To study the specificity of gut hyperpermeability in primary glomerulonephritis, we investigated intestinal permeability by means of 51Cr-EDTA testing in 20 healthy individuals and in 30 patients with Immunoglobulin A nephropathy (IgA GN), 25 with idiopathic nephrotic syndrome (INS) and 20 with immune complex glomerulonephritis (IC-GN; membranous + membranoproliferative glomerulonephritis). Gut permeability was statistically increased in each patient group versus the controls [controls: 2% (0.4-3.9); IgA GN: 3.25% (0.7-17.70); INS: 3.71% (0.82-10); IC-GN: 3.40% (0.30-16); results are median (range); p < 0.005, nonparametric Mann-Whitney test]. An increase in intestinal permeability exceeding the upper limit of control values (95th percentile) was observed in 36% of IgA GN, 60% of INS and 50% of IC-GN patients. We conclude that intestinal permeability is frequently increased in primary glomerulonephritis and may also be increased in types of glomerulonephritis other than IgA GN.
The mechanisms controlling erythropoietin (EPO) synthesis by the kidney in patients with chronic obstructive lung disease (COLD) or congestive left heart failure (CLHF) remain incompletely understood. Renal dysfunction occurs as a consequence of decreased renal blood flow (RBF) in these diseases. Because alterations in renal haemodynamics may affect EPO synthesis and red blood cell production, we investigated the potential relationships between renal function and plasma EPO synthesis in patients with COLD or CLHF. Thirty-two patients with COLD and 13 with CLHF underwent determination of renal physiology parameters, plasma EPO levels and haemoglobin levels. Plasma EPO concentrations were increased in patients with COLD or CLHF as compared to normal subjects, and were inversely correlated to haemoglobin concentrations. In patients with COLD or CLHF, plasma EPO was negatively correlated with both RBF and renal oxygen delivery (ROD) and positively correlated with filtration fraction. Plasma EPO was not correlated with glomerular filtration rate, fractional excretion of sodium, PO2 or PCO2. Among the patients with COLD, those with polycythemia (haemoglobin > 150 g L-1) had lower plasma EPO and higher RBF and ROD values than those with normocythemia (haemoglobin < or = 150 g L-1). Taken together, our data suggest that in patients with COLD or CLHF the critical determinant for EPO production is impairment of renal haemodynamics.
The volumes of distribution of many acidic drugs have been shown to be close to that of their binding protein, i.e. serum albumin. The distribution of basic drugs mainly bound to alpha 1-acid glycoprotein (AAG) can be questioned with respect to its dependency upon the distribution of this plasma protein. So, a pharmacokinetic study was performed in 7 subjects with human 125I-labelled alpha 1-acid glycoprotein. The steady-state volume of distribution was found to be 5.37 +/- 0.82L. The central volume was 3.23 +/- 0.33L, close to that of plasma volume and the peripheral volume was 2.14 +/- 0.63L. These data allowed the establishment of an equation giving access to the volume of distribution of a basic drug by relating its unbound fraction to physiological distribution of alpha 1-acid glycoprotein. The values yielded by this equation show that the actual and calculated volumes of distribution of basic drugs mainly bound to AAG are discrepant. This protein is thus not the main factor controlling the distribution of basic drugs within the body.
Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.
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