Phosphorus-31 and water proton relaxation in living erythrocytes. Application to uremia.

We measured the spin-lattice and spin-spin relaxation times (T1 and T2, respectively) and the nuclear Overhauser effect (NOE) of 31P nuclei of 2,3-diphosphoglycerate (2,3-DPG) in living erythrocytes. The relaxation of water protons was also studied. Phosphorus relaxation is pH-dependent due to a modification of the binding of 2,3-DPG to hemoglobin. We compared the results obtained with normal and uremic erythrocytes. In uremic erythrocytes the 31P relaxation rates are increased, but the intraerythrocytic pH variation in uremic erythrocytes cannot itself explain this increase. A possible role of dialysable substances may explain the increased relaxation rate.

Inhibition of microtubule formation by uremic toxins: action mechanism and hypothesis about the active component.

We show in vitro inhibitory effect of a mixture of uremic toxins on tubulin 6S polymerization. It proves the existence of a direct interaction protein-toxin where micro-tubule associated proteins are not involved. A similar phenomenom could occur in uremic neuropathy. The action mechanism of this interaction is quite different from that of classical tubulin inhibitors: Vinca alcaloïdes and colchicine. Finally we hypothesize about the active molecule.

A continuous hemofiltration system using sorbents for hemofiltrate regeneration.

Plasma ultrafiltrate obtained by glomerular filtration undergoes tubular modification which leads to the elimination of toxic substances, excess water and electrolytes, and consequently maintains homeostasis. Using normal urine and the substances it contains as a reference, we have developed a wearable device capable of replacing both the renal excretion function and maintaining fluid and electrolyte equilibrium in uremics within acceptable biological limits. Our device includes a hemofilter allowing continuous plasma ultrafiltration and sorbents obtained from a Redy sorbent cartridge to treat 85% of the ultrafiltrate, whereas 15% of this UF is rejected untreated. After calculating the quantity of ultrafiltrate (about 13 l) containing an amount of waste products of metabolism equivalent to 24-h urine elimination, we determined in vitro the amount of sorbent required to eliminate these waste products from the ultrafiltrate (e.g., 20 g of urea/day) and we have evaluated the quantities of other substances which must be replaced using a tailored diet. This extra-corporeal detoxification process was used in a uremic patient who had been on traditional hemodialysis for the past two years. The continuous treatment permitted maintenance of fluid and electrolyte equilibrium at the desired level and allowed rapid improvement of patient clinical status: elimination uf nausea, vomiting, diarrhea and edema, which had previously reappeared during the interdialytic periods, as well as a rapid decrease in heart size as ascites disappeared. In addition, the patient regained sexual drive and the ability to have an erection. In conclusion, traditional hemodialysis and hemofiltration techniques allow intermittent elimination of products retained by the body and reestablish nearly normal fluid and electrolyte balance.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of acute reversible renal failure associated with halothane induced liver disease.

A case of acute renal failure associated with halothane-induced hepatitis is reported which responded to treatment. The possible mechanisms of rare disease association are discussed and precautions advised.

Sequential sodium therapy allows correction of sodium-volume balance and reduces morbidity.

We investigated whether individually adjusting Na+ dialysis levels (Na+Di) combined with Na+ and UFR (ultrafiltration rate) programming, and a sodium/volume model (sequential sodium therapy, SST) can improve the end stage renal failure (ESRD) patient's homeostatic equilibrium intra- and interdialytically. One hundred and fifty patients were included in the study over a one year period. The results show that the patients are divided into two groups: 50 patients respond according to the sodium/volume model developed by F. Gotch [1983]. In this group it is possible to predict pre- and post dialysis plasma Na+ concentration (Na+o, Na+t) as a function of Na+Di and it becomes possible to choose Na+Di to allow Na+o and Na+t to virtually coincide, eliminating severe shifts in plasma tonicity. In the second group two subgroups can be distinguished: excess Na+ or excess H2O post dialysis, without possible correction at a single sodium level. SST corrects sodium/volume balance in this group by using sequential intermittent hypo or hypertonic dialysate, combined with fluid removal adapted to each episode. In both groups there was a significant improvement in the clinical condition of the patients who previously were less equilibrated. It is possible to conclude that SST improves tolerance intradialytically and achieves better equilibrium interdialytically. Implementation of SST requires precise control of the concentrate and the water, and equipment adapted for accurate, programmable sequential control of Na+Di and ultrafiltration rate.

