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Biomedical subjects

P Jungers

Publications and source records attributed to P Jungers.

At least 19 recordsLinked to original sources

A circulating inhibitor of the RBC membrane calcium pump in chronic renal failure.

A humoral inhibitor of the membrane calcium pump was studied in plasma from 28 normal controls, 33 patients receiving long-term hemodialysis, and 26 with chronic renal failure (CRF; creatinine clearance range was 6 to 97 ml/min). Calcium pump activity was measured as the rate of Sr2+ efflux in normal erythrocytes (RBCs) loaded with Sr2+ (a substitute of Ca2+ in the calcium pump). Plasma, and plasma ultrafiltrates from hemodialysis patients strongly inhibited calcium pump activity compared with controls without plasma (36 +/- 18 vs. 25 +/- 12, %INHIBITION/CONTROL, P < 0.05). Inhibition markedly decreased with acute hemodialysis (16 +/- 12 vs. 5 +/- 14, %INHIBITION/NORMAL PLASMA, N = 15, P < 0.001). In CRF, degree of inhibition correlated with the serum creatinine concentration (r = 0.75, P < 0.001). A kinetic study showed that plasma decreased the maximal rate of the Ca2+ pumps (Vmax) without affecting the apparent affinity for internal cations (KSr). Moreover, the plasma inhibitory factor had a low molecular weight, and was dialyzable and heat stable. In conclusion, we found evidence for an RBC membrane calcium pump inhibitor in uremic plasma, which correlates with the degree of renal insufficiency. Possibly, it may increase calcium content in RBCs and other cells and could thus be related to uremic toxicity and/or hypertension.

Adult

Plasma inhibitors of the erythrocyte hexose monophosphate shunt in uraemia.

Sulphaemoglobin production, induced by an oxidative stress (ascorbate and cyanide) has been studied in uraemic patients. Results are expressed as the ratio of optic density of sulphaemoglobin (620nm) to optic density of total haemoglobin (540nm). The mean (+/- SEM) ratio found was 0.35 +/- 0.03 in 28 controls and 0.56 +/- 0,03 in 51 uraemic subjects (p less than 0.001). Cross incubation tests demonstrated that the anomaly was caused by a plasma factor. In vitro studies - guanidinic compounds added to control erythrocyte suspensions before incubation - suggest that this factor might be guanidinic propionic acid.

Anemia, Hypochromic

The effect of 1alpha(OH)D3 and 1alpha,25(OH)2D3 on the bone in patients with renal osteodystrophy.

Six patients with chronic renal disease and variable degrees of renal osteodystrophy were treated for three weeks with either 1alpha,25-dihydroxyvitamin D3 (1alpha25(OH)D3) or 1alpha,hydroxyvitamin D3 (1alpha(OH)D3) and both the biochemical and osseous responses measured. The most consistent changes seen were an increase in serum calcium concentration to normal, a decrease in immunoreactive parathyroid hormone toward normal, an increase in the extent of the calcification front and a decrease in the extent of fibrous dysplasia in the marrow cavity. Two important parameters which did not change significantly were serum alkaline phosphatase activity and the osteoid volume. These data, in conjunction with that from previous studies, indicate that therapy with 1alpha,25(OH)2D3 or 1alpha(OH)D3 does not heal the osteomalacia of renal osteodystrophy, but that it does suppress the secondary hyperparathyroidism, and ameliorate the osteitis fibrosa seen in patients with chronic renal disease. They raise the likelihood that additional factors, such as metabolites of vitamin D other than 1alpha,25(OH)2D3, play a role in regulating bone formation and/or mineralization.

Aged

Tolerance to high ultrafiltration rates during closed batch hemodialysis.

The tolerance to high levels of ultrafiltration that has been observed when using a RP-6 dialyzer with polyacrylonitrile membrane and a closed batch dialysate delivery system has led the authors to put patients on a free sodium and fluid intake. Eight patients were put on such a diet for six months. They have been dialyzed four to five hours, three times per week, on a RP-6-Rhodial 75. The mean intersession weight gain was 4.29+/-0.18 Kg after three days for a mean predialytic body weight of 63.55+/-2.54 Kg. Mean predialytic blood pressure was 1.38+/-4 mmHg for systolic pressure and 82+/-5 mmHg for diastolic pressure. Mean ultrafiltrate volume was 4.86+/-0.36 liters which corresponds to a sodium output of 661.3+/-49.5 mEq. Total plasma protein and hematocrit increased 18.8+/-3.34% and 19.13+/-3.22%, respectively, when the pre and post-dialytic values were compared. No clinical sign of fluid overload (dyspnea, edema, etc.) was noted in these patients. Cardiothoracic index remained in the normal range. This tolerance is due, possibly, to the high sodium concentration (145 mEq/L) in the dialysate. The free sodium and water diet may contribute to a better rehabilitation.

Adult

[Arterial hypertension and mortality due to cardiovascular complications in patients on chronic hemodialysis].

Cardiovascular accidents are the commonest cause of death in patients on intermittent haemodialysis. Our study concerns 158 adult patients in terminal renal failure who were treated by periodic dialysis; it was carried out at Necker Hospital between January 1967 and December 1970. Between these dates, 35 patients died, 17 of the deaths being due to unequivocal or probable cardiovascular complications. The diagnosis of cerebrovascular accident was made in 13 cases. The mean age of the patients who died was 38 years. Fatal cerebrovascular accidents occurred especially during the first 12 to 24 months of treatment. The incidence of fatal vascular accidents is greatest in patients who were hypertensive at the beginning of periodic dialysis, and who remained so after six months of dialysis. Our study has therefore shown that hypertension in patients on chronic haemodialysis is a major vascular risk factors; other risk factors, especially metabolic ones, may also play a part.

Adolescent

Evaluation of plasma neurotoxin concentration in uraemic polyneuropathic patients.

Purification of b4-2 sub-peak obtained on DEAE Sephadex A25 chromatography gave us the possibility of quantifying the plasma concentration of the neurotoxin present in uraemic patients with active polyneuropathy. From the purified neurotoxin isolated by kieselguhr and cellulose chromatography we calibrated analytic columns for b4-2 analysis. Plasma concentration, measured in 6 uraemic neuropathic patients, is between 13 and 19 mg/litre. In 52 uraemic patients without neuropathy, the plasma concentration is between 3 and 9 mg/litre. In 20 healthy subjects the plasma concentration is less than 1 mg/litre. The weekly neurotoxin removal in uraemic patients without neuropathy, treated by a five hours RP6 session 3 times a week, is of the same order of magnitude as the weekly urinary excretion in healthy subjects. Preliminary results of a tentative identification of this purified product indicate that it is not a polypeptide but an acid-polyol with carbohydrate structure.

Chromatography, Ion Exchange

Anemia and secondary hyperparathyroidism.

Anemia has been recognized recently as a possible complication of primary hyperparathyroidism. If the hyperparathyroid state can induce anemia in patients with normal kidney function, the extremely high levels of circulating parathyroid hormone usually observed in hyperparathyroidism secondary to chronic renal failure may have an unfavorable influence on the anemia of uremic patients. We investigated the influence of subtotal parathyroidectomy on the severity of the anemia of 18 uremic subjects undergoing long-term hemodialysis therapy. Subtotal parathyroidectomy resulted in a significant increase of mean hematocrit value. RBC count, and hemoglobin level. Serial bone biopsies suggested a relationship between the amount of marrow fibrosis and the improvement of anemia after surgery, but the precise mechanism of this phenomenon is still unknown.

Adult

[Nephrotoxicity of gentamicin. Conditions for the use of this antibiotic in the elderly and in the patient with renal insufficiency].

Reversible acute renal failure was observed in 13 patients after combined antibiotic therapy using gentamicin. High and prolonged doses were used in 7 patients whose initial renal function was normal, while 6 other patients with preceding chronic renal insufficiency received usual doses of gentamicin. Precipitating factors were: increasing age, previous renal impairment, and combined use of other antibiotics, mainly cefalotin (8 patients). The nephrotoxicity of gentamicin is poor but well established, and may be prevented by checking the initial renal function, adjusting the dosage subsequently, and monitoring the renal function and gentamicin serum levels during therapy.

Acute Kidney Injury

Effects of high dialysate calcium concentration on bone remodelling, serum biochemistry, and parathyroid hormone in patients with renal osteodystrophy.

The influence of a dialysate calcium concentration of 8.0 mg/100 ml (treatment period 2) vs. 7.0 mg/100 ml (treatment period 1) on plasma calcium, phosphorus, serum immunoreactive parathyroid hormone (iPTH), bone histology, intestinal calcium absorption, and calcium transfer across the dialysis membrane was investigated in six patients with renal osteodystrophy undergoing intermittent hemodialysis. During the periods 1 and 2, the plasma calcium changes before and after dialysis were not significantly different. A significant increase in mean postdialysis plasma calcium level was observed during both periods when compared to mean predialysis level. A significant, inverse relation was found between predialysis plasma calcium and the increase in plasma calcium during hemodialysis runs. Calcium transfer across the dialysis membrane and fractional intestinal absorption of calcium in the postdialysis state were determined in four out of the six patients. During period 2, calcium transfer was higher in all four patients but intestinal calcium absorption was moderately higher only in one and strikingly lower in the remaining three patients when compared to period 1. Although brought up to 8.0 mg/100 ml, this higher dialysate calcium significantly decreased the level of serum iPTH only in one out of the six patients; in this patient, osteoclast count, active resorption surface, and periosteocytic osteolysis decreased. In a second patient, although the level of serum iPTH seemed to decrease markedly osteoclastic and osteocytic resorption did not change. In the remaining four patients, the level of serum iPTH was unchanged and bone resorption parameters were found unchanged or aggravated. It is concluded that providing additional calcium (using a dialysate calcium concentration of 8.0 mg/100 ml), the goal of which was to decrease secondary hyperparathyroidism, proved to be successful only in one patient and failed to do so in the five others. Secondary hyperparathyroidism was even found aggravated in three of them. Thus, the use of a dialysate calcium concentration of 8.0 mg/100 ml did not result in any advantage over that of 7.0 mg/100 ml in five out of six patients studied.

Adult

Detection of hepatitis B antigen in circulating immune complexes in acute and chronic hepatitis.

By using polyethylene glycol precipitation at low concentration (PEG test) and the radiolabeled C1q binding test, immune complexes were detected sera from acute (23/28) and chronic (28/32) hepatitis patients, hemodialyzed patients with chronic hepatitis B surface (HBs) antigenemia (7/19), and asymptomatic HBs antigen carriers (2/11). After treatment of PEG precipitates with acidic pH, heating, or proteolytic enzyme (protease), electroimmunodiffusion or radioimmunoassay revealed the presence of HBs antigen or antibody in dissociated immune complexes in sera from several acute and chronic hepatitis patients. Electron microscopy showed immune complexes of HB virus in 9 of 12 PEG precipitates obtained from PEG-test-positive sera; these 9 precipitates were from patients with acute or chronic hepatitis and the other three from chronic HBs Ag carriers. Free HB virus particles were observed after protease digestion of PEG precipitates. Neither immune complexes nor virus particles were seen in precipitates from PEG-test-negative but HBs-Ag-positive sera from chronic carriers.

Acute Disease

HLA-A1, B8-phenotype association and HBs antigenemia evolution in 440 hemodialyzed patients.

HBs antigen (HBsAg) has been followed up every month in 440 hemodialyzed patients, typed for 26 HLA alleles of the A and B loci. An abnormally high rate of the HL-A-A1, B8 association (18.6%) was found in the group of patients able to eliminate HBsAg, when compared with the normal French population (5.05%, p less than 10(-4), and with the group of patients unable to eliminate HBsAg (7.0%, less than 0.01). Chronic aggressive hepatitis was only found in the latter. This high frequency of the HLA-A1, B8 association has also been found in patients with seronegative active chronic hepatitis and suggests that this phenotype might be associated with high immune response against HBsAg.

Chronic Disease