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Biomedical subjects

G Colussi

Publications and source records attributed to G Colussi.

At least 37 records · Page 2Linked to original sources

Distal nephron function in Bartter's syndrome: abnormal conductance to chloride in the cortical collecting tubule?

Five patients with the clinical patterns of Bartter's syndrome underwent a series of clearance studies in order to characterize the underlying tubule defect. Free water generation during maximal water diuresis (CH2O), expressed as percentage of the distal delivery (CH2O + CCl), was lower in the patients (72.5 +/- 3.2%) than in controls (84.4 +/- 5.5, p < 0.0001). During maximal water diuresis and furosemide administration (40 mg i.v. as bolus), NaCl reabsorption along the diluting nephron segments could be separated into 2 components, that occurring in the loop of Henle (DRNaHL) and that occurring in tubule segments beyond the macula densa (DRNaDT): DRNaHL was normal, while DRNaDT was reduced (3.1 +/- 0.8 vs. 6.2 +/- 2.5 ml/min in controls, p < 0.015). Thus, according to this furosemide protocol, our patients had normal solute reabsorption in the loop of Henle but reduced NaCl reabsorption in tubule segments beyond the macula densa. During 0.9% saline infusion (2 liters in 2 h, after stimulation of distal Na reabsorption with fludrocortisone) fractional excretion (FE) of K showed a linear rise with the increase of FECl-FEK, however, was much higher in the patients than in controls for every FECl level. In contrast, the infusion of Na2SO4, after fludrocortisone administration, induced similar FEK increases in patients and in controls. Thus, in these patients Na reabsorption in the distal nephron (possibly the cortical collecting tubule) was associated with the generation of a higher than normal electric potential gradient in the presence of Cl but not of another poorly reabsorbable anion, such as SO4(2-). These observations indicate that, in our patients, Henle's loop function is normal, while the collecting tubule function is abnormal. We suggest that NaCl wasting and enhanced tubular secretion of H+ and K in our patients might result from an abnormally low conductance to Cl in distal nephron site(s) where Na reabsorption is electrogenic, possibly the cortical collecting tubule. A larger than normal transtubular electric gradient would be generated by Na reabsorption, causing: (1) a direct stimulation of tubular secretion of K and H+ (leading to hypokalemia and alkalosis) and (2) inhibition of the reabsorption of Na ('trapped' into the tubular lumen by electric forces), with consequent extracellular volume contraction, hyperreninemia and hyperaldosteronism.

Adolescent↗

Effects of acute administration of acetazolamide and frusemide on lithium clearance in humans.

To investigate the mechanism(s) of acute frusemide-induced increases in FELi, the effects of frusemide and acetazolamide, the carbonic anhydrase inhibiting agent, were evaluated in 19 healthy subjects either before or after pretreatment with acetazolamide or frusemide (11 subjects and eight subjects respectively). Acetazolamide pretreatment did not modify frusemide-induced increases in FELi (delta FLi 12.8 +/- 4.1% compared to 14.6 +/- 7.3%, P = NS); similarly, frusemide pretreatment did not modify acetazolamide-induced increases in FELi (delta FLi: 11.3 +/- 5.9% compared to 9.8 +/- 3.8%, P = NS). Acetazolamide-induced changes of FELi were correlated significantly with acetazolamide-induced increases of FEHCO3 (r = 0.61, P less than 0.05), FENa (r = 0.46, P less than 0.05) but not of FECl (r = 0.25, P = NS). On the other hand, frusemide-induced changes of FELi were correlated significantly with frusemide-induced increases of FENa (r = 0.62, P less than 0.005), FEC1 (r = 0.52, P less than 0.025) but not of FEHCO3 (r = 0.3, P = NS). Thus, frusemide effects on tubular lithium reabsorption are not related to carbonic anhydrase inhibition; furthermore, it appears that frusemide and acetazolamide affect lithium reabsorption by different and independent mechanism(s), possibly acting at different nephron site(s).

Acetazolamide↗

Adequacy of haemodiafiltration.

In this study we have evaluated the influence of blood and ultrafiltration flow rate on the performance of five different high-flux membrane dialysers during haemodiafiltration. On the basis of clearance data we optimised the haemodiafiltration schedule of six uraemic patients to maintain an adequate midweek blood urea nitrogen concentration, while reducing the treatment time from 285 +/- 23 min to 210 min. After a follow-up of 6 months, we observed no difference in the clinical tolerance or in the biochemical parameters, compared to those found during the preceding haemodialysis period. Our data confirm the suggestions of other authors that haemodiafiltration is an effective alternative to conventional haemodialysis.

Adult↗

Pharmacological evaluation of urate renal handling in humans: pyrazinamide test vs combined pyrazinamide and probenecid administration.