Inhibition in vitro of the polymerization of tubulin by uremic middle molecules: corrective effect of isaxonine.

The polymerization of tubulin leads to the formation of microtubules which are one of the components of the axons of nerve cells. This reaction is the limiting factor in the growth of axons. Uremic middle molecules inhibit in vitro the polymerization of tubulin in a dose dependent way. It is possible that a similar phenomenon could occur in vivo in uremic patients, and this might be involved in the development of neuropathy. In addition, isaxonine phosphate counteracts the inhibitory effect of uremic middle molecules on the polymerization of tubulin.

Kinetic modeling of intracellular pH and comparison with 31P NMR experimental values in dialysed uremic patients.

Changes in intra-erythrocytic pH values over time, during and after bicarbonate hemodialysis, were studied with 31P Nuclear Magnetic Resonance. Simultaneously, pH values of whole blood were obtained by a gazometric method. A two-compartment model appeared to be the simplest kinetic model to explain the shifts in proton concentrations in extra- and intra-cellular media. Non-linear regression was used to determine exchange constant values. There was a very good correlation between the experimental and calculated proton concentrations. This model can describe all patients but individual experimental constants must be determined. Under these conditions a single blood pH determination before dialysis will permit determination of the initial intra-erythrocytic pH and monitoring of intra-erythrocytic pH during hemodialysis.

[Pseudo-hypertrophic pelvi-crural amyloid myopathy in lambda light-chain myeloma. Clinical, morphological and immunocytochemical study]. / Myopathie amyloide pelvicrurale pseudo-hypertrophique au cours d'un myélome a chaines légères lambda. Etude clinique, morphologique et immunocytochimique.

The case of 65 year old woman with progressive enlargement and "wooden" induration of the pelvic girdle and thigh muscles due to an amyloid infiltration is reported. Muscle changes appeared two years after a diagnosis of myeloma with free lambda light chains. The patient complained of muscle pain, lassitude and weakness. Macroglossia was present. Skeletal muscle (vastus lateralis) contained large amounts of amyloid substance and showed type 2B atrophy. There was no fiber type grouping. Some amyloid deposits abutted on the muscle fiber, destroyed the basal lamina and sarcolemma, but never infiltrated it. Besides the amyloid phagocytosis by macrophages, a relationship between amyloid filaments and fibroblasts was present. Another non-congophilic substance was revealed using the Avidin-Biotin peroxidase complex to localize lambda light chains by light microscopy and corresponded to a granular substance in electron microscopy. Clinicopathological results are discussed with a review of thirteen similar cases previously reported.

Partial purification of a calcium ionophore from human uremic plasma and normal urine.

A fraction is isolated from human uremic plasma and normal urine using a three step chromatographic separation :gel permeation on Sephadex G15, then chromatography on hydroxyapatite and finally desalting operation on Sephadex G15. The fraction thus separated is ninhydrine positive and uncouples mitochondria principally releasing the resting respiration. Calcium potentiates the uncoupling, while red ruthenium and magnesium inhibit it. These results are in good agreement with a ionophorous activity of the isolated fraction. An hypothetic physiological role of this compound is there being discussed.

Identification by nuclear magnetic resonance and mass spectrometry of a glucuronic acid conjugate of o-hydroxybenzoic acid in normal urine and uremic plasma.

An endogenous compound (included in the fraction of uremic toxins often called the "uremic middle molecules") was separated from plasma of uremic patients and urine from normal persons. As elucidated by mass spectrometry, enzymatic hydrolysis, and 1H, 13C nuclear magnetic resonance, it appears to be a conjugate of o-hydroxybenzoic acid with glucuronic acid. Its presence in urine of healthy subjects indicates its physiological character.

