conventional equations. Ureteral obstruction markedly increased PT from 12.9 +/- 1.4 to 36.8 +/- 6.1 (SD) mm Hg. The fall in SNGFR (from 23.3 +/- 6.4 to 17.9 +/- 5.2 [SD] nl/min) was blunted by the rise in PG (from 45.5 +/- 3.6 to 59.3 +/- 4.0 [SD] mm Hg) and AABF (from 130.0 +/- 59.1 to 144.2 +/- 69.0 [SD] nl/min), secondary to a fall in Ra. These results demonstrate that SNGFR is maintained early after complete ureteral obstruction because of afferent arteriole dilatation.
Hemodynamic pressure in glomerular capillaries (GCP) and in first order peritubular capillaries (EAP) in superficial nephrons of mutant Wistar rats with surface glomeruli was measured by micropuncture with a servo-nulling device in the following conditions: 1) control;2) norepinephrine infusion (NE); 3) epinephrine infusion (E): 4) dopamine infusion (D); 5) hemorrhagic hypotension (HH); 6) HH + NE; 7) HH + E; 8) HH + D; 9) acute hypertension secondary to bilateral cervical vagotomy and occlusion of both common carotid arteries. BP was also recorded. Both GCP/BP and EAP/GCP ratios averaged 0.40 in control conditions, but only the EAP/GCP ratio remained constant in all conditions under study, indicating that approximately 60% of the hydrostatic pressure in glomerular capillaries is constantly dissipated by the efferent arteriole. When all values of EAP were plotted against the respective values of GCP, a liner relationship was detected (r=0.843). These results indicate that changes of pressure in the first order peritubular capillaries of superficial nephrons are merely secondary to changes in glomerular capillary pressure.
In haemorrhagic rats norepinephrine normalises BP but maintains renal cortical pressures at low levels. Dopamine, however, can normalise both BP and renal cortical pressures. Dopamine is therefore useful in treating haemorrhagic hypotension in addition to or while awaiting blood transfusion. The efferent arteriole in superficial nephrons is a passive resistance in glomerular haemodynamics.
Gel filtration through Sephadex (g 75 and 15) and ultrafiltration and diafiltration through selective membrances have been carried out on 172 uremic sera, 89 normal sera, uremic and normal urines and hemodialysis fluid. The accumulation in uremic sera of substances wwith molecular weights between 500 and 3,500 (so called "middle molecules") was demonstrated. Molecular weight evaluation was verified on single effluent fractions using different added isotopes. Evaporation of serum to dry weight revealed a 2-3 fold increase in solids compared to normal values. Estimation of the fractional content of individual elements and quantitative amino acid analysis (before and after acid hydrolysis) did not show any difference between normal and uremic subjects, but there was a significant increase of peptides in uremic serum. The accumulation of peptides was confirmed by high voltage electrophoresis. Urinary excretion of substances with comparable molecular weights to those found in uremic serum was demonstrated, but there was no significant difference between urine from normal and from uremic subjects. A steady state of chronic uremia with high urinary volume is therefore consistent with a normal urinary excretion of middle molecules with increased concentrations in serum and glomerular filtrate. Tubular reabsorption may also be decreased because the urinary excretion of middle molecules increases with the development of tubular proteinuria in patients with pyelonephritis. Dialysis treatment removes moderate amounts of middle molecules; their serum concentration decreases slightly after dialysis and they are detectable in dialysis fluid. The identification, metabolism and biological effects of middle molecules are discussed in relationship to uremic toxicity and the effects of different forms of dialysis treatment.
The plasma concentration and urinary excretion after a single 500 mg dose of Aminosidine have been studied in 12 patients with different degrees of renal failure and 4 normal subjects. In normal subjects the plasma half-life is 2.47 hr; in patients with creatinine clearance (Ccr) of 30-60 ml/min, its 6.7 hrs.; in patients with Ccr of 10-30 ml/min, it is 16.7hrs.; in patients with Ccr less than 10 ml/min, it is 36.6 hrs. A dose of 0.5 g of Aminosidine should be given to normal subjects every 12 hr. When renal function is reduced, the interval (in hr) between doses should be the following: Ccr 60-40 ml/min: 19-28;Ccr 40-30 ml/min; 28-35; Ccr 30-20 ml/min: 35-47; Ccr 20-10 ml/min: 47; Ccr less than 10 ml/min: 76.
One hundred and one patients were treated for up to two years for three hours every other day (10.5 hr/week), or four hours thrice-weekly with conventional disposable 1m2 dialysers have been investigated. Rigorous control of water balance and the maintenance of predialysis serum K and PO4 within normal limits were the main criteria for judging the adequacy of the treatment. The results regarding blood pressure, phosphate problems, haematocrit, peripheral nerve status, pericarditis and range of rehabilitation are discussed.
The present paper reports some aspects of glycolipid metabolism observed during and after dialysis of varying duration, and the effects of glucose content in dialysis fluid. Some substances used in dialysis interfere with glycolipid metabolism: heparin (Robinson and French, 1960; Wolff and Wolff, 1960); sodium acetate (Bloch, 1947; Ghosal et al, 1969; Mion et al, 1964); and glucose in high (Leonards et al, 1961; Mendelssonhn et al, 1967) or low concentrations (Drukker et al, 1964; Hagstam et al, 1969) or, more recently, completely eliminated (Alwall et al, 1970; Hubner et al, 1971).
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