Uricosuric and antiuricosuric drugs have been utilised widely for the study of tubular urate transport in humans. A normal suppression of urate excretion after pyrazinamide is usually taken as evidence of normal presecretory reabsorption. However, in patients with reduced presecretory reabsorption, during pyrazinamide inhibition of urate secretion unreabsorbed urate might still undergo reabsorption along postsecretory sites, allowing for a normal pyrazinamide suppression of urate excretion. To test this possibility, we have performed the pyrazinamide test both alone and after pretreatment with probenecid, which should block postsecretory urate reabsorption. The test was performed in 8 controls, in 9 patients with 'low-excretory' hyperuricaemia, and in 7 patients with tubular urate wasting. Pyrazinamide-non-suppressible urate excretion after pretreatment with probenecid did not differ from the excretion obtained after pyrazinamide alone in hyperuricaemic patients (mean difference 1.33 +/- 2.3% of filtered urate; P = NS); it was slightly higher in controls (3.4 +/- 3.4; P less than 0.05), but was much higher in patients with tubular urate wasting (19.6 +/- 12.7; P less than 0.005). The pyrazinamide test, performed alone, was normal in three patients with tubular urate wasting, but it was abnormal in all patients after pretreatment with probenecid. These results are consistent with the possibility that, during maximal pyrazinamide effect, some uric acid escaping reabsorption at presecretory sites may undergo reabsorption along postsecretory sites, leading to a quantitative overestimation of presecretory reabsorption. This phenomenon appears to have clinical relevance, especially in patients with abnormal urate reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The influence of dialysis fluid composition on dialysis tolerance.

To evaluate the role of bicarbonate loss through the dialyser and acetate flux to the patient in the development of symptoms during acetate dialysis, bicarbonate loss during acetate dialysis was prevented by using a combination of acetate and bicarbonate in the dialysate. Seven uraemic patients were treated for 4 months with acetate dialysis and, successively, for a similar period of time with bicarbonate, and a combination of acetate and bicarbonate dialysis. Blood-pressure drop and the incidence of hypotension and symptomatic episodes were similar in bicarbonate and combination dialysis, and significantly lower than in acetate dialysis. Serum acetate concentrations were similar during acetate and combination dialysis. These findings indicate that bicarbonate loss rather than the presence of acetate was responsible for the patients' intolerance to acetate dialysis.

Acetates↗

Clinical evaluation of segmental tubular reabsorption of sodium and fluid in man: lithium vs free water clearances.

Segmental sodium reabsorption in the proximal and distal tubule was evaluated by different methods in seven healthy subjects, seven patients with recurrent calcium nephrolithiasis, five patients with isolated renal glucosuria and three patients with Fanconi syndrome. In all the subjects, the delivery of fluid from the proximal tubule, evaluated as 'chloride' factor during maximal water diuresis (DDCl, 12.4 +/- 5.5 ml/dl GFR), was lower (P less than 0.001) than 'volume' or 'chloride' factors during maximal water diuresis plus frusemide administration (40 mg i.v.) (Vf, 22.5 +/- 7.5 and DDClf, 27.1 +/- 8.9 ml/dl GFR, respectively), and of lithium clearance (FELi, 28.1 +/- 12.6%). Vf was lower than DDClf (P less than 0.001) and FELi (P less than 0.005), while DDClf and FELi did not differ; these unequal results are likely to represent different degrees of free water back-diffusion along distal tubule segments in the free water clearance studies. Accordingly, estimation of sodium reabsorption in the distal tubule showed corresponding differences within the four methods as those observed for the distal delivery: it was 25.5 +/- 12.2% when evaluated as [FELi-FECl]; 24.8 +/- 8.3 ml/dl GFR when evaluated as [CH2Of/GFR + delta FECl] (i.e. free water clearance during frusemide plus the frusemide-induced absolute increase in FECl); 19.5 +/- 6.7 ml/dl GFR (P less than 0.001 vs [FELi-FECl] and [CH2Of/GFR + delta FECl] when evaluated as [(CH2O + CH2OBD)/GFR] (i.e. CH2O before frusemide plus the frusemide-induced absolute increase in urine flow rate); and 10.0 +/- 4.8 ml/dl GFR when evaluated as CH2O (P less than 0.001 vs all the other evaluations).(ABSTRACT TRUNCATED AT 250 WORDS)

Furosemide↗

The changes in plasma diffusible levels and renal tubular handling of magnesium during pregnancy: a longitudinal study.

Magnesium fasting plasma levels (total, PMg, and ultrafiltrable, PMgUF), daily urinary excretion and tubular reabsorption in the fasting state were measured in 14 healthy women along an uncomplicated gestation and compared with the values observed 3-6 months after delivery (C). PMg and PMgUF progressively fell during gestation (from 1.96 +/- 0.14 and 1.38 +/- 0.09 mg/dl in C, respectively, to 1.67 +/- 0.13 (P less than 0.0005) and 1.2 +/- 0.09 (P less than 0.0005) after 17-26 weeks of gestation and to 1.66 +/- 0.10 (P less than 0.0005) and 1.17 +/- 0.08 (P less than 0.0005) after 27 weeks to term). The decrease in PMg and PMgUF was further apparent in an additional group of 46 pregnant women in comparison with 20 sex-matched non-pregnant controls. Urinary Mg excretion remained unchanged throughout gestation, as did glomerular filtered load of PMgUF and tubular Mg reabsorption in the fasting state, due to the increase in GFR. Moreover, urinary Mg excretion per unit GFR (MgE, mg/dlGFR) and fractional excretion of MgUF filtered load (FEMgUF, %) fell (from 41 +/- 25 and 3.0 +/- 0.9 in C, respectively, to 26 +/- 12 (P less than 0.01) and 2.2 +/- 1.0 (P less than 0.05] in the last period, indicating that a greater fraction of filtered Mg was being reabsorbed by renal tubules. There was a significant inverse correlation between PMgUF and GFR in all the periods studied (r = 0.39, P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