[Captopril (Capoten) as a therapeutic adjuvant in the treatment of therapy-resistant hypertension].
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Biomedical subjects
Publications and source records attributed to J Ladefoged.
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Natural and synthetic steroids and mineralocorticoids were tested for their in vitro suppressive activity on phytohemagglutinin (PHA) stimulated lymphocytes. Three different (p less than 0.05) groups were identified. Methylprednisolone and betamethasone were very potent, dexamethasone, hydrocortisone and prednisolone were of intermediate potency, and aldosterone, prednisone and the metabolites of hydrocortisone were of low potency. In general, synthetic steroids were considerably more potent than naturally occurring compounds, but the relatively low potency of dexamethasone was unexpected. These in vitro findings rank glucocorticoid potency differently from the relative anti-inflammatory activities reported in the literature.
In vitro lymphoblastic transformation and sensitivity to methylprednisolone (MP) was studied in lymphocyte cultures obtained from patients on continuous ambulatory peritoneal dialysis (CAPD), on haemodialysis (HD) and control subjects. The PHA and Con A responses of peripheral blood lymphocytes (PBL) and T cells were identical in CAPD and control cultures, and in both significantly higher than in HD cultures (p less than 0.05). Both PBL and T cells from CAPD and control cultures were more resistant to the suppressive effects of MP than those from HD cultures. There was no relation between the duration of the dialysis period and the lymphocyte mitogen response in HD patients. Enhanced in vitro cell transformation and resistance to steroids during CAPD treatment may reflect an improved form of dialysis of importance for the general immune defence of the uraemic patient.
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Renal structure and function were investigated in two groups of long-term lithium treated patients. Lithium was administered in two different ways either in a one-dose per day schedule where the whole dose of lithium was given between 8 and 10 p.m. or in a schedule where the lithium dose was given, divided into two or three doses, during the day. Kidney biopsy was performed, and structural changes in the kidney tissue were determined together with 24-h urine volume in the individual patients. The functional as well as the structural changes were most pronounced in patients given their lithium in divided doses during the day. Lithium may be more harmful to the kidney when the lithium administration gives a relatively constant serum lithium level than when the administration causes greater variations including peak values and low minimum levels in serum lithium. The reason for this might be that a number of regenerative processes only occur in periods with low lithium concentrations.
A comparison was carried out regarding peritoneal dialysis using acetate in preference to lactate as the buffer anion in the dialysis solution. The investigation was made with 5 patients on long-term peritoneal dialysis once a week, first for 5 weeks with dialysis solution containing acetate and then, correspondingly, 5 dialyses with peritoneal solution containing lactate. A tendency to a slightly higher standard bicarbonate level at the end of dialysis was found when using the solution containing acetate. Furthermore, it appeared that total calcium and ionized calcium values were higher at the end of dialysis with the solution containing lactate. The latter may be ascribed to a difference in the degree of chelate binding of calcium in the two solutions. There were no differences in hemoglobin, s-sodium, s-potassium, s-urea, s-creatinine, s-phosphate and blood pressure values before and after dialysis with the two solutions. It is concluded that lactate scarcely offers any advantages in preference to acetate in peritoneal dialysis.
To evaluate the relative influence of changes in plasma renin activity, potassium, ACTH, and sodium concentrations on the secretion of aldosterone, a multifactorial analysis was performed on different sets of investigations in anephric as well as non-nephrectomized patients on regular hemodialysis. During steady-state conditions the relationship between the stimulating effect of each of these factors and combinations between these factors and the resultant plasma aldosterone concentration was analyzed. Linear models could not explain all variations in plasma aldosterone, especially not a variation found within patients. The stimulus-response curve is therefore probably non-linear and at least one or more additional factors may take part in the aldosterone regulation.
Warfarin was administered intravenously twice at an interval of six months to rabbits with surgically-induced impairment of renal function and to control animals. Pharmacokinetic analysis showed that the elimination rate of warfarin was significantly decreased in the uraemic group after 2 weeks duration of uraemia and was even further decreased at the second examination 6 months later. No significant changes in the volumes of distribution were found. Renal function tests indicated stable renal function between the two examinations.
To elucidate whether the kidney hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3) directly feedback regulates the secretion of parathyroid hormone (PTH), 10 patients with acute oliguric renal failure were studied. Serum ionized calcium (Ca++) was kept constant and subnormal by continuous peritoneal dialysis with low Ca++ dialysis fluid. In the control period (24 h), PTH was found to be constantly increased. In the treatment period (30 h), five patients received 250 ng 1,25-(OH)2D3 iv every 6 h, while five comparable patients served as controls. A significant suppression of PTH-levels was observed in the treatment group after a lag-period of 12-18 h during stable low Ca++. In the control group, PTH remained constantly increased throughout the trial. Since Ca++ was kept constant by the dialysis procedure, the observed reduction of PTH-levels cannot be explained by the calcemic effect of 1,25-(OH)2D3. The data suggest that 1,25-(OH)2D3 directly feedback regulates PTH secretion in humans with normal parathyroid glands.