[Nephrologic criteria for reoperation (in the framework of abdominal surgery)]. / Les critères néphrologiques de réintervention (dans le cadre des réinterventions en chirurgie abdominale)

38 cases of abdominal surgery in acute renal failure, checked anatomically by reintervention or autopsy, were analyzed. The authors emphasize the frequency of the state of shock (2/3 of the cases) and the misleading nature of local signs. They stress the value of routinely checking creatinine clearance in the preoperative check-up in order to screen for latent renal failure.

[Epilepsy in renal insufficiency and accidental epileptic seizures during hemodialysis (artificial kidney)]. / Epilepsie de l'insuffisance rénale et crises épileptiques accidentelles survenant au cours de l'épuration extra-rénale (rein artifiel)

The authors, referring to 29 observed cases, review the characteristics of true renal epilepsy with regard both to attacks and to interictal periods. Their research shows that this type of epilepsy cannot be explained by any specific anatomical lesion but is probably functional and more specifically metabolic; it disappears when renal dialysis is performed. The authors accept that the factors liable to provoke this kind of epilepsy include cellular hyperhydration possibly associated with hypocalcaemia and with a genetic predisposition to convulsions. They reject the role of uraemia. This type of renal epilepsy is compared to the epileptic attacks provoked by renal dialysis.

23Na nuclear magnetic resonance study of Na+-K+ pump inhibition by a fraction from uremic toxins.

An in vitro inhibitor of Na+/K+-transporting ATPase (EC 3.6.1.37) was isolated from uremic plasma and normal urine by liquid chromatography. A 23Na nuclear magnetic resonance study involving living erythrocytes showed that this inhibitor causes impairment of the Na+-K+ pump of intact erythrocytes. This finding may explain the high intra-erythrocytic sodium concentration in those uremic patients exhibiting a high concentration of this inhibitor. The presence of this same inhibitor in normal urine suggests that it may play a physiological role.

"In vitro" inhibition of platelet aggregation by uremic middle molecules.

"Uremic middle molecules" are isolated from the urine of normal subjects and the blood in chronic renal insufficiency treated by hemodialysis. Their action is tested in vitro on platelets aggregation induced by ADP. Some fractions of these middle molecules (fractions 7b, 7c and 7 "fg") are without any effect. The 7 "de" fractions give an inhibition of platelets aggregation. The percentage variations of first phase inhibition as a function of the middle molecules concentrations is studied.

Modification of intra-erythrocytic homeostasis in uremic patients, as studied with 31P nuclear magnetic resonance.

Intra-erythrocytic pH, ATP concentrations, and 2,3-diphosphoglycerate relaxation times were studied in living erythrocytes by "high-resolution" 31P NMR spectroscopy to assess homeostasis within the cells. In uremic patients, intra-erythrocytic pH is significantly decreased before hemodialysis, but is corrected equally well by hemodialysis against either acetate or bicarbonate. This acidic pHi may be correlated with the increased concentration of ATP in erythrocytes in uremia, which is partly corrected by these two types of hemodialysis. Similarly, the significant decrease of spin-spin relaxation times in uremic patients is corrected by hemodialysis.

[Modifications of pure pancreatic secretion in patients with chronic renal failure treated by hemodialysis (author's transl)]. / Modifications de la sécrétion pancréatique pure chez les patients atteints d'insuffisance rénale chronique traités par hémodialyse.

In 20 patients suffering from chronic renal failure treated by hemodialysis (CRFH) the pure pancreatic juice (PPJ) collected via endoscopic cannulation of the papilla was studied. PPJ was collected during 20 minutes in 1 minute samples. Secretin and pancreozymin (CCK-PZ) were given as boluses respectively at the beginning and at the 10th minute of the test. Volumes, total protein and bicarbonate concentrations, total protein and bicarbonate outputs, Lactoferrin (LF) levels were measured. The results observed in patients were compared to those of ten subjects free of any organic disease. The volume of PPJ was significantly more important in CRFH than in controls. Bicarbonate and protein concentrations were not significantly modified. Protein output was not significantly more important in CRFH at the exception of the 12th sample. Bicarbonate output was not significantly increased at the exception of the 9th and the 11th samples. LF level was more than 0.03% of total proteins in 4 CRFH.