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Biomedical subjects

J Zingraff

Publications and source records attributed to J Zingraff.

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

Permeability of cellulosic and non-cellulosic membranes to endotoxin subunits and cytokine production during in-vitro haemodialysis.

The possibility of endotoxin transfer across haemodialysis membranes remains a controversial issue. Additional concern has arisen because of the recent introduction in clinical practice of highly permeable, synthetic dialysis membranes and of bacteria-contaminated bicarbonate concentrate with potential short-term and long-term hazards for haemodialysis (HD) patients. Therefore, we performed experiments in an in-vitro dialysis recirculation system using three different types of HD membranes, namely standard regenerated cellulose (Cuprophan, CU), polyacrylonitrile AN-69 (PAN), and polysulphone F-60 (PS). When radiolabelled lipopolysaccharide (125I M-LPS) from E. coli, together with 10 micrograms/ml unlabelled LPS, was added to the recirculating solution in the dialysis compartment, radioactivity could be detected in the blood compartment after 15 min and increased progressively with time up to respectively 6.7% (CU), 10.3% (PAN), and 10.3% (PS) of initial activity on the dialysate side. The addition of albumin to the solution on the blood side led to a decreased permeability of radioactivity (7.3% vs 10.3%), compared to the absence of albumin (tested only for PS membrane). Furthermore, 73% of 125I M-LPS transferred across the PS membrane in the presence of albumin was TCA-precipitable. In contrast, free iodine (Na 125I) incubated in an albumin-containing solution did not precipitate with albumin after the addition of TCA (precipitation of only 0.6%). Moreover, kinetics of transmembranous transfer of Na-125I were strikingly different from that of 125I M-LPS. Analysis by the method of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the blood side solution, after LPS addition in the dialysis solution and 30 min of back-filtration, revealed the presence of several silver-stainable and autoradiographic bands of low-molecular-weight range, probably LPS fragments. Finally, the presence of LPS in the dialysate compartment led to a moderate increase in interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF) concentrations in plasma as well as in monocyte culture supernatants after isolation from recirculating normal human whole blood exposed to CU, PAN, or PS membrane. In conclusion, our study provides evidence for the permeation of low-molecular-weight LPS subunits across cellulosic and non-cellulosic HD membranes. The clinical significance, if any, of such a transfer has, however, still to be demonstrated.

Cellulose

Angiocardiographic and haemodynamic studies in chronic haemodialysis patients with cardiomegaly.

Twenty-one chronic haemodialysis patients with cardiomegaly and repeated episodes of heart failure were selected for left ventricular cineangiography and haemodynamic studies. Left ventricular end-diastolic (LVED) volume was augmented in eleven, LVED pressure increased in fourteen, and ejection fraction decreased in nine patients. A decrease of maximum velocity of myocardial fibre shortening was observed in fifteen, and of normalised ventricular rigidity index in eleven. Many patients had diminished cardiac performance in the absence of demonstrable coronary heart disease, hypertension, or chronic volume overload. The diagnosis of congestive cardiomyopathy of unknown aetiology, possibly related to uraemia, was reached in ten patients.

Adolescent

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

Porphyria cutanea tarda-like syndrome in hemodialyzed patients.

Among 500 patients on maintenance hemodialysis, 6 patients (5 young women and a 49-year-old man) developed bullous dermatosis, 2-54 months after initiating dialysis treatment. The skin lesions occurred mainly in sunlight-exposed areas, and 4 out of the 6 patients showed increased cutaneous fragility in response to trauma. Skin biopsy revealed subepidermal blisters for all of them, and skin immunofluorescence studies were negative for 2 patients. No increase in fecal or red cell coproporhyrin and protoporphyrin levels was found in any of the 6 patients. The syndrome was clinically and histologically indistinguishable from porphyria cutanea tarda.

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

Congestive cardiomyopathy in uraemic patients on long term haemodialysis.

Five uraemic patients who developed progressive cardiac failure with clinical evidence of congestive cardiomyopathy at the start or during haemodialysis treatment were studied. The diagnosis of cardiomyopathy, for which there was no apparent cause, was confirmed by angiocardiographic and haemodynamic studies. These showed a significant increase in left ventricular end-diastolic volume over normal values obtained in 12 patients without uraemia. The mean velocity of myocardial fibre shortening was significantly decreased, as was the index of normalised rigidity. Three of the five patients presented the complete picture of the disease. The other two also had considerable ventricular dilatation and a decreased index of normalised rigidity but normal ejection fraction and only moderately decreased myocardial contractility indices. This suggests that there may be primary involvement of normalised heart muscle rigidity followed by secondary changes in myocardial contractility in uraemic patients with congestive cardiomyopathy.

Adult

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

Possible persistent endocrine function of a rejected renal allograft.

The case is described of a patient on intermittent hemodialysis who had had a bilateral nephrectomy but had hypertension and a surprisingly mild degree of anemia. Repeated determinations showed high plasma renin activity and plasma erythropoietin activity within the detectable range. These results were thought to be related to a completely calcified renal allograft which had been inserted 8 years before and which had been rejected four years later, but left in situ. The patient had become anuric. It is suggested that chronically rejected renal allografts, even calcified, may maintain some endocrine activity in the absence of any excretory function.

Adult