Among 224 cadaver kidney transplantations performed since Spring 1977, successful DR typing of both donor and recipient could be done in 149 cases. Assessment of DR match grade and clinical data was done independently. The minimum observation time was 3 months and the time of follow up was 1 December, 1980. There was an effect of DR matching which became significant when only 1. transplants were considered and high risk recipients (i.e. diabetics) excluded. Transfusions were of minor importance on graft survival and the difference was only obvious in the first year after transplantation. Matching for HLA-A, B antigen had no obvious effect on graft survival in this material.
The relationship between plasma osmolality (pOsm) and plasma vasopressin (pAVP) was studied in 13 human subjects during dehydration. The fit of linear, log-linear, parabolic, and exponential models was tested. For all of the data, the nonlinear models had the best fit. However, when individual differences in either gain or threshold were allowed for, the linear models were better than log-linear models. Finally, analyses were made with individual data points. Linear models had the best fit in half of the subjects, whereas for the others the parabolic model gave the best fit. For those subjects investigated in the low range of the osmoregulatory curve, a linear relationship was found, whereas, for those having the most pronounced increase in pOsm, the most significant improvement was found with the parabolic model. This finding indicates that the relationship is not stable during dehydration in the whole range and that hypovolemia probably can influence the secretion rate and/or metabolic clearance rate and thereby the relationship.
The effect of whole blood ionized calcium levels on vasopressin (AVP) secretion has been studied in 12 uremic hemodialysis patients (6 nephrectomized and 6 nonnephrectomized), 6 healthy subjects, and a sprue patient, first while she was hypocalcemic and again after her blood calcium had normalized. Changes in whole blood ionized calcium were induced by calcium infusion (3.15 mg Ca/kg BW h-1). In uremic patients, an increase in plasma AVP took place during infusion, and the changes in AVP were correlated to the changes in whole blood ionized calcium. In normals, no changes in AVP were found. In the sprue patient, an increase in plasma AVP correlated to whole blood ionized calcium was found in the hypocalcemic state, but this could not be demonstrated after treatment. Parathyroid hormone has been shown to facilitate calcium entry into cells, and it is proposed that the pathophysiological effect of calcium on AVP secretion in uremic patients is caused by the elevated parathyroid hormone level found in these patients.
During a period of one year, spleen lymphocytes from cadaver kidney donors were cryopreserved for later investigations. The HLA-D types of 33 donors and the corresponding 39 recipients were determined in six experiments and the reactivities of the lymphocytes of the individual recipients towards those of the donors were assayed in MLC. The MLC experiments included a sufficient number of unrelated responders and stimulators to allow an estimate of the specific MLC reactivity by the stabilized relative response. A strong and significant correlation was found between specifically low reactivity of recipient lymphocytes against donor lymphocytes and graft survival. A correlation was also found between HLA-D compatibility and graft survival. DR typing was performed on the same donor-recipient pairs. In sixteen cases the DR typing of the recipients was initially a technical failure but successful when repeated on cryopreserved lymphocytes. There was a significant correlation between HLA-DR compatibility and graft survival. HLA-A, B matching and pretransplant blood transfusion did not significantly affect graft survival in this material.
To elucidate whether the kidney hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates the secretion of parathyroid hormone (PTH) by direct feed-back, 10 patients with acute oliguric tubulo-interstitial nephropathy were investigated. Serum ionised calcium (Ca++) was kept constant and subnormal by continuous peritoneal dialysis with low Ca++ dialysis fluid. In the control period (24h) PTH was found to be constantly increased. In the treatment period (30h) 1,25(OH)2D3 was injected i.v. every 6 hours. A significant suppression of PTH-levels was observed after a lag-period of 12-18h during stable low Ca++. In the control group PTH remained constantly increased throughout the trial. The data suggest that 1,25(OH)2D3 regulates PTH-secretion in humans with normal parathyroid glands by direct feed-back.
During the period 1965-1977, a total of 339 patients with polycystic renal disease received at least 1 renal transplant at one of 10 transplant centres in Scandinavia. Patient survival at one year was 67%. The one year graft survival of 319 cadaveric grafts was 40%. The average age of the patient was 56.7 years. Patients who were 60 years or older (93 patients) had a significantly poorer patient and graft survival at one year (50% and 29.5% respectively). Patients receiving kidneys with O incompatibilities did significantly better than other donor-recipient combinations. Previous blood transfusions were associated with better graft prognosis, though the difference was only significant for 2 years. The incidence of posttransplant urinary tract infection (present in 47% of all the patients) was twice as common in patients with a history of pretransplant urinary tract infection (seen in 41% of all the patients). There was no association between posttransplant septicaemia and either pre- or post-transplant urinary tract infection. Only 10.5% of the patients were nephrectomized at the time of transplantation, half of these had urinary tract infection. Twenty-four per cent of the patients were nephrectomized in the posttransplant period, half of these because of infection. There was no difference in the graft survival data of the patients with or without pretransplant urinary tract infection. These findings justify a restrictive practice with regard to pretransplant nephrectomy in patients with polycystic renal disease.
